Breast Cancer Screening, Management, and a Review of Case Study Literature in Transgender Populations

Abstract

Because of a lack of uniform collection of gender identity data, population-level breast cancer statistics in the transgender community are unknown. With recent estimates that at least 0.6% (1 in every 167 people) of the U.S. population is transgender, guidance on breast cancer risk, screening, and management in this population is needed. Such guidance should examine modifications, if any, to recommendations in cisgender populations, taking into consideration any history of hormone therapy exposure or breast surgery. This article describes existing evidence on breast cancer incidence in transgender women and men, and attempts to make rational recommendations regarding the screening for and approach to managing breast cancer in transgender populations. Current data are mostly limited to case reports which are reviewed here. More prospective, population-level research is needed to better understand the risks and predictors of breast cancer in this population, as well as to better inform the most appropriate screening modality, age of starting screening, and interval. Ultimately, a risk score calculator similar to existing risk models such as the Gail score, as well as an approach to shared decision making that involves patient-centered perspectives, is needed to best guide practices in this area.

 

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Keywords

transgender - breast cancer - screening - treatment

Breast cancer is the most common cancer in cisgender women worldwide.[1] A cisgender person is someone who holds a gender identity that aligns with the sex assigned at birth (i.e., a non-transgender person). An estimated 252,000 cisgender women are expected to be diagnosed with, and 40,000 are expected to die of, this disease in the United States in 2017. More than 2,000 cisgender men will be diagnosed with more than 400 deaths.[2] Because of a lack of uniform collection of gender identity data, population-level breast cancer statistics in the transgender community are unknown.[3] With recent estimates that at least 0.6% (1 in every 167 people) of the U.S. population are transgender,[4] guidance on breast cancer risk, screening, and management in this population is needed. Such guidance should examine modifications, if any, to recommendations in cisgender populations, taking into consideration any history of hormone therapy exposure or breast surgery. However, consensus on the approach to screening in cisgender women is lacking with respect to the age to begin screening, frequency of screening, and modality of choice.[5] [6] [7] [8] [9] [10] [11]

The potential and nontrivial harms of false positives or over diagnosis further complicate efforts to develop consensus on approach.[12] [13] Such cases can lead to exposure to additional radiation, invasive biopsies, psychological distress, and costs.[12] [14] In the general population, the cumulative 10-year false-positive rate among cisgender women has been found to be 61% when mammography is performed yearly, and 42% when performed biannually.[15] With the growing recognition that some cases of ductal carcinoma-in-situ (DCIS) or invasive breast cancer resolve without intervention, over-screening for breast cancer represents identification of (and subsequent treatment for) low-risk breast neoplasms, with the resultant treatment having greater harms than no treatment on outcomes. Long-term follow-up studies suggest that the rate of overdiagnosis in cisgender woman ranges from 10 to 22%.[16] [17]

An approach to breast cancer screening should optimize patient outcomes, while at the same time minimizing false positives and overdiagnosis. The approach to minimizing false positives should include consideration of a screening test's positive predictive value (PPV) for a given individual. The PPV is the probability (0–100%) that a positive test result represents a true positive (as opposed to a false positive). The PPV depends on the prevalence of a disease in the population being studied. As the prevalence of the disease goes down, the likelihood of a positive test representing a true positive also goes down. As the prevalence of a disease gets very low, the PPV also gets very low, greatly increasing the risk of a false positive.[18] At the individual level, the concept of prevalence can be replaced with an individual's pretest probability. For example, the Breast Cancer Risk Assessment Tool developed by the National Cancer Institute (“Gail Model”) allows the calculation of an individual 5-year and lifetime risk of breast cancer for cisgender women. However, current practice does not include the next step of using this pretest probability to calculate the likelihood that a positive screening test is truly positive. However, for example, the PPV of a coronary artery computed tomography angiography (CTA) is calculated based on the pretest probability of an individual having coronary artery disease, which itself is calculated from multivariate prediction models. This PPV then allows the provider to have a meaningful discussion with a patient on how to proceed given their test results.[19] This explains, for example, why cisgender men are not routinely screened for breast cancer, as the PPV would be very low since the prevalence in the population is so low (0.1% lifetime cumulative risk), and most positive test results would be false positives.[20] As such, efforts to develop recommendations for screening (or not to screen) for breast cancer in transgender populations are impaired by a lack of an understanding of the prevalence of the disease. Further lacking is an understanding of how factors such as hormone use, breast surgery, or breast prostheses (i.e., implants) used in the course of gender-affirming care impact cancer risk among transgender people.

