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Neoadjuvant Chemotherapy Shifts Breast Tumor Microbiota Populations to Regulate Drug Responsiveness and the Development of Metastasis.

Publication ,  Journal Article
Chiba, A; Bawaneh, A; Velazquez, C; Clear, KYJ; Wilson, AS; Howard-McNatt, M; Levine, EA; Levi-Polyachenko, N; Yates-Alston, SA; Diggle, SP ...
Published in: Mol Cancer Res
January 2020

Breast tumors have their own specific microbiota, distinct from normal mammary gland tissue. Patients with breast cancer that present with locally advanced disease often undergo neoadjuvant chemotherapy to reduce tumor size prior to surgery to allow breast conservation or limit axillary lymph node dissection. The purpose of our study was to evaluate whether neoadjuvant chemotherapy modulates the tumor microbiome and the potential impact of microbes on breast cancer signaling. Using snap-frozen aseptically collected breast tumor tissue from women who underwent neoadjuvant chemotherapy (n = 15) or women with no prior therapy at time of surgery (n = 18), we performed 16S rRNA-sequencing to identify tumoral bacterial populations. We also stained breast tumor microarrays to confirm presence of identified microbiota. Using bacteria-conditioned media, we determined the effect of bacterial metabolites on breast cancer cell proliferation and doxorubicin therapy responsiveness. We show chemotherapy administration significantly increased breast tumor Pseudomonas spp. Primary breast tumors from patients who developed distant metastases displayed increased tumoral abundance of Brevundimonas and Staphylococcus. We confirmed presence of Pseudomonas in breast tumor tissue by IHC staining. Treatment of breast cancer cells with Pseudomonas aeruginosa conditioned media differentially effected proliferation in a dose-dependent manner and modulated doxorubicin-mediated cell death. Our results indicate chemotherapy shifts the breast tumor microbiome and specific microbes correlate with tumor recurrence. Further studies with a larger patient cohort may provide greater insights into the role of microbiota in therapeutic outcome and develop novel bacterial biomarkers that could predict distant metastases. IMPLICATIONS: Breast tumor microbiota are modified by therapy and affects molecular signaling.

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Published In

Mol Cancer Res

DOI

EISSN

1557-3125

Publication Date

January 2020

Volume

18

Issue

1

Start / End Page

130 / 139

Location

United States

Related Subject Headings

  • Retrospective Studies
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Neoadjuvant Therapy
  • Microbiota
  • Mice
  • Humans
  • Female
  • Developmental Biology
  • Breast Neoplasms
 

Citation

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Chicago
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Chiba, A., Bawaneh, A., Velazquez, C., Clear, K. Y. J., Wilson, A. S., Howard-McNatt, M., … Cook, K. L. (2020). Neoadjuvant Chemotherapy Shifts Breast Tumor Microbiota Populations to Regulate Drug Responsiveness and the Development of Metastasis. Mol Cancer Res, 18(1), 130–139. https://doi.org/10.1158/1541-7786.MCR-19-0451
Chiba, Akiko, Alaa Bawaneh, Christine Velazquez, Kenysha Y. J. Clear, Adam S. Wilson, Marissa Howard-McNatt, Edward A. Levine, et al. “Neoadjuvant Chemotherapy Shifts Breast Tumor Microbiota Populations to Regulate Drug Responsiveness and the Development of Metastasis.Mol Cancer Res 18, no. 1 (January 2020): 130–39. https://doi.org/10.1158/1541-7786.MCR-19-0451.
Chiba A, Bawaneh A, Velazquez C, Clear KYJ, Wilson AS, Howard-McNatt M, et al. Neoadjuvant Chemotherapy Shifts Breast Tumor Microbiota Populations to Regulate Drug Responsiveness and the Development of Metastasis. Mol Cancer Res. 2020 Jan;18(1):130–9.
Chiba, Akiko, et al. “Neoadjuvant Chemotherapy Shifts Breast Tumor Microbiota Populations to Regulate Drug Responsiveness and the Development of Metastasis.Mol Cancer Res, vol. 18, no. 1, Jan. 2020, pp. 130–39. Pubmed, doi:10.1158/1541-7786.MCR-19-0451.
Chiba A, Bawaneh A, Velazquez C, Clear KYJ, Wilson AS, Howard-McNatt M, Levine EA, Levi-Polyachenko N, Yates-Alston SA, Diggle SP, Soto-Pantoja DR, Cook KL. Neoadjuvant Chemotherapy Shifts Breast Tumor Microbiota Populations to Regulate Drug Responsiveness and the Development of Metastasis. Mol Cancer Res. 2020 Jan;18(1):130–139.

Published In

Mol Cancer Res

DOI

EISSN

1557-3125

Publication Date

January 2020

Volume

18

Issue

1

Start / End Page

130 / 139

Location

United States

Related Subject Headings

  • Retrospective Studies
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Neoadjuvant Therapy
  • Microbiota
  • Mice
  • Humans
  • Female
  • Developmental Biology
  • Breast Neoplasms