Sparing breast cancer patients chemotherapy

More women who are diagnosed with breast cancer may be spared chemotherapy, based on a somatic gene expression panel that has now been proven to identify women at low risk of recurrence. The study was published in September 2015 in the New England Journal of Medicine. In the international clinical trial, 10,253 women diagnosed with hormone receptor–positive, HER2-negative cancer that had not spread to lymph nodes had their tumor tested for an expression panel of 21 genes. After assessing the expression level of each gene, the test returns a score between 0 and 100. The lower the score, the lower the chance the cancer will recur. In the trial, 15.9% of the women had a multigene test score of 10 or lower and received standard hormone therapy such as tamoxifen but did not undergo chemotherapy. An additional 68% of patients scored 11 to 25. These women were randomly assigned to receive either hormone therapy plus chemotherapy or hormone therapy alone. Continued follow-up will be needed to determine whether women in the group with mid-range scores can also safely forgo chemotherapy. However, after five years, less than 2% of the patients in this group had had a recurrence. The five-year overall patient survival was 98%. These findings, the researchers concluded, provide the highest level of evidence yet that a multigene expression panel can spare the use of chemotherapy in women with low-scoring tumors. —Karyn Hede, News Editor

Genomics of menopause

We have now tripled the number of genes known to be associated with the age a woman undergoes menopause, thanks to a new large-scale genomic analysis published in Nature Genetics. In European populations, menopause occurs on average at age 51 but can vary by a decade or more in either direction. Risk of infertility and development of diseases such as breast cancer have been known to be associated with the timing of natural menopause, but little information has been available about how genetics affects both menopause timing and subsequent disease risk. Previous genome-wide association studies identified gene variants that explained only a tiny fraction of the natural variation in age of menopause. The new study included low-frequency coding variants that produced substantially more significant associations. These include links between reproductive aging and hypothalamic signaling, as well as DNA repair. The research team studied 70,000 women to identify common gene variants and identified 44 regions, including two regions with rare missense alleles that have a large effect: DNA helicase B (encoded by HELB), a DNA helicase that unwinds DNA during replication, transcription, repair and recombination, and SLCO4A1 (solute carrier organic anion transporter family, member 4A1), which transports organic molecules such as thyroid hormones. Pathway analyses identified DNA damage-response genes, including the first common coding variant in BRCA1 associated with any complex trait. Taken together, the findings implicate a relatively narrow set of pathways, with a large role for major known forms of DNA repair, determining the age of menopause. —Karyn Hede, News Editor