Abstract
Case Report
A 55
What is the most appropriate recommendation for breast cancer screening in this patient?
Screening mammogram
Diagnostic mammogram
Whole breast ultrasound
Breast cancer screening imaging is not recommended for transgender women.
Begin breast cancer screening imaging next year.
Discussion
Breast cancer risk in transgender women
Breast cancer is the leading cause of cancer in cisgender women, with a lifetime risk of 12%. 1,2 Cisgender men carry a 0.1% lifetime risk of breast cancer, 2 but limited data exist for rates in transgender people. Transgender is an umbrella term for people whose gender identity does not align with their designated birth sex. Transgender women are designated male at birth and identify as women. Transgender men are designated female at birth and identify as men. Breast cancer has been reported in transgender women since 1968. Limited research regarding the risk and pathogenesis of breast cancer in transgender women exists, who are often on varying regimens of gender-affirming hormone therapy (GAHT). 3
GAHT in transgender women often has two major goals; to reduce endogenous sex hormone levels and to replace them with exogenous sex hormone levels consistent with the individual's gender identity. Typical regimens include oral estradiol (2–6 mg/day), transdermal estradiol patches, or parenteral intramuscular injections every 2 weeks, along with adjunctive anti-androgen therapy such as spironolactone (100–300 mg/day), or Gonadotropin-releasing Hormone agonists. 4 GAHT regimens can lead to physical changes in transgender women in the first 3–12 months of therapy, including increased breast tissue growth. Transgender women may experience mammary development with the formation of ducts, lobules, and acini, histologically identical to cisgender females. 5 Limited data exist fully exploring the medical risks, but likely include breast cancer. 4 Despite the likely increased risk of breast cancer for transgender women on GAHT, the physiological and psychological benefits of GAHT typically outweigh this risk.
Several case reports and retrospective cohort studies have documented breast cancer in transgender women on GAHT. 6 A 2019 cohort study of 2260 transgender women in the Netherlands identified 15 cases of invasive breast cancer with a median duration of GAHT of 18 years. Compared with cisgender women, transgender women had a lower risk for breast cancer but compared with cisgender men they had a 46-fold increased lifetime risk of breast cancer. 2
The lack of long-term follow-up data regarding breast cancer risk in the transgender population could lead to late diagnosis with a higher risk for advanced-stage invasive breast cancer at the time of diagnosis. 7 Additional barriers to care exist, which could contribute to a delayed diagnosis in this population. For example, poor adherence to the most up-to-date screening recommendations due to patient and/or clinician lack of knowledge, patients avoiding the health care system due to stigma/discrimination, and health insurance plans that may not cover screening mammograms for this population.
Breast cancer screening recommendations for transgender women
Owing to the lack of evidence-based studies in this population, recommendations based on expert consensus, retrospective cohort studies, and extrapolation from cisgender populations have recently been created to help guide clinicians. Recommendations for transgender women are based on age and length of time on GAHT. These recommendations vary with respect to frequency of screening, initial screening age, length of use of hormone therapy, and method of screening.
The American College of Radiology (ACR) has developed the most robust set of guidelines to date for breast cancer screening in the transgender population based on the best available evidence and expert consensus. 5 The ACR Appropriateness Criteria guidelines include multiple breast cancer screening recommendations for transgender men and women depending on their personal risk for breast cancer (e.g., BRCA mutation), history of gender-affirming hormonal or surgical interventions, and age.
Past or current hormone use ≥5 years.
Average risk: Digital breast tomosynthesis (DBT) or mammography screening may be appropriate for an average breast cancer risk transfeminine patient who is ≥40 years of age.
Higher than average risk: DBT or mammography screening is usually appropriate for transfeminine patients ≥25–30 years of age with past or current hormone use ≥5 years. This includes patients with
a personal history of breast cancer or chest irradiation at 10–30 years of age,
a genetic predisposition to breast cancer,
a family history of breast or ovarian cancer, and
untested patients with a first-degree relative with a genetic predisposition to breast cancer.
DBT or mammography screening may be appropriate in high-risk transfeminine patients 25–30 years old with no hormone use or <5 years of hormone use. This includes patients with a personal history of breast cancer or chest irradiation at 10–30 years of age, patients with a genetic predisposition to breast cancer, patients with a family history of breast or ovarian cancer, and untested patients with a first-degree relative with a genetic predisposition to breast cancer.
In addition to ACR, there are several different authorities that have breast cancer screening guidelines for transgender people, including the Fenway Health Institute, the University of California San Francisco Transgender Care and Treatment Guidelines, the American College of Obstetrics and Gynecologists, and the Endocrine Society. 8 –10 Generally, they recommend initiation of screening for transgender women on GAHT for ≥5 years and >50 years of age, which can then be continued every 2 years. Special considerations should be given to transgender women with a family history of BRCA mutation as it is unclear what role the age of start of hormone therapy and length of exposure might play in the risks for breast cancer development. 9
Answer: E
Since this patient is 55 years old, at average risk for breast cancer, and has been on GAHT for only 4 years, it is usually not appropriate to proceed with any breast cancer screening according to the ACR and other guidelines. After 5 years of GAHT, DBT or mammography screening may be appropriate in her situation. So, for this patient, it is recommended to begin breast cancer screening next year.
Screening mammogram is incorrect because this patient has been on GAHT for only 4 years.
Diagnostic mammogram is incorrect because diagnostic mammograms are only appropriate when working up a specific breast-related symptom/complaint or callback from a screening mammogram in both cisgender and transgender women.
Whole breast ultrasound can be considered for supplemental screening for women with dense breasts. Although transgender women often have dense breasts, this would not be the initial imaging screening recommendation and is, therefore, incorrect.
Breast cancer screening imaging is not recommended for transgender women is incorrect. Based on the best available evidence and recommendations, transgender women who have been on GAHT for at least 5 years and are at least 40–50 years of age may benefit from breast cancer screening mammograms.