Transgender women — individuals born male who identify with a female gender — faced a nearly 50-fold increase in breast cancer risk by going on feminizing hormonal therapy, a Dutch study suggested
An incidence ratio of 46.7 (95% CI 27.2-75.4) was seen among adult trans women on hormone treatment versus cisgender men in the general Dutch population after a median 18 years of follow-up, reported Martin den Heijer, MD, PhD, of VU University Medical Centre in Amsterdam, and colleagues.
However, trans women’s risk for breast cancer associated with hormone therapy was still substantially lower compared with cisgender women in the general population (IR 0.3, 95% CI 0.2-0.4), they wrote in The BMJ.
As for adult trans men — individuals born female who identify with a male gender — those on gender affirming hormone therapy had a nearly 60-fold higher risk for developing breast cancer compared with cisgender men with median 15 years of follow-up (IR 58.9, 95% CI 18.7-142.2).
Similarly, trans men’s risk for breast cancer was still lower compared with cisgender women’s risk (IR 0.2, 95% CI 0.1-0.5).
“This suggests that hormone treatment alters the risk of breast cancer in transgender people compared with initial risk based on their birth assigned sex,” the research group explained.
Notably, though, in all cases the risks among transgender individuals remained small in absolute terms. Among the 2,260 trans women in the study receiving hormone therapy, only 18 cases of breast cancer were diagnosed (including 15 invasive tumors); and among 1,229 trans men on hormone therapy, four cases were diagnosed (all invasive).
The retrospective analysis included patients seen during 1972-2016 at a VU University Medical Centre Amsterdam clinic that provided care for more than 95% of the Netherlands’ transgender population.
Trans women receiving gender affirming hormone treatment most typically received combination antiandrogens and estrogens. Antiandrogens, which were usually stopped following orchiectomy, were usually in the form of 10-100 mg daily of cyproterone acetate or 100-200 mg daily spironolactone. As for estrogens, 25-100 μg daily ethinyl estradiol, 0.625-1.25 mg daily conjugated estrogens, 50-150 μg/24 hours twice weekly of estradiol patches, 20 mg every 3 to 6 months of estradiol implants, 10-100 mg every 2 to 4 weeks of estradiol injections, 2-6 mg daily of estradiol valerate, or 0.75-3.0 mg daily of estradiol gel were prescribed. However, the group noted that recently, estradiol valerate, estradiol patches, or estradiol gel have been the preferred forms of estrogen.
Hormonal therapy for trans men were prescribed in the form of 20-100 mg daily testosterone gel, 150-250 mg every 2 to 3 weeks intramuscular testosterone esters, or oral or intramuscular testosterone undecanoate (40-160 mg daily oral; 1000 mg every 10 to 14 weeks intramuscularly).
Individuals younger than 18 or those who alternated using estrogen and testosterone due to regret about their transition were excluded from the analysis.
Most tumors developing in transgender women were of ductal original (10 of 15 of invasive cancers). Most were positive for estrogen and progesterone receptors, but only one was HER2 positive.
Among trans women who developed breast cancer, median levels of estradiol (64.3 pg/mL; 236 pmol/L) and testosterone (0.4 ng/mL; 1.3 nmol/L) were generally comparable to the rest of the cohort of transwomen.
Three of the four breast tumors in trans men were of the ductal origin, while half were estrogen and progesterone receptor positive, and only one was HER2 positive. Three of these cases were also diagnosed many years after a subcutaneous mastectomy, while one was diagnosed at the time of mastectomy.
Similar to what was seen with trans women, trans men who developed breast cancer had median estradiol levels in the same range as the larger cohort of trans men (31.6 pg/mL; 116 pmol/L). However, trans men with breast cancer had lower median levels of testosterone (3.8 ng/mL vs 6.7 ng/mL; 13.2 nmol/L vs 23.3 nmol/L).
“Current recommendations suggest that trans women and trans men who have not undergone mastectomy should be biennially screened with mammography from the age of 50 years and if they are using hormone treatment for more than five years,” the researchers highlighted. However, for trans men after subcutaneous mastectomy, mammography isn’t feasible due to the lack of breast tissue, so self-examinations are recommended, although den Heijer’s group noted that there is “no evidence for effectiveness.”
Commenting on the study, Joshua Safer, MD, of the Mount Sinai Health System and the Icahn School of Medicine at Mount Sinai told MedPage Today that “in the absence of trans-specific surveillance data, providers should be aware that breast cancers do occur among trans women and occur much less among trans men.”
Safer, who wasn’t involved with the study, suggested that in order to not miss cancers, providers should use general guidelines to inform screening practices.
Den Heijer’s group underscored the importance of screening for this population: “We believe therefore that awareness in both doctors and transgender people is of more importance than the start of screening at a younger age or intensifying available screening, even though the median age at diagnosis in the current study was lower than in cisgender women.”
“It is important to remember that transgender people who changed their legal sex might not be automatically invited for population based screenings, including breast cancer screening,” they noted.
De Blok and co-authors reported no conflicts of interest.