Role of Hormones in Breast Cancer Pathogenesis

Breast cancer can result from a combination of environmental, genetic, and hormonal influences.[21] Among transgender people, an exploration of the hormonal implications in breast cancer pathogenesis is warranted when gender-affirming hormones are to be administered. Hormonal influences should also be considered in the context of family history, especially in the presence of a BRCA genetic mutation. No studies to date have explored interactions between gender-affirming hormone therapy and breast cancer pathogenesis; in cisgender women, both endogenous and exogenous estrogens are implicated. Estrogen has been a long suspected and recently confirmed carcinogen of breast tissue.[22] [23] Reviews of the evidence from prospective and in vitro studies suggest that estrogen is known to directly stimulate neoplastic breast tissue proliferation as well as cellular level chromosomal changes that lead to tumor development[22] [23]; estrogen also metabolizes into genotoxic metabolites that have been implicated in breast cancer pathogenesis.[23]

The length and amount of exposure to endogenous estrogen is also thought to contribute to breast cancer risk in cisgender people.[22] [23] Cumulative lifetime exposure to estrogens, impacted by number of years between menarche and menopause, obesity, and serum androgen levels, has been associated with increased risk for breast cancer development in postmenopausal cisgender women.[22] Transgender women, individuals assigned male sex at birth but who identify as female or on a feminine gender spectrum, may take exogenous estrogen to promote breast development. Therefore, hormonal factors may contribute to risk in transgender women as well. Large studies of postmenopausal cisgender women taking combined estrogen–progesterone hormone replacement therapy found an increased risk for breast carcinoma in combined hormone replacement groups, but not among estrogen-only replacement groups, however it should be noted that this study involved the use of conjugated equine estrogens rather than the bio-identical 17-β estradiol most commonly used by transgender women.[24] The specific mechanism by which combined estrogen–progesterone hormone replacement causes breast cancer is still unclear and requires further study.[22]

Transgender men, individuals assigned female sex at birth but who identify as male or on a masculine gender spectrum, may take exogenous testosterone to induce and maintain masculine secondary sex characteristics. Androgens have also been implicated in breast cancer pathogenesis, primarily due to androgen aromatization into estrogens. In a prospective study of postmenopausal cisgender women, high serum levels of androstenedione and testosterone have been associated with relative risk for noninvasive, in situ estrogen receptor–positive breast cancer.[25] Finally, small numbers of breast cancer are androgen-receptor positive,[26] suggesting a direct role of androgens in breast cancer pathogenesis.[27] A prospective study of five Austrian transgender men found both up- and downregulation of breast cancer gene expression signatures, as well as significant heterogeneity between individual patients.[27] Of note, participants in this study were given both testosterone undecanoate therapy (a 3-month depo-injectable form of testosterone available only under very limited access in the United States) and lynastrenole (an oral progestagen) for undetermined length of time prior to the histological evaluation of the breast tissue.[27] Therefore, application of these findings may have limited usefulness for clinicians using more common approach of testosterone-only therapy for transgender men, nevertheless testosterone may play a direct role in altering breast tissue.

