The rising incidence of breast cancer and its related deaths especially among Asian population is alarming that requires more intense measures for its prevention and treatment. This doctoral research emphasizes on the role of adipocytokines in breast carcinogenesis. The study was conducted in Department of Biochemistry, University of Karachi in collaboration with the Breast clinic, Department of Surgery, Civil Hospital Karachi. It encompasses 175 breast cancer cases and 175 age, sex and BMI matched healthy controls. In addition to adipocytokines, demographic factors, basic clinical characteristics, histopathology, and other related biochemical parameters were also observed. In our study we found increased breast cancer risk with younger age at menarche, older age at menopause, exposure to higher reproductive years, older age at first live birth and increased period from menarche to first birth, while no significant differences were found for parity and breast feeding. However, early marriages, multiparity, and breast-feeding are the largely practiced norms in Pakistan. In our study population nearly half of the breast cancer cases were diagnosed with advance stage (stage III & stage IV) of the disease at presentation. This observation is due to the inverse association of education level and disease stage, with the largest number of advance stage breast cancer cases that have not received any type of formal education. Thus higher incidence of advance stage at diagnosis is probably due to lack of education, lack of cancer awareness, inaccessibility to screening and diagnosing services for women in Pakistan. Thus epidemiological observations of our study have greater repercussion for government and non-government organizations. We have also observed increased risk of advance stage breast cancer for combine absence of both estrogen and progesterone receptor expression due to its biologically aggressive type. Obesity increases the breast cancer risk plausibly via increasing the serum leptin, insulin resistance and free serum estradiol concentration. This study reiterates the link between abdominal obesity and breast carcinogenesis by demonstrating positive association of BMI and abdominal circumference with serum estrogen, insulin, leptin and HOMA-IR. On the other hand, inverse association was found with serum adiponectin, SHBG and serum progesterone. To further elucidate we investigated the risk of breast cancer for overweight and obesity and found increased risk in premenopausal, whereas decreased risk in postmenopausal subjects. This disparity between pre-and postmenopausal subjects in our study population is may be attributed due to higher frequency of advance stage disease cases among postmenopausal leading to lower BMI. Serum estrogen and progesterone have been linked with breast carcinogenesis. Results of our study suggest that higher serum estradiol and lower serum progesterone levels were found in both pre-and postmenopausal breast cancer cases, with higher significance of serum estrogen in postmenopausal group. This is explained by enhanced peripheral aromatase activity in the adipose tissue, which is attributed by obesity, hyperinsulinemia and high serum leptin level, converting androgens into estrogens particularly in postmenopausal state. Besides decreased SHBG levels also helps to increase the free serum estradiol levels promoting the breast carcinogenesis. Insulin along with hyperglycemia has been indicted for its growth stimulating effects in various cancers including breast cancer. The results of our study ascertain elevated fasting blood glucose, serum insulin and HOMA-IR levels as a breast cancer risk in both pre-and postmenopausal subjects. Insulin has direct mitogenic properties via its receptor and indirectly by increasing IGF-I and estrogen synthesis among breast cancer cells and adipose tissue. In this study we confirmed that hyperinsulinemia increases free estradiol levels via rising estrogen production and reduces synthesis of serum hormone binding globulin by demonstrating positive association of serum insulin with serum estrogen while inverse association with SHBG. Hyperinsulinemia raises the serum leptin levels by increase expression of ob gene, which is indicated in our results by showing positive association between the variables. The role of adipocytokines in the breast carcinogenesis has been under investigation. Leptin that act in an autocrine, paracrine and endocrine fashion, exerts its mitogenic effect on mammary tissue. Evidences provided by the observations of our study suggests that higher serum leptin levels increases breast cancer risk among pre-and postmenopausal women, both independently and in relation with obesity, and has a slight influence on the progression (stage) of breast cancer disease. This can be explained by the increase expression of aromatase enzyme by serum leptin leading to higher estradiol production in adipose tissue and breast cancer cells. This study also demonstrated the positive correlation of serum estrogen with BMI and serum leptin strengthening the fact. Adiponectin has a protective role from breast cancer directly by promoting apoptosis and decrease cell growth via its receptor. In addition, adiponectin lowers insulin resistance, binds to mitogenic growth factors and inhibits estrogen related cell growth via decreasing expression of aromatase enzyme and estrogen receptor in breast cancer cells. Observations of this study signifies that serum adiponectin levels exposes to higher breast cancer risk in both pre-and postmenopausal women, is inversely associated with measures of obesity and has found no effect on the stage of breast cancer disease. In addition, serum adiponectin has also shown to attenuate the serum levels of estradiol, insulin, fasting blood glucose, and insulin resistance denoted by HOMA-IR indicated in this study. Therefore, the results of our study support our proposition that altered secretion of adipocytokines from the adipose tissue supports breast carcinogenesis in our local studied population. These findings along with obesity, hyperinsulinemia and hyperglycemia depict metabolic dysregulation among breast cancer cases that could possibly be modulated as future preventive and therapeutic measures.