Clinicopathologic features and models predicting for high-risk 21-gene recurrence score (RS) are unreliable in predicting primary tumor downstaging with neoadjuvant chemotherapy (NACT).

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Conference Proceeding

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Annals of surgical oncology : the official journal of the Society of Surgical Oncology


10-25% of hormone receptor-positive (pos), HER2/neu-negative (neg), node-neg breast cancer patients (pts) will have a high-risk RS, indicating survival advantage associated with adjuvant chemotherapy. Samples for RS testing are typically selected from primary surgery specimens. Extent to which elevated RS or models predicting for an elevated score might identify pts that would benefit from NACT to downstage the primary tumor/improve lumpectomy eligibility is uncertain. Neoadjuvant endocrine therapy is limited in improving lumpectomy eligibility. Our goal was to determine whether clinicopathologic features and models predicting for high-risk RS could accurately identify pts that respond to NACT. We queried an IRB-approved, prospectivelymaintained database to evaluate pts with hormone receptor-pos, HER2-neg breast cancer 2009-2016 that had primary surgery with RS testing or that received NACT without RS. Clinicopathologic features, including MIB1/Ki67 proliferative index and the web-based Magee scores were evaluated for accuracy in identifying (i) cases with high-risk RS (≥31) and (ii) cases with significant tumor downstaging from NACT likely to improve lumpectomy eligibility (defined as complete pathologic response or ≥1 centimeter decrease in primary tumor size). 302 primary surgery pts had RS; 21 (7%) had high-risk score. Univariate features associated with high-risk score were: high Ki67 and grade (p<0.001); lower ER/PR expression (p<0.001) and high Magee score (p<0.001). Among 38 NACT pts, 6 (15.8%) had complete pathologic response; 29 (76.3%) had significant tumor downstaging. None of the clinicopathologic features associated with elevated RS were significantly associated with tumor downstaging (p-values 0.112 to 1.0) but younger pts were more likely to be downstaged (median age 49.1 vs. 58.6; p=0.03). Standard clinicopathology and existing models that predict for high-risk RS do not reliably predict for response to NACT and improved lumpectomy eligibility. Hormone receptorpos, HER2-neg breast cancer pts should undergo primary surgery.





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