Breast cancer is a public health problem; In the Latino population, a high incidence of TNBC has been described, 21.3%, concerning all breast cancers11. Once this group has been identified, it has been proposed to search for the expression of AR in tumor tissue because it can provide the opportunity for targeted treatment to these patients, since, in the absence of these, the standardized treatment is neoadjuvant chemotherapy at the beginning of treatment with high response rates, but with short-lasting results, due to resistance mechanisms that develop12; At UMAE N° 1, Guanajuato, Mexico, this group received treatment with chemotherapy based on platinum and taxanes, as well as the addition of anthracyclines in advanced stages, with excellent responses at the beginning, but with early relapses at 2 years.
Our study identified 12.2% of TNBC cases, documenting Lehmann et al that this molecular type constitutes 10 to 20% of all breast cancer cases13; the result of this protocol follows the international bibliography. Regarding the prevalence of AR expression in TNBC, it varies from 13.7–75% 29, finding our result in this range, where the presence of AR was confirmed in 18.42% of the tumors studied.
In the bivariate analysis, we did not find statistical significance in the correlation of the expression of AR with any of the variables evaluated. The mean age of the patients in the cases studied with positive AR was 54 years; Breast cancer, in general, is considered in women of childbearing age with an increase directly proportional to the increase in age, McGuire et al mentioned that more than 40% of affected patients are over 65 years of age14, and the cases with triple-negative immunophenotype occur in younger women than those with another immunophenotype15. Most authors consider it to be a non-associated factor16. Tumor size has been described as not associated with the presence of AR, while other studies have mentioned that the tumors that present them tend to be smaller.
In our study, it was observed that NOS-IDC was the predominant morphology, however, this characteristic was not generally found associated with the presence of these receptors; On the other hand, it has been observed that some of the special types of carcinomas (metaplastic, mucinous and medullar) express AR to a lower percentage16,17, finding in the case series of this study a small but existing percentage of tumors with this histology: 6 cases (9.68% of all positive cases). It has been reported that breast carcinomas with histological grade 1 mostly express AR18, however, we did not find any AR-positive case histological grade 1 of the Nottingham scale, rather there was an expression in grades 2 and 3. The lymphovascular invasion is a predictor of greater aggressiveness of the disease, regardless of the expression of AR19, we found 7 cases with lymphatic invasion (50%) and 3 cases with angioinvasion (21.43%).
Numerous molecular sub-classifications have been made in the group of TNBC, one of the frequently used classifications is the one proposed by Lehmann et al, which includes 6 sub-groups: two of the basal-like (BL-1 and 2), immunomodulatory (IM), mesenchymal (M) and luminal androgen receptor (LAR) subtype9. This same classification was reduced to 4 categories (BL1, BL2, M, and LAR) after a subsequent review. Low-claudin tumors are another less common subtype20. Also, this molecular classification includes tumors with apocrine differentiation that comprise neoplasms with apocrine morphology and that are positive for AR. It can be found: negative ER and PR with positive HER2/neu + and AR or as triple-negative with AR21 expression.
Current therapy can be effective, but with significant unwanted effects: decreased immunity to other diseases, changes in liver enzymes, hair loss, loss of appetite, nausea, vomiting (temporary or permanent), frigidity or impotence, as well such as anxiety and depression21; it also carries a high cost. Patients with a complete response have a good prognosis 22. The ARs are physiologically found in healthy breast tissue, they are expressed in up to 90% of primary breast tumors and 75% of metastatic lesions23. Together with ERs and PRs, they are the main members of the steroid superfamily that induce mammary cell growth by binding to their corresponding receptors (ligands), resulting in the clonal proliferation of non-neoplastic and neoplastic cells24. The fundamental role of estrogen and progesterone receptors regarding the prognosis and treatment of these neoplasms is widely known. In contrast, little is known about the exact role of the androgen receptor in breast cancer tumorigenesis.
The ligands of these receptors, androgens, influence the risk of contracting breast cancer through direct binding to their receptors or indirectly through their transformation to estradiol, or by competing for steroid-binding proteins25. During postmenopause, there is a decrease in estrogen levels, so adrenal androgens are responsible for an estrogenic replacement for the cells. This supplemental metabolic pathway represents the main source of circulating estrogens and androgens in this age group26.
There is evidence to suggest that androgen receptors can inhibit or promote tumorigenesis of the breast. In some reports, it antagonizes the union of DNA with the alpha estrogen receptor, this prevents the transcription of proliferative genes; other authors have shown that they assume the role of alpha estrogen pseudoreceptors, particularly in triple-negative breast cancer. There has also been reports of breast cancer resistant to endocrine treatment associated with high expressions of AR. The first clinical trial on the therapeutic possibility of ARs was published by Gucalp et al in 2013, with an AR antagonist, where a clinical benefit rate of 19% was found with a median disease-free survival of 12 weeks, corroborating the therapeutic potential of these27.
Among the drugs mentioned in case series reports are bicalutamide and enzalutamide, which belong to the first and second generation of androgen receptor antagonists; by proposing the standardized search for androgen receptors to triple-negative tumors, is an option for adjuvant targeted therapy that could be applied in patients with this type of tumor. Other therapeutic targets are currently under study, including PARP1, receptor and non-receptor tyrosine kinases, immune checkpoints, epigenetic proteins, and STAT328,29.