Addressing Provider Misconceptions in Ovarian Cancer Genetic Testing

By John Chan, MD, Gynecologic Oncologist, Sutter Health

Despite major advances for genetic testing in ovarian cancer, misconceptions persist about when and how to use it. One frequent assumption is that BRCA testing is already universal, but compliance with guidelines remains inconsistent across the U.S. This practice gap is driven by provider awareness, patient understanding, and systemic barriers.

Heading into 2026, comprehensive testing is no longer optional, it’s foundational to treatment planning, trial access, and hereditary risk management. Yet many patients still aren’t getting the testing they need, or they’re only receiving part of it.

Misconceptions #1: “BRCA screening is widespread because everyone follows national guidelines.”

While many assume BRCA screening is universal, compliance with guidelines is inconsistent. Gaps in provider awareness, patient understanding, and healthcare infrastructure leave many high-risk individuals unscreened, reflecting a persistent practice gap.

A recent report of patients diagnosed with ovarian cancer between 2013–2019 in California and Georgia showed that only 38.6% underwent germline testing—meaning over 60% were not tested despite recommendations.¹ By 2025, national data revealed only ~52% of U.S. patients with ovarian cancer had germline or somatic testing, with even lower rates among older, Medicare/Medicaid, and minority populations.²

Testing has advanced well beyond BRCA1/2. Roughly 50% of high-grade serous ovarian cancers are HRD-positive, many without BRCA mutations.³ Relying on BRCA status alone is insufficient. Updated FDA approvals and NCCN/ASCO guidelines reinforce the importance of biomarkers such as HRD and folate receptor expression for therapy selection.⁴ ⁵ For example, niraparib is no longer approved for all patients, but only for biomarker-defined disease.⁵

Yet misconceptions persist. Tumor genomic testing alone cannot distinguish germline from mutations found only in the tumor, an important distinction for treatment, family risk, and cascade testing. NCCN and ASCO therefore recommend germline testing for all epithelial ovarian cancer patients, regardless of age, stage, or family history, with confirmatory germline testing when tumor testing reveals a pathogenic variant.⁴

Structural barriers also drive under-utilization. In many clinics, testing requires referral, leading to delays and attrition. Pathology-driven tumor testing workflows may further disconnect oncologists from test ordering and follow-up. “Mainstreaming” models, where oncologists initiate testing directly, have improved uptake to over 90% at centers such as Memorial Sloan Kettering,³ and are now being adapted in community settings.

Heading into 2026, comprehensive testing is not optional, it is foundational to treatment planning, trial access, and hereditary risk management. Addressing knowledge gaps, streamlining workflows, and setting up mainstreaming models will be critical to achieving equitable, guideline-based testing for all patients with ovarian cancer.

Misconception #2: “Germline BRCA-negative means biomarker-negative and/or tumor negative means germline negative.”

A common myth is that a negative BRCA test leaves no actionable targets. In reality, homologous recombination deficiency (HRD) represents a broader genomic vulnerability beyond BRCA1/2. About 15% of ovarian cancer patients carry germline BRCA1/2 mutations, with another 5–7% carrying somatic (tumor) BRCA mutations.⁴ Overall, ~50% of high-grade serous ovarian cancers show HRD, arising from BRCA1/2 mutations, promoter methylation, epigenetic silencing (e.g., BRCA1 inactivation), or genomic instability.¹ Thus, a BRCA-negative result does not rule out biomarker-driven options such as PARP inhibitors.

At the same time, tumor genomic testing alone is insufficient. Some assume it can replace germline testing, but tumor-only testing can miss inherited BRCA mutations due to heterogeneity or variant filtering. For comprehensive care—including risk assessment and family counseling—both germline (inherited) and somatic (tumor) testing are essential.

Reflecting this, ASCO guidelines recommend dual testing⁵:

• Germline multigene testing for all women with epithelial ovarian cancer at diagnosis.
• Tumor testing for BRCA and HRD if germline results are negative.

These practices are not only clinical best standards but also quality measures. For example, Medicare’s MIPS program tracks germline BRCA testing rates in ovarian cancer, signaling their importance as benchmarks in patient care.

