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. 2022 Mar;29(2):368-376.
doi: 10.1007/s12282-021-01319-9. Epub 2022 Jan 5.

Predictive and prognostic significance of BRCAness in HER2-negative breast cancer

Aiko Sueta  1 , Mutsuko Yamamoto-Ibusuki  1 , Mai Tomiguchi  1 , Yoshitaka Fujiki, Lisa Goto-Yamaguchi  1 , Hirotaka Iwase  2 , Yutaka Yamamoto  3
Affiliations

Predictive and prognostic significance of BRCAness in HER2-negative breast cancer

Aiko Sueta et al. Breast Cancer. 2022 Mar.

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.

Keywords: BRCAness; Neoadjuvant chemotherapy; pCR.

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