Review

Breast cancer risk and screening for transgender and gender-diverse individuals

Dzhuliyan V. Vasilev, MD, MMSc, Juliana M. Kling, MD, MPH and Evelyn F. Carroll, MD
Cleveland Clinic Journal of Medicine July 2025, 92 (7) 439-447; DOI: https://doi.org/10.3949/ccjm.92a.24088

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  • Release date: July 1, 2025
  • Expiration date: June 30, 2026
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ABSTRACT

Evidence from well-established studies of breast cancer risk in transgender and gender-diverse (TGD) people is lacking. As a result, current screening guidelines are based on extrapolation from cisgender populations, expert consensus, and retrospective cohort studies. Guideline recommendations focus on knowing patient baseline breast cancer risk and the risks associated with chosen gender-affirming hormone therapy and gender-affirming chest surgery. While existing guidelines are helpful, tailored protocols and research on effective breast cancer screening specific to TGD people are needed.

KEY POINTS

  • Because gender identity data are not systematically collected, high-quality population-level information on breast cancer risk in TGD people is not available.

  • Current data suggest that transgender women on gender-affirming hormone therapy have a higher risk of breast cancer than cisgender men and a much lower risk than cisgender women. Screening initiation in these patients is influenced by age and hormone therapy duration (> 5 years).

  • Routine screening mammography is not recommended in transgender men who have had gender-affirming chest surgery; those who have not undergone this surgery or have only had a breast reduction should follow screening guidelines designated for cisgender women.

Approximately 1.6 million people in the United States identify as transgender.1 Transgender individuals have a gender identity that differs from their assigned sex at birth, while cisgender individuals have a gender identity that aligns with their assigned birth sex (Table 1).2,3 Many transgender and gender-diverse (TGD) individuals experience significant discomfort owing to a mismatch between their gender identity and their physical body, a condition known as gender dysphoria or incongruence. They often opt for gender-affirming hormone therapy (GAHT) to bring their physical appearance in line with their gender identity, thereby enhancing their psychological, social, and cultural well-being.

View this table:
TABLE 1

Terminology and definitions

TGD individuals face diverse health challenges, including a paucity of data regarding breast cancer risk and a lack of consistent guidelines and recommendations for breast cancer screening and management.4,5 For example, feminizing GAHT doses are typically higher than what is used in menopausal hormone therapy or contraceptive pills used by cisgender women. How GAHT doses either alone or in combination with surgical affirmation such as gonadectomy impact breast cancer risk has not been fully elucidated. Further, a 2024 systematic review of 12 studies on breast cancer screening in TGD individuals found mixed results, but generally indicated lower screening rates in TGD people compared with cisgender women,2 highlighting the need for more research to develop culturally safe, equitable, and high-quality breast cancer screening and preventive care protocols for TGD individuals to ensure access to care.6

Largely based on expert opinion, the most current and often applied guidelines are those from the World Professional Association for Transgender Health, American College of Radiology (ACR), University of California San Francisco (UCSF) Center of Excellence for Transgender Health, the Endocrine Society, the American College of Obstetrics and Gynecologists, and the Fenway Health Institute.7–12 This review of breast cancer screening in TGD patients discusses the evidence base of breast cancer risk in this population, summarizes the most current screening guidelines, and highlights healthcare disparities and barriers to screening.

RISKS OF GAHT

Estrogen, progestogens, antiandrogens, testosterone

The use of GAHT in TGD individuals aims to align physical characteristics with gender identity. For transgender women, estrogen is primarily delivered orally or via patches or gel, with goals including breast development and body feminization.13 In addition to estrogen, some transgender women may take progesterone, though its use is not widely recommended due to lack of benefit and concerns about breast cancer risk.13 Shufelt et al14 reviewed data from various studies involving cisgender women, including the Women’s Health Initiative, and noted that estrogen plus progestin was associated with a small increased risk of breast cancer after more than 5 years of use, an effect that was not seen in the estrogen-alone arm.