 

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Breast Cancer Risk in Transgender Women

In transgender women, factors that may contribute to a reduced risk of breast cancer include potentially less lifetime overall or cyclical exposure to estrogen and in some cases the absence of or minimal exposure to progesterone. However, transgender women have a high prevalence of dense breasts, an independent risk for breast cancer and also a predictor of increased rates of false-negative mammograms; a Dutch study of 50 transgender women found that 60% had “dense” or “very dense” breasts on mammography.[28] [29]

Existing retrospective data on transgender women have mixed findings. Two retrospective population-based studies of breast cancer in transgender women have been reported; both reported only on cases of breast cancer that were detected as part of routine clinical care, as opposed to through a structured and broad screening program. A retrospective study of 2,307 Dutch transgender women treated at a single center found an estimated incidence of 4.1/100,000 person-years, in comparison to the incidence of 155/100,000 person-years in the general Dutch cisgender female population.[29] A retrospective review of 3,566 transgender women receiving care in the U.S. Veterans Administration Healthcare System found a total of three cases, translating to a nonsignificant standardized incidence ratio (SIR) of 0.7 (95% confidence interval [CI]: 0.03–5.57) in comparison to cisgender women, and a significant SIR of 33.3 (95% CI: 21.9–45.1) in comparison to cisgender men.[30] It is unclear how many cases of breast cancer went undetected in these two populations, and were then otherwise lost to follow-up or to mortality (known to be high in transgender women) from other causes.[31] Data on breast cancer in transgender women have been limited to the above studies, and is overall reassuring with regard to risk being not higher, and possibly lower than in the cisgender female population.

 

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Age to First Consider Screening

The only known large population-based study of mammography screening in cisgender women before the age of 50 years was conducted in the United Kingdom on 160,921 women and found no difference in overall breast cancer mortality as compared to beginning screening at age 50.[32] Given the equivocal value of screening before the age of 50 years and the likely lower incidence in transgender women, we recommend not to begin screening mammography in transgender women before the age of 50 years.

 

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Length of Exposure to Feminizing Hormones

The length of exposure to estrogens as well as variable exposure to progestagens differs between transgender women and cisgender women. Therefore, we recommend not commencing screening in transgender women until after a minimum of 5 years of feminizing hormone use, regardless of age. Some providers may choose to discuss the risks of overscreening with patients and delay screening until 10 years after initiation of feminizing hormones, regardless of age. Note that transgender women older than 50 years do not meet screening criteria until they have at least 5 to 10 years of feminizing hormone use.

 

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Frequency of Screening

Existing recommendations in cisgender women vary with respect to the frequency of screening. As with the age of onset, given the likely lower incidence in transgender women, we recommend screening mammography be performed every 2 years, once patients reach 50 years of age, and 5 to 10 years of feminizing hormone use. Screening more frequently than once a year in cisgender women has not been found to be cost-effective.[14]

 

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Modality of Screening

Screening mammography is the primary recommended modality for breast cancer screening in transgender women. Transgender women are often concerned with their breast appearance and development, and may perform frequent unguided self-examinations. Early breast development may be associated with breast pain, tenderness, and nodularity. Transgender women may request breast exams for these symptoms, or may find breast examinations to be gender affirming. As such providers may consider periodic clinical breast exams, and/or a discussion with patients about general breast awareness and health; however, formal clinician or self-breast exams for the purpose of breast cancer screening are not recommended in transgender women.

 

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Special Considerations

Clinicians may choose to reduce the age of onset of screening, number of years of feminizing hormone exposure, or frequency of screening in patients with significant family risk factors. Transgender women with a family history suggestive of (or known) BRCA mutation should be referred for genetic counseling and screening. No data exist to guide the use of estrogens in transgender women found to have a BRCA mutation: 5.6% of cisgender men (as compared with 78% of cisgender women) with a BRCA-1 mutation will develop breast cancer before the age of 70 years. It is unclear if transgender women with the BRCA-1 mutation and using estrogen have a risk above that of cisgender men with a BRCA-1 mutation. A single case report of a transgender woman with the BRCA-1 mutation involved the continued use of estrogen under informed consent.[33] Transgender women with a BRCA mutation should be referred for oncologic consultations prior to initiating hormone therapy. Patients on established hormone therapy who are then found to have a BRCA mutation should also be referred for oncologic consultation.

