PS5-06-26: Androgen Receptor Positive Breast Cancer in a Female-to-Male Transgender Individual

Abstract Background: Limited guidelines exist regarding breast health in the transgender population. The method of gender-affirming transition undergone by a transgender individual has been shown to influence the risk of developing breast cancer. The role between exogenous testosterone and the pathogenesis of breast cancer remains unclear. Here, we report a case of invasive ductal carcinoma of the breast in a female-to-male transgender patient after receiving gender-affirming hormonal therapy. Case Presentation: A 36-year-old female-to-male transgender individual presented with a palpable left breast mass for evaluation. The patient began testosterone and aromatase inhibitor for transitioning six years prior. They reported menarche at age 12 with continued monthly menstrual cycles since initiation of gender-affirming hormonal therapy. Family history was significant for multiple family members with breast cancer and colon cancer. Clinical exam was significant for 3cm mobile mass at 6 o’clock position and matted level one tender lymph node. The patient underwent mammogram and biopsy that confirmed a 3.8cm mass in the lower inner left breast. Histopathological exam of the biopsy revealed invasive ductal carcinoma, grade III, estrogen receptor positive (39%), progesterone receptor negative (0%), human epidermal growth factor receptor 2 negative (0%), with Ki67 85%. Androgen receptor was positive (34%). The patient then underwent PET scan that confirmed locally advanced disease with 4.1cm left breast mass with left axillary adenopathy. Genetic testing was obtained that was negative for BRCA 1/2. The patient was recommended neoadjuvant chemotherapy and has begun treatment with dose-dense doxorubicin, cyclophosphamide and paclitaxel regime. The patient was advised to discontinue testosterone therapy. They are planned for hysterectomy with bilateral salpingo-oophorectomy following treatment for breast cancer. Conclusion: Our case highlights the importance of identifying personal risk factors for breast cancer such as family history, genetic predispositions, and surgical procedures performed for this patient population. Most notably, our case identifies the need for further research into the role of gender-affirming hormonal therapy on breast cancer risk specifically in patients receiving testosterone therapy without luteinizing hormone-releasing hormone or oophorectomy. Discussion: From review of literature, female-to-male individuals who have undergone chest reconstruction surgery to remove breast tissue have significantly reduced risk of breast cancer. These individuals face higher breast cancer risk compared to cisgender men but lower than cisgender women. The use of testosterone therapy and effects on breast cancer are controversial. One theory is protective by decreasing glandular tissues, ultimately reducing the amount of tissue susceptible to cancer. The counter theory is causative in that testosterone is aromatized to estradiol leading to increased proliferation and breast cancer risk. Our case highlights the risk of inadequate estrogen suppression and prolonged androgen stimulation leading to breast cancer in our female-to-male transgender patient. More research with randomized controlled trials is necessary to determine the overall effect on each patient’s risk to ensure clinicians that are prescribing these hormonal therapies for medical transition can have open risk-versus-benefit discussions with these patients. It will also be necessary to gain surveillance data on gender affirming hormones effect on breast cancer to aid clinicians in screening and clinical recommendations, as current screening guidelines vary among organizations. Citation Format: K. Wilson, F. Raza, K. Donthireddy. Androgen Receptor Positive Breast Cancer in a Female-to-Male Transgender Individual abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-26.