2023 ASCO Annual Meeting Education Symposium Spotlight: “Managing Cancer Risk Transgender Patients with Inherited Cancer Predisposition”

June 22, 2023

Irby Hunter, Jr., MD Medical Director Oncology Independent Medical Education Inc & Executive Publisher Oncology Disparities Peer Reviewed Scientific Journal

On June 21, 2023, the Biden administration declines Supreme Court appeal for transgender surgery mandate ⁽¹⁾. For the second time, the federal government has decided not to pursue a high court review for unfavorable decisions on its mandate that would have forced doctors to prescribe cross-sex hormones and puberty blockers, as well as perform genital mutilation surgeries, against their conscience ⁽¹⁾. The Biden administration missed the June 20 deadline to appeal the case from the 8^th U.S. Court of Appeals ⁽¹⁾. This snippet of a press release published by the Washington Examiner highlights the importance of sharing the practice changing lessons learned from a 2023 ASCO education symposium. During the symposium, contributors crafted a framework for managing cancer risk in transgender patients facing inherited cancer predisposition.

Background

Discrimination, psychosocial issues, gaps in patient-provider communication and quality care are documented reasons why members of the Sexual and gender minority (SGMs) community, including individuals who are lesbian, gay, bisexual, transgender, and intersex (LGBTI) bear a disproportionate share of the cancer burden ⁽²⁾. For example, people who are LGBTI are more likely to smoke cigarettes than their heterosexual cisgender counterparts ⁽²⁾. Lesbian and bisexual women have higher rates of obesity and a greater risk of breast cancer, gay men have a greater risk of anal cancer. ⁽²⁾ In addition, SGM populations exhibit low rates of uptake for cancer screenings, in part because of lower rates of insurance coverage, exclusion from traditional cancer screening campaigns, and previous experiences of discrimination when interacting with health care systems and providers ^(3-5). Inadequate evidence-based knowledge and patient-provider communication have led to poor care and less than optimal survivorship care planning. Also, members of SGM populations often fail to disclose their sexual orientation to their health care providers, and this creates an additional barrier to care ⁽⁶⁾.

In 2015, the American Society of Clinical Oncology (ASCO) Health Disparities Committee developed the organization’s strategy for addressing the needs of the SGM population as a diverse group of patients at risk for experiencing less than adequate cancer care. The committee identified five areas of need: Patient Education and Support, Workforce Development and Diversity, Quality Improvement Strategies, Policy Solutions, and Research Strategies. The need for patient education and support stems for the unique psychosocial challenges experienced by SGM individuals with cancer, such family estrangement, discrimination, stress, anxiety and depression. ASCO promotes patient navigation and care coordination including safe disclosure of identities, support network and advocacy. Additionally, ASCO’s position statement calls for readily available education and culturally competent support services. Workforce development and diversity trends reveal that majority of oncology providers are not trained to provide care for SGM patients. Oncology providers in training as well as those already in practice lack the knowledge and sensitivity to appropriately meet the needs and concerns of the SGM cancer population. ASCO recommends the incorporation of SGM directed cultural competence training into provider training curricula, requirements, and certifications. Cancer centers should foster a safe environment for SGM providers by disseminating and enforcing antidiscrimination policies. Quality improvement strategies include the collection of SGM relevant data as well as ensuring prompt follow up. ⁽⁷⁾

Ensuring adequate insurance coverage to meet the needs of SGM Individuals affected by cancer through state and federal advocacy efforts is key ASCO plank. In particular, insurance coverage policies should be based on anatomy such that, for example, no matter what one’s sex assignment is, a person who has a prostate has access to appropriate prostate cancer screening. ASCO is committed to promoting research among SMG populations including SGM status a required data element and raising awareness among future research scientists. ⁽⁷⁾

2023 ASCO Annual Meeting Education Symposium Coverage

In congruence with ASCO’s position statement on SGM patients diagnosed with cancer, a stimulating education symposium was held on June 4, 2023 at 11:30 AM. The symposium was chaired by Swati Patel, MD, MS, University of Colorado, Anschutz Medical Center, Aurora, Colorado. Key thought leaders participated in the case-based panel discussion entitled “Managing Cancer Risk in Transgender Patients with Inherited Cancer Predisposition”: 1) Megha Ranganathan, MS, Memorial Sloan Kettering Cancer Center, New York, New York 2) Oluwadamilola Motunrayo Fayaniu, MD, FACS, University of Pennsylvania Health System, Philadelphia, Pennsylvania and 3) Judith Balmana Gelpi, MD, PhD, V’all d’Hebron University of Hospital, Barcelona, Spain. Oncology Independent Education Incorporated (OIE) is delighted to share a in depth review of the symposium. ⁽⁸⁾

