Unanswered Questions: Hereditary breast and gynecological cancer risk assessment in transgender adolescents and young adults

Transgender (TG) individuals have higher rates of mortality associated with cancer diagnoses, in part due to avoidance of gender-assigned cancer screenings resulting in later stages at diagnosis. Knowledge about the risks of breast or gynecological cancer in TG and nonbinary (NB) persons receiving gender-affirming hormone therapy is limited. Even less information exists regarding the subset of individuals with genetic predisposition for these malignancies. We performed a retrospective literature review of studies from the last 15 years on breast cancer rates and identified risks in TG persons. An accumulating body of data on breast cancer incidence in TG persons suggests higher than previously believed rates of breast cancer in TG women compared with cisgender men and risk correlating with duration of hormone use. Few studies have examined other cancer risks in TG populations. To date, only three publications address the association with BRCA1/2 mutation presence and breast cancer incidence in TG persons. Meanwhile, there is growing awareness and social acceptance of TG/NB identities coupled with recognition of gender dysphoria at increasingly earlier ages. No information directly addressing cancer risk counseling in TG/NB adolescents and young adults with a family history of cancer or hereditary cancer syndrome exists. Whether the presence of a known genetic predisposition or strong family cancer history may affect cancer risk in these populations is unknown, leading to significant gaps in clinicians' ability to accurately and appropriately estimate cancer risks and counsel those with genetic predisposition on the risks/benefits associated with surgical options and the initiation, duration, and dosing of gender-affirming hormone therapies. A series of three cases illustrates the utility of cancer risk assessment and genetic testing in TG/NB adolescents and young adults, and the unique challenges and unanswered questions that are encountered in the process.