would be earned if no price differential existed is examined. The analysis reveals that New York and Illinois are, by a large margin, losing the most yearly tax revenue (nearly $140M each) to out-of-state cigarettes. Other top ranking revenue-loss states in order include Florida, Washington, Minnesota, Massachusetts, Arizona, and Ohio. On the other end of the spectrum, states gaining the most revenue under the current price regime are in order, Pennsylvania, New Hampshire, Indiana, West Virginia, Delaware, Missouri, Virginia, and Iowa. When all state gains (or losses) are summed, the net is a loss at $294.6M nationwide. In a second analysis of the fitted model, state-specific consumption estimates are derived under a regime in which a pack of cigarettes always costs the consumer $10 and in which there is no border price differential. The analysis reveals that the 2014 consumption estimate of approximately 13 billion packs of cigarettes drops to just under 8 billion under the nationwide $10 per pack regime. Conclusions: The analysis results suggest that state excise tax revenues are unfairly distributed due to tax avoidance or evasion behavior, and the net effect is a nationwide loss of almost $300 million in state revenues. This is money that could have been spent by high tax states towards their tobacco control goals, but instead went at a discount to states that have a lower excise tax, and likely weaker tobacco control goals. The analysis also revealed that a nationwide minimum price on tobacco could have a very strong effect on cigarette consumption, cutting out over a third of current consumption. These estimates are drawn from a model fitted to real and recent data. Moreover, the nature of the model allows for state specific idiosyncrasies that may affect price and adjacent state price effects to bear on the results, an approach not seen in the literature to date. However, the calculations involve assumptions that may not be realistic. For example, it is not clear that the price effect will remain the same at all price levels (i.e., the price effect may be non-linear). Also, a minimum price on cigarettes would not necessarily remove price differentials as assumed in the 10$ per pack scenario. Thus, the results of this study are best viewed as somewhat stylized views of what we are losing in the current price regime, and what we could achieve under another. Effects of Surgical vs. Non-Surgical Weight Loss on Mammary Tumor BurdenRossi EL, Bowers LW, Khatib SA, Smith LA, Doerstling SS, Lewis A, Seeley RJ, Hursting SD Background: Obesity is associated with increased incidence of basal-like breast cancer (BLBC), the most aggressive and lethal breast cancer subtype. Epidemiological data is conflicting on whether weight loss offers protection against BLBC in obese women; only interventions that typically result in significant sustained weight loss, such as bariatric surgery, produce a consistent anti-cancer benefit. Purpose: We sought to determine the differential effects of surgical and non-surgical weight loss...

Background Obesity is an established risk and progression factor for several intrinsic subtypes of breast cancer, including basal-like breast cancer (BLBC). Increased local and systemic levels of pro-inflammatory mediators, which typically accompany obesity, can independently influence tumor growth. Currently, it is unclear whether weight loss can reverse the enhancing effects of obesity on breast tumorigenesis. We hypothesize that chronic obesity results in epigenetic reprogramming, which may mediate residual inflammation, and lead to persistent mammary tumor growth despite moderate weight loss. Methods Female C57BL/6 mice (n=51) were administered a control (10% kcal from fat) or diet-induced obesity (DIO; 60% kcal from fat) regimen. After 17 weeks, DIO mice either continued on DIO diet or were switched to control diet to stimulate gradual weight loss, subsequently designated as Formerly Obese (FOb). Mice were orthotopically injected with Wnt-1 mammary tumor cells (a model of BLBC) at week 25, and monitored for an additional 9 weeks, then killed and their tumors excised, measured and stored for subsequent analysis. In an ongoing tumor study, we will randomize mice to the control or DIO regimen, switching half the DIO mice to the control diet after 15 weeks, resulting in normal weight, obese, and FOb mice. Within each of these groups, the mice will be further randomized to +/- supplementation with Sulindac, a non-steroidal anti-inflammatory drug (NSAID), starting at the time of the diet switch. After 10 weeks of +/- Sulindac supplementation, mice will receive orthotopic injections of a mesenchymal derivative of an MMTV-Wnt-1 transgenic tumor, the M-Wnt cell line, and will continue on diet and treatment until euthanization. Results In our initial study, body weight, adiposity, and serum levels of leptin and insulin were similar in FOb and control mice, but serum levels of IL-6 were similar in FOb and DIO mice, and significantly higher than controls. Moreover, tumor burden, the mammary gland expression of key inflammatory genes, and the prevalence of hypermethylated inflammation-related genes in DNA from mammary tissue were comparable in DIO and FOb mice and significantly higher than in control mice, and there was high concordance with DNA methylation profiles in breast DNA from obese versus normoweight women participating in the UNC Normal Breast Study. Conclusions Our preclinical findings suggest that modest weight loss may not be sufficient to reverse the effects of chronic obesity on epigenetic reprogramming and inflammatory signals that are associated with obesity-related mammary tumor progression. Moreover, we have identified several genes with concordant obesity-related hypermethylation in humans and mice; which were unchanged in FOb mice. Thus combining weight loss regimens with epigenetic or inflammatory modulators may be an effective strategy for breaking the obesity-breast cancer link. We are currently assessing whether combining moderate weight loss with anti-inflammatory interventions (Sulindac or omega-3 fatty acids), or reprograming metabolism with a bariatric surgical intervention, is more effective than moderate weight loss alone at offsetting the persistent enhancing effects of chronic obesity on BLBC. Citation Format: Rossi EL, Bowers LW, Khatib SA, Doerstling SS, Hursting SD. Pre-clinical findings on obesity reversal and breast cancer progression: Targeting persistent inflammation. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-22.