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 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

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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

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Recurrence
Survival
Hormones
Neoplasms
Breast Neoplasms
Drug Therapy
Molecular Imaging
Survival Analysis
Tumor Biomarkers
human ERBB2 protein
Multivariate Analysis
Genes
Trastuzumab
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pathologic complete response predicts recurrence-free survival more effectively by cancer subset : Results from the I-SPY 1 TRIAL - CALGB 150007/150012, ACRIN 6657. / Esserman, Laura J.; Berry, Donald A.; DeMichele, Angela; Carey, Lisa; Davis, Sarah E.; Buxton, Meredith; Hudis, Cliff; Gray, Joe; Perou, Charles; Yau, Christina; Livasy, Chad; Krontiras, Helen; Montgomery, Leslie; Tripathy, Debasish; Lehman, Constance; Liu, Minetta C.; Olopade, Olufunmilayo I.; Rugo, Hope S.; Carpenter, John T.; Dressler, Lynn; Chhieng, David; Singh, Baljit; Mies, Carolyn; Rabban, Joseph; Chen, Yunn Yi; Giri, Dilip; Van't Veer, Laura; Hylton, Nola.

In: Journal of Clinical Oncology, Vol. 30, No. 26, 10.09.2012, p. 3242-3249.

Research output: Contribution to journalArticle

Esserman, LJ, Berry, DA, DeMichele, A, Carey, L, Davis, SE, Buxton, M, Hudis, C, Gray, J, Perou, C, Yau, C, Livasy, C, Krontiras, H, Montgomery, L, Tripathy, D, Lehman, C, Liu, MC, Olopade, OI, Rugo, HS, Carpenter, JT, Dressler, L, Chhieng, D, Singh, B, Mies, C, Rabban, J, Chen, YY, Giri, D, Van't Veer, L & 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, vol. 30, no. 26, pp. 3242-3249. https://doi.org/10.1200/JCO.2011.39.2779
Esserman, Laura J. ; Berry, Donald A. ; DeMichele, Angela ; Carey, Lisa ; Davis, Sarah E. ; Buxton, Meredith ; Hudis, Cliff ; Gray, Joe ; Perou, Charles ; Yau, Christina ; Livasy, Chad ; Krontiras, Helen ; Montgomery, Leslie ; Tripathy, Debasish ; Lehman, Constance ; Liu, Minetta C. ; Olopade, Olufunmilayo I. ; Rugo, Hope S. ; Carpenter, John T. ; Dressler, Lynn ; Chhieng, David ; Singh, Baljit ; Mies, Carolyn ; Rabban, Joseph ; Chen, Yunn Yi ; Giri, Dilip ; Van't Veer, Laura ; Hylton, Nola. / Pathologic complete response predicts recurrence-free survival more effectively by cancer subset : Results from the I-SPY 1 TRIAL - CALGB 150007/150012, ACRIN 6657. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 26. pp. 3242-3249.
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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.",
author = "Esserman, {Laura J.} and Berry, {Donald A.} and Angela DeMichele and Lisa Carey and Davis, {Sarah E.} and Meredith Buxton and Cliff Hudis and Joe Gray and Charles Perou and Christina Yau and Chad Livasy and Helen Krontiras and Leslie Montgomery and Debasish Tripathy and Constance Lehman and Liu, {Minetta C.} and Olopade, {Olufunmilayo I.} and Rugo, {Hope S.} and Carpenter, {John T.} and Lynn Dressler and David Chhieng and Baljit Singh and Carolyn Mies and Joseph Rabban and Chen, {Yunn Yi} and Dilip Giri and {Van't Veer}, Laura and Nola Hylton",
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TY - JOUR

T1 - Pathologic complete response predicts recurrence-free survival more effectively by cancer subset

T2 - Results from the I-SPY 1 TRIAL - CALGB 150007/150012, ACRIN 6657

AU - Esserman, Laura J.

AU - Berry, Donald A.

AU - DeMichele, Angela

AU - Carey, Lisa

AU - Davis, Sarah E.

AU - Buxton, Meredith

AU - Hudis, Cliff

AU - Gray, Joe

AU - Perou, Charles

AU - Yau, Christina

AU - Livasy, Chad

AU - Krontiras, Helen

AU - Montgomery, Leslie

AU - Tripathy, Debasish

AU - Lehman, Constance

AU - Liu, Minetta C.

AU - Olopade, Olufunmilayo I.

AU - Rugo, Hope S.

AU - Carpenter, John T.

AU - Dressler, Lynn

AU - Chhieng, David

AU - Singh, Baljit

AU - Mies, Carolyn

AU - Rabban, Joseph

AU - Chen, Yunn Yi

AU - Giri, Dilip

AU - Van't Veer, Laura

AU - Hylton, Nola

PY - 2012/9/10

Y1 - 2012/9/10

N2 - 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.

AB - 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.

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