Can BRCA Expression Predict Response to Chemotherapy?

Maurie Markman, MD


April 22, 2013

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Hello. I'm Dr. Maurie Markman from Cancer Treatment Centers of America. I'd like to briefly discuss a very interesting paper that recently appeared in British Journal of Cancer. The paper was titled, "BRCA1 Expression and Improved Survival in Ovarian Cancer Patients Treated With Intraperitoneal Cisplatin and Paclitaxel: A Gynecologic Oncology Group Study."[1]

This is a retrospective analysis of a trial that had previously been reported by the Gynecologic Oncology Group,[2] which demonstrated that patients who were treated with intraperitoneal cisplatin-based therapy had improved survival compared with those individuals treated with cisplatin-based intravenous chemotherapy. However, the study results remain somewhat controversial; and even the whole strategy of intraperitoneal chemotherapy remains somewhat controversial because, even though an improved survival was seen with intraperitoneal platinum therapy in patients with small-volume residual advanced ovarian cancer, there's considerable toxicity with this approach.

In this retrospective analysis, investigators looked at BRCA staining by immunohistochemistry in the tumors of patients treated on the trial. It has been known for a long time that BRCA is associated with the ability to repair DNA damage. It was thought that if individuals had low levels of expression of BRCA protein, it doesn't necessarily mean that they have a BRCA mutation. Rather, because they don't express as much of the BRCA protein, they may have a reduced ability to repair DNA damage and, quite possibly, be more susceptible to the cytotoxic effects of cisplatin.

In this retrospective analysis of a previously reported prospective trial, approximately half of patients were found to have low levels of what the investigators described as "aberrant" expression of BRCA protein. Quite impressively, they found that, in patients who were treated with intraperitoneal cisplatin on this trial who had low levels of BRCA1 expression, there was an improvement in median overall survival of approximately 3 years; that is, they had an 84-month median overall survival compared with a 47-month median overall survival in the patient population who received intravenous platinum.

Of note, and what might have been expected based on this hypothesis, in patients who had normal BRCA1 levels of expression and were therefore able to more easily or rapidly repair DNA damage, there was no difference in overall survival between the patients who had received intraperitoneal vs intravenous platinum. This suggests that BRCA expression may be an excellent biomarker for a patient population who might be anticipated to have the greatest opportunity to benefit from regional administration of platinum.

I would encourage those who are interested in the topic of the management of ovarian cancer -- and in the question of how one can select optimal patients who might benefit from this important treatment that is clearly associated with an increased risk for toxicity compared with systemic administration -- to read this very interesting paper in British Journal of Cancer.

I thank you for your attention.