Amelie G. Ramirez Edward J. Trapido *Editors*

# Advancing the Science of Cancer in Latinos

## Building Collaboration for Action

Advancing the Science of Cancer in Latinos

Amelie G. Ramirez • Edward J. Trapido Editors

# Advancing the Science of Cancer in Latinos

### Building Collaboration for Action

*Editors* Amelie G. Ramirez Department of Population Health Sciences Institute for Health Promotion Research UT Health San Antonio San Antonio, TX, USA

Edward J. Trapido Epidemiology Program LSU Health Sciences Center School of Public Health New Orleans, LA, USA

This book is an open access publication.

ISBN 978-3-031-14435-6 ISBN 978-3-031-14436-3 (eBook) https://doi.org/10.1007/978-3-031-14436-3

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### **Preface**

The *Advancing the Science of Cancer in Latinos* national conference was a call to action for addressing cancer health disparities in Hispanic/Latino communities. It emerged from the need for Latino disparities researchers to seek solutions through multidisciplinary collaborations and to keep pace with the substantial advancement in cancer prevention, screening, diagnosis, treatment, and survivorship. Held in San Antonio from February 26 to 28, 2020, the conference was co-hosted by the Mays Cancer Center and the Institute for Health Promotion Research at UT Health San Antonio and sponsored by the National Institute on Minority Health and Health Disparities. The conference offered a robust platform that fostered discussion on the latest fndings in Latino cancer disparities research.

While most conferences on cancer health disparities focus solely on policy and public health issues, this conference also focused on Latino-centric perspectives from basic scientists, clinicians, population health experts, and patient advocates to emphasize the need for timely translation of research. The conference assembled an international, multidisciplinary group of speakers and attendees who explored wideranging issues, including Latino cancer-related health disparities, survivorship, patient advocacy, and recent developments in research approaches. A primary aim of the conference was to promote collaboration to stimulate development of new transdisciplinary research in Latino cancer health disparities. By bridging research and disciplinary silos, the conference fostered interactions and collaborations that would not have occurred otherwise, allowing discussions of broader, systemic cross-cutting issues and promoting translation from one discipline to another.

This book documents conference outcomes and highlights recommendations and priority areas for future research in Latino cancer health disparities; it is a resource for physicians, researchers, scientists, patient advocates, and students at all levels. With the ongoing rise in the US Latino population and cancer burden, we believe these pages hold many key insights into actionable targets for basic science research, suggestions for clinical best practices and community interventions, as well as other novel strategies and advocacy opportunities to reduce Latino cancer health disparities.

As you explore the papers and posters from *Advancing the Science of Cancer in Latinos,* we hope that you will gain a fresh perspective on Latino cancer health disparities and that it will inform your own thinking, research, and practice at your program, institution, business, and nonproft. We are optimistic that discussions and interactions at our scientifc conference and the information in these proceedings will be a catalyst for more conferences, collaboration, research, and success in reducing Latino cancer health disparities in these challenging times.

**Amelie G. Ramirez, DrPH, MPH**  San Antonio, TX, USA

**Edward J. Trapido, ScD, FACE** New Orleans, LA, USA

### **Acknowledgments**

We would like to express our extreme gratitude to the 2020 *Advancing the Science of Cancer in Latinos* conference Scientifc Planning Committee: Program Co-chair Edward J. Trapido, ScD, FACE, at Louisiana State University School of Public Health and the Stanley S. Scott Cancer Center; Anna M. Nápoles, MPH, PhD, at the National Institute on Minority Health and Health Disparities; Barbara Segarra Vasquez, MT, DHSc, University of Puerto Rico; Elena V. Rios, MD, MSPH, from the National Hispanic Medical Association; Filipa C. Lynce, MD, at the Lombardi Comprehensive Cancer Center, Georgetown University Medical Center; Frank J. Penedo, PhD, at the Sylvester Comprehensive Cancer Center, University of Miami; Laura Fejerman, PhD, University of California San Francisco; Laura Magana Valladares, PhD, Association of Schools and Programs of Public Health; Laura Tenner, MD, at the Mays Cancer Center, UT Health San Antonio; Marcia R. Cruz-Correa, MD, PhD, University of Puerto Rico; Mariana C. Stern, PhD, at the Norris Comprehensive Cancer Center, University of Southern California; Martin Mendoza, PhD, at the Food & Drug Administration; Matthew P. Banegas, PhD, MPH, Kaiser Permanente; Patricia I. Moreno, PhD, Northwestern University; and Sandi Stanford from the Alamo Breast Cancer Foundation. Gratitude is also expressed to our distinguished speakers: Sandro Galea, MD, MPH, DrPH, Boston University; Douglas R. Lowy, MD, National Cancer Institute; Eliseo Pérez-Stable, MD, Director of the National Institute on Minority Health and Health Disparities; Otis Brawley, MD, John Hopkins University; Robert Croyle, PhD, National Cancer Institute; and Edith Perez, MD, Professor of Medicine at the Mayo Clinic College of Medicine.

Our sincere appreciation to Nina Caris, PhD, for her editorial contributions to this publication. Finally, we are grateful to our lead program coordinator, Harriet Van Loggerenberg, MS, for her signifcant efforts in organizing the *Advancing the Science of Cancer in Latinos* conference from concept to completion.

Preparation of this book was supported (in part) by the Mays Cancer Center at UT Health San Antonio, Institute for Health Promotion Research at UT Health San Antonio, and the National Institute on Minority Health and Health Disparities (R13MD012457-01). The views expressed in this publication do not necessarily refect the offcial policies of the Department of Health and Human Services, nor does mention by trade names, commercial practices, or organizations imply endorsement by the US Government.

### **Contents**

#### **Part I Introduction**

### **About the Editors**

#### **Amelie G. Ramirez, DrPH, MPH**

Program Chair Professor and Chair, Department of Population Health Sciences Director, Institute for Health Promotion Research Dielmann Chair in Health Disparities Research & Community Outreach Max and Minnie Tomerlin Voelcker Endowed Chair in Cancer Health Care Disparities

UT Health San Antonio San Antonio, TX, USA

#### **Edward J. Trapido, ScD, FACE**

Program Co-Chair Associate Dean for Research, Professor and Wendell H. Gauthier Chair of Cancer Epidemiology, LSU School of Public Health Deputy Director, Stanley S. Scott Cancer Center Professor of Medicine and Senior Liaison to the Dean of the School of Medicine, LSU Health Sciences Center

LSU Health Sciences Center New Orleans, LA, USA

### **Contributors**

**Carolina Aristizabal** USC Norris Comprehensive Cancer Center and Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

**Elva M. Arredondo** Division of Health Promotion and Behavioral Science, School of Public Health, San Diego State University, San Diego, CA, USA

**Lourdes Baezconde-Garbanati** USC Norris Comprehensive Cancer Center and Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

**Sharon H. Baik** Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

**Elisa V. Bandera** Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

**Rosa Barahona** USC Norris Comprehensive Cancer Center and Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

**Austin L. Brown** Baylor College of Medicine, Houston, TX, USA Texas Children's Hospital, Houston, TX, USA

**Diana Buitrago** Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

**Joanna Buscemi** Department of Psychology, DePaul University, Chicago, IL, USA Institute for Health Research and Policy, University of Illinois at Chicago, Chicago, IL, USA

**Mariana Chavez Mac Gregor** Health Services Research Department, Breast Medical Oncology Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

**Elam Day-Friedland** Albany High School, Albany, CA, USA

**Randa El-Zein** Houston Methodist Hospital, Houston, TX, USA

**Laura Fejerman** Department of Public Health Sciences, Division of Epidemiology, University of California, Davis, CA, USA

UC Davis Comprehensive Cancer Center, University of California, Davis, CA, USA

**Anna R. Giuliano** Center for Immunization and Infection Research in Cancer, Mofft Cancer Center, Tampa, FL, USA

**Melissa Gonzales** Genentech, San Francisco, CA, USA

**Stefano Guerra** University of Arizona, Tucson, AZ, USA

**Dolores D. Guest** University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA

Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA

**Judith Guitelman** ALAS-WINGS, Latina Association for Breast Cancer, Chicago, IL, USA

**Chi-Chen Hong** Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

**Darryl B. Hood** Department of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH, USA

**Francisco Iacobelli** Department of Computer Science, Northeastern Illinois University, Chicago, IL, USA

**Shoshana Adler Jaffe** University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA

**Paul D. Juarez** Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA

**Nanette V. Lopez** Department of Health Sciences, Northern Arizona University, Flagstaff, AZ, USA

**Philip J. Lupo** Baylor College of Medicine, Houston, TX, USA

Texas Children's Hospital, Houston, TX, USA

**Catalina Malinowski** Health Services Research Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

**Katie M. Marker** Human Medical Genetics and Genomics Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

**Bibiana Martinez** Division of Health Behavior, Institute for Prevention Research, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA

**Dinorah Martinez Tyson** College of Public Health, University of South Florida, Tampa, FL, USA

**Jean A. McDougall** University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA

Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA

**Angela L. W. Meisner** University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA

New Mexico Tumor Registry, Albuquerque, NM, USA

**Sheila Murphy** Annenberg School for Communication and Journalism, University of Southern California, Los Angeles, CA, USA

**Gila Neta** Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, MD, USA

**Carol Ochoa** Division of Health Behavior, Institute for Prevention Research, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA

**Alexander N. Ortega** Department of Health Management and Policy, Center for Population Health and Community Impact, Drexel Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA

**Laura B. Oswald** Department of Health Outcomes and Behavior, Mofftt Cancer Center, Tampa, FL, USA

**V. Shane Pankratz** University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA

Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA

**Frank J. Penedo** Department of Psychology, University of Miami, Coral Gables, FL, USA

**Bo Qin** Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

**Kimberly P. Raghubar** Baylor College of Medicine, Houston, TX, USA Texas Children's Hospital, Houston, TX, USA

**Aramandla Ramesh** Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, USA

**Amelie G. Ramirez** Department of Population Health Sciences, Institute for Health Promotion Research, UT Health San Antonio, San Antonio, TX, USA

**Kenneth S. Ramos** Texas A&M Health Science Center, Houston, TX, USA

**Yaneth L. Rodriguez** Division of Health Behavior, Institute for Prevention Research, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA

**Erik L. Ruiz** College of Public Health, University of South Florida, Tampa, FL, USA

**Rogelio Sáenz** University of Texas at San Antonio, San Antonio, TX, USA

**Michael E. Scheurer** Baylor College of Medicine, Houston, TX, USA Texas Children's Hospital, Houston, TX, USA

**Melissa A. Simon** Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA

**Min-ae Song** Department of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH, USA

**Sandra Soto** School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

**Andrew L. Sussman** University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA

Department of Community and Family Medicine, University of New Mexico, Albuquerque, NM, USA

**Lizeth I. Tamayo** Department of Public Health Sciences, The University of Chicago, Chicago, IL, USA

**Marisa S. Torrez-Ruiz** Division of Health Promotion and Behavioral Science, School of Public Health, San Diego State University, San Diego, CA, USA

School of Public Health, University of California, San Diego, CA, USA

**Edward J. Trapido** Epidemiology Program, LSU Health Sciences Center, School of Public Health, New Orleans, LA, USA

**Charles L. Wiggins** University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA

Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA

New Mexico Tumor Registry, Albuquerque, NM, USA

**Betina Yanez** Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA

**Valentina A. Zavala** Department of Public Health Sciences, Division of Epidemiology, University of California, Davis, CA, USA

### **Part I Introduction**

### **Chapter 1 Advancing the Science of Cancer in Latinos**

**Amelie G. Ramirez and Edward J. Trapido**

#### **Introduction**

Cancer is the second leading cause of death among non-Hispanic white (NHW) men and women in the United States—but is the leading cause of death among Latinos [1]. The US Latino population was 60.6 million in 2019, as one of the largest, youngest, and fastest growing minority groups in the United States, its population will nearly double by 2060, making up 27.5% of the projected US population [2, 3]. Thus, advancing the science of cancer in Latinos has become an imperative for the nation, as Latinos will contribute a signifcant portion to its future cancer burden.

