Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer
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Invasive lobular carcinoma (ILC) has been reported to be less responsive to neoadjuvant chemotherapy (NAC) than invasive ductal carcinoma (IDC). We sought to determine whether ILC histology indeed predicts poor response to NAC by analyzing tumor characteristics such as protein expression, gene expression, and imaging features, and by comparing NAC response rates to those seen in IDC after adjustment for these factors. We combined datasets from two large prospective NAC trials, including in total 676 patients, of which 75 were of lobular histology. Eligible patients had tumors ≥3 cm in diameter or pathologic documentation of positive nodes, and underwent serial biopsies, expression microarray analysis, and MRI imaging. We compared pathologic complete response (pCR) rates and breast conservation surgery (BCS) rates between ILC and IDC, adjusted for clinicopathologic factors. On univariate analysis, ILCs were significantly less likely to have a pCR after NAC than IDCs (11 vs. 25 %, p = 0.01). However, the known differences in tumor characteristics between the two histologic types, including hormone receptor (HR) status, HER2 status, histological grade, and p53 expression, accounted for this difference with the lowest pCR rates among HR+/HER2− tumors in both ILC and IDC (7 and 5 %, respectively). ILC which were HR− and/or HER2+ had a pCR rate of 25 %. Expression subtyping, particularly the NKI 70-gene signature, was correlated with pCR, although the small numbers of ILC in each group precluded significant associations. BCS rate did not differ between IDC and ILC after adjusting for molecular characteristics. We conclude that ILC represents a heterogeneous group of tumors which are less responsive to NAC than IDC. However, this difference is explained by differences in molecular characteristics, particularly HR and HER2, and independent of lobular histology.
KeywordsNeoadjuvant chemotherapy Lobular breast cancer Gene expression arrays Predictive factors
The NKI study was carried out within the framework of CTMM, the Center for Translational Molecular Medicine (www.ctmm.nl), Project Breast CARE Grant 030-104. The authors would like to thank Lennart Mulder for technical assistance in generating the gene expression profiles and Andrew Vincent for statistical review.
Conflict of interest
Laura J. van‘t Veer declares an employment/leadership role and has stock or other ownership interests at Agendia Inc. (Chief Research Officer). The other authors declare no conflict of interest.
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