Impact of low estrogen/progesterone receptor expression on survival outcomes in breast cancers previously classified as triple negative breast cancers

Abstract

Purpose To evaluate the impact of low ER/PR expression and effect of endocrine therapy on survival outcomes in HER2-negative tumors with ER/PR < 10%, previously labeled as triple negative. Methods In a retrospective review, 1257 patients were categorized according their ER/PR percentages into three groups, ER/PR <1% (Group A), ER/PR 1–5% (Group B) and ER/PR 6–10% (Group C). Kaplan-Meier product limit method was used to estimate survival outcomes. Cox proportional hazards models was used to adjust for patient and tumor characteristics. Results Group A, B and C had 897 (71.4%), 241 (19.2%) and 119 (9.4%) patients respectively. After a median follow up of 40 months there was no significant difference in 3-year recurrence free survival (RFS): 64%, 67% and 77% (P = 0.34) or overall survival (OS): 79%, 81% and 88% (P = 0.33) for groups A, B and C respectively. ER/PR expression was not an independent predictor for RFS (HR=1.10, 95% CI: 0.86–1.39, P=0.46 for group B and HR=0.96, 95% CI: 0.66–1.38, P=0.81 for group C, compared to group A), or OS (HR=1.11, 95% CI: 0.84–1.46, P=0.46 for group B and HR=0.94, 95% CI: 0.63–1.42, P=0.78 for group C, compared to group A). Endocrine therapy had no impact on survival outcomes (RFS: P=0.10; OS: P=0.45) among groups. Conclusions In this cohort, a low ER/PR level (1–5%) does not appear to have any significant impact on survival outcomes. There was a tendency for survival advantages in the ER/PR 6–10% is seen. Benefit of endocrine therapy in these patients is unclear.

Mesothelin Expression and Survival Outcomes in Triple Receptor Negative Breast Cancer

“…Additionally, in our study, we used cut off values of ER, PR expression different that the current ASCO/CAP guidelines considered as positive (1%) 26 since we have shown the lack of efficacy of adjuvant endocrine therapy in patients with < 5% ER or PR expression. 27 We don't believe this influence our results on mesothelin expression. Recent studies reported an association between mesothelin expression and clinical outcomes in patients with ovarian cancer, pancreatic cancer and gastric cancer.…”

Interobserver Concordance in Implementing the 2010 ASCO/CAP Recommendations for Reporting ER in Breast Carcinomas

“…They did report a trend for a recurrence-free survival advantage with tumors in the 6% to 10% range of staining (n = 119). In the study by Raghav et al, 6 ER results were based on central review, but the authors do not comment on whether their results arise from a single observer reviewing all cases or if any interobserver discrepancy existed in the reporting of results in the case of multiple observers. Although some might advocate raising the threshold to 6% or higher based on the data of Raghav et al, 6 doing so will not completely remove the discrepancy problems highlighted in our study.…”

“…6 This retrospective study reported overall survival and recurrence-free survival in a large number of low-level ER-expressing tumors, including a subset of patients who received endocrine therapy, albeit with limited follow-up. Raghav et al 6 found no significant recurrence-free survival advantage at 3 years in patients with tumors that stained less than 1% (n = 897) or between 1% and 5% (n = 241), while those with ER staining between 6% and 10% (n = 119) showed a recurrence-free survival advantage trend.…”

“…With the 2010 ASCO/CAP recommendations in mind and the publication by Raghav et al, 6 which highlights outcome in a large series of tumors with low ER expression, we aimed to review our concordance as a group of dedicated breast pathologists at reporting the intensity and percentage of ER expression using 2 different antibodies and 2 different scoring methods, the Allred and the more complex H-score methods. We wanted to determine the spread of ER expression with particular interest in the subset of tumors with low levels of ER expression and to establish our concordance at reporting ER in borderline threshold cases.…”

Clinical relevance of the reappraisal of negative hormone receptor expression in breast cancer

“…Our data seem to indicate that the pros (therapeutic benefit) and cons (potential side effects) of giving hormonal therapies for patients with minimal ER and PR positive expression should be cautiously evaluated. In a recent study, aiming to investigate the impact of low ER and PR expression (<10%) as well as the effect of endocrine therapy on survival outcomes of 1,257 previously classified triple negative breast cancer patients, Raghav et al (Raghav et al 2012) observed that for both ER/PR 1%-5% and 6%-10% level subgroups, no prognostic utility and only a tendency for survival advantages were found, respectively. These controversial findings reveal that the application of endocrine therapy in these patients needs further investigation (Brouckaert et al 2013).…”