Antiandrogens such as cyproterone acetate are also commonly used to lower testosterone levels into the female range for transgender women to match their reaffirmed gender.13 Cyproterone has progestogenic properties, and long-term safety and breast cancer risk need to be carefully considered in patients taking antiandrogens.

Transgender men undergo masculinizing changes through testosterone therapy, typically administered by injections or gel, and achieve outcomes like voice deepening and increased muscle mass.15 However, individual responses to hormone therapy can vary.

Duration

The duration of estrogen exposure in relation to breast cancer risk must be considered because, in cisgender postmenopausal women, longer exposure to hormones (estrogens plus progestogens) has been associated with an increased risk of breast cancer.16 As trends shift toward transgender women starting hormone therapy at younger ages, the cumulative duration of exogenous hormone exposure may increase, potentially affecting breast cancer risk estimates for this population in the future.

BREAST CANCER RISK IN TRANSGENDER WOMEN

When transgender women use GAHT, the emergence of acinar and lobular formations within breast tissue is expected.17 Breast development in transgender women is typically modest and predominantly manifests within the initial 6 months of starting hormone therapy.17,18 No studies have explored correlations between breast density and serum estrogen levels or the regimen of GAHT administered in transgender women, resulting in a significant evidence gap.19 Overall, the breast tissue characteristics of transgender women are similar to those of cisgender women.17

The risk of developing breast cancer in transgender women while on GAHT has been the focus of several research investigations. In the de Blok et al15 cohort of 2,260 transgender women receiving GAHT, 15 cases of invasive breast cancer were identified after a median hormone treatment duration of 18 years. The incidence of invasive breast cancer was found to be 46 times higher in transgender women compared with cisgender men, but lower than that observed in cisgender women.15 Notably, 67% of breast tumors in transgender women originated from ductal tissue and demonstrated hormone-receptor expression profiles similar to those more commonly seen in cisgender women, with estrogen receptor being positive in 83% and progesterone receptor being positive in 67%.15

We believe that these outcomes imply that transgender women on GAHT have a slightly elevated susceptibility to breast cancer compared with cisgender men, yet their risk remains lower than that of cisgender women. As noted earlier, a full understanding of the risks related to type and duration of GAHT is not fully elucidated as it relates to breast cancer risk. Therefore, cultivating awareness among both patients and clinicians and conducting suitable screening procedures are pivotal to facilitating early detection and effective management.15

BREAST CANCER RISK IN TRANSGENDER MEN

The introduction of testosterone in transgender men similarly triggers changes in breast characteristics during imaging evaluations, notably resulting in a substantial reduction of glandular tissue.17 Chest masculinization surgery, which is completed or desired by up to 97% of transgender men,20 typically involves the removal of breast tissue and excess skin to create a masculine chest contour. All breast tissue is not always completely removed, however, as the amount of fibroglandular breast tissue removed depends on patient preference and often varies between surgeons.21

In the de Blok et al15 cohort, among 1,229 transgender men, 4 instances of invasive breast cancer were identified, with a median duration of hormone treatment of 15 years. The incidence in transgender men was lower compared with cisgender women.15 Transgender men had a higher overall risk of breast cancer compared with cisgender men. Most of the identified breast tumors in transgender men were of ductal origin and exhibited estrogen and progesterone receptor positivity, similar to findings in cisgender women.15 These outcomes imply that transgender men carry a diminished risk of breast cancer compared with cisgender women, which may be at least partially attributable to gender-affirming chest surgery performed as part of the gender-affirmation process.

A study analyzing breast tissue from transgender men receiving GAHT found that androgen exposure causes involution of ductal structures and induced transcriptional changes that diminish estrogen signaling.22 This reprogramming of hormone receptor–expressing cells, along with changes in immune composition and metabolism, may contribute to lowering susceptibility to developing breast cancer in transgender men.

