Panel testing for genetic variants linked to more cancers is cost-effective than just testing or BRCA1/2 mutations, says a clinical director for a women's health company.
If caught early, the survival rate for ovarian cancer (stage I or II) can be 70% to 90%, according to data collected by the National Cancer Institute. After that, the odds drop below 50%, which elevates the importance of catching cancer early or preventing it if a woman’s family history suggests her risk of cancer is high.
Both steps rely on testing, and that makes payer coverage for tests essential. A 2013 Supreme Court ruling that opened the door to competition among tests for BRCA1/2 mutations appears to have created access to those tests, but access to broader panel testing hasn’t been universal or straightforward. This has been persisted even though the connection between genomic testing and precision medicine is clear.
To better understand the connections among testing, prevention, and treatment in ovarian cancer, The American Journal of Managed Care® (AJMC®) spoke with Jessica Greenwood, MS, who was recently named senior director of Clinical Implementation and Innovation for Aspira Women’s Health. Greenwood discussed Aspira’s OVA1 test, which uses an algorithm to evaluate masses prior to surgery, and Aspira GenetiX, which screens for a woman’s risk of hereditary breast and ovarian cancer through genetic testing.
This interview has been edited lightly for clarity.
AJMC®: Can you briefly describe the company’s test for ovarian cancer and the hereditary cancer test?
Greenwood: OVA1 is our test for ovarian cancer. It's an FDA-cleared blood test for women with an adnexal mass that utilizes 5 biomarkers and a proprietary algorithm to assess the malignancy risk of the mass. The test results can help determine which provider should perform surgery, a [gynecological] oncologist or an OB/GYN, and that really leads to the most effective treatment plan for patients. Add to that Aspira GenetiX hereditary cancer testing. That's a multigene panel test that's specifically curated to include genes with a known or suspected associated risk of breast and gynecologic cancers. Those gynecologic cancers include not just ovarian but also endometrial or cervical cancer. So, that panel includes genes such as BRCA1/2, as well as all of the Lynch syndrome genes, but also some less well-known genes like ATM or STK11 or PTEN.
AJMC®: In 2013, we experienced what some called the Angelina Jolie effect, which was described as a watershed event in raising awareness about BRCA testing after Jolie revealed that she’d had her breasts removed to reduced her chances of developing breast cancer. (Jolie later had her ovaries removed as well.) How would you describe today’s awareness level about BRCA testing, as well as the knowledge about preventive surgery? What is the level of awareness of ovarian cancer risk relative to breast cancer risk?
Greenwood: Angelina Jolie’s willingness to share her personal experience certainly brought hereditary cancer testing as a whole to mainstream media. And this significantly increased patient awareness, and subsequently led to patients asking their providers about BRCA testing—and to heightening the importance of that testing across the gynecological care spectrum.
However, what the movement failed to do is raise attention for all the cancers associated with the BRCA1/2 cancers, including ovarian and endometrial, pancreatic, and high-grade prostate cancer, which is interesting because even though the focus was largely on breast cancer, Angelina Jolie's mother actually died of ovarian cancer, which is really what [prompted her] to get tested.
While the focus on BRCA1/2 is appropriate, as they make up the majority of pathogenic variants associated with hereditary breast and ovarian cancer syndromes, there are several other genes that also confer extremely high risks for gynecologic cancers. So, testing only for BRCA1/2 will miss those other genes and may falsely reassure women that they're not at increased risk for breast or ovarian cancer. We really feel like the awareness should not only be on BRCA, but also on those other high penetrance genes that can confer those elevated risks.
AJMC®: Advocacy groups have tried to educate patients and providers about the need to test men as well as women, for BRCA and other related mutations, because fathers are equally capable of passing these mutations down to their daughters. Has the reimbursement landscape caught up with this need?
Greenwood: That’s such an important point. And I'd add that not only do men have the ability to pass on one of those themes to their children, but if they're carriers themselves, they may also be at risk for developing cancer. It’s really an important awareness point on both sides. Many hereditary cancer syndromes confer increased risk for things like high-grade prostate cancer, male breast cancer, pancreatic cancers, and others that directly impact men. I did review some of the major payers’ most recent policies, and it's clear that coverage exists for men who have a known family history of a hereditary cancer syndrome, a personal history of an associated cancer, or an extensive family history of cancer. However, the coverage is different and much more well defined for BRCA1/2 only, versus panel testing. But if a patient has cancer themselves, or an extensive history of cancer, most policies would also likely cover that testing. So, I think the bigger issue is maybe less about coverage here, but more about men actually presenting for this testing, and recognizing the relevance both for their own health and for their family's health.
