Breast cancer in a transgender man

A 52-year-old transgender man presented for evaluation of a new diagnosis of breast cancer. The patient was designated female at birth. Three months after initiation of gender-affirming hormone therapy (GAHT) with testosterone gel, he underwent bilateral mastectomy for gender affirmation. Final pathology revealed a left-sided, pathologic T1 tumor (pT1) that was identified as grade 2 invasive ductal carcinoma and as estrogen receptor (ER)-positive, progesterone receptor-negative, and human epidermal growth factor receptor 2 (HER2)-negative by immunohistochemistry (score, 1+). The patient reported no preoperative symptoms of breast lumps or any changes to the skin of the breast or the nipples. He had a past medical history of Barrett esophagus, depression, and orthopedic surgeries. He had no history of chest irradiation. Family history was negative for breast or ovarian cancer. Of note, he had a negative screening mammogram performed 5 years earlier; repeat screening had not been obtained. This patient's presentation as a transgender man with incidentally found breast cancer raises several considerations regarding his gender-related health needs. An overview of frequently used terms in gender health and recommendations on how best to deliver quality cancer care to transgender and gender-diverse (TGD) individuals is provided in a 2025 review by Cathcart-Rake et al.1 For many TGD individuals, gender-affirming medical interventions are an important component of addressing gender incongruence and alleviating gender dysphoria.2 For trans men, a key intervention is GAHT with testosterone gel or injections.3 Testosterone treatment leads to suppression of the hypothalamic–pituitary–ovarian axis, which reduces estrogen and progesterone production and leads to cessation of menses. In addition, numerous physical changes are seen after 1–2 years of testosterone treatment, including voice deepening, increased facial and body hair growth, clitoromegaly, fat redistribution, and increased muscle mass (Figure 1). Such treatment has been associated with lower rates of depression, gender dysphoria, and suicidality.4, 5 For example, in one study5 of 64 TGD patients seeking GAHT with testosterone, early treatment with testosterone was found to significantly relieve gender incongruence, depression, and suicidal ideation within 3 months of treatment (Figure 2). Expected physical changes from gender-affirming hormone therapy with testosterone. Created in BioRender (Hamnvik O. [2025]; https://BioRender.com/z99l900). Changes in scores for gender incongruence (GPSQ), depression (PHQ-9) and suicidal ideation (SIDAS) scores after 3 months of gender-affirming hormone treatment with testosterone (intervention group) versus no treatment (standard group). The numbers refer to the difference in the change of scores between the intervention group and the standard group and the 95% confidence interval. GPSQ indicates Gender Preoccupation and Stability Questionnaire; PHQ-9, Patient Health Questionnaire-9; SIDAS, Suicidal Ideation Attributes Scale. Based on data from Nolan BJ, Zwickl S, Locke P, Zajac JD, Cheung AS. Early access to testosterone therapy in transgender and gender-diverse adults seeking masculinization: a randomized clinical trial. JAMA Netw Open. 2023;6(9):e2331919.5 Several studies have attempted to elucidate the risk of breast cancer in transgender populations, and the results generally indicate that transgender men have a lower breast cancer risk than cisgender women, but it is higher than the risk for cisgender men.6 The reduced risk compared with cisgender women has largely been attributed to the effect of gender-affirming mastectomy leading to a lower volume of tissue susceptible to developing breast cancer, although direct effects of testosterone on breast cancer risk have also been posited.7 Physicians must also consider the barriers to care that may be experienced by some TGD individuals. Studies have demonstrated that TGD people may be diagnosed with cancer at a later stage of disease and may be less likely to receive treatment, contributing to worse survival.8 Although it is multifactorial, an important driver of these disparities is discrimination within the medical system, resulting in health care mistrust.9 This becomes a barrier to accessing care, often resulting in a reduced uptake of health-promoting interventions like cancer screening.10 Screening, medical care, and treatments for these cancers are typically gendered in their protocols and environments, and this poses additional challenges for TGD patients. Many of these findings are magnified in patients who also belong to other minoritized groups, such as people of color.11 Therefore, the importance of building trust with transgender patients and communities cannot be overemphasized. This requires clinician understanding of the basics of gender-affirming care and its importance to patients; asking patients for their chosen name and pronouns and using these; and providing context for asking questions regarding transition-related procedures, and asking these questions only if relevant to their current presentation.12 Clinical spaces can help build trust by training all personnel in the appropriate terminology and approach to the patient, displaying visual cues of safety, inclusivity, and provider knowledge (e.g., rainbow flags, imagery featuring individuals with a variety of genders), ensuring that answer options on forms are inclusive of all gender identities, and ensuring that electronic health records are updated with the patient's chosen name and pronouns.1, 12 Gender-affirming chest masculinization surgery typically includes resection of breast tissue (mastectomy), relocation and resizing of the nipple and areola, and removal of excess skin.13 The choice of technique depends on several factors, including skin laxity, degree of breast ptosis, breast volume, and patient goals and expectations. Depending on patient and surgeon preference, a variable amount of breast tissue may remain after the procedure. Some surgeons resect all grossly identifiable breast tissue, whereas other surgeons may leave residual breast tissue either as a pedicle for the nipple–areola or to provide chest wall contour. Most often, the pectoralis fascia remains intact, and axillary lymph nodes are not sampled. Because gender-affirming chest masculinization surgery and oncologic mastectomy may differ, it is important to establish the patient's cancer risk before proceeding with surgery. This starts with a complete history focusing on major cancer risk factors, such as a previous personal history of invasive or in-situ breast cancer, a history of radiation exposure to the breast (for example, as part of treatment for Hodgkin lymphoma), or a family history of breast or ovarian cancer or of known hereditary cancer syndromes. In addition, the evaluation should include