Triple-Negative Breast Cancer: New Subtype Classifications Shed Light on Targeted Treatments

BCRF researcher Dr. Charles Perou has helped categorize TNBC tumors into 4 distinct molecular subtypes.

Triple-negative breast cancer (TNBC) is so named because TNBC cells lack the three common breast tumor markers: estrogen receptor, progesterone receptor and the HER2 protein. Unlike breast cancers with these markers, there are currently no FDA-approved targeted therapies for TNBC. One of the prevailing challenges in these efforts is the complex molecular diversity of TNBC tumors.

BCRF investigator Dr. Charles Perou and others have been directing considerable effort into the molecular characterization TNBC to identify potential targets for therapy. Using the same methods of genomic analysis used to identify the four major classes of breast cancer (Luminal A, Luminal B, HER2-enriched and basal-like), Dr. Perou and colleagues have identified four molecular subtypes of TNBC.

During the AACR Annual Meeting, Dr. Perou chaired a session discussing the TNBC classifications and potential targeted therapies in each case:

Luminal: These tumors resemble ER-positive breast cancers under the microscope, but do not have the estrogen receptor. Instead, they have another hormone receptor—the androgen receptor (AR)—most commonly associated with prostate cancer. With several anti-androgen drugs in use to treat prostate cancer, Dr. Perou discussed the potential of testing these in AR-positive TNBC. Clinical trials are ongoing or under development for several approved anti-androgen drugs in breast cancer.

Basal-like: This category of TNBC comprises two types of tumors, one that is immune enriched and one that is not. The immune enriched type of TNBC tumor contains immune cells. These tend to have a better prognosis and are more likely to respond to immunotherapy. Clinical trials are ongoing to test combinations of immune-based therapies, such as anti-PD-L1 drugs, with conventional therapy in TNBC.

The basal TNBC without immune enrichment tend to be very sensitive to chemotherapy, so even though there is not a specific targeted therapy, these patients often benefit from standard chemotherapy.

BRCA-mutated TNBC: About 70 percent of BRCA-mutated breast cancers are basal-like triple-negative. Olaparip (Lynparza) belongs to a class of drugs called PARP inhibitors that are effective against BRCA-deficient tumors. They work by blocking a DNA repair process that BRCA-mutated breast cancer cells depend on to survive. Previously approved for advanced ovarian cancer with BRCA mutations, olaparib is the first FDA-approved PARP inhibitor for advanced BRCA-mutated breast cancers.

Another drug, known as sacituzumab govitecan (IMMU-132 for short), may benefit a wider group of TNBC patients. It is an antibody-drug conjugate that targets a protein called Trop2, which is present on most TNBC cells. The drug works by attaching to Trop2 on the surface of TNBC cells and then injecting a deadly toxin into the cell. The drug is currently in Phase III clinical trials.

You can watch the full interview Facebook Live with Dr. Perou below: