Borderline estrogen receptor-positive breast cancers in black and white women

BACKGROUND: Some breast tumors expressing ≥1% and <10% estrogen receptor (ER) positivity ("ER-borderline") are clinically aggressive; others exhibit luminal biology. Prior ER-borderline studies included few black participants.

METHODS: Using the Carolina Breast Cancer Study (Phase 1: 1993 - 1996, 2: 1996 - 2001, 3: 2008-2013), a population-based study that oversampled black women, we compared ER-borderline (n = 217) to ER-positive (n = 1,885) and ER-negative (n = 757) tumors. PAM50 subtype and risk of recurrence score (ROR-PT, incorporates subtype, proliferation, tumor size) were measured. Relative frequency differences (RFD) were estimated using multivariable linear regression. Disease-free interval (DFI) was evaluated by ER category and endocrine therapy receipt, overall and by race using Kaplan Meier and Cox models. Statistical tests were two-sided.

RESULTS: ER-borderlines were more frequently Basal-like (RFD = +37.7%, 95% CI = 27.1, 48.4) and high ROR-PT (RFD = +52.4%, 95% CI = 36.8, 68.0) relative to ER-positives. Having a high ROR-PT ER-borderline tumor was statistically significantly associated with black race (RFD = +26.2%, 95% CI = 9.0, 43.3). Compared to ER-positives, DFI of ER-borderlines treated with endocrine therapy was poorer but not statistically significantly different (hazard ratio [HR]=2.03, 95% CI = 0.89, 4.65), whereas DFI was statistically significantly worse for ER-borderlines without endocrine therapy (HR = 3.33, 95% CI = 1.84, 6.02). However, black women with ER-borderline had worse DFI compared to ER-positives, even when treated with endocrine therapy (HR = 2.77, 95% CI = 1.09, 7.04).

CONCLUSIONS: ER-borderline tumors were genomically heterogeneous with survival outcomes that differed by endocrine therapy receipt and race. Black race predicted high-risk ER-borderlines and may be associated with poorer endocrine therapy response.