Single-center retrospective study links subcutaneous trastuzumab to higher complete-response odds in HER2-positive breast cancer

A single-center retrospective cohort study reported that neoadjuvant subcutaneous trastuzumab was associated with higher odds of total pathological complete response in patients with HER2-positive breast cancer than intravenous administration. The study included 450 patients treated at an East Asian center, with 83 receiving subcutaneous trastuzumab and 367 receiving the intravenous formulation. According to the published abstract, the unadjusted total pathological complete response rate was 68.7% in the subcutaneous group and 56.1% in the intravenous group.

Researchers used inverse probability weighting regression adjustment to reduce confounding by measured baseline variables. In that adjusted model, subcutaneous administration was associated with higher odds of total pathological complete response, with an odds ratio of 1.79, a 95% confidence interval of 1.02 to 3.14 and a P value of 0.044. The abstract states that the direction of the association was consistent across complementary analyses, but the retrospective design means the results do not establish that the administration route caused the difference in response.

The investigators also examined whether baseline body weight modified the association between route of administration and total pathological complete response. Body weight was comparable between the groups, and the analysis found no significant interaction with continuous body weight after adjustment, with an interaction P value of 0.961. As a secondary radiological endpoint, serial ultrasound measurements showed broadly similar tumor and lymph-node size trajectories at the assessed treatment time points and did not discriminate the difference in final pathological response.

The findings are limited by the study’s single-center, retrospective nature and the imbalance between treatment groups, as well as its reliance on adjustment for measured baseline variables. The available abstract also identifies a need for prospective multicenter validation and longer oncological follow-up. It notes that randomized trials have demonstrated non-inferiority of subcutaneous versus intravenous trastuzumab, but those trial findings do not remove the uncertainties surrounding the path-completion association observed in this routine-practice cohort.

Subject of Research: Association between trastuzumab administration route and pathological complete response in HER2-positive breast cancer

Article Title: Association of neoadjuvant subcutaneous trastuzumab with higher pathological complete response in HER2-positive breast cancer: a real-world doubly robust study

Article References: Zhang, R., Liu, J., Wang, Z., Liu, Y., Shi, B., Zhang, C., Li, X., Feng, K., Li, X., Zheng, S., & Zhang, H. (2026). Association of neoadjuvant subcutaneous trastuzumab with higher pathological complete response in HER2-positive breast cancer: a real-world doubly robust study. BMC Cancer. https://doi.org/10.1186/s12885-026-17025-8

Image Credits: AI Generated

DOI: 10.1186/s12885-026-17025-8

Keywords: HER2-positive breast cancer, subcutaneous trastuzumab, intravenous trastuzumab, pathological complete response, neoadjuvant therapy, retrospective cohort, inverse probability weighting, serial ultrasound, body-weight interaction, Association, neoadjuvant, subcutaneous