Of note, transgender men who have not had gender-affirming chest surgery and have increased breast cancer risk due to familial predisposition (eg, carrier of the breast cancer gene [BRCA], elevated Tyrer Cuzick risk score) are advised to undergo increased breast surveillance, which may include earlier and more frequent imaging, similar to their cisgender female relatives.15

Mammography in transgender men

After gender-affirming chest surgery, monitoring with mammography is not considered feasible due to minimal residual breast tissue. For transgender male patients with any palpable areas of concern on physical examination, diagnostic ultrasonography may be necessary.23 Of note, there have been documented instances of breast cancer in transgender men after gender-affirming chest surgery.24,25 Transgender men who have not undergone gender-affirming chest surgery should follow the same screening mammography protocols as cisgender women.23 This is in line with the ACR Appropriateness Criteria.7

IDENTIFYING PATIENTS AT HIGH RISK FOR BREAST CANCER

Thoughtful assessment and management strategies are needed for TGD individuals with a higher susceptibility to breast cancer, such as those with a BRCA mutation or strong family history of breast cancer. Conducting genetic risk evaluation based on family history of breast, ovarian, prostate, and pancreatic cancer and ancestry (eg, Ashkenazi Jewish heritage) is key to identifying patients prone to mutations that increase breast cancer risk.3

The timing of investigation for BRCA and other genetic mutations has been found to impact surgical decisions for women with breast cancer.26 In cisgender women with breast cancer, those aware of their BRCA mutation before surgery displayed a higher likelihood of opting for bilateral mastectomy compared with those who discovered their mutation after surgery.26 Among patients who underwent lumpectomy or unilateral mastectomy and later discovered their BRCA mutation, more than 50% underwent delayed bilateral mastectomy.26 For example, transgender individuals assigned female at birth with a BRCA mutation or elevated lifetime risk of breast cancer may consider risk-reducing mastectomy as opposed to gender-affirming chest surgery to minimize their breast cancer risk.

Clinicians should proactively evaluate and assess breast cancer family history in TGD patients to determine whether further genetic testing is needed before gender-affirming surgical interventions, allowing for informed surgical decision-making and tailored management protocols.27 For example, genetics services in the United Kingdom are seeing more TGD patients referred for advice on inherited cancer risks before and after starting gender-affirming medical or surgical treatments.28 Multidisciplinary collaboration among genetics clinicians, gender identity specialists, and other healthcare professionals is essential for shared decision-making to determine breast cancer risk.

Of note, BRCA is just one of many genetic mutations associated with an increased risk of breast cancer. Notably, transgender people diagnosed with Klinefelter syndrome face an elevated lifetime breast cancer risk just as any male diagnosed with Klinefelter syndrome.29 Further, the lifetime risk of developing male breast cancer is estimated to be up to 5% for BRCA1 and 5% to 10% for BRCA2 mutation carriers, compared with a risk of 0.1% in the general male population.30

CURRENT SCREENING GUIDELINES

Given the limited availability of evidence from well-established studies in transgender patients, recent guidelines have been developed to offer guidance to clinicians. These guidelines are primarily based on expert consensus, retrospective cohort studies, and extrapolation from cisgender populations.7–12 The recommendations depend on factors such as age, duration of GAHT for transgender women, and whether transgender men have undergone gender-affirming chest surgery.

The ACR Appropriateness Criteria for transgender breast cancer screening are the most comprehensive and up-to-date breast cancer screening guidelines for TGD people.7 The guidelines are based on the strongest available evidence and expert consensus. The specific recommendations are contingent on factors such as individual breast cancer risk (eg, BRCA mutation status), history of GAHT or gender-affirming surgical procedures, and age.

In addition to the ACR, the UCSF Center of Excellence for Transgender Health, the World Professional Association for Transgender Health, the Endocrine Society, and others have established guidelines for transgender people,7–12 with the most comprehensive and up to date noted in Table 2 and Table 3.7–10 The full guidelines can be found online (Table 4).

