Aiko Sueta1, Mutsuko Yamamoto-Ibusuki1, Mai Tomiguchi1, Yoshitaka Fujiki, Lisa Goto-Yamaguchi1, Hirotaka Iwase2, Yutaka Yamamoto3. 1. Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. 2. Department of Breast Surgery, Kumamoto City Hospital, 4-1-60, Higashimachi, Higashiku, Kumamoto, 862-8505, Japan. 3. Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan. yyamamoto@kumamoto-u.ac.jp.
Abstract
BACKGROUND: BRCAness is characterized as the phenotypes shared between some sporadic tumors and BRCA1/2 mutation cancers resulting in defective homologous recombination. The predictive or prognostic value of BRCAness in HER2-negative breast cancer patients who have received neoadjuvant chemotherapy (NAC) is not fully elucidated. METHODS: We retrospectively selected 101 high-risk HER2-negative patients diagnosed with stage I-III breast cancer who underwent NAC treatment and evaluated BRCA1-like phenotype using multiplex ligation-dependent probe amplification assay. In an analysis of BRCAness, 95 out of 101 patients were analyzed. RESULTS: In total, 70 (74%) patients had sporadic-type tumors and 25 (26%) had BRCA1-like tumors according to pre-treatment samples. The BRCA1-like phenotype was not associated with pathological complete response (pCR) rate in the entire cohort. In survival analysis, pre-treatment BRCA1-like phenotype was not associated with survival. On the other hand, post-treatment BRCA1-like patients apparently showed shorter relapse-free survival (log-rank P = 0.016) and breast cancer-specific survival (P < 0.001) compared with sporadic features. In multivariate analysis, only the post-treatment BRCA1-phenotype was significant prognostic factors (HR 5.67, 95% CI 1.19-29.3). Furthermore, we found phenotype change between BRCA1-like and sporadic type through NAC in 19% of non-pCR patients. Post-treatment Ki67 significantly decreased in the persistent sporadic tumors during treatment or sporadic tumors changed after NAC (P < 0.0001, P = 0.0078, respectively). CONCLUSIONS: BRCAness may be useful biomarkers to predict prognosis for HER2-negative breast cancer refractory to standard chemotherapy. Our results pave the way for identifying patients who require alternative therapies.
BACKGROUND: BRCAness is characterized as the phenotypes shared between some sporadic tumors and BRCA1/2 mutation cancers resulting in defective homologous recombination. The predictive or prognostic value of BRCAness in HER2-negative breast cancer patients who have received neoadjuvant chemotherapy (NAC) is not fully elucidated. METHODS: We retrospectively selected 101 high-risk HER2-negative patients diagnosed with stage I-III breast cancer who underwent NAC treatment and evaluated BRCA1-like phenotype using multiplex ligation-dependent probe amplification assay. In an analysis of BRCAness, 95 out of 101 patients were analyzed. RESULTS: In total, 70 (74%) patients had sporadic-type tumors and 25 (26%) had BRCA1-like tumors according to pre-treatment samples. The BRCA1-like phenotype was not associated with pathological complete response (pCR) rate in the entire cohort. In survival analysis, pre-treatment BRCA1-like phenotype was not associated with survival. On the other hand, post-treatment BRCA1-like patients apparently showed shorter relapse-free survival (log-rank P = 0.016) and breast cancer-specific survival (P < 0.001) compared with sporadic features. In multivariate analysis, only the post-treatment BRCA1-phenotype was significant prognostic factors (HR 5.67, 95% CI 1.19-29.3). Furthermore, we found phenotype change between BRCA1-like and sporadic type through NAC in 19% of non-pCR patients. Post-treatment Ki67 significantly decreased in the persistent sporadic tumors during treatment or sporadic tumors changed after NAC (P < 0.0001, P = 0.0078, respectively). CONCLUSIONS: BRCAness may be useful biomarkers to predict prognosis for HER2-negative breast cancer refractory to standard chemotherapy. Our results pave the way for identifying patients who require alternative therapies.
Authors: Werner Schroth; Florian A Büttner; Siarhei Kandabarau; Reiner Hoppe; Peter Fritz; Jörg Kumbrink; Thomas Kirchner; Heather A Brauer; Yuqi Ren; David Henderson; Stephen F Madden; Georg Sauer; Tanja Fehm; Diethelm Wallwiener; Peter A Fasching; Thomas Mürdter; Matthias Schwab; Hiltrud Brauch Journal: Clin Cancer Res Date: 2020-10-02 Impact factor: 12.531