A retrospective cohort study of 1,263 transgender women receiving care at a large urban community health center in the United States found that transgender individuals between ages 50 and 74 years and with a history of at least 5 years of hormone therapy were significantly less likely than cisgender individuals to have a mammogram per guidelines (adjusted odds ratio = 0.53; 95% CI = 0.31, 0.91).[34] Further research is needed to understand barriers and other factors which underlie this disparity.

Little study has been conducted on breast cancer screening in individuals who have undergone breast augmentation surgery, a procedure highly prevalent in transgender females. Alternative approaches to screening mammography have been described which displace the implant out of the radiographic field of view.[35] The risk of mammography-induced implant rupture is low, with a study of adverse events reported to the U.S. Food and Drug Administration between 1991 and 2002 revealing only 66 cases of implant rupture or other mammography complication.[36] However, the presence of implants may complicate efforts for needle biopsies.[35]

 

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Soft-Tissue Fillers (“Silicone”)

Transgender women may undergo injection of soft-tissue fillers into the breasts, especially when access to medically supervised hormone therapy or breast augmentation is lacking.[37] Such fillers may result in complications such as breast tissue inflammation, granulomas, cosmetic deformity, silicone migration, skin necrosis, ulceration, and skin and soft-tissue infection.[38] [39] The breast examination of women who have undergone soft-tissue injections is often abnormal, resulting in nodular breasts and induration.[38] [39] In addition, the presence of granulomas and scarring can complicate mammography interpretation, and an ultrasound or magnetic resonance imaging (MRI) may be necessary.[38] [39] In one case report, soft-tissue filler injection was associated with granulomatous changes and scirrhous carcinoma of the breast.[40]

 

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Breast Cancer Screening and Considerations in Transgender Men

Transgender men who have not undergone bilateral mastectomy, or who have undergone only breast reduction, should undergo screening according to current guidelines for cisgender women. Some experts anecdotally recommend annual chest wall exams in transgender men after mastectomy; however, this is not based on evidence, and is in conflict with the move away from clinician exams in general for cisgender women. No reliable evidence exists to guide the screening of transgender men who have undergone mastectomy. Since most, but not all, breast tissue has been removed, mammography for the evaluation of a palpable lesion may not be technically feasible, and alternatives such as ultrasound or MRI may be necessary. Some surgeons perform routine preoperative mammography, though there is no evidence to support this practice, and incidental breast cancers identified through this practice in younger transgender men may represent overdetection of neoplasms which would have resolved without intervention. Currently, no evidence exists to guide the approach to transgender men who have a BRCA mutation. If the mutation is detected prior to gender-affirming mastectomy, the patient should be counseled on pursuing a more invasive prophylactic bilateral mastectomy, which may result in an inferior cosmetic result than the usual subcutaneous mastectomy performed in transgender men, but will remove effectively all breast tissue. Transgender men determined to have a BRCA mutation after subcutaneous mastectomy has been performed should be offered consultation with a breast surgeon to discuss possible revision surgery; if additional surgery is not pursued, increased screening efforts using a combination of chest wall exams, ultrasound, and MRI should be considered in consultation with an oncologist.

 

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Case Reports of Breast Cancer in Transgender Populations: Review of the Literature

With the exception of the two previously described retrospective studies, existing data on breast cancer in transgender populations are limited to case reports, with the first one published in 1968. While several publications have reviewed existing case reports, none, to our knowledge, have conducted a systematic review of the literature. A comprehensive literature review was conducted by searching for English language articles, including original case reports, case series, and cohort studies, published after 1945 in PubMed/MEDLINE, EBSCOhost, CINAHL, and Google Scholar. Search terms for transgender populations (including “transsexual,” “trans-sexual,” “transgender,” “transsexualism,” “male-to-female,” and “female-to-male”) were cross-referenced with terms for breast cancer (including “breast cancer,” “carcinoma in situ,” “breast neoplasms”). All abstracts were reviewed for relevance with full-text review for data abstraction. Several existing review articles also served as sources for case report citations.[29] [41] [42] [Tables 1] and [2] represent all case reports identified by these techniques in transgender women ([Table 1])[29] [30] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] and transgender men ([Table 2]).[29] [30] [45] [54] [55] [56] [57] Unfortunately, many of the case reports lack important details including type and duration of hormones used, family history, type of tumor, hormone receptor and BRCA status, and outcomes. Future case reports of breast cancer in transgender populations should aim to report as much relevant information as possible.

