Cancer Res Treat.  2019 Oct;51(4):1527-1539. 10.4143/crt.2018.598.

BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy

Affiliations
  • 1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 2Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 3Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
  • 4Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
  • 5Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
  • 6Department of Medicine, San Juan De Dios Hospital, Manila, Philippines.
  • 7Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 8Department of Medical Oncology and Severance Biomedical Research Institute, Yonsei University College of Medicine, Seoul, Korea.
  • 9Department of Internal Medicine, Dong-A University Hospital, Busan, Korea.
  • 10Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, China.
  • 11The Center for Anti-Cancer Companion Diagnostics, Bio-MAX/N-Bio, Seoul National University, Seoul, Korea.
  • 12Department of Hematology-Oncology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea.
  • 13Division of Medical Oncology, Yonsei Cancer Center, Seoul, Korea.
  • 14Division of Hematology-Oncology, Inha University Hospital, Incheon, Korea.
  • 15Department of Hematology-Oncology, Pusan National University Hospital, Busan, Korea.
  • 16Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea.
  • 17Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea.
  • 18Novartis Pharmaceuticals Corporation, APSA, Midrand, South Africa.
  • 19Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea. jungsro@ncc.re.kr

Abstract

PURPOSE
BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents.
MATERIALS AND METHODS
Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored.
RESULTS
p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib.
CONCLUSION
The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.

Keyword

Biomarkers; Breast neoplasms; HER2; Lapatinib; Trastuzumab

MeSH Terms

Asian Continental Ancestry Group*
Biomarkers
Biopsy
Breast Neoplasms*
Breast*
Diagnosis
Disease-Free Survival
Female
Humans
Neoplasm Metastasis
Prevalence
RNA, Messenger
Trastuzumab
Biomarkers
RNA, Messenger
Trastuzumab

Figure

  • Fig. 1. Progression-free survival (PFS) with lapatinib based regimens for all patients and biomarker subgroups. (A) All patients. (B) Patients with p95HER2 expression. (C) Patients with PTEN deletion/down-regulation. (D) Patients with PIK3CA mutation. Note: Log-rank test of survival distribution equality for subgroups was defined by positive and negative biomarker status. CI, confidence interval.

  • Fig. 2. Progression-fee survival (PFS) with trastuzumab-based regimens for all patients and biomarker subgroups. (A) All patients. (B) Patients with p95HER2 expression. (C) Patients with PTEN deletion/down-regulation. (D) Patients with PIK3CA mutation. Note: Log-rank test of survival distribution equality for subgroups was defined by positive and negative biomarker status. CI, confidence interval.

  • Fig. 3. Biomarker status for the three biomarkers, at primary diagnosis (A) and at recurrence/metastasis (B), for the analysis population.

  • Fig. 4. Conversion/conservation of biomarker status.


Cited by  1 articles

PIK3CA Mutation Is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Cancer Res Treat. 2023;55(2):531-541.    doi: 10.4143/crt.2022.221.


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