Identifying Breast Cancer Risk in Patients Undergoing Gender‐Affirming Chest Masculinization Surgery

ABSTRACT

Background and Objectives

Breast cancer risk among transgender and gender‐diverse individuals undergoing gender‐affirming chest masculinization (“top”) surgery remains poorly defined. This study aimed to characterize breast cancer risk and management in this population.

Methods

We conducted retrospective chart review of patients undergoing top surgery within an academic plastic surgery practice. Variables included family and reproductive history, genetic testing, International Breast Intervention Study (IBIS) scores, and final pathology. The primary outcome was elevated breast cancer risk, defined as IBIS ≥ 20% (high risk) or 15%–19% (intermediate). Significance was set at p < 0.05.

Results

From April 2019 to December 2024, 284 individuals underwent top surgery. One‐third reported a family history of breast cancer, and two of fifteen genetically tested patients carried pathogenic variants. IBIS scores were calculable in 79 patients, with 43% demonstrating intermediate or high risk (IBIS ≥ 15%). Seven patients were referred to breast surgical oncology and fifteen to genetics; four high‐risk individuals elected risk‐reducing mastectomy. One case of ductal carcinoma in situ was identified during risk‐reducing mastectomy.

Conclusion

A subset of top surgery patients exhibit elevated familial, genetic, or IBIS‐based breast cancer risk. Although incidental malignancy was rare, structured risk assessment and selective referral may improve screening and management in this population.

1. Introduction

Breast cancer remains a significant global health concern, with well‐established risk factors such as genetic predisposition, family history, and hormonal exposure [1]. However, breast cancer risk profiles for transgender and gender‐diverse (TGD) individuals undergoing gender‐affirming chest masculinization (“top”) surgery are poorly defined, with limited data on interplay of family history, genetic variants, and incidental pathology findings in this population [2, 3, 4]. Top surgery is a critical intervention for alleviating gender dysphoria and improving quality of life in transmasculine individuals [5, 6]. Despite its increasing prevalence in reported literature, there is little evidence to guide preoperative breast cancer risk assessment and clinical management in this patient population [7, 8].

TGD individuals may have distinct risk factors for breast cancer as compared to cisgender populations, influenced by hormone therapy, residual post‐surgical breast tissue, lack of consistency with screening, and genetic predispositions [9, 10]. Tools such as the International Breast Intervention Study (IBIS) model, which incorporates family history, reproductive history, and genetic information, are commonly used to stratify breast cancer risk in cisgender women but have not been extensively validated in TGD populations [11, 12]. Additionally, although incidental high‐risk or malignant lesions have been reported in mastectomy specimens, the prevalence and the role of preoperative screening, including genetic testing and imaging, remain understudied [13, 14]. The lack of standardized guidelines for identifying high‐risk patients or when to refer to breast surgical oncology or genetics counseling further complicates clinical decision‐making [15, 16]. The purpose of this study was to characterize breast cancer risk factors, including IBIS scores, family history, and genetic predispositions, and to evaluate current clinical management trends in TGD individuals undergoing top surgery.

2. Materials and Methods

A retrospective chart review was conducted on all TGD adult patients (18 years of age and older) who underwent top surgery within our academic plastic surgery practice. Patients undergoing top surgery were identified using Current Procedural Terminology code‐based queries, supplemented by manual review of institutional surgical schedules to ensure complete case ascertainment and minimize omission of eligible cases due to coding variability. Inclusion criteria were adult patients who self‐identified as TGD and underwent primary top surgery at our institution. Patients were excluded if they underwent only revision top surgery at our institution. Top surgery procedures were performed by four attending plastic surgeons within a single academic practice.

