Screening for breast cancer in transgender women

Introduction

Adaptation of recommendations for screening in transgender women are complicated by the lack of consensus on breast cancer screening in non-transgender women. Existing recommendations vary widely in each of these critical considerations, and are subject to numerous biases based on the interests of the organization and its constituency.[1-7]

Ideal breast cancer screening recommendations minimize mortality and missed diagnoses, while at the same time avoiding over-screening, with its inherent risks of unnecessary follow-up studies, emotional distress, and potentially invasive biopsies and other procedures. It is noteworthy that the positive predictive value (PPV), defined as the likelihood of a positive screening test representing a true presence of the disease (as opposed to a being a false positive) declines as the prevalence of the disease within a specific population declines.

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.[8]

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 which 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 non-transgender female population.[9] A retrospective review of 3,566 transgender women receiving care in the U.S. Veterans Administration Healthcare System found 3 cases total, translating to a non-significant standardized incidence ratio (SIR) of 0.7 (95% CI 0.03 to 5.57) in comparison to non-transgender women, and a significant SIR of 33.3 (95% CI 21.9 to 45.1) in comparison to non-transgender men.[10] 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.[11]

Data on breast cancer in transgender women has been limited to the above studies as well as several case reports, and is overall reassuring with regards to risk being not higher, and possibly lower than in the non-transgender female population.

Age to first consider screening

The only large population based study of mammography before age 50 was conducted in the UK on 160,921 women and found no difference in overall breast cancer mortality.[12] Given the equivocal value of screening before age 50 and the likely lower incidence in transgender women, it is recommended that screening mammography in transgender women not begin before age 50.

Length of exposure to feminizing hormones

Transgender women differ from non-transgender women in the length of exposure to estrogens as well as variable exposure to progestogens. As such it is recommended that screening not commence 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 and unknowns with patients and delay screening until after up to 10 years of feminizing hormone use, regardless of age. Note that transgender women over age 50 do not meet screening criteria until they have at least 5-10 years of feminizing hormone use.

Frequency of screening

Existing recommendations in non-transgender women vary with respect to the frequency of screening. As with the age of onset, given the likely lower incidence in transgender women, it is recommended that screening mammography be performed every 2 years, once the age of 50 and 5-10 years of feminizing hormone use criteria have been met. Providers and patients should engage in discussions that include the risks of overscreening and an assessment of individual risk factors (Grading: T O W). Risk score calculators such as the GAIL method may be unreliable when used in transgender women.

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 as with non-transgender women,[13] formal clinician or self breast exams for the purpose of breast cancer screening are not recommended in transgender women.

Special considerations

As with non-transgender women, 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) a BRCA mutation should be referred for genetic counseling. No data exists to guide the use of estrogens in transgender women found to have a BRCA mutation. Data on breast cancer risk in non-transgender men with BRCA mutations are limited, with data on BRCA-1 suggesting a lifetime risk of 1.2-5.8%, [14-16] and data on BRCA-2 suggesting a lifetime risk of 6.8%. The risk is much higher for non-transgender women with a BRCA mutation, at 78% lifetime risk. [14, 17] It is unclear if transgender women with the BRCA-1 mutation and using estrogen have a risk above that of non-transgender men, and what role the age at start and total length of exposure to estrogen might play. A single case report of a transgender woman with the BRCA-1 mutation involved the continued use of estrogen under informed consent.[18]

A retrospective cohort study of 1,263 transgender women receiving care at a large urban community health center patients in the United States found that transgender individuals between ages 50 and 74, and with a history of at least 5 years of hormone therapy were significantly less likely than non-transgender individuals to have a mammogram per guidelines (AOR = 0.53; 95% confidence interval = 0.31, 0.91).[19] Further research is needed to understand barriers and other factors which underlie this disparity.

References

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4. American Cancer Society Guidelines for the Early Detection of Cancer. [cited 2016 Jan 28].
5. American College of Radiology: ACR Appropriateness Criteria (Breast Cancer Screening). [cited 2016 Jan 28].
6. American Cancer Society recommendations for early breast cancer detection in women without breast symptoms. [cited 2016 Jan 28].
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