Article: Breast cancer risk for transgender women with inherited mutations

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What is this study about?

Very little research has been done to understand the breast cancer risk of transgender women who have an inherited mutation linked to breast cancer risk. For this reason, it is not well known how gender-affirming medical care (such as hormone therapy and surgery) may impact risk.

This XRAY review summarizes what is known and highlights what is missing for transgender women with inherited mutations that increase breast cancer risk.

Unique challenges and unanswered questions

Transgender women may choose to take medications, including hormone therapy, or have surgeries to reflect their gender. Some of these gender-affirming treatments may affect breast cancer risk. The lack of research on breast cancer risk and health outcomes for high-risk transgender women limits experts’ ability to make risk-management recommendations.

How genetic testing can help assess risk
For transgender women with a family history of breast cancer or a known family mutation, genetic counseling and testing can help inform their decisions about gender-affirming care. While genetic testing for inherited mutations linked to adult-onset cancers is not typically offered to minors, genetic testing for transgender patients may affect their decisions related to gender-affirming hormone therapy, such as puberty blocker.

Breast cancer risk
Tools used to calculate breast cancer risk are based on research from cisgender people (people who identify with the gender that was assigned to them at birth).  These tools have not been tested on transgender individuals, which means they may or may not be accurate for them. 

Evidence relating to breast cancer in the trans population is limited.  There is not enough data to estimate risk. Even less data is available on how to estimate the risk for a transgender person with a family of breast cancer or a known gene mutation. 

People who are assigned male at birth typically have a low lifetime risk for breast cancer. However, inheriting a mutation in any of the genes listed below is linked to an increased risk for male breast cancer and breast cancer in people assigned male at birth.  Transgender women who have an increased breast cancer risk due to an inherited mutation may want to consider increased breast screening or risk-reducing mastectomies (removal of their at-risk breast tissue) with or without reconstruction if they are considering gender-affirming surgery such as breast augmentation or hormonal therapy that could increase breast tissue.

Genes linked to increased risk for people assigned male at birth include:

• BRCA1
• BRCA2
• CHEK2
• PALB2

Hormone therapy
Gender-affirming care for transgender women may include the use of the hormone estrogen with or without progestin, as well as hormones to decrease testosterone.

Long-term exposure to estrogen is a well-known risk factor for breast cancer in cisgender women. Since transgender women may use estrogen for a long period (sometimes for the rest of their lives) or at higher doses than cisgender women, there is concern that this may increase their risk for breast cancer.

The most complete study of breast cancer risk relative to the use of hormone therapy for transgender women with no inherited mutation linked to cancer found that the lifetime risk for breast cancer among transgender women who had short or long-term hormone therapy is greater than cisgender men. The risk was similar to or lower than the risk among cisgender women. It is important to note that the study did not look at how hormone therapy may impact breast cancer risk among transgender women with an inherited mutation.

This highlights an important research gap and the need to better understand how gender-affirming hormone therapy impacts breast cancer risk for transgender women with an inherited mutation.

Despite this gap, the National Comprehensive Cancer Network (NCCN), a panel of experts that creates health guidelines, added a new section to their 2024 guidelines for risk management of transgender women at high risk for breast cancer. While the NCCN acknowledges the lack of relevant research, it considers hormones used for gender-affirming care to be acceptable for high-risk transgender women.

Screening
How to best image and screen for breast cancer depends on the type of treatment, if any, transgender women have had. Gender-affirming care may include breast augmentation or breast enlargement injections (the latter are prohibited in the United States, but are available in other countries). Numerous professional organizations, such as the American College of Radiology, provide guidelines for breast cancer screening of transgender women.

For cisgender men with a BRCA1, BRCA2 or PALB2 mutation, clinical breast exams and self-exams are recommended beginning at age 35. The guidelines also recommend considering beginning annual mammograms (especially for men with BRCA2 mutations) beginning around age 50. However, there are no specific guidelines for when, how or how often transgender women with an inherited BRCA1, BRCA2 or PALB2 mutation should undergo breast cancer screening. Nor do specific breast screening guidelines exist for transgender women with mutations in other genes who take hormones as part of their gender-affirming care.

The 2024 NCCN guidelines update acknowledges the lack of research in this area but supports the idea of breast screening using MRI and/or mammograms for high-risk transgender women.

In the absence of more specific guidelines, transgender women with an inherited mutation that increases breast cancer risk should try to find a healthcare team that is knowledgeable in transgender care and risk management for people with inherited mutations. These experts may often be found at larger medical centers.

What does this mean for me? 

If you are a transgender woman with an increased risk of breast cancer due to an inherited mutation, try to find a healthcare system that has expertise in transgender care and cancer genetics. Talk with your healthcare team about your risk for breast cancer, the benefits and risks of different types of screenings and risk reduction options. These may differ based on the gender-affirming care you receive.   

Reference

Sutherland N, Espinel W, Grotzke M, Colonna S. Unanswered Questions: Hereditary breast and gynecological cancer risk assessment in transgender adolescents and young adults. J Genet Couns. 2020; 29:625–633.

Clarke CN, Cortina CS, Fayanju OM, Dossett LA, Johnston FM, Wong SL. Breast Cancer Risk and Screening in Transgender Persons: A Call for Inclusive Care. Ann Surg Oncol. 2022;29(4):2176-2180.

Lienhoop T, Green L. Breast imaging in transgender women: a review. Clin Imaging. 2021;80:283-289.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 11/29/23