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Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients

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Abstract

The CAN-NCIC-MA22 phase I/II clinical trial evaluated women with locally advanced or inflammatory breast cancer treated with epirubicin and docetaxel at 2 or 3 weekly intervals in sequential cohorts. The relationship between various biomarkers and treatment response was assessed. Breast biopsy cores were obtained from 50 patients pre-, mid-, and post-treatment. Immunohistochemical staining was performed to determine baseline levels of estrogen receptor (ER), progesterone receptor (PR), Her2/Neu protein (HER2), and topoisomerase II (Topo 2), expressed as percent positive stain. Tumor RNA integrity (RIN) and tumor cellularity were measured pre-, mid- and post-treatment by capillary electrophoresis and light microscopy after hematoxylin/eosin staining, respectively. Associations between 1) maximum RIN and 2) tumor cellularity at the three time points with baseline levels of ER, PR, Her2, and topo II were assessed using Spearman and Pearson correlation coefficients. Associations between RIN and tumor cellularity with chemotherapy dose level or pathologic response were assessed using one-way ANOVA. In this study, we observed that low mid-treatment maximum RIN (but not tumor cellularity) was associated with high chemotherapy drug dose level (P = 0.05) and eventual pathologic complete response (pCR) (P = 0.01). Post-treatment, low maximum RIN was found to be associated with low tumor cellularity (P = 0.004), and low tumor cellularity with pCR (P = 0.01). Post-treatment tumor cellularity was lowest in patients with tumors having high baseline PR levels (P = 0.05). The association of mid-treatment RIN with drug dose level and with pCR suggests that tumor RIN may represent an important new biomarker for measuring response to chemotherapy in breast cancer patients.

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Acknowledgments

This work was supported by funding from Sanofi-Aventis Pharamceuticals and a grant from the Cancer Research Fund of the Ontario Institute for Cancer Research [02-MAY-0159 to A.M.P.]. Funding is also acknowledged from the Canadian Cancer Society (who supports the NCIC CTG). We are extremely grateful to the patients who consented to be a part of this study.

Conflicts of Interest/Disclosure:

A PCT application has been filed by A.M.P. with the U.S. Patent Office related to the use of tumor RNA integrity as a biomarker of response to chemotherapy in cancer patients.

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Authors and Affiliations

  1. Regional Cancer Program, Sudbury Regional Hospital, Laurentian University, Sudbury, ON, P3E 5J1, Canada

    Amadeo M. Parissenti & Baoqing Guo

  2. NCIC Clinical Trials Group, Queen’s University, Kingston, ON, K7L 3N6, Canada

    Judy-Anne W. Chapman, Lei Han, Patti O’Brien & Lois E. Shepherd

  3. Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, M4N 3M5, Canada

    Harriette J. Kahn, Roberta Jong, Rebecca Dent, Kathleen I. Pritchard & Maureen E. Trudeau

  4. Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, ON, M5G 2M9, Canada

    Mark P. Clemons & Barbara Fitzgerald

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  1. Amadeo M. Parissenti
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  2. Judy-Anne W. Chapman
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Correspondence to Amadeo M. Parissenti.

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Parissenti, A.M., Chapman, JA.W., Kahn, H.J. et al. Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients. Breast Cancer Res Treat 119, 347–356 (2010). https://doi.org/10.1007/s10549-009-0531-x

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  • DOI: https://doi.org/10.1007/s10549-009-0531-x

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