an evaluation for symptoms and signs of breast cancer, including examining for masses in the breast or axilla, skin changes/skin retraction, and nipple retraction and/or discharge. The chest examination also includes measurement of breast dimensions and an assessment of skin laxity (which may be affected by chest binding). Any abnormal findings should be evaluated further before proceeding with surgery.13 Depending upon the patient's age and personal/family history of breast cancer, breast imaging may be warranted before breast surgery, typically following breast cancer screening guidelines for cisgender women.2, 3, 14, 15 There are geographic variations in recommendations for breast cancer screening for the general population, and guidelines have evolved over time. This patient, who had no apparent risk factors for breast cancer, qualified for breast cancer screening when he lived in the United States, where current guidelines recommend breast cancer screening starting at age 40 years. At the time of presentation, he had moved to the United Kingdom, where, at age 52 years, he was eligible for the national breast cancer screening program with mammography, although this had been postponed and had not yet been performed because of the coronavirus disease 2019 (COVID-19) pandemic. The preoperative assessment is a good opportunity to ensure that routine cancer screening has been completed. In addition, patients should be empowered with information about which method of screening is recommended for them and which is not needed. Studies have indicated that 0.7%–8.8% of pathologic specimens from gender-affirming mastectomy have high-risk or malignant findings,16, 17 with the lowest rates seen in patients younger than 25 years. Our opinion is that all breast specimens should be sent for pathologic evaluation. Should a patient decline pathologic examination (in some cases because of cost), they should be made aware of the risk of occult malignancy. At this point, a multidisciplinary team should review the case. Depending on the surgical technique, an assessment of the amount of residual breast tissue (at risk of synchronous or metachronous cancer) needs to be made. At times, surgical resection of residual tissue should be considered. The patient will need axillary sampling to fully stage the cancer, although sentinel lymph node biopsy has a lower rate of success,18 so full axillary node dissection may be required or targeted biopsy if lymph nodes are enlarged on imaging. After the diagnosis of invasive breast cancer, the patient was referred to his local breast cancer service for review. Review of the operative technique confirmed that there was very little residual breast tissue. After ultrasound and biopsy of the left axilla, staging investigations, and multidisciplinary meeting discussion, he underwent a left axillary node dissection. In the axillary clearance, five of 10 lymph nodes were involved, including the apical node, equating to N2 disease. Given node positivity, he underwent formal staging; neither a computed tomography (CT) scan of the chest, abdomen, and pelvis nor a bone scan provided evidence of distant disease. He received adjuvant chemotherapy with four cycles of epirubicin and cyclophosphamide followed by four cycles of paclitaxel. This was followed by adjuvant radiotherapy to the chest wall. Oophorectomy was planned but delayed, in part because of the COVID-19 pandemic. Throughout his cancer treatment, the patient continued to take testosterone gel with serum testosterone monitoring. The dose varied between 20.25 and 40.5 mg daily to achieve serum testosterone concentrations in the target range (12–20 nmol/L; 350–580 ng/dL). Because his testosterone levels were much higher than those seen in cisgender women, there was concern that an aromatase inhibitor (AI) might not adequately block testosterone aromatization to estradiol. Therefore, tamoxifen 20 mg daily was selected as antiestrogen hormone therapy. Despite multiple attempts, the patient was unable to tolerate this because of fatigue, hot flushes, and “brain fog”. Trial of an unlicensed reduced dose of 10 mg was also unsuccessful. He also received three of the planned 6 infusions of 6-monthly adjuvant zoledronic acid. In TGD patients with hormone-responsive cancers, considering how to manage the GAHT is critical. A frequent reaction to the diagnosis of a potentially hormone-responsive cancer is to recommend complete cessation of all GAHT. However, we recommend against this approach because overwhelming data consistently confirm the benefit of GAHT on psychosocial outcomes, including depression, gender dysphoria, suicidality, quality of life, and psychological functioning.19, 20 Therefore, discontinuation of hormones risks having a severe negative impact on the patient. This is especially the case for patients who have only been on testosterone for a few months before the cancer diagnosis (as in this patient) because they would be unlikely to have seen many physical changes and thus would likely prefer to remain on testosterone. In addition, patients who are also around the average age of menopause, and thus may be rendered hypogonadal, would likely experience the attendant adverse effects of vasomotor symptoms and bone loss should testosterone be discontinued. Furthermore, it can be helpful to consider how a cisgender man with the same tumor would be treated; typically, this would not involve androgen-deprivation, thus discontinuation of testosterone should not be routinely recommended. There have been concerns about the potential for gender-affirming hormones increasing the risk of venous thromboembolism, something that is particularly relevant in patients with cancer who are already in a procoagulant evidence not an increased risk of venous with testosterone in TGD people However, testosterone can the and in has been that this leads to if the best approach to regarding GAHT should be made on an and assessment of the potential risks and of and hormone treatment and the with a multidisciplinary approach that includes the patient's hormone and with the patient and are key because they are best to any potential concerns from GAHT and because many effects from gender-affirming hormones are as voice clitoromegaly, and hair growth from with potential of the effects of GAHT (e.g., and muscle and fat oncologic treatment for TGD people with breast cancer should include the same breast care as that for cisgender people the current and hormone cancer their for gender-affirming care, their goals of treatment, and their of In TGD patients testosterone, frequent concerns include direct effects of testosterone on tumor growth, effects on tumor growth because of testosterone aromatization to and effects other than those on tumor there is evidence to or testosterone, the of this in the treatment must also be considered. 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