Sex steroids, carcinogenesis, and cancer progression

The relationship between sex steroids and cancer has been studied for more than a century. Using an original intact cell analysis, we investigated sex steroid metabolism in a panel of human cancer cell lines, either hormone responsive or unresponsive, originating from human breast, endometrium, and prostate. We found that highly divergent patterns of steroid metabolism exist and that the catalytic preference (predominantly reductive or oxidative) is strictly associated with the steroid receptor status of cells. We explored intra-tissue concentrations and profiles of estrogens in a set of human breast tumors as compared to normal mammary tissues, also in relation to their estrogen receptor status. In particular, we showed that, with hydroxyestrogens representing the majority of all tissue estrogens, concentrations of individual metabolites, as well as their ratios, significantly differ when comparing normal tissue with cancer tissues or when they are related to the overall survival of cancer patients. © 2004 New York Academy of Sciences

High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease

Purpose: We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003–2005 and followed up to the end of 2008. Methods: For 1607 Italian women (⩾15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (⩽84.0, 84.1–94.0, &gt;94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (⩽23.4, 23.5–27.3, &gt;27.3 kg/m2, unspecified), stage (T1–3N0M0, T1–3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER−PR−, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER−PR− cases were also run. Results: Patients often had T1–3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER−PR−. Diabetic patients were older and had more often high BMI (&gt;27 kg/m2), ER−PR−, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5–27.3 kg/m2 (hazard ratio (HR) = 2.9, 95% confidence interval (CI) 1.2–6.9). Breast cancer mortality was also higher in women with high (&gt;94 mg/dl) blood glucose compared to those with glucose 84.1–94.0 mg/dl (HR = 2.6, 95% CI 1.2–5.7). Conclusion: Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis.</br