Counseling gap may worsen endometrial cancer disparities in Black women

Abstract

Cancer of the endometrium, or the lining of the uterus, is the most common gynecologic cancer. Its incidence is accelerating, especially in younger women and among racial and ethnic minorities; it is one of the few cancers with worsening mortality rates.¹ The trend is most pronounced in Black women, who are two-fold more likely to die of endometrial cancer than their White counterparts.

Research has shown that mutations in dozens of cancer predisposition genes, or germline pathogenic variants, can increase the risk. A recent study that grouped 1625 women with endometrial cancer by self-reported race, ethnicity, and Ashkenazi Jewish ancestry, however, has pointed to a more troubling contributor to disparities in patient outcomes. Although the genetic mutation rates were lowest in women who identified as being Black or of African ancestry, so too were their rates of genetic counseling, which could help them to assess treatment options.²

The study, led by oncologist Ying Liu, MD, MPH, at Memorial Sloan Kettering Cancer Center in New York, suggests that the counseling disparities also could dampen subsequent counseling rates for at-risk relatives. Social determinants then could be making endometrial cancer morbidity and mortality disparities worse in Black women despite a genetic contribution to risk that is equivalent to or lower than that in White women.

Given the growing use of such germline assessments, Dr Liu and her colleagues emphasize the need to understand variations related to patients’ ancestry, correlations between genetic findings and tumor traits, and “downstream implications on treatment and cancer prevention and the potential contribution to racial disparities in outcomes.”

Oladapo Yeku, MD, PhD, assistant professor of medicine at Harvard University, says that he is not surprised by Dr Liu’s findings “but very concerned because it gave numbers to some of the things that a lot of doctors in the community and academic centers have known for some time.” Many physicians had sensed that women in underserved communities were not getting appropriate referrals for genetic counseling. “But it was hard to get a number on it; it hadn’t been rigorously studied,” Dr Yeku says. “What this single institution report did was actually put some numbers to what some people had feared the whole time.”

The referral gap is even more concerning because tumor mutation testing and guideline-based recommendations for managing newly diagnosed, advanced, and recurrent endometrial cancer generally have increased in availability. As Dr Yeku wrote in an editorial accompanying the study, “disparities in testing, referral to clinical genetics, and participation in clinical trials are persistent contributors to poor outcomes in this patient population.”³

Lack of access, in fact, has been a consistent theme in multiple aspects of care for minority women with endometrial cancer. For a subset of patients with a deficiency in their DNA mismatch repair mechanism, the arrival of two potent drugs (known as immune checkpoint inhibitors) has been “game changing” in extending lives, says Dr Yeku. The US Food and Drug Administration’s (FDA’s) approval of pembrolizumab and dostarlimab for treating women with advanced or recurrent endometrial cancer was “unequivocally a home run,” he says.

Even so, the seminal clinical trials leading to that FDA approval were similarly plagued by what Dr Yeku calls an “abysmal” representation of minority women. In theory, he says, anyone with the right genetic mutation could have had access to the lifesaving precision medicine. However, what happened in practice was fundamentally different. “There was a population of people who had access to it and were doing very well, and a similar population who had the same mutations but never got early access to these drugs,” he says. In other words, some women are being boxed out of cutting-edge cancer care at both ends: diagnosis and treatment.

The same general phenomenon has been documented in other cancers. Dr Liu and her colleagues, for example, noted in their recent study that their previous research reported similar disparities in care across all tumor types. “Even after removing many roadblocks, non-White and especially Black patients were less likely to get recommended genetics care, which may affect their cancer treatments and families.”⁴

Researchers are trying to parse the potential socioeconomic contributors to these troubling disparities, and some have suggested that access to testing and counseling—and therefore to informed care—may depend in part on where someone lives. A highly cited 2008 study of older women with breast cancer, for instance, concluded that “individuals who live in more segregated areas are less likely to receive adequate breast cancer care.” This research report was one of the first to explicitly link racial segregation and poorer care.⁵

In light of the latest study, some researchers are suggesting that the pivot point at which eligible minority patients are referred or not referred for genetic testing and counseling may be a major contributor to cancer disparities—and a key target for practical solutions. Moving forward, Dr Yeku says, one of the biggest priorities should be educating both patients and practitioners, particularly patients’ primary care physicians.

Patients should be made aware of the results and implications of their genetic profiling, including the germline variants that they can pass along to their offspring and the tumor-related profile that helps them to determine their treatment options. One critical question, therefore, is whether the results should prompt a referral to a clinical geneticist to discuss the risk to the patient and the patient’s family. Another is whether the results might point toward a clinical trial in which the patient could enroll.

On its own, however, patient education is not enough, Dr Yeku says. The primary oncologist, referring oncologist, primary care provider, gynecologist, or other providers should be aware of the need to inquire about genetic testing results, ask how they are being discussed, consult with the patient about the most relevant questions, and then refer them to a clinical geneticist for answers. “That would be, in my mind, one of the best ways to increase that education at the grassroots level,” he says.

A patient navigator—often a nurse—or trusted primary care provider might be better suited to bridging the diagnosis and treatment gap than an unfamiliar physician at a tertiary care center. “If you think about it in the community, for a lot of patients it’s a family member who does that role for them,” Dr Yeku says. “Those are the patients I suspect who tend to get better access to referrals, who might be more savvy.”

In practice, education also means alerting patients and physicians to the heightened endometrial cancer risk associated with genetic conditions, such as Lynch syndrome, and to the early warning signs, such as postmenopausal bleeding—a red flag that often goes unreported by women. “They may be seeing practitioners who are not adequately attuned to what those risk factors might be in a post-menopausal person,” Dr Yeku says.

The lack of attention can contribute to a cascade of downstream effects that lower the patient’s survival odds, such as diagnosis at a later stage of disease and a lack of genetic testing, counseling, or enrollment in a clinical trial. “Early diagnosis, early testing has to be the way,” Dr Yeku says. When patients from underserved populations do get a referral to see a clinical geneticist, he says, the vast majority follow through. Figuring out how to give them better access to that critical resource could then yield a welcome turnaround in a disease with increasingly worrisome trends.