Variables of interest included patient demographics (e.g., age, body mass index [BMI], etc.), reproductive history, family history of cancer (first‐ or second‐degree relatives), preoperative genetic testing, preoperative mammography and associated findings, calculated IBIS cancer risk scores, referrals to genetic counseling or breast surgical oncology, and surgical pathology findings. IBIS scores were retrospectively calculated using the Tyrer‐Cuzick model version 8 (https://magview.com/ibis-risk-calculator/) based on available chart data, which integrates multigenerational family history of breast and ovarian cancer, reproductive factors, and genetic information [17]. IBIS was not routinely used in clinical decision‐making during the study period. Relevant variables were obtained from clinician‐documented history during routine preoperative evaluations rather than from a standardized patient survey or structured data collection tool. As such, documentation was variable, with missing data most commonly including age at menarche, detailed multigenerational family history, and reproductive history variables. Elevated breast cancer risk was defined as an IBIS lifetime risk score of 15–19% (intermediate risk) or > 20% (high risk) [18, 19, 20]. The primary outcome was prevalence of elevated breast cancer risk based on IBIS scores. Secondary outcomes included frequency of referrals to genetic counseling and/or breast surgical oncology, and the incidence of high‐risk (e.g., atypical hyperplasia) or malignant findings on imaging and/or final surgical pathology.

Insurance status (public vs. private) was variably documented and therefore not included in the primary analysis. Exploratory review did not demonstrate a consistent association between insurance status and availability of data required for IBIS calculation or referral patterns; however, incomplete documentation limited formal analysis. Data on testosterone use and prior gender‐affirming surgeries (e.g., hysterectomy or bilateral salpingo‐oophorectomy) were inconsistently documented and therefore not included in the primary analysis.

Data was analyzed using Statistical Packages for the Social Sciences (SPSS) version 29.0.2.0 (Armonk, NY: IBM Corp.). Descriptive statistics were conducted using frequencies and percentages for categorical variables and means with standard deviations and ranges for continuous variables. Pearson's correlation coefficient was used to assess relationships between IBIS scores and continuous variables, including age, BMI, and age at first menses. Statistical significance was set at p < 0.05, using two‐tailed tests when applicable. This study was reviewed and approved by the Colorado Multiple Institutional Review Board (COMIRB #24‐2593) and conducted in accordance with the Declaration of Helsinki.

3. Results

Between April 2019 and December 2024, 284 individuals underwent top surgery. Cohort demographics are available in Table 1. Mean age at time of surgery was 26.8 ± 7.3 years (range 18‐54 years), and the mean BMI was 27.6 ± 6.0 kg/m² (range 16.5–50.5 kg/m²). Patients predominantly identified as transgender male (n = 198, 69.7%) or non‐binary (n = 86, 30.3%). The majority identified as White (209/284, 73.6%), with smaller proportions identifying as Hispanic/Latino (39/284, 13.7%), Black (14/284, 4.9%), Asian (5/284, 1.8%), or other/multiracial (17/284, 6.0%). Six patients had documented Ashkenazi Jewish inheritance.

Table 1.

Patient demographics and baseline characteristics (N = 284).

Characteristic	n (%) or mean ± SD (range)
Age (years)	26.8 ± 7.3 (18–54)
BMI (kg/m²)	27.6 ± 6.0 (16.5–50.5)
Gender identity
Transgender male	198 (69.7)
Non‐binary	86 (30.3)
Race/Ethnicity
White	209 (73.6)
Hispanic/Latino	39 (13.7)
Black	14 (4.9)
Asian	5 (1.8)
Other/multiracial	17 (6.0)

Abbreviations: BMI, body mass index, SD, standard deviation.

Reproductive history and genetic characteristics are available in Table 2. Ninety‐three patients (93/284, 32.7%) reported a family history of breast cancer, including 85 (85/284 29.9%) with affected first‐degree (n = 12) or second‐degree (n = 73) relatives. In terms of reproductive history, most individuals (239/284, 84.2%) had a documented history of menses and 86 (86/284, 30.3%) had documentation of the age at first menses; most were pre‐menopausal (243/284, 85.6%), had never given birth (269/284, 94.7%), and had never used estrogen‐based birth control (282/284, 99.3%). Fifteen patients (15/284, 5.3%) underwent preoperative genetic testing with two testing positive for pathogenic variants (PALB2 and TP53).

Table 2.

Reproductive and genetic characteristics (N = 284).

