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).

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 state. Current evidence does not suggest an increased risk of venous thromboembolism with testosterone in TGD people without cancer.^{21, 22} However, testosterone can increase the hematocrit, and polycythemia occurs in 3%–5%. It has been hypothesized that this leads to arterial thrombosis if untreated.²³

Determining the best approach to regarding GAHT should be made based on an individualized and detailed assessment of the potential risks and benefits of both continuing and discontinuing hormone treatment and the adjunctive endocrine therapies available, ideally with a multidisciplinary approach that includes the patient's hormone prescriber and oncologist. Close discussions with the patient and shared decision making are key because they are best positioned to balance any potential cancer-related concerns from GAHT and because many effects from gender-affirming hormones are permanent (such as voice change, clitoromegaly, and facial/body hair growth from testosterone), with potential regression of the reversible effects of GAHT (e.g., amenorrhea and muscle and fat redistribution).

Optimal oncologic treatment for TGD people with breast cancer should include the same breast practice guideline–concordant care as that for cisgender people alongside the individual's current endogenous and exogenous hormone status, cancer stage, their preferences for gender-affirming care, their goals of treatment, and their perception of risk.¹ In TGD patients taking testosterone, frequent concerns include direct effects of testosterone on tumor growth, indirect effects on tumor growth because of testosterone aromatization to estradiol, and effects other than those on tumor growth. If there is evidence to warrant stopping or pausing testosterone, the timing of this in the treatment pathway must also be considered.

Two years and 10 months after his initial diagnosis, the patient was admitted with chest pain and diagnosed with COVID-19 infection. A CT of the chest showed a pathologic fracture of the left seventh rib (Figure 4), a sclerotic focus in the T4 vertebra (Figure 5), and several subcentimeter lung lesions, all consistent with metastases (Figure 6). Treatment was initiated with letrozole, abemaciclib, and denosumab, but abemaciclib was discontinued after an idiosyncratic reaction with extreme dizziness, vertigo, nausea, and vomiting for 48 hours after the first dose. At that time, the patient opted to proceed with previously planned total hysterectomy and bilateral salpingo-oophorectomy, with the dual goal of removing the ovarian source of estradiol and providing gender-affirming benefits for the patient. Further treatment was held until after his surgery.

One month postoperatively, he started palbociclib but was unable to tolerate this because of severe fatigue and brain fog, so he asked to discontinue after 2 months. He was treated with letrozole, which was stopped after 9 months because of intolerable joint pains and brain fog. The patient remained on treatment with denosumab. Second-line systemic therapy with capecitabine was offered, but the patient declined. Because of a combination of slow disease biology and difficulty managing side effects, it was initially decided, in collaboration with the patient, that further endocrine therapies (e.g., fulvestrant) and other systemic therapies would be reserved until radiologic progression and that he would remain off systemic therapy. Testosterone gel was continued, with additional monitoring of estradiol to confirm undetectable levels. Follow-up CT scans after 3 and 6 months revealed stable appearances in his low-volume metastatic disease. However, at 9 months, the patient developed increasing bone pain at the site of his T4 metastases, although radiologic appearances remained stable. Therefore, he was started on oral capecitabine for systemic disease control with a view to enrolment on a trial of stereotactic ablative radiotherapy for oligometastatic disease.

In general, the first-line treatment for ER-positive, HER2-negative metastatic breast cancer consists of a CDK4/6 inhibitor alongside endocrine therapy, unless there is organ-threatening disease, in which case chemotherapy would be a reasonable alternative.^{44, 45} Endocrine therapy may be with an AI or with fulvestrant.^{44, 45} Concerns about QTc prolongation and thromboembolism on tamoxifen mean that it is not generally recommended in combination with a CDK4/6 inhibitor.^{46, 47}

In trans men, these guidelines should be followed, but the patient should be engaged in a process of shared decision making regarding whether to continue testosterone therapy. If a decision is made to continue therapy, then testosterone gels are preferable alongside AIs, with concurrent estradiol monitoring. Testosterone dosage can be lowered if estradiol levels are not suppressed, which proved to be an effective strategy for this patient. For those unwilling to switch to gel preparations, fulvestrant may be an alternative because it both blocks and degrades the ER, which can mitigate the effect of high levels of estradiol caused by aromatization at the peak testosterone. Estradiol monitoring is then not required and in fact may lead to spurious results.⁴⁸

This patient's difficulty tolerating endocrine therapies and the side effects of brain fog, fatigue, and arthralgia were similar to those reported in cisgender women. To our knowledge, no studies to date have looked at the adverse effects of endocrine therapy in a population of trans men or nonbinary patients and how they are best mitigated. It may be important to ensure that testosterone is optimally dosed to avoid excessive fatigue.

There is increasing use of genomic profiling in breast cancer, including for the selection of therapies in metastatic disease.⁴⁹ There is currently no published literature on genomic profiling of breast tumors from trans men. Genomic testing should be performed as clinically indicated, according to local guidelines. In this case, the patient did not yet meet local criteria for ESR1 or PIK3CA mutation testing.