The good news is that age-adjusted cancer mortality rate in the US population has steadily declined, dropping 31% from 1991 to 2018 [4]. Later in the decade, Latino cancer mortality rate also declined and is now lower than most other groups in the United States. For example, the overall cancer mortality rate (per 100,000 population) during 2014–2018 for Hispanics was 110.8–30.8% lower than NHWs [5].

Despite this encouraging news, cancer health disparities stubbornly persist among the US Latino population. While Hispanics as a group have lower incidence rates than NHWs for most cancers including breast, colorectal, lung, and prostate, they experience higher incidences of gallbladder cancer and infection-related cancers of the stomach, liver, and uterine cervix [1]. For some cancers such as liver and stomach cancers and pediatric acute lymphoblastic leukemia, Hispanics are diagnosed with more aggressive or advanced disease and experience higher mortality

A. G. Ramirez (\*)

E. J. Trapido Epidemiology Program, LSU Health Sciences Center, School of Public Health, New Orleans, LA, USA

Department of Population Health Sciences, Institute for Health Promotion Research, UT Health San Antonio, San Antonio, TX, USA e-mail<EMAIL_ADDRESS>
rates than other groups [6]. Furthermore, compared to NHWs, Hispanics are more likely to be diagnosed with cancer at a later stage when it is more diffcult to treat, and they are also more likely to experience longer delays from diagnosis to treatment leading to poorer treatment outcomes.

Why these disparities exist is the result of a complex interplay of many factors. One determinant is socioeconomic status (SES). Compared to NHWs, Hispanics are more likely to live in poverty, which also means they are less likely to have health insurance and access to health care, including cancer screening and preventive care. They are also more likely to have fewer cancer treatment options, more treatment delays, and lower treatment adherence rates [7]. Other important factors are in the cultural domain. Hispanic ethnic identity, values, and beliefs can infuence healthy behavior, engagement with health providers, and how one copes with cancer diagnosis and treatment. Generational status, level of acculturation, and country of origin are also associated with varied cancer outcome. Paradoxically, low acculturation is associated with lower cancer burden despite being associated with lower income and less access to health care. As individuals become more acculturated to the United States, however, their cancer incidence rates rise and may even surpass that of NHWs [1]. Finally, differences in cancer burden and treatment outcomes may be a function of inherited genetic variation. Hispanics are not a homogeneous group, but rather comprise subgroups that differ by geographic regions of origin and varying degrees of genetic admixture from predominantly Indigenous American, African, and European ancestries.

#### **Building Collaboration for Action**

Because of the multifactorial nature of cancer disparity, fnding solutions requires a collaborative and transdisciplinary approach. The second national conference— Advancing the Science of Cancer in Latinos—was designed to provide opportunities for collaboration to build implementation science to better address cancer health disparities and reduce the burden of cancer in Latino communities. Held in San Antonio on February 26–28, 2020, the conference was co-hosted by the Mays Cancer Center and the Institute for Health Promotion Research at UT Health San Antonio and was sponsored by the National Institute on Minority Health and Health Disparities. Bringing people together from across the cancer continuum, it included those with expertise in genetics, social determinants of health, early detection and screening, diagnosis, treatment, and survivorship. Furthermore, it brought the voice of the community, researchers, educators, and intervention specialists. Attending were people from academia, government, professional organizations, businesses, and non-governmental organizations. So, the breadth of expertise and experience was wide. There were opportunities for formal and informal discussions during the meeting, and the material presented refected this diversity of backgrounds and interests. Joining people with these backgrounds was meant to serve as a stimulus for developing new joint research and interventions—particularly in implementation and dissemination science.

The following sections set some context and briefy describe the papers contributed by many of the conference presenters. Note that the terms Hispanic, Latino/a, and Latin(x) are used interchangeably and refect the preferences of the authors or US federal designation.

#### **Vulnerable Populations and Health Threats in the Latino Community**

Vulnerable populations experience signifcant health disparities, suffering greater disease risk, morbidity, and mortality than the general population. The vulnerable among them includes racial/ethnic minorities, the poor, those with chronic health conditions or disabilities, the elderly and the young, those who are socially vulnerable such as members of the LGBTQ+ community, and those who are geographically isolated.

**Acute Lymphoblastic Leukemia (ALL) in Latino Children** Latino children are a vulnerable population who experience a higher incidence of acute lymphoblastic leukemia (ALL) and poorer treatment outcomes than non-Latino children. This cancer disparity, like many others, is cross-cutting along the cancer treatment continuum from heightened risk to less favorable treatment outcome and untoward treatment effects that last into survivorship. Brown et al. describe research that suggests Latino children with ALL may be more vulnerable to the adverse neurotoxic effects of CNS-directed therapy with methotrexate. From their own study of pediatric patients, they found a nearly 2.5-fold increased risk of neurotoxicity in Latino pediatric patients compared to non-Latino patients. In addition to these short-term adverse effects of therapy, they propose that Latino survivors may also be more vulnerable to long-term neurocognitive impairment that affects quality of life in survivorship. Why these disparities exist is unknown and may be related to inherited genetic variation and sociocultural differences such as acculturation and socioeconomic status.

**Population Health Challenges and the Affordable Care Act** The Patient Protection and Affordable Care Act (ACA) became the US law in 2010. Its purpose was to make health insurance more affordable and accessible by offering insurance plans through marketplaces, expanding Medicaid, and providing incentives to improve cost and quality of care. In Part II, Ortega describes how the ACA affects healthcare access and utilization among Latinos. His research confrms that, in general, Latino adults and youth overall have beneftted from the ACA; however, they still fared worse when compared to non-Latino whites. A subgroup comparison of Latino heritage groups (Puerto Rican, Mexican, Cuban, Central American, and other Latino) showed that most reductions in disparities were experienced between Puerto Ricans and non-Latino whites; Mexicans and Central Americans experienced more pervasive inequities—especially non-citizens and those in states that have not expanded Medicaid as part of the ACA.

**Financial Hardship and Food Insecurity** For cancer patients and survivors, the high cost of cancer treatment and care can cause fnancial hardship such as inability to pay medical bills, debt, and bankruptcy. Such hardship may put cancer survivors at risk for food insecurity—the inability to access enough food for a healthy lifestyle because of insuffcient money or other resources. McDougall et al. present results from a cross-sectional survey comparing fnancial hardship and food insecurity among population-based Hispanic and non-Hispanic cancer survivors in New Mexico. They found that Hispanic cancer survivors were more likely than non-Hispanic cancer survivors to be unable to cover the cost of medical bills and were more likely to reduce spending on food and clothing as a result of cancer treatment. The prevalence of food insecurity among Hispanic cancer survivors in the year after cancer diagnosis was about 47%—considerably higher than the 36% for the overall project and 11% for US adults. While there were no signifcant differences by ethnicity, new and persistent food insecurity for the project was strongly associated with forgoing, delaying, or having to make changes to cancer care. The results of the study point to the need for food-insecurity screening and interventions that specifcally address fnancial hardship and food insecurity among cancer survivors.

#### **Disparities Research Along the Cancer Control Continuum**

#### *Cancer Prevention and Screening*

**Strength-Based Approach to Cancer Prevention** US Latinos overall have a lower cancer burden than other groups; however, as Latinos become acculturated to US culture, their risk for cancer rises [1]. Torrez-Ruiz et al. point out that less acculturated Latinos still retain the cultural and behavioral patterns of their home country, which infuences the quality of diet and the level of physical activity—two lifestyle factors that contribute to cancer risk. They consume more nutrient dense foods such as fruits, vegetables, and whole grains and are more physically active than their more acculturated US counterparts. As Latinos become more exposed to US culture, they often become less active and adopt a less healthy diet. To lessen these effects of acculturation, the authors advocate using a strength-based approach that focuses on the positive aspects of Latino culture to inform intervention research. Specifcally, they propose developing culturally appropriate interventions that leverage values such as collectivism, *personalismo*, and *familismo*—Latino cultural elements that can promote healthy protective behaviors and lower cancer risk.

**Cervical Cancer Elimination** Some viral and bacterial infections are linked to cancer; the four most common cancer-related infectious agents are human papilloma virus (HPV), hepatitis B virus (HBV), hepatitis C virus (HCV), and *Helicobacter pylori*. Fortunately, many of these infections can now be treated or prevented, making them potentially modifable risk factors [8]. In her paper, Giuliano describes the goal and strategy for preventing HPV-related cancers (cervical, vulvar, vaginal, anal, oropharyngeal, and penile), the majority of which are preventable with the use of three readily available tools—HPV vaccine (e.g., Gardasil and Gardasil 9), cervical cancer screening, and treatment for pre-cancerous lesions. Despite the fact that these tools exist, the cervical cancer incidence in the US Hispanic population is higher than in other groups; Hispanic women are about 40% more likely than non-Hispanic white women to be diagnosed with cervical cancer [9]. Furthermore, among non-Hispanic white women, the incidence of cervical cancer declines after age 40, but among Hispanic women, the incidence of cervical cancer continues to increase with age. These disparities in incidence likely result from women either skipping screening or not receiving treatment. Compared to other groups in the United States, vaccine uptake is as high or higher in the adolescent Hispanic population, but to eliminate cervical cancer, we must promote all three prevention tools—vaccination, screening, and follow-up treatment for abnormal dysplasia.

#### *Cancer Treatment*

**Treatment Delays among Latino Breast Cancer Patients** Breast cancer incidence among Hispanic women is lower than that of non-Hispanic white women, yet Hispanic women are more likely to be diagnosed with more aggressive disease and to experience delays in treatment, contributing to worse outcomes. Malinowski and Chavez Mac Gregor describe some of the unique challenges in cancer care delivery that Hispanic breast cancer patients face including the detrimental effects of treatment delays. To determine whether biological factors alone can explain disparities in outcome, the authors evaluated breast cancer patients treated with similar neoadjuvant preoperative chemotherapy and found that race or ethnicity was not associated with the rates of pathological complete response. In another study, they analyzed patients taking part in phase II/III clinical trials and found that when Hispanic breast cancer patients received uniform treatment and follow-up in a highly controlled setting, their survival outcomes were similar to that of non-Hispanic women. The authors hypothesized that differences in outcomes between Hispanics and non-Hispanics may be less a function of biology and more the result of differences in social determinants of health such as lower economic stability, language differences, lower health literacy, lack of health insurance, and poorer access to regular medical services.

 These disparities run the gamut from lower mammography screening prevalence and diagnostic delays to longer times from diagnosis to surgery and delays in chemotherapy, radiation therapy, and endocrine therapy. To address this issue, the authors are beginning a new qualitative study to identify why breast cancer patients experience delays in the start of chemotherapy. Using validated instruments, they will examine factors at the operational, medical, and personal/social level including social support, health literacy, and trust in health providers.

#### *Genetic Ancestry and Precision Medicine Approaches*

**Genetic Ancestry and Breast Cancer Subtypes** Breast cancer is the most common cancer among Hispanic women.  There are intrinsic biological subtypes of breast cancer, each associated with different prognoses. In clinical practice, these subtypes are inferred by immunohistochemical markers for the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Compared to the other subtypes, ER−/PR− tumors [10] have fewer treatment options and poorer prognosis. Tamayo et al. describe results of studies examining correlations between genetic ancestry and breast cancer subtypes among US Hispanic or Latin American patients. According to the authors, studies show that Hispanic women have a 20–40% higher risk than non-Hispanic white women of developing ER−/PR− HER2+ and ER−/PR− HER2− breast cancer. There is also an emerging body of research that suggests there is an association between genetic ancestry of Hispanic women and breast cancer subtype. For example, evidence points to an association between the degree of Indigenous American ancestry and HER2+ tumors and an association between degree of African ancestry and ER− tumors. The authors conclude that more studies are needed to improve understanding of tumor subtype etiology of breast cancer in admixed minority populations.

**Precision Medicine Approaches for Patients at Risk of Lung Cancer** African ancestry is associated with worse clinical outcomes for chronic obstructive pulmonary disease (COPD) and lung cancer, and the degree of African ancestry varies among some Latinx subgroups. Thus, there is a need to develop risk stratifcation strategies and targeted lung cancer therapies that consider genetic admixture among Latinx populations. Lung cancers in all racial and ethnic groups are often diagnosed too late for a surgical cure, so there is also a need for early biomarkers of disease.

