Abstract P6-16-08: Prognostic factor of HER2-positive breast cancer patients developed brain metastasis: A multicenter retrospective analysis
Authors: Hayashi Naoki , Niikura Naoki , Masuda Norikazu , Takashima Seiki , Nakamura Rikiya , Watanabe Ken-Ichi , Kanbayashi Chizuko , Ishida Mayumi , Hozumi Yasuo , Tsuneizumi Michiko , Kondo Naoto , Naito Yoichi , Honda Yayoi , Matsui Akira , Fujisawa Tomomi , Oshitanai Risa , Yasojima Hiroyuki , Yamauchi Hideko , Saji Shigehira , Iwata Hiroji 
Published: May 2015

Abstract
Background:
HER2-positive breast cancer has a high risk of developing brain metastasis compared to other subtypes of breast cancer. However, the clinical course and prognostic factors of HER2-positive breast cancer patients with brain metastases are not well known because of the relatively small population. The aim of this study was to determine clinicopathological factors associated with prognosis of HER2-positive patients developed brain metastasis.
Methods:
A retrospective large dataset of 432 HER2-positive patients who were diagnosed with brain metastases between 2001 and 2012 were collected from 24 institutions of the Japan Clinical Oncology Group: Breast Cancer Study Group. We assessed the clinicopathological factors associated with prognosis of these populations with brain metastases.
Results:
The median age of the 432 patients was 54 years (range, 20–86 years). Of the patients, 162 patients (37.5%) had ER-positive/HER2-positive (ER+HER2+) breast cancer and 270 patients (62.5%) had ER-negative/HER2-positive (ER-HER2+) breast cancer. Nineteen of the 162 patients with ER+HER2+ (12%) and 53 of the 270 patients with ER-HER2+ (20%) underwent surgery for brain metastases. After the diagnosis of brain metastasis, 108 patients with ER+HER2+ (63%) and 175 patients with ER-HER2+ (64%) received HER2-targeting agents, including trastsuzumab and/or lapatinib.
The median brain metastasis-free survival period from the diagnosis of primary breast cancer was 33.5 month in both subtypes. In 63.4% of patients with ER+HER2+subtype and 75.6% of patients with ER-HER2+, brain metastases were detected within 2 years after development of first distant metastasis. Eighty-four patients with ER+HER2+ subtype (52%) and 133 patients with ER-HER2+ (49%) had more than 3 brain metastases at the diagnosis.
The median survival period after developing brain metastasis was 16.5 months (95% confidence interval [CI], 11.9–21.1 months) in patients with ER+HER2+ and 11.5 months (95% CI, 9.1–13.8 months) in patients with ER-HER2+ (p = 0.117).
Patients with more than 3 brain metastases had significantly shorter OS period than patients with equal or less than 3 brain metastases in both of ER+HER2+ (p &lt; 0.001) and ER-HER2+ (p = 0.018). According to receiving HER2-targeting agents, patients receiving both of trastsuzumab and lapatinib had significantly longer survival period than patients who had received trastsuzumab alone, lapatinib alone, or no HER2-targeting agent (p &lt; 0.001).
Conclusions:
Our results showed that HER2-positive patients with more than 3 brain metastases at the diagnosis had poor prognosis regardless of ER-positivity, and receiving both of trastsuzumab and lapatinib might improve their survival. Further studies are needed to determine the best treatment strategy including these HER2-targeting agents for these populations.
Citation Format: Naoki Hayashi, Naoki Niikura, Norikazu Masuda, Seiki Takashima, Rikiya Nakamura, Ken-Ichi Watanabe, Chizuko Kanbayashi, Mayumi Ishida, Yasuo Hozumi, Michiko Tsuneizumi, Naoto Kondo, Yoichi Naito, Yayoi Honda, Akira Matsui, Tomomi Fujisawa, Risa Oshitanai, Hiroyuki Yasojima, Hideko Yamauchi, Shigehira Saji, Hiroji Iwata. Prognostic factor of HER2-positive breast cancer patients developed brain metastasis: A multicenter retrospective analysis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-16-08.