While breast cancer in males is relatively uncommon, accounting for about 0.1% lifetime risk, little is known about the risk in transgender persons.
A retrospective, nationwide cohort study from the Netherlands sought to help address this lack of information. Data gathered from medical records from the VU University Medical Center in Amsterdam, a facility that managed the care of over 95% of transgender people in the country, were used to follow 2,260 transgender women (TW; assigned male at birth but identify as female) and 1,229 transgender men (TM; assigned female at birth but identify as male) for a median person-time of 13 years and 8 years, respectively.
Person-time was calculated as the number of years from the first known start date of hormonal therapy (HT) to a breast cancer (BC) diagnosis, death, or the cutoff date for the trial, which was August 31, 2017.
TW started HT at a later age compared with TM (31 years versus 23 years). TW were treated with antiandrogens (e.g., cyproterone acetone or spironolactone) until orchiectomy, as well as with estrogen hormonal therapy. TM received testosterone only.
There were 18 cases of BC (15 invasive cases and 3 noninvasive cases) among 17 TW who had received HT for a median of 18 years. Over two-thirds of the BCs were ductal, 83% were estrogen receptor–positive (ER+), 67% were progesterone receptor–positive (PR+), and 8% were human epidermal growth factor receptor 2–positive (HER+). There was a higher overall risk of BC in TW than in cisgender men (CM; assigned male and identify as male), but this risk was less than in cisgender women (CW; assigned female and identify as female).
The number of both invasive (standardized incidence ratio [SIR], 46.7) and noninvasive (SIR, 96.1) BCs as well as HER2+ BC were markedly higher in TW compared with CM; however, these numbers were still quite low. On the other hand, the incidence of both invasive and noninvasive BCs (SIR for both, 0.30) were markedly lower in TW compared with CW. The median age of BC diagnosis in TW was 52 years, and diagnosis occurred after a relatively short exposure to HT. In CW, the average age of BC diagnosis was age 61 years.
There were four cases of BC among TM after having received HT for a median of 15 years. Of these BC cases, 75% were ductal, two were ER+/PR+, one was HER2+, and one was androgen receptor–positive. The risk of BC in TM was lower than in CW but higher than in CM. The number of invasive BCs was markedly higher in TM compared with CM but significantly reduced (SIR, 0.2) for TM compared with CW. There were no cases of noninvasive BC in TM. The median age of BC diagnosis in TM was 46 years.
Despite the elevated rates of BC in TW and TM compared with CM, the absolute risk of BC in transgender people, which was 43.0 per 100,000 person-years for TW and TM combined, was considered low and was not increased compared with CW. Based on these findings, the authors believe that current recommendations for BC screening in CW are adequate for transgender people. Therefore, TW and TM who have not undergone a mastectomy should start biennial mammography at age 50 years or younger if they have been receiving HT for more than 5 years. After a mastectomy, mammography is no longer feasible.
This study offers insight to pharmacists who care for transgender patients on how to monitor and advise them about their risk of BC from HT.
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