Lack of Androgen Receptor Protein May Contribute to Racial Disparities in Triple-Negative Breast Cancer Outcomes
Triple-negative breast cancer in African American women is much more likely to lack the androgen receptor protein compared with triple-negative breast cancer in European American women, and this may contribute to the racial disparity in survival outcomes among these two populations, according to a study (B12) presented at the 9th American Association for Cancer Research (AACR) Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held September 25 to 28 in Fort Lauderdale, Florida.
Lack of Targetable Proteins
A major characteristic of triple-negative 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. Triple-negative breast cancer thus has high recurrence and mortality rates, especially within the first 5 years after diagnosis, explained Shristi Bhattarai, a PhD student under the supervision of Ritu Aneja, PhD, at Georgia State University. African American women have a higher prevalence of triple-negative breast cancer and worse prognosis from this disease compared with European American women, she added.
“Studies have shown that androgen receptor (AR) signaling can influence the tumor biology of triple-negative breast cancer, but there are conflicting reports about the influence of AR on clinical outcomes,” said Ms. Bhattarai. Since biogeographic ancestry can also impact triple-negative breast cancer tumor biology, the researchers wanted to evaluate whether AR status tends to differ between African American and European American triple-negative breast cancers and whether that difference contributes to the disparity in breast cancer–related outcomes between African American and European American women.
“In our study, the triple-negative breast cancers in African American 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 African American women may be a plausible contributor to the ethnic disparity in outcomes among triple-negative breast cancer 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 triple-negative breast cancers in African American and European American women,” she added.
Study Findings
For their study, Bhattarai and colleagues used breast cancer samples from 813 triple-negative breast cancer 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 European American, 138 African American) information were available.
The team studied formalin-fixed, paraffin-embedded samples from the patients for the presence of AR protein. Triple-negative breast cancer samples were considered quadruple-negative if they had less than 1% of the cells positive for AR; samples that had AR in more than 1% of the cells were considered positive for AR.
Overall, 45.6% of the triple-negative breast cancer samples were quadruple-negative, but the rate of quadruple-negative breast cancer in African American women was twice as that of European American women—80.8% of African Americans vs 40.1% of European Americans. 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 triple-negative breast cancer and the therapeutic implications of AR status for triple-negative breast cancer 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 triple-negative breast cancer patients,” Ms. Bhattarai added.
A key limitation of the study is the lack of ancestry genotype information for the patients, she noted. The African American 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 African American women in the study can help get deeper insights into the interplay between genetic ancestry, AR status, and the tumor biology of triple-negative breast cancer, she said.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
