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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 mitogen-activated 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 anti-androgen 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 TMB-high). Therefore, a comprehensive cancer profiling of apocrine carcinomas is necessary to identify potential therapeutic targets for a truly individualized treatment approach.
While invasive breast carcinoma of no special type (NST) constitutes ∼70% of all breast malignancies, the remaining 30% include various and rare (special) subtypes, defined by distinct morphology, molecular expressions, and/or genetic features; consequently, clinical course and treatment options vary significantly.
to bring attention to the apocrine breast carcinoma, critically appraise and summarize the recent literature on molecular and clinical studies in the field.
WHO Definition of Apocrine Carcinoma
The 2019 WHO classification of breast tumors recognized apocrine carcinoma as a distinct, special type of breast cancer (under the name "carcinoma with apocrine differentiation").
It is characterized by a distinct apocrine morphology (described and illustrated in Figure 1), which must be present in >90% of cancer cells (=essential criteria). As desirable criteria, the WHO proposed a characteristic steroid receptor profile: Estrogen receptor (ER)-negative and androgen receptor (AR)-positive. When strictly defined using the essential and desirable criteria, apocrine carcinoma is a rare breast malignancy, constituting ∼1% of all breast cancers.
The WHO classification also proposed a diagnostic algorithm and differential diagnostic approach for breast tumors whose cells exhibit eosinophilic or foamy cytoplasm (Summarized and updated in Table 1). The diagnosis of apocrine carcinoma can occasionally be challenging due to the overlapping/similar/ morphology with some other, even rarer neoplasms, such as oncocytic carcinomas. However, the combination of morphology and specific immunohistochemical biomarkers (eg, mitochondrial stains) can be helpful in such difficult cases (Table 1). Other differential diagnoses (eg, granular cell tumors, histiocytic lesions) can also be ruled out using simple immunohistochemical algorithms (Table 1).
Figure 1An invasive breast carcinoma composed of nests and sheets of neoplastic cells with abundant, granular eosinophilic cytoplasm, well-defined cell borders, and large nuclei with prominent nucleoli (Hematoxylin and Eosin stain, 20x).
We believe that this approach will substantially improve the diagnosis of apocrine carcinoma, which has been a subject of discussion and controversy for a long time. The lack of clearly defined diagnostic criteria has also contributed to the contradictory and inconsistent data in the published literature, including diagnostics, clinical presentation, and outcome of the patients with apocrine carcinoma (please refer to the paragraphs on molecular and clinical characteristics, the results of these studies are summarized in Tables 2 and 3). A distinct "molecular apocrine carcinoma/tumor/" subtype was defined based on the analysis of the gene expression data and is characterized by the consistent AR activity and the lack of ER activity (with or without HER2 activity).
Gene expression studies also revealed that these tumors exhibit predominantly luminal features (eg, expression of luminal cytokeratins and the lack of basal features) and are therefore called "luminal androgen receptor"/LAR/ tumors.
However, molecularly defined apocrine carcinoma does not necessarily correlate with morphologically and immunohistochemically (ER-/AR+) defined apocrine carcinomas with the estimated overlap of ∼70% to 80%.
In addition, a vast majority of LAR carcinomas are of triple-negative phenotype while 30% to 60% of morphologically and immunohistochemically defined apocrine carcinomas exhibit ERBB2/HER2 overexpression. This was confirmed in a recent study by Bonnefoi et al, who showed the concordance between molecularly and immunohistochemically confirmed apocrine carcinomas to be 88%. They also found that 2/3 of these apocrine carcinomas were HER2 positive.
These data indicate that apocrine carcinomas are heterogeneous. Even when strictly defined by morphology and immunohistochemistry, two molecular subtypes of apocrine carcinomas exist (HER2-positive and triple-negative). Within both molecular subtypes, a small proportion of cases may show basal phenotype (eg, expression of basal cytokeratins and/or EGFR).
Table 2Overview of the Recent (≥2018) Molecular Studies and Novel Biomarkers Described in Apocrine Carcinoma of the Breast
Author (year)
Biomarker (molecular pathway) in Apocrine Carcinoma
Clinical Relevance
Gatalica-Vranic (unpublished data)
AMACR positive in 100% apocrine lesions, including apocrine carcinomas
Diagnostic utility; the study also revealed AMACR expression in non-apocrine lesions of the breast
Epithelial to mesenchymal transition and microRNA expression are associated with spindle and apocrine cell morphology in triple-negative breast cancer.
