Presence of an in-situ component predicts reduced tumor aggressiveness in luminal subtype of invasive breast cancer

Abstract

GOALS: We have previously shown that primary breast invasive ductal carcinoma co-existing with ductal-carcinoma-in-situ (IDC-DCIS) is characterized by lower proliferation rate and metastatic propensity than sizematched pure IDC, especially if the ratio of DCIS to IDC size is high. On the other hand, IDC-DCIS is more often ER-positive, PR-positive and/or HER2-positive than is pure IDC. This analysis aims to clarify whether the presence of co-existing DCIS in IDC affects tumor aggressiveness in various biological subtypes of breast cancer respectively. METHODS: Tumor data obtained from 1355 consecutive female patients undergoing upfront surgery for primary breast cancer were analyzed retrospectively; 196 patients with pure DCIS were excluded. Based on evidence that immunohistochemistry (IHC) provides a reasonable approximation of molecular phenotypes, the tumor samples were divided into 4 groups: (i) luminal A (ER and/or PR-positive, HER2-negative, Ki67_12), (ii) luminal B (ER and/or PR-positive, HER2-negative, Ki67 > 12), (iii) HER2 (HER2-positive) and (iv) basal-like (triple-negative) disease. Ki67 expression and nodal involvement of IDC with or without DCIS in these groups were compared. RESULTS: The number of patients with luminal A, luminal B, HER2 and basal-like breast cancer were 458, 315, 247 and 128 respectively. Ki-67 was lower in IDC-DCIS than in size-adjusted pure IDC of both luminal A and luminal B subtypes (p = 0.15 and <0.005 respectively). Pure IDC of these biological subtypes were also associated with more advanced lymph node status as compared to IDC-DCIS, although not statistically significant. In HER2 or basal-like tumors, there were no significant difference between pure IDC and IDC-DCIS. CONCLUSION: The presence of co-existing DCIS in IDC predicts lower biological aggressiveness in luminal cancers but not in the conventionally more aggressive HER2-positive and triple-negative subtypes.