AJMC®: About 18 months ago, we published a special issue on reimbursement issues in genetic testing and hereditary cancers. And not long after that, the National Comprehensive Cancer Network (NCCN) updated its recommendations for testing for persons of Ashkenazi Jewish heritage. Have you seen the testing and reimbursement landscape change since the late 2019 update for this population?
Greenwood: Universally, it seems at-large payers are covering at least BRCA1/2 testing for women and sometimes men of Ashkenazi Jewish ancestry. So, it's important to understand how that Ashkenazi Jewish ancestry term is defined. It's defined as having at least 1 grandparent who is of Ashkenazi Jewish descent. The challenge here is that only covering BRCA1/2 testing, and not multigene panel testing for those women, presumes that they're only at risk for the 3 founder mutations that are found in the Ashkenazi Jewish population. Given that women who qualify as Ashkenazi Jewish can have up to 75% of their ethnic makeup accounted for by a different ancestry, that's really an inaccurate and potentially dangerous assumption, however. Panel testing is more clinically and relevant and frankly, more cost-effective as a means of assessing hereditary cancer risk. But panel testing is not routinely covered for women who are Ashkenazi Jewish, just based on that criteria alone.
AJMC®: Are some payers better than other about coverage for tests? And is there a divide between the commercial and public payers? And is Medicaid better in some states than others?
Greenwood: As you can imagine, that's kind of a loaded question, but the short answer is yes. Under the Affordable Care Act, BRCA testing for women with specific, personal or family history should be covered with no copayment. However, men and women who are being treated for cancer are not included under that provision. So, it's helpful but not sufficient. And obviously, the provision doesn't cover multigene panel testing, and of course, you know, all provisions under the ACA are subject to what happens with that program moving forward. As far as Medicaid is concerned, all but 3 state Medicaid programs do cover BRCA1/2 testing for qualifying individuals. And the criteria basically follow NCCN guidelines as it does for most commercial payers. Unfortunately, again, most state Medicaid programs do not cover panel testing or testing for any gene outside of BRCA1/2 or the Lynch syndrome genes. And that really leaves a huge gap in care for individuals with that particular coverage, because testing is going to miss variants that confirm a significant associated cancer risk in genes like STK11, that significantly increases the risk for ovarian, cervical, and potentially endometrial cancer is not going to be included or covered by those Medicaid plans. The bottom line is that coverage is fairly universal for BRCA1/2 only testing, at least for women. But it varies greatly from there.
AJMC®: Should population-based screening occur for women based on clinical factors beyond family history or ethnic background, such as obesity?
Greenwood: I'm not sure we're at the point of population-based screening for hereditary cancer testing for any group or any subgroup. We certainly know that other medical factors such as obesity increase the risk for certain cancers, but the data just are not there to suggest that those medical factors are also associated with a history of a hereditary cancer syndrome, and are, therefore, an indicator of an enriched population. So, this is where you're starting to see multimodal risk assessment techniques like polygenic risk scores come into play. Those are risk assessments that are based on a variety of factors, including other genetic components, lifestyle factors, age, and family history. Instead of thinking about population-based screening, based on a particular factor like obesity, it may be more clinically effective to think about the combination of all of those factors and how that influences risk.
AJMC®: Is there anything that we haven't covered that you'd like to add?
Greenwood: One other challenge is the lack of coverage for diagnostic testing to confirm the results of direct-to-consumer (DTC) genetic testing. It’s recommended that anyone who receives a positive result, indicating the presence of a pathogenic variant through a DTC test gets a confirmatory test through a diagnostic laboratory. And given some of the recent data that's come out demonstrating the high rates of false positive results for some of the DTC labs, as well as the limitation of DTC testing in general, like not covering all variants in a particular gene, that diagnostic testing is really important to ensure that patients don't make clinical decisions based on results that haven't been verified by standard of care measures.
AJMC®: Would most payers cover surgery based on a direct-to-consumer test?
Greenwood: Not necessarily, but they would cover it if it was medically necessary. So, it would be up to the provider to determine if they would be willing to call something medically necessary based on that particular result.