Role of HER2-Related Biomarkers (HER2, p95HER2, HER3, PTEN, and PIK3CA) in the Efficacy of Lapatinib plus Capecitabine in HER2-Positive Advanced Breast Cancer Refractory to Trastuzumab.

Abstract

OBJECTIVE:

The aim of this study was to investigate the correlation between human epidermal growth factor receptor 2 (HER2)-related biomarkers and the treatment outcomes using lapatinib plus capecitabine (LC) and to evaluate the influence of the estrogen receptor (ER) status in trastuzumab-refractory HER2-positive advanced breast cancer.

METHOD:

Eighty patients were enrolled in this study. Total HER2, p95HER2, and total HER3 expression were quantified using the VeraTag assays. PTEN (phosphatase and tensin homolog) and p95 expression was evaluated using immunohistochemistry and PIK3CA mutation using direct sequencing.

RESULTS:

The response rate to LC was 30%, clinical benefit rate was 51.3%, and the median progression-free survival (PFS) was 174.5 days. ER negativity significantly correlated with higher HER2 and p95HER2. The lower HER2 and PIK3CA mutations were often observed in the nonresponders. A high p95HER2 expression correlated with longer PFS especially in the high HER2- and ER-positive cases. Patients without the PIK3CA mutation showed longer PFS in the same subset. Overall survival after LC significantly correlated with the number of recurrence organs.

CONCLUSION:

LC therapy is effective in trastuzumab-refractory HER2-positive breast cancer. Moreover, the biomarker expression differed depending on ER status, and a high p95HER2 expression and wild-type PIK3CA gene correlated with longer PFS especially in the ER-positive cases.

• Authors: Reiki Nishimura, Uhi Toh, Maki Tanaka, Michiyo Saimura, Yasuhiro Okumura, Tsuyoshi Saito, Toshihiro Tanaka, Megumi Teraoka, Kazuo Shimada, Kazuhisa Katayama, Toshihiro Koga, Kaname Kurashita, Satoshi Hasegawa, Hidekazu Todoroki, Yuichiro Kai, Yasuyo Ohi, Satoshi Toyoshima, Nobuyuki Arima, Shoshu Mitsuyama, Kazuo Tamura
• Journal: Oncology (Oncology) Vol. 93 Issue 1 Pg. 51-61 ( 2017) ISSN: 1423-0232 [Electronic] Switzerland
• PMID: 28478451 (Publication Type: Journal Article)
• Copyright: © 2017 S. Karger AG, Basel.

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers, Tumor
• Quinazolines
• Lapatinib
• Capecitabine
• ERBB2 protein, human
• Receptor, ErbB-2
• PTEN Phosphohydrolase
• PTEN protein, human
• Trastuzumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols
• Biomarkers, Tumor (metabolism)
• Breast Neoplasms (drug therapy, metabolism, mortality, pathology)
• Capecitabine (administration & dosage, therapeutic use)
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lapatinib
• Middle Aged
• Neoplasm Recurrence, Local
• PTEN Phosphohydrolase (drug effects)
• Quinazolines (administration & dosage, therapeutic use)
• Receptor, ErbB-2 (metabolism)
• Trastuzumab (administration & dosage, therapeutic use)
• Treatment Outcome
• Young Adult