Abstract 264P
Background
Breast cancer (BC) is a common cause of brain metastases occurring in at least 10–16 % of patients. Tucatinib is FDA-approved for patients with metastatic HER2-positive BC, including patients with brain metastases, whereas no approved targeted therapies are available for HER2-negative brain metastasis. This study aims to elucidate the expression patterns of HER2 and HER3 in primary tumors and brain metastases.
Methods
This retrospective study included BC patients (n=44) diagnosed with brain metastases of BC and treated with surgical intervention for the brain metastases, between Jan/2000 and Dec/2017 at the National Cancer Center Hospital in Japan. Patient demographics were obtained through chart review. HER2 and HER3 immunohistochemical (IHC) staining was performed for each of primary brain metastasized tissue. IHC scoring (0, 1+, 2+, 3+) of membranous staining intensity was according to HER2 IHC gastric scoring guideline, and H-score (0-300) was calculated based on membranous staining using the following formula: 1x(percentage of 1+ tumor cells[1+ %]) + 2x(2+ %) + 3x(3+ %).
Results
Median age was 53 (34 – 78) years at brain surgery, with duration range of 0.5–22 years between collection of primary and metastatic tissues. BC subtypes were identified in 8/18/14/4 patients for TNBC/HR+HER2-/HR+HER2+/HR-HER2+. HER3 2+/3+ in primary tumor was observed in 26 patients (59%), and 40 patients (91%) in brain metastases. HER3 H-score was significantly higher (135 ± 60) in the brain tissue, compared to the primary tumor (79 ± 63; p = 0.00012). HER3 2+/3+ was observed in brain metastases of 6/8 (75%) for TNBC, 16/18 (89%) for HR+HER2-, 14/14 (100%) for HR+HER2+, and 4/4(100%) for HR-HER2+. HER2 expression was largely kept in the similar level of 16/18 (89%) in HR+HER2+/HR-HER2+ subtypes, showing little change of IHC score between primary and metastatic brain tissues.
Conclusions
Tissue from BC brain metastases showed significantly higher levels of HER3 expression than primary tumors, indicating that HER3 is a potential target for BC brain metastases. Further prospective study of HER3-directed therapy is warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Toru Mukohara.
Funding
Daiichi Sankyo, Inc.
Disclosure
T. Kogawa: Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo, Eisai, Oncotherapy, AstraZeneca, Ono Pharma; Financial Interests, Personal, Speaker’s Bureau: Chugai. K. Harano: Financial Interests, Institutional, Funding: Merk, Daiichi Sankyo Inc.; Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda; Financial Interests, Personal, Advisory Board: Chugai, Takeda. N. Matsubara: Financial Interests, Personal, Invited Speaker: Janssen, Sanofi; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Institutional, Invited Speaker: Janssen, AstraZeneca, Bayer, Roche, MSD, Taiho, Astellas, Amgen, Esai, Eli Lilly, Pfizer, Chugai. Y. Naito: Financial Interests, Personal, Invited Speaker, Speakers Bureau: Chugai, Pfizer, Eli Lilly, Eisai, AstraZeneca, Fuji Film Toyama Chemistry, Novartis, Gardant, Ono, Takeda, Taiho, Bayer, Nihon Kayaku; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Invited Speaker: ABBVIE, Boehringer Ingelheim, Daiichi Sankyo, Ono, Chugai, Taiho, Pfizer, AstraZeneca; Non-Financial Interests, Principal Investigator, JCOG: Natera. T. Ohnishi: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo. K. Yonemori: Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, MSD, Ono Pharma; Financial Interests, Personal, Advisory Board: Novartis, Eisai, Astrazeneca, Chugai, Takeda, Genmab, OncXerna; Financial Interests, Institutional, Funding: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Pfyzer, Novartis, Takeda, Chugai, Ono, Sanofy, Seattle genetics, Eisai, Eli Lilly, Genmab, Boeringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Seagen, Haihe. K. Koyama: Financial Interests, Personal, Other, company member: Daiichi Sankyo. N. Maeda: Financial Interests, Personal, Other, company member: Daiichi Sankyo. Y. Narita: Financial Interests, Institutional, Funding: Daiichi Sankyo. T. Mukohara: Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo, Eisai, MSD, Pfizer, Novartis, Sanofi, Chugai, AstraZeneca, Ono; Financial Interests, Personal and Institutional, Research Grant: Sysmex; Financial Interests, Personal, Other, lecture fee: Eli Lilly, Kyowa Kirin, Taiho. All other authors have declared no conflicts of interest.