Diabetes mellitus and obesity have long been recognized as cardiovascular risk factors. They also have a negative effect on breast cancer patients: Compared to metabolically healthy and normal-weight patients, the risk of recurrence after neoadjuvant chemotherapy is increased, as is the risk of death in diabetic women.
(ka) The new data come from an analysis of a total of 10,727 breast cancer patients. 8872 of them were treated in German Breast Group trials, 1855 in EORTC/Breast International Group (BIG) trials, informed Caterina Fontanella, MD, Udine, Italy [1]. Only half of these women were of normal weight, 30% were overweight, and 20% were even obese.
With increasing body weight, the 5-year rate for distant metastasis-free survival decreased linearly. This was true for women with luminal A/B subtype tumors (n=3977) and for women with triple-negative breast cancer (TNBC; n=1570). In the first group, the worsening of prognosis in overweight women is probably due to increased aromatase levels in adipose tissue. This increases the synthesis of estrogen, which stimulates the growth of breast cancer cells. In women with TNBC, the poorer treatment outcomes may be due in part to the increased levels of proinflammatory cytokines associated with obesity, Dr. Fontanella explained. “Secondly, it must be taken into account that obese patients probably receive chemotherapy doses that are too low. This is because doses of cytostatic drugs are usually calculated on a body surface area (KOF) of 2 m². In obese women, however, a larger KOF can be assumed.”
Special case HER2-negative
Only in patients with HER2-negative breast cancer (n=2418) no negative effect of obesity on treatment outcome could be determined. According to Dr. Fontanella, this is probably due to the markedly potent antitumor effect of anti-HER2 therapy.
Type 2 diabetes as a comorbidity
In the second evaluation, Dr. Fontanella and associates examined the prevalence of type 2 diabetes among participants in the GeparQuatro and GeparQuinto trials at the time of breast cancer diagnosis and the impact of this comorbidity on treatment outcomes. In this cohort, 112 patients (2.8%) had type 2 diabetes; only one-third received antidiabetic therapy. Diabetic patients were older than nondiabetic patients (61 vs. 49 years), more often obese (52 vs. 18%), and more often had more than two comorbidities (51 vs. 12%). Diabetic patients were also more likely than non-diabetic patients to already have a locally advanced tumor at diagnosis (28 vs. 14%) and more than three affected lymph nodes (14 vs. 5%). In addition, distant metastasis-free and overall survival were significantly shorter in diabetic patients than in metabolically healthy women (p<0.001 and p=0.001, respectively). Their risk of recurrence was significantly increased by a factor of 2 (p<0.001).
Hyperinsulinemia as a cause
According to Dr. Fontanella, the cause of higher tumor stage and poorer therapy results in diabetic women could be hyperinsulinemia, since the increased insulin level stimulates tumor cell growth. Tight glycemic control is therefore essential in this population to improve therapeutic outcome.
Source: European Breast Cancer Conference (EBCC) 9, March 19-21, 2014, Glasgow.
Literature:
- Fontanelle C, et al: EBCC 9; Abstr. O-417.
InFo ONCOLOGY & HEMATOLOGY 2014; 2(4): 21-22.