Misconception #3: “All genetic testing platforms and homologous recombination deficiency (HRD) assays are essentially the same.”

Not all BRCA testing platforms and HRD assays are equivalent, as significant variability exists across laboratories in sequencing technologies, gene panel content, interpretation standards, and HRD scoring methods, making results non-interchangeable and potentially impacting treatment decisions.

Some assays measure only the percentage loss of heterozygosity (LOH), which captures a limited aspect of tumor genomic damage. In contrast, broader genomic instability scoring, such as the MyChoice^® CDx HRD Companion Diagnostic Test, integrates LOH, telomeric allelic imbalance (TAI), and large-scale state transitions (LSTs) into a composite Genomic Instability Score. This approach identifies approximately 34% more HRD-positive tumors than LOH alone and can detect tumors without BRCA mutations that may still respond to PARP inhibitors.⁷ Genomic instability reflects cumulative tumor damage when homologous recombination repair is impaired, manifesting as chromosomal breaks, LOH, TAI, and LSTs.

Another actionable biomarker is FRα testing, which is assessed via Myriad Oncology’s FOLR/FRα Companion Diagnostic Testing. About 35–40% of patients with platinum-resistant ovarian cancer⁸ overexpress FRα, making them eligible for targeted therapy with mirvetuximab soravtansine.⁹ While mirvetuximab carries potential adverse events, it provides a novel mechanism of action and demonstrates efficacy in later-line settings, particularly in patients who have progressed on PARP inhibitors or are no longer candidates for platinum-based therapy.

In Summary

By 2026, comprehensive testing should be integral to ovarian cancer care, not an extra step. This begins with multigene germline testing at diagnosis, including BRCA1/2 and other relevant genes linked to Lynch syndrome (e.g., EPCAM, MLH1, MSH2, MSH6, PMS2), which have implications for broader screening and risk reduction. Simultaneously, tumor genomic testing can identify somatic BRCA mutations and assess HRD status via genomic instability scores, as in MyChoice^® CDx.

For clinicians, the most effective workflows are seamless and reflexive rather than reactive. Integrating germline and tumor insights into the upfront workup ensures patients receive personalized care without delays.

The tools exist, guidelines align, and the clinical benefit is clear. By 2026, testing should be the starting point in ovarian cancer care.

References:

1. Kurian AW, et al. Germline genetic testing after cancer diagnosis in California and Georgia. JAMA. 2023;330(1):30–32.
2. Ovarian Cancer Research Alliance. Nearly half of women with ovarian cancer are not receiving critical genetic testing. Press release. Published March 25, 2025.
3. Feng, Z., et al. Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma. J Ovarian Res 16, 53 (2023). https://doi.org/10.1186/s13048-023-01129-x
4. Andrikopoulou, A., et al. Germline and somatic variants in ovarian carcinoma: A next-generation sequencing (NGS) analysis. Front Oncol. 2022 Dec 1;12:1030786. doi: 10.3389/fonc.2022.1030786. PMID: 36531003; PMCID: PMC9754718.
5. Konstantinopoulos PA, et al. Germline and somatic tumor testing in epithelial ovarian cancer: ASCO guideline. J Clin Oncol. 2020;38(11):1222-1245. doi:10.1200/JCO.19.02960
6. Centers for Medicare & Medicaid Services. Quality Measure 507: Appropriate Germline Testing for Ovarian Cancer Patients. 2025 Measure Specifications. Accessed July 24, 2025. https://qpp.cms.gov/docs/QPP_quality_measure_specifications/CQM-Measures/2025_Measure_507_MIPSCQM.pdf
7. Mills et al. Presentation for 2020 SGO Annual Meeting. SGO Annual Meeting on Women’s Cancer (Abstract 1).
8. Platinum-resistant ovarian cancer is defined as disease recurrence within six months of completing platinum-based chemotherapy, indicating reduced likelihood of response to further platinum treatment.
9. Liu H. Mirvetuximab Soravtansine Positioned as New Standard in FRα–Platinum-Resistant Ovarian Cancer. OncLive. Published December 21, 2022. Accessed July 24, 2025. https://www.onclive.com/view/mirvetuximab-soravtansine-positioned-as-new-standard-in-fr-platinum-resistant-ovarian-cancer