“Two weeks after my gender-affirming mastectomy, my private plastic surgeon phoned me urgently. He received the routine postoperative pathology results from the dissected breast tissue: I had breast cancer. Upon diagnosis, I was referred to the NHS Breast Clinic for further investigation, staging, and subsequent treatment. From that point forward, every aspect of my care—every medical conversation, every treatment discussion, and even the assumption of desired outcomes—all typically geared toward cisgender, heterosexual women—entered a blind spot. No medical professional I encountered was intentionally discriminatory; there simply was no established protocol for treating breast cancer in a transgender man. They had so little training about trans men's experiences and concepts of self, that they didn't know what they didn't know. Every appointment for every procedure was a learning experience for all of us and sometimes left me feeling misunderstood, unheard, invalidated in my decision to transition from female to male, and alone in my cancer journey.

Therefore, having this opportunity to share my perspective with medical professionals is remarkably empowering and one for which I am deeply grateful. There are three primary points that I would like to emphasize to assist medical professionals in treating trans people with cancer. First and foremost, endocrine management, without cessation of hormone therapy for gender transition, is essential. In my case, with ER-positive breast cancer, continuing to take testosterone has risks of aromatization, but it is not optional nor secondary treatment. My gender treatment is as essential to my health and well being as treating my cancer. I can state this no more emphatically than to insist that, for me, de-transitioning would be a death in and of itself, and one I would not necessarily choose over death by cancer, if that becomes my ultimatum. I was fortunate to have an oncology team who understood my position on this issue and did not ask me to stop taking testosterone. Instead, they worked with me to find alternative endocrine management solutions.

Second, being diagnosed with breast cancer tossed me into an exclusively cisgender, feminine, heterosexual, microcosm—everything from information pamphlets to support networks to waiting rooms. At my first appointment at the breast clinic, I was left sitting in the waiting room because it was assumed that I was the husband/male partner of a patient, not the patient myself. Further, it was generally presumed that the loss of my breasts, as the primary characteristic of femininity and female sexuality, was a significant trauma; when in actuality, having had the mastectomy when I did significantly reduced my gender dysphoria and probably saved my life. Later, when I was told I would have chemotherapy and subsequently lose my hair (another cherished aspect of femininity), I was offered a wig no fewer than four times by different nurses. However, becoming a bald man at 52 years old was actually normalizing for my appearance, and I embraced it. While I do not wish to detract from any support that cis/hetero females receive from these gendered paradigms, there could, and should, be alternative protocols—not everyone diagnosed with breast cancer feels comforted and emboldened by cis-normative culture.

Third, there are many practical considerations that could be made in advance of treating a trans person, such as: informing nurses in advance of a trans person's gender and pronouns, anticipating that medical needs will be different (can I wear my packer [the genital prosthesis] for my pelvic CT scan?), providing a private room for surgery and recovery, and giving trans patients advance warning of treatments that may be triggering for them. For example, I was not told that, after my oophorectomy and hysterectomy, I would have vaginal bleeding for several days. This may seem obvious but, unlike a premenopausal cis woman who might likely have had sanitary products on hand, it never crossed my mind. When blindsided by this simple, foreknown consequence, and coupled with the fact that the surgery, in my mind, was the final riddance of female parts, I experienced a time-warping, gender-dysphoric whiplash back to my female identity from 2 years prior. This emotionally derailing aftermath could have been largely avoided with unassuming, advance communication.

In sum, treating trans patients with equity does not mean treating them identically to cisgender patients: it means learning, understanding, anticipating, and implementing strategies to address the differing needs, perspectives, and goals of trans patients. Simply put: if you don't know, ask. If you ask, listen. If you listen, create and implement inclusive patient protocols. We, of the gender-diverse community, aren't asking you to upend your support for the cisgender majority of your patients—simply to carve out a space for us that currently does not exist in mainstream health care.”

The key oncologic considerations in transmasculine individuals with breast cancer are outlined in Table 1. Like for any patient, care for TGD people with cancer requires a multidisciplinary and person-centered approach. This patient was referred to the UK Cancer and Transition Service,^{50, 51} a hybrid clinic and multidisciplinary team that brings together oncologists, surgeons, gender-affirming care clinicians and the patient. We advocate for services that adopt this model to disseminate expertise, coordinate care, and facilitate shared decision making.

Prospective real-world studies are required to evaluate patient-reported outcomes and quality of life for TGD people with breast cancer who require endocrine therapies. In addition, TGD people should be supported and encouraged to participate in clinical trials.

Alison M. Berner reports grants/contracts from Gilead Sciences Inc., and Eli Lilly & Company; personal/consulting fees from Pfizer Ltd.; and support for other professional activities from Astellas Pharma, AstraZeneca UK Ltd., Gilead Sciences Inc., Ipsen Biopharm Ltd., and NHS Health Scotland outside the submitted work. Loren Schechter is currently President-Elect of World Professional Association for Transgender Health (WPATH) outside the submitted work. The remaining authors disclosed no conflicts of interest.