Claire LeGall, Lauren Darrigues, Jonathan Sabah, Anne-Sophie Hamy, Floriane Jochum, Florence Coussy, Luc Cabel, Virginie Fourchotte, Fatima Laki, Anne Salomon, Kim Cao, Thomas Gaillard, Enora Laas
Initial tumor size is not predictive of pCR after NAC. Small tumors, including those ≤ 2 cm, do not demonstrate higher pCR rates. Tumor size alone should therefore not be used to exclude patients-particularly those with TNBC or HER2-positive disease-from neoadjuvant treatment strategies that enable post-neoadjuvant therapeutic adaptation.
BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used in early breast cancer (BC) to assess chemosensitivity and guide postneoadjuvant treatment strategies. Although small tumors < 2 cm are often treated with upfront surgery because of their operability and presumed favorable prognosis, it remains uncertain whether patients with small tumors who do not achieve pathological complete response (pCR) might miss the opportunity for effective postneoadjuvant escalation strategies. We aimed to evaluate whether initial tumor size predicts pCR and residual disease burden across molecular subtypes.
METHODS: We conducted a retrospective analysis of 714 patients with stage T1-T3N0-3M0 BC treated with NAC at Institut Curie between 2002 and 2012. Pathological response was assessed by using the Residual Cancer Burden (RCB) index (continuous and categorical). Pathological complete response was defined as ypT0/is ypN0. Associations between tumor size and response were evaluated by using univariate analyses, stratified by molecular subtype.
RESULTS: The overall pCR rate was 28%, reaching 38% in triple-negative BC (TNBC) and 39% in HER2-positive tumors, but only 5% in estrogen receptor/HER2-negative (luminal) tumors. Initial tumor size was linearly associated with continuous RCB score (p < 0.001); larger tumors showed greater residual disease. Tumor size was not associated with the likelihood of achieving pCR in any molecular subtype. Among tumors ≤ 2 cm, most had residual disease: 87% of luminal tumors, 46% of TNBC, and 34% of HER2-positive tumors were classified as RCB-II/III. Tumor size remained non-predictive of pCR in multivariate analysis (p = 0.8).
CONCLUSIONS: Initial tumor size is not predictive of pCR after NAC. Small tumors, including those ≤ 2 cm, do not demonstrate higher pCR rates. Tumor size alone should therefore not be used to exclude patients-particularly those with TNBC or HER2-positive disease-from neoadjuvant treatment strategies that enable post-neoadjuvant therapeutic adaptation.