Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: Results from the I-SPY 1 TRIAL - CALGB 150007/150012, ACRIN 6657

Laura J. Esserman, Donald A. Berry, Angela DeMichele, Lisa Carey, Sarah E. Davis, Meredith Buxton, Cliff Hudis, Joe W. Gray, Charles Perou, Christina Yau, Chad Livasy, Helen Krontiras, Leslie Montgomery, Debasish Tripathy, Constance Lehman, Minetta C. Liu, Olufunmilayo I. Olopade, Hope S. Rugo, John T. Carpenter, Lynn DresslerDavid Chhieng, Baljit Singh, Carolyn Mies, Joseph Rabban, Yunn Yi Chen, Dilip Giri, Laura Van't Veer, Nola Hylton

Research output: Contribution to journalArticle

262 Scopus citations

Abstract

Purpose: Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. Patients and Methods: Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. Results: In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2- negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets. Conclusion: In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.

Original languageEnglish (US)
Pages (from-to)3242-3249
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number26
DOIs
StatePublished - Sep 10 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Esserman, L. J., Berry, D. A., DeMichele, A., Carey, L., Davis, S. E., Buxton, M., Hudis, C., Gray, J. W., Perou, C., Yau, C., Livasy, C., Krontiras, H., Montgomery, L., Tripathy, D., Lehman, C., Liu, M. C., Olopade, O. I., Rugo, H. S., Carpenter, J. T., ... Hylton, N. (2012). Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: Results from the I-SPY 1 TRIAL - CALGB 150007/150012, ACRIN 6657. Journal of Clinical Oncology, 30(26), 3242-3249. https://doi.org/10.1200/JCO.2011.39.2779