Despite representing densely populated and diverse communities, each of the panelists reported caring for very few transgender patients. Recent epidemiology data was cited. Less than 2% of the US population identifies as transgender, however 5% of US individuals who are under the age of 30 identify as transgender. It is important to note that 18% of US individuals identifying as transgender fall between the ages of 13 to 17. ⁽⁸⁾

A significant barrier to healthcare access is present among transgender individuals. Approximately 20% of patients have been denied access to care based on their gender identity. Unfortunately, 22% of transgender patients report avoiding the US health system as a result of being denied care in the past. Surveillance, Epidemiology, and End Results Program (SEER), National Cancer Database (NCDB), and majority of US electronic health records (EHRs) do not include any information on sexual orientation or gender identity; thereby, making it difficult for bio-statisticians to determine cancer rates at the transgender population level. ⁽⁸⁾

There were several symposium objectives: 1) define important terms and concepts in caring for transgender patients with hereditary cancer syndromes, 2) understand gender-affirming treatment approaches for transgender individuals, and 3) examine how aspects of the transgender care may influence medical and surgical management of hereditary cancer syndromes. Two case studies were discussed and clinical recommendations were shared. ⁽⁸⁾

Case 1

A 40-year-old trans woman (a person assigned male at birth but identifies as a woman) undergoing gender affirming hormone therapy since the age of 30 presented for counseling. The patient has native breast tissue. The patient’s mother, 65 years of age, was recently diagnosed with ovarian cancer. The tumor was identified as being Germline BRCA2+. The patient underwent germline genetic testing for familial BRCA2+ variant. Testing results identified a pathogenic mutation in the BRCA2+ gene. The test results sparked several questions for the patients:

1. What is my risk for breast cancer?
2. What can I do to reduce my risk or prevent a future breast cancer?
3. What other cancers am I at risk for?
4. What other cancer surveillance or risk reduction measures could I be taking?

Dr. Gelpi led the panels dialogue in response to the patient’s questions. Innovated options are available for trans women seeking gender affirming treatment. Plastic surgery and gender affirming hormone therapy (estrogen and anti- androgen), breast augmentation, and genital surgery (vaginoplasty and orchiectomy) anchor these options. Western cis women hold an average risk of 12.9%, 1.7%, and 1.1% for developing breast, pancreas, and ovarian cancers respectively. In contrast, Western BRCA2+ cis women hold an average risk of 68%, 5-8%, 13-29% for developing breast, pancreatic, and ovarian cancer respectively. The case 1 patient has a greater risk for developing breast cancer than cis men but a lower risk for developing breast cancer than cis women. When polled, 100% of symposium attendees elected to continue the patients gender affirming hormone therapy. Dr. Gelpi advised that in her practice she would prescribe estrogen therapy to patient even if she were 20 years younger. She cited a recent study from the Netherlands which revealed that estrogen therapy increases breast cancer risk in average-risk transwomen, but the risk is still lower that of cisgender women. ⁽⁸⁾

Dr. Gelpi shared that breast cancer surveillance for transwomen who are BRCA2+ should begin after 5 years of gender affirming hormone therapy. Further stratification of the surveillance is based on multiple factors: the amount of breast tissue, family history, and the type of hormonal therapy. The patient can possibly reduce the risk of developing breast cancer via radiographic surveillance or mastectomy. The patient is a greater risk for prostate and pancreatic cancer in comparison to cis men. The final treatment plan for the case 1 patient included continuing gender reaffirming hormone therapy, mastectomy with reconstruction, orchiectomy, undergo annual PSA tests, and annual pancreatic surveillance. ⁽⁸⁾

Case 2

A 16-year-old trans man (a person assigned female at birth but identifies as a man) interesting in initiating gender affirming treatment presented to a breast surgeon to discuss gender affirming top surgery (surgery to remove breast tissue and make the chest look more masculine). The patient reported a family history of early-onset breast cancer. The surgeon ordered genetic testing for several genes associated with breast cancer. A pathogenic variant was found in BRCA1. The patient has several questions after learning the test results:

1. Can I still get top surgery?
2. Does testosterone increase my cancer risk?
3. Will I be able to have children?
4. Will I need additional surgery in the future?

