Some Triple-Negative Breast Cancers Express Androgen Receptor



ORLANDO – Triple-negative breast tumors are notorious for their ability to evade hormonal agents and targeted therapies. But a subset of these intractable tumors expresses androgen receptors, and may be vulnerable to antiandrogen drugs, investigators suggested at the symposium of the Society of Surgical Oncology.

An evaluation of cancerous and normal breast tissues from 94 patients with triple-negative breast tumors (lacking estrogen-, progesterone-, and HER2-receptor expression), showed that the androgen receptor (AR) was expressed in 23% of tumors, reported Dr. Barbara Pockaj of the Mayo Clinic in Scottsdale, Ariz., and colleagues.

AR–positive cancers occurred more frequently in older patients and were significantly associated with lymph node metastases, compared with AR-negative, triple-negative breast cancers in this small study, she said.

There was a trend toward higher tumor stage at diagnosis among patients with AR-positive tumors, but AR-positive and AR-negative patients did not differ significantly in overall or recurrence-free survival, said Dr. Pockaj.

Previous studies have suggested that 10%-43% of triple-negative breast cancers bear the androgen receptor, but the antibodies and methods used for characterizing the presence of the receptor varied significantly, making it difficult to nail down actual numbers, Dr. Pockaj said.

The investigators examined 177 tissue biopsy cores from 94 patients with triple-negative breast cancer to see whether AR-receptor expression correlated with patient and tumor factors and survival, and where expression of the receptors in different tissues from the same patients correlated with tumor progression.

The receptor was expressed in 88% of normal breast tissues in the samples, a proportion identical to that of the estrogen receptor in normal tissues from the same patients.

AR expression was detected in all 6 of 6 adjacent DCIS (ductal carcinoma in situ) samples from AR-positive patients, and in 9 of 15 DCIS samples from patients with AR-negative cancer.

All lymph node metastases from AR-positive patients were also positive, whereas no lymph node metastases from AR-negative patients were found to express the androgen receptor.

There were no significant differences between AR-positive and -negative patients in tumor grade, angiolymphatic invasion, TNM (tumor, node, metastasis) stage, or tumor size. In contrast, 16 of the 72 (22%) of the AR-negative patients had lymph node metastases, compared with 10 of 22 (46%) AR-positive patients (P = .033).

There were no significant differences in locoregional recurrences, overall survival, or disease-specific survival between positive and negative patients.

Among all 94 patients, however, the presence of lymph node metastases was associated with a significantly worse recurrence-free survival (hazard ratio, 5.502; P = .017). Chemotherapy significantly reduced that risk (HR, 0.099; P = .0004).

In multivariate analysis, the investigators found that AR expression was associated with older age (63 years vs. 57 years; P = .051) and with the presence of lymph nodes metastases (P = .033).

Although larger studies are needed, the data suggest that AR-positive, triple-negative breast cancer "has unique clinical behavior and may need different treatment," Dr. Pockaj said.

A phase II, open-label trial of the antiandrogen bicalutamide (Casodex) in patients with AR-positive, estrogen- and progesterone-receptor–negative, metastatic breast cancer is currently underway in eight U.S. cancer centers.

The current study was supported by the Translational Genomics Research Institute, Phoenix, and the Mayo Clinic, Scottsdale, Ariz. Dr. Pockaj is an employee of the Mayo Clinic.

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