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

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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.

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Availability of data and materials

All data generated or analyzed in this study are available from the corresponding author.

Abbreviations

BCSS:

Breast cancer-specific survival

CI:

Confidential interval

ER:

Estrogen receptor

HER2:

Human epidermal growth factor receptor-2

HR:

Hazard ratio

MLPA:

Multiplex ligation-dependent probe amplification

NAC:

Neoadjuvant chemotherapy

OS:

Overall survival

pCR:

Pathological complete response

PARP:

Poly ADP-ribose polymerase

PR:

Progesterone receptor

RFS:

Relapse-free survival

TNBC:

Triple-negative breast cancer

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Acknowledgements

The authors are grateful to I. Suzu and H. Moriyama for excellent technical support, and to M. Kawakami for clinical data management.

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

    Aiko Sueta, Mutsuko Yamamoto-Ibusuki, Mai Tomiguchi, Lisa Goto-Yamaguchi & Yutaka Yamamoto

  2. Department of Breast Surgery, Kumamoto City Hospital, 4-1-60, Higashimachi, Higashiku, Kumamoto, 862-8505, Japan

    Hirotaka Iwase

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  1. Aiko Sueta
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  2. Mutsuko Yamamoto-Ibusuki
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Contributions

AS contributed to the conception and design of the study, performed experiments, and wrote the manuscript. MYI contributed to performing experiments and analysis of raw data. YY participated in the study design and coordination and helped to draft the manuscript. HI participated in study design. LGY, YY, and MT helped to draft the manuscript. All authors reviewed and approved the submitted manuscript.

Corresponding author

Correspondence to Yutaka Yamamoto.

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Conflict of interest

Y. Yamamoto has relevant conflicts of interest, as follows: personal fees from Chugai, AstraZeneca, Kyowa-Kirin, Pfizer, Novartis, Essai, Takeda, Taiho, GE Health Care Japan, Nippon Kayaku, Daiichi-Sankyo, Sysmex, and Lilly; grants from Chugai, Pfizer, AstraZeneca, Kyowa-Kirin, Daiichi-Sankyo, Nippon Kayaku, and Lilly.

The other authors have no conflicts of interest to declare.

Ethical approval

The entire study was approved by the ethics committee of Kumamoto University Graduate School of Medical Sciences.

Consent to participate

Written informed consent was obtained from all subjects for the collection and research use of serum samples. All relevant methods were performed according to the relevant guidelines and regulations.

Patients consent for publication

Not applicable.

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Sueta, A., Yamamoto-Ibusuki, M., Tomiguchi, M. et al. Predictive and prognostic significance of BRCAness in HER2-negative breast cancer. Breast Cancer 29, 368–376 (2022). https://doi.org/10.1007/s12282-021-01319-9

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  • DOI: https://doi.org/10.1007/s12282-021-01319-9

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