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Multigene Test Extends Life Expectancy for Cancer Patients

By LabMedica International staff writers
Posted on 04 May 2017
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Image: A histopathology of breast cancer:  intraductal carcinoma, noncomedo type, distended duct with intact basement membrane, micropapillary, and early cribriform growth pattern membrane and central tumor necrosis (Photo courtesy of Dr. Peter Abdelmessieh).
Image: A histopathology of breast cancer: intraductal carcinoma, noncomedo type, distended duct with intact basement membrane, micropapillary, and early cribriform growth pattern membrane and central tumor necrosis (Photo courtesy of Dr. Peter Abdelmessieh).
Testing for variants in seven cancer-associated genes, versus the usual process of testing in just two genes, followed by risk-reduction management could cost-effectively improve life expectancy for women at risk of hereditary breast cancer.

Breast cancer is the most commonly diagnosed non-cutaneous cancer and the second leading cause of cancer death among women in the USA. •n 2017, an estimated 252,710 new cases of invasive breast cancer are expected to be diagnosed in women in the USA, along with 63,410 new cases of non-invasive (in situ) breast cancer. Women with a family history of breast cancer are at increased risk, with about 13% of women with breast cancer having one or more first-degree relatives with the disease.

Scientists at Quest Diagnostics investigate whether using a seven-gene test to identify women who should consider risk-reduction strategies could cost-effectively increase life expectancy. They estimated effectiveness and lifetime costs from a payer perspective for two strategies in two hypothetical cohorts of women (40-year-old and 50-year-old cohorts) who meet the National Comprehensive Cancer Network, defined family history criteria for multigene testing.

The two test strategies for detecting pathogenic genetic variants was: 1) the usual breast cancer 1, early onset, (BRCA1/2) test strategy, and 2) a Quest Diagnostics’ BRCAvantage Plus, next-generation seven gene strategy that tests for variants not only in BRCA1 and BRCA2, but also in Tumor protein p53 (TP53), Phosphatase and tensin homolog (PTEN), Cadherin-1 (CDH1), Serine/threonine kinase 11 (STK11), and Partner and localizer of BRCA2 (PALB2). Individuals who carry a pathogenic variant in any one of these genes are considered test-positive; otherwise, they are considered test-negative.

In the base-case scenario for 50- and 40-year-old women undergoing genetic testing, the incremental cost-effectiveness ratio (ICER) for the 7-gene test strategy compared with the BRCA1/2 test strategy was USD 42,067 and USD 23,734 per life-year gained, or USD 69,920 and USD 48,328 per quality-adjusted life-year gained, respectively. In probabilistic sensitivity analysis, the seven-gene test strategy cost less than $100,000 per life-year gained in 95.7% of the trials for the 50-year-old cohort.

Yonghong Li, PhD, the lead author of the study said, “Pathogenic variants in the BRCA1 and BRCA2 genes explain only about 15% of the breast cancer familial relative risk, while pathogenic variants in other genes, including TP53, PTEN, CDH1, and PALB2 contribute further to the familial relative risk. The results of this study demonstrate the potential value of newer testing options that allow for the simultaneous analysis of expanded panels of additional genes whose pathogenic variants confer moderate to high risk for breast cancer.” The study was published in the April 2017 issue of the journal Value in Health.

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