Triple-negative breast cancer (TNBC) accounts for approximately 15 percent of all breast cancers. This type of breast cancer is named because the tumor cells lack the expression of the estrogen, progesterone, and HER2 receptors and is an aggressive disease for which there are no known targeted therapies. Treatment of TNBC is further complicated by the heterogeneous nature of the disease, meaning that every TNBC is unique in its cellular and genetic makeup.
One subtype of TNBC that has recently emerged is called luminal androgen receptor (LAR). While LAR tumor cells do not have the estrogen receptor, they do have the androgen receptor (AR), a hormone found in both men and women and commonly associated with prostate cancer. Recent research suggests that LAR TNBC are resistant to chemotherapy but may respond to anti-androgen drugs used to treat AR-positive prostate cancers.
In a recent article published in npj Breast Cancer, BCRF investigators, Nadine Tung, Judy Garber and Stuart Schnitt of the Dana Farber Cancer Institute reported new data suggesting that patients with LAR TNBC may be candidates for one of the new immunotherapy drugs called checkpoint inhibitors.
Checkpoint inhibitors work by blocking the activity of a protein pair called PD-1/PD-L1. When these proteins are upregulated in tumor cells or immune cells around the tumor, they can essentially mask the tumor cell, making it invisible to the immune cells. Clinical trials in melanoma, lung and some breast cancers have shown that tumors with high PD-1/PD-L1 expression are good candidates for these therapies. Recent clinical trial results in TNBC showed that about 19 percent of TNBC respond to the anti-PD-L1 therapy.
Based on the data from this study, anti-androgen and anti-PD-L1 therapies could potentially emerge as new treatment options for TNBC, but knowing which patients are most likely to respond will be important in selecting patients for these therapies.
To address this challenge, Drs. Tung, Garber and Schnitt looked at both AR and PD-L1 expression in primary tumors from 193 patients with TNBC. They found that approximately 18 percent of the TNBC tumors had AR and about 26 percent had PD-L1. The tumors with AR were also three times more likely to have PD-L1. While further confirmation of these findings is an important next step, they may provide the basis for combination therapy with AR inhibitors and anti PD-L1 immune therapy for this subset of TNBC.
This research was supported in part by BCRF.
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