Postmenopausal Women with HR+/HER2– Early Breast Cancer, 1–3 Positive Nodes, and a Low Risk of Recurrence Can Safely Forego Chemotherapy

Short abstract

Postmenopausal women with hormone receptor‐positive, HER2‐negative, early breast cancer involving 1–3 lymph nodes who are undergoing endocrine therapy and have an Oncotype DX recurrence score of 0–25 can safely avoid chemotherapy, according to findings from the phase III RxPonder study.

The 21‐gene Oncotype DX recurrence score has been used to identify which women with node‐negative, hormone receptor (HR)‐positive, human epidermal growth factor receptor 2 (HER2)‐negative early breast cancer can safely forgo chemotherapy without increasing the risk of recurrence. The phase III TAILORx trial showed that women aged >50 years with node‐negative breast cancer and an Oncotype DX risk score of 0–25 derived no benefit from chemotherapy [1].

To date, it is unclear whether findings from the TAILORx trial can be extrapolated to patients with node‐positive breast cancer. The phase III Southwest Oncology Group (SWOG) S1007 RxPonder trial was designed to evaluate the benefit of chemotherapy added to standard adjuvant endocrine therapy in women with node‐positive, HR‐positive, HER2‐negative early breast cancer with an Oncotype DX recurrence score of 0–25.

Kevin Kalinsky, M.D., of Emory University, presented results from the interim analysis of the ongoing RxPonder trial [2].

Study Design

The SWOG S1077 RxPonder trial enrolled 5,015 patients with HR‐positive, HER2‐negative, stage 2–3, breast cancer involving 1–3 axillary lymph nodes and no distant metastasis. Eligible patients had an Oncotype DX recurrence score of 0–25, indicating a low risk of recurrence. Patients were randomly assigned to receive chemotherapy plus standard adjuvant endocrine therapy (n = 2,547) or endocrine therapy alone (n = 2,536).

Baseline characteristics were similar in both treatment groups. One‐third of patients (33.2%) were premenopausal and two‐thirds (66.8%) were postmenopausal. Most patients (65.5%) had one positive lymph node; 25.3% had two positive nodes, and 9.2% had three positive nodes.

The primary endpoint is invasive disease‐free survival (IDFS). The median follow‐up of the current interim analysis is 5.1 years.

Key Findings

Compared with endocrine therapy alone, the addition of chemotherapy increased 5‐year IDFS by 19% in the overall study population (91.0% vs. 92.4%; p = .026). However, when evaluated by menopausal status, the benefit persisted only for premenopausal women (Table 1).

Table 1.

Invasive disease‐free survival by adjuvant therapy regimen and menopausal status

5‐year IDFS	Chemotherapy plus ET (n = 2,509)	ET alone (n = 2,506)	HR (95% CI)	p value
All patients	92.4%	91.0%	0.81 (0.67–0.98)	.026
Postmenopausal	91.9%	91.6%	0.97 (0.78–1.22)	.82
Premenopausal	94.2%	89.0%	0.54 (0.38–0.76)	.0004

Abbreviations: CI, confidence interval; ET, endocrine therapy; HR, hazard ratio; IDFS, invasive disease‐free survival.

Among premenopausal women, the 5‐year IDFS was 94.2% with chemotherapy plus endocrine therapy and 89.0% with endocrine therapy alone (p = .0004). This represents a 46% reduction of the risk of an IDFS event for premenopausal women with the addition of chemotherapy to endocrine therapy.

In contrast, among postmenopausal women, there was no benefit to adding chemotherapy to endocrine therapy. The 5‐year IDFS rates were 91.9% vs. 91.6% with and without chemotherapy, respectively, for postmenopausal women with a low risk of recurrence (p = .82).

The analysis of overall survival (OS) showed a similar pattern, with chemotherapy improving OS only among premenopausal women. In this group, the 5‐year OS rates were 98.6% and 97.3% with and without chemotherapy, respectively, translating to a 53% decrease in the risk of death with the addition of chemotherapy to endocrine therapy (HR, 0.47; 95% CI, 0.24–0.94; p = .032).

By comparison, postmenopausal women experienced no survival benefit from chemotherapy. The 5‐year OS rates were 96.2% and 96.1% with and without chemotherapy, respectively (p = .79).

According to the RxPonder investigators, these findings indicate that postmenopausal women with 1–3 positive lymph nodes and an Oncotype DX recurrence score of 0–25 can safely forgo adjuvant chemotherapy without compromising IDFS. By comparison, premenopausal women with 1–3 positive notes and an Oncotype DX recurrence score of 0–25 are likely to benefit from chemotherapy added to standard adjuvant endocrine therapy.