Variable	n (%)
History of menses	239 (84.2)
Age at first menses documented	86 (30.3)
Pre‐menopausal	243 (85.6)
Ever given birth	15 (5.3)
Ever used estrogen‐based birth control	2 (0.7)
Family history of breast cancer	93 (32.7)
First‐degree relative	12 (4.2)
Second‐degree relative	73 (25.7)
Preoperative genetic testing performed	15 (5.3)
Positive for pathogenic variant	2 (PALB2, TP53)

Breast cancer risk assessment and pathology findings are available in Table 3. Thirty‐five patients (35/284, 12.3%) had preoperative mammography. Among those with available breast density data, 11 (11/35, 31.4%) had scattered fibroglandular density (BI‐RADS B), 3 (3/35, 8.6%) had heterogeneously dense tissue (BI‐RADS C), and 4 (4/35, 11.4%) were classified as extremely dense (BI‐RADS D). No patients had predominantly fatty breasts (BI‐RADS A). Breast density was not recorded for 17 patients (17/35, 48.6%). One mammogram (1/35, 2.9%) demonstrated findings consistent with a complex fibroadenoma with sclerosing adenosis and microcalcifications; all other studies were unremarkable.

Table 3.

Breast cancer risk assessment and pathology findings (N = 284).

Variable	n (%) or mean ± SD
Preoperative mammography performed	35 (12.3)
BI‐RADS A (mostly fatty tissue)	0 (0.0)
BI‐RADS B (scattered fibroglandular density)	11 (31.4)
BI‐RADS C (heterogeneously dense)	3 (8.6)
BI‐RADS D (extremely dense)	4 (11.4)
BI‐RADS E (unknown)	17 (48.6)
High‐risk finding (complex fibroadenoma)	1 (2.9)
IBIS risk score calculable	79 (27.8)
Mean IBIS score	15.8 ± 4.7 (6.7–28.6)
Average risk (< 15)	45 (57.0)
Intermediate risk (15–19)	19 (24.0)
High risk (≥ 20)	15 (19.0)
Correlation of IBIS score with age	r = 0.06, p = 0.57
Correlation of IBIS score with BMI	r = 0.05, p = 0.67
Correlation of IBIS score with age at first menses	r = −0.39, p = 0.06
Referred to breast surgical oncology	7 (2.5)
Referred to genetics counseling	15 (5.3)
High‐risk (IBIS score ≥ 20) who had risk‐reducing mastectomy	3/15 (20.0)
Final surgical pathology
Benign breast tissue	283 (99.6)
Ductal carcinoma in situ	1 (0.4)

Abbreviations: SD, Standard deviation; IBIS, International Breast Intervention Study; BI‐RADS, breast imaging reporting and data system.

IBIS scores were calculable for 79 patients (79/284, 27.8%), with an overall mean score of 15.8 ± 4.7 (range 6.7–28.6). Of these 79 patients, 45 (45/79, 57.0%) had average risk scores ( < 15), 19 (19/79, 24.0%) had intermediate risk scores (15–19), and 15 (15/79, 19.0%) had high risk scores (≥ 20). The incidence of elevated breast cancer risk (IBIS score ≥ 15) was 43.0% (34/79) in this cohort. No significant correlations were observed between IBIS scores and age (r = 0.06, p = 0.57), BMI (r = 0.05, p = 0.67), or age at first menses (r = −0.39, p = 0.06). Among patients without calculable IBIS scores (205/284), missing data most commonly included age at menarche, detailed multigenerational family history, and reproductive history variables. These data elements were not routinely or systematically captured in clinical documentation and overlap between missing variables was common.

Overall (N = 284), 15 patients (15/284, 5.3%) were referred to genetics preoperatively, seven (7/284, 2.5%) were referred to breast surgical oncology, and four (4/284, 1.4%) underwent risk‐reducing mastectomy. Among the 15 high‐risk patients (IBIS ≥ 20), four (4/15, 26.7%) were referred to genetic counseling based on family history, and three (3/15, 20.0%) were referred to breast surgical oncology‐two with pathogenic variants (PALB2 and TP53) and one with a first‐degree family history of breast cancer and Ashkenazi Jewish ancestry. All three subsequently underwent risk‐reducing mastectomy. The remaining 12 high‐risk patients (12/15, 80.0%) underwent standard top surgery with plastic surgery; one of these underwent genetic testing (negative for pathogenic variants), while none were recommended or elected to pursue additional screening or risk‐reducing procedures. Three additional patients referred to breast surgical oncology ultimately declined consultation. Of note, both pathogenic variants (PALB2 and TP53) were known familial variants, previously identified in affected relatives and consistent with established hereditary cancer syndromes.