View this table:
TABLE 2

Breast cancer screening recommendations for transgender women

View this table:
TABLE 3

Breast cancer screening recommendations for transgender men

View this table:
TABLE 4

Online breast cancer screening guidelines

American College of Radiology

Transgender women. The ACR guidelines recommend screening mammography and digital breast tomosynthesis starting at age 40 for average-risk transgender women who have been on GAHT for 5 years or more.7

Transgender men who have not undergone gender-affirming chest surgery should start screening at age 40.7 Screening mammography is not recommended for those who have undergone gender-affirming chest surgery, although yearly chest examinations should be considered. For transgender men at high risk, such as those with a BRCA mutation or strong family history, who have not undergone risk-reducing mastectomies, the guidelines suggest considering additional imaging modalities like magnetic resonance imaging breast screening and starting screening at an earlier age.7

The ACR does not provide specific guidelines for breast cancer screening in nonbinary individuals.

UCSF Center of Excellence for Transgender Health

Transgender women typically should not start screening mammography before age 50 or before they have had a minimum of 5 years of feminizing hormone use, irrespective of age, according to the UCSF Center of Excellence for Transgender Health guidelines.8 Once a patient meets age and hormone therapy duration criteria, screening mammography should be conducted every 2 years starting at age 50.

Transgender men who have not undergone gender-affirming chest surgery or have only had a breast reduction should follow the prevailing screening guidelines designated for cisgender women.8 There isn’t substantial reliable evidence to direct the screening of transgender men who have undergone gender-affirming chest surgery with residual breast tissue in place. Patients and clinicians are advised to engage in a shared decision-making process about potential screening options, such as a self-examination. If no breast tissue is present, there is no role for screening mammograms.

World Professional Association for Transgender Health Standards of Care Version 8

Transgender women. The World Professional Association for Transgender Health does not provide specific breast cancer screening guidelines for transgender women.9 In caring for transgender women who have undergone estrogen therapy, clinicians are advised to adhere to the breast cancer screening guidelines applicable to cisgender women. Patients with a confirmed BRCA1 mutation should receive comprehensive counseling about the uncertainties involved (the guidelines do not discuss BRCA2).

Transgender men with breasts from natal puberty who have not had gender-affirming chest surgery are advised to adhere to the localized breast cancer screening protocols created for cisgender women, taking into account their baseline risk profile.9 However, the optimal timing and strategy for breast cancer screening in transgender men who have undergone any form of chest masculinization surgery have not been definitively established. Rather, the recommendation is that decisions should be personalized and based on shared decision-making, taking into account individual risk factors and the extent of breast tissue removed.

Endocrine Society

The Endocrine Society clinical practice guideline advises that transgender women without an elevated breast cancer risk adhere to breast cancer screening recommendations for cisgender women.10 Breast cancer screening recommendations for transgender men are not addressed.

HEALTHCARE DISPARITIES AND BARRIERS TO SCREENING

Healthcare disparities among the TGD population are well-documented and pose significant challenges to accessing quality care.31–37 The 2022 US Trans Survey results revealed limited access to healthcare as a major barrier faced by TGD individuals, with discrimination and difficulty in finding clinicians contributing to disparities.31

Clinicians’ lack of knowledge regarding TGD health and stigmatized healthcare encounters, such as misgendering and denial of services, further compound the challenges faced by this population.31,32 Leone et al34 highlighted the discrimination, discomfort, and overall lack of knowledge among clinicians regarding specific health needs pertaining to TGD individuals and hurdles in cancer prevention, care, and survivorship for TGD individuals. This review revealed that transgender and gender-diverse people had a high prevalence of tobacco consumption and alcohol use and high rates of infection with human papillomavirus and human immunodeficiency virus (HIV). Transgender and gender-diverse individuals were less likely to adhere to cancer screening programs and had a higher incidence of cancers associated with HIV and human papillomavirus. Social and economic determinants seemed to drive these disparities in risk factors and outcomes.34 In a recent national survey of 450 oncologists from National Cancer Institute– designated comprehensive cancer centers, only 20% were confident in their knowledge of the health needs of TGD people.35

