Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 132, Issue 3, Pages 1049-1062Publisher
SPRINGER
DOI: 10.1007/s10549-011-1895-2
Keywords
Breast cancer; Neoadjuvant chemotherapy; Molecular biomarkers; Pathologic complete response
Categories
Funding
- National Cancer Institute [CA58207]
- American College of Radiology Imaging Network [CA079778, CA080098]
- Cancer and Leukemia Group B [CA31964, CA33601]
- National Cancer Institute Center for Bioinformatics
- Breast Cancer Research Foundation
- Bruce and Martha Atwater
- Terry Fox Foundation
- Give Breast Cancer the Boot
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Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and to judge the impact of response to therapy on recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with a parts per thousand yen3 cm tumors by using early imaging and molecular signatures, with outcomes of pathologic complete response (pCR) and RFS. The current analysis was performed using data from patients who had molecular profiles and did not receive trastuzumab. The various molecular classifiers tested were highly correlated. Categorization of breast cancer by molecular signatures enhanced the ability of pCR to predict improvement in RFS compared to the population as a whole. In multivariate analysis, the molecular signatures that added to the ability of HR and HER2 receptors, clinical stage, and pCR in predicting RFS included 70-gene signature, wound healing signature, p53 mutation signature, and PAM50 risk of recurrence. The low risk signatures were associated with significantly better prognosis, and also identified additional patients with a good prognosis within the no pCR group, primarily in the hormone receptor positive, HER-2 negative subgroup. The I-SPY 1 population is enriched for tumors with a poor prognosis but is still heterogeneous in terms of rates of pCR and RFS. The ability of pCR to predict RFS is better by subset than it is for the whole group. Molecular markers improve prediction of RFS by identifying additional patients with excellent prognosis within the no pCR group.
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