December 14, 2009 (San Antonio, Texas) — In women who have early breast cancer, being overweight or obese at diagnosis is associated with a higher risk for distant recurrences and disease-specific death later on, according to a new long-term study presented here at the 32nd Annual San Antonio Breast Cancer Symposium.
Being overweight or obese was also associated with being diagnosed at a more advanced stage of disease.
In the study, overweight (body mass index [BMI], 25 to 30 kg/m2) and obese (BMI ≥ 30 kg/m2) women were compared with normal-weight women (BMI <>2).
With nearly 19,000 women, the study has more cases than any other study examining this issue, said Michelle D. Holmes, MD, DrPH, from Harvard University in Boston, Massachusetts.
"Most studies in women with breast cancer have found increased mortality with increased BMI," said Dr. Holmes, who acted as a discussant of the study, which was presented by Marianne Ewertz, MD, from Odense University Hospital in Denmark.
"These Danish data confirm other results and add detail," said Dr. Holmes.
Among the new details is evidence that adjuvant treatment seems to be less effective in obese women, said Dr. Holmes.
"Previous research has shown that obese women have not gotten correct weight-based doses," Dr. Holmes explained.
In addition to having an unprecedented number of cases, the new study followed patients for 30 years (1977 to 2006). "That's a very long time," said Dr. Holmes.
In Time, the Extra Weight Is Costly
Using the Danish Breast Cancer Cooperative Group database, Dr. Ewertz and colleagues examined the influence of obesity at diagnosis on the risk for breast cancer recurrence and mortality in relation to adjuvant treatment.
Information from almost 54,000 women with early breast cancer was evaluated, including age and menopausal status at diagnosis, tumor size, number of lymph nodes removed, number of positive lymph nodes, histological type, grade of malignancy, estrogen-receptor status, and treatment protocol.
The investigators were able to calculate BMI for 35% (n = 18,967) of the women for whom height and weight information was available.
The researchers grouped the distant recurrence data into 2 periods: 0 to 5 years and 5+ years.
A multivariate analysis of the effect of obesity on the risk for distant metastases showed a "clear relationship," between the 2, said Dr. Ewertz. However, the increased risk did not show up immediately.
In years 0 to 5, there was no increased risk for distant metastases for overweight women (BMI, 25 to 30 kg/m2). However, after 5 years, for these women, there was an adjusted hazard ratio of 1.42 (95% confidence interval [CI], 1.17 - 1.73; P = .0005). The women with a BMI under 25 kg/m2 served as the reference group for the calculations.
For the obese women (BMI ≥ 30 kg/m2), the same pattern held true. There was no increased risk for distant metastases for the first 5 years; thereafter, the hazard ratio was similar to that for the overweight women.
The researchers grouped the mortality data into 2 periods: 0 to 10 years and 10+ years. For both overweight and obese women, the first 10 years after diagnosis carried no increased risk for disease-specific death.
At 10+ years, there was an adjusted hazard ratio of 1.26 (95% CI, 1.09,1.46; P = .002) for the overweight women and of 1.38 (95 CI, 1.11 - 1.71; P = .003) for the obese women.
However, although the risk for distant metastases increased with BMI, being overweight did not influence loco-regional recurrence, the investigators reported.
Adjuvant Therapy Less Effective?
Adjuvant treatment seemed to lose its effect more rapidly in obese patients, according to Dr. Ewertz.
The adjuvant therapy included the chemotherapy regimens of cyclophosfamide, metotrexate, and fluorouracil up to 1999 and of cyclophosfamide, epirubicin, and fluorouracil from 1999 onward. In addition, endocrine therapy, of which tamoxifen was most common, consisted of durations of 1 to 5 years. Only 294 patients were recorded as having received trastuzumab (Herceptin, Genentech).
The researchers created 3 groups for the purposes of analysis: chemotherapy, endocrine therapy, and the combination of chemotherapy and endocrine therapy.
For the first 10 years, among the overweight women, there was no impact on survival by treatment. But at 10+ years, there was increased risk for death among those treated with chemotherapy and combination therapy but not those treated with endocrine therapy alone
The obese women had an increased risk for death both in the first 10 years (combination therapy) and at 10+ years (all treatment groups).
"More research is needed into the mechanisms behind the poorer response to adjuvant treatment among obese women with breast cancer," said Dr. Ewertz.
The study was conducted without support from pharmaceutical companies. Dr. Ewertz's participation at the meeting was sponsored by GlaxoSmithKline and she reports receiving a research grant from Novartis. Dr. Holmes has disclosed no relevant financial relationships.
32nd Annual San Antonio Breast Cancer Symposium (SABCS): Abstract 18. Presented December 10, 2009.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου