BRCA-related cancers are treated based on the clinical characteristics of each cancer. For example, in early stage breast cancer, tumor size, involvement of lymph nodes, and results from testing the tumor for specific molecular markers (such as estrogen and progesterone receptors and Her2/neu) influence treatment recommendations regarding chemotherapy, hormonal therapy and other targeted therapies. In general, BRCA1 carriers are more likely to develop cancers that are triple negative, meaning they do not express estrogen, progesterone, or Her2/neu receptors. These triple negative cancers typically require chemotherapy even if they are diagnosed at an early stage.
In addition, women who carry BRCA mutations are at increased risk of developing a subsequent new breast cancer. Women with BRCA mutations who are diagnosed with breast cancer have about a 50% risk of developing a second breast cancer in their lifetime, although this is dependent on the age of the first breast cancer and other factors. Therefore, removal of both breasts is discussed with women with BRCA mutations at the time of cancer diagnosis, though it remains a personal decision as the cancer can also be treated by less extensive surgery followed by radiation.
In BRCA1/2-related cancers which are metastatic (meaning that cancer has spread outside the breast area) there are clinical trials currently investigating whether certain chemotherapy regimens and medications improve outcomes. Some clinical trials investigate new drugs, while others compare medications that are already on the market. Chemotherapies that contain platinum are commercially available and seem to be particularly effective for later stage BRCA-related cancers. Research studies are underway to determine the efficacy of platinum-based chemotherapies in treating BRCA-related cancers both in metastatic disease and also in earlier stage cancers in which chemotherapy is being given prior to surgery.
One new class of drugs being studied in BRCA1/2 carriers is called PARP inhibitors. PARP inhibitors have been studied in individuals with cancers associated with BRCA1/2 mutations. In some of the women and men on these trials, tumors decreased in size, and in many others, the tumors stopped growing. Therefore, there has been significant enthusiasm for further exploring these drugs. PARP inhibitors have also been studied in individuals with advanced tumors that were not related to inherited BRCA1/2 mutations. Although there does seem to be therapeutic activity in women with non-inherited BRCA1/2 ovarian cancer, little therapeutic activity has been seen in non-BRCA1/2 breast cancer. One challenge with the information from research done in advanced breast cancers that were not related to BRCA1/2, is that the largest study to date employed a drug that was not actually a PARP inhibitor, though it was believed to be one at the time.
There are currently many different PARP inhibitors made by different companies but none are approved by the Food and Drug Administration. Therefore, access to PARP inhibitors can be gained through clinical trials and to a limited extent, by compassionate use.
Although developing PARP inhibitors has been challenging, they are still an exciting area of investigation. Researchers and pharmaceutical companies are currently conducting clinical trials to evaluate PARP's in BRCA carriers, since initial studies in carriers showed promise. BRCA carriers are excellent candidates for these clinical trials and it is hoped that the trials will result in more therapeutic options for individuals with BRCA-related cancers.
To learn more about the different BRCA-related cancers and common approaches to diagnosis and management, visit the Abramson Cancer Center's Oncolink website: