of their tumors presentation and histopathology, almost all patients are further treated with a) radiation therapy to the involved areas, administered as adjuvant therapy after surgery or as neoadjuvant therapy before surgery; b) a chemotherapy regimen, administered after or before surgery; and/or c) in her2/neu-positive cases, trastuzumab, which is a monoclonal antibody that binds to her2/neu protein thereby suppressing its pro-cancerous actions. in a study of 41 cases, the 5 year overall survival rate was 100% for individuals with her2/neu-positive pacb tumors and ~72% for individuals with her2/neu-negative pacb tumors. since 9 of the 17 her2/neu-positive individuals in this study received a her2/neu-targeting drug, trastuzumab (brand name herceptin), these results, although not statistically significant, suggest that individuals with her2/neu-positive pacb may be benefited by adding a her2/neu-targeted drug to their treatment regimen. paradoxically, the 5 year overall survival rate in this study for individuals with slower proliferating tumors (ki-67 ≤20%) was lower, 67%, than that for individuals with faster growing tumors (ki-67 >20%), ~94%; again, this difference was not statistically significant. in a study of 18 individuals with ner2/neu-negative pacb, 17 were treated with mastectomy and one was treated with breast-conserving surgery; 14 of these individuals were also treated with chemotherapy and 4 with radiation therapy. none of these individuals were treated with a drug targeting her2/neu. after a median follow-up of 76.5 months, 15 individuals had no disease-related morbidity or mortality while 2 individuals developed distant tissue metastases and one had died. there is little data on the optimal treatment for, or long term (e.g. >10 years) results of, these currently used treatments for pacb. many researchers have recommended a) conducting a much larger study to verify the results suggesting that the addition of a her2/neu inhibitor to standard therapeutic regimens improves the overall survival of individuals with her2/neu-positive pacb; b) studies to determine if androgen receptor inhibitors (e.g. bicalutamide) or treatments that target the dysregulated pi3k/akt/mtor pathway, the cyclin-dependent kinase pathways, and/or the ras-raf-mek-erk pathway have a role in treating pacb; and c) conducting more comprehensive studies that profile pacb tumors to identify other potential therapeutic targets and regimens for treating this carcinoma. other types of apocrine carcinomas apocrine ductal carcinoma in situ fig 4. apocrine ductal carcinoma in situ non-invasive apocrine carcinoma of the breast, i.e. apocrine carcinoma in situ, is classified as a variant of the ductal carcinoma in situ tumors of the breast; it is therefore termed apocrine ductal carcinoma in situ (adcis). adcis tumors have appreciable areas with apocrine tissue-like histopathology, i.e. areas composed of apocrine cells that have, to varying extents, the abnormal cytoplasmic, nuclear, and nucleolar features found in pacb (see fig 4). unlike pacb, the apocrine carcinoma cells in adcis have by definition not spread beyond their ducts of origin to invade nearby non-ductal tissue and have not metastasized to local lymph nodes or distant tissues. while there is no consensus on the criteria used for its diagnosis, adcis is most often defined as a non-invasive breast tumor consisting of lactiferous ducts that are filled with neoplastic apocrine cells; the cells in these tumors, similar to those in pacb, are estrogen receptor-negative, progesterone-receptor negative, and, in at least 10% of these cells, androgen receptor-positive. some studies have classified adcis as low, intermediate, or high nuclear grade based on how closely the nuclei of their tumor's apocrine cells resemble the nuclei of normal breast cells. in general, high nuclear grade tumor cells have more abnormal nuclei and indicate that this tumor is more aggressive than a lower grade tumor. low- and intermediate-grade adcis tumors may be misdiagnosed as non-cancerous lesions (e.g. as atypical apocrine metaplasia or atypical apocrine hyperplasia) because of their more benign microscopic appearance. adcis tumors often have architectural patterns consisting of cribriform (riddled with small holes), micropapillary (thin finger-like growths) and/or solid growth (i.e. do not contain cysts or liquid areas), sites with necrosis, and/or sites with microcalcifications; while these microscopic findings are more common in high nuclear grade adcis, their presence supports the diagnosis of adcis in low and intermediate tumors. some authors have proposed that in situ ductal tumors with apocrine histopathology should be larger than 0.2 centimeters in order to be diagnosed as adcis. a study of 22 females aged 31 to 84 years (average age: 59 years) diagnosed with adcis reported that on presentation, 9 were asymptomatic (tumors detected