Expert Advocates Universal Genetic Testing in Breast Cancer

OncologyLive, Vol. 20/No. 15, Volume 20, Issue 15

Although research findings have established many applications for genetic information in breast cancer, not enough patients are being tested for the risk of germline mutations and new strategies are needed to broaden the clinical application of genomic advancements.

Pat W. Whitworth, MD

Although research findings have established many applications for genetic information in breast cancer, not enough patients are being tested for the risk of germline mutations and new strategies are needed to broaden the clinical application of genomic advancements, according to experts in the field.

Less than 20% of patients with breast or ovarian cancer who met certain criteria for genetic testing under National Comprehensive Cancer Network (NCCN) guidelines actually received testing, investigators found in a study involving more than 47,000 women.1 Other study findings suggest that only 30% of an estimated 35,000 patients with breast cancer who harbor pathogenic BRCA1/2 variants have been identified.2

Figure. Gene Mutations in a Breast Cancer Population2

Table. Guideline Definition of Patients Testing Positive2

“Our understanding of gene function has progressed to the point that genetic testing can provide actionable insights that would improve care for millions of women—and the tests are now cheap enough to justify widespread screening—but clinical practice hasn’t kept pace,” Pat W. Whitworth, MD, said in an interview with OncologyLive®. Whitworth, a breast cancer surgeon at Saint Thomas Health in Nashville, Tennessee, is among those advocating for change. The failure to screen sufficiently for potentially deleterious BRCA mutations stems from systemic problems, Whitworth maintained during a presentation at the 36th Annual Miami Breast Cancer Conference® (MBCC).3

Study results have shown that up to 50% of BRCA carriers do not meet testing guidelines, less than 20% of primary care providers assess family history to identify candidates for BRCA testing, a majority of the eligible relatives of patients with BRCA aberrations are not evaluated for mutations (ie, cascade testing), and most families with a high incidence of mutations are not referred for counseling.3

The first major step toward correcting the problem would be routine genetic testing for all patients with breast cancer, combined with the optimal cascade testing for relatives, Whitworth said.

Currently, NCCN guidelines recommend genetic counseling for patients considered at high risk for hereditary breast cancer based on such factors as age at diagnosis and personal and family history of cancer, with a focus on assessing patients for pathogenic or likely pathogenic variants in BRCA1/2, TP53, and PTEN.4

The argument for dramatically expanded testing hinges on recent research, including a clinical registry study that Whitworth coauthored.2 Investigators offered an 80-gene test panel to patients with previously or newly diagnosed breast cancer at 20 community and academic practices and recruited more than 1000 participants who had not yet undergone any genetic screening.

In all, investigators analyzed data from 959 patients, 49.95% of whom met NCCN screening guidelines. They found pathogenic or likely pathogenic mutations in 9.39% of patients who met guidelines and in 7.9% of those who did not. The difference in mutation frequency was not statistically significant (P = .4241), which led the study authors to recommend that screening guidelines be expanded to include all patients with breast cancer (Figure, Table).2

Such a policy, if adopted and embraced by patients, would necessitate significant changes to current practices. NCCN guidelines currently call for extensive counseling before patients even decide whether to undergo testing. The guidelines note that a genetic counselor, a medical geneticist, an oncologist, a surgeon, an oncology nurse, or another trained health professional may participate in counseling.4

Under a model that Whitworth discussed, patients would receive minimal pretest counseling followed by intensive counseling for those who test positive.3 The decision, he said in his MBCC presentation, is whether to “continue extensive counseling for a small number of patients versus making genetic testing available to the millions who need it.”

Under this model, counselors would mostly move from gatekeepers who participate in every step of the testing process to specialists who help patients deal with potentially distressing results and help them choose the best responses to those results.

“Under traditional standards of care, patients have face-to-face meetings with counselors before they decide whether to have tests, and the counselors are supposed to go through every possible finding and the implications of those findings,” Whitworth said. “That was feasible when we were testing for 2 BRCA genes, but it’s not practical for a panel that reports on 80 or more genes. A single thorough consultation would take hours.

“Counselors are also required to discuss the worst-case emotional impact of discovering any harmful mutations, and that scares many patients away from getting tests that can only improve their health,” Whitworth added. “Nearly every medical test that physicians order can come back with scary results, but patients are almost better off knowing any truth, no matter how upsetting, if that knowledge can guide care.”

The shift away from using counseling specialists before testing would require oncologists and other physicians to provide basic pretest counseling to their patients. Whitworth identified several messages that should be conveyed to patients before they are tested:

  • Testing is important because it may affect treatment recommendations for the patient and allow precautionary steps for the health of relatives.
  • The results could make the patient eligible to participate in a clinical trial.
  • Actionable genes are found in only about 10% of patients, so the results probably will not immediately change prognosis or treatment.
  • The cost of the test may be covered by insurance but, if it is not, the price for the patient can be as low as $250.
  • Testing will not affect health insurance coverage and is unlikely to have any impact on life insurance availability for a patient who already has a breast cancer diagnosis.

If pathogenic mutations are discovered, most patients would speak with a professional counselor. Meanwhile, Whitworth says, there are several key points to discuss with patients whose test results are negative:

  • Relatives of patients with cancer still face an elevated risk of developing cancer, even when genetic screens come back negative, so they should still receive whatever regular screenings current guidelines recommend.
  • A test that shows “variants of undetermined significance” is a negative test. Although these are not known to cause disease, future research might uncover an association with disease. Patients should be assured that they will be notified of significant new research findings.

Expanded genetic counseling and testing would place another burden on oncology practices, Whitworth acknowledged.

“Physicians are already being pressed by the current payment structure to treat more patients by spending less time with each, and this additional counseling duty would obviously add to time pressure, but the benefits associated with testing more patients would more than justify the effort,” Whitworth said. “We have been talking about personalized medicine for decades now, but we finally know enough about genetic risks that this testing will allow us to provide it for a significant and growing number of patients. And the arguments in favor of widespread testing only grow stronger with each new discovery.”


  1. Childers CP, Childers KK, Maggard-Gibbons M, Macinko J. National estimates of genetic testing in women with a history of breast or ovarian cancer [erratum in J Clin Oncol. 2018;36(4):432. doi: 10.1200/JCO.2017.77.5114].. J Clin Oncol. 2017;35(34):3800- 3806. doi: 10.1200/JCO.2017.73.6314.
  2. Beitsch PD, Whitworth PW, Hughes K, et al. Underdiagnosis of hereditary breast cancer: are genetic testing guidelines a tool or an obstacle? J Clin Oncol. 2019;37(6):453-460. doi: 10.1200/ JCO.18.01631.
  3. Whitworth P. Nontraditional genetic counseling: solving the challenge of the undetected carrier. Presented at: 36th Annual Miami Breast Cancer Conference®; March 7-10, 2019; Miami Beach, FL. breast-cancer-conference.
  4. NCCN Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: Breast and Ovarian, version 3.2019. National Comprehensive Cancer Network website. physician_gls/pdf/genetics_screening.pdf. Updated January 18, 2019. Accessed July 22, 2019.