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. 2020 Jul 1;112(7):728-736.
doi: 10.1093/jnci/djz206.

Borderline Estrogen Receptor-Positive Breast Cancers in Black and White Women

Halei C Benefield  1 , Emma H Allott  2 , Katherine E Reeder-Hayes  3 , Charles M Perou, Lisa A Carey, Joseph Geradts  4 , Xuezheng Sun  1 , Benjamin C Calhoun  5   3   6 , Melissa A Troester  1
Affiliations

Borderline Estrogen Receptor-Positive Breast Cancers in Black and White Women

Halei C Benefield et al. J Natl Cancer Inst. .

Abstract

Background: Some breast tumors expressing greater than 1% and less than 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 I: 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 = 1885) 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% confidence interval [CI] = 27.1% to 48.4%) and high ROR-PT (RFD = +52.4%, 95% CI = 36.8% to 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% to 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% to 4.65%), whereas DFI was statistically significantly worse for ER-borderlines without endocrine therapy (HR = 3.33, 95% CI = 1.84% to 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% to 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.

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Figures

Figure 1.
Figure 1.
Intrinsic subtype distribution by estrogen receptor (ER) category in Carolina Breast Cancer Study phases I, II, and III. ER-negatives and ER-borderlines had a statistically significantly higher frequency of HER2-enriched (17.7% ER-negative, relative frequency difference [RFD] = +67.5%, 95% confidence interval [CI] = 58.6 to 76.4, P < .001; 14.3% ER-borderline, RFD = +27.2%, 95% CI = 12.2 to 42.2, P <.001; two-sided χ2 test) and basal-like subtypes (71.7% ER-negative, RFD = +80.3%, 95% CI = 76.1 to 84.4, P <.001; 41.8% ER-borderline, RFD = +37.7%, 95% CI = 27.1 to 48.4, P <.001; two-sided χ2 test) relative to ER-positive (2.7% HER2-enriched, 5.1% basal-like).
Figure 2.
Figure 2.
Kaplan-Meier disease-free interval (DFI) curves among HER2-negative case patients by estrogen receptor (ER) category in Carolina Breast Cancer Study phase III. Included ER-positive case patients who received endocrine therapy (ET) and ER-negative case patients who did not receive ET. Pairwise two-sided log-rank tests were performed with Bonferroni correction for multiple comparisons. ER-negative and ER-positive case patients had statistically significantly different DFI (P < .001). Similarly, ER-borderline case patients not receiving endocrine therapy and ER-positive case patients had statistically significantly different DFI (P < .001). All other pairwise comparisons were not statistically significant.
Figure 3.
Figure 3.
Kaplan-Meier disease-free interval (DFI) curves among HER2-negative white women by estrogen receptor (ER) category in Carolina Breast Cancer Study phase III. Included ER-positive case patients who received endocrine therapy (ET) and ER-negative case patients who did not receive ET. Pairwise two-sided log-rank tests were performed with Bonferroni correction for multiple comparisons. ER-negative and ER-positive case patients had statistically significantly different DFI (P < .001). All other pairwise comparisons were not statistically significant.
Figure 4.
Figure 4.
Kaplan-Meier disease-free interval (DFI) curves among HER2-negative black women by estrogen receptor (ER) category in Carolina Breast Cancer Study phase III. Included ER-positive case patients who received endocrine therapy (ET) and ER-negative case patients who did not receive ET. Pairwise two-sided log-rank tests were performed with Bonferroni correction for multiple comparisons. ER-negative and ER-positive case patients had statistically significantly different DFI (P < .001). All other pairwise comparisons were not statistically significant.
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