December 5, 2017

The Impact of Multigene Panel Testing on Surgical Decisions for Breast Cancer Patients

Finding variants of uncertain significance does not increase the rate of contralateral prophylactic mastectomies

Pederson_650x450

Testing for the BRCA1 and BRCA2 genes has been routine for women diagnosed with breast cancer who have risk factors for hereditary breast or ovarian cancer. In consultation with genetic counselors and physicians, positive results for BRCA1/2 inform a woman’s treatment decisions. Women with positive genetic test results who choose to undergo contralateral prophylactic mastectomy (CPM) may reduce their risk of dying from breast cancer.

Advertisement

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

Many additional genes have been found to be associated with an increased risk of breast cancer, and in the past several years, multigene panel testing (MPT) has become common for this population. MPT can provide women who are diagnosed with breast cancer valuable knowledge about their hereditary risk. However, patients may be confused by the implications of positive results to variants of low or moderate penetrance. Findings that show variants of uncertain significance (VUS), which are mutations that have an unknown effect on protein function, may also confuse patients. Recent research at Cleveland Clinic sought to address concerns that positive results from MPT might cause women to choose CPM even when their overall risk profile does not indicate a strong necessity for such treatment.

“We investigated the hypothesis that multigene panel testing in patients with triple negative breast cancer (TNBC) does not result in an inappropriately high rate of bilateral mastectomy when patients are provided pre- and post-test genetic counseling,” says lead researcher Holly Pederson, MD, Director of Medical Breast Services at Cleveland Clinic’s Breast Center. Dr. Pederson presented the results of the study at the Southern Surgical Association Conference on December 5.

Study design and findings

Dr. Pederson and her team conducted a retrospective electronic medical records-based study of women who were treated for triple negative breast cancer at Cleveland Clinic and who underwent MPT between Sept. 2013 and Feb. 2017. “We chose to investigate patients with TNBC since the majority of these patients qualify for genetic counseling, and their surgical choices are not as likely to be influenced by tumor-biology-related factors,” says Dr. Pederson.

The study identified 331 patients with TNBC who met the criteria for genetic counseling, and 226 opted for genetic testing (MPT – 130, BRCA1/2 – 96). All of the patients received genetic counseling before the tests, and patients with significant results were also counseled afterward. Results were as follows:

Advertisement
  • Pathogenic mutations (Mut+) in BRCA1/2 or PALB2 were found in 29 (12.8 percent) of patients, and 88 percent of the Mut+ patients underwent CPM.
  • VUS were detected in 42 (18.6 percent) of patients, and 21.4 percent of VUS+ patients underwent CPM.
  • No mutations (Mut-) were found in 155 (68.6 percent), and 20.1 percent of Mut- patients underwent CPM.

The decision to undergo CPM did not differ significantly between VUS+ and Mut- (P = 0.368) patients, within different age groups (< 40, 40-60 and > 60 years). Within the VUS+ group, Caucasians were more likely to choose CPM than other races (25.8 percent vs 9.1 percent), although this difference did not reach statistical significance (P = 0.162).

In five patients, MPT showed non-breast cancer related genetic alterations that were clinically actionable. Following is a summary of those findings:

Implications

“We are seeing a shifting paradigm away from single syndrome testing and towards next generation sequencing of multiple genes in clinical cancer genetics,” says Dr. Pederson. “This is particularly important for patients with triple negative breast cancer as mutations are not uncommon and can inform surgical decision making.”

Advertisement

The study found that with appropriate genetic counseling, detection of VUS — which are more common in gene panels — did not lead to excessive rates of CPM.

Dr. Pederson adds that in this study, MPT allowed for the identification of other gene mutations that supported management of the patients and their family members.

Related Articles

Doctors working on MGUS screening study
March 18, 2024
Pilot Study Aims for Early Identification of Multiple Myeloma Precursor Among Black Patients

First-of-its-kind research investigates the viability of standard screening to reduce the burden of late-stage cancer diagnoses

Physician with patient
March 6, 2024
Targeting Uncontrolled Erythrocytosis in Polycythemia Vera with Rusfertide

Study demonstrates ability to reduce patients’ reliance on phlebotomies to stabilize hematocrit levels

Doctor measuring patient's waist size
February 26, 2024
Impact of Obesity on GVHD & Transplant Outcomes in Hematologic Malignancies

Findings highlight an association between obesity and an increased incidence of moderate-severe disease

Physician with patient
February 21, 2024
Strategies for Improving Clinical Trial Equity

Cleveland Clinic Cancer Institute takes multi-faceted approach to increasing clinical trial access

How antibody drug conjugates work
February 13, 2024
Real-World Use of Trastuzumab Deruxtecan

Key learnings from DESTINY trials

24-CNR-4545611-CQD-Podcast-967&#215;544
February 1, 2024
Possibilities of CRISPR Technology (Podcast)

Gene editing technology offers promise for treating multiple myeloma and other hematologic malignancies, as well as solid tumors

Disparities in multiple myeloma
January 25, 2024
Major Study Identifies Global Disparities in Drug Toxicity for Multiple Myeloma Treatment

Study of 401,576 patients reveals differences in cancer burdens as well as overall survival

Dr. Shilpa Gupta
December 27, 2023
A New Standard Emerges in Advanced Urothelial Carcinoma After Decades of First-Line Chemotherapy

Enfortumab plus pembrolizumab reduced risk of death by 53% compared with platinum-based chemotherapy

Ad