Further publications on BRCA1/2 variants and their impact on transitioning

Disclaimer: I am not a doctor and this is not medical advice.

Zinnia JonesLast year, I wrote about case studies of pathological BRCA1 and BRCA2 gene variants in trans people, and how clinicians take these mutations into account during transition treatment. While harmful BRCA mutations are best known for their effect of drastically increasing breast cancer and ovarian cancer risk in cisgender women, these variants represent a concern for transgender women as well, as transitioning with hormone therapy produces the growth of breast tissue considered histologically identical to that of cis women. Trans women can get breast cancer – UCSF Transgender Care has even published recommendations for when trans women should begin receiving regular mammograms – and having a harmful BRCA1/2 variant can increase their risk. (BRCA1/2 variants are also a concern for transgender men, who may still have breast tissue or ovaries, and even for cis men, who can face a higher risk of various cancers from these harmful variants as well.)

Cases of BRCA mutations and BRCA-associated breast cancer in trans women have previously been reported in the literature (Li et al., 2018; Corman et al., 2016), and a recent article describes a case series of three trans patients who were at a high risk for familiar BRCA1 variants and sought genetic counseling (Sacca et al., 2019):

Case 1 is a 20‐ year‐old transgender female initiating hormonal agents. Case 2 is a 19‐year‐old transgender male considering surgical decisions who has a BRCA1 pathogenic variant on both sides of the family. Case 3 is a 24‐year‐old transgender male who had previ‐ ously undergone gender‐affirming mastectomy (top surgery) and is taking androgen therapy.

While the first patient ultimately tested negative for pathogenic variants, they were advised that if they did test positively, they should consider breast imaging screening, as well as prophylactic mastectomy of the breast tissue they developed if they decided to begin feminizing HRT. The second patient likewise tested negative for these variants, but it was noted that he was already considering mastectomy as part of chest reconstruction surgery as well as bilateral salpingo-oophorectomy (removal of both of the ovaries and fallopian tubes), and that a positive test could affect the nature and timing of these procedures:

We discussed that we often defer testing individuals for these pathogenic variants until they are closer to 25 years old, as breast surveillance per multiple guidelines begins at that age in cisgender female pathogenic variant carriers. However, this patient was planning to have breast reduction surgery before graduating from college. If he were found to have the familial BRCA1 pathogenic variant, he would have RRBM [prophylactic mastectomy] rather than the standard breast reduction for gender affirmation purposes. He was already considering having a bilateral salpingo‐oophorectomy (BSO) regardless of genetic testing results to avoid some of the side‐effects of testosterone therapy. … Genetic testing could affect the timeline of these surgeries for financial reasons. If he were found to carry the BRCA1 pathogenic variant, he would likely be able to have RRBM and risk‐reducing salpingo‐oophorectomies (RRSO) covered by insurance. If he tested negative for the familial pathogenic variant, he might have to finance the surgeries himself.

The third patient, who had already undergone chest reconstruction surgery, tested positive for a pathogenic variant, and was advised to undergo bilateral salpingo-oophorectomy as well as either yearly breast imaging or removal of the remaining breast tissue:

Medical recommendations for this patient required ongoing coordination with his physician and surgeon to address his risk, given that he had had a “Top” surgery rather than more complete RRBM. Determining the optimal timing of RRSO would also require consideration of the fact that the patient may experience early bone loss and symptoms of menopause. However, given that he was amenorrhoeic due to his testosterone therapy, in this particular patient it may not be as much of a concern. He was found to have residual breast parenchyma on MRI and annual MRI follow‐up was advised despite prior mastectomy, unless completion surgery was performed.

The authors further note that the presence of a pathogenic BRCA1 variant should not generally preclude trans people from receiving hormone therapy. However, trans people who are at risk of carrying a BRCA variant may need to be tested at an earlier age than cis people, as this can come to bear on their decisions regarding transition procedures:

We often recommend our cisgender patients at 50% risk for a BRCA1 pathogenic variant to wait until they are closer to 25 years old to pursue genetic testing because that is the age at which we typically start breast imaging in BRCA positive cisgender women. However, as transgender individuals begin to transition at younger ages, it may become necessary to offer genetic testing at younger ages, potentially even to minors, as it can have a large impact on their surgical course.

Additionally, a recent set of interviews with 21 cancer genetic counselors who’d seen transgender patients revealed numerous themes and concerns specific to providing care to this population (Zayhowski et al., 2019). These included the lack of documentation systems in genetic counseling that can record transgender identities and medical transition history, how these risks can affect decisions about transition surgeries, and concern over the lack of data available to provide to trans patients on how these variants can affect their cancer risk in the context of transition.

Contrary to this desire for the best available information to help patients in making healthcare decisions, I’ve frequently been met with overt hostility and dismissive attitudes from transphobes when I’ve brought up the known facts that trans women develop breast tissue, will require mammograms, and should know their BRCA status. One user in Reddit’s /r/gendercritical hate group even claimed that trans women just want to “do cancer better than us”, as if this were a matter of superficial jockeying for social position rather than the important public health goal of reducing preventable deaths from cancer. It’s clear that expanding the available research on trans people and genetic cancer risk, as well as increasing providers’ comfort and familiarity with trans patients, are essential goals to pursue – particularly in a society where even on the subject of cancer, trans women themselves are instead the ones seen as invasive and aggressive.

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About Zinnia Jones

My work focuses on insights to be found across transgender sociology, public health, psychiatry, history of medicine, cognitive science, the social processes of science, transgender feminism, and human rights, taking an analytic approach that intersects these many perspectives and is guided by the lived experiences of transgender people. I live in Orlando with my family, and work mainly in technical writing.
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