From the Journals

Multigene testing for all patients with breast cancer may be cost-effective, life-saving

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Beware of hidden risks and costs

Although detection of more pathogenic variants among patients with breast cancer may initially appear beneficial, the hidden risks and costs associated with broader multigene testing would likely outweigh the benefits.

Present guidelines, such as those provided by the National Comprehensive Cancer Network, already include effective strategies for detecting BRCA1/2 variants, as only 0.6% of patients who do not meet screening guidelines are estimated to test positive

Beyond BRCA1/2, the clinical relevance of pathogenic variants becomes dubious, as many genetic aberrations are not actionable. Furthermore, misinterpretation of unfamiliar results may increase risks of treatment decisions that might actually harm patients. While some argue that broader testing could have benefits for family members, this is poorly supported with evidence.

Behind the allegedly falling costs of genetic sequencing, true costs are hidden with corporate policies that reduce patient financial liability. It is worth noting that two publicly held testing companies recently reported annual revenues of $144 million and $498 million, representing money drawn largely from third-party payers covering guideline-recommended testing. Instead of concrete science, the popularity of multigene testing is more likely driven by active marketing and technological convenience. More independent studies are needed.

Mark Robson, MD, is with the department of breast cancer medicine and clinical genetics at Memorial Sloan Kettering Cancer Center in New York. Susan Domchek, MD is with the Basser Center for BRCA at the University of Pennsylvania in Philadelphia. Dr. Robson disclosed financial relationships with AstraZeneca, McKesson, and Pfizer. Dr. Domchek reported personal fees from Clovis, AstraZeneca, and BMS. Their remarks are adapted from an editorial (JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.4004).


 

FROM JAMA ONCOLOGY

High-risk multigene testing for all patients with breast cancer may be a cost-effective way to reduce rates of breast cancer and ovarian cancer, according to investigators.

A microsimulation modeling study suggested that moving from standard BRCA testing based on clinical criteria or family history to widespread adoption of multigene testing could potentially save more than 2,400 lives per year in the United States, reported lead author Li Sun, MSc, of the London School of Hygiene & Tropical Medicine, and colleagues.

“Moving toward unselected BC testing may give an impetus for prevention in unaffected family members along with clinical implications for the patient with BC. Pathogenic variant carriers with newly diagnosed BC can opt for bilateral mastectomy rather than breast conservation at initial BC surgery,” the investigators wrote in JAMA Oncology. They noted that, presently, only 20%-30% of eligible patients are actually tested. “Testing all patients with breast cancer at diagnosis can increase testing access and uptake and identify many more pathogenic variant carriers for screening and prevention.”

To see if such a broad roll-out would be economically and medically feasible and beneficial, the investigators performed a modeling study involving 11,836 women with breast cancer, with data drawn from four large databases in the United Kingdom, the United States, and Australia.

The model compared annual costs, number of detected cases of breast cancer and ovarian cancer, and related rates of mortality between standard BRCA testing based on clinical criteria or family history versus high-risk multigene testing (BRCA1/BRCA2/PALB2) for all patients with breast cancer.

Resultant incremental cost-effectiveness ratios (ICERs) showed that in both the United Kingdom and the United States, multigene testing would cost, on average, significantly less than minimum willingness-to-pay thresholds of £30,000 per quality-adjusted life-year (QALY) and $100,000/QALY, respectively. In the United Kingdom, the estimated cost of multigene testing was £10,464/QALY from a payer’s perspective and £7,216/QALY from a societal perspective, the latter of which incorporates economic costs beyond the health care system. In the United States, these values rose to $65,661/QALY (payer perspective) and $61,618/QALY (societal perspective). Probabilistic sensitivity analysis suggested that multigene testing would be cost-effective for almost all health system simulations in the United Kingdom (98%-99%) and approximately two-thirds of those in the United States (64%-68%).

Epidemiologically, in the United Kingdom, multigene testing could potentially prevent 2,101 cases of breast cancer and ovarian cancer and 633 deaths per year, while in the United States, 9,733 cases might be prevented, with 2,406 lives saved.

“Our analysis suggests that an unselected testing strategy is extremely cost-effective for U.K. and U.S. health systems and provides a basis for change in current guidelines and policy to implement this strategy,” the investigators said.

The study was funded by the National Cancer Institute, the State of Washington, the Fred Hutchinson Cancer Research Center, and others. The investigators reported additional relationships with AstraZeneca, the Manchester National Institute for Health Research Biomedical Research Centre, Cancer Research UK, an others.

SOURCE: Sun et al. JAMA Oncol. 2019 Oct 3. doi: 10.1001/jamaoncol.2019.3323.

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