Impact on care

The disparities and obstacles in breast cancer screening can hinder TGD individuals’ access to appropriate screenings. Grimstad et al33 found that 38% of TGD individuals reported unexpected emotional discomfort with mammography examinations and 49% with ultrasonography examinations, which comprise the majority of breast cancer screening imaging services. For all TGD patients, coverage of screening mammograms may be denied by health insurers due to the incongruence between their recorded sex and gender identity.33 Further, a lack of systematic collection of gender identity data contributes to the absence of high-quality population-level information on breast cancer risk in TGD people. Without these data, systematic screening programs may overlook assigned male-at-birth individuals not registered as female or assigned female-at-birth individuals registered as male, further perpetuating disparities in access to appropriate screenings.

A retrospective case-control study found that compared with 92 cisgender heterosexual patients, sexual and gender minorities (74 lesbian, 12 bisexual, 6 transgender) experienced delays in diagnosis, were more likely to decline recommended treatments (multivariable adjusted odds ratio 2.27), and, possibly as a result of this, have a recurrence of breast cancer (multivariable adjusted hazard ratio 3.07).36 Additionally, institutions, physicians, and patients primarily focus on the active process of transitioning and not on primary care guidelines, which decreases the likelihood of any sort of cancer screening.37 Improving education for both patients and clinicians and increasing research about breast cancer screening and risk could lead to better access and quality of care.

FUTURE RESEARCH

Several recent systematic reviews highlight the ongoing methodologic limitations in this field, including the small number and size of longitudinal cohort studies, limited follow-up durations, and predominance of case report data rather than robust incidence denominators.24,38,39 This is compounded by insufficient detail on hormone regimens and a lack of inclusion of transgender populations in most large studies.

Given the limited data, more longitudinal research is warranted regarding the long-term impact of GAHT on breast cancer risk across the lifespan for all TGD people. As noted earlier, a review of data from the Women’s Health Initiative reported that the use of estrogen therapy alone in average-risk cisgender women did not increase the incidence of breast cancer.14 The meta-analysis by the Collaborative Group on Hormonal Factors in Breast Cancer16 found a modest but clear increase in breast cancer risk with long-term estrogen-only therapy in cisgender women, particularly when started around menopause. These contradictory findings highlight the complexity of extrapolating data specific to transgender women on GAHT.

Better systematic collection and consistent recording of sex assigned at birth, gender identity data, and use of hormone therapy in electronic health records is essential to improving our understanding of breast cancer risk in TGD populations. Future studies should be initiated with the TGD community to ensure that research questions, study design, and interpretation of findings are grounded in the lived experiences of TGD individuals.

Finally, research should investigate optimal communication strategies to facilitate shared decision-making around breast cancer screening for TGD patients. Studies can identify best practices for patient-clinician discussions that overcome knowledge gaps, honor patient preferences, and encourage routine screening engagement. Findings can shape cultural humility training, clinical protocols, and educational materials to support equitable, patient-centered breast cancer prevention across the full diversity of gender identities.

CONCLUSION

Breast cancer screening and risk assessment for TGD patients require an understanding of gender-affirming care and the differences for transgender men and transgender women based on hormone exposure and surgical status. Overall, the risk of breast cancer in TGD individuals on GAHT appears to be lower than in cisgender women; however, the absolute risk is still unclear. Screening guidelines vary slightly across healthcare organizations and institutions, with the ACR and World Professional Association for Transgender Health recommendations being the most current. Delivering patient-centered breast cancer care across the diversity of gender identities requires open dialogue and the development of individualized preventive services that will evolve as data accumulate. Ongoing investigation and education ensure the health of all TGD people.

DISCLOSURES

Dr. Kling has disclosed teaching and speaking for AiCME Answers in CME, Arizona Public Services, City of Mesa, EPG Health, Let’s Talk Menopause, Paradise Valley Country Club, and Vindico Medical Education; and consulting for Bayer and Elsevier. Dr. Carroll and Dr. Vasilev report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.

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