After a median follow-up of 5.1 years, among women with lymph node-positive early-stage breast cancer and a recurrence score of 25 or lower who received adjuvant endocrine therapy with or without chemotherapy, postmenopausal patients had no added benefit from chemotherapy, while premenopausal patients who received chemotherapy had improved invasive disease-free survival (IDFS) and an early indication of improved overall survival (OS), according to data from the SWOG S1007 RxPONDER clinical trial presented at the 2020 San Antonio Breast Cancer Symposium, held Dec. 8-11.
The most common form of breast cancer is hormone receptor (HR)-positive and HER2-negative, comprising about two-thirds of all invasive breast cancers."
Kevin Kalinsky, MD, MS, Director of the Glenn Family Breast Center, Winship Cancer Institute of Emory University
RxPONDER was designed and run by SWOG Cancer Research Network with support from the National Cancer Institute. It set out to determine which patients with HR-positive, HER2-negative breast cancer and one to three positive axillary lymph nodes benefit from chemotherapy and which patients could safely avoid chemotherapy and still achieve similar outcomes with endocrine therapy alone, Kalinsky said. "Up until now, there were no data from a large randomized clinical trial to guide this decision," he added.
"At the time of this analysis, our data show that postmenopausal women with HR-positive, HER2-negative breast cancer with one to three positive nodes and a recurrence score of 25 or lower can safely avoid receiving adjuvant chemotherapy. On the other hand, premenopausal patients with HR-positive, HER2-negative breast cancer with one to three positive nodes and a recurrence score of 25 or lower should consider adjuvant chemotherapy. The invasive disease-free survival rate improved by 5 percent with chemotherapy in this group," Kalinsky said.
In this clinical trial, 5,083 patients with stage 2-3 breast cancer involving one to three axillary lymph nodes and whose tissue had a recurrence score of 25 or lower were randomly assigned (1:1) to endocrine therapy alone or endocrine therapy plus chemotherapy. Roughly two-thirds of the patients were postmenopausal. Data were stratified by recurrence score (0-13 versus 14-25), menopausal status, and axillary nodal dissection versus sentinel node biopsy.
The recurrence score, which can range from zero to 100, was determined using the Oncotype Dx test. The test provides a genome-based individualized risk assessment (by evaluating 16 cancer-related genes) for early-stage invasive breast cancer.
The study was designed to assess whether the difference in IDFS for patients treated with chemotherapy, compared with no chemotherapy, was related to the recurrence score. The investigators found no association between chemotherapy benefit and recurrence score values between 0-25 when evaluating the entire study population including both premenopausal and postmenopausal women.
However, there was a significant association between chemotherapy benefit and menopausal status, triggering further analyses of the data by menopausal status.n postmenopausal patients with recurrence scores of 25 or lower, there was no difference in the five-year IDFS between those who received chemotherapy and those who did not (91.6 percent vs. 91.9 percent, respectively).
In premenopausal patients with recurrence scores of 25 or lower, five-year IDFS was 94.2 percent for those who received chemotherapy, versus 89 percent for those who did not receive chemotherapy. Data also showed a 53 percent OS benefit in premenopausal patients, although this result is considered early due to the limited number of events at the time of evaluation. The results were similar in premenopausal women with recurrence scores 0-13 and those with recurrence scores 14-25.
"For premenopausal patients with node-positive breast cancer, we know from other studies that the most effective adjuvant endocrine therapy is ovarian suppression combined with an aromatase inhibitor. We also know that chemotherapy induces ovarian suppression that is often permanent in premenopausal women," explained Kalinsky.
Among the premenopausal women in this study, ovarian suppression was performed in 15.9 percent of those in the endocrine therapy alone arm, versus in 3.7 percent of those in the chemotherapy plus endocrine therapy arm. "To what extent the chemotherapy benefit observed in our trial is due to chemotherapy-induced menopause remains unknown," Kalinsky noted.
"We are reporting these data at 53.7 percent of expected IDFS events. We will continue to report updates from this study as more follow-up data are collected," he said.
Limitations of the study include that these data represent an interim analysis. Future studies will allow for additional subset data analyses and time for continued follow-up, Kalinsky said.