Ramos et al. propose that the current precision medicine approaches for treating lung cancer should be refned by improving risk stratifcation for patients with COPD, who are at heightened risk for lung cancer. In their paper, Ramos and his colleagues review their research on ORF1p—a protein encoded by the retroelement, Long Interspersed Element-1 (LINE-1). Overexpression of ORF1p is associated with genetic instability and poor prognosis in patients with non-small-cell lung cancer (NSCLC). Because it accumulates in lung cancer cells and is found in circulating exosomes, the authors hypothesized that circulating ORF1p may be used as a sensitive biomarker of genetic instability in patients with COPD and lung cancer. Further, the authors found that the cellular protein, nucleolin (NCL), regulates ORF1p expression and that using NCL antagonists can stop NSCLC growth in a mouse model of lung cancer.

#### *Outcomes and Survivorship*

**Obesity and Breast Cancer Survivorship** The number of Hispanic breast cancer survivors in the United States is increasing as the Hispanic population grows and breast cancer survival improves. Further, this growing population is more likely than non-Hispanic whites to experience increased obesity and related comorbidities into survivorship. To address these issues, Bandera, Hong, and Qin compared Hispanic and Black breast cancer survivors in a pilot study and found that the cohort of Hispanic breast cancer survivors had lower patient-reported health-related quality of life (QoL) scores, particularly those who were obese. Among breast cancer survivors, the association between obesity and patient-reported outcomes is poorly understood and not well studied among Hispanic women, emphasizing the need for more research on cancer survivorship in this vulnerable population.

**Latino Men Cancer Survivors** Compared to Hispanic women and other racial/ ethnic groups, Hispanic men overall experience higher incidence of most cancers and higher cancer-related mortality. The number of Hispanic men cancer survivors (HMCS) continues to grow and their unique supportive care needs have not been adequately addressed. Based on evidence from recent preliminary research, Martinez Tyson and Ruiz describe unmet supportive care needs of Hispanic men cancer survivors. HMCS participants reported the need to overcome language barriers so that they not only can understand treatment information but also can ask clarifying questions; they prefer bilingual conversation and do not trust that interpreters accurately convey their concerns. These men want culturally competent care that includes, for example, the constructs of *confanza* and *personalismo* so that they can build better rapport with providers and speak more openly about their concerns. Many participants felt the need for more information about their treatment and its effects, a better understanding of post-treatment follow-up including screenings, and a more holistic approach that focuses on overall health and wellbeing. Along with the demands of cancer therapy or employment changes, many were troubled by changing gender role expectations within the family brought about by the fnancial and emotional burden placed on female family members. Furthermore, the authors found many HMCS want to connect with other survivors and discuss their shared experiences. How do HMCS cope with their cancer diagnosis? Many survivors believe that overall attitude is important in overcoming the disease process; they advocate maintaining a positive outlook through optimism, humor, and faith in God. For some, incorporating home remedies into the overall treatment plan and making lifestyle changes gave them a sense of agency and self-effcacy. They also reported their social support systems helped them feel less isolated and more able to contend with the logistics of attending appointments and going to treatments.

**E-health Interventions in Cancer Control and Survivorship** Now that cell phone use is becoming commonplace among US Hispanics, smartphone applications can be used to deliver scalable, evidence-based supportive care interventions, reaching out to those who may have logistical barriers to in-person cancer care. Hispanic breast cancer survivors (BCS) experience worse health-related quality of life (HRQOL) and symptom burden than non-Hispanic BCS. To reduce these disparities in psychosocial outcomes, Baik et al. used community-engaged research approaches to develop and evaluate two culturally informed, bilingual smartphone applications—*My Guide* (intervention) and *My Health* (control)—tailored to address the unique needs of Hispanic women. Even though the results were similar between the intervention and control groups, the researchers were able to demonstrate the feasibility and effcacy of these applications in improving cancer symptom burden and HRQOL. Participants of both groups said they would have liked to have also used these applications during breast cancer treatment, so the researchers expanded the scope of *My Guide* to address the needs of Hispanic women in active breast cancer treatment. *My Guide* and the newer *My Guide for Breast Cancer Treatment* are among the frst bilingual, supportive-care smartphone applications, which have the potential to improve patient-reported outcomes among Hispanic women during both active cancer treatment and into survivorship.

#### **Cross-cutting Research and the Future of Cancer Care**

**Optimizing Engagement of the Latino Community in Cancer Research** Baezconde-Garbanati et al. describe signature initiatives designed to engage Latino communities in cancer research by reducing barriers toward inclusion. Two of their population-based studies in Los Angeles—*Es Tiempo* and *Tamale Lesson*—were designed using a community-based participatory research approach to optimize participation and retention of Latinos in cervical cancer and HPV trials. These model interventions included *promotores de salud* and community members who took part in all stages of research, from conceptualization, recruitment, translation, cultural adaptation, and information dissemination. The intent was to make the members of the participating communities feel they were an essential part of the research. A promising third exploratory study used virtual reality to better understand vaccine hesitancy and explore end-of-life improvements for immigrant Latinos. To infuence attitudes and behaviors that place Latinos at risk for cancer, the researchers used bidirectional communication; educational information was broadcast out to the community while knowledge was received by academic researchers who learned about community issues and barriers to participation. Their strategies for increasing Latino participation in cancer research focused on three key areas: (1) information delivery or knowledge transfer; (2) consultation with Latino community stakeholders and partners, including community advisory boards, patient advocates, and citizen scientists; and (3) collaboration with community opinion leaders.

**Advancing Inclusive Research** Melissa Gonzales from Genentech describes how one biotechnology company is addressing clinical research disparities to achieve personalized healthcare for everyone, including the most vulnerable Hispanic communities. Their initiative—*Advancing Inclusive Research*—aims to expand inclusion of diverse patient populations into their clinical research. To accomplish this, they intend to imbed inclusive research principles so that clinical trial enrollment refects real-world populations; expand site networks to include more diverse catchment areas; and identify and remove barriers to participation in clinical trials such as providing transportation and child care. Further, they will increase genomic data and scientifc insights from underrepresented populations and will leverage relationships with external partners to develop strategies for increasing participation of underrepresented groups in clinical trials.

**Exposome-wide Association Study Approach** Because Latino cancer disparities are so persistent and their underlying causes so varied, Juarez et al. propose that we need a new way of conducting disparities research that accounts for environmental, endogenous, and social factors. They suggest using a research strategy based on the exposome—all of the external and internal exposures experienced by individuals across their lifespans from conception to death and how these exposures affect health. Applying an ExWAS approach can help identify how environmental exposures alter key biological pathways at the cellular, molecular, and system level, and help explain the increased risk for population-level cancer disparities among Latinos. Measured exposures can be linked to biochemical and molecular changes through the use of prognostic and diagnostic biomarkers based on "omics" technologies such as genomics, epigenomics, transcriptomics, metabolomics, proteomics, and lipidomics.

**Implementation Science** There is often an unacceptable lag time of years and even decades before new research evidence becomes part of broadly adopted medical practice, and many new, effective, health interventions are not reaching Latino populations to the same degree as the general public. Gila Neta from the National Cancer Institute (NCI) points out that to ensure new cancer discoveries reduce the cancer burden for Latinos, researchers must focus not only on what evidence-based interventions can improve outcomes but also on how those interventions can be adopted, implemented, and sustained. To bridge the gap between research and practice, NCI supports research in implementation science—the study of strategies to adopt and integrate evidence-based health interventions into clinical and community settings, improving individual outcomes and beneftting population health [11]. This science also includes studying strategies to de-implement practices that are ineffective, unproven, low value, or harmful. In her paper, the author describes the discipline and goals of implementation science and the role of the National Institutes of Health (NIH) in providing trans-NIH funding opportunities in this feld. Neta further emphasizes that implementation science must consider the multilevel context and engage stakeholders in two-way communication so that strategies not only address critical barriers but are also workable and appropriate for the relevant settings and populations, and are likely to be integrated, sustained, and scaled.

**The Changing Demography of Cancer** Even though Latinos have a lower cancer burden than other groups in the United States, their disproportionate growth will likely shift the demography of cancer in the future [12]. Sáenz examined this trend by analyzing recent cancer statistics from the CDC and population projections from the US Census Bureau. The analysis was based on two time periods—past (1999–2016) and future (2016–2060).

Sáenz found that compared to non-Latino whites and blacks during 1999–2016, US Latinos had the lowest age-adjusted cancer incidence and death rates, and they made up only a fraction of the nation's cancer cases (8.2%) and deaths (6.6%) in 2016. However, because of their growing population, Latinos contributed to nearly one-ffth (18.8%) of the increase in US cancer cases and two-ffths (39.5%) of the increase in cancer deaths between 1999 and 2016. Because the population growth of Latinos is expected to outpace that of non-Latinos, the percentage of Latino cancer cases and deaths will likely double from 2016 to 2060. Latinos will account for one-third of the US projected increase in cancer cases and one-fourth of the projected increase in cancer deaths during this time frame. By 2060, Latinos will still be a younger group, so they will make up a larger share (25%) of cancer cases and deaths among those less than 45 years.

The author points out that the growing presence of Latinos in the future has implications for public policy. For example, current inequities in access to affordable health care and lack of health insurance will increase the risk of Latinos having cancer and dying from the disease. In addition, public policy that discourages migration from Mexico to the United States could erode the Latino morbidity and mortality advantages they currently possess.

#### **Conclusion**

The Advancing the Science of Cancer in Latinos conference brought together a diverse group of health professionals to encourage collaboration and a free exchange of ideas from different perspectives; the papers in the following chapters show the breadth of their research across the cancer care continuum. Exploring this book, you

will learn about vulnerable Latino populations, Latino lifestyles, and health threats in the Latino community; cancer prevention, cancer outcomes, and survivorship among Latinos; genetic ancestry and precision medicine; advances in cancer therapy, clinical trials, and engaging Latinos in cancer research; and implementation science and innovative technologies. The papers and posters presented here are part of an ongoing dialogue, providing new insights and solutions to the problem of cancer disparities among Latinos.

#### **References**

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

### **Part II Health Threats in the Latino Community**

### **Chapter 2 Applying an Exposome-wide Association Study (ExWAS) Approach to Latino Cancer Disparities**

**Paul D. Juarez, Darryl B. Hood, Min-ae Song, and Aramandla Ramesh**

#### **Introduction**

#### *Exposome*

The exposome was introduced into the literature by Dr. Christopher Wild in 2005 [1] as all exposures a person has in one's lifetime and the biological mechanisms and processes through which those exposures affect health. Introduction of the exposome paradigm has challenged us to reconsider how we consider the causes of cancer and other chronic diseases; research methods and analytics we use to understand them; and the implications for clinical practice, health disparities, and public health policy. Key elements of the exposome include a real-world approach, inclusion of multiple environmental exposures and internal and external environments, and the ability to assess the effects of exposures at key developmental periods across the life course and trans-generationally. The main aim of exposomics is to provide an early warning system for understanding disease pathways, which will allow early targeting of prevention and early intervention strategies.

P. D. Juarez (\*)

Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA e-mail<EMAIL_ADDRESS>
D. B. Hood · M.-a. Song Department of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, OH, USA e-mail<EMAIL_ADDRESS><EMAIL_ADDRESS>
A. Ramesh

Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, USA e-mail<EMAIL_ADDRESS>
The exposome consists of one's internal and external environments. The external or eco-exposome has been operationalized by Juarez [2] as four broad domains: the natural, built, social, and policy environments. He later added health and healthcare as a ffth domain. Each domain consists of subdomains: natural (air, water, land), built (places you live, work, and play), social (demographic, social, economic, and political factors), and policy (federal, state, and local government policies and regulations). Each subdomain is further broken down into categories, subcategories, and variables. Juarez and colleagues have developed a national, public health exposome, relational-data repository with metadata, comprising over 55,000 variables covering the period 2003–2018 [3].

The internal or endo-exposome, on the other hand, has been described as the body's endogenous metabolic response to environmental infuences, which modulate vulnerability to subsequent exposures [4]. Understanding the biological effects and responses to environmental exposures can shed light onto the mechanistic connections between exposures and health [5]. An exposome approach provides a dynamic risk profle of multiple risk and protective factors and thus is particularly applicable to chronic disease onset, progression, and outcomes.

