Trans Women on Hormones Had 46 Times Male Breast Cancer Risk — Still Below Women's Risk, Dutch Cohort Finds

Breast cancer risk in transgender people receiving hormone treatment: nationwide cohort study in the Netherlands

Cohort & registry studies Cross-sex hormones

Authors: Christel J.M. de Blok, Chantal M. Wiepjes, Nienke M. Nota, Klaartje van Engelen, Muriel A. Adank, Koen M.A. Dreijerink, Ellis Barbé, Inge R.H.M. Konings, Martin den Heijer
Journal: BMJ
Year: 2019
Source: https://doi.org/10.1136/bmj.l1652

Summary

Researchers used records from the Amsterdam gender clinic, which treats over 95% of Dutch transgender patients, linked to the national record of cancer diagnoses. They counted breast cancers in about 3,500 people on cross-sex hormones. Trans women got breast cancer far more often than men normally do (about 46 times), but still less often than women. Their tumours looked like the typical hormone-sensitive breast cancers seen in women. This suggests estrogen, and possibly the testosterone-blocking drug cyproterone acetate, shifts risk toward the female pattern. Trans men had a lower risk than women, likely helped by having had their breasts removed. The authors concluded the overall risk is low and normal screening is enough. With only 15 and 4 cases, missing data on major risk factors, and comparisons with the general population, the numbers are rough.

Key findings

The study followed 2,260 trans women and 1,229 trans men on hormone treatment, adding up to about 34,000 and 15,000 years of follow-up.
Trans women had 15 breast cancers after a typical 18 years on hormones (range 7 to 37 years), typically at age 50.
Breast cancer was about 46 times as common in trans women as in men (likely between 27 and 75 times), but only about a third as common as in women.
Most tumours in trans women were the hormone-sensitive kind (83% fed by estrogen, 67% by progesterone), like those usually seen in women.
Trans men had 4 breast cancers, about a fifth of the rate in women but 59 times the rate in men; three happened years after breast removal.
The researchers could not compare different hormone drugs, because treatments changed often and most trans women took cyproterone acetate.
The authors concluded that the normal breast screening rules are enough for transgender people on hormones.

Abstract

OBJECTIVE: To investigate the incidence and characteristics of breast cancer in transgender people in the Netherlands compared with the general Dutch population. DESIGN: Retrospective, nationwide cohort study. SETTING: Specialised tertiary gender clinic in Amsterdam, the Netherlands. PARTICIPANTS: 2260 adult trans women (male sex assigned at birth, female gender identity) and 1229 adult trans men (female sex assigned at birth, male gender identity) who received gender affirming hormone treatment. MAIN OUTCOME MEASURES: Incidence and characteristics (eg, histology, hormone receptor status) of breast cancer in transgender people. RESULTS: The total person time in this cohort was 33 991 years for trans women and 14 883 years for trans men. In the 2260 trans women in the cohort, 15 cases of invasive breast cancer were identified (median duration of hormone treatment 18 years, range 7-37 years). This was 46-fold higher than in cisgender men (standardised incidence ratio 46.7, 95% confidence interval 27.2 to 75.4) but lower than in cisgender women (0.3, 0.2 to 0.4). Most tumours were of ductal origin and oestrogen and progesterone receptor positive, and 8.3% were human epidermal growth factor 2 (HER2) positive. In 1229 trans men, four cases of invasive breast cancer were identified (median duration of hormone treatment 15 years, range 2-17 years). This was lower than expected compared with cisgender women (standardised incidence ratio 0.2, 95% confidence interval 0.1 to 0.5). CONCLUSIONS: This study showed an increased risk of breast cancer in trans women compared with cisgender men, and a lower risk in trans men compared with cisgender women. In trans women, the risk of breast cancer increased during a relatively short duration of hormone treatment and the characteristics of the breast cancer resembled a more female pattern. These results suggest that breast cancer screening guidelines for cisgender people are sufficient for transgender people using hormone treatment.

Conclusion

This large nationwide cohort study in the Netherlands showed an increased risk of breast cancer in trans women compared with cisgender men. The risk in trans women is still lower than in Dutch cisgender women and resembles a more female type of breast cancer and hormone receptor status. In trans men, a lower risk compared with Dutch cisgender women was observed. Based on this study, we conclude that the absolute overall risk of breast cancer in transgender people remains low and therefore it seems sufficient for transgender people using hormone treatment to follow screening guidelines as for cisgender people. As the risk of breast cancer in trans women increased during a relatively short duration of hormone treatment, it would be worthwhile for future studies to investigate in more detail the cause of breast cancer in transgender people receiving hormone treatment.

Methodological limitations

Very few cases: The results rest on 15 cancers in trans women and 4 in trans men, so the true risk could be much higher or lower (for trans women, anywhere from about 27 to 75 times men's rate).
Missing risk factors: The authors say details on hormone use, family history, cancer genes, harmless breast lumps, breast density, smoking, alcohol and weight were missing or incomplete, so these could not be taken into account.
Compared with the general population: Risks were compared with Dutch cancer rates for people of the same age, not with a matched group from the clinic, and without allowing for how closely each group is checked by doctors.
Some cancers may be missing: The cancer records only go back to 1991, but follow-up was counted from when people first started hormones (as early as the 1970s for some), so earlier cancers could be missed.
Cannot tell which drugs matter: Types and doses of estrogen and testosterone blockers (mostly cyproterone acetate, which acts like progesterone) changed over time, so the effect of each drug, including the older estrogen pill ethinylestradiol, cannot be separated.
Breast removal muddies the trans men result: Most trans men had their breasts removed, so their lower risk than women cannot be put down to testosterone.
Some people left out: People who never used hormones, whose start date was unknown, or who switched between estrogen and testosterone because of regret were excluded.
Screening advice goes beyond the data: The study did not test screening. Trans women were diagnosed younger (typically 50) than Dutch women (typically 61), which does not sit easily with the claim that normal screening is enough.
Little on treatment results: Many patients were treated elsewhere, so the cancer's stage, treatment and survival were not studied.

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Summary

Key findings

Abstract

Conclusion