[18] Effect of Obesity on Prognosis after Early Breast Cancer.

Ewertz M, Jensen M-B, Gunnarsdottir K, Cold S Odense University Hospital, Odense, Denmark; University of Southern Denmark, Odense, Denmark; Danish Breast Cancer Co-operative Group, Copenhagen, Denmark

Background: Obesity is associated with an increased risk of dying from breast cancer. There may be several explanations for this such as obese women being diagnosed at a more advanced stage of disease or that treatment is less effective in obese patients. The aim of this study was to examine the influence of obesity on the risk of recurrence and death from breast cancer or other causes in relation to adjuvant treatment.
Material and methods: From the database of the Danish Breast Cancer Co-operative Group (DBCG) we identified 53816 women who received treatment for early breast cancer according to the DBCG protocols between 1977 and 2006 with complete data on follow up. Information was available on age and menopausal status at diagnosis, tumor size, number of lymph nodes removed, number of positive lymph nodes, deep fascia invasion, histological type, grade of malignancy, estrogen receptor status, treatment regimen, and protocol version (year), while data on height and weight to derive the body mass index (BMI, weight in kilograms divided by the square of height in meters) were available for 18967 patients or 35 % of the patients. The chemotherapy regimens included cyclophosfamide, metotrexate, and fluorouracil (CMF) up to 1999 and cyclophosfamide, epirubicin, and fluorouracil (CEF) from 1999 onwards. Endocrine therapy included mainly tamoxifen of durations from one to five years depending on time period. Associations between BMI (<25 vs ≥25,<30 vs ≥30) and other prognostic factors were analyzed by using the chi square test. Cause specific survival and invasive disease-free survival (type of first failure) were analysed by univariate and multivariate methods using Cox proportional hazards regression models.
Results: Compared with patients with a BMI less than 25, those with a higher BMI were older, more often postmenopausal, had larger tumors, more lymph nodes removed and more positive lymph nodes, more often invasion into deep fascia (all p<0.0001), and more often grade III tumors (p=0.04). Univariate analyses showed that the risk of a loco-regional recurrence was not related to BMI while the risk of distant metastases increased with increasing BMI after 3 years of follow up. The risk of dying from breast cancer remained elevated for patients with high BMI throughout 30 years of observation. Adjusting for the effect of other prognostic factors, multivariate analyses confirmed an independent prognostic effect of obesity. Within the first 10 years of follow-up chemotherapy and endocrine treatment were equally effective in lean and obese patients. However, after 10 or more years of follow-up, the treatment effect did not last in obese patients who had a poorer survival despite treatment.
Conclusion: Results from this population-based cohort of almost 19000 patients followed for up to 30 years confirmed that obesity is associated with a poorer prognosis after breast cancer. This is likely to be due to obese patients having a higher risk of developing distant metastases than lean patients and that adjuvant treatment seems to loose its effect more rapidly in obese patients.

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