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Abstract In a 3-arm presurgical trial, four-six weeks exemestane 25 mg three times/week (TIW) was non-inferior to 25 mg/day (QD) in suppressing circulating estradiol in postmenopausal women with ER-positive breast cancer. Since obesity may decrease exemestane efficacy, we analyzed changes in sex steroids, adipokines, Ki-67, and drug levels in relation to obesity. Postmenopausal women with early-stage ER-positive breast cancer were randomized to either exemestane 25 mg QD (n = 57), 25 mg TIW (n = 57), or 25 mg/week (QW, n = 62) for 4–6 weeks before breast surgery. Serum and tissue pre- and post-treatment biomarkers were stratified by body mass index (BMI)< or ≥30 kg/m2. Post-treatment median exemestane and 17-OH exemestane levels were 5–6 times higher in the QD arm compared to the TIW arm. For obese women, TIW maintained comparable reductions to QD in systemic estradiol levels, although the reduction in estrone was less with the TIW regimen. There was less suppression of SHBG with the TIW versus the QD dose schedule in obese women which should result in less systemic bioavailable estrogens. Metabolically, the effect of the TIW regimen was similar to the QD regimen for obese women in terms of leptin suppression and increase in the adiponectin-leptin ratio. Reduction in tissue Ki-67 was less for obese women on the TIW regimen than QD, although changes were similar for non-obese women. Our findings suggest that TIW exemestane should be explored further for primary cancer prevention in both normal weight and obese cohorts.

Breast cancer (BC) prevention remains the ultimate cost-effective method to reduce the global burden of invasive breast cancer (IBC). To date, surgery and chemoprevention remain the main risk-reducing modalities for those with hereditary cancer syndromes, as well as high-risk non-hereditary breast lesions such as ADH, ALH, or LCIS. Ductal carcinoma in situ (DCIS) is a preinvasive malignant lesion of the breast that closely mirrors IBC and, if left untreated, develops into IBC in up to 50% of lesions. Certain high-risk patients with DCIS may have a 25% risk of developing recurrent DCIS or IBC, even after surgical resection. The development of breast cancer elicits a strong immune response, which brings to prominence the numerous advantages associated with immune-based cancer prevention over drug-based chemoprevention, supported by the success of dendritic cell vaccines targeting HER2-expressing BC. Vaccination against BC to prevent or interrupt the process of BC development remains elusive but is a viable option. Vaccination to intercept preinvasive or premalignant breast conditions may be possible by interrupting the expression pattern of various oncodrivers. Growth factors may also function as potential immune targets to prevent breast cancer progression. Furthermore, neoantigens also serve as effective targets for interception by virtue of strong immunogenicity. It is noteworthy that the immune response also needs to be strong enough to result in target lesion elimination to avoid immunoediting as it may occur in IBC arising from DCIS. Overall, if the issue of vaccine targets can be solved by interrupting premalignant lesions, there is a potential to prevent the development of IBC.

Therapies originating from traditional medical systems are widely used by patients in both India and the United States. The first India-US Workshop on Traditional Medicine was held in New Delhi, India, on March 3 and 4, 2016, as a collaboration between the Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH) of the Government of India, the US National Cancer Institute (NCI), National Institutes of Health, and the Office of Global Affairs, US Department of Health and Human Services. It was attended by Indian and US policymakers, scientists, academics, and medical practitioners from various disciplines. The workshop provided an opportunity to open a dialogue between AYUSH and NCI to identify promising research results and potential topics for Indo-US collaboration. Recommendations that emerged from the workshop underlined the importance of applying rational and scientific approaches for drug development; standardizing traditional medicine products and procedures to ensure reliability and reproducibility; promotion of collaboration between Indian traditional medicine practitioners and researchers and US researchers; greater integration of evidence-based traditional medicine practices with mainstream medical practices in India; and development of training programs between AYUSH and NCI to facilitate crosstraining. Several positive developments took place after the thought-provoking deliberations.

Disparities between African American and Caucasian men in prostate cancer (PCa) diagnosis and treatment in the United States have been well established, with significant racial disparities documented at all stages of PCa management, from differences in the type of treatment offered to progression-free survival or death. These disparities appear to be complex in nature, involving biological determinants as well as socioeconomic and cultural aspects. We present a review of the literature on racial disparities in the diagnosis of PCa, treatment, survival, and genetic susceptibility. Significant differences were found among African Americans and whites in the incidence and mortality rates; namely, African Americans are diagnosed with PCa at younger ages than whites and usually with more advanced stages of the disease, and also undergo prostate-specific antigen testing less frequently. However, the determinants of the high rate of incidence and aggressiveness of PCa in African Americans remain unresolved. This pattern can be attributed to socioeconomic status, detection occurring at advanced stages of the disease, biological aggressiveness, family history, and differences in genetic susceptibility. Another risk factor for PCa is obesity. We found many discrepancies regarding treatment, including a tendency for more African American patients to be in watchful waiting than whites. Many factors are responsible for the higher incidence and mortality rates in African Americans. Better screening, improved access to health insurance and clinics, and more homogeneous forms of treatment will contribute to the reduction of disparities between African Americans and white men in PCa incidence and mortality.

Background. Prostate cancer (PCa) racial disparity is multifactorial, involving biological, sociocultural, and lifestyle determinants. We investigated the association between selected potentially functional polymorphisms (SNPs) and prostate cancer (PCa) risk in Black (AAM) and White (EAM) men. We further explored if these associations varied by the body mass index (BMI) and height. Methods. Age-matched DNA samples from 259 AAM and 269 EAM were genotyped for 10 candidate SNPs in 7 genes using the TaqMan allelic differentiation analysis. The dominant, recessive, and additive age-adjusted unconditional logistic regression models were fitted. Results. Three SNPs showed statistically significant associations with PCa risk: in AAM, HNF1B rs7501939 (OR=2.42, P=0.0046) and rs4430796 (OR=0.57, P=0.0383); in EAM, CTBP2 rs4962416 (OR=1.52, P=0.0384). In addition, high BMI in AAM (OR=1.06, P=0.022) and height in EAM (OR=0.92, P=0.0434) showed significant associations. Interestingly, HNF1B rs7501939 was associated with PCa exclusively in obese AAM (OR=2.14, P=0.0103). Conclusion. Our results suggest that variation in the HNF1B may influence PCa risk in obese AAM.