TBCRC 032 IB/II multicenter study: molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR(+) metastatic triple-negative breast cancer.
PTEN and HRAS mutations in apocrine DCIS with progression to spindle cell metaplastic carcinoma with the same mutations; EMT was supported by the loss of E-cadherin (CDH1 gene wild type) and nuclear Beta-catenin expression in invasive component; Loss of AR expression in the invasive component
Invasive apocrine carcinoma of the breast: clinicopathologic features and comprehensive genomic profiling of 18 pure triple-negative apocrine carcinomas.
94% of triple-negative apocrine carcinomas had at least one actionable genomic alteration (PIK3CA/mTOR inhibitors, CDK4/6 inhibitors, RAS/RAF/MEK inhibitors)
EGFR positive in 86.5% “molecular apocrine cases” (ER-/PR-/AR+) 32% co-expressed EGFR and HER2 EGFR negatively affected the prognosis; correlated with AR and higher Ki-67
Invasive apocrine carcinoma of the breast: clinicopathologic features and comprehensive genomic profiling of 18 pure triple-negative apocrine carcinomas.
Table 3Review of the Recent (≥2018) Studies Exploring the Clinical Characteristics, Treatment Response, And Outcome of the Patients With Apocrine Carcinoma of the Breast
TBCRC 032 IB/II multicenter study: molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR(+) metastatic triple-negative breast cancer.
Characteristics and prognosis of 17 special histologic subtypes of invasive breast cancers according to World Health Organization classification: comparative analysis to invasive carcinoma of no special type.
Invasive apocrine carcinoma of the breast: clinicopathologic features and comprehensive genomic profiling of 18 pure triple-negative apocrine carcinomas.
Clinicopathological characteristics and prognosis of breast cancer with special histological types: a surveillance, epidemiology, and end results database analysis.
Avoidance and period-shortening of neoadjuvant chemotherapy against triple-negative breast cancer in stages I and II: importance of Ki-67 labeling index and the recognition of apocrine-type lesions.
Androgen receptor expression and association with distant disease-free survival in triple negative breast cancer: analysis of 263 patients treated with standard therapy for stage I-III disease.
Pathological response in a triple-negative breast cancer cohort treated with neoadjuvant carboplatin and docetaxel according to Lehmann's refined classification.
It is still a common practice to diagnose apocrine carcinomas by their morphologic features. Given the recent recommendations from the WHO Classification of Breast Tumors,
we advise the practicing pathologists to adopt a new diagnostic algorithm, which combines a steroid receptor profile and the characteristic apocrine morphology. We believe that this approach will improve diagnostic accuracy and consistency in reporting of apocrine carcinomas and ultimately contribute to a better clinical characterization of this peculiar mammary malignancy.
Novel Molecular Characteristics and Biomarkers of Apocrine Carcinoma
The results of the recent molecular studies on apocrine carcinoma are summarized in Table 2.
AR expression is a characteristic, diagnostic hallmark of apocrine carcinoma but itself is not specific, as AR is expressed in a variety of breast carcinomas, both ER-positive (70%-90%) and ER-negative (20%-40%).
Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation.
Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation.
Prognostic and predictive value of androgen receptor expression in postmenopausal women with estrogen receptor-positive breast cancer: results from the Breast International Group Trial 1-98.
A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1).
showed low to modest therapeutic benefits of antiandrogens in a mixed group of AR+ breast carcinomas. Both studies included ER-positive and ER-negative AR-positive breast carcinomas with a pretreatment assessment of the AR positivity. Furthermore, other important biomarkers, including those involved in a potential anti-AR resistance, have not been explored. Other clinical trials with anti-AR are explored in more detail in a recent review of Cipriano et al.
explored the CAG repeat number of the AR gene in a cohort of fibroadenomas, DCIS, and invasive breast carcinomas. The authors found the highest CAG repeats in DCIS, particularly in DCIS with apocrine differentiation.
A study by Lee et al exploring the CAG polymorphisms of the AR gene revealed no association with the development of breast cancer, but patients with more (23+) CAG repeats of the AR gene had a poor prognosis.
