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Association of Adjuvant Endocrine Therapy With Overall Survival in Small HR-Positive, HER2-Negative Breast Cancer


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In a National Cancer Database cohort study reported in a research letter in JAMA Network Open, Ma et al found that receipt vs no receipt of adjuvant endocrine therapy was associated with improved overall survival in women with small hormone receptor (HR)-positive, HER2-negative breast cancers.

As stated by the investigators, “With routine screening mammography, nearly one in five breast cancer cases are invasive tumors smaller than 1 cm. However, for HR-positive, HER2-negative, node-negative breast cancer, pT1a tumors (ie, tumors measuring more than 0.1 cm but not more than 0.5 cm in greatest dimension) were underrepresented in prior prospective trials, ranging from 6% to 13% of participants in prior trials. In the absence of strong prospective evidence, the National Comprehensive Cancer Network® [NCCN®] recommends consideration of adjuvant endocrine therapy for patients with pT1aN0 breast cancer without the routine use of multigene assay. Thus, we sought to examine the association of overall survival with endocrine therapy in this cohort of patients.”

Study Details

The study involved data from the National Cancer Database on women diagnosed with HR-positive, HER2-negative pT1aN0 breast cancer between January 2010 and December 2015 who were treated with or without adjuvant endocrine therapy. Follow-up occurred through December 2016.

Key Findings

KEY POINTS

  • On multivariate analysis adjusting for multiple factors, receipt vs no receipt of adjuvant endocrine therapy was associated with significantly improved overall survival.
  • In analysis of 7,544 matched pairs of patients receiving vs not receiving endocrine therapy, receipt of endocrine therapy was associated with significantly improved overall survival.

A total of 42,708 patients (86.6% white; median age = 63 years) were included in the analysis. Of these, 31,509 patients (73.8%) received and 11,199 (26.2%) did not receive adjuvant endocrine therapy. Median follow-up was 42.1 months.

On multivariate analysis adjusting for facility type, facility volume, age, race, income, insurance, Charlson/Deyo comorbidity score, year of diagnosis, surgery, radiation, number of lymph nodes examined, and hospital readmission, receipt vs no receipt of adjuvant endocrine therapy was associated with significantly improved overall survival, with a hazard ratio (HR) of 0.69 (95% confidence interval [CI] = 0.63–0.76; P < .001).

In analysis of 7,544 matched pairs of patients receiving vs not receiving endocrine therapy, receipt of endocrine therapy was associated with significantly improved overall survival (HR = 0.76, 95% CI = 0.66–0.88; P < .001). No significant interactions of endocrine therapy with baseline characteristics including age, comorbidity score, or tumor grade were observed. In analysis excluding 1,659 patients (3.9%) with survival of less than 6 months, receipt of endocrine therapy remained associated with improved overall survival (HR = 0.74, 95% CI = 0.67–0.81; P < .001).

The 11,199 patients who did not receive adjuvant endocrine therapy included 3,942 (31.2%) who refused clinician-recommended treatment. Compared with these patients, receipt of endocrine therapy was associated with improved overall survival (HR = 0.80, 95% CI = 0.69–0.94; P = .007).

The investigators stated: “To our knowledge, this is the largest cohort study to evaluate the overall survival outcome of endocrine therapy for pT1aN0 breast cancer using a national registry database. The survival benefit identified in our study supports the NCCN’s recommendation of adjuvant endocrine therapy in this cohort and is consistent with favorable outcomes previously described. However, the benefit of adjuvant endocrine therapy should be weighed against potential long-term toxic effects in select patients. The risk of relapse from very small tumors remains significant enough to warrant adjuvant therapy. Our study further affirms clinicians’ decisions to recommend adjuvant endocrine therapy in this cohort of patients.”

Anurag K. Singh, MD, of the Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, is the corresponding author for the JAMA Network Open article.

Disclosure: For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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