Comprehensive genome screening may not play as big a role in whether or not patients with advanced cancers actually act on available therapy or information about relevant clinical trials, according to a study by Cleveland Clinic researchers presented at the 2020 American Association for Cancer Research Virtual Meeting II (Abstract 4638).
The investigators conducted a retrospective cohort study to evaluate the clinical benefit of therapy associations identified by FoundationOne (FO) testing, one of the most widely used comprehensive genome profiling (CGP) assays for cancer variants.
FoundationOne offers a list of clinically relevant genomic alterations and cancer biomarkers, a list of related clinical trials, as well as on-label and off-label therapies that might benefit the patient.
They discovered that for 85 percent of patients, FO screening data did not result in any therapeutic action. Even so, the researchers also reported that the data indicated that application of FO therapy associations was not correlated with a statistically significant difference in overall survival (OS), said the authors, led by Alex Milinovich, MD, Director of Research at Cleveland Clinic Taussig Cancer Center.
"In the pan-cancer analysis, we found no statistically significant difference in OS among the therapy groups or any of the adjusted covariates except for metastasis status. Similarly, when evaluating the top cancer diagnoses individually, we found no significant differences in OS."
The investigators collected demographics, therapy records, and clinical outcomes for 1,004 patients with a history of advanced cancer who had received a FO report between 2012 and 2017. Patients were 55 percent male, 85 percent white, 92 percent non-Hispanic, and had a median age of 60 years when they underwent FO screening results. The most common diagnoses were lung adenocarcinoma (14%), glioblastoma (8%), colon adenocarcinoma (8%), and breast cancer (4%).
Therapy was considered applied if a patient received an order for therapy for the first time after their FO report, and patients were classified as the following: No Associated Therapy (NAT) if the patient did not receive any recommendations, Therapy Applied (TA) if at least one associated therapy was ordered after report date, and Therapy Not Applied (TNA) if none of the associated therapies were pursued.
Fully 64 percent of patients were classified as TNA and 21 percent were NAT, while only 15 percent fell into the TA category. There was no statistical significance in demographic distribution between the categories.
"This suggests that larger studies should be performed to better understand how CGP services provide clinical benefits to patients, and how we can maximize these benefits in the real-world community setting."
Genetic Risk & Race
In another paper, researchers reported that polygenic risk screening for breast cancer mutations is applicable for women of African ancestry, even though the group is significantly underrepresented in risk studies used in developing screening tools (Abstract 2320).
Investigators evaluated whether 313 common breast cancer variants developed by the Breast Cancer Association Consortium (BCAC), most of which were identified in women of European ancestry, applied to Black women as well. They also evaluated polygenic risk score (PRS) that included 179 variants reaching genome-wide significance in previous genome-wide association studies in women of African ancestry.
The researchers also collected genotype data for women of African ancestry from 28 breast cancer studies, including a total of 9,241 cases and 10,193 controls. They constructed the 179-variant and 313-variant PRSs with relative risk weights for each variant as estimated in women of European ancestry by the BCAC risk dataset.
The associations between the two PRSs and overall ER+ and ER- breast cancer risk were estimated using logistic regression adjusting for age, study site, and principal components.
Both the PRSs were found to be significantly associated with overall ER+ and ER- breast cancer risk, with a standard deviation of 1.21-1.37, reported Zhaohui Du, PhD, with the Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine at the University of Southern California, Los Angeles.
The 179-variant PRS outperformed in ER- cancer (1.31), while the 313-SNP PRS was better for overall (1.27) and ER+ cancer (1.37). Compared to women with average risk (40-60th PRS percentiles), women in the top 10 percent of PRS had a 1.54-fold increased risk.
"Our study shows that both 179 and 313 variant PRS stratify breast cancer risk in women of African ancestry, with attenuated performance compared to that reported in European and in Latina populations. Future work is needed to improve breast cancer risk stratification for women of African ancestry," the researchers concluded.
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