Do non-classic invasive lobular carcinomas derive a benefit from neoadjuvant chemotherapy?

Purpose: Invasive lobular breast cancers (ILCs) respond poorly to neoadjuvant chemotherapy (NAC). The degree of benefit of NAC among non-classic ILC (NC-ILC) variants compared with classic ILCs (C-ILCs) is unknown.

Methods: Consecutive patients with Stage I-III ILC treated from 2003 to 2019 with NAC and surgery were identified, and grouped as C-ILC or NC-ILC as per the original surgical pathology report, with pathologist (A.G.) review performed if original categorization was unclear. A subset of similarly treated invasive ductal cancers (IDCs) was identified for comparison. Clinicopathologic characteristics and pathologic complete response (pCR) rates were evaluated.

Results: Of 145 patients with ILC, 101 (70%) were C-ILC and 44 (30%) were NC-ILC (IDC cohort: 1157 patients). ILC patients were older, more often cT3/T4 and cN2/N3, and less often high-grade compared to IDC patients. Those with NC-ILC were less often ER+/HER2- (55% versus 93%), and more often HER2 + (25% versus 7%) and TN (21% versus 0%, all p < 0.001). Breast pCR was more common among NC-ILC, but most frequent in IDC. Nodal pCR rates were also lowest among C-ILC patients, but similar among NC-ILC and IDC patients. On multivariable analysis, C-ILC (OR 0.09) and LVI (OR 0.51) were predictive of lack of breast pCR; non-ER+/HER2- subtypes and breast pCR were predictive of nodal pCR. When our analysis was repeated with patients stratified by receptor subtype, histology was not independently predictive of either breast or nodal pCR.

Conclusion: NC-ILC patients were significantly more likely to achieve breast and nodal pCR compared with C-ILC patients, but when stratified by subtype, histology was not independently predictive of breast or nodal pCR.