Abstract B037: Effect of cross-sex estrogen therapy on olaparib treatment in mice
Authors: Heng Yujing J. , Wang Lin , Thavamani Abhishek , Massicott Erica S. , Bret-Mounet Vanessa C. , Baker Gabrielle M. , Clohessy John G. , Wulf Gerburg M. 
Published: December 2023

Background: Transfeminine individuals—assigned male at birth—pursue gender-affirming estrogen therapy to treat their gender dysphoria. When a transmasculine individual is diagnosed with breast cancer, there are no clinical guidelines on how to manage gender-affirming estrogen therapy during breast cancer treatment. There are limited studies on the effects of estrogen therapy during breast cancer treatment. In this study, we used a BRCA-deficient breast cancer mouse model to investigate the effect of estrogen on olaparib treatment outcomes. Method: We established a cross-sex hormone model of femininity using 60 µg of weekly subcutaneous estrogen and implanted viable fragments of female K14-Cre Brca1f/fp53f/f murine tumors into healthy recipient mice (n=184): female controls, male controls, male castrated controls, males receiving estrogen, and castrated males receiving estrogen. When the tumors reached 5 mm, mice receiving estrogen were first randomized to stop or continue estrogen. Then, mice were further randomized in every arm to be treated with olaparib or vehicle. Mice were euthanized when the tumor reached 20 mm. Only olaparib treated arms are reported here, and all comparisons are with female controls. Results: Female control mice receiving olaparib have the longest median tumor-specific survival times (n=17; 103 days). Male controls (n=16) had significantly shorter survival than female controls (75 versus 103 days; p=0.031). Survival times for males that stopped estrogen (n=10; 39 days), males that continued estrogen (n=10; 50 days), and castrated males that stopped estrogen (n=19; 58 days) were significantly shorter than females (all p&lt;0.01). Survival for male castrated mice that continued estrogen (n=10) was also shorter than females, but did not achieve significance (68 days; p=0.09). All mice that did not receive olaparib had a median survival of 14 days, validating the stability of our tumor model. Conclusion: When the same tumor is treated with olaparib, females had better outcomes then males, regardless of castration status or whether the male mice stopped or continued estrogen during olaparib treatment. Our work indicates that the gender at birth, rather than the hormonal milieu, affects outcomes for hormone-independent BRCA1-related breast cancer. Molecular analysis of the tumors is underway to understand the hormonal effects on the tumors and interaction with olaparib treatment.

Citation Format: Yujing J. Heng, Lin Wang, Abhishek Thavamani, Erica S. Massicott, Vanessa C. Bret-Mounet, Gabrielle M. Baker, John G. Clohessy, Gerburg M. Wulf. Effect of cross-sex estrogen therapy on olaparib treatment in mice [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B037.