Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes.
OBJECTIVE
The clinical relevancy of the 7-subtype classification of triple-negative breast cancer (TNBC) reported by Lehmann and colleagues is unknown. We investigated the clinical relevancy of TNBC heterogeneity by determining pathologic complete response (pCR) rates after neoadjuvant chemotherapy, based on TNBC subtypes.


METHODS
We revalidated the Lehmann and colleagues experiments using Affymetrix CEL files from public datasets. We applied these methods to 146 patients with TNBC with gene expression microarrays obtained from June 2000 to March 2010 at our institution. Of those, 130 had received standard neoadjuvant chemotherapy and had evaluable pathologic response data. We classified the TNBC samples by subtype and then correlated subtype and pCR status using Fisher exact test and a logistic regression model. We also assessed survival and compared the subtypes with PAM50 intrinsic subtypes and residual cancer burden (RCB) index.


RESULTS
TNBC subtype and pCR status were significantly associated (P = 0.04379). The basal-like 1 (BL1) subtype had the highest pCR rate (52%); basal-like 2 (BL2) and luminal androgen receptor had the lowest (0% and 10%, respectively). TNBC subtype was an independent predictor of pCR status (P = 0.022) by a likelihood ratio test. The subtypes better predicted pCR status than did the PAM50 intrinsic subtypes (basal-like vs. non basal-like).


CONCLUSIONS
Classifying TNBC by 7 subtypes predicts high versus low pCR rate. We confirm the clinical relevancy of the 7 subtypes of TNBC. We need to prospectively validate whether the pCR rate differences translate into long-term outcome differences. The 7-subtype classification may spur innovative personalized medicine strategies for patients with TNBC.
Authors' Affiliations: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic; Departments of Breast Medical Oncology, Bioinformatics and Computational Biology, Pathology, and Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Department of Biochemistry, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
Hiroko
H
Masuda
Keith A
KA
Baggerly
Ying
Y
Wang
Ya
Y
Zhang
Ana Maria
AM
Gonzalez-Angulo
Funda
F
Meric-Bernstam
Vicente
V
Valero
Brian D
BD
Lehmann
Jennifer A
JA
Pietenpol
Gabriel N
GN
Hortobagyi
W Fraser
WF
Symmans
Naoto T
NT
Ueno
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D018740:Genetic Heterogeneity; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D012008:Recurrence; D015203:Reproducibility of Results; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology