By ecancer reporter Clare Sansom

Breast cancer is one of a number of tumour types where obesity has been identified as a risk factor both for cancer development and, in some cases, for poor outcomes after diagnosis. Large studies have shown that women who are obese – defined as those with a body mass index (BMI¹) over 30 – have an increased risk of dying from breast cancer than lean women (BMI < 25); the risk for women who are overweight, with a BMI between 25 and 29, is assumed to be somewhere in between. The precise reasons for this, and the stages of cancer development that are most affected by obesity, remain unclear.

The Danish Breast Cancer Cooperative Group (DBCG) includes in its database detailed records for almost 19,000 women diagnosed with early-stage breast cancer in Denmark between 1977 and 2006. A group of researchers from hospitals participating in the DBCG has now analysed these records for an association between high BMI and breast cancer prognosis.

The researchers identified database records with complete follow-up data for 53,818 women who had received treatment for early-stage breast cancer following the DBCG protocols. Body mass index data was only available for 18,967 (35%) of these women, most often for women who had received adjuvant chemotherapy and least often for those treated with surgery alone. All patients had been followed up for at least ten years or until first failure, defined as breast cancer recurrence, another malignancy, or death. Data on causes of death after the end of follow-up was obtained from the Danish national registries. Patients were divided into four BMI categories, less than 25, between 25 and 29, 30 and above, and "unknown", and associations between BMI, tumour characteristics, and disease prognosis calculated using the chi-squared test.

Patients with any known BMI – the majority of whom had received chemotherapy, with or without endocrine treatment – were younger than those with no recorded BMI, most often pre-menopausal, and their tumours had more aggressive characteristics and were more often estrogen receptor negative. Not surprisingly, therefore, patients with unknown BMI had a consistently lower risk of developing either loco-regional or distant metastases at all times during the follow-up period.

Data from the group of patients with known BMI were analysed for associations between BMI and the risk of disease recurrence. No significant association was observed between BMI and the risk of local or regional metastases, but there were significant differences in the risk of distant metastases. There was a clear trend towards increasing risk of distant metastases with increasing BMI that became significant after three years' follow-up and subsequently increased with time. After ten years, 20.1% of lean women, 22.4% of overweight women and 24.3% of obese women had developed distant metastases. The risk of death from breast cancer also increased with BMI; 46.4% of lean women and 57.2% of obese women died as a result of breast cancer during the entire 30-year follow-up period. Both chemotherapy and endocrine therapy seemed to be less effective in protecting against recurrence in obese than in lean women.

Most previous studies of the relationship between obesity and breast cancer prognosis have recorded data only for disease free survival and these have given inconsistent results. This study shows that this may be because of differences in the definition of "disease-free". It indicates a clear association between obesity and the risk of developing distant, but not local or regional, breast cancer metastases, and suggests that adjuvant therapy may be less effective in obese women over the long term.

1. BMI defined as weight in kg divided by the square of height in m.

Reference

Ewertz, M., Maj-Britt Jensen, M.-B., Gunnarsdóttir, K.A., Højris, I., Jakobsen, E.H., Nielsen, D., Stenbygaard, L.E., Tange, U.B. and Cold, S. (2010) Effect of Obesity on Prognosis After Early-Stage Breast Cancer J. Clin. Oncology, published online ahead of print 29 November 2010 doi:10.1200/JCO.2010.29.7614