Efficacy evaluation

The RECIST version 1.1 was referred to in the assessment of clinical efficacy. Complete response (CR): all target lesions disappeared; partial response (PR): the sum of the maximum diameter of target lesions decreased by ≥30%; progressive disease (PD): the sum of the maximum diameter of target lesions increased by at least 20%, or a new lesion occurred; stable disease (SD): changes of the sum of the maximum diameter of target lesions were between PR and PD; objective response rate (ORR): ORR = (CR + PR)/total lesions ×100%. Pathological efficacy was evaluated in samples before NAC versus after surgery, according to the Miller-Payne histological classification, as follows: G1—ineffectiveness: no noticeable changes in cancer cell morphology or number; G2—mild effectiveness: presence of degeneration and necrosis of cancer cells (<1/3), or the density of residual living cells was more than 2/3 of that before treatment; G3—moderate effectiveness: presence of necrosis and lysis of cancer cells (1/3–2/3), or the density of residual living cells was 1/3–2/3 of that before treatment; G4—high efficacy: presence of necrosis and lysis of cancer cells (>2/3), or the density of residual living cells was less than 1/3 of that before treatment; G5—pathological complete response (pCR): presence of necrosis or disappearance of all cancer cells, and tumors were replaced by granulation or fibrous tissue. Total pCR (tpCR, ypT0/isypN0) was defined by the absence of invasive lesions in the breast tissue and axillary lymph nodes, and possible presence of carcinoma in situ components. No pCR was defined by the presence of visible invasive cancer components in the breast tissue or axillary lymph nodes in the majority of surgical resections. Pathological complete response of the breast tumor (bpCR) was defined by the absence of invasive carcinoma in the primary breast tumor. Effective pathological efficacy was indicated by G3 + G4 + G5. The primary endpoint was tpCR and the secondary endpoint was bpCR and ORR. In addition, AEs during the NAC were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) version 5.0 (https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf). The main data were from laboratory results, and a few subjective indicators were collected from outpatient review and telephone follow-up.

Imaging examinations such as magnetic resonance imaging (MRI) were applied to monitor target lesions every 2 cycles before neoadjuvant therapy and after administration. Pathological efficacy was based on routine pathology and immunohistochemical (IHC) results of preoperative and postoperative samples from the department of pathology. All medical imaging diagnostic reports and histopathological results were doubly confirmed by 2 senior investigators.