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 Article


Authors: 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.; Dressler, L.; Chhieng, D.; Singh, B.; Mies, C.; Rabban, J.; Chen, Y. Y.; Giri, D.; van't Veer, L.; Hylton, N.
Article Title: Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: Results from the I-SPY 1 TRIAL - CALGB 150007/150012, ACRIN 6657
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. © 2012 by American Society of Clinical Oncology.
Keywords: adult; cancer survival; controlled study; human tissue; treatment outcome; treatment response; aged; disease-free survival; middle aged; major clinical study; cancer recurrence; doxorubicin; disease marker; cancer adjuvant therapy; biological markers; multiple cycle treatment; breast cancer; tumor volume; epidermal growth factor receptor 2; aromatase inhibitor; recurrence; cyclophosphamide; diagnostic imaging; breast neoplasms; multicenter study; tamoxifen; receptor, erbb-2; receptors, estrogen; receptors, progesterone; taxane derivative; trastuzumab; hormone receptor; breast biopsy; cancer prognosis
Journal Title: Journal of Clinical Oncology
Volume: 30
Issue: 26
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2012-09-10
Start Page: 3242
End Page: 3249
Language: English
DOI: 10.1200/jco.2011.39.2779
PUBMED: 22649152
PROVIDER: scopus
PMCID: PMC3434983
DOI/URL:
Notes: --- - "Cited By (since 1996): 7" - "Export Date: 28 January 2013" - "CODEN: JCOND" - "Source: Scopus"
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MSK Authors
  1. Clifford Hudis
    840 Hudis
  2. Dilip D Giri
    122 Giri