Dr. Gelphi led the panelists in rendering responses to the case 2 patient’s questions. The latest gender affirming treatment options for trans men include hormone replacement therapy (testosterone), top surgery, gynecologic based surgeries (oophorectomy and hysterectomy), and genital surgery (vaginectomy, scrotoplasty, metoidioplasty vs phalloplasty. Western cis women hold an average risk of 12.9% developing breast cancer. While BRCA1+ cis women hold an average risk of 70% of developing breast cancer. The case 2 patient has greater risk of developing breast cancer than cis men but lower risk than cis women. Mastectomy and top surgery may reduce the cancer risk aligned with gender-affirming surgery. There are no guidelines available for cancer surveillance after undergoing top surgery. Fifty percent of BRCA1 and BRCA2 carriers who opt of preventive mastectomy at 25 to 30 years of age are noted not to have developed breast cancer by the age of 50. Clinicians should be advised that transgender individuals express an interest to parenthood at similar rates as cisgender individuals. The patient is able to undergo top surgery; however, optimal surveillance of residual tissue is unclear. Therefore, bilateral mastectomy with reconstruction could be considered instead. No evidence supports that testosterone therapy increases the risk of developing breast cancer in trans men. A referral to fertility specialists should occur prior to initiating gender affirming hormone therapy. The case 2 patient has an average risk of 39-58% of developing ovarian cancer due to the BRCA 1 mutation; therefore, symposium speakers recommend undergoing a bilateral salpingo-oophorectomy between the age of 35 to 40 years old. ⁽⁸⁾

Clinical Recommendations

The panel recommends moving towards more favorable genetic pedigree symbols to represent transgender individuals as well as the adoption of genetic pedigree symbol for non- binary individuals. Clinicians recommend adding MRI to PSA for prostate cancer surveillance for BRCA2+ cis males undergoing gender affirming hormone therapy. Seventy percent of polled symposium attendees reported their native EHR’s account a patient’s chosen pronoun, gender, and name. Dr. Fayaniu shared best practices related to patient contracting for the purposes of building a repour with patients. She informed the audience that contracting should be viewed based on three considerations: “what you say,” “what you know,” and “what you say”. Clinicians should avoid terms that assume gender identity and sexual orientation. Clinicians should use neutral languages and state their own pronouns initially thereby providing a save space for the patient to do the same. We want to avoid relying on the patient educating you as the clinicians. We want to avoid focusing on gender identify. Do not over apologize for errors. Providers should create welcoming imagery, representation and signage. Make sure the patient demographic information is gender neutral and welcoming to the transgender and non-binary populations. Ninety two percent of the attendees reported making a mistake in addressing transgender and non-binary patients. There is little data on the impact of long- term gender affirming hormone therapy on fertility. Finally, 89% of the polled symposium attendees think genetic testing is a warranted for this 16-year-old patient highlighted in case 2. ⁽⁸⁾

Closing Symposium Thoughts

The growing number of individuals identifying as trans gender or non-binary has prompted the immediate need to adopt evidence-based practice guidelines for caring for gender-diverse individuals with hereditary cancer predisposition syndromes. Equitable, individualized and gender-inclusive care is critical to validating gender identity and improving outcomes. ⁽⁸⁾

Commentary

Hodan et al. confirmed the need for appropriate cancer surveillance and risk-reducing procedures for transgender and gender diverse (TGD) populations with hereditary cancer syndromes ⁽⁹⁾. There are no clinical guidelines specific for transgender and gender diverse individuals with Lynch syndrome, a common hereditary cancer syndrome ⁽⁹⁾. Globally health care organizations are moving towards the promotion of specific practice guidelines for (TGD) populations. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health ⁽¹⁰⁾. WPATH’s Standards of Care (SOC) is the organizations main vehicle to promote the standards of care for transgender and gender diverse populations ⁽¹⁰⁾. Rolle et al. recently affirmed the need for specialized genetic counseling for members of the TGD population. An article published in the Journal of Genetic Counseling, revealed results from a pilot study suggesting that TGD patients experience anticipatory anxiety before genetic counseling as well as for subsequent physical examinations ⁽¹¹⁾. Study results demonstrated that TGD patients experience disrupted family relationships that impact access to family history information and support ⁽¹¹⁾. Rolle et al. recommend genetic counselors to inclusive language when discussing cancer risk; the research group calls for additional research to provide more accurate cancer risk predictions for TGD patients ⁽¹¹⁾.

OIE Inc applauds the session speakers for an enlightening session. OIE Inc also calls for specific cancer surveillance guidelines and will continue champion equitable care for the TGD population. Remain tuned into www.oncodisparities.com for further information.

References:

1. Thies, B. 2023. Biden administration declines Supreme Court appeal for transgender surgery mandate. June 21, 2023. Washington Examiner. Retrieved on June 22, 2023 from https://www.msn.com/en-us/health/other/biden-administration-declines-supreme-court-appeal-for-transgender-surgery-mandate/ar-AA1cQWzC?ocid=msedgntp&cvid=5beda3001c224d429f
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9. Hodan, R., Rodgers-Fouche, L., Chittenden, A. et al. 2023. Cancer surveillance for transgender and gender diverse patients with Lynch syndrome: a practice resource of the Collaborative Group of the Americans on Inherited Gastrointestinal Cancer. June 21, 2023. Familial Cancer. https://doi.org/10.1007/s10689-023-00341-4
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