Background: Trastuzumab shows excellent benefits for HER2+ breast cancer patients, although 20% treated remain unresponsive. We conducted a retrospective cohort study to optimize neoadjuvant chemotherapy and trastuzumab treatment in HER2+ breast cancer patients.
Methods: Six hundred patients were analyzed to identify clinical characteristics of those not achieving a pathological complete response (pCR) to develop a clinical predictive model. Available RNA sequence data was also reviewed to develop a genetic model for pCR.
Results: The pCR rate was 39.8% and pCR was associated with superior disease free survival and overall survival. ER negativity and PR negativity, higher HER2 IHC scores, higher Ki-67, and trastuzumab use were associated with improved pCR. Weekly paclitaxel and carboplatin had the highest pCR rate (46.70%) and the anthracycline+taxanes regimen had the lowest rate (11.11%). Four published GEO datasets were analyzed and a 10-gene model and immune signature for pCR were developed. Non-pCR patients were ER+PR+ and had a lower immune signature and gene model score. Hormone receptor status and immune signatures were independent predictive factors of pCR.
Conclusion: Hormone receptor status and a 10-gene model could predict pCR independently and may be applied for patient selection and drug effectiveness optimization.
Keywords: HER2; breast cancer; immune signature; neoadjuvant chemotherapy; predictive model; trastuzumab.
Copyright © 2021 Li, Chen, Zheng, Li, Chi, Xiu, Zhang, Hou, Wang and Wu.