Lack of Androgen Receptor Protein May Contribute to Racial Disparities in Triple Negative Breast Cancer Outcomes

Triple-negative breast cancer (TNBC) in African-American women is much more likely to lack the androgen receptor protein compared with TNBC in European-American women, and this may contribute to the racial disparity in survival outcomes among these two populations, according to a study presented at the Ninth AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held Sept. 25-28.

A major characteristic of TNBC, an aggressive subtype of breast cancer, is that these cancers do not express any of the three proteins, estrogen receptor (ER), progesterone receptor (PR), and Her2/neu, which can be targeted by available therapies. TNBC thus has high recurrence and mortality rates especially within the first five years after diagnosis, explained Shristi Bhattarai, a PhD student under the supervision of Ritu Aneja, PhD, at Georgia State University in Atlanta.Shristi Bhattarai

African-American (AA) women have a higher prevalence of TNBC and worse prognosis from this disease compared with European-American (EA) women, she added.

“Studies have shown that androgen receptor (AR) signaling can influence the tumor biology of TNBC, but there are conflicting reports about the influence of AR on clinical outcomes,” said Bhattarai. Since biogeographic ancestry can also impact TNBC tumor biology, the researchers wanted to evaluate if AR status tends to differ between AA and EA TNBCs, and if that difference contributes to the disparity in breast cancer-related outcomes between AA and EA women.

“In our study, the TNBCs in AA women tended to be AR-negative, and multivariable analyses showed that the loss of AR expression was associated with poorer survival. The higher prevalence of quadruple-negative breast cancer [lack of ER, PR, HER2/neu, and AR] among AAs may be a plausible contributor to the ethnic disparity in outcomes among TNBC patients,” Bhattarai said.

“We are excited about our findings because one of the biggest questions confronting clinicians and researchers pertains to the inherent differences in the tumor biology between the TNBCs in African-American and European-American women,” she added.

For their study, Bhattarai and colleagues used breast cancer samples from 813 TNBC patients treated at Emory, Northside, or Grady Memorial Hospitals in Atlanta, or at Nottingham Hospital in the United Kingdom, for whom complete clinicopathologic data, overall survival, and ethnicity (675 EA, 138 AA) information were available.

The team studied formalin-fixed, paraffin-embedded samples from the patients for the presence of AR protein. TNBC samples were considered quadruple-negative if they had less than 1 percent of the cells positive for AR; samples that had AR in more than 1 percent of the cells were considered positive for AR.

Overall, 45.6 percent of the TNBC samples were quadruple-negative, but the rate of quadruple-negative breast cancer in AA women was twice as that of EA women—80.8 percent of AAs versus 40.1 percent of EAs. The researchers measured the time interval between the date of diagnosis and the date of death or last follow-up and found that after adjusting for grade, stage, and adjuvant therapy, women with quadruple-negative breast cancer were almost three times as likely to die as those whose tumors had AR expression.

“Since AR can serve both as a predictive as well as a prognostic biomarker, routine screening of AR along with ER, PR, and HER2 may be beneficial,” Bhattarai said. Further translational studies are required to gain clarity on the mechanisms of androgen action in TNBC and the therapeutic implications of AR status for TNBC patients, she noted.

“Our study shows that genetic ancestry and AR status are key factors that should be taken into consideration while designing and enrolling patients for clinical trials aimed at finding new targeted therapies for TNBC patients,” Bhattarai added.

A key limitation of the study is the lack of ancestry genotype information for the patients, Bhattarai noted. The AA population in the United States is highly admixed and information about race in this study was all self-proclaimed. Knowledge of the proportion of African genetic ancestry among the AA women in the study can help get deeper insights into the interplay between genetic ancestry, AR status, and the tumor biology of TNBC, she said.

This study was funded by the National Institutes of Health. Bhattarai declares no conflicts of interest.