Abstract
Background
HER2-positive breast cancer is an aggressive subtype of breast cancer that overexpresses human epidermal growth factor receptor 2 promoting cancer cell growth. Monoclonal antibodies targeting the HER2 receptor have improved survival for this patient population. Achieving pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) has correlated with disease-free survival in multiple trials, but we do not know why some HER2-positive tumors respond better to these therapies. We evaluated the correlation between HER2/CEP17 ratio and partial versus complete response following NAC. We evaluated whether patients with higher HER2/CEP17 ratios would have higher rates of pCR after NAC.
Methods
Using the National Cancer Database (NCDB), we performed a retrospective review comparing pCR rates after NAC based on HER2 ratio between 2005 and 2014. Patients were excluded if they were HER2 negative, did not undergo NAC, or if the HER2 ratio was not recorded. Trends in percentage of pCR versus partial response were analyzed using SPSS.
Results
The NCDB included 237,118 patients with HER2 equivocal or HER2-positive breast tumors. 29,291 of these patients underwent NAC, and HER2/CEP17 ratios were recorded in 14,597 of the NAC cases. A pCR was noted in 9752 patients and 11,402 patients had a partial response. The ratios were significantly different between complete vs. partial response groups (include ratios), P < 0.001. Using linear regression analysis, we identified a direct relationship between increasing the ratio and response to NAC.
Conclusion
Our study demonstrates a linear relationship between HER2/CEP17 ratio and pCR to NAC in patients included in the NCDB. The NCDB reflects current clinical practices across the country, and in this patient population, higher HER2 ratio is predictive of pCR to NAC and thus may be used in guiding decisions regarding the therapies that a patient receives in order to enhance pCR.
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Data availability
The data that support the findings of this study are available from the National Cancer Database, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.
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Funding provided by the Trihealth Cancer Institute.
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Kathriena Greenwell contributed in design contributions; Lala Hussain contributed in data interpretation; David Lee contributed in data interpretation; Apurva Mehta contributed in data interpretation; Amie Jackson contributed in data interpretation; Barbara Wexelman contributed in design contributions, data interpretation.
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IRB approval was obtained prior to the initiation of this study.
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Greenwell, K., Hussain, L., Lee, D. et al. Complete pathologic response rate to neoadjuvant chemotherapy increases with increasing HER2/CEP17 ratio in HER2 overexpressing breast cancer: analysis of the National Cancer Database (NCDB). Breast Cancer Res Treat 181, 249–254 (2020). https://doi.org/10.1007/s10549-020-05599-1
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DOI: https://doi.org/10.1007/s10549-020-05599-1