Marshall, James R.

Abstract Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and toxicity limits use of these agents. Vitamin D is a potential prevention therapy for both ER+ and ER− disease and is safe with few side effects. This study evaluates the effect of 1-year of vitamin D supplementation on mammographic density (MD), a biomarker of breast cancer risk in a multicenter randomized controlled trial. Premenopausal women with ≥25% MD and no history of cancer were randomly assigned to 2,000 international units (IU) of vitamin D or placebo orally daily for 1 year. Change in percent MD was evaluated using Cumulus software after all participants completed treatment. Three hundred women enrolled between January 2011 and December 2013 with a mean age of 43 and diverse ethnicity [14% Hispanic, 12% African American (AA)]. Supplementation significantly increased vitamin D levels compared with placebo (14.5 ng/mL vs. −1.6 ng/mL; P < 0.0001) with all participants on the vitamin D arm achieving vitamin D sufficiency at 12 months. Vitamin D was safe and well tolerated. After adjustment for baseline MD, the mean between-arm difference (vitamin D vs. placebo) at 1 year was −0.75 (−0.26, 1.76; P = 0.56). A greater effect was seen for women with ≥50% MD and AA women, although neither reached significance. This randomized controlled trial demonstrated significant improvement in vitamin D levels with 2,000 IU for 1 year, with 100% of supplemented women achieving sufficiency. However, a null effect was seen regarding change in MD for premenopausal women (the primary outcome of the study). Prevention Relevance: Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and are underutilized due to toxicity and side effects. Vitamin D is a potential prevention therapy for both ER+ and ER− disease and is safe with few side effects.

TPS1608 Background: Metformin may have growth inhibitory effects on many cancer types including breast cancer. NCIC MA.32 is a randomized placebo-controlled trial examining the effects of 5 years of metformin in women with breast cancer ( http://clinicaltrials.gov/show/NCT01101438 ). This trial offers us the opportunity to explore the effects of metformin on breast cancer biomarkers to gain an understanding of the potential chemo preventive effects of this drug. The primary aim of this companion to MA.32 (Alliance trial # A211201) is to examine the effects of 1 year of metformin vs placebo on breast density for women with Estrogen Receptor negative (ER-) breast cancer. Secondary aims of this study include: evaluation of breast density following 2 years of metformin use, and correlation of density with fasting insulin, glucose and Homeostasis Model Assessment (HOMA). Exploratory aims include examination of the effects of metformin on second cancer rates. Methods: Eligible women must have been enrolled on MA.32 (North America accrual completed January 23, 2013), have hormone receptor-negative breast cancer, and breast composition on mammography >25% glandular density, have a digital mammogram within 12 months of registration on MA.32 and have an intact, unaffected contralateral breast. Women enrolled on this study must provide menstrual cycle data (if premenopausal) and digital mammograms. All other study related information is gathered through participation in MA.32. Mammographic density will be calculated using Cumulus software (the Boyd method). Our accrual goal is 458 patients (229 per arm) and with an assumption of 20% drop out due to drug intolerance and another 20% due to ineligibility. Therefore, with a sample size of 274 (137 per arm) we will have at least 85% power to detect a 4% difference between study arms, i.e., 5% change from baseline to one year of treatment for metformin vs. 1% for placebo, using the two-sided two-sample t-test at a significance level of 5%. This study was activated in the United States on 8/22/2012 and 15 patients have been accrued to date. This study is sponsored by the NCI and the Alliance for clinical trials. Clinical trial information: NCT01666171.

Abstract This abstract was withdrawn by the authors.

An effort over 3 years to conduct a data pooling project regarding the association between smoking and lung cancer treatment outcomes has shown that, of 32 completed studies of lung cancer treatments in 1 National Cancer Institute Cooperative Group, only a minority have usable data concerning smoking‐related variables. Clinical trials research is needed to inform patients with cancer and their physicians about the impact of smoking, and how smoking cessation may affect the course of their disease.

Abstract Purpose: The purpose of this study was to evaluate oncologists' preferences for methods to increase delivery of tobacco cessation support to cancer patients. Methods: An email list of 6844 physicians at NCI Designated Cancer Centers was generated using publically available online resources. An online survey was conducted in the fall of 2013 to assess tobacco assessment and cessation practices by physicians, barriers to providing cessation support, and methods to improve access to cessation services for cancer patients. Results of this survey are compared to similar survey findings by the American Society of Clinical Oncology (ASCO) and the International Association for the Study of Lung Cancer (IASLC). Results: Of 6844 electronically delivered survey invitations, we received 887 responses (13%). Consistent with previously published ASCO and IASLC surveys, 90% of physicians agreed that tobacco use by patients affects cancer treatment outcomes (vs. 87-92% in ASCO/IASLC), 90% of respondents reported that they ask patients about their tobacco use (vs. 90% in ASCO/IASLC), and 83% routinely advise tobacco users to quit (vs. 80-82% in ASCO/IASLC). However, only 37% of respondents regularly discussed medications, and 35% actively treated patients (vs. 39-44% in ASCO/IASLC). Most (71%) responding oncologists preferred cessation support be provided at the initial patient consult, and few (11%) were concerned about the use of tobacco cessation medications. Lack of time and lack of available resources were the dominant barriers to the administration of tobacco cessation support to cancer patients by oncologists. Only 10% of oncologists believed they were adequately trained to counsel patients on smoking cessation, but 55% reported that training for someone else in their clinic would increase tobacco cessation support. When asked what provider they prefer to administer cessation support to cancer patients, 16% reported a primary care physician, 18% reported a mid-level (nurse practitioner or physician assistant), 50% reported any other clinical staff, and only 1% preferred to personally provide cessation support. Whereas most (58%) oncologists preferred to have dedicated cessation services within their institution, 38% reported they would use dedicated services either within, or outside their institution. Conclusions: Most oncologists at NCI Designated Cancer Centers recognize the importance of tobacco cessation, but prefer to have tobacco cessation support for cancer patients provided by another trained professional. Citation Format: Alix Pommerenke, Anthony Alberg, Thomas H. Brandon, Ivana Croghan, Michael K. Cummings, Carolyn Dresler, Ellen R. Gritz, Roy Herbst, Scott Leischow, James R. Marshall, Benjamin Toll, Graham Warren. Physician preferences in tobacco cessation support for cancer patients: A survey of physicians at National Cancer Institute Designated Cancer Centers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5049. doi:10.1158/1538-7445.AM2014-5049