Cremonini et al recently reported a small (n = 20), well-defined apocrine cohort exploring the status of the AR gene. They found AR loss (monosomy) in most of the tested cases, along with the retained transcriptional activity of several AR regulatory genes, including the MAGE family, UXT, and FLNA genes.
Based on these findings, the authors speculated that the patients with apocrine carcinoma might benefit from androgen-deprivation therapy, but this requires a clinical validation. Androgen receptor variant 7 (ARv7), a splice variant of AR, is another essential biomarker closely related to anti-AR effectiveness (resistance) as confirmed in prostate carcinoma,
The AR-V7 encodes a truncated AR protein that possesses only the transactivating N-terminal domain without the C-terminal ligand-binding domain, resulting in constitutive activation of AR.
Similar effects have been shown in breast cancer. Thus, ARv7 variants might induce proliferation of the apocrine cell line MDA-MB-453 in the presence of antiandrogen enzalutamide.
The overall frequency was ∼10% but was significantly higher (42%) in AR+ carcinomas with apocrine morphology. Notably, ARv7 was also detected in primary, therapy-naïve breast carcinomas (without previous exposure to anti-androgens), indicating a potentially different mechanism of ARv7 activation in the breast compared with prostate carcinomas, but similar to the findings of ARv7 in salivary duct carcinomas.
The authors proposed routine ARv7 testing for all patients with AR-positive apocrine tumors that are being considered for the treatment with AR inhibitors.
Interestingly, ARv7 and co-amplification of AR and the nuclear co-receptor NCOA2, both of which are associated with anti-AR resistance in prostate cancer,
TBCRC 032 IB/II multicenter study: molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR(+) metastatic triple-negative breast cancer.
ARv7 was also identified among the non-responders to antiandrogens, indicating its role in the resistance to the therapy. Although LAR patients had better therapeutic response to the combined AR/PIK3CA inhibition than non-LAR TNBC patients, overall therapeutic benefit was limited.
TBCRC 032 IB/II multicenter study: molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR(+) metastatic triple-negative breast cancer.
This study is one of the properly designed clinical trials that included a comprehensive molecular assessment prior and after the targeted treatments. Owing to such a design, the authors were able to identify biomarkers of response and resistance.
Gross cystic disease fluid protein 15 (GCDFP-15 or PIP-3), along with AR expression, has been considered a biomarker of apocrine differentiation in the breast.
Nakamura et al recently reported that α-Methylacyl-CoA racemase (AMACR) is expressed with a marked preponderance in apocrine breast carcinomas (both in situ and invasive). AMACR has been a biomarker of prostate and several other cancers (eg, papillary renal cell carcinoma, urothelial carcinoma in situ).
They found that AMACR was expressed in 96% of apocrine ductal carcinoma in situ (DCIS) cases and 97% of invasive apocrine carcinomas, in contrast to non-apocrine carcinomas that exhibited AMACR positivity in only 22% of the cases. The study revealed a comparable sensitivity of AMACR with GCDFP-15 for apocrine carcinomas, whereas the AMACR specificity was significantly higher (78% vs. 32%). Notably, AMACR protein expression correlated well with its mRNA expression.
The expression of AMACR (Figure 2) raises an interesting possibility of the role of diet and the interplay with the hormonal status and apocrine breast carcinomas. High animal fat consumption is associated with an increase in triple-negative breast cancer (TNBC) risk in premenopausal women.
Figure 2A case of apocrine carcinoma with micropapillary growth pattern (A) exhibiting diffuse expression of α-Methylacyl-CoA racemase (AMACR) protein by immunohistochemistry (B).
. The claudins are transmembrane proteins that regulate the tight junctions between epithelial cells and are involved in signaling between the epithelial cells and their environment
Sousha et al recently demonstrated claudin 1 and claudin 3 expressions and the lack of claudin 4 protein expression in a small cohort of apocrine lesions, including invasive apocrine carcinoma with the triple-negative phenotype.
The diagnostic and potential therapeutic utility of these findings remains unknown.
MicroRNAs (miRNAs) represent small non-coding RNAs that act as post-transcriptional regulators of various cellular functions. miRNAs negatively regulate gene expression by their binding to their selective messenger RNAs (mRNAs), causing either mRNA degradation or translational repression, depending on their complementarity with target mRNA sequences.
