Exercise prevents cancer incidence and recurrence, yet the underlying mechanism behind this relationship remains mostly unknown. Here we report that exercise induces the metabolic reprogramming of internal organs that increases nutrient demand and protects against metastatic colonization by limiting nutrient availability to the tumor, generating an exercise-induced metabolic shield. Proteomic and ex vivo metabolic capacity analyses of murine internal organs revealed that exercise induces catabolic processes, glucose uptake, mitochondrial activity, and GLUT expression. Proteomic analysis of routinely active human subject plasma demonstrated increased carbohydrate utilization following exercise. Epidemiologic data from a 20-year prospective study of a large human cohort of initially cancer-free participants revealed that exercise prior to cancer initiation had a modest impact on cancer incidence in low metastatic stages but significantly reduced the likelihood of highly metastatic cancer. In three models of melanoma in mice, exercise prior to cancer injection significantly protected against metastases in distant organs. The protective effects of exercise were dependent on mTOR activity, and inhibition of the mTOR pathway with rapamycin treatment ex vivo reversed the exercise-induced metabolic shield. Under limited glucose conditions, active stroma consumed significantly more glucose at the expense of the tumor. Collectively, these data suggest a clash between the metabolic plasticity of cancer and exercise-induced metabolic reprogramming of the stroma, raising an opportunity to block metastasis by challenging the metabolic needs of the tumor. Significance: Exercise protects against cancer progression and metastasis by inducing a high nutrient demand in internal organs, indicating that reducing nutrient availability to tumor cells represents a potential strategy to prevent metastasis. See related commentary by Zerhouni and Piskounova, p. 4124

Patient preferences regarding the gender of their physicians is a highly sensitive issue, which can be particularly salient in intimate medical situations. Previously published studies found that women tend to prefer female physicians, especially in the case of obstetricians and gynecologists. Data regarding other intimate specialties, such as breast surgery, are scarce. The present study was undertaken to assess gender preferences of women regarding their choice of a breast surgeon. Five hundred and fifteen consecutive women who attended breast clinics in two university-affiliated tertiary hospitals were prospectively enrolled. A 25-item anonymous questionnaire was completed by women independently and used to assess their preferences in selecting their breast surgeon. Of the 515 women, 500 (97 % response rate; mean age 50.6 ± 15.4 years) completed the anonymous questionnaire. Overall, 160 (32 %) women preferred to undergo breast examination by a female breast surgeon, 296 (59 %) had no preference, and only 44 (9 %) preferred a male surgeon. A same-gender preference was significantly and independently associated with younger age of the patients (Odds Ratio = 0.978, 95 % Confidence Interval 0.962–0.994, P = 0.007) and being married (Odds Ratio = 0.563, 95 % Confidence Interval 0.347–0.916, P = 0.021). However, only small and equal numbers of patients preferred to undergo breast surgery by a female (14 %) or a male (13 %) surgeon, and most patients (73 %) had no gender preferences. Furthermore, the three most important factors, which affected in general the actual selection, were surgical ability (93 %), experience (91.2 %) and knowledge (78.6 %), rather than physician gender per se. Overall, about a third of women prefer a female breast surgeon for their breast examination. Embarrassment during the examination was the major reason for same-gender preference. In contrast, when it comes to breast operations, preference for a female surgeon is less pronounced, with the professional skills of the surgeons becoming the predominant consideration. The fact that almost a third of the potential patients prefer female surgeons with regard to their breast examinations emphasizes the need to increase the number of female surgeons. Such an increase can be achieved through academic and economic changes that will enable more women to specialize in general surgery. Trial registration is not required for this type of research.