Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome

Abstract

Macrophages, a key cell in the inflammatory cascade, have been associated with poor prognosis in cancers, including breast cancer. In this study, we investigated the relationship of a subset of macrophages—proliferating macrophages (promacs)—with clinicopathologic characteristics of breast cancer, including tumor size, grade, stage, lymph node metastases, hormone receptor status, subtype, as well as early recurrence, and survival. This study included a discovery and validation set that was conducted at two institutions and laboratories (University of California, San Francisco and University of Chicago) using two independent cohorts of patients with breast cancer. Formalin-fixed, paraffin-embedded sections and/or tissue microarrays were double-stained with anti-CD68 (a macrophage marker) and anti-PCNA (a proliferation marker) antibodies. The presence of intratumoral promacs was significantly correlated with high grade, hormone receptor negative tumors, and a basal-like subtype. In contrast, there was no correlation between promacs and tumor size, stage, or the number of the involved lymph nodes. These findings were consistent between the two study cohorts. Finally, promac numbers were a significant predictor of recurrence and survival. In the pooled analysis, elevated promac levels were associated with a 77% increased risk of dying (P = 0.015). The presence of promacs in human breast cancer may serve as a prognostic indicator for poor outcomes and early recurrence and serve as a potential cellular target for novel therapeutic interventions.

Clinicopathological Features of Indonesian Breast Cancers with Different Molecular Subtypes

“…These subtypes of breast cancer have a fairly poor prognosis and more prone to early and frequent recurrence and metastasize. Prognosis of Her-2+ subtype is better compared with triple negative/ basal-like subtype since it can be treated with the drug trastuzumab /Herceptin (Sorlie et al, 2003;Chanrion et al, 2007;Campbell et al, 2011).…”

Microenvironnement tumoral

“…La valeur pronostique de cette signature stromale est particulièrement puissante pour les tumeurs HER2 + [10]. Parallèlement à ces signatures issues des analyses transcriptomiques à haut débit, de multiples études se sont focalisées sur le rôle pronostique des différents compartiments cellulaires du microenvironnement tumoral (adipocytes, fibroblastes et macrophages activés, lymphocytes, cellules endothéliales) [11][12][13][14][15][16][17][18]. Mais, c'est sans aucun doute la caractérisation de la réponse immunitaire qui occupe actuellement le devant de la scène [19,43] ( §).…”

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

“…For example, high numbers of TAMs are, among others, indicative of bad prognosis in colorectal cancer [203,204], non small cell lung cancer (NSCLC) [98,[205][206][207], Hodgkin's lymphoma [208], breast cancer [209,210], liver cancer [211,212] and prostate cancer [213].…”