Applying an exposome-wide association study (ExWAS) approach to cancer and cancer disparities provides a novel way for conceptualizing the relationships of multiple chemical and non-chemical exposures in the etiology and progression of cancer at key developmental periods, over the life course, and across generations. Understanding the biological effects of exposures provides new opportunities for measuring why populations with similar exposure profles experience similar poor health outcomes [6].

#### *Public Health Exposome*

Juarez [2] created an ontology, called the public health exposome (PHE), to represent the vast array of external environmental exposures. In addition, he has curated a database, that to date, includes over 55,000 variables. The PHE data repository contains both annual and county measures of health and environmental exposures from the natural, built, social, and policy environments for 3141 counties and county equivalents over 15 years (2003–2018) (Fig. 2.1). The PHE is fully curated with metadata and a searchable data dictionary. Metadata include names and defnitions of variables; units of measurement; date, time, and location of data collection; the identity of the individual who collected the data; and sampling design. The PHE data repository has been geocoded and harmonized at an annual and county level and provides spatial–temporal and contextual environmental data for understanding place-based health disparities. The data repository includes crosswalks that allow for the aggregation of data obtained in smaller geographic and temporal units upward to the county or annual levels. Other spatial resolutions included in the data repository are point, polygon, block groups, census tracts, zip codes, 3 km grids,

1 km grids, metropolitan statistical areas (MSAs), states, and regions. Other temporal units included in the dataset are daily, monthly, quarterly, and annual measures.

Most of the data in the PHE data repository were obtained from publicly available web sites at no or low cost, such as Centers for Disease Control and Prevention (WONDER, BRFSS, CDC Tracking Network, National Center for Health Statistics, National Diabetes Surveillance System), National Cancer Institute (small area estimates for cancer-related measures), North American Land Data Assimilation System, National Oceanic and Atmospheric Administration, Federal Emergency Management Agency (National Flood Hazard Layer), US Environmental Protection Agency (EJ Screen, Superfund sites, Environmental Quality Index, National Air Toxics Assessment), US Geological Survey (water usage), HRSA Data Warehouse (health professions shortage areas, medically underserved areas), Health Indicators Warehouse (morbidity, mortality), US Department of Agriculture (Food Environment Atlas), Robert Wood Johnson (County Health Rankings), US Census (2000, 2010, decennial census, bridged race population estimates, small area income and poverty estimates), American Community Survey, Agency for Toxic Substances and Disease Registry (Social Vulnerability Index), Dartmouth Atlas (Medicare claims data), AIDSVU, Department of Labor (unemployment statistics), Department of Education (graduation rate, student enrollment, adult literacy), US Department of Interior (National Land Cover/Land Use), and US Post Offce (residential and business vacancies).

**Natural Environment** The natural environment consists of datasets of climate, weather, and natural resources that affect human survival and economic activity. It includes chemical exposures found in the air, water, and land that humans interact with on a daily basis. Studies have shown that exposure to different components of the natural environment can have an independent, positive or negative effect on health and health-related behaviors. While much is known about the adverse effects of chemical emissions that are released into the air, water, and land, there is growing evidence that exposure to positive attributes of the natural environment, such as green space and state and national parks and forests, can mitigate the impact of chemical and non-chemical stressors on health and health-related behavior. The PHE database includes spatial–temporal measures of exposure from the air, water, and land that humans interact with on a daily basis such as meteorological conditions (particulate matter, minimum/maximum temperature, and maximum Heat Index); EPA Air Quality System (criteria pollutants, particulates, toxins); and chemicals from emissions, pesticides, and land cover/land use.

Fine particulate matter measures (PM2.5) and heat metrics data were determined using models developed by Dr. Mohammad Al-Hamdan (USRA) for an EPA STAR grant; he developed algorithms to generate high resolution, daily, 3-km, PM2.5 and 1-km, heat exposure products (minimum/maximum and maximum heat index) for the period 2003–2018 for 12 southern states. Through a subcontract with the HDRCOE at Meharry (Juarez, PD, PI), Dr. Al-Hamdan applied a novel spatial surfacing algorithm to estimate daily, 3-km, PM2.5 surfaces/grids in the 12 southeastern states. He did this by combining PM2.5 data derived from MODIS AOD satellite data (12 km grid) with ground observations of PM2.5 data reported from EPA ambient air quality monitoring stations of the EPA Air Quality System (AQS). To generate high resolution daily exposure measures, Al-Hamdan frst validated AOD-PM2.5 regression models for 36 cities across the 12 southeastern states of the SCCS. These combined regional regression models then were integrated into a modifed version of a spatial surfacing algorithm that merges the MODIS-derived and EPA/AQS PM2.5 data to create daily, 3-km, PM2.5 spatial surfaces/grids for the 12 southeastern states, geographic region of the SCCS. These data are available to center investigators [7].

**Built Environment** The built environment includes the physical characteristics of places we live, work, and play (e.g., homes, buildings, streets, open spaces, and infrastructure) as well as patterns and types of development, building location and design, and transportation infrastructure in communities that can have a direct or indirect impact on health. The degree to which the built environment is important to health may differ, depending on the broader social context. For instance, the location of supermarkets, fast-food restaurants, farmers' markets, liquor stores, pharmacies, and health-care facilities can have a signifcant effect on people's diets and their health. Likewise, inaccessible or nonexistent sidewalks and bicycle or walking paths may contribute to sedentary habits and a person's level of physical activity and can contribute to poor health outcomes such as obesity, cardiovascular disease, stroke, and diabetes. Measures of the built environment included in the public health exposome database include land use, TRI facilities, highways, neighborhood resources, health-care facilities, green space, parks, and occupational codes.

**Social Environment** The social environment (i.e., social determinants of health) constitutes the conditions in which people are born, grow, work, live, and age and are shaped by social/cultural norms, economic and employment policies and systems, the distribution of money, power, and resources, and political systems. Social determinants constitute the conditions of daily life and include factors like socioeconomic status, poverty, education, employment, crime, residential segregation, and social support networks, and provision of and access to culturally and linguistically appropriate health-care services. Social environmental stressors in the public health exposome database include population level measures of social, demographic, economic, and political variables derived principally from the US Census/ American Community Survey, as well as measures of crime and social stress, such as GINI (measure of economic inequality), residential segregation, and multidimensional measures of social deprivation.

#### **Applying an Exposome-wide Association Study (ExWAS) Approach to Latino Cancer Disparities**

There is no single cause of Latino cancer disparities. First, cancer is not a single disease. Rather, cancer can start anywhere in the body; where it starts is how it is named (lung, breast, colorectal, etc.). The causes of cancer arise from genetic mutations, often caused by the body's response to chemical and non-chemical exposures in one's environment. Cancers are alike in some ways, but they are different in the ways they grow and spread. An ExWAS approach to Latino cancer disparities provides a framework for understanding how multiple environmental exposures lead to biological changes that produce certain health outcomes and lead to populationlevel disparities (Fig. 2.1).

Population-level cancer disparities may arise from common exposures experienced by subpopulations across a state or region or from place-based environmental exposures experienced by people who live in a neighborhood. While much attention has been given to the role of social determinants in Latino cancer disparities, to date, much remains unknown about how social determinants get under the skin to actually cause cancer and lead to disparate outcomes. The exposome provides a model for understanding the biological mechanisms and pathways through which nonchemical stressors, such as social factors, can lead to cancer.

#### **Cancers in Latinos and Health Disparities**

Cancer statistics compiled by the American Cancer Society [8] for the years 2018–2020 indicate that among Latinos, lung, liver, and colorectal cancer were expected to account for 16, 12, and 11%, respectively, of the deaths in men; while breast, lung, and colorectal were expected to contribute to 16, 13, and 9%, respectively, of the deaths in women. In regard to the emergence of new cases, prostate, colon, and lung cancers were expected to constitute 21, 12, and 8%, respectively, in men; while breast, thyroid, and uterine cancers amount to 29, 8, and 8%, respectively, in women. From a health disparities standpoint, the following are the predominant cancers in Latinos.

#### *Lung Cancer*

Even though lung cancer is one of the leading causes of deaths in Latinos, mortality due to this disease is low compared to other racial groups [9]. A study conducted in South Florida revealed that men of Cuban decent have higher mortality rates than their counterparts from Puerto Rico and South America [10]. It has been reported that 48% of Latino patients with metastatic lung adenocarcinomas have epidermal growth factor receptor (EGFR) gene mutations [11].

#### *Breast Cancer*

A greater incidence of breast cancer was noticed among Latinas living in the Southwestern United States and South Florida [12]. However, in a cohort of breast cancer patients from Puerto Rico, the prominent subtypes were found to be Luminal A (69%), followed by triple negative (15%), Luminal B (10%), and human epidermal growth factor receptor 2 positive (HER2+; 6%). The clinicopathological characterization of breast cancer in this cohort was incomplete because of study limitations (late-stage diagnosis, missing mammography records) and lack of insurance coverage, which presents a health disparity [13].

#### *Liver Cancer (Hepatocellular Carcinoma; HCC)*

Chronic liver disease, including cancer, ranked fourth in terms of deaths for Latino men between ages 55 and 64, and Latinos are 1.6 times more likely to die from liver disease compared to the US general population [14]. Consumption of contaminated diet and viral infections were the reported contributors to liver cancer in Latinos. A study conducted by Ramirez et al. [15] found that Latinos in Texas who had liver cancer had greater levels of afatoxins (carcinogenic chemicals found in contaminated corn, nuts, seeds, and rice) than those without the disease. The Ramirez team also reported that Latinos in Texas had the highest incidence of liver cancer in the United States [16].

Hepatitis C virus (HCV) infection is another risk factor for liver cancer. HCV infection was found to be signifcantly higher in Latinos from South Texas compared to controls [16]. Afatoxin exposures and Hepatitis B infections were reported to show an additive effect toward development of HCC [17]. A systematic review of HCC among Latinos in South Texas revealed that metabolic syndrome (diabetes and obesity), viral hepatitis (B and C), genetic predisposition, environmental exposures, diet (consumption of afatoxin-contaminated diet), and lifestyle (smoking) were the most likely risk factors [18].

#### *Colorectal Cancer (CRC)*

CRC was the second most diagnosed cancer accounting for 13% of cancer deaths (in each sex) in Puerto Rico, and lack of knowledge about this disease was responsible for a low screening rate [19]. The incidence of CRC was reported to be high in Latinos living near the United States–Mexico border [20] and also in New Mexico [21]. Latinos were reported to develop distal colon tumors more frequently compared to the general population [22] and when detected they were at a late-stage CRC compared to their non-Latino counterparts [21]. The development of CRC has been attributed to environmental exposures, smoking, diet, and obesity [20].

#### *Prostate Cancer*

Even though prostate cancer incidence among Latino men is lower than other racial groups, it still ranks fourth in terms of mortalities [23], and frst among the new cancer cases to be detected [8]. Prostate cancer shows heterogeneity among Latinos. A 20-year Surveillance Epidemiology and End Results Program (SEER) data analysis revealed that prostate cancer characteristics in Latinos living in the United States were specifc to their country of origin. Mexicans, Cubans, and Puerto Ricans registered higher prostate-specifc antigen scores and advanced stage cancer compared to Dominicans and South-Central Americans [24].

#### *Thyroid Cancer*

The SEER data revealed that the age-adjusted incidence of papillary thyroid carcinoma was high in Puerto Rican women compared to the mainland Latinos, non-Latino Whites and Blacks [25]. Thyroid cancer in Puerto Rican men showed a similar trend, with a lower incidence than women. The follicular histology, occurrence of large tumors, localization of disease, and single nucleotide polymorphisms are some characteristics of Latino thyroid cancer patients [26].

#### *Uterine and Cervical Cancer*

The SEER database review revealed that both endometrioid and non-endometrioid carcinoma rates are on the rise among Latinos [27]. Latinos had more advanced cervical cancer disease and higher mortalities compared to Caucasians, African Americans, Asians, and other racial groups [28, 29]. The incidence of HPV-related cancers was also high in Latinos, and the risk was higher among HIV-infected Latinos than in the general population [30].

#### **Biomarkers of Cancer**

#### *Biomarkers from the Perspective of Exposure Biology*

As mentioned, environmental and life-style factors play a major role in assessing the etiology of cancer. In this regard, biomarkers play a dominant role in delineating the exposome as they are measures of either healthy or carcinogenic processes. The three major categories of biomarkers that assist in cancer risk assessment are as follows.

**Biomarkers of Susceptibility** These are markers of increased vulnerability to the effects of suspected environmental carcinogens, which can be measured in a tumor sample or organ system. As most cancers arise from gene–environment interactions (individuals' genetic susceptibilities against their chemical exposure histories), these markers are used to identify individuals/populations that are at risk from carcinogenic exposures. The biomarkers that come under this category are variants in genes that encode biotransformation enzymes such as cytochrome P450 (CYP) isozymes CYP1A1, CYP2C9, CYP2E1; N-acetyltransferase 2 (NAT2); serum paraoxonase and arylesterase 1 (PON1); epoxide hydrolase 1 (EPHX1); aryl hydrocarbon receptor (AhR); glutathione S-transferase theta 1 (GSTT1) null phenotype; DNA repair and oxidative damage repair genes (risks for leukemia and non-Hodgkins Lymphoma) [31].

**Biomarkers of Exposure** These markers highlight the signifcance of various exposure pathways and cancer risk; they allow measurement of carcinogens of interest in the body from an accessible biological matrix such as blood, urine, normal, and tumor tissues. For individuals who are either occupationally or dietarily exposed to polycyclic aromatic hydrocarbons (PAHs) (risks for lung cancer [32]) or afatoxin B (risks for liver cancer [15]) either individually or in mixtures, metabolites of these chemicals in serum or urine serve as markers of exposure.

**Biomarkers of Effect** These markers are responses elicited as a result of interaction of an organism with the exposome mentioned in the earlier sections. The responses are measured at the level of tissue, organ, and whole organism etiology. The widely measured biomarkers of cancer are F2 isoprostanes (risks for prostate cancer [33], C-reactive protein (CRP), interleukin (IL) 6 (risks for lung cancer [34]), expression of p53, estrogen receptor α and β, progesterone receptor, cytokeratin 5 and 6, cell proliferation marker Ki-67, cancer antigen 125 marker (risks for breast and ovarian cancers [13]), and micro RNAs (risks for CRC [35]).

#### *Biomarkers from the Perspective of Systems Biology*

Most of the cellular macromolecules such as proteins, DNA, RNA, and lipids are regulated in cancer through various pathways. Their altered profles in blood and tissues provide clues on their role in tumor formation, progression, and metastasis. Some omics data are potential biomarkers of aggressiveness of dysplastic cells and underlying pathways (diagnostic markers), while in some instances the altered pathways may serve as markers of intermediate steps or likelihood of more changes downstream (prognostic markers). Gaining awareness of the dynamics of various systems in the body and how vulnerabilities in one system and the associated symptoms (tumor growth) could impact other systems brought into light the importance of the systems biology concept in cancer research [36]. The systems biology approach could be capitalized by employing "omics" approaches. These approaches will unravel new biomarkers, which when standardized and validated could provide information on mechanism of action for carcinogens and the key biochemical and molecular pathways involved. Mentioned below are some examples of different omics approaches used by researchers to study the cancer disparities in Latinos. Most of the studies reported herein are one-step omics studies (discovery only). Very few studies have conducted two-step studies (discovery and validation). In addition to lack of literature, the small sample size used in the published studies is another limitation.

**Genomics** Single nucleotide polymorphism (SNP) studies have revealed that polymorphisms associated with nicotine metabolism and DNA repair genes are responsible for higher lung cancer risk in Latinos. Additionally, the predominant driver oncogenes reported were EGFR, Kirsten Rat Sarcoma (KRAS), and c-raf murine sarcoma viral oncogene homolog B1 (BRAF) [37]. Genome-wide association studies (GWAS) conducted to fnd SNPs associated with colon cancer in Latinos discovered 17 genetic variants across four independent regions [38]. Another GWAS with Latino breast cancer patients revealed SNPs at 6q25 locus were associated with a low risk of estrogen receptor (ER) negative breast cancer risk in Latinas with indigenous American ancestry [39]. A signifcant association between thyroid cancer and fve specifc SNPs were detected in Latinos living in Columbia [26].

**Epigenomics** Changes in DNA methylation, a well-known epigenetic modifcation, are dynamic and infuenced by both intrinsic (genetic) and extrinsic (environmental, lifestyle) factors [40]. Unlike DNA sequence mutations, DNA methylation can be changeable throughout a lifetime and can be altered by environmental exposure [41]. Associated with cancer, DNA methylation can alter the regulation of diverse cellular processes [42]. The global loss of methylation, often measured by Long Interspersed Element-1 (LINE-1), is associated with cancer incidence and mortality [43–46]. Additionally, genome-wide methylation studies have revealed numbers of cancer site-specifc, hyper- and hypo-methylation across the genome as potential biomarkers for diagnosis, treatment, and prognosis [47–49]. Thus, many studies have focused on the relationship between DNA methylation and cancer, but notably in Caucasians [50, 51] and far more limited for Latinos. Based on individuals (*n* = 573) from diverse Hispanic origins, one study identifed 916 methylation sites that differ between ethnic subgroups (Mexican, Puerto Rican, Mixed Latino, Other Latino) [52]. Among those sites, 66% were associated with intrinsic factors (ancestry) and 34% were associated with extrinsic factors (e.g., cultural, economic, environmental, and social exposures) [52]. Compared to non-Latino whites, Latinos have increased risk for hypermethylation of some lung cancer-related tumor suppressor genes, for example, transcription factors that bind to the DNA sequence GATA, sulfatase 2 (SULF2), and protocadherin 20 (PCDH20) in exfoliated lung cells [53]. In global DNA, signifcantly lower levels of LINE-1 were found in Latinos relative to non-Latino whites [54].  Thus, in Latinos, DNA methylation differs by a combination of factors, including genetic susceptibility, socioeconomic status, lifestyle factors, and the environment, suggesting an epigenetic biomarker for understanding cancer disparities.

**Transcriptomics** Latino patients have been reported to experience a greater incidence of gastric cancer compared to Asians and Whites, and they have a greater proportion of genomically stable subtype tumors. Transcriptomic studies (whole-exome and RNA sequencing) revealed that 16% of patients possess unique molecular signatures, including a high proportion of cadherin 1 (CDH1) germline variants, which could be responsible for the aggressive gastric cancer phenotypes [56]. Transcriptomic studies of kidney cancer patients showed differential expression of almost 300 genes between tumors with different stage, size, and stage of kidney tumors, while advanced stage tumors showed overexpression of glucose-6 phosphate dehydrogenase (G6PD), amyloid-like protein 1 (APLP1), glucosaminyl (N-acetyl) transferase 3, mucin type (GCNT3), and phospholipid phosphatase 2 (PLPP2) genes [57].

**Proteomics** A proteomics study of Puerto Rican CRC patients revealed lower frequency of microsatellite instability (MSI)-related proteins, which result from DNA mismatch repair genes (MMR). Higher prevalence of the mismatch repair gene MutL homolog 1, colon cancer, nonpolyposis type 2 (MLH1) was found in 6–9% of colon tumors [58].

**Metabolomics** In a study on plasma metabolic profling of breast cancer patients, Zhao et al. [59] reported that 14 metabolites showed a signifcant difference between Latino and non-Latino African American women. The identifed metabolites were associated with citrate cycle, arginine-, proline-, and linoleic acid metabolic pathways.

**Lipidomics** No studies have been done on altered lipid profles in US-based Latino breast cancer patients. However, lipidomic and metabolomic fngerprints of Latina women from Columbia who had breast cancer revealed a specifc pattern of metabolites that were associated with glycerolipid, glycerophospholipid, amino acid, and fatty acid metabolism. These profles were similar but not identical to those from non-Latina women [60].

#### **Knowledge Gaps and Future Directions**

The trans-omics approach, also known as multi-omics, poly-omics, and pan-omics, embraces integration of multidimensional omics data to provide a comprehensive assessment of a cancer in question [61]. This is an interesting approach to adopt because the etiology of a disease such as cancer is complex owing to its multiple causative factors. Single-level omics approaches help in identifying specifc cancerrelated mutations, epigenetic changes, and molecular characterization of tumors to different subtypes on the basis of gene–protein expressions. However, multi-omics approaches offer several advantages as they can dissect cancer cells in multiple dimensions and probe deeper to bring into light the mechanisms (molecular and biochemical) that underlie different phenotypes of a particular cancer. Additionally, these strategies can not only examine the response to suspected causative agent (carcinogen) exposure but also to chemo- and/or immunotherapies. Another benefcial outcome of these trans-omics approaches is the discovery of new diagnostic/ prognostic markers for various types of cancer [62].

One shortcoming in assessing cancer disparities in Latinos is viewing health outcomes as a whole instead of taking subgroup heterogeneity into consideration [63]. Given the fact that Latinos comprise European, Native American (Amerindian), and African ancestries [23], assessing health disparities among Latinos is a daunting task. In this context, employing the trans-omics approach is expected to yield robust information.

These advantages aside, the trans-omics approach has some challenges as well. Each omics cancer dataset by itself is complex for reasons such as the quality of output in analytical platform and heterogeneity of data [64]. Issues pertaining to processing these enormous data volumes could be resolved by the Big Data to Knowledge (BD2K) technologies mentioned in Paten et al. [65] and Juarez et al. [66].

Another research area worth considering from a trans-omics perspective is the microbiome. Microbiota of the gut has been implicated in cancer [67]. Microbes contribute to cancer both in direct and indirect ways. While some microbes such as the bacterium *Helicobacter pylori* contribute to gastric cancer and some viruses such as HPV and HIV contribute to cervical cancers, other microbes contribute to cancer through altered metabolism. However, the role of microbiome in cancer is not completely understood and may require additional investigations [68].

#### **References**

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

### **Chapter 3 Population Health Challenges for Latinos in the United States**

**Alexander N. Ortega**

#### **Latino Health-Care Access and the Patient Protection and Affordable Care Act**

The Patient Protection and Affordable Care Act (ACA) became law in 2010 and was nationally implemented in 2014 to make insurance more affordable and accessible. This comprehensive health insurance reform emphasizes community engagement and population health and has multiple provisions—insurance plans that are offered through marketplaces, Medicaid expansion, and incentives to improve cost and quality of care.

#### *Racial and Ethnic Disparities in Health-Care Access and Utilization Under the ACA*

Shortly after the roll out of the Affordable Care Act, our research team wanted to answer a simple question: What impact has the ACA had on health-care inequities, particularly for African Americans and Latinos? Using a pre-post study design, we analyzed combined data from the National Health Interview Survey (NHIS) and Medical Expenditure Panel Survey (MEPS) [1]. We found that all groups—non-Latino whites, African Americans, Latinos, and other race/ethnicity—experienced improvements in health-care access and utilization post-ACA, but that Latinos fared worse than all the other groups. For example, from 2011 to 2014, the probability of being uninsured dropped from 0.14 to 0.11 for non-Latino whites; from 0.24 to 0.17

A. N. Ortega (\*)

Department of Health Management and Policy, Center for Population Health and Community Impact, Drexel Dornsife School of Public Health, Drexel University, Philadelphia, PA, USA e-mail<EMAIL_ADDRESS>
for African Americans; and from 0.39 to 0.32 for Latinos. The other race/ethnicity category dropped from 0.18 to 0.14. The probability of delaying any necessary care also improved for every group; African Americans fared worse than Latinos (probability dropped from 0.17 to 0.14 and 0.18 to 0.12, respectively). The probability of having any physician visit increased post-ACA in all groups, but Latinos were consistently lower for all four years.

#### *ACA's Impact Among Latino Subgroups*

Are these observed trends in health-care access and utilization consistent for all Latinos or for just some Latino subgroups? To answer this question, we performed a simple analysis of trends in Latinos by subgroups defned by heritage group (Puerto Rican, Mexican, Cuban, Central American, and other Latino), citizenship status, and interview language (Spanish or English) [2]. Measures of access to health care included health insurance status and forgoing necessary care because of cost; measures of utilization included any emergency department (ED) visit and any physician visit within the past 12 months. Our fndings showed that the ACA, which was implemented in 2014, has reduced gaps in access and utilization of health care, and most reductions in disparities were experienced between Puerto Ricans and non-Latino whites; disparities remain for noncitizens [2].

