Abstract
Epidemiological studies suggest a possible association between BMI, diagnosis and clinical-pathological breast cancer characteristics but biological bases for this relationship still remain to be ascertained. Several biological mechanisms play a role in the genesis and progression of breast cancer. This study aimed to investigate relationships between BMI and breast cancer diagnosis/progression in a Southern Italian population and to try to interpret results according to the serum proteomic profile of healthy and breast cancer patients.BMI, presence or absence of breast cancer and its clinical-pathological characteristics were analyzed in a series of 300 breast cancer women and compared with those of 300 healthy women prospectively. To investigate whether obesity is associated with alterations in serum protein profile, SELDI-ToF approach was applied.Alcohol consumption (22.7% vs 11.3%; p<0.001) and postmenopausal status (65.7% vs 52%; p<0.001) but not BMI resulted significantly different in patients vs controls. Conversely, BMI was significantly associated with a larger-tumour size (BMI> = 30 respect to normal weight: OR = 2.49, 95% CI 1.25–4.99, p = 0.0098) and a higher probability of having positive axillary lymph node (OR = 3.67, CI 95% 2.16–6.23, p<0.0001). Multivariate analysis confirmed the association of breast cancer diagnosis with alcohol consumption (OR = 2.28;CI 1.36–3.83; p<0.0018). Serum protein profile revealed the presence of significant (p-value <0,01) differentially expressed peaks m/z 6934, m/z 5066 in high BMI breast cancer patients vs healthy subjects and m/z 6934, m/z 3346 in high vs low BMI breast cancer patients.The analysis of pathological features of cancer indicates that normal weight women have a significantly higher probability of having a smaller breast cancer at time of diagnosis and negative axillary lymph nodes while increased BMI is associated with an altered protein profile in breast cancer patients. Further studies to identify specific proteins found in the serum and their role in breast cancerogenesis and progression are in progress.
Highlights
In the last recent years, body-weight has been suggested as a possible factor associated with breast cancer [1] and, nowadays, the link between obesity and postmenopausal breast cancer can be confirmed
The aim of the present study was: 1) to analyze Body Mass Index (BMI), as a risk factor for breast cancer and/or predictive factor for its pathological characteristics in a prospective consecutive and monoinstitutional series of 300 breast cancer women compared to 300 healthy women; 2) to perform serum proteomic profiles by SELDI-ToF-Mass Spectrometry (MS) in the same consecutive and prospective series of subjects in order to discover serum protein related with breast cancer and body mass index (BMI)
The two groups did not show any significant difference in frequency of different BMI categories even though a trend for higher percentage of high BMI cases in breast cancer women was clearly evident (p = 0.0721 by chisquare test)
Summary
In the last recent years, body-weight has been suggested as a possible factor associated with breast cancer [1] and, nowadays, the link between obesity and postmenopausal breast cancer can be confirmed. This link has generally been attributed to the action of some hormones relevant in fat metabolism and in particular to direct serum concentration increase of bioavailable oestradiol [2]. The concentration of circulating estrogens, which is related to both increased adipose tissue mass and up-regulation of aromatase enzyme, has been reported to be a contributing factor towards the increased risk for hormone receptor – positive breast cancer in obese women [4]. The mitogenic, antiapoptotic, and proangiogenic properties of insulin have been suggested as an explanation of its implication in cancer progression; insulin is able to stimulate the synthesis of IGF-1, which has multiple effects that have been linked to tumor growth and metastasis [8]
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