Obesity is an established risk factor for most hormone-dependent cancers, including breast cancer. The pathology underlying this phenomenon may be related to the endocrine and metabolic profile of this state. In the present case–control study, our results indicate that metabolic changes among newly diagnosed breast cancer patients are consistent with a systemic stress response, possibly because of the presence and/or diagnosis of cancer activating the stress-system that, in turn, alters further the existing metabolic state to an environment conducive to tumor growth. It has been well established that stress, both acute and chronic induces a powerful cascade of immune, metabolic and inflammatory reactions . On the other hand, we cannot exclude preexisting metabolic syndrome manifestations as a risk factor for the development of breast cancer and the two explanations are not mutually exclusive.
Our current data suggest that there is a positive association between triglycerides and ANG II levels in patients newly diagnosed with breast cancer. ANG II is a biologically active peptide of the renin-angiotensin system (RAS) involved in blood pressure regulation, tissue remodeling and angiogenesis, as well as in vascular and inflammatory pathologies. Consequently, the major functions attributed to ANG II (inflammation, angiogenesis and migration) are also related to cancer progression [26–28]. We also showed that there is a negative association of ANG II with HDL and aPAI which were in agreement with previous studies [29, 30]. However, other studies reported a positive association between ANG II and breast cancer [31, 32]. On the other hand, a very recent study involving more than 230,000 women (Swedish AMORIS Study) showed no association between HDL and breast cancer risk, while it demonstrated a weak protective association between circulating triglycerides and risk for breast cancer .
Obesity is increasingly associated with postmenopausal breast cancer risk , whereas, in premenopausal women there is an inverse relation between BMI and breast cancer risk [35, 36]. We have previously demonstrated in our cross-sectional study that inflammatory biomarkers known to be elevated in breast cancer patients (IL-6 and CRP) are also increased in obese and insulin resistant pre-menopausal women . The present findings, therefore, confirm that inflammatory markers, specifically CRP and TNF-α are elevated in newly diagnosed patients with breast cancer.
Inflammation is associated with poor prognosis and decreased survival in many cancers. As obesity per se is considered a subclinical inflammation, the increased levels of TNF-α and CRP in breast cancer cases in the present study are consistent with stress-induced inflammation among newly diagnosed breast cancer patients. In addition, CRP was positively correlated with BMI and inversely with adiponectin levels, in agreement with previous reports [22, 23]. Thus, in obesity, the adipocytokines and in particular, adiponectin and the inflammatory mediators might exert an additive effect to positively impact breast cancer pathogenesis.
Our data showed significantly elevated mean level of serum glucose, diastolic blood pressure and reduced HDL in the breast cancer group. Previous studies reported that high fasting glucose levels were directly correlated with breast cancer both in pre-menopausal and postmenopausal women [38, 39]. In addition, reduced HDL-cholesterol and increased blood pressure contributed to increased risk for breast cancer [40, 41]. Furthermore, low HDL-cholesterol, hypertension, and hyperglycemia have all been associated with breast cancer [38, 40, 42–44].
The authors acknowledge some limitations. The case–control cross-sectional design limits the findings to at best, suggestive. The small sample size might explain the failure to produce significant associations in parameters that were expected to associate with clinical variables. Furthermore several confounders were excluded such as family history of breast cancer and medications and as such the findings cannot be generalized. Despite these limitations, the present study is among the few to observe pathologic changes in the adipocytokine, metabolic and immune biomarkers among early diagnosed breast cancer patients. These changes may reflect an earlier risk or a stressful environment conducive to tumor growth and/or both.