Invasive lobular carcinoma predicts micrometastasis in breast cancer

Invasive lobular carcinomas (ILCs) are almost always estrogen receptor (ER) positive. Most delayed breast cancer recurrences occur in ER-positive patients. Disseminated tumor cells (DTCs) and circulating tumor cells (CTCs) have been implicated in recurrence. The purpose of this study was to determine whether DTCs and CTCs are associated with ILCs in stage I-III breast cancer.

Clinical stage I-III breast cancer patients consented to participate in an institutional review board-approved study involving collection of bone marrow and blood at surgery for primary breast cancer. We assessed DTCs by anti-CK antibody cocktail after cytospin. We detected CTCs using CellSearch, and defined them as nucleated cells lacking CD45 but expressing cytokeratin. One or more cells per 5 mL bone marrow or 7.5 mL blood was considered positive. We performed statistical analyses using chi-square and Fisher's exact tests.

We prospectively enrolled 422 patients, 64 with ILC and 358 with invasive ductal carcinoma. Estrogen receptor positivity was higher in ILCs (92.2% versus 66.2%) {P = .001}. We identified DTCs to be 43.4% with ILC compared with 28.9% with IDC {P = 0.03}. The CTC rates were similar. Either DTCs or CTCs were identified in 75.6% with ILC, compared with 51.7% with invasive ductal carcinoma {P = .002}. We observed no correlation between the presence of DTCs and CTCs in ILC patients and tumor size, grade, hormone receptor status, stage, lymph node status, or administration of NACT.

Invasive lobular carcinomas independently predicted micrometastatic disease. Because most late recurrences are ER positive, this raises the question of whether DTCs and CTCs are indeed responsible for late breast cancer recurrence.