Final surgical pathology was benign in 283 cases (283/284, 99.6%), with one patient (1/284, 0.4%) diagnosed with intermediate‐grade ductal carcinoma in situ. Notably, the patient had a strong family history of breast cancer, had an IBIS score > 20, was referred to breast surgical oncology as well as genetics, and underwent formal risk‐reducing mastectomy as part of their gender transition. No invasive malignancies or high‐risk lesions were identified in the remaining surgical specimens.

4. Discussion

This study is among the first to systematically characterize breast cancer risk factors and management practices in TGD individuals undergoing top surgery. Nearly half of patients with calculable IBIS scores demonstrated elevated lifetime breast cancer risk (24.0% intermediate; 19.0% high), and one‐third reported a positive family history. Pathogenic germline variants were identified in two patients (PALB2 and TP53), and one patient was diagnosed with intermediate‐grade ductal carcinoma in situ. These findings highlight the importance of incorporating oncologic risk assessment into preoperative evaluation for TGD patients seeking top surgery.

The elevated prevalence of family history of breast cancer in our cohort (32.7%), together with identification of hereditary cancer syndromes such as PALB2 and TP53, reinforces emerging evidence that genetic predispositions may be underrecognized in TGD individuals due to inconsistent screening and documentation [2, 9]. Nevertheless, only 5.3% of patients underwent preoperative genetic testing, underscoring significant underutilization of this resource and inconsistent approaches to identifying high‐risk individuals. Integrating structured family history screening, automated risk assessment tools, or standardized referral protocols into preoperative workflows could improve early recognition of at‐risk patients, particularly as many TGD individuals may have limited engagement with traditional gynecologic or primary care services [21, 22]. Although not systematically captured in this study, insurance status and structural barriers to care likely contribute to incomplete risk assessment and referral patterns in this population and warrant further prospective evaluation. Previous authors have advocated for a more holistic preoperative evaluation framework that includes genetic counseling and testing in high‐risk patients [3]. The variability in management among high‐risk individuals further reflects the absence of consensus on how oncologic risk should influence surgical planning. While standard top surgery may offer adequate risk reduction for some, others, particularly those with pathogenic variants or compelling family history, may benefit from formal risk‐reducing mastectomy with preservation or reconstruction. Clear criteria for when to involve breast surgical oncology, and even multidisciplinary preoperative case discussions may help standardize care and avoid both undertreatment and overtreatment.

Use of the IBIS model revealed substantial variability in risk classification, with no significant correlations between IBIS scores and traditional predictors such as age, BMI, or age at first menses. These findings underscore the structural limitations of applying cisgender female‐validated risk models to gender‐diverse patients. The inability to calculate IBIS scores in the majority of patients reflects inconsistent documentation of key risk variables, rather than absence of risk factors, highlighting an important gap in preoperative evaluation workflows. Key contributors to IBIS risk (i.e., parity, menopausal status, and endogenous estrogen exposure) may be absent or atypical in TGD individuals, while other relevant factors, including duration of testosterone therapy and extent of residual breast tissue after surgery, are not captured by the model [11, 12]. These discrepancies highlight the need for TGD‐specific risk calculators that incorporate gender‐affirming hormone therapy, postoperative tissue distribution, and sociodemographic determinants of screening access. Consistent with findings by Cortina et al., elevated IBIS classification influenced clinical management decisions in only a subset of high‐risk patients; in our cohort, 20% (3/15) ultimately underwent risk‐reducing mastectomy [12]. These observations underscore the importance of developing standardized, evidence‐based protocols to guide risk counseling and surgical decision‐making in this population.

