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Gene recurrence score helps predict successful combination therapy for early breast cancer


 

FROM JAMA ONCOLOGY

Women with early breast cancer and a high genetic risk for recurrence at a distant site achieved greater freedom from recurrence when treated with chemoendocrine therapy than with endocrine therapy alone in a study of 1,389 women with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer.

“The 21-gene recurrence score (RS) assay provides prognostic information for distant recurrence in hormone-receptor–positive, ERBB2-negative early breast cancer that is independent of clinicopathologic features and is also predictive of chemotherapy benefit when the RS is high,” wrote Joseph A. Sparano, MD, of Montefiore Medical Center, New York, and his colleagues. However, little is known about how this risk score applies to women with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer, they said.

In the study published in JAMA Oncology, they identified 1,389 women with a recurrence score of 26-100 (the definition of a high recurrence risk). The average age of the patients was 56 years, and 71% were postmenopausal.

In addition to receiving endocrine therapy, the women were randomized to no chemotherapy (89 patients) or one of several chemotherapy regimens including docetaxel/cyclophosphamide (589 patients), anthracycline without a taxane (334 patients), an anthracycline and taxane (244 patients), cyclophosphamide/methotrexate/5-fluorouracil (52 patients), and other regimens (81 patients). Among those treated with chemotherapy, overall survival (OS) at 5 years was 96% and estimated rates of freedom from recurrence of breast cancer at a distant site, and from a distant and/or local regional site, at 5 years were 93% and 91%, respectively. At 5 years, the estimated rate of invasive disease–free survival (IDFS) was 88%.

When broken down by chemotherapy regimen, 5-year rates of freedom from recurrence of breast cancer at a distant site ranged from 92.3% to 95.5%, except for 88.5% for the cyclophosphamide/methotrexate/5-fluorouracil (CMF) group; the rate was 92.6% for patients in the no-chemotherapy group.

The 5-year rates of IDFS ranged from 84% to 91.3% in the chemotherapy groups, compared with 79.7% in the no-chemotherapy group.

The expected rates of distant recurrence in the overall patient population if treated with endocrine therapy alone was 78.8% at 5 years and 65.4% at 9 years, the researchers said. Rates among the patients with an RS of 26-30 if treated with endocrine therapy alone were 89.6% at 5 years and 80.6% at 9 years; rates for those with an RS of 31-100 were 70.7% and 54% for 5 and 9 years, respectively.

The study findings were limited by several factors including a lack of randomization to endocrine therapy alone and the relatively short follow-up period, the researchers noted. However, strengths include the large sample size and high rate of compliance with chemotherapy.

The results support data from previous studies and “add to the evidence base supporting the use of the 21-gene RS assay to guide the use of adjuvant chemotherapy in patients with hormone receptor–positive, ERBB2-negative, axillary node–negative breast cancer,” they concluded.

The study was supported in part by the National Cancer Institute, the Canadian Cancer Society Research Institute, the Breast Cancer Research Foundation, the Komen Foundation, and the Breast Cancer Research Stamp issued by the United States Postal Service. Dr. Sparano disclosed grants from the National Cancer Institute. Of the remaining authors, several disclosed receiving personal or speaker fees from the assay manufacturer, Genomic Health; one author received funding from the company during the study.

SOURCE: Sparano J et al. JAMA Oncol. 2019 Sep 30. doi: 10.1001/jamaoncol.2019.4794.

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