Abstract A127: Parental influence on breast cancer penetrance in BRCA1/2 mutation carriers: Impact of oral contraceptive use before age 20 years
Authors: Ellberg Carolina , Jernstrom Helena , Olsson Hakan 
Published: May 2015

Abstract
Introduction: Recent data indicate that paternal inheritance may be associated with an earlier age a breast cancer (BC) diagnosis in BRCA1 mutation carriers. OC use prior to age 20 increases the risk for early onset BC (&lt;36 years) independent of BRCA1/2 status. The aim of the present study was to determine if there was a similar pattern among the registered mutation carriers in the southern health care region of Sweden. Secondly, to elucidate whether use of oral contraceptives (OCs) before age 20 could influence the age of diagnosis, especially in BRCA1/2 carriers with paternal inheritance.
Material and Methods: Data on 587 BRCA1/2 carriers from the OnkGen registry was retrieved; an additional 170 were added after pedigree review. Out of 757 BRCA1/2 carriers, 598 were eligible for analysis after excluding men, BRCA1/2 double carriers, and carriers screened for mutation after 01/12/2011. There were 414 BRCA1 carriers: 70 and 147 with a known paternal and maternal origin of mutation respectively. There were 184 BRCA2 carriers: 34 and 57 with a known paternal and maternal origin of mutation respectively. Information regarding OC use was obtained from questionnaires that were answered by registered carriers in the OnkGen registry. There was information regarding OC use before age 20 for 179 BRCA1 carriers and 76 BRCA2 carriers.
Results: Paternal inheritance in BRCA1 carriers was associated with a lower age at BC diagnosis; crude HR 1.38 (0.98-1.94). A similar risk was observed in BRCA2 carriers but was not statistically significant crude HR 1.28 (0.81-2.00). Early OC use was more common in BRCA1 carriers with a maternal inheritance, OR 2.58 (1.30-5.11) compared to BRCA1 carriers with paternal inheritance. This was not observed in BRCA2 carriers; OR 0.81 (0.29-2.26). Paternal inheritance in BRCA1 carriers was not associated with paternal inheritance after adjustment for early OC use; HR 1.07 (0.63-1.81). For BRCA2 carriers, the risk remained similar after adjustment for early OC use, HR 1.33 (0.65-2.73).
Conclusion: A borderline significant tendency towards younger age at BC diagnosis was observed in BRCA1 carriers with paternal inheritance, which is in line with previous findings. The tendency was lost after adjustment for early OC use. Since it has been previously shown that early OC use influences the risk of very early onset BC before and BRCA1 carriers with maternal inheritance were more than twice as likely to have used OCs prior to age 20 compared to those with paternal inheritance, we had expected a higher rate of early OC use in women with paternal inheritance.
Citation Format: Carolina Ellberg, Helena Jernstrom, Hakan Olsson. Parental influence on breast cancer penetrance in BRCA1/2 mutation carriers: Impact of oral contraceptive use before age 20 years. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A127.