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


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.


CONCLUSIONS
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.
Breast Care Center, University of California at San Francisco, 1600 Divisadero St, 2nd Floor, Box 1710, San Francisco, CA 94115, USA. laura.esserman@ucsfmedctr.org
Laura J
LJ
Esserman
Donald A
DA
Berry
Angela
A
DeMichele
Lisa
L
Carey
Sarah E
SE
Davis
Meredith
M
Buxton
Cliff
C
Hudis
Joe W
JW
Gray
Charles
C
Perou
Christina
C
Yau
Chad
C
Livasy
Helen
H
Krontiras
Leslie
L
Montgomery
Debasish
D
Tripathy
Constance
C
Lehman
Minetta C
MC
Liu
Olufunmilayo I
OI
Olopade
Hope S
HS
Rugo
John T
JT
Carpenter
Lynn
L
Dressler
David
D
Chhieng
Baljit
B
Singh
Carolyn
C
Mies
Joseph
J
Rabban
Yunn-Yi
YY
Chen
Dilip
D
Giri
Laura
L
van 't Veer
Nola
N
Hylton
D015415:Biomarkers / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003952:Diagnostic Imaging; D018572:Disease-Free Survival; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012008:Recurrence; D016896:Treatment Outcome
D015415:Biomarkers; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone