Transsexualism is rare, and breast cancer in transgendered persons is uncommon.

For these reasons, the recent reporting of 10 cases of breast cancer among transgendered persons—bringing the known cases worldwide to 25—represents an important advance in understanding how best to screen, counsel, and care for this population, which often receives or self-treats with cross-sex hormones (CSH).

The 10 cases of breast cancer occurred in 7 birth sex females and 3 birth sex males among a cohort of 5,135 transgender veterans identified using Veterans Health Administration data from 1996 to 2013. The birth sex males all presented with late-stage disease that was fatal. In contrast, most of the birth sex females presented with treatable, earlier stage disease.

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Cancer Therapy Advisor asked George R. Brown, MD, DFAPA, Professor and Associate Chairman of Psychiatry at East Tennessee State University, Quillen College of Medicine in Johnson City, TN, who detailed the 10 cases in an article in a recent issue of LGBT Health, to place these findings in perspective.

CTA: With the 10 cases expanding the known cases of breast cancer in transgender persons to 25, why are so few cases documented? Is it lack of cases or lack of reporting in general? Would you advocate for a national registry or expanding existing databases, such as SEER (Surveillance, Epidemiology, and End Results)? 

Dr. Brown: Few cases are documented, in part because transsexualism (gender dysphoria) is rare, breast cancer is uncommon, and there are very few databases of large numbers of transsexual persons. I do not think there is a lack of reporting, since even a small case series of 10, which I recently published, is still big news in this field. We utilized SEER data as a comparison, but it would be excellent if there were a national registry or an expansion of SEER to include transgender persons. It is a substantial amount of effort to publish case series, and if there were an easier way for clinicians to report cases to a registry on a one or two page form, more cases might be discovered.

CTA: Do you know of any other database of transgendered persons that tracks breast cancer?

Dr. Brown: Other than our database, which is the largest cohort ever studied, there is a database in Amsterdam that has been in existence for about 30 years. Louis Gooren and colleagues have published results from this database intermittently over the past 10 years. They have found very few cases in The Netherlands, which has a national healthcare system (single payer) and excellent data, but the population is obviously rather small. Their studies are the longest duration studies of transsexual persons treated with CSH. 

CTA: CSH aside (whether prescribed or self-treated), was it possible to determine whether the incidence of breast cancer in the VA population was consistent with the general population, by birth sex?

Dr. Brown: We used female birth sex comparators in the United States population as the comparison group for our male-to-female transgender cohort who may, or did, receive CSH treatment with an estrogen component. We found that the rate did not differ significantly between these two groups. Given that male-to-female transsexual persons may supplement prescribed CSH prescribed by physicians, it is not possible for any investigator to develop a valid dose-response relationship between dose of estrogen and incidence of breast cancer. That is why we did not attempt to do so. Our data studied transgender veterans, 95% or more of whom had gender dysphoria. It is not possible for us, or for any other investigators, to determine the estrogen exposure with any degree of certainty in this population.

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CTA: As you noted, male breast cancer is rare and the effect of a CSH regimen was not determined in these 10 cases. Might it ever be possible to determine whether the CSH regimen may have contributed?

Dr. Brown: Breast cancer in natal males is indeed uncommon, and was rare in our study irrespective of birth sex. It is not possible to determine the effects, if any, of CSH from our, or the European, studies with any degree of certainty. What we can say, based on our studies and the Amsterdam data, is that breast cancer in either natal male or female transgender persons, with or without CSH treatment, over a follow up period of 10 to 30 years, is rare. This should provide some comfort to both prescribers and consumers of CSH treatments. We do not know the effects at more than 30 years out. This is difficult to study, but it should be noted that natal females who develop breast cancers (outside of those with familial genetic abnormalities that are associated with early onset breast cancers) are exposed to estrogens for at least 40 years or more, which is outside the range of any existing studies of breast cancer in transgender persons treated with CSH.