Summary

Gene Panel Sequencing and the Prediction of Breast Cancer Risk.

Authors: Easton DF, Pharoah P, Antoniou AC, et al.

Source: NEJM 2015; 372 (23):2243-2257.

www.nejm.org/doi/full/10.1056/NEJMsr1501341

A recent New England Journal of Medicine article has reviewed the most up to date risk estimates for breast cancer for other genes “beyond” BRCA. There are now 11 companies offering genetic testing for breast cancer and many offer “panel testing” in which up to 100 genes can be tested. In this study, the authors go through the relative risks of breast cancer associated with some of these genes and explain some shortcomings to “panel testing”. The authors define moderate risk as conferring 2-3 times relative risk or about an 18% lifetime risk. High risk is defined as greater than a 4 times relative risk or 32% lifetime risk. BRCA 1 and 2 confer an 11 times relative risk and TP53 confers a 105 times relative risk and therefore both of these genes fall into a high-risk category. CDH1 and PALB2 carry a 5-6 times relative risk and also fall into a high-risk category. ;NF1, CHEK2, ATM and NBN confer only a 2-3 times relative risk and would fall into a moderate risk category. There is insufficient data for the genes PTEN and STK11 to place them into a high-risk category and they likely carry risks closer to the moderate category. RAD51C, RAD51D, and BRIP1 have been associated with ovarian cancer risk but association with breast cancer is limited.

Despite these data these risk estimates may not be entirely accurate. Risk estimates may decline with age, and many studies do not contain older age patients. Some risk estimates may be overestimates since these studies were restricted to certain populations in certain regions of the world and may not reflect the general population. Indeed, most of these studies are on patients of European ancestry. Additionally, there are other lifestyle or environmental factors that could influence the true risk a gene confers that were not tracked in these studies. Moreover, different types of gene variants can lead to different risk estimates for each gene.

The authors explicitly state that there is insufficient evidence for any other genes besides the ones mentioned in this study. Future studies that systematically collect data on patients with these gene mutations are needed to further refine their risk of breast cancer.  Once these studies are completed, more reliable risk estimates will inform changes in the current guidelines for patients with these other gene mutations that are “beyond BRCA 1/2.”