Effect of obesity on prognosis after early-stage breast cancer.
ABSTRACT This study was performed to characterize the impact of obesity on the risk of breast cancer recurrence and death as a result of breast cancer or other causes in relation to adjuvant treatment.
Information on body mass index (BMI) at diagnosis was available for 18,967 (35%) of 53,816 women treated for early-stage breast cancer in Denmark between 1977 and 2006 with complete follow-up for first events (locoregional recurrences and distant metastases) up to 10 years and for death up to 30 years. Information was available on prognostic factors and adjuvant treatment for all patients. Univariate analyses were used to compare the associations of known prognostic factors and risks of recurrence or death according to BMI categories. Cox proportional hazards regression models were used to assess the influence of BMI after adjusting for other factors.
Patients with a BMI of 30 kg/m(2) or more were older and had more advanced disease at diagnosis compared with patients with a BMI below 25 kg/m(2) (P < .001). When data were adjusted for disease characteristics, the risk of developing distant metastases after 10 years was significantly increased by 46%, and the risk of dying as a result of breast cancer after 30 years was significantly increased by 38% for patients with a BMI of 30 kg/m(2) or more. BMI had no influence on the risk of locoregional recurrences. Both chemotherapy and endocrine therapy seemed to be less effective after 10 or more years for patients with BMIs greater than 30 kg/m(2).
Obesity is an independent prognostic factor for developing distant metastases and for death as a result of breast cancer; the effects of adjuvant therapy seem to be lost more rapidly in patients with breast cancer and obesity.
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ABSTRACT: The prevalence of risk factors contributing to metabolic syndrome (MetS) is increasing, and numerous components of MetS are associated with increased primary breast cancer (BC) risk. However, less is known about the relationship of MetS to BC outcomes. The aim of this study was to evaluate whether MetS, characterized by increased weight, hypertension, low HDL-cholesterol, high triglycerides, and diabetes or impaired glucose tolerance, is associated with risk of second breast cancer events (SBCE) and BC-specific mortality. Retrospective cohort study of women diagnosed with incident early-stage (I-II) BC between 1990 and 2008, enrolled in an integrated health plan. Outcomes of interest were SBCE, defined as recurrence or second primary BC, and BC-specific mortality. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95 % confidence intervals (CI) for time-varying exposure to MetS components while accounting for potential confounders and competing risks. Among 4,216 women in the cohort, 26 % had >/=3 MetS components and 13 % developed SBCE during median follow-up of 6.3 years. Compared to women with no MetS components, presence of MetS (>/=3 components) was associated with increased risk of SBCE (HR = 1.50, 95 % CI 1.08-2.07) and BC-specific mortality (HR = 1.65, 95 % CI 1.02-2.69). Of the individual components, only increased weight was associated with increased risk of SBCE (HR = 1.26, 95 % CI 1.06-1.49). MetS is associated with modestly increased risk of SBCE and BC-specific mortality. Given the growing population of BC survivors, further research in larger and more diverse populations is warranted.Breast Cancer Research and Treatment 10/2014; · 4.20 Impact Factor
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ABSTRACT: It is increasingly evident that not only breast cancer cells, but also the tissue embedding these cells: the tumor microenvironment, plays an important role in tumor progression, metastasis formation and treatment sensitivity. This review focuses on the current knowledge of processes by which the microenvironment affects breast cancer, including formation of the metastatic niche, metabolic stimulation, stimulation of tumor cell migration, immune modulation, angiogenesis and matrix remodeling. The number of drugs targeting key factors in these processes is expanding, and the available clinical data is increasing. Therefore current strategies for intervention and prediction of treatment response are outlined. At present, targeting the formation of the metastatic niche and metabolic stimulation by the breast cancer microenvironment, is already showing clinical efficacy. Intervening in the stimulation of tumor cell migration and immune modulation by the microenvironment is an upcoming field of great research interest. In contrast, targeting microenvironmental angiogenesis or matrix remodeling appears to be of limited clinical relevance in breast cancer treatment so far. Further research is warranted to optimize intervention strategies and develop predictive tests for the relevance of targeting involved factors within the microenvironment in order to optimally personalize breast cancer treatment.Pharmacology [?] Therapeutics 11/2014; 147. · 7.75 Impact Factor
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ABSTRACT: Epidemiological data suggest a close link between obesity and breast cancer, the most frequently occurring cancer in women. The metabolic syndrome is typically associated with abdominal obesity and comprises disturbances in glucose and/or lipid metabolism and/or hypertension. Recent studies have established a specific association between the metabolic syndrome - as well as its components - and breast cancer, indicating both an increased risk of developing breast cancer and a poorer prognosis. In premenopausal women, obesity might have a protective effect only on receptor-positive tumors, whereas a positive association was observed between obesity/abdominal obesity and an increased risk of triple-negative breast cancer (TNBC). Overall survival and disease-free survival were reported to be significantly shorter in premenopausal obese women with TNBC compared to non-obese women, but these results are still inconsistent and need further research. The metabolic syndrome is characterized by a state of insulin resistance/hyperinsulinemia and subacute chronic inflammation, with both conditions offering a plausible mechanistic link towards breast cancer. Thus, in addition to their increased risk of cardiovascular morbidity and mortality, women with this syndrome represent a group at elevated risk of developing breast cancer and with poorer prognosis.Breast Care 04/2014; 9(4):277-81. · 0.91 Impact Factor