Genomic Assays Aid Individualized Treatment Decision-Making for HR–Positive, HER2–Negative Breast Cancer

Greater reliance on genomic assays has reduced the use of adjuvant chemotherapy in women with early-stage, hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer who are free of axillary node disease and at low genomic risk, according to a recent editorial by Keerthi Gogineni, MD, MSHP and Kevin Kalinsky, MD, MS, Department of Hematology and Medical Oncology, Emory School of Medicine, Atlanta, GA (JCO Oncol Practice. 2022; doi:10.1200/OP.21.00780). 

Multigene assays are able to identify patients with this type of node-negative breast cancer who have a favorable genomic risk. In particular, the 21-gene recurrence score (RS) obtained from the Oncotype DX test (Exact Sciences, Madison, WI) has been shown to identify women at high risk of distant recurrence who benefit from adjuvant chemotherapy while enabling those unlikely to benefit from chemotherapy to avoid this treatment and its toxicity.

Nevertheless, approximately one-third of women with HR–positive, HER2–negative breast cancer have node-positive disease, and increasing evidence indicates that genomic assays are useful in making treatment decisions for these patients as well.  

For example, consider the results of the Plan B study of 1008 women with node–positive breast cancer, in which women with an RS <12 received endocrine therapy alone and those with an RS ≥12 received chemotherapy. This trial found that 5-year distant DFS was an impressive 94.4% for patients with 1 to 3 positive axillary nodes and an RS <12 who therefore received endocrine therapy alone.

In addition, the Southwest Oncology Group (SWOG) 8814 trial found that an RS of at least 31 identified postmenopausal patients with node-positive breast cancer who would benefit from anthracycline-based chemotherapy before receiving tamoxifen. Patients who received this combination treatment had better disease-free survival (DFS) and overall survival during the first 5 years after diagnosis than those who received tamoxifen alone.

Results of the Rx for Positive Node, Endocrine Responsive Breast Cancer (RxPONDER) trial (SWOG S1007) have further confirmed the value of the RS in formulating a treatment strategy for patients with early (N1) breast cancer that is HR positive, HER2 negative, and node positive. In this trial, women with 1 to 3 positive nodes and an RS ≤25 were randomized either to chemotherapy followed by endocrine therapy or to endocrine therapy alone. During a median follow-up of 5.3 years, the rate of invasive DFS was 92.2% for sequential therapy vs. 91% for endocrine therapy alone (hazard ratio [HR], 0.86; 95% CI, 0.72 to 1.03; log-rank P = .1) in the intention-to-treat population (n = 5083). Moreover, after adjustment for chemotherapy and menopausal status, a lower RS was associated with greater invasive DFS. 

Nevertheless, a lower RS was not associated with fewer benefits from chemotherapy. Instead, the benefits of chemotherapy were found to depend on menopausal status. Prespecified analysis found no difference between treatment arms in invasive DFS for postmenopausal women. However, for premenopausal women, a 5% absolute improvement in 5-year invasive DFS was found for chemotherapy followed by endocrine therapy compared with endocrine therapy alone (HR, 0.6; 95% CI, 0.43 to 0.83; P = .002). “Premenopausal women with HR-positive N1 disease with an RS of <26 derive significant benefit from adjuvant chemotherapy,” Dr Gogineni and colleagues concluded.