Tamoxifen metabolism in breast cancer treatment: Taking the focus off the CYP2D6 gene

Tamoxifen (TAM) has been widely used to treat estrogen receptor (ER)-positive breast cancer, and has led to reduction of 50% in the annual recurrence rate and 30% in breast cancer mortality after 5 years of treatment.1 The prodrug TAM is a selective ER modulator that antagonizes ERs in cancer cells. However, compared with its two active metabolites 4-hydroxy-TAM (4-OH-TAM) and endoxifen, it is a relatively weak antiestrogen.

Validity of the physical activity questionnaires IPAQ-SF and GPAQ for Cancer Survivors: Insights from a Spanish cohort

Regular physical activity (PA) decreases mortality risk in survivors of breast and colorectal cancer. Such impacts of exercise have prompted initiatives designed both to promote and adequately monitor PA in cancer survivors. This study examines the validity of 2 widely used self-report methods for PA determination, the International Physical Activity Questionnaire short version (IPAQ-SF) and Global Physical Activity Questionnaire (GPAQ). Both instruments were compared with the triaxial accelerometry (Actigraph) method as an objective reference standard. Study participants were 204 cancer survivors (both sexes, aged 18-79 years). Compared with accelerometry, both questionnaires significantly overestimated PA levels (across all intensities) and underestimated physical inactivity levels. No differences were detected between the 2 questionnaires except for a shorter inactivity time estimated by GPAQ (p=0.001). The Bland and Altman method confirmed that both questionnaires overestimated all PA levels. Receiver operating characteristic (ROC) analysis classified IPAQ and GPAQ as fair and poor predictors, respectively, of the proportions of survivors fulfilling international PA recommendations (≥150 min·week-1 of moderate-vigorous PA). IPAQ-SF showed a higher sensitivity but lower specificity than GPAQ. Our data do not support the use of IPAQ-SF or GPAQ to determine PA or inactivity levels in cancer survivors.

Physical exercise minimizes the toxic triad for cancer: Physical inactivity, low fitness, and obesity

The so-called toxic triad of factors linked to cancer, namely obesity, poor cardiorespiratory fitness and physical inactivity, increase the risk of cancer and, when cancer is present, worsen its prognosis. Thus, obesity and a sedentary lifestyle have been linked to an elevated cancer risk whereas regular physical exercise and good cardiorespiratory function (CRF) diminish this risk. Despite genetic risk factors, there is evidence to show that some lifestyle modifications are capable of reducing the incidence of cancer and its associated morbidity and mortality. Regular physical exercise targeted at maintaining body weight within healthy limits and improving CRF will reduce a person's cancer risk and, once diagnosed, will also improve its prognosis, reducing mortality and the risk of disease recurrence through similar effects. In this review, we describe how physical activity can be used as a pleiotropic, coadjuvant tool to minimize the toxic triad for cancer and update the mechanisms proposed to date for the effects observed.