Puneet Singh

Objective: In this study, we quantified the global macroeconomic burden of breast cancer to underscore the critical importance of improving access to oncologic surgical care internationally. Summary Background Data: Breast cancer mortality in many low and middle-income countries (LMICs) is dramatically higher than in high-income countries. Prior to identifying solutions, however, it is important to first define the burden of disease. Methods: Data from the Institute of Health Metrics and Evaluation (2005–2015) were used to assess epidemiologic trends for 194, middle, and low-income countries. Economic burden defined by Welfare Loss (WL) was calculated by measuring disability-adjusted-life-years lost to breast cancer alongside the dollar equivalent of a value of statistical life year and as a function of each country's gross domestic product (GDP). Results: Annual mortality rates among breast cancer patients were significantly greater in LMICs in South Asia (3.06 per 100 women) and Sub-Saharan Africa (2.76 per 100 women), compared with high-income countries like the United States (1.69 per 100 women). From 2005–2015, mortality in South Asia increased by 8.20% and decreased by 6.45% in Sub-Saharan Africa; mortality rates in 2015 were observed as 27.9 per 100,000 in South Asia and 18.61 per 100,000 in Sub-Saharan Africa. Countries in South Asia demonstrated the greatest rise in WL due to breast cancer, from 0.05% to 0.08% of GDP. Conclusions: The burden of disease and economic impact of breast cancer is intensifying in LMICs. Global efforts to improve access to surgical care for women with breast cancer could reduce mortality and mitigate the social and financial impact of this disease in LMICs.

Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein-coupled receptors, has been implicated in many physiologic and pathologic processes, including cancer. LPA is converted from lysophosphatidylcholine (LPC) by the secreted phospholipase autotaxin (ATX). Although various cell types can produce ATX, adipocyte-derived ATX is believed to be the major source of circulating ATX and also to be the major regulator of plasma LPA levels. In addition to ATX, adipocytes secrete numerous other factors (adipokines); although several adipokines have been implicated in breast cancer biology, the contribution of mammary adipose tissue-derived LPC/ATX/LPA (LPA axis) signaling to breast cancer is poorly understood. Using murine mammary fat-conditioned medium, we investigated the contribution of LPA signaling to mammary epithelial cancer cell biology and identified LPA signaling as a significant contributor to the oncogenic effects of the mammary adipose tissue secretome. To interrogate the role of mammary fat in the LPA axis during breast cancer progression, we exposed mammary adipose tissue to secreted factors from estrogen receptor-negative mammary epithelial cell lines and monitored changes in the mammary fat pad LPA axis. Our data indicate that bidirectional interactions between mammary cancer cells and mammary adipocytes alter the local LPA axis and increase ATX expression in the mammary fat pad during breast cancer progression. Thus, the LPC/ATX/LPA axis may be a useful target for prevention in patients at risk of ER-negative breast cancer. Cancer Prev Res; 9(5); 367-78. ©2016 AACR.

BACKGROUND: The role of postmastectomy radiation therapy (PMRT) after neoadjuvant chemotherapy (NAC) and mastectomy is unclear, especially in patients that have post-treatment tumor negative axillary nodes (ypN0). METHODS: The National Cancer Data Base was used to identify women that had PMRT after NAC and mastectomy for clinically node positive (cN1-2) disease from 2004 to 2008. Median follow-up time was 69 months. RESULTS: 8,321 patients were included for analysis, and 6140 (65.6%) had cN1 disease and 2181 (23.3%) had cN2 disease. On adjusted survival analysis, PMRT was associated with an overall survival (OS) benefit in both patients with cN1 (5-yr OS 75.8% vs. 71.9%, P < 0.01) and cN2 (5-yr OS 69.2% vs. 58.6%, P < 0.01) disease. In the subgroup of patients that were ypN0 after NAC, there was no significant survival difference (P > 0.11) for PMRT compared to those patients who were not ypN0, except for patients with hormone-receptor negative tumors, who had improved OS with PMRT (HR 0.65, P < 0.01). CONCLUSIONS: PMRT is associated with improved OS in patients with cN1 and cN2 disease after NAC and mastectomy. However, in the subgroup of patients that were ypN0 after NAC, PMRT improved OS for hormone-receptor negative patients but not hormone-receptor positive patients.