An Update on the Molecular and Clinical Characteristics of Apocrine Carcinoma of the Breast

Abstract

Apocrine carcinoma of the breast is a rare malignancy. According to 2019 WHO classification, apocrine cellular features and a characteristic steroid receptor profile (Estrogen receptor (ER)-negative and androgen receptor (AR)-positive) define apocrine carcinoma. Her-2/neu protein expression is reported in ∼30-50% of apocrine carcinomas, while NGS analysis showed frequent PIK3CA/PTEN/AKT and TP53 mutations Followed by deregulation in the mitogen-activated protein kinase pathway components (mutations of KRAS, NRAS, BRAF ). A recent miRNA study indicates various miRNAs (downregulated hsa-miR-145-5p and upregulated 14 miRNAs such as hsa-miR-182-5p, hsa-miR-3135b, and hsa-miR-4417) may target the commonly altered pathways in apocrine carcinomas such as ERBB2/HER2 and mitogenactivated protein kinase signaling pathway. Although AR expression is a hallmark of apocrine carcinoma, little is known regarding the efficacy/resistance to antiandrogens. Success of bicalutamide, a non-steroidal anti-androgen, was reported in a case of Her2-negative apocrine carcinoma. Two recent studies, however, described presence of antiandrogen resistance biomarkers (a splice variant ARv7 and AR/NCOA2 co-amplification) in a subset of AR + apocrine carcinomas, cautioning the use of anti-androgens in AR + triple-negative breast carcinomas. Apocrine carcinomas rarely show biomarkers predictive of response to immune checkpoint inhibitors (PD-L1 expression, MSI-H status, and TMBhigh). Therefore, a comprehensive cancer profiling of apocrine carcinomas is necessary to identify potential therapeutic targets for a truly individualized treatment approach.

Triple-Negative Apocrine Breast Carcinoma Has Better Prognosis despite Poor Response to Neoadjuvant Chemotherapy

“…Despite these differences, TNAC is treated in the same manner as other TNBC, although the benefit of the AR antagonist bicalutamide was investigated in advanced ER- and PR-negative patients [ 30 ]. In concordance with previous studies [ 31 , 32 , 33 , 34 ], our results demonstrate that apocrine carcinoma has better prognosis than invasive breast carcinoma of no special type. More significantly, our results showed that TNAC patients have a poor chemotherapy responsiveness and no benefit from chemotherapy in terms of BCSS.…”

HER2-positive apocrine carcinoma of the breast: a population-based analysis of treatment and outcome

“…We observed some clinically relevant differences between the APO and NST groups. Thus, HER2+/SR−/APO had significantly lower histological grade than the NST carcinomas, which is in line with several previous studies and is probably due to the lower mitotic activity (and lower Ki-67 labeling) of apocrine cells [ 9 , 17 , 19 , 20 ]. Lower tumor grade may also contribute to the less aggressive behavior of HER2+/APO, as confirmed in a large cohort of IBS NST in which a high histological grade was a strong predictor of an adverse outcome [ 15 ].…”

“…APO is a rare (frequency ~ 1%) subtype of breast carcinoma whose diagnosis and clinical data, including outcome, remain challenging and controversial [ 14 , 19 ]. Based on the SEER data (2010–2016), the current study represents the largest HER2-positive APO cohort reported to date.…”

“…In contrast, APO consistently overexpress AR [ 6 ], but the AR status was not provided in the SEER database. This is understandable given the timeline of the collected data (2010–2016) and the fact that AR testing was only recently incorporated into a recommended diagnostic work-up of the breast's APO [ 14 , 19 ]. Consequently, some of the tumors in the study, particularly ER/PR-positive, may not be true molecular APO.…”

“…The available clinical data on APO are contradictory due to the rarity of the disease and the use of different diagnostic criteria for APO [ 14 , 19 , 21 ]. Several recent studies have reported a worse clinical outcome in patients with APO than invasive breast carcinoma of no special type (IBC NST) [ 4 , 24 ].…”