Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy

• Published in: Clinical cancer research Vol. 11; no. 16; pp. 5678 - 5685
• Main Authors: ROUZIER, Roman, PEROU, Charles M, MORANDI, Paolo, CHANG FAN, RABIUL, Islam, ROSS, Jeffrey S, HORTOBAGYI, Gabriel N, PUSZTAI, Lajos, SYMMANS, W. Fraser, IBRAHIM, Nuhad, CRISTOFANILLI, Massimo, ANDERSON, Keith, HESS, Kenneth R, STEC, James, AYERS, Mark, WAGNER, Peter
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.08.2005
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biopsy, Needle; Breast - drug effects; Breast - metabolism; Breast - pathology; breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cluster Analysis; Doxorubicin - administration & dosage; Female; Fluorouracil - administration & dosage; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; microarray; Middle Aged; Multivariate Analysis; neoadjuvant therapy; Oligonucleotide Array Sequence Analysis; Paclitaxel - administration & dosage; pharmacogenomics; Pharmacology. Drug treatments; Predictive Value of Tests; Preoperative Care; Receptor, ErbB-2 - genetics; Tumors; Antineoplastic agent; Mammary gland diseases; Chemotherapy; Treatment; Breast cancer; Preoperative; Malignant tumor; Subtype
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-2421

Purpose: Molecular classification of breast cancer has been proposed based on gene expression profiles of human tumors. Luminal, basal-like, normal-like, and erbB2+ subgroups were identified and were shown to have different prognoses. The goal of this research was to determine if these different molecular subtypes of breast cancer also respond differently to preoperative chemotherapy. Experimental Design: Fine needle aspirations of 82 breast cancers were obtained before starting preoperative paclitaxel followed by 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Gene expression profiling was done with Affymetrix U133A microarrays and the previously reported “breast intrinsic” gene set was used for hierarchical clustering and multidimensional scaling to assign molecular class. Results: The basal-like and erbB2+ subgroups were associated with the highest rates of pathologic complete response (CR), 45% [95% confidence interval (95% CI), 24-68] and 45% (95% CI, 23-68), respectively, whereas the luminal tumors had a pathologic CR rate of 6% (95% CI, 1-21). No pathologic CR was observed among the normal-like cancers (95% CI, 0-31). Molecular class was not independent of conventional cliniocopathologic predictors of response such as estrogen receptor status and nuclear grade. None of the 61 genes associated with pathologic CR in the basal-like group were associated with pathologic CR in the erbB2+ group, suggesting that the molecular mechanisms of chemotherapy sensitivity may vary between these two estrogen receptor–negative subtypes. Conclusions: The basal-like and erbB2+ subtypes of breast cancer are more sensitive to paclitaxel- and doxorubicin-containing preoperative chemotherapy than the luminal and normal-like cancers.