**Insurance Coverage** Central American and Mexican Latinos showed the lowest percentage of being insured currently (72.26% and 68.47% after the ACA, respectively); Puerto Ricans, who are citizens at birth, fared better (88.57%).

**Forgoing Care** Results showed that Cubans and Mexicans were more likely to forgo necessary care in the past 12 months because of costs, and Puerto Ricans did better in forgoing care pre- and post-ACA.

**Emergency Department Visit** We observed that emergency department utilization improved for all groups. Interestingly, while Puerto Ricans were much more likely to be insured and less likely to forgo seeking care, they had signifcantly higher percentage of visiting the emergency department in the last 12 months. We observed that ED use among other Latinos followed second to Puerto Ricans and that ED use among non-Latino whites did not change from 2011 to 2015.

**Physician Visit** Trends were fat for any physician visits in the past 12 months; Mexican Latinos fared worse than the other heritage groups, followed by Cuban Latinos.

**Citizenship and Language Use** We were also interested in knowing whether or not these associations were moderated by citizenship status or language use. We found that noncitizens had lower odds than US-born citizens of being insured (OR = 0.34; 95% CI, 0.31–0.37; *P* < .01), visiting an ED (OR = 0.78, 95% CI, 0.69–0.88; *P* < .01), and seeing a physician (OR = 0.74, 95% CI, 0.68–0.80; *P* < .01). Those whose interview language was Spanish had lower odds than those whose interview language was English of being insured (OR = 0.79; 95% CI, 0.71–0.87; *P* < .01), visiting an ED (OR = 0.62; 95% CI, 0.55–0.71; *P* < .01), and seeing a physician (OR = 0.80; 95% CI, 0.74–0.87; *P* < .01) [2].

#### *ACA's Impact on Reducing Disparities in Hypertension Treatment Among Mexican-Heritage Latinos*

The cardiovascular literature shows that Latinos, in general, have lower rates of cardiovascular disease than other groups [3, 4]. Mexican-heritage Latinos, in particular, have lower rates of hypertension than non-Latino whites, but they are more likely to be undiagnosed; they are also more likely to be diagnosed later in disease, are much more diffcult to treat, and are less likely to be on hypertensive medication.

In light of these disparities, we asked the question: Has the ACA made a difference in the treatment of hypertension in Mexican-heritage Latinos? Using data from the 2009–2014 California Health Interview Survey [5], we predicted trends in access, utilization, and hypertension control under the ACA for Mexican-heritage Latinos and non-Latino whites with hypertension. We found a signifcant initial uptake in insurance coverage for Mexican-heritage Latinos in 2013 followed by a slight decline in 2014, and there was a clear disparity in predicted insurance when compared to non-Latino whites even after implementation of ACA provisions. (These data refect the fact that California adopted several provisions of the ACA before 2014.) Notably, the odds of taking hypertension medication increased among Mexican-heritage Latinos; that is, they were signifcantly more likely to report taking the medication after the ACA.

#### **Impact of the ACA on Latino Children**

#### *Disparities Among Latino Children: Pre-ACA*

About one in four US children under the age of 18 are Hispanic/Latino, making up the largest minority group among US children [6]. We thus had an interest in documenting disparities in health care among Latino children that existed before the ACA was implemented. Because family-centered care has been demonstrated to reduce disparities and improve the quality of health care, we examined racial and ethnic disparities in the receipt of family-centered care among the general pediatric population in the United States [7]. Using a linked dataset of MEPS and the NHIS from 2003 to 2006 (pre-ACA), we measured family-centered care using four questions adopted by the NHIS: "How often did your child's doctors or other health providers (1) listen carefully to you, (2) explain things in a way you could understand, (3) show respect for what you had to say, and (4) spend enough time with you?" We found that compared to non-Latino whites, Latino youth experienced pediatric care with less of the four core processes of family-centered care—showing respect, sharing information, encouraging participation, and promoting collaboration. Their parents were less likely to say that their child's doctors listened to them, explained things carefully, or spent enough time with them.

What is the source of the health-care disparities between Latino youth and other children? To identify explanatory factors, we used the Blinder-Oaxaca decomposition method to analyze the 2006–2011 NHIS (pre-ACA) data on parent-reported health-care access and utilization for white, Latino, and African American children in the United States [8]. We found that Latino children were less likely than non-Latino white children to have a usual source of care, receive at least one preventive care visit, and visit a doctor; Latino children were also more likely to have delayed care. These disparities could largely be explained by differences in socioeconomic status and health policy factors, such as having health insurance and having access to care.

#### *Insurance Coverage and Latino Youth: Post-ACA*

Did the ACA change the level of insurance coverage and health-care utilization or improve health-care disparities among Latino youth? Did Latino children show the same pattern of insurance coverage as Latino adults before and after implementation of the ACA? We analyzed national data from the 2011–2015 NHIS child component, which included parent-reported health-care utilization and access for youth aged 0–17 years. Using a pre-post study design, we found that insurance coverage and well-child visits improved for all youth post-ACA, but like their adult counterparts, Latino youth lagged signifcantly behind non-Hispanic whites, non-Hispanic blacks, and other race/ethnicity [9]. Even though Latino youth showed the largest gain in insurance coverage, they made up the highest proportion of uninsured post-ACA, largely because they had a much higher uninsured rate pre-ACA (Fig. 3.1). Although differences for well-child visits were minimal, Latino youth were also less likely to have a well-child visit.

Since our original analysis of insurance coverage for youth and well-child visits post-ACA [9], there have been changes in the implementation of the ACA. In an effort to determine if insurance coverage and disparity levels are still improving, we reanalyzed our original data to include more recent 2018 NHIS data [10]. For the total of all youth, the prevalence of uninsured initially decreased from 6.6% in 2011–2013 (pre-ACA) to 4.8% in 2014–2015 (post-ACA); however, there was an uptick to 5.1% by 2016–2018. While these percentage differences may seem small, note that the denominator is in the millions—the 0.3% increase in uninsured from 2014–2015 to 2016–2018 is 196,000 uninsured children. The uninsured rate for

**Fig. 3.1** Insurance coverage and well-child visits for youth (0–17 years) in the United States pre-ACA (2011–2013) and post-ACA (2014–2015). (Reprinted from Ortega et al. [9]. © 2018 with permission from Elsevier)

non-Latino white and non-Latino black youth showed a similar pattern of change as the total of all youth, but Latino youth continued to improve over the three time periods (11.4%, 2011–2013; 8.4%, 2014–2015; 7.6%, 2016–2018). Signifcant disparities remain, however, as the uninsured rate for Latino youth is still higher than non-Latino white and non-Latino black youth. All the three groups continued to improve on well-child visits over the three time periods. We hypothesize that this is largely attributable to the mandatory preventive visits that are provided by the ACA, so children are going in for immunizations and screening well-child visits, which are covered regardless of insurance coverage.

It has been established that the effect of the ACA on health-care disparities between Latinos and non-Latino whites varies among Latino-heritage groups [2], and the question is whether the same disparity patterns exist among Latino youth. Using data from the 2011–2016 NHIS, we compared insurance coverage and healthcare utilization by subgroups of Latino youth (Puerto Rican, Mexican, Cuban, Central or South American, and other subgroups) [11]. We found that the uninsured rate dropped signifcantly post-ACA for most Latino subgroups and non-Latino whites; children of Mexican heritage and Central or South American heritage experienced the greatest decline in uninsured rate (13.1% pre-ACA to 9.9% post-ACA and 12.4% to 9.1%, respectively)—a similar pattern to their adult counterparts [11]. However, disparities remained as both subgroups still experienced greater uninsured rates post-ACA than the other subgroups and non-Latino whites. Similarly, the proportion for a well-child visit in the past 12 months increased for most groups post-ACA, but the proportion of Mexican children going to a well-child visit still lagged behind all other groups both pre-ACA and post-ACA [11]. Interestingly and contrary to popular belief, Mexican-heritage children were very low utilizers of the emergency department [11]. This was true for both citizens and noncitizens.

#### **Health-Care Access Among Undocumented Latinos**

Are health-care disparities among Latinos in the United States associated with US citizenship and documentation status? In a pre-ACA study analyzing the 2003 data from the California Health Interview Survey (CHIS), we found that undocumented Mexicans and other Latinos have worse health-care access and utilization patterns than those born in the United States [12]. In a more recent post-ACA study, we compared health-care access and utilization among Latinos in California stratifed by the continuum of documentation status—US-born citizen, naturalized citizen, permanent resident with a green card, and undocumented immigrant. An analysis of the 2011–2015 CHIS data showed signifcant health-care disparity along this continuum with undocumented Latinos faring the worst [13]. Interestingly, we also found that undocumented immigrants were the least likely to report having chronic disease, physical health problems or mental health issues than other immigrant groups, even though they were also the least likely to report excellent or very good health.

The Affordable Care Act holds the promise of ameliorating some of the health disparities that the Latino population experiences in the United States, but coverage needs to be extended to undocumented immigrants to narrow disparities and improve utilization and access to health care [14]. For example, California offers Medicaid to eligible children who are undocumented and also provides health benefts to adult undocumented immigrants through Medicaid, which is covered by state funds.

#### **Conclusion**

The ACA has positively impacted health-care disparities in the United States for both adults and children. While there have been gains in insurance coverage and primary health-care access and utilization across all racial and ethnic groups, disparities remain, especially for Latinos in states that have not expanded Medicaid. Moreover, among Latinos, disparities are particularly striking for Mexican and Central American subgroups and for noncitizen and undocumented immigrants. Any revision in the implementation of the ACA must consider these unremitting disparities, especially as the Latino population continues to grow and expand across the country. Some states, like California, are leading the way in implementing policies that ensure health care is a right afforded to all its citizens, which includes noncitizens who have been in the country for less than fve years and undocumented immigrants, and this should be a model for national health-care reform.

#### **References**

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

### **Part III Vulnerable Populations and Cancer Health Disparities**

### **Chapter 4 Acute and Long-term Neurological Complications of Acute Lymphoblastic Leukemia (ALL) Therapy in Latino Children**

**Austin L. Brown, Kimberly P. Raghubar, Michael E. Scheurer, and Philip J. Lupo**

#### **Introduction**

Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed during childhood [1]. Once considered a terminal diagnosis, pediatric ALL is now curable in approximately 90% of cases with contemporary therapy [2]. Despite signifcant improvements in the treatment of pediatric ALL, racial and ethnic disparities still persist. In particular, compared to non-Latino White populations, Latinos have both a higher incidence of pediatric ALL and less favorable outcomes [3]. Disparities in pediatric ALL outcomes are likely due to a number of factors, including ethnic variability in somatic molecular profles, comorbidities, treatment adherence, and response to chemotherapy. Notably, exposure to central nervous system (CNS)-directed chemotherapy during ALL treatment is associated with a risk of acute and long-term neurotoxicity [4, 5]. Emerging research from our group and others suggests Latino patients with ALL may be particularly vulnerable to the adverse neurologic side effects of CNS-directed therapy [6–8]. Therefore, we provide an overview of ethnic disparities in treatment-related neurotoxicity and recommendations for future research directions.

A. L. Brown · K. P. Raghubar · M. E. Scheurer · P. J. Lupo (\*) Baylor College of Medicine, Houston, TX, USA

Texas Children's Hospital, Houston, TX, USA e-mail<EMAIL_ADDRESS>
#### *Acute Neurotoxicity During ALL Therapy*

The antifolate agent methotrexate is an important component of contemporary curative pediatric ALL protocols. Current ALL chemotherapy regimens typically include intravenous (IV), intrathecal (IT), and oral methotrexate. The antineoplastic effects of methotrexate are attributed to the competitive inhibition of the dihydrofolate reductase (DHFR) enzyme involved in tetrahydrofolate synthesis. The resulting tetrahydrofolate defciency disrupts DNA and RNA synthesis, leading to cell cycle arrest. Methotrexate preferentially inhibits rapidly dividing cells, such as leukemic cells. However, because methotrexate is a folic acid analogue, prolonged use or exposure to high doses of methotrexate may deplete folate stores and result in adverse side effects. Specifcally, approximately 10% of pediatric patients with ALL experience acute or subacute neurotoxicity, typically occurring within 14 days of receiving CNS-directed high-dose IV or IT methotrexate [4, 5]. Acute and subacute methotrexate-related neurotoxicity often manifests clinically as a combination of seizure, aphasia, altered mental status, stroke-like symptoms, and encephalopathy [6–8]. Although these symptoms are typically transient [9], the clinical management of methotrexate-related neurotoxicity often leads to delays or modifcation of cancer therapy, potentially limiting treatment effcacy. In fact, recent evidence from our group suggests that patients with suspected neurotoxic events during ALL therapy receive an average of two fewer doses of IT methotrexate [8]. Although follow-up was limited in this cohort, we also observed a statistically signifcant (*p* < 0.05) trend toward an increased risk of relapse in patients with a history of methotrexate-related neurotoxicity.

