Breast Cancer Res Treat (2008) 107:249–257 DOI 10.1007/s10549-007-9546-3 P R E C L I N I C A L S T U D Y Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases Ashish B. Rajput Æ Dmitry A. Turbin Æ Maggie CU Cheang Æ David K. Voduc Æ Sam Leung Æ Karen A. Gelmon Æ C. Blake Gilks Æ David G. Huntsman Received: 7 February 2007 / Accepted: 12 February 2007 / Published online: 13 March 2007 Springer Science+Business Media B.V. 2007 Abstract Purpose We have previously demonstrated in a pilot study of 348 invasive breast cancers that mast cell (MC) inﬁltrates within primary breast cancers are associated with a good prognosis. Our aim was to verify this ﬁnding in a larger cohort of invasive breast cancer patients and exam- ine the relationship between the presence of MCs and other clinical and pathological features. Experimental design Clinically annotated tissue micro- arrays (TMAs) containing 4,444 cases were constructed and stained with c-Kit (CD-117) using standard immun- operoxidase techniques to identify and quantify MCs. For statistical analysis, we applied a split-sample validation technique. Breast cancer speciﬁc survival was analyzed by Kaplan–Meier [KM] method and log rank test was used to compare survival curves. Results Survival analysis by KM method showed that the presence of stromal MCs was a favourable prognostic factor in the training set (P = 0.001), and the validation set A. B. Rajput D. A. Turbin M. CU Cheang D. K. Voduc S. Leung C. B. Gilks D. G. Huntsman Department of Pathology, Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, BC CanadaV6H 3Z6 D. K. Voduc Department of Radiation Oncology, BC Cancer Agency, Vancouver, BC, Canada K. A. Gelmon Department of Medical Oncology, BC Cancer Agency, Vancouver, BC, Canada D. G. Huntsman (&) British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC, CanadaV5Z 4E6 e-mail: dhuntsma@bccancer.bc.ca group (P = 0.006). X-tile plot generated to deﬁne the optimal number of MCs showed that the presence of any number of stromal MCs predicted good prognosis. Multi- variate analysis showed that the MC effect in the training set (Hazard ratio [HR] = 0.804, 95% Conﬁdence interval [CI], 0.653–0.991, P = 0.041) and validation set analysis (HR = 0.846, 95% CI, 0.683–1.049, P = 0.128) was independent of age, tumor grade, tumor size, lymph node, ER and Her2 status. Conclusions This study concludes that stromal MC inﬁltration in invasive breast cancer is an independent good prognostic marker and reiterates the critical role of local inﬂammatory responses in breast cancer progression. Keywords Breast cancer Inﬂammatory inﬁltrate Mast cells Stroma Introduction Mast cells (MCs) are part of the innate immune system and are recruited to and activated in the microenvironment of a developing tumor. MCs originate from multipotential hemopoietic stem cells in the bone marrow, and express the proto-oncogene c-kit, a transmembrane type III tyrosine kinase receptor protein [1]. After leaving the vascular bed they differentiate and acquire functional maturity. MC inﬁltrates have been described in a variety of human cancers, including non-small-cell lung cancer [2–4], breast cancer [5], colorectal cancer [6], basal cell carcinoma [7] and pulmonary adenocarcinoma [8]. MCs are attracted to the tumor by tumor-derived chemo attractants where they either degranulate to release potential tumor cytotoxic compounds or become innocent bystanders depending on local tumor conditions [9]. There is controversy about the 123