Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy☆
Section snippets
Background
Over the past decade, neoadjuvant (pre-operative) chemotherapy has emerged as the standard of care in the treatment of inoperable and operable locally advanced breast cancer.1, 2 Neoadjuvant chemotherapy (NAC) has also been increasingly used in operable breast cancer, where it has been shown to be as effective as adjuvant chemotherapy3 while offering potential advantages that include: downsizing the primary tumour with resulting conversion of mastectomy candidates to breast conserving surgery
Methods
We performed a study-level meta-analysis of studies reporting data that allow calculation of the proportion of subjects with pCR by tumour subtype in the NAC setting. Studies were systematically identified and considered eligible if they reported data for all breast cancer subtypes within the study cohort; studies declaring some subjects with unknown subtypes were eligible. We considered studies characterising tumour subtype on the basis of traditional markers [hormone receptor (HR: ER/PR, at
Results
Thirty primary studies4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 met our defined eligibility criteria, and provided data on 11,695 subjects in evidence synthesis (an additional paper2 provided supplementary data on five of these studies4, 6, 7, 8, 9 – Appendix 1). Characteristics of the 30 studies and descriptive analysis, including the distribution of covariates, are shown in Table 1. Study-specific median pCR% was 19.8%
Discussion
The biological heterogeneity of breast cancer has been known for decades, and has been confirmed in the recent decade in gene expression profiling studies that highlighted various intrinsic breast cancer subtypes.34 In this meta-analysis, we report summary estimates of pCR% for breast cancer subtype, defined by HR and HER2 status, given that pCR following NAC is an established surrogate end-point for prognosis. Furthermore, it appears likely that in the future the construct of conventional
Authors’ contributions
N.H. conceived the study idea, conducted the literature searches and review of studies, performed data extraction, interpreted analyses and drafted the manuscript; P.M. performed statistical analyses and advised on data interpretation, advised on methodological aspects and contributed to drafting the manuscript; G.v.M. advised on clinical content and on data resolution, provided additional data and contributed to drafting the manuscript; M.L.M. assisted with the literature searches and review
Conflict of interest statement
None declared.
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