Despite neurotoxicity being a serious complication of methotrexate chemotherapy, information on the factors which modify the risk of methotrexate-related neurotoxicity is limited. Several independent studies have reported associations between older age at diagnosis and treatment intensity and the incidence of acute and subacute neurotoxicity [4, 5, 8, 10]. Recent case series further suggest that susceptibility to methotrexate-related neurotoxicity may vary across racial and ethnic groups. Giordano et al. [7] presented information on fve ALL patients with acute or subacute neurotoxicity, all of whom were Latino, while Afshar et al. [6] described the presentation of clinical neurotoxicity in 18 pediatric oncology patients, including 12 Latino cases. Most recently, we conducted one of the largest evaluations of acute and subacute methotrexate-related neurotoxicity in a multisite study of patients treated on recent pediatric ALL protocols [8] and found signifcant differences in the incidence of neurotoxicity by ethnic group (Fig. 4.1). This analysis of 280 newly diagnosed (between 2012 and 2017) patients found that neurotoxicity occurred in 21.8% of Latino compared to 6.8% of non-Latino patients, corresponding to a nearly 2.5-fold increased risk of neurotoxicity after accounting for other clinical and demographic factors.

Growing evidence supports an association between genome-wide genetic ancestry and racial/ethnic disparities in pediatric ALL outcomes, including relapse [11], suggesting that genetic variants, which impact antileukemia therapy

**Fig. 4.1** Cumulative hazard of acute and subacute methotrexate-related neurotoxicity between Latino and non-Latino White patients with pediatric ALL

pharmacodynamics and pharmacokinetics, may co-segregate with areas of the genome associated with differing ancestral populations [12]. Because Latino ethnicity encompasses a genetically diverse population with various degrees of European, African, and Native American genetic admixture, we sought to evaluate the association between genetic ancestry and methotrexate-related neurotoxicity in a prospective cohort of pediatric patients with ALL. We estimated the proportions of European, African, East Asian, and Native American genetic ancestry using genome-wide genotype data available on 190 pediatric patients with ALL, including 35 individuals with a history of acute and subacute methotrexate-associated neurotoxicity, and publicly available reference populations [13, 14]. The proportion of genetic variation that co-segregates with Native American ancestry was overrepresented in individuals with methotrexate-related neurotoxicity (mean = 34.9%; Fig. 4.2) compared to individuals without a history of neurotoxicity (mean = 23.2%, *p* = 0.025). In multivariable proportional hazards regression models accounting for sex, age at diagnosis, and treatment risk group, every 10% increase in the proportion of Native American genetic ancestry was associated with a 16% increase in neurotoxicity incidence (HR = 1.16; 95% CI: 1.02–1.32). These fndings highlight that ethnic-specifc differences in inherited genetic variation likely contribute to disparities in the incidence of treatment-related toxicity.

**Fig. 4.2** Observed variability in the proportions of African, European, and Native American genetic ancestry among pediatric cases of acute lymphoblastic leukemia by self-reported race/ ethnicity (**a**) and the incidence of methotrexate-related neurotoxicity (**b**)

#### *Neurocognitive Late Effects of ALL Therapy*

Contemporary treatment protocols for childhood ALL have largely eliminated the use of prophylactic cranial radiation in favor of CNS-directed chemotherapy [4, 15, 16]. Efforts to reduce exposure to cranial radiation have also reduced many adverse effects of ALL therapy, including neurocognitive defcits. Although cognitive functioning in survivors treated with contemporary chemotherapy is better preserved than in those treated with cranial radiation, survivors treated with chemotherapy alone continue to demonstrate defcits relative to their unaffected peers [17–21]. In fact, neurocognitive diffculties are estimated to be one of the most prevalent late effects of childhood ALL chemotherapy, affecting nearly 50% of survivors [22]. Neurocognitive diffculties are commonly detected in the domains of attention, executive functioning, working memory, and processing speed among long-term survivors of childhood ALL [17, 23, 24]. Neurocognitive changes in this population appear to be related to the effects of methotrexate, which have been associated with demyelinating white matter injury and vascular damage in the developing brain. Specifcally, survivors treated with chemotherapy only have been found to have total white matter volume loss [25], notably in the frontal [26] and subcortical regions [27], and abnormal or reduced white matter connectivity [27–29], with children diagnosed at younger ages being particularly vulnerable to these adverse effects of treatment [27]. Children and adolescents experiencing clinical fndings of acute or subacute methotrexate neurotoxicity during treatment may be at particularly increased risk for long-term neurocognitive defcits [30]. For example, children who experienced seizures during treatment for ALL demonstrated reduced attention, working memory, and processing speed relative to children who did not develop seizures and had normative scores at the end of treatment; additionally, these diffculties persisted over a two-year follow-up period [30]. However, other therapeutic exposures, including anesthesia, have been associated with persistent neurocognitive issues among survivor [31]. These cognitive defcits not only impede learning and academic achievement but also have long-term educational and economic consequences [32–34].

Despite increased incidence of ALL and neurotoxic events during therapy among Latino patients coupled with increased neurocognitive risk among Latinos more broadly, there is an extreme lack of population diversity in neurocognitive outcomes research for pediatric ALL to date. According to recent meta-analyses summarizing sociodemographic factors and neurocognitive outcomes in ALL, only one-third of studies reported the ethnic/racial composition of their sample, and when race/ethnicity was reported, the overwhelming majority (almost 80%) self-identifed as White or Caucasian [21, 35]. Two studies have been conducted among Latino cohorts, and they indicate that survivors are at risk for neurocognitive late effects and school-based learning diffculties [36, 37]. Specifcally, Latino survivors of pediatric ALL demonstrated reduced performance relative to the normative mean in neurocognitive domains typically affected in non-Latino patients including working memory, processing speed, visual reasoning, executive functioning, and visual learning [37]. In addition, Latino survivors demonstrated reduced verbal reasoning and reading comprehension skills, which are not typically implicated in late effects research of predominantly non-Latino populations. Despite a focus on Latino survivors, models did not account for socioeconomic status (SES), though proxies for the general socioeconomic standing of the sample were described.

#### **Emerging Research Needs**

Most models of neurotoxicity in pediatric patients with ALL have focused on clinical predictors, often excluding sociodemographic and molecular factors known to infuence neurologic development and outcomes in unaffected populations. For example, neurocognitive abilities of children in the general population are adversely impacted by many factors, including SES and native language [38, 39], which disproportionately affect racial and ethnic minorities. Despite the fact that ethnic disparities in ALL outcomes and toxicity are well documented [3, 11, 40–43], few studies have evaluated neurotoxicity in multiethnic populations, much less evaluated the role of SES and acculturation [24, 36, 37, 44]. Moreover, the considerable inter-patient variability in susceptibility to neurotoxicity might be partly explained by underlying molecular variation. However, the role of these factors in treatmentrelated neurotoxicity has received limited attention. Additional research on the roles of socioeconomic, cultural, and biologic factors in ethnically diverse populations is needed to advance our understanding of neurological outcomes in vulnerable populations.

#### *Incorporating Information on SES and Acculturation*

Survivors of childhood ALL who are from racial/ethnic minority groups and lower SES are at increased risk for cognitive defcits. SES refers to a combination of income, education, and occupation [45]. Therefore, generally speaking, the relationship between ethnicity and neurocognitive outcome is complex, given that ethnicity and SES can be highly related, particularly among Latino families [46]. In particular, Latinos who immigrate to the United States have, on average, a lower SES [47], though there is considerable variability depending on country of origin. For example, Cuban-Americans graduate from college at three times the rate of Mexican-Americans [48]. Among healthy children, associations are documented between SES and cognitive abilities. The domains most affected by SES disparities include language abilities, executive functioning, attention, and memory [38, 39]. Overall, few studies have considered SES in relation to neurocognitive outcome among survivors of childhood leukemia; however, when these factors are considered the observed associations are typically consistent with individuals of lower SES having an increased risk of impairment [49].

Among Latino families, acculturation may simultaneously impact cognitive and academic skill development along with socioeconomic factors, though acculturation is not necessarily related to such factors. Language is an important aspect of determining an individual's level of acculturation. Parent language acculturation in Latino families, namely English profciency and primary language in the home, is important for children's academic readiness and academic success in higher grades [50, 51]. Furthermore, Latino children whose native language is Spanish perform signifcantly worse than non-Latino children on the Wechsler Intelligence Scales, the most commonly used measure of intelligence in childhood, with specifc adverse effects exhibited on verbal subtests [52]. While there are a number of proxies for acculturation, such as generational status and number of years of US residency, none of them are adequate for providing insight into the infuence on the acculturative experience on neurocognitive development and performance.

#### *Molecular Predictors of Neurotoxicity*

In addition to variability in patient characteristics and therapeutic exposures, a number of factors likely contribute to disparities in pediatric ALL toxicity and outcomes, including underlying genetic variation. To date, few studies have evaluated inherited single nucleotide variants; however, associations have been reported between clinical neurotoxicity and candidate variants in *SHMT1*, *MTHFR*, and *GSTP1* [53, 54]. In particular, the missense C677T polymorphism in *MTHFR* (rs1801133) has been associated with adverse responses to methotrexate therapy in pediatric and adult patients treated for rheumatoid arthritis and various malignancies [55–57]. Several publications have speculated that inherited variation in *MTHFR* may also contribute to the risk of methotrexate-related neurotoxicity in children with ALL [54, 58], but direct evidence that *MTHFR* genetic variation affects neurotoxicity susceptibility is limited. Compared to individuals who are homozygous for the reference allele (CC), carriers of the alternate allele (CT/TT) exhibit decreased *MTHFR* enzymatic activity and increased plasma homocysteine levels [59]. Homocysteine concentrations are transiently elevated following methotrexate therapy, and cerebrospinal fuid levels of homocysteine have been linked to neurotoxicity in children undergoing treatment of ALL [60, 61]. Notably, the frequency of the C677T missense variant appears to vary across ancestral populations. Based on the 1000 Genomes data [62], the C677T alternate allele frequency is approximately 9.0% in individuals of African ancestry, 36.5% in individuals of European ancestry, and 47.0% in admixed American populations comprised individuals of Latino ethnicity. Additional research is needed to better characterize the genetic contribution to methotrexaterelated neurotoxicity and disparities in susceptibility. However, genome-wide association studies have not yet successfully identifed and replicated susceptibility loci due to challenges in assembling large cohorts to suffciently power these studies [4]. Alternative approaches that examine the association between local Native American genetic ancestry and neurotoxicity risk using methods such as admixture mapping may prove more powerful at identifying novel susceptibility loci responsible for the ethnic disparities observed in neurotoxicity risk.

#### **Conclusion**

Current treatment strategies for pediatric ALL are associated with acute and longterm neurotoxicity. The incidence of acute and subacute neurotoxicity during pediatric ALL therapy potentially jeopardizes treatment effcacy, while long-term neurocognitive impairment profoundly affects quality of life in survivors of ALL. Emerging evidence indicates that Latino patients may be particularly susceptible to these adverse side effects of therapy. In fact, we recently reported that Latino patients with ALL experience acute and subacute neurotoxic events at a rate far exceeding their non-Latino counterparts [8]. Some evidence suggests that acute toxicity predisposes affected individuals to long-term neurocognitive and behavior complications as survivors [30]; therefore, Latino survivors may be particularly vulnerable. Unfortunately, studies of neurotoxicity during pediatric ALL therapy have largely neglected Latino populations. Future well-designed studies are needed to characterize neurotoxicity outcomes in Latino patients, while considering factors associated with disparities in cognitive performance in the general population, including SES and acculturation. Ultimately, a better understanding of the various factors likely responsible for disparities in neurotoxicity, including inherited genetic variation, clinical characteristics, and sociocultural differences, is needed to improve outcomes for Latino populations.

