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PURPOSE: Almost two percent of individuals in the United States identify as gender non-conforming. In the female-to-male (FTM) transgender population, masculinizing hormone therapy with testosterone is commonly prescribed in gender transition. To date, the effects of exogenous androgens on breast tissue and its roles in altering breast cancer risk are poorly understood. This study examines the histopathologic findings in gender affirming mastectomy (GAM) in transgender FTM patients and the effects of exogenous androgens on estrogen receptors (ER) and androgen receptors (AR). METHODS: A retrospective review of pathology specimens obtained between 2017 and 2020 was performed comparing androgen exposed breast tissue with breast tissue without androgen exposure. Breast specimens were obtained from patients who underwent FTM GAM with recorded exogenous androgen exposure. Control breast specimens were obtained from reduction mammoplasty (RM) procedures in cisgender women which were aged matched to the GAM cohort, as well as postmenopausal women with benign/prophylactic mastectomy procedures; all controls were without androgen exposure. The histopathologic findings were assessed. Immunohistochemistry for AR and ER was performed and the score interpreted by digital image analysis. RESULTS: Androgen-exposed breast tissue revealed dense fibrotic stroma, lobular atrophy, thickened lobular basement membranes, and gynecomastoid changes. Longer duration of androgen exposure resulted in a more pronounced effect. The incidence of atypia or cancer was lower in GAM than RM cohort. ER and AR expression was highest in transgender male breast tissue with intermediate duration of exogenous androgen exposure. CONCLUSION: Increased androgen exposure is associated with lobular atrophy and gynecomastoid changes in breast parenchyma. Overall, ER and AR are expressed strongly in lobular epithelium in patients with prolonged androgen exposure. Exogenous testosterone does not appear to increase risk for breast cancer. Additional studies are needed to investigate the mechanism responsible for these changes at a cellular level and its role in cancer development.

Estrogen and progesterone have been extensively studied in the mammary gland, but the molecular effects of androgen remain largely unexplored. Transgender men are recorded as female at birth but identify as male and may undergo gender-affirming androgen therapy to align their physical characteristics and gender identity. Here we perform single-cell-resolution transcriptome, chromatin, and spatial profiling of breast tissues from transgender men following androgen therapy. We find canonical androgen receptor gene targets are upregulated in cells expressing the androgen receptor and that paracrine signaling likely drives sex-relevant androgenic effects in other cell types. We also observe involution of the epithelium and a spatial reconfiguration of immune, fibroblast, and vascular cells, and identify a gene regulatory network associated with androgen-induced fat loss. This work elucidates the molecular consequences of androgen activity in the human breast at single-cell resolution.

The human mammary gland is the major organ involved in lactation. In the mammary gland, alveoli secrete milk and myoepithelial cells contract to propel the milk through branched structures called ducts and eventually to the nipple. It is through this process of lactation that infants receive milk, which is essential for proper infant growth and development. The lactation process is comprised of sophisticated interactive networks at the cellular level that are not well understood. Whereas the majority of published mammary gland lactation studies have relied on mouse mammary glands, recent advancements in techniques to study mammary glands enable in vitro reproduction of lactation using human-representative frameworks. Currently, the 3D breast organoid is the state-of-the-art model in human mammary gland research, utilizing induced pluripotent stem cells (iPSCs) or processed patient-derived breast tissues embedded in a special matrix that are then able to grow into complex structures that recapitulate aspects of native human breast tissue. Gaining comprehensive biological insight into the process of lactation through these breast tissue-mimetic 3D models is essential for further studies on lactation-associated human mammary gland diseases, human milk composition, and potential solutions to challenges in maternal milk accessibility. In this short review, the benefits and potential utility of 3D breast organoids in understanding the underlying science of lactation and advancing further human mammary gland studies are discussed. [ABSTRACT FROM AUTHOR]

Background: As the number of gender-affirming procedures performed in the United States increases, physicians caring for gender-nonconforming patients, regardless of practice location and focus, will likely encounter transgender women with breast implants. Increasingly, transgender women are seeking breast feminization. However, this population is less consistently receiving surveillance and routine breast care than cisgender women. Aim: This report aims to add to the growing body of knowledge addressing breast augmentation complications in transgender women and to highlight disparities in healthcare. Methods: A case of breast implant–associated seroma at our institution was analyzed through chart review. A literature review was conducted using PubMed to gather all articles discussing breast implant–associated fluid collections in transgender patients. Prior to publication of this report, a Waiver of Consent was granted by the E.R.'s Institutional Review Board for the study under which this article was prepared. Results: Our patient was an African American transgender woman presenting initially at age 60 with significant asymmetry due to dramatic swelling of her left breast. The patient underwent bilateral breast augmentation outside of the United States 2 decades prior. The patient noted a gradual painless increase in her left breast size starting 3 years prior. She admitted that she was hesitant to seek a second opinion after being treated dismissively by another surgeon. Subsequent management included mammography and mirrored recommendations for late breast implant–associated seromas in cisgender patients: ultrasound, aspiration for cytology and culture, and removal of the implant and capsule. Outcomes: The fluid collection in our patient was determined to be a chronic hematoma and was managed surgically. Though this patient eventually achieved a good outcome, treatment was delayed due to barriers she faced as a transgender woman. Clinical Implications: Literature demonstrates that recommended management of late-onset breast-implant-associated seroma does not differ based on gender identity; however, transgender and GNC adults are more likely to receive less thorough care than cisgender women. Any patients undergoing breast augmentation with implants should be routinely evaluated for late complications, including seromas, which require prompt attention and methodical evaluation due to their potentially malignant nature. Strengths and Limitations: This article is limited in that it is a single report of breast seroma. It is strengthened by a PubMed review gathering all articles discussing breast-implant-associated fluid collections in transgender patients. Conclusion: We propose better education of physicians on how to care for transgender and gender-diverse patients should help mitigate the neglect and late presentation of such medical conditions in this vulnerable and marginalized population. [ABSTRACT FROM AUTHOR]

Discusses emerging trends in university service and outreach, the plans and programs underway at Ohio State University to ensure that outreach remains central to the university's role, and some key issues concerning faculty involvement in service and outreach activities. Argues that the tenure and promotion process should give appropriate weight to outreach and engagement activities. (MSE)