The low incidence of malignant or high‐risk pathology (0.4%) aligns with prior reports demonstrating malignancy rates between 0.1% and 0.6% and high‐risk lesions in 1%–6% of top surgery specimens and supports ongoing discussion regarding the utility of routine pathologic examination in young, low‐risk patients [3, 7, 14, 16]. However, the identification of ductal carcinoma in situ in a patient with elevated IBIS risk and significant family history emphasizes the importance of selective vigilance for individuals with concerning clinical or hereditary factors. Residual breast parenchyma after top surgery represents another unresolved challenge. Because degree of tissue removal varies substantially by surgeon, technique, and patient anatomy, determining long‐term cancer risk and corresponding surveillance strategies remains difficult [23, 24]. This uncertainty is compounded by the absence of screening guidelines specific to TGD individuals. Preoperative mammography was obtained in 12.3% of patients, with one concerning finding, suggesting selective imaging based on family history or IBIS scores may be an appropriate strategy [3]. Current national recommendations, which are based on sex assigned at birth, do not account for gender‐affirming surgical or hormonal factors [10]. Our findings support selective preoperative imaging and genetic counseling for individuals with elevated IBIS scores (≥ 15%) or significant family history to guide both risk‐reduction strategies and postoperative surveillance planning.

This study has several limitations to consider. The retrospective nature of this analysis precludes standardized data collection and limits temporal or causal inference. Calculation of IBIS scores were feasible for 79 patients (27.8%), which may introduce both selection and information bias due to non‐routine calculation and incomplete documentation of required risk factors. The single‐institution setting may limit generalizability, particularly given variations in hormone therapy usage and demographic diversity. The low observed malignancy rate may reflect the relatively young age of our cohort and short‐term follow‐up, limiting conclusions about long‐term cancer incidence after top surgery [3, 16]. Additionally, important variables such as testosterone exposure and prior gender‐affirming surgeries were not consistently available, limiting assessment of their potential impact on breast cancer risk.

Future studies should prospectively validate breast cancer risk models in TGD populations, assess the predictive value of existing tools such as IBIS/Tyrer‐Cuzick or the Gail model, and explore the development of tailored validated models incorporating gender‐affirming hormone therapy and surgical variables [25, 26]. Longitudinal follow‐up studies are also needed to define optimal surveillance protocols for residual breast tissue following top surgery. Collaborative, multidisciplinary efforts between plastic surgeons, breast surgical oncologists, and genetic counselors will be critical to developing standardized, evidence‐based guidelines for preoperative evaluation and long‐term risk management in this population.

5. Conclusion

In conclusion, our findings demonstrate that a significant proportion of gender‐affirming chest masculinization surgery patients presented with elevated breast cancer risk, driven by family history or genetic predispositions, though incidental malignancy remained rare. Standardized preoperative risk assessment using tools such as the IBIS model, coupled with selective referrals to breast surgical oncology and genetics counseling, can enhance clinical decision‐making and improve patient outcomes. These findings underscore the need for standardized guidelines to address the unique risk profile of gender‐diverse individuals undergoing gender‐affirming chest masculinization surgery, ensuring comprehensive, patient‐centered care.

Funding

The authors have nothing to report.

Synopsis

This retrospective study of 284 transgender and gender‐diverse individuals undergoing chest masculinization surgery found that a substantial proportion exhibited elevated breast cancer risk based on family history, genetic predisposition, or IBIS scores, though risk assessment was inconsistently performed. Among patients with calculable risk (n = 79), 43% had intermediate or high lifetime risk, yet genetic testing and specialist referrals were underutilized, and management varied widely. Despite a very low incidence of malignancy (0.4%), the findings support the need for standardized, structured preoperative risk assessment and referral pathways to optimize oncologic care in this population.

Cronin J. E., Aryanpour Z., Durden J. A., et al., “Identifying Breast Cancer Risk in Patients Undergoing Gender‐Affirming Chest Masculinization Surgery,” Journal of Surgical Oncology 134 (2026): 25‐30, 10.1002/jso.70272.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.