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Accepted (AM)Open Access (License Unspecified), Open
Journal article
RB-Pathway Disruption Is Associated with Improved Response to Neoadjuvant Chemotherapy in Breast Cancer
Clinical cancer research, v 18(18), pp 5110-5122
15 Sep 2012
PMCID: PMC4436088
PMID: 22811582
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Purpose: We sought to determine whether dysregulation of the retinoblastoma (RB) tumor suppressor pathway was associated with improved response to neoadjuvant chemotherapy in breast cancer.
Experimental Design: An RB-loss signature was used to analyze the association between pathway status and pathologic complete response in gene expression datasets encompassing three different neoadjuvant regimens. Parallel immunohistochemical analysis of the RB pathway was conducted on pretreatment biopsies to determine the association with pathologic response to neoadjuvant chemotherapy.
Results: An RB-loss gene expression signature was associated with increased pathologic complete response in datasets from breast cancer patients treated with 5-fluorouracil/adriamycin/cytoxan (FAC; P < 0.001), T/FAC (P < 0.001), and Taxane/Adriaymcin (P < 0.001) neoadjuvant therapy encompassing approximately 1,000 patients. The association with improved response to neoadjuvant chemotherapy was true in both estrogen receptor (ER)-positive and ER-negative breast cancer. Elevated expression of p16ink4a is associated with the RB-loss signature (R = 0.493-0.5982), and correspondingly p16ink4a mRNA levels were strongly associated with pathologic complete response in the same datasets analyzed. In an independent cohort, immunohistochemical analyses of RB and p16ink4a revealed an association of RB loss (P = 0.0018) or elevated p16ink4a (P = 0.0253) with pathologic complete response. In addition, by Miller-Payne and clinicopathologic scoring analyses, RB-deficient tumors experienced an overall improved response to neoadjuvant chemotherapy.
Conclusion: Disruption of the RB pathway as measured by several independent methods was associated with improved response to neoadjuvant chemotherapy. The RB-pathway status was relevant for pathologic response in both ER-positive and ER-negative breast cancer with similar results observed with multiple chemotherapy regimens. Combined, these data indicate that RB status is associated with the response to neoadjuvant chemotherapy in breast cancer and could be used to inform treatment. Clin Cancer Res; 18(18); 5110-22. (c) 2012 AACR.
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Details
- Title
- RB-Pathway Disruption Is Associated with Improved Response to Neoadjuvant Chemotherapy in Breast Cancer
- Creators
- Agnieszka K. Witkiewicz - Thomas Jefferson UniversityAdam Ertel - Thomas Jefferson UniversityJeanne McFalls - Thomas Jefferson UniversityMatias E. Valsecchi - Thomas Jefferson UniversityGordon Schwartz - Thomas Jefferson UniversityErik S. Knudsen - Thomas Jefferson University
- Publication Details
- Clinical cancer research, v 18(18), pp 5110-5122
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 13
- Grant note
- R01CA129134 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000309965700028
- Scopus ID
- 2-s2.0-84866433516
- Other Identifier
- 991019176639704721
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- Web of Science research areas
- Oncology