P4-11-04: Risk of Primary (PBC) and Contralateral Breast Cancer (CBC) after Ovarian Cancer (OC) in BRCA1 and BRCA2 Mutation Carriers; Implications for Surveillance and Risk Reducing Mastectomy.
Authors: Seynaeve C , Vencken P , Hooning M , Menke-Pluymers M , Heemskerk-Gerritsen A , Van Doorn L , Collee M , Jager A , Van Montfort K , Burger C , Kriege M 
Published: June 2012

Background In view of the increased risk of developing breast (BC) cancer, BRCA mutation carriers are offered intensive surveillance or risk reducing mastectomy (RRM) and/or salpingo-ovariectomy (RRSO). It is insufficiently clear how to counsel mutation carriers who have been treated for OC, and it may be questioned whether RRM is indicated. It is possible that BC risk, both of primary (PBC) and contralateral BC (CBC), may be modified by the treatment given for OC mostly including surgery and platinum-based chemotherapy. Further, the BC risk has to be weighted against the risk of death after OC. So far, there are no data available on the PBC or CBC risk after OC in BRCA mutation carriers.

Patients and Methods From the database of the institutional Family Cancer Clinic (FCC), we selected BRCA-associated OC patients either without (n= 79, at risk of PBC) or with a history of unilateral BC (n=37, at risk of CBC). Controls were BRCA mutation carriers without OC, either without (n=351) or with a history of unilateral BC (n=294). Follow-up started at OC diagnosis, and for controls at date of first visit at the FCC or the 35th birthday. Exclusion criteria were: other malignancy besides epithelial OC or BC, inadequate follow-up data, bilateral breast cancer or mastectomy. Data analyses were performed using t- and chi-squared tests, and Kaplan-Meier survival method with death prior to BC as competing risk event.

Results Only six OC patients (5.1%) did not receive chemotherapy as part of primary therapy for OC, five at risk of PBC and one at risk of CBC. Chemotherapy schedules were mainly platinum-based (92%). RRSO was performed in 45% of the controls.

The risks of PBC at 2, 5, and 10 years in BRCA-associated OC patients were 3%, 6% and 11%, respectively, versus 6%, 16% and 28% in unaffected BRCA mutation carriers (p=0.03). The mortality rate at those time points in the OC group was 13%, 33% and 61%, respectively, versus 1%, 2% and 2% in unaffected mutation carriers (p&lt;0.001).

In patients with a history of unilateral BC, the risks of CBC at 2, 5, and 10 years in OC patients were 0%, 7% and 7%, respectively, versus 6%, 16% and 34% in the BC patients without OC (p=0.06). The mortality rate at similar time points was 19%, 34%, and 55%, respectively, in the OC group versus 4%, 11%, and 21% for the non-OC patients (p&lt;0.001).

Conclusions The risk of developing a PBC or CBC was much lower in BRCA mutation carriers with a history of OC than in mutation carriers without OC. Also, since the 10-year mortality rate after ovarian cancer was 55–60% and the risk of developing a PBC or CBC at the highest was 11% over the same time period, our data suggest that intensive breast cancer surveillance strategies for the BRCA-associated ovarian cancer group might be reconsidered, while risk reducing mastectomy is not indicated unless in specific cases requiring careful consideration in a multisciplinary setting. Further studies in larger groups are warranted.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-04.