Epithelial to mesenchymal transition and microRNA expression are associated with spindle and apocrine cell morphology in triple-negative breast cancer.
demonstrated that triple-negative breast carcinomas with apocrine and spindle cell (metaplastic) morphology exhibited a distinct miRNA profile compared with other breast cancers. In particular, they showed the downregulation of hsa-miRNA-143-3p and hsa-miRNA-205-5p and upregulation of the hsa-miR-22-3p, hsa-miRNA-185-5p, and hsa-miR-4443 (Table 2). Apocrine carcinomas also had decreased expression of hsa-miR-145-5p and increased expression of additional 14 miRNAs, including hsa-miR-182-5p, hsa-miR-3135b, and hsa-miR-4417. The pathway analysis revealed that these miRNAs closely interfere with several important signaling pathways, such as Wnt, ErbB/HER2, and MAPK pathways; the authors also speculated that these miRNAs might contribute to EMT in special types of TNBC – apocrine and spindle cell (metaplastic) carcinomas, concluding that further mechanistic studies are essential to confirm their observations.
Epithelial to mesenchymal transition and microRNA expression are associated with spindle and apocrine cell morphology in triple-negative breast cancer.
Notably, we also demonstrated the active EMT in a case of morphologically apocrine DCIS (AR+) harboring PTEN and HRAS mutations with progression to spindle cell metaplastic carcinoma that had the same mutational profile and a loss of AR expression.
EMT was supported by the loss of E-cadherin protein (without CDH1 gene mutations or loss) and nuclear ß-catenin expression in invasive spindle cell component.
Further studies are required to elucidate the EMT in apocrine carcinomas and its clinical relevance (therapy response and resistance).
The recent studies indicate that EMT might be actively involved in the pathogenesis of apocrine carcinomas via several molecular mechanisms. However, these studies do not reflect the full spectrum of signaling pathways that are involved in EMT in apocrine tumors.
Also, the clinical relevance of the observed alterations in apocrine carcinomas should be confirmed.
Immune Checkpoint Inhibitors in Apocrine Carcinoma
Immune checkpoint inhibitors (ICI) have markedly improved the treatment options and outcome of various solid and hematologic malignancies, including triple-negative breast cancer (TNBC). Thus, FDA approved pembrolizumab in both neoadjuvant and adjuvant settings along with its companion diagnostic test for PD-L1 testing (22c3 pharmDx assay, Agilent Technologies). In contrast, atezolizumab and its CDx SP142 were initially approved in 2019 but were withdrawn in August 2021 from use in TNBC patients.
Most of the clinical trials and randomized studies with ICI have not specifically addressed the role of apocrine morphology among TNBC. In addition, the response of HER2-positive apocrine carcinomas to ICI remains largely unknown despite the recently published promising therapeutic effects of atezolizumab combined with anti-HER2 drugs on HER2-positive breast carcinomas.
Impact of Anti-HER2 treatments combined with atezolizumab on the tumor immune microenvironment in early or metastatic breast cancer: results from a phase Ib study.
Several predictive biomarkers of response to ICI have been validated, including PD-L1 expression (on cancer, immune cells or both), high tumor mutational burden (TMB-H), and high microsatellite instability status (MSI-H). In TNBC samples, PD-L1 expression (positivity defined as Combined Positive Score [CPS] ≥10) detected by immunohistochemistry has been approved as a companion diagnostic (CDx) test for pembrolizumab.
Three recent studies indicate that apocrine carcinomas show low PD-L1 expression in both tumor and immune cells, low tumor mutational burden, and are consistently microsatellite stable (MSS).
Invasive apocrine carcinoma of the breast: clinicopathologic features and comprehensive genomic profiling of 18 pure triple-negative apocrine carcinomas.
the studies reported low TIL in apocrine carcinomas, which along with a low percentage of intratumoral CD8+ and CD3+ lymphocytes, and a loss of MHC class I (including PD-L1+ apocrine cases), make patients with this cancer less likely responsive to ICIs.
Numerous studies have been published on various subtypes of breast cancer, but those exploring molecular features specifically of apocrine carcinoma remain sparse. Sun et al profiled eighteen "pure" triple-negative apocrine carcinomas (apocrine morphology + AR positivity), revealing PIK3CA (72%), PTEN (33%), and TP53 (28%) alterations as the most common in apocrine carcinomas.
