Observational studyBreast cancer research and treatment2026
Defining prognostic subgroups and treatment outcomes in estrogen receptor low-positive de novo metastatic breast cancer.
Observational study in Breast cancer research and treatment, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPrognostic factors and treatment outcomes have been identified in estrogen receptor (ER) low-positive early-stage breast cancer. This study evaluates outcomes in ER low-positive de novo metastatic breast cancer (dnMBC) patients.
methodsWe conducted a retrospective cohort study of adults with human epidermal receptor-2 negative dnMBC diagnosed from 2018 to 2021 in the National Cancer Database. We classified ER status as negative (< 1%), low-positive (1-10%), or positive (11-100%). We compared overall survival by ER status using Cox regression, adjusting for age, metastatic sites, race/ethnicity, comorbidities, insurance, and treatment receipt. We then analyzed the cohort with ER low-positive patients stratified by progesterone receptor (PR) status, defined as negative (< 1%) or positive (1-100%). Among ER low-positive patients, we evaluated survival by first-course treatment. We distinguished cytotoxic chemotherapy from cyclin-dependent kinases 4 and 6 inhibitor (CDK4/6i) therapy based on the timing of endocrine therapy and chemotherapy.
resultsAmong 27,672 patients, 3% had ER low-positive dnMBC. ER low-positive/PR-positive patients had longer median (95% CI) survival [19.8 (14.8-24.8) months] compared to both ER low-positive/PR-negative [11.8 (10.6-13.5) months] and ER-negative [12.9 (12.5-13.6) months] patients. ER low-positive/PR-positive patients had decreased risk of death compared to ER-negative patients (hazard ratio = 0.84, 95% CI 0.71-1.00), while ER low-positive/PR-negative patients did not. ER low-positive dnMBC patients who received chemotherapy followed by endocrine therapy (± CDK4/6i) or endocrine therapy + CDK4/6i had improved or similar survival compared to patients who received chemotherapy alone.
conclusionsPR-positivity identifies a subgroup of ER low-positive dnMBC patients with superior survival compared to ER-negative patients. First-line treatment incorporating endocrine therapy may be appropriate to consider for ER low-positive patients.
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