Abstract IA07: Systemic regulation of breast cancer progression

Abstract

Abstract Recurrent disease affects approximately 30% of breast cancer patients but, unfortunately, by the time overt metastases are detected, it is no longer possible to treat breast cancer patients with curative intent. Clinical evidence indicates that in women who are diagnosed with metastatic breast cancer, tumor cells disseminate from the primary tumor prior to surgical resection but can remain indolent for varying periods of time before the patient becomes symptomatic. The reasons why certain disseminated cells remain indolent while others erupt into malignant tumors remain unknown; it is therefore currently difficult to predict with any degree of accuracy which patients will experience disease relapse. Our lab uses various mouse and xenograft models of breast cancer progression to study the early phases of metastatic disease when patients harbor indolent disseminated tumor cells in the periphery at the time of their primary diagnosis. Using triple-negative models, we previously showed that certain tumor systemically support the outgrowth of distant, otherwise indolent disseminated tumors, doing so by secreting cytokines into the host circulation and activating bone marrow hematopoietic cells to become pro-tumorigenic (McAllister, et al., Cell, 2008; Elkabets, et al., JCI, 2011; Castano, et al, Ca Disc, 2013). Using models of luminal breast cancer, we discovered that certain tumors promote the outgrowth of distant tumors by supporting angiogenesis (Kuznetsov, et al., Ca Disc, 2012). More recently, we have begun to identify the properties of disseminated tumor cells that are poised to respond to systemic factors and importantly, the phenotype of those that do not respond to systemic regulation. We have learned that certain systemic factors (cytokines and hematopoietic cells) elicited by primary breast tumors can sustain tumor-initiating properties of disseminated cells. Our findings highlight the systemic environment as an important component of disease progression that can be exploited to more accurately identify patients who would benefit from neoadjuvant or adjuvant therapy. Moreover, we hope that this work will pave the way to designing new therapies that can be delivered at a time when what has previously been an inexorable progression to terminal metastatic disease may be prevented. Citation Format: Sandra S. McAllister. Systemic regulation of breast cancer progression. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr IA07.