Small breast tumors did not have a higher chance of a complete pathological response after neoadjuvant chemotherapy, meaning chemotherapy given before surgery, than larger tumors, according to a retrospective analysis. Tumor size was not associated with the chance of that response in any molecular subtype examined, including triple-negative breast cancer (TNBC), HER2-positive tumors and luminal tumors. But size was not irrelevant: larger initial tumors were associated with greater residual disease when response was measured with a continuous Residual Cancer Burden score.
The study reported a pathological complete response rate of 28% across the cohort. The rate was 38% in TNBC, 39% in HER2-positive tumors and 5% in luminal tumors. In this analysis, pCR meant meeting the study's pathology-based staging criterion, recorded as ypT0/is ypN0. Researchers also used the Residual Cancer Burden, or RCB, index to describe how much disease remained, treating it both as a continuous score and as categories.
Small did not mean complete response
That distinction mattered for the smallest tumors. Among tumors measuring 2 centimeters or less, RCB-II/III classification was reported in 87% of luminal tumors, 46% of TNBC tumors and 34% of HER2-positive tumors. RCB-II/III is a category-based description of residual cancer burden, so the figures indicate that disease could remain even when the initial tumor measured no more than 2 centimeters.
The researchers asked whether initial tumor size could predict both complete response and residual disease burden across molecular subtypes. They used univariate analyses within each subtype, then examined the relationship between size and the continuous RCB score. This approach tested whether the association between tumor size and response differed among TNBC, HER2-positive and luminal tumors.
What the analysis examined
The cohort consisted of 714 patients with stage T1–T3N0-3M0 breast cancer who received neoadjuvant chemotherapy at Institut Curie between 2002 and 2012. The analysis was retrospective. The supplied methods do not report randomization or a separate control group, so the findings describe associations within this treated cohort rather than the effect of choosing one treatment strategy over another.
The team also ran a multivariate analysis of pCR. After that adjustment, tumor size still did not predict pCR, and the reported p-value was 0.8. Taken together with the subtype analyses, the result suggests that initial size alone was a poor guide to whether a patient would meet the study's complete-response endpoint, even though size was related to the amount of residual disease captured by continuous RCB.
The result has a narrow message
The authors say tumor size alone should not be used to exclude patients, particularly those with TNBC or HER2-positive disease, from neoadjuvant treatment strategies that enable treatment changes after surgery. Their conclusion rests on the finding that small tumors did not have higher pCR rates and that RCB-II/III disease remained common among tumors 2 centimeters or less.
The study's limits are important. It was a single-institution retrospective analysis of patients treated during 2002–2012, without randomization or a separate control group. It does not establish that neoadjuvant chemotherapy caused the response patterns or that one treatment strategy was better than another. Nor does it show that tumor size is unrelated to residual disease: in the continuous RCB analysis, larger tumors had more residual disease. The evidence supports caution about using size alone as an exclusion rule, not a universal treatment recommendation.
Paper data and sources
Original title: Impact of Tumor Size on Neoadjuvant Chemotherapy Outcomes in Breast Cancer.
Authors: Claire LeGall, Lauren Darrigues, Jonathan Sabah et al.
Journal/Repository: Annals of surgical oncology
Status: Peer-reviewed
First online: 2026-08-21
DOI: 10.1245/s10434-026-20307-x
Original paper · Full text