by mammography), 11 were palpable breast masses with 2 of them associated with a nipple discharge and 2 of them diagnosed in females with paget's disease of the breast (two cases had no information on their presentations). none of the 22 individuals had invasive or metastatic disease including 9 who had armpit lymph node removals to investigate for metastases. the tumors ranged from 0.7 to 6 cm (mean: 2.3 cm) in size. on microscopic examination, the tumors had a microscopic histopathology similar to pacb tumors with 10 cases showing a cribriform pattern and 5 showing a micropapillary pattern. the tumors were estrogen receptor-negative, progesterone receptor-negative, and androgen receptor-positive in all cases except for one case with borderline estrogen receptor-positivity and another case with progesterone receptor-positivity. ten of these individuals had her2/neu-positive tumors. in the 17 individuals for whom this information was available, mastectomy, modified mastectomy, and simple mastectomy were performed in 8, 7, and 1 case, respectively; 5 also received adjuvant (i.e. post-surgery) radiotherapy. all of the treated individuals were alive without evidence of disease or recurrences from 9 to 194 months (average observation time: 37 months) after surgery. in a more recent study of 28 females (mean age:56 years) presenting with adcis: 28 had estrogen receptor-negative and androgen receptor-positive tumors; 25 (89.3% ) had progesterone-negative tumors; 9 (32.1%) had her2/neu-positive tumors; 27 had tumors cells that expressed the α-methylacyl-coa racemase protein; and 27 had tumor cells that expressed the prolactin-inducible protein. these results were virtually identical to those found in pacb tumor cells except for the 3 individuals with progesterone receptor-positive adcis tumor cells. during the follow-up period (15–55 months, mean: 32.0 months), all of the females were alive. the potential for adcis tumors to progress to a more malignant form is unclear but must be considered as a possibility. apocrine-like invasive carcinoma apocrine-like invasive carcinoma (alic), also termed apocrine-like carcinoma or invasive carcinoma with apocrine differentiation, has been defined as an invasive carcinoma that consists of a pacb-like microscopic histopathology in 10% to 90% of its tumor tissues or a pacb-like microscopic histopathology in >90% of its tumor tissues but, unlike pacb, has tumor cells which are estrogen receptor-positive and/or progesterone receptor-positive. reports on individuals with alic have been rare. a study published in 2013 compared 25 individuals presenting with alic to 44 with pacb. there were no significant differences between the two groups in age, tumor size, or lymph node metastases although patients with pacb had higher (50%), but statistically insignificant, rates of lymph note metastases than patients with alic (36%). these metastases were found in 1 to 10 lymph nodes of the patients. pabc tumors did have statistically significant increased aggressive histopathology and higher grades compared to alic tumors. tumor grading was based on the nottingham system, also termed the elston and ellis modification, which scores the tumor cells' tubule formation, nuclear pleomorphism, and mitotic counts (see nottingham system for grading breast cancer tumors). a higher grade tumor is more likely to have a poorer prognosis than a lower grade tumor. the patients were treated with mastectomy or more conservative breast surgery in all cases and, where deemed appropriate, with intraoperative electron radiation therapy or post-surgery radiotherapy in 35 and 24 individuals with pabc and alic, respectively. possibly due to their tumors' greater rate of metastases, more aggressive histopathology, and higher grade, more than half of the individuals with pabc were also treated with chemotherapy and/or hormone therapy; individuals with alic did not receive these additional treatments. relapse rates including those occurring at or near the original tumor site, spread to distant tissues, and/or occurrences in the opposite breast were 7.3% and 3.3% for individuals with pabc and alic, respectively. (patients with either pacb or alic had an increased risk of developing a cancer in the opposite breast compared to a control group of patients with invasive carcinoma of no special type). ten year disease-free survival rates were about 50% and 70% and ten year overall survival rates (i.e. surviving patients minus patients who died from any cause) were about 80% and 90% for individuals with pabc and alic, respectively. the difference in disease-free survival rates (but not the overall survival rates) between individuals with pabc and alic was significant. further studies with larger numbers of patients are required to further define the features of alic and accurately compare its long-term prognosis to pacb as well as other breast cancer tumors.