Invasive apocrine carcinoma of the breast: clinicopathologic features and comprehensive genomic profiling of 18 pure triple-negative apocrine carcinomas.
A proportion of the cases also harbored genetic alterations within the MAPK pathway (BRAF, HRAS, KRAS, MAP3K1), cell cycle regulators (CDKN2A, CDKN2B, CDK6), and FGF pathways (FGFR2 amplification and fusion) (Table 2). Notably, one apocrine case had a well-described TERT gene promoter mutation (c.-124C > T), while another had a novel FGFR2-TACC2 fusion, not previously reported in breast cancer.
Invasive apocrine carcinoma of the breast: clinicopathologic features and comprehensive genomic profiling of 18 pure triple-negative apocrine carcinomas.
The authors concluded that a vast majority of apocrine carcinomas harbored potentially targetable but diverse genomic alterations, making their detection a requirement for successful personalized medicine approach (eg, PIK3CA/mTOR inhibitors
Invasive apocrine carcinoma of the breast: clinicopathologic features and comprehensive genomic profiling of 18 pure triple-negative apocrine carcinomas.
TBCRC 032 IB/II multicenter study: molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR(+) metastatic triple-negative breast cancer.
explored anti-AR Enzalutamide combined with PIK3CA inhibitor Taselisib in a small cohort of AR-positive metastatic TNBCs (phase Ib/II study, TBCRC032). Seventeen pretreated patients randomly received enzalutamide with or without taselisib. Although all the patients experienced disease progression at 16 weeks except for one patient with LAR who was on the combined treatment and had not progressed within 18 months when the study was terminated.
TBCRC 032 IB/II multicenter study: molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR(+) metastatic triple-negative breast cancer.
In addition, the authors found AR expression to be insufficient in predicting the response although the LAR carcinomas had a substantially higher clinical benefit (75%) compared with other TNBC molecular subtypes (12.5%).
TBCRC 032 IB/II multicenter study: molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR(+) metastatic triple-negative breast cancer.
Dysregulation of the cell cycle regulators (CDKN2A and B, CDK6) in a subset of apocrine carcinomas indicates a potential for the treatment with CDK4/6 inhibitors, as shown in the study of Asghar et al.
The authors performed comprehensive in vitro and in vivo experiments using various breast cancer cell lines, including the apocrine MDA-MB-453 cells. They demonstrated that the apocrine cells were highly sensitive to CDK4/6 inhibitors. More importantly and relevant to apocrine carcinomas, CDK4/6 inhibitors exhibited a synergistic effect with PIK3CA inhibitors in PIK3CA-mutant cell lines including MDA-MB-453, extending the use of combined treatment with both CDK4/6 and PIK3CA inhibitors.
Taken together, the recent data confirm the relevance of comprehensive molecular profiling in identifying the targetable biomarkers in apocrine carcinomas. Further translational and clinical studies (basket trials) are needed to verify the findings from the cell lines and molecular studies. These could pave new treatment modalities for patients with advanced disease.
Clinical Studies on Apocrine Carcinoma
We systematically reviewed the recent literature (≥2018) on apocrine carcinoma exploring PubMed/MEDLINE, Scopus, and Web of Science Core Collection databases, using the following keywords: "Apocrine carcinoma", "carcinoma with apocrine differentiation", "molecular apocrine carcinoma", "luminal androgen receptor carcinoma", and "breast", "clinical characteristics/features", "outcome", and "survival". The studies exploring non-invasive carcinomas (=apocrine DCIS) and benign apocrine lesions (eg, adenosis, metaplasia) were excluded from the analysis and review. Case reports and small case series (<5 patients) were also excluded.
Our literature search in the databases revealed 32 clinical studies that have been published since 2018 (the studies and their major results are summarized in Table 3). The number of the patients in the studies shows marked differences, varying from small studies involving 8 to 10 patients
Androgen receptor expression and association with distant disease-free survival in triple negative breast cancer: analysis of 263 patients treated with standard therapy for stage I-III disease.
to a large series (>1000 patients) retrieved from the publicly available databases such as the Surveillance, Epidemiology, and Ends of Results (SEER) and National Cancer Center Database (NCDB). Notably, most of the reported studies focused on the triple-negative apocrine carcinomas, while very few specifically explored HER2-positive apocrine carcinomas.