#### **References**

**Open Access** This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

### **Part IV Cancer Outcomes and Survivorship in Latinos**

### **Chapter 5 Supportive Care Needs and Coping Strategies Used by Latino Men Cancer Survivors**

**Dinorah Martinez Tyson and Erik L. Ruiz**

#### **Introduction**

Over 1.8 million Americans will be diagnosed and over 600,000 are estimated to die from cancer by the end of 2020, making it the second leading cause of death in the United States [1]. Modern developments in cancer treatment have facilitated increased survival, and there is a growing population of cancer survivors that is expected to reach 18 million within the next decade [2, 3]. Cancer survivors may experience long-term physical and psychosocial effects which extend beyond the treatment phase and which require additional supportive care to cope with these effects and enhance quality of life [1, 4–7].

In this chapter we will provide a brief overview of the epidemiology of cancer within the US Hispanic population with a specifc focus on health disparities experienced by Hispanic men cancer survivors (HMCS). Next, we explore the emerging themes derived from research of the cultural, social, and environmental supportive care needs of HMCS and the coping mechanisms they use. Finally, we propose implications for research and practice for those working with HMCS. In this chapter we will use the terms Hispanic/Latino and Latinx interchangeably. While we recognize the term Latinx has recently emerged, many of the communities we work with still prefer and use the terms Hispanic/Latino.

D. Martinez Tyson (\*) · E. L. Ruiz

College of Public Health, University of South Florida, Tampa, FL, USA e-mail<EMAIL_ADDRESS><EMAIL_ADDRESS>
#### **Epidemiology of Cancer Within the Latinx Population**

Overall, Hispanics in the United States experience lower incidence and mortality rates of most cancers compared to other racial and ethnic groups within the nation; however, they experience a signifcantly higher rate of infection-associated cancers including cervical, liver, and gastrointestinal [1]. It should be noted that the Hispanic population is not homogeneous; cancer incidence, morbidity, mortality rates, and quality of life can vary by a Hispanic person's country of origin, generational status, and time spent in the United States. For example, US Hispanic men are 85% more likely to die from stomach cancer than non-Hispanic Whites [8]. Additionally, when compared to US non-Hispanic White men, Cuban born men experience higher incidence and mortality rates of prostate cancer, and the incidence of colorectal cancers has been observed to be lower for Hispanics with low socioeconomic status (SES) compared to those with high SES [8–10]. Finally, whereas the population of Hispanic cancer survivors is growing, the psychosocial distress experienced by these survivors also varies according to sociocultural factors; more acculturated US Hispanics have reported a lower quality of life than less acculturated Hispanics due in part to a lack of supportive care [10–12].

#### *Disparities in Diagnosis and Survivorship*

Although US Hispanics experience lower incidence rates of most cancer types, they do suffer from disproportionately high barriers to care access and have lower cancer survival rates when compared to non-Hispanic Whites [11, 13–16]. For example, 18% of US Hispanics are likely to be uninsured compared to only 5% of non-Hispanic Whites, which can make US Hispanics vulnerable to delayed cancer diagnosis, resulting in more involved, costlier, and potentially less successful treatments [1]. Similarly, Hispanic men and women experience lower rates of cancer-related mortality compared to their non-Hispanic counterparts. However, Hispanic men of all country-of-origin subgroups experience higher incidence rates of all cancer types, except gallbladder cancer, and higher rates of cancer-related mortality compared to Hispanic women [13, 17]. Special attention to the supportive care needs of Hispanic men is required as they are a part of the largest ethnic minority group in the United States and their number of cancer survivors continues to grow [15, 18]. The remainder of this chapter focuses on understanding the supportive care needs of Hispanic men cancer survivors and describes how they cope with cancer. At the end of the chapter, we describe strategies to address these identifed needs.

#### *Supportive Care Needs of Hispanic Men Cancer Survivors*

Hispanic men report worse cancer-related morbidities including reduced sexual and physical functioning, increased bowel-related issues, decreased quality of life, and worse mental health outcomes compared to their non-White male counterparts [19– 22]. These poor conditions are further complicated by disparities in and access to culturally competent care, health information exchange, and disease management education [4, 19]. Additionally, compared to Hispanic women, Hispanic men who have been diagnosed with cancer may have more psychosocial needs and tend to engage less with supportive care services [23, 24]. Finally, there is a dearth of data and research pertaining to the supportive care needs of HMCS, so the full extent of their needs both during and after cancer treatment is not yet fully understood.

An emerging body of research has sought to capture the unique needs of Hispanic men diagnosed with cancer [10, 14, 15, 25]. We draw on fndings from recent research that has sought to explore and understand the needs of HMCS. A detailed description of the mixed methods used is described elsewhere [26–29]. The overarching themes expressed by HMCS include the needs: for better communication with providers and for culturally competent care; for comprehensive survivorship care and more cancer treatment-related information; to still provide for their family and also navigate changing gender role expectations; and to connect with other cancer survivors.

#### *Need for Better Communication with Providers and for Culturally Competent Care*

HMCS discussed the need for culturally competent care; they specifcally identifed language barriers which inhibit communication relating to care, barriers associated with the use of interpreters, and a lack of *confanza* (confdence in the personal relationship with the care provider) [28]. HMCS who mentioned language barriers cited a need for bilingual communication of cancer-specifc treatment information due in part to a lack of confdence in their English-speaking abilities which inhibited them from asking clarifying questions. Furthermore, even with the use of a bilingual interpreter, some HMCS had reservations about their care as they expressed a lack of confdence that the interpreter was accurately describing their sentiments and concerns. An additional element that surfaced was the importance of having *confanza* (trust) and *personalismo* (friendly and personal relationships) with providers, which allows men to build rapport and be able to talk more openly with providers. This affects disclosure of potentially important information about treatment side effect management [28].

#### *Need for Comprehensive Survivorship Care and More Cancer Treatment-Related Information*

In addition to cancer recurrence, the major concerns and sources of stress discussed by participants were related to not having enough information about the availability of other treatment options and/or alternative/complimentary medicine, the treatment they received, and the long-term side effects (e.g., impotency, incontinence, and fatigue) [28]. Additionally, many HMCS participants indicated that they lacked understanding of posttreatment care and follow-up, including additional cancer screenings that may need to be done. Many HMCS felt as if the care they received for their cancer should have been more comprehensive and holistic with goals which extended beyond treatment and that were more focused on maintaining overall health and well-being.

#### *Need to Provide for Family While Navigating Changing Gender Role Expectations*

HMCS identifed impairment of both physical and social aspects of their masculine identities [28]. Common physical complaints centered around impotence and incontinence (potential side effects of prostate cancer treatments), whereas common social complaints identifed were the fnancial and emotional burden placed on female family members due to employment changes or the physical demands of cancer treatments. Both physical and social concerns troubled HMCS because they brought into question their traditional masculine roles in their families, and many HMCS did not feel they were equipped to navigate those expectations.

#### *Need to Connect with Other Cancer Survivors*

Finally, HMCS expressed a need to socialize with other HMCS in order to connect and *distraerse* (to distract themselves) through the discussion of shared experiences in the fnal emergent needs-based theme [28]. Some HMCS indicated that the only time they had discussed their cancer process with other HMCS was during the interview or focus groups for this study. We observed that participants openly shared their experiences and concerns without inhibition. They expressed a desire to connect with others who had gone through similar experiences.

Data from the S-CaSUN survey (Table 5.1) show that the most highly endorsed items included needs related to comprehensive care/provider communication (46% said yes to their worries about their health being adequately addressed and 45% need to feel their opinion is important to their doctors), information needs and emotional support (42% said they need more information about follow-up care that is

needed), and existential survivorship (35% said they need help with their concerns about cancer coming back and knowledge about what to do to stay healthy) [26]. With regards to interpersonal/partner-related issues, 35% said they needed help to deal with the impact that cancer has had on the relationship with their partner.

#### **Coping Mechanisms for Hispanic Men Cancer Survivors**

Next, we will describe the coping mechanisms of HMCS in response to their cancer diagnosis, which include maintaining a positive attitude, optimism, humor, faith, incorporation of home remedies into the broader care plan, and lifestyle changes [29]. Having a positive outlook and utilizing optimism and humor were identifed as important factors in navigating through a successful care plan after the initial shock of cancer diagnosis. In this way, HMCS felt that the overall attitude was a signifcant factor in succumbing to or overcoming the disease process. Having faith in God was also observed to be a signifcant coping mechanism as HMCS perceived their faith to facilitate positive cancer treatment outcomes. Finally, incorporating home remedies and engaging in lifestyle changes, including diet and exercise, were important coping mechanisms for HMCS, as they provided a sense of agency and self-effcacy over their cancer diagnosis and treatment processes. HMCS identifed relying on their social support systems, both proximate and distal family members, as an important mechanism to alleviate the feeling of isolation associated with their cancer diagnosis and also as a way to facilitate the physical and logistical demands of attending appointments, receiving treatment, and managing treatment side effects. Similarly, maintaining a positive and supportive relationship between the HMCS and their care provider was identifed as an essential coping mechanism because the care provider's attitude throughout the cancer treatment process carried a signifcant weight on the HMCS' positive outlook as it reduced their perceived stress.

#### **Implications for Research and Practice**

Innovative public health research and practice is essential for addressing the disparities in supportive care needs experienced by HMCS. This work will require the focused efforts of public health researchers, practitioners, HMCS, Latinx community stakeholders, and care providers in order to identify and implement culturally relevant interventions, which may reduce the illness burden of HMCS. Efforts should center on provision of culturally competent care delivery, transcreation of existing evidence-based interventions to engage and meet the psychosocial needs of HMCS, and the dissemination of research fndings to Latinx community members to address the health information needs of HMCS and their families. We also need to develop programs that build on the strengths of the Latino community and facilitate opportunities for HMCS to connect with one another and build their support networks to relieve the burden of isolation frequently experienced by HMCS [30–32].

Our fndings illustrate the importance of health-care provider communication through listening and building a relationship built on trust with both the HMCS and their families. We also need to address the survivorship care planning needs of HMCS and provide ample health information and psychosocial resources to ease the transition from cancer treatment to survivorship and to enhance quality of life. Finally, public health practitioners in clinical settings should evaluate the role of interpreters in HMCS care as they are pivotal to successful patient-provider communication for both monolingual and bilingual Spanish-speaking patients. We need to ensure that the physical, psychosocial, and supportive care needs of HMCS are adequately addressed.

#### **Conclusion**

Although US Hispanics experience lower incidence of most cancer types, cancer remains a leading health burden for the population, particularly for Hispanic men. Additionally, disparities in access to care and delayed diagnoses pose continuing threats to the health of Hispanics in the United States. Furthermore, advances in cancer treatment have facilitated the growth of the HMCS population, which experiences unique supportive care needs and coping styles, many of which remain unaccounted for and unaddressed. We need to build on and recognize community strengths and acknowledge personal agency and coping strategies that will enable HMCS to not only survive but thrive after a cancer diagnosis and treatment.

**Acknowledgments** A special thanks to the members of our community advisory board, LUNA Inc., Hispanic Health Initiatives, *Creando Conciencia por Reina*, Dr. Pow-Sang, Mr. Jim West, Dr. Cathy Meade, Dr. Paul Jacobsen, and the Tampa Bay Community Cancer Network. This work was supported by the NCI under Grant R03CA168403. The content is solely the responsibility of the authors and does not necessarily represent the offcial views of the National Institutes of Health.

63 5 Supportive Care Needs and Coping Strategies Used by Latino Men Cancer Survivors

#### **References**

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### **Chapter 6 Cancer Care Delivery Among Breast Cancer Patients: Is it the Same for All?**

**Catalina Malinowski and Mariana Chavez Mac Gregor**

#### **Introduction**