Tau and PTEN status as predictive markers for response to trastuzumab and paclitaxel in patients with HER2-positive breast cancer.
Trastuzumab (H)-based chemotherapy has been an active treatment in patients with HER2-positive breast cancer; however, primary and secondary resistance has occurred in patients treated with H alone or in combination with chemotherapy. Biomarkers were searched using tissue microarrays (TMA) in HER2-positive advanced breast cancer patients treated with H and paclitaxel (P) combination chemotherapy between October 2004 and August 2010. Tumor blocks were analyzed for Tau-protein, beta-III tubulin, PTEN, p27, IGF-1R, c-Met, CD44, and MUC4 by immunohistochemical (IHC) analysis. The correlation between IHC status and clinical outcomes, including response rate (RR), progression free survival (PFS), and overall survival (OS), was investigated. With a median follow-up duration of 54.1 months (range, 42.3-72.7 months), 65 patients received H + P chemotherapy. The overall RR was 63 % (95 % CI, 51-75 %), and seven patients (11 %) with high Tau/low PTEN expression showed a significantly lower RR (14 % vs. 69 %; p = 0.008). The odds ratio for a poor response was 13.3 (95 % CI, 1.5-119.0; p = 0.020). In addition, patients with high Tau/low PTEN showed a trend of poor survival in terms of PFS (6.6 months vs. 9.6 months, p = 0.052). Subsequent multivariate analysis showed that high Tau/low PTEN (hazard ratio [HR] 2.40, 95 % CI, 1.06-5.47; p = 0.037) was the poor prognostic factor independently associated with PFS after adjusting for possible confounding factors such as recurrence/metastasis, age, performance status, visceral metastasis, and hormone receptor status. High Tau-protein and low PTEN expression showed a significant association with poor response to H + P chemotherapy in patients with HER2-positive advanced breast cancer.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
Dong-Hoe
DH
Koo
Hee Jin
HJ
Lee
Jin-Hee
JH
Ahn
Dok Hyun
DH
Yoon
Sung-Bae
SB
Kim
Gyungyub
G
Gong
Byung Ho
BH
Son
Sei Hyun
SH
Ahn
Kyung Hae
KH
Jung
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis* / Q000235:genetics; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D000068878:Trastuzumab; D016875:tau Proteins / Q000096:biosynthesis* / Q000235:genetics
D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D051059:PTEN Phosphohydrolase; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D016875:tau Proteins; C508053:ERBB2 protein, human; C494929:PTEN protein, human