HER2 expression and efficacy of preoperative paclitaxel/FAC chemotherapy in breast cancer.

Abstract

PURPOSE:

We examined the correlation between HER2 expression and pathologic complete response (pCR) to paclitaxel/FAC (T/FAC) preoperative chemotherapy in breast cancer.

PATIENTS AND METHODS:

Retrospective analysis of data including 534 patients treated with preoperative T/FAC was performed. Gene expression results were available from two datasets of 132 and 286 patients, and were used to examine the co-expression of HER2 and topoisomerase II alpha (TOP2A) and microtubule associated protein tau (MAP-Tau).

RESULTS:

Of the 534 patients, 105 (20%) had HER2-overexpressing breast cancer. The pCR rates were 33% and 15% for patients with HER2+ and HER2- tumors (P<0.001). The 5-year relapse-free survival rates were 94% and 70% in HER2+ tumors with and without pCR (P=0.009). HER2 overexpression (odds ratio 2.3, 95%CI: 1.3-3.9, P=0.004), estrogen receptor (ER) status, grade and weekly schedule of paclitaxel were each significantly and independently associated with pCR in multivariate analysis. When patients were stratified by ER status, the pCR rates were 50% for HER2+/ER-, 30% for HER2-/ER-, 19% for HER2+/ER+, and 6% for HER2-/ER+ tumors. HER2 overexpression was associated with lower expression of MAP-tau (P=0.001 and P<0.001) and higher expression of TOP2A mRNAs (P=0.048 and P=0.001) in patients with ER+ disease. ER- cancers had low MAP-tau expression regardless of HER-status.

CONCLUSION:

HER2 overexpression is associated with higher rate of pCR to preoperative T/FAC chemotherapy regardless of ER status. HER2 overexpression also correlates with increased TOP2A and decreased MAP-tau expression in ER-positive cancers.

• Authors: Fabrice Andre, Chafika Mazouni, Cornelia Liedtke, Shu-Wan Kau, Debby Frye, Marjorie Green, Ana M Gonzalez-Angulo, W Fraser Symmans, Gabriel N Hortobagyi, Lajos Pusztai
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 108 Issue 2 Pg. 183-90 (Mar 2008) ISSN: 0167-6806 [Print] Netherlands
• PMID: 17468948 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• DNA-Binding Proteins
• MAPT protein, human
• Poly-ADP-Ribose Binding Proteins
• RNA, Messenger
• Receptors, Estrogen
• tau Proteins
• Doxorubicin
• Cyclophosphamide
• ERBB2 protein, human
• Receptor, ErbB-2
• DNA Topoisomerases, Type II
• TOP2A protein, human
• Paclitaxel
• Fluorouracil

Topics

• Antigens, Neoplasm (genetics)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, genetics, pathology, surgery)
• Cyclophosphamide (administration & dosage)
• DNA Topoisomerases, Type II (genetics)
• DNA-Binding Proteins (genetics)
• Disease-Free Survival
• Doxorubicin (administration & dosage)
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage)
• Gene Amplification
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic
• Humans
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Staging
• Oligonucleotide Array Sequence Analysis
• Paclitaxel (administration & dosage)
• Patient Selection
• Poly-ADP-Ribose Binding Proteins
• RNA, Messenger (analysis)
• Receptor, ErbB-2 (genetics)
• Receptors, Estrogen (analysis)
• Retrospective Studies
• Time Factors
• Treatment Outcome
• tau Proteins (genetics)