ABSTRACT

PURPOSE Adjuvant endocrine therapy (ET) improves overall survival (OS) in estrogen receptor (ER)–positive early-stage breast cancer (BC). However, the benefit of ET for those with ER-low BC (ER 1%-10%) is unclear.
METHODS Using the National Cancer Database, we studied patients with high-risk stage I to III, ER-low BC (defined as immunohistochemistry 1%-10%) who received (neo)adjuvant chemotherapy and did or did not initiate ET. OS was analyzed with ET initiation as a time-dependent covariate using Cox proportional hazards regression.

RESULTS Of 10,362 patients with stage I to III ER-low BC, 7,018 received chemotherapy and met inclusion criteria. ET omission was 42% at 12 months and more common in patients with tumors that were progesterone receptor–negative, human epidermal growth factor receptor 2–negative, higher-grade (grade 2/3) and higher Ki-67 (≥20%; all P < .001) and those who received neoadjuvant chemotherapy (NAC; P < .001). With a median follow-up of 3 years, 586 deaths were observed. In a multivariable analysis, ET omission was associated with a higher risk of death (hazard ratio [HR], 1.23 [95% CI, 1.04 to 1.46]; P 5 .02), with a greater impact in those with higher ER levels: ER 1%-5% (HR, 1.15 [95% CI, 0.91 to 1.45]; P 5 .24) versus ER 6%-10% (HR, 1.42 [95% CI, 1.00 to 2.02]; P 5 .048). Among patients treated with NAC (n 5 4,377, 62%), ET omission was associated with worse OS in those with residual disease (RD; HR, 1.26 [95% CI, 1.00 to 1.57]; P 5 .046) but not in those who achieved a pathologic complete response (HR, 1.06 [95% CI, 0.62 to 1.80]; P 5 .84).

CONCLUSION In ER-low, early-stage BC, ET omission is associated with significantly worse OS, especially in patients with RD after NAC and those with higher (6%-10%) ER levels. Until prospective data are available, patients w Name: Grace M. Choong, MD1 ; Tanya L. Hoskin, MS2 ; Judy C. Boughey, MD3 ; James N. Ingle, MD1 ; and Matthew P. Goetz, MD1