Germline Genetic Testing and Treatment Decisions in Early-Stage Breast Cancer

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“These findings emphasize the need to address challenges in personalized communication about genetic testing.”
— Allison W. Kurian, MD, and colleagues

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As reported in the Journal of Clinical Oncology by Allison W. Kurian, MD, of Stanford University School of Medicine, and colleagues, surveys in a population-based sample of patients recently diagnosed with breast cancer indicate that many undergo genetic risk testing without seeing a genetics counselor. The investigators also found that many patients with BRCA1/2 variants of uncertain significance or no mutations undergo bilateral mastectomy.1

Study Details

The study involved a population-based sample of women aged 20 to 79 years with stage 0 to II breast cancer diagnosed from 2014 to 2015 identified through Georgia and Los Angeles Surveillance, Epidemiology, and End Results (SEER) registries. Subjects were surveyed about genetic testing experiences at approximately 2 months after surgery. Patients with bilateral disease, tumors larger than 5 cm in diameter, or more than 3 involved nodes were excluded. 

A total of 666 eligible patients reported undergoing genetic testing. The patient population was racially diverse, with 57% being white, 18% black, 14% Hispanic, and 9% Asian. 

Patients were categorized at higher or average pretest risk for genetic mutation carriage on the basis of National Comprehensive Cancer Network® (NCCN®) Guidelines. Higher risk was defined as one or more of the following criteria: age at breast cancer diagnosis < 45 years; triple-negative breast cancer diagnosed at age < 60 years; any relative with ovarian cancer, sarcoma, or male breast cancer; ≥ 2 first-degree relatives with breast cancer (for patients diagnosed at age ≤ 50 years, ≥ 1 first-degree relative with breast cancer); Ashkenazi Jewish ancestry; or family history of a mutation conferring high risk (eg, BRCA1/2). 

Enrolled patients’ attending surgeons (n = 377) were surveyed about the number of new patients with breast cancer they had treated in the past year, confidence in discussing the pros and cons of genetic testing, and how often they performed the following for testing candidates: referred patient for genetic counseling; ordered testing without counseling referral; and delayed surgery until testing results were obtained. Surgeons were also asked whether they would offer breast-conserving surgery to some BRCA1/2 mutation carriers as a reasonable option or manage a patient with a BRCA1/2 variant of uncertain significance or other variants of uncertain significance the same way as a carrier of a known pathogenic BRCA1/2 or other mutation (eg, TP53). 

Genetic Testing in Breast Cancer

Overall, 57% of patients at higher pretest risk and 42% at average risk discussed testing results with a genetic counselor. Bilateral mastectomy was common among patients with genetic variants of uncertain significance.

Testing and Counseling

Among all tested patients, 59% met criteria for higher pretest risk of pathogenic mutation carriage, and 39% did not (average risk). The timing of testing for patients at higher vs average risk was before diagnosis for 6% vs 2%, after diagnosis but before surgery for 67% vs 64%, and after surgery for 27% vs 34%. 

Providers ordering testing were surgeons for 48% for higher-risk patients vs 42% for average-risk patients, medical oncologists for 31% vs 40%, and genetic counselors for 21% vs 18%. Patients reported discussion of results by surgeons only for 19% vs 18%, medical oncologists alone for 17% vs 31%, genetic counselors alone for 57% vs 42%, and multiple health professionals for 7% vs 10%. 

In multivariate analysis adjusting for age, race, education, stage, comorbidities, and study site, patients were more likely to be tested after surgery if they had Medicare (odds ratio [OR] = 2.6, 95% confidence interval [CI] = 1.6–4.2), Medicaid (OR = 2.3, 95% CI = 1.1–4.5), or no insurance (OR = 2.5, 95% CI = 1.5–4.3) compared with those with private insurance, and average-risk patients were more likely to be tested after surgery than higher-risk patients (OR = 1.4, 95% CI = 1.0–2.1).

Likelihood of Bilateral Mastectomy

Overall, 72% of patients reported that no mutation was detected, 9% reported variants of uncertain significance, 7% indicated a pathogenic mutation in BRCA1/2 or another risk-associated gene, and 12% did not report results. On multivariate analysis, receipt of bilateral mastectomy was more likely for patients with a pathogenic mutation vs no mutation (OR = 7.7, 95% CI = 3.9–15.3), white vs black patients (OR = 3.2, 95% CI = 1.7–5.0), those aged ≤ 50 years vs > 50 years (OR = 2.5, 95% CI = 1.6–3.9), and those with private insurance vs Medicare (OR = 3.3, 95% CI =1.6–6.9). 

In analysis adjusting for age, race, insurance type, and site, the probability of receiving bilateral mastectomy among higher-risk women was 80% for those with a pathogenic BRCA1/2 or other pathogenic mutation, 43% for those with BRCA1/2 variants of uncertain significance, and 34% for those with no mutation. For average-risk patients, the probabilities were 85% for those with pathogenic mutation, 51% for those with variants of uncertain significance, and 42% for those with no mutation.

Surgeon Practices

Among surgeons, 38% had a lower volume of breast cancer patients (1–20 in prior year), 30% had a moderate volume (21–50), and 29% had a higher volume (> 51 patients). For lower-, moderate-, and higher-volume surgeons, 35%, 54%, and 73% reported being confident in discussing genetic testing with patients; 33%, 28%, and 24% referred patients for genetic counseling ; 26%, 35%, and 37% ordered genetic testing without referring to a counselor; 38%, 27%, and 17% did not delay surgery for test results; 36%, 25%, and 43% offered breast-conserving surgery to patients with BRCA1/2 mutation; and 50%, 42%, and 24% indicated they would manage patients with variants of uncertain significance the same as pathogenic BRCA1/2 mutation carriers. 

The investigators concluded: “Many patients with breast cancer are tested without ever seeing a genetic counselor. Half of average-risk patients with variants of uncertain significance undergo bilateral mastectomy, suggesting a limited understanding of results that some surgeons share. These findings emphasize the need to address challenges in personalized communication about genetic testing.”  ■

Disclosure: The study was supported by the National Cancer Institute. Dr. Kurian has received research funding from Invitae, Myriad Genetics, Ambry Genetics, GenDx, and Genomic Health. For full disclosures of the other study authors, visit


1. Kurian AW, Li Y, Hamilton AS, et al: Gaps in incorporating germline genetic testing into treatment decision-making for early-stage breast cancer. J Clin Oncol. April 12, 2017 (early release online).