Discussion
RS, N0), breast cancer, toxicities, early-stage HR, tumors
RECURRENCE, BREAST CANCER, DISEASE, SECONDARY, EVENTS, TUMORS
In this study, we observed that patients with intermediate RS results had no statistically significant differences in pathologic outcomes at the time of surgery based on whether they received neoadjuvant endocrine therapy or neoadjuvant chemotherapy. While our study did not include secondary analyses of pCR based on lymph node involvement or menopausal status among RS groups, the results suggest that a subgroup of women with a RS 0–25 may omit chemotherapy without compromising rates of clinical and pathologic complete response. This aligns with data from the Trial Assigning Individualized Options for Treatments (TAILORx), establishing no benefit of chemotherapy among women over the age of 50 years with HR + node-negative (N0) breast cancer and RS 11–25, as well as RxPONDER, which demonstrated that postmenopausal women with HR + node-positive (1–3 positive nodes) breast cancer and RS ≤ 25 can safely avoid chemotherapy [Our study findings suggest that the RS result may be an impactful tool to help guide treatment decisions in the neoadjuvant setting and reinforces the clinical feasibility of the RS assay using core biopsy specimens. The use of NET, which has been more often used in Europe than in the US, is a reasonable approach to downstaging some HR + tumors to allow de-escalation of surgery, particularly to allow breast conservation that might otherwise not be possible. Currently validated for use in the adjuvant setting, gene expression profiles like the Oncotype DX assay and the 70-gene signature MammaPrint assay have significantly contributed to better understanding of the heterogeneity among early-stage HR + breast cancer and, in doing so, have decreased the number of women exposed to the potential toxicities of chemotherapy [Ongoing trials evaluating the use of neoadjuvant endocrine therapy in combination with cyclin-dependent kinase (CDK) 4/6 inhibitors have shown promising results [Finally, it is important to note the difference in duration of neoadjuvant endocrine therapy between the two institutions. Despite patients in the Emory cohort receiving significantly longer courses of neoadjuvant endocrine therapy (median 10 months versus 5.5), there were no significant differences in pCR across RS result groups between the two institutions, and nearly three quarters of the VCU patients were able to receive breast-conserving treatment despite the pre-treatment assessment that they would require total mastectomies. Duration of neoadjuvant endocrine therapy has historically ranged from 12 to 24 weeks, although adequate duration to optimize outcomes has not been defined [Limitations of this study include the narrow scope in assessing pCR, lack of long-term follow-up and limited number of premenopausal patients. We did not assess the differences in side effects (both immediate or long-term) between treatment groups, nor did we evaluate for differences in disease recurrence. While the difference in RS result groupings (11–24 for Emory, 11–25 for VCU) created an inconsistency between studies, the sensitivity analysis illustrated that it had no impact on the results. Due to the low number of patients as described above and events for each study, we were unable to provide more than a descriptive explanation of the study differences. We explored adjusted analyses accounting for random effects of study and fixed effects for variables including length of endocrine therapy to determine the impact of differences between studies on pooling the data, but were unable to achieve model convergence. Finally, secondary analyses of data from previously designed studies can be subject to bias, even though these two studies had similar objectives. Despite these limitations, this study importantly highlights the potential for the Oncotype DX assay use in the neoadjuvant setting for therapeutic decision-making and the impact this may have on further personalizing treatment plans for a large group of patients with breast cancer.