Adding chemo to endocrine therapy may benefit premenopausal women with early breast cancer

Roshini Claire Anthony
25 Jan 2021

The addition of chemotherapy to endocrine therapy improved invasive disease-free survival (IDFS) in premenopausal women with lymph node-positive early stage hormone receptor-positive (HR+) HER2-negative (HER2-) breast cancer with recurrence score 25, according to early results of the phase III SWOG S1007 RxPonder* trial presented at SABCS 2020. However, the benefits did not appear to extend to postmenopausal women.

“At the time of this analysis, our data show that postmenopausal women with HR+, HER2- breast cancer with 1–3 positive nodes and a recurrence score of 25 can safely avoid receiving adjuvant chemotherapy. On the other hand, premenopausal patients with HR+, HER2- breast cancer with 1–3 positive nodes and a recurrence score of 25 should consider adjuvant chemotherapy. The IDFS rate improved by 5 percent with chemotherapy in this group,” said first author Dr Kevin Kalinsky, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, Atlanta, Georgia, US.

A total of 5,083 women aged 18 years with HR+, HER2- stage 2–3 breast cancer with 1–3 positive nodes and recurrence score 25 were randomized 1:1 to receive standard endocrine therapy alone or in addition to chemotherapy (chemo-endocrine therapy). They were followed up for a median 5.1 years, during which time 447 IDFS events were observed.

Higher continuous recurrence score was tied to poorer IDFS (hazard ratio [HR], 1.06, 95 percent confidence interval [CI], 1.04–1.07; p<0.001). In contrast, receipt of chemotherapy was associated with improved IDFS (HR, 0.81, 95 percent CI, 0.67–0.98; p=0.026). [SABCS 2020, abstract GS3-00]

There was no apparent association between chemotherapy benefit and recurrence score in the overall population. However, a prespecified analysis suggested that the addition of chemotherapy had different outcomes based on menopausal status (p=0.004).

After adjusting for continuous recurrence score, the addition of chemotherapy to endocrine therapy significantly improved IDFS in premenopausal patients compared with endocrine therapy alone (n=1,665; HR, 0.54, 95 percent CI, 0.38–0.76; p=0.0004; 5-year IDFS: 94.2 percent vs 89.0 percent).

Conversely, chemo-endocrine therapy did not confer an IDFS benefit compared with endocrine therapy alone in the 3,350 postmenopausal women (HR, 0.97, 95 percent CI, 0.78–1.22; p=0.82), with a comparable rate of IDFS at 5 years (91.6 percent vs 91.9 percent).

Overall survival (OS) data was immature but showed a trend toward improvement in premenopausal patients (HR, 0.47, 95 percent CI, 0.24–0.94; p=0.032).

Ovarian suppression was performed in 3.7 and 15.9 percent of premenopausal patients who received chemo-endocrine and endocrine therapy, respectively, with 26.4 and 47.9 percent, respectively, reporting resumption of menstruation after 6 months of treatment.

“To what extent the chemotherapy benefit observed in our trial is due to chemotherapy-induced menopause remains unknown,” Kalinsky pointed out.

“[All in all,] the current data show that adjuvant therapy can be de-escalated to endocrine therapy alone in postmenopausal patients with a recurrence score 25 and 1–3 positive lymph nodes,” said Kalinsky and co-authors. “However, there is a strong IDFS benefit for chemo-endocrine therapy in premenopausal patients, with an early indication of an OS improvement,” they said.

They noted that these findings represent early outcomes, as patients will continue to be followed up for 15 years.

 

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