Gene Signature ID’s Breast Cancer Patients Who Could Skip Chemotherapy

A 70-gene expression score can identify women with indolent breast cancer at “ultralow” risk, according to a new study. Women with such a score have extremely low risk of disease-specific mortality over 20 years without systemic therapy.

Breast cancer screening has increased detection of cancers. “The bulk of the increase has been in early-stage tumors (stage 0, I), suggesting that screening contributes disproportionately to the diagnosis of biologically more indolent forms of breast cancer,” wrote study authors led by Laura J. Esserman, MD, MBA, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. “While screening is associated with a relative mortality reduction of 20%, it has increased the diagnosis of low-risk lesions and contributes to overtreatment.”

The new study was a secondary analysis of the STO-3 trial, which included postmenopausal women with clinically detected node-negative breast cancer treated with mastectomy or lumpectomy and radiation; they were then treated with either two years of tamoxifen or no systemic therapy. This analysis included 652 women with results from the MammaPrint 70-gene expression assay; results were published online ahead of print in JAMA Oncology.

Of the full cohort, 377 women (58%) were MammaPrint low risk, 275 women (42%) were high risk, and 98 women (15%) were ultralow risk. The ultralow-risk patients had better breast cancer–specific survival than both the low- and high-risk patients (log rank P < .001).

In ultralow-risk patients who received tamoxifen, there were no breast cancer–specific deaths at 15 years, and breast cancer–specific survival at 20 years was 97%. Patients without any systemic therapy had a 97% breast cancer–specific survival rate at 10 years, and 94% at 20 years.

A multivariate analysis found that patients with high-risk MammaPrint scores had a long-term risk of breast cancer–specific death of 4.73 (95% CI, 1.38–16.22) compared with ultralow-risk tumors. Those with low-risk-but not ultralow-risk-tumors also had an increased risk of breast cancer–specific death, of 4.54 (95% CI, 1.40–14.80), compared with ultralow-risk tumors.

“The ultralow-risk threshold of the 70-gene signature, in postmenopausal women with node-negative tumors 3 cm or smaller, reliably identifies women with minimal risk of death from breast cancer out to 20 years in the absence of any systemic therapy and negligible risk of death with 2 or more years of tamoxifen therapy alone,” the authors concluded.

They noted that the frequency of ultralow-risk cancers in a screened population of postmenopausal women is likely in the range of 25%. “Such tools, if integrated into screening, treatment, and trials, can prevent inadvertent overtreatment and enable excellent outcomes with less toxic effects.”