Table 1 Published case reports of breast cancer in transgender women, 1968–2017

Age at dx	Estrogen use	Progestagen use	Hormone use, years, cumulative lifetime	Fam hx	Presenting finding	Surgical augmentation hx	Type of tumor as reported	Estrogen receptor status	Progesterone receptor status	HER2 receptor status	Androgen receptor status	BRCA mutation present	Outcome	Citation
53	Y	Y	7	Multiple relatives with BRCA-2-related cancers	Screening mammogram	−	Undiff invasive ductal	+	+	−	+	2	Local recurrence at 30 mo	Corman et al[43]
71	Y		7	Neg	Lump found by pt	−	Unk	+	−	Unk	Unk	Unk	Died from mets 22 mo later	Brown and Jones[30]
55	Unk		Unk	Sister	Unk	−	Unk	+	−	+	Unk	Unk	Died from mets 6.5 y later	Brown and Jones[30]
54	Unk		Unk	Neg	Large mass and nipple discharge	−	Stage 1 infiltrating ductal	−	−	Unk	Unk	Unk	Died 54 d after dx	Brown and Jones[30]
51	Y		37	Maternal grandmother and aunt	Lump found by pt	−	DCIS, invasive ductal	−	−	−	−	−	Unk	Gondusky et al[44]
52	Y	Y	30	Unk	Lump found	−	Adenocarcinoma	+	−	Unk	Unk	−	Unk	Gooren et al[45]
46	Unk		6–10 y	Paternal grandmother, maternal aunt	Lump found by pt	−	Invasive ductal	+	+	+	Unk	Unk	Death at age 49 due to complications	Gooren et al[45]
60	Unk		8 y unknown type	Neg	Screening mammogram	−	Infiltrating ductal	+	+	−	Unk	Unk	5-y follow-up event free after treatment	Sattari[42]
41	Y		14	Neg	Lump found	Implants unk type	Invasive ductal	−	−	−	Unk	Unk	Unk	Teoh et al[46]
65	Y		13	Father, maternal aunt; mother hx ovarian CA	Screening mammogram	−	DCIS	−	Unk	Unk	Unk	−	Unk	Maglione et al[41]
55	Y		30 y	Unk	Bloody nipple discharge	Silicone injections	Poorly differentiated invasive ductal carcinoma, apocrine type, Paget's disease	−	−	+	Unk	Unk	Unk	Maglione et al[41]
43	Y	Y	15	Neg	Painful breast and mass	−	Invasive ductal	−	−	−	Unk	Unk	Extensive mets, pt died of drug overdose	Pattison and McLaren[47]
57	Y		36	Unk	Unk	−	Ductal	−	−	−	Unk	Unk	Unk	Gooren et al[29]
58	Y		11	?	Lump noted by provider	Silicone implants	Adenocarcinoma	+	+	Unk	Unk	Unk	Unk	Dhand and Dhaliwal[48]
53	Y		Unk	3 sisters with breast cancer	Breast skin changes and disfigurement	Saline implants	High-grade phylloides	−	−	−	Unk	Unk	Unk	Kelley[59]
46	Unk		Unk	Unk	Incidental finding during implant revision	Silicone implants	Secretory carcinoma	−	−	−	−	Unk	Unk	Grabellus et al[50]
36	Y		14	Unk	Painful breast lump found by pt	−	Invasive ductal	+	Unk	Unk	Unk	Unk	Unk	Ganly et al[51]
45	Y		10	Mother	Lump found by pt	−	High-grade infiltrating ductal	+	+	Unk	Unk	Unk	Disease free 14 mo after treatment	Pritchard et al[52]
30	Y	Y	4 y	Unk	Lump found by pt	Silicone implants, possibly intramammary silicone and estrogen injections	Poorly differentiated adenocarcinoma	Unk	Unk	Unk	Unk	Unk	Died due to sepsis	Symmers[53]
30	Y		<5 y	Unk	Lump found by pt	“Rubber” implants	Infiltrating ductal adenocarcinoma	Unk	Unk	Unk	Unk	Unk	Died due to mets	Symmers[53]