Similarly, most studies also reported the clinical outcome (overall- or disease-specific survival) of the patients with apocrine carcinoma alone or compared with the matched NST subgroup.
Consistent with the previous data, our literature survey confirms contradictory results about the response to chemotherapy and clinical outcome of patients with apocrine carcinoma. This is likely to be caused by the inconsistent diagnostic criteria used to define apocrine carcinomas. We believe that the new WHO definition of apocrine carcinoma with diagnostic utilization of essential and desirable criteria will help better define this category and hence identification of clinically useful information.
Very few studies specifically explored the effects of (neo) adjuvant chemotherapy in patients with apocrine carcinoma.
Pathological response in a triple-negative breast cancer cohort treated with neoadjuvant carboplatin and docetaxel according to Lehmann's refined classification.
Several studies clearly pointed the limited response of molecularly defined triple-negative apocrine carcinomas (LAR) to neoadjuvant chemotherapy in comparison with other non-apocrine TNBC.
Pathological response in a triple-negative breast cancer cohort treated with neoadjuvant carboplatin and docetaxel according to Lehmann's refined classification.
In addition, a systematic review of Trapani et al. revealed that triple-negative, AR+ positive apocrine carcinomas had no benefit of adjuvant chemotherapy if treated in the early stage (pN0).
As discussed above, the response to anti-AR may also be limited due to the various resistance mechanisms as shown in a detailed clinical and molecular study by Lehmann et al.
TBCRC 032 IB/II multicenter study: molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR(+) metastatic triple-negative breast cancer.
Recent advances have contributed to the improved diagnostics of apocrine carcinoma of the breast. These efforts should also reduce the considerable variability and discrepancy in apocrine carcinomas' definition, molecular and clinical characteristics. Novel biomarkers have also been described, but their diagnostic and clinical (predictive and prognostic) utility has to be confirmed. The current evidence indicates that AR-positive breast carcinomas, including apocrine subtype, may have limited clinical benefit of (neo) adjuvant chemotherapy. Apart from the Her-2/neu target, advanced and/or metastatic apocrine carcinomas still have limited targeted treatment options. The role of antiandrogens in apocrine and other AR-positive breast carcinomas also require further research as limited data (small number of studies and small sample size) on the potential mechanisms of response/resistance are currently available. Therefore, a comprehensive genomic cancer profiling of apocrine carcinomas appears to be a promising approach that could reveal potential targets for an individualized therapeutic treatment.
Disclosure
The authors declare no conflict of interest.
Acknowledgments
The Qatar National Libary (QNL) funded the publication of this article.
Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation.
Prognostic and predictive value of androgen receptor expression in postmenopausal women with estrogen receptor-positive breast cancer: results from the Breast International Group Trial 1-98.
A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1).
TBCRC 032 IB/II multicenter study: molecular insights to AR antagonist and PI3K inhibitor efficacy in patients with AR(+) metastatic triple-negative breast cancer.
Epithelial to mesenchymal transition and microRNA expression are associated with spindle and apocrine cell morphology in triple-negative breast cancer.
Impact of Anti-HER2 treatments combined with atezolizumab on the tumor immune microenvironment in early or metastatic breast cancer: results from a phase Ib study.
Invasive apocrine carcinoma of the breast: clinicopathologic features and comprehensive genomic profiling of 18 pure triple-negative apocrine carcinomas.
Androgen receptor expression and association with distant disease-free survival in triple negative breast cancer: analysis of 263 patients treated with standard therapy for stage I-III disease.
Pathological response in a triple-negative breast cancer cohort treated with neoadjuvant carboplatin and docetaxel according to Lehmann's refined classification.
Characteristics and prognosis of 17 special histologic subtypes of invasive breast cancers according to World Health Organization classification: comparative analysis to invasive carcinoma of no special type.
Clinicopathological characteristics and prognosis of breast cancer with special histological types: a surveillance, epidemiology, and end results database analysis.
Avoidance and period-shortening of neoadjuvant chemotherapy against triple-negative breast cancer in stages I and II: importance of Ki-67 labeling index and the recognition of apocrine-type lesions.
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