BRCA germline positive breast cancer patients are indeed a special subgroup of breast cancers; it's about 8% of all breast cancers. Patients with BRCA mutations and breast cancer have certain characteristics - they tend to develop more triple negative breast cancer, age onset is a little bit younger. Though they respond to standard therapies such as anthracyclines and taxanes, studies have shown that we might further improve outcome if we add some other agents such as the platinums and, of course, recently now the PARP inhibitors.

In terms of surgical management, the management of the tumours is really not different but the surgical implications are more in the preventive options. So women with breast cancer who also have a BRCA mutation often discuss with their providers bilateral mastectomies, the contralateral mastectomy being preventive because it reduces breast cancer risk by more than 90%. These patients are also at increased risk for ovarian cancer so after they complete their treatment for breast cancer ovarian screening and doing bilateral salpingo-oophorectomy in their late 30s, early 40s is also highly recommended.

So the medical aspects, actually the timing is great because in the US February 12th or 13th one of the oral PARP inhibitors, olaparib, was FDA approved for the treatment of metastatic BRCA germline positive breast cancer. That is based on a study in metastatic breast cancer patients with BRCA mutations that compared olaparib at 300mg b.i.d. to physician choice chemotherapy that consisted of capecitabine, eribulin, or vinorelbine. The primary endpoint of that study was to look at progression free survival and, indeed, the study met its primary endpoint, progression free survival was significantly higher for patients who received the oral olaparib PARP inhibitor. Secondary endpoints were overall objective response rate, that was also significantly higher, around 30% for the chemotherapy arm versus around 60% for the olaparib arm, that was also statistically significant. So I'm actually very excited to say that olaparib has now become standard of care for metastatic breast cancer management in women with germline mutations, that's the OlympiAD trial, exactly.

Another recent trial, the EMBRACA trial was also presented at the San Antonio Breast Cancer Symposium looking as talazoparib versus physician choice of therapy and that study also met its primary endpoint, that was progression free survival favouring talazoparib, and secondary endpoint was objective response rate that was also met in that study.

Is there any indication that these PFS improvements may translate into OS?

Not yet, not yet. But hopefully with follow-up we'll see some improvements.