Abbreviations: DCIS, ductal carcinoma in situ ; dx, diagnosis; hx, history; mets, metastases; Neg, negative; N, no; pt, patient; Undiff, undifferentiated; Unk, unknown; Y, yes.

Notes: “Unk” entry in “estrogen use” column indicates that the patient was described as taking hormone therapy of some kind, but estrogen use was not specified. Blank entries in the “progesterone use” column indicate that there was no mention of progestagen use in the report. Progestagens are used commonly in hormone therapy regimens, especially outside of the United States. None of the case reports specifically indicated that a patient was not using a progestagen. An entry of “lump found” in the “presenting finding” column indicates that it was not clear if the lump was identified by a self-exam or clinician exam. “Unknown” outcome indicates that either no follow-up data are available or available data do not explicitly indicate both time frame and status. Gooren et al 2013 also report a case of a transgender woman found to have poorly undifferentiated axillary metastases with unknown primary; this case was excluded from this table.

Table 2 Published case reports of breast cancer in transgender men, 1968–2017

Age at dx	Testosterone use	Hormone use, years, cumulative lifetime	Masculinizing chest surgery performed prior to dx	Family history	Presenting finding	Type of tumor as reported	Estrogen receptor status	Progesterone receptor status	HER2 receptor status	Androgen receptor status	BRCA mutation present	Outcome	Citation
41	Y	15	Y	Neg	Pt found a lump	Invasive ductal	+	+	−	+	Unk	Unk	Katayama et al[54]
74	Y	13	N	Unk	Pt found a lump	Infiltrative ductal	+	−	+	Unk	Unk	Died due to mets after 2 y	Brown and Jones[30]
42	Y	<4 y	N	Single female relative	Unk	Unk	+	+	Unk	Unk	Unk	Survival at end of 10-y surveillance	Brown and Jones[30]
42	Y	3	N	N	Unk	Unk	Unk	Unk	Unk	Unk	Unk	Survival at end of 9-y surveillance	Brown and Jones[30]
48	Y	9	Y	Unk	Palpable lump at scar	Infiltrating ductal	−	−	−	Unk	Unk	Unk	Gooren et al[45]
41	Y	1	N	Unk	Discovered via pathology studies on breast tissue after mastectomy	Tubular adenocarcinoma	+	+	−	Unk	Unk	Unk	Gooren et al[45]
27	Y	3	N	Unk	Discovered via pathology studies on breast tissue after mastectomy	Tubular adenoma	+	+	Unk	Unk	Unk	Unk	Gooren et al[29]
42	Y	3	Y	Neg	Pt found a lump	Invasive ductal	−	−	+	+	Unk	Unk	Nikolic et al[55]
53	Y	5	N	Maternal aunt breast at 32, maternal grandmother ovarian at 60	Pt found a lump	Invasive ductal	+	−	+	Unk	−	2 y cancer free	Shao et al[56]
27	Y	6	N	Maternal grandmother breast cancer	Pt found a lump	Invasive ductal	+	+	+	Unk	−	Unk	Shao et al[56]
33	Y	13	Y	Neg	Pt found a lump	Infiltrating ductal	+	+	Unk	Unk	Unk	5 y cancer free	Burcombe et al[57]

Abbreviations: dx, diagnosis; Neg, negative; N, no; Unk, Pt, patient; unknown; Y, yes.

Notes: Unknown if the lesion identified via “Palpable lump at scar” was found by patient or provider exam. “Unknown” outcome indicates that either no follow-up data are available or available data do not explicitly indicate both time frame and status. Five case reports of breast cancer in people with a transgender male/masculine gender identity but who had not undergone any gender-affirming hormone therapy or surgeries are excluded from this table (Brown and Jones 2015 report four such cases; Gooren et al 2015 report one such case).

 

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Treatment Considerations for Transgender People Diagnosed with Breast Cancer

The general approach to the treatment of breast cancer is highly individualized, with both individual-level and tumor-specific factors coming into play. Staging depends on the size of the primary tumor, whether there is involvement of axillary lymph nodes and presence/absence of metastases. Also important to treatment is whether the cancer has hormone receptors (estrogen and/or progesterone receptor positive) or with HER-2 (ERBB2 or neu) protein overexpression, and the age hormonal history/status of the patient. Early-stage cancers are often treated with surgery, usually breast conservation surgery (lumpectomy) and radiation therapy. Adjuvant therapy may include chemotherapy and/or hormonal treatment, such as selective estrogen receptor modulators (SERMs) or aromatase inhibitors for estrogen receptor–positive tumors and anti-HER2 therapy for HER-2–positive cancers.[58]

The general treatment approach to breast cancer in transgender women undergoing hormone therapy would be similar to that for cisgender women, with the exception that in circumstances which would usually warrant a recommendation for oophorectomy or anti-estrogen therapy with a SERM or aromatase inhibitor, a recommendation to discontinue estrogen hormone therapy should be made. However, since hormone therapy can profoundly improve quality of life and have a strong impact on one's sense of gender affirmation, discontinuation of estrogen therapy in a transgender woman diagnosed with breast cancer is not straightforward. Providers are advised to engage in informed consent discussions with their patients, considering such variables as the type and stage of breast cancer, the presence of metastases, hormone receptor status, and the presence of a BRCA mutation. Input from an oncologist is also recommended. Ultimately, if the patient insists on continuing hormone therapy after a breast cancer diagnosis for which discontinuation of hormones has been recommended by an oncologist, the provider may encounter a conflict between a desire to affirm a patient's gender and the core Hippocratic principle of “first do no harm.” Ultimately each case will be decided differently, and in cases where a patient indicates that they will obtain self-managed hormones from unregulated sources if the prescriber discontinues treatment, a harm reduction approach may be appropriate.

The approach to treatment of breast cancer in transgender men should include these same considerations, and also consider the less clear link between androgens and breast cancer, as well as potential for aromatization of testosterone to estrogens. Unlike cisgender women who may opt for breast-conserving nonsurgical treatment or for breast reconstruction after a therapeutic mastectomy, transgender men often seek a masculine chest contour. In this situation, the breast surgery approach should include a discussion with a surgeon who is experienced in chest reconstruction for transmasculine individuals. Breast cancer diagnosed in a transgender man who has already undergone chest reconstruction may require further surgery after a breast cancer diagnosis.

 

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Conclusion

Screening for breast cancer in cisgender women is a complex and evolving area with consensus lacking in key areas such as the age to begin screening and frequency of screening. The approach to screening in transgender women and men is further complicated by a lack of clear understanding of the role gender-affirming hormones may play in breast cancer pathogenesis, and by a lack of reliable data on the prevalence of these conditions in the general transgender population. Existing case reports of breast cancer in transgender women and men lack important details. In addition to exploring these questions, further study and guidelines on the approaches to dense breasts and the role of alternative strategies such as MRI, ultrasound, and tomosynthesis in this population are needed. Lastly, the development of shared decision-making models informed by individualized risk and limitations of the screening procedures to be used should be developed based on such research to allow approaches to breast cancer screening in transgender populations to become truly evidence based.

 

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Die Autoren geben an, dass kein Interessenkonflikt besteht.

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