Admin Suppl Gender-affirming estrogen therapy and breast cancer treatment outcome

点击翻译按钮获取中文摘要

Project Summary Our parent R21 grant (R21 CA267088) was to understand transfeminine patients’ risks and benefits of continuing gender-affirming estrogen therapy (ET) during their breast cancer (BC) treatment. Transfeminine individuals are assigned male at birth and most pursue ET to affirm their feminine identity. As the transgender population increases, there will be a substantial number of transgender individuals at risk for cancer as they age within the next 20 to 50 years. For transfeminine patients diagnosed with BC, there is no clinical guideline whether they can continue receiving ET during BC treatment, and whether ET affects their BC prognosis. The discontinuation of gender-affirming hormones for a transgender individual is undesirable as it greatly affects their emotional well-being and body image, and compounds their cancer-induced emotional distress. In order to address the clinical question of the risks and benefits of transfeminine patients continuing ET during BC treatment, the overall strategy of our parent R21 was to use three mouse models of BC—Pik3camut, Brca1mut, or Tp53mut—to understand the effect of ET on BC treatment outcomes. We will compare tumor growth rates, breast histology, and treatment outcomes between male mice that continue and discontinue ET during BC treatment with alpelisib (for Pik3camut tumors), olaparib (for Brca mut tumors), or eribulin (for Tp53mut tumors). In Year 1, we completed the experiments for Brca1mut tumors and olaparib treatment. For the first half of Year 2, we will focus on completing experiments for Tp53mut tumors to complement our Brca1mut findings. This will allow us to obtain a general overview of how ET affects estrogen receptor negative (ER-) BC treatment. This supplement proposes three additional molecular assays to explain our findings for Brca1mut and Tp53mut tumor models: 1) to measure olaparib/eribulin levels in the tumors using mass spectrometry; 2) to profile ER- tumors using RNASeq to identify gender and sex-hormone related molecular mechanisms influencing BC treatment outcomes; and 3) assess the effect of gender and/or sex-hormone on tumor immune contexture using multiplex immunofluorescence staining. Collectively, our work will have direct and immediate clinical translation to inform ER- BC treatment options and decisions for the transfeminine community. Our findings will also inform us why BC occurring in males are more aggressive than in females, thus improving treatment strategies for cisgender men and women with BC as well.