Abstract P4-21-25: The importance of hormone receptor status on biomarker expression and the efficacy of lapatinib plus capecitabine therapy after progression on trastuzumab in HER2 positive recurrent and advanced breast cancer

Autor: Hiroaki Ueo, H Todoroki, S Toyoshima, Michiyo Saimura, Reiki Nishimura, Kazuo Tamura, M Teraoka, Kaname Kurashita, T Koga, K Shimada, Takehiro Tanaka, S Mitsuyama, Nobuyuki Arima, Y Ohi, Masao Tanaka, Uhi Toh, Yasuhiro Okumura, Tsuyoshi Saito
Rok vydání: 2017
Předmět:
Zdroj: Cancer Research. 77:P4-21
ISSN: 1538-7445
0008-5472
DOI: 10.1158/1538-7445.sabcs16-p4-21-25
Popis: Background: Anti-HER2 treatment using trastuzumab (Tmab) has contributed to improving the clinical outcome of HER2-positive breast cancerpatients. However, some patients do not respond to Tmab therapy and the combination of Lapatinib and capecitabine (LC) is an effective treatment option after progression on Tmab. Hormone receptor status is also an important factor for deciding if the patient should be treated with endocrine therapy as well. The aim of this study was to investigate the clinical significance of hormone receptor status in biomarker expression and to evaluate the efficacy of lapatinib therapy. Materials and Methods: Eighty patients with HER2 positive breast cancer refractory to Tmab were enrolled in this prospective trial (KBC-SG 1107) between December 2011 and March 2014. The following treatment began after enrollment; lapatinib 1250-mg tablets were administered orally once daily and capecitabine (2000 mg/m2 per day) on days 1 to 14 every 21 days until disease progression or until severe adverse events. Total HER2 (H2T), p95HER2 (p95), and total HER3 (H3T) expression levels were quantified in formalin-fixed paraffin embedded samples using VeraTag assays. ER and progesterone receptor (PgR), PTEN and p95 expressions were evaluated using immunohistochemistry (IHC) and PIK3CA mutation using direct sequencing. Statistical analyses were performed using SPSS (ver. 21). A two-sided P Results: The ER- and PgR-positive rates were 55.0% and 33.8%, respectively. The response rate to LC was 30% (CR: 1 case; PR: 23 cases), the clinical benefit rate was 51.3% and the median progression-free survival (PFS) was 174.5 days. Both ER and PgR negativity significantly correlated with higher H2T (cutoff: 13.8), p95HER2 (cutoff: 2.8) and PTEN expression levels (cutoff: H score of 100). Lower H2T expression levels and PIK3CA mutation rates were often observed in the non-responders (both: p=0.087). The ER and PgR status did not correlate with response. A high p95 and PTEN expression significantly correlated with longer PFS in ER and/or PgR positive cases (p=0.02 and 0.03), respectively. The overall survival (OS) after LC significantly correlated with the number of recurrence organs (p=0.0002) but not with the p95 and PTEN expression levels. Conclusion: LC therapy was effective in Tmab-refractory HER2 positive breast cancer. Moreover, the biomarker expression differed depending on the ER/PgR status and a high p95 and PTEN expression correlated with longer PFS in ER and/or PgR positive cases. Further study is necessary to validate these findings. Citation Format: Arima N, Nishimura R, Toh U, Tanaka M, Saimura M, Okumura Y, Saito T, Tanaka T, Teraoka M, Shimada K, Koga T, Kurashita K, Todoroki H, Ueo H, Ohi Y, Toyoshima S, Mitsuyama S, Tamura K. The importance of hormone receptor status on biomarker expression and the efficacy of lapatinib plus capecitabine therapy after progression on trastuzumab in HER2 positive recurrent and advanced breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-25.
Databáze: OpenAIRE
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