Objective  We compared the efficacy and safety of trastuzumab (H) chemotherapy alone or in combination with pertuzumab (P) or pyrrolitinib (Py), and explored factors that affect patient total pathologic complete response (tpCR) rate.

  Methods  We performed a retrospective analysis of the clinicopathological data of 330 patients with HER-2 positive breast cancer who received neoadjuvant treatment in Fujian Medical University Union Hospital from January 2021 to December 2022. We compared the efficacy and safety of H+Py combined chemotherapy (47 cases), H+P chemotherapy (268 cases), and H chemotherapy alone (15 cases), and analyzed factors influencing patient tpCR rates using statistical methods.

  Results  The average tpCR rate for all patients was 56.7% (187/330), with 60.4% (162/268) and 44.7% (21/47) for the H+P group and H+Py group, respectively. The highest rate of grade 3 adverse reactions 21.3% (10/47) was observed in the H+Py group. Drug reduction and grade 3 adverse reactions affected the tpCR rate in the H+Py group. Independent factors influencing the tpCR rate among all patients include hormone receptor (HR) and HER-2 status. The tpCR rate of HR negative patients is 3.217 times higher than that of HR positive patients, while the tpCR rate of HER-2 (+++) patients is 3.710 times higher than that of HER-2 (++) patients.

  Conclusions  The therapeutic efficacy of H+Py chemotherapy is inferior to that of H+P treatment, but superior to treatment with H alone. Level 3 adverse reactions and drug reduction negatively impact the therapeutic efficacy of H+Py chemotherapy. The management and control of adverse drug reactions should be strengthened to ensure sufficient dosage of drugs. H+Py combined chemotherapy is still a viable option for neoadjuvant treatment of HER-2 positive breast cancer patients. HR and HER-2 status are predictive factors for patient tpCR rate.