Study: expanded genetic testing for all breast cancer patients is cost-effective

Payers are the last gatekeeper between patients and tests used in oncology, but a new analysis suggests that it is cost effective to genetically test all breast cancer patients for a variety of genetic markers, rather than limit such testing to those with a family history of the disease. Researchers from the U.S., the U.K., Australia and China had enrolled more than 11,800 women diagnosed with breast cancer between Jan. 1, 2018, and June 1, 2019, into four studies. The first testing strategy (strategy A) called for all breast cancer patients to be tested for both BRCA genes and PALB2 gene testing, while the second strategy (strategy B) provided such testing only for women with a family history of the disease. The analysis used an incremental cost-effectiveness ratio that was based on substantially different standards for a quality-adjusted life year (QALY). That set point for the U.S. patients was $100,000 while the analysis of the U.K. patients assumed a benchmark of £30,000. The results suggested that the full panel of tests for all breast cancer patients would cost £10,464 (US$11,670) per QALY from a payer perspective and a mere £7,216 per QALY from a societal perspective. For the U.S. data, the payer perspective QALY cost was slightly more than $65,600 while the societal-perspective QALY cost was roughly $61,600. The authors pointed out that both returns fall easily within the respective cost-effectiveness thresholds. They also noted that one year’s testing in the U.K. could prevent more than 2,100 cases of breast and ovarian cancer per year and save 633 lives, while more than 9,700 cases of breast and ovarian cancer in the U.S. would be prevented along with more than 2,400 fatalities. These findings appear in JAMA Oncology.

Getting, and keeping, antitumor T cells energized

Two separate research teams have reported new insights into the prerequisites for an antitumor T cell response. Natural and CAR T cell immune responses alike can lead to cures of even advanced cancers if they are sufficiently strong. But some tumors do not provoke a T cell response in the first place, while in other cases, T cells mount an initial response that exhausts itself over time. In the Dec. 12, 2019, issue of Nature, researchers from Emory University have described an immune niche within tumors that is critical for a T cell response to form. They identified a population of stem-like T cells directly within tumor niches that also contained antigen-presenting cells. The stem-like cells could retain their stem-like properties while giving rise to mature daughter cells. Those daughter cells had high levels of PD-1 expression, making them prone to shutdown by PD-L1 expressing tumor cells. The authors concluded that “these observations are not well explained by a model of T cell exhaustion whereby continuous antigen exposure leads to accumulation of checkpoint molecules, resulting in a decline of the T cell response.” Instead, they proposed that “stem-like cells require a region within the tumor that resembles the T cell zone of secondary lymphatic tissues, made up of dense areas of antigen-presenting cells. … The scarcity of these niches in tumors that rapidly progress after surgery suggests that tumors may be interfering with the formation or continued maintenance of immune niches and that this may be a novel mechanism of immune evasion requiring further investigation.” The report comes a week after Stanford investigators reported in the Dec. 5, 2019, issue of Nature that overexpression of the transcription factor c-JUN could prevent exhaustion in CAR T cells. “functional deficiency in c-Jun mediates dysfunction in exhausted human T cells, and that engineering CAR T cells to overexpress c-Jun renders them resistant to exhaustion, thereby addressing a major barrier to progress for this emerging class of therapeutic agents.

Cyclin D1 seen as possible predictor of cancer survival

Cyclin D1 has been studied in the context of several cancers, but a new study suggests that this protein is predictive of outcomes for a number of cancers. Researchers in the U.S. and Iran conducted a meta-analysis of eight studies to evaluate the expression of this protein and overall survival in more than 19,000 patients with 10 types of cancer. The pooled analysis suggested that patients with high expression of cyclin D1 were subject to a hazard ratio of 1.1, while a sub-group analysis of head and neck cancers suggested that high cyclin D1 is associated with a hazard ration of greater than 2. However, the difference in breast cancer was too small to reach statistical significance (HR 1.033, P=0.702), which in this analysis appears to be true also of bladder, lung and gastrointestinal cancers. The authors recommended further study to flesh out the relationship. These findings appear in the Dec. 12 online issue of Gene.

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