Roxanne Nelson

May 16, 2014

Obesity increases the risk of dying from breast cancer by a third, a huge new study shows.

However, the effect of obesity was only observed in premenopausal women with estrogen-receptor (ER)-positive disease. Surprisingly, obesity seemed to have little effect on outcome in postmenopausal women with ER-positive disease.

In addition, in women with ER-negative disease, obesity had little effect on outcome.

Results from the study, which involved more than 80,000 breast cancer patients, were discussed at a presscast held in advance of the 2014 Annual Meeting of the American Society of Clinical Oncology® (ASCO), where they will be presented in full.

"Previous studies have reported an association between obesity and ER-positive cancers, but those studies were too small to distinguish the direction of that association," said study investigator Hongchao Pan, PhD, from the University of Oxford in the United Kingdom.

And unlike previous studies, this study had a sufficient number of ER-negative patients to address the association between morbidity and obesity. "We saw none," he reported.

Their findings, however, were surprising and opposite of what was expected. Dr. Pan explained that although there was an association between obesity and risk for death in a specific breast cancer population, it did not prove a cause-and-effect link. "We don't know why," he said. "We know it's definite and its real, but we don't know the underlying mechanism at this time."

Negative Associations

A growing number of studies have highlighted a negative association between being overweight or obese and breast cancer. One recent retrospective analysis of 3 clinical trials found that women who were overweight or obese at the time they were diagnosed with hormone-receptor-positive operable breast cancer had an increased risk for recurrence and death, despite receiving optimal treatment. The effect was observed in both pre- and postmenopausal women.

 
All patients need to be counseled about losing weight and having a healthy lifestyle.
 

In addition, a large retrospective analysis found obesity to be an independent prognostic factor for mortality and distant metastases after a diagnosis of breast cancer. In addition, adjuvant therapy appeared to be less effective, on a long-term basis, in obese patients with breast cancer.

Applies Across the Board

Results from the study by Dr. Pan's team "are interesting, in that only younger women were affected," said Heather Han, MD, a medical oncologist from the Center for Women's Oncology at the H. Lee Moffitt Cancer Center in Tampa, Florida. "This is an analysis that includes 80,000 women, which is unprecedented. This is a very high level of evidence from a very reputable study group."

 
Obesity is slated to replace tobacco as the leading overall modifiable risk factor for cancer.
 

That said, the data are not really new or practice-changing, because obesity has been linked to an ever-widening array of detrimental effects on health. "Even though this study found an increased risk of death in younger women with ER-positive disease, it doesn't mean that they are the only group that needs to be concerned about being overweight," Dr. Han told Medscape Medical News. "Regardless of age and disease, all patients need to be counseled about losing weight and having a healthy lifestyle."

But this is easier said than done. "We know that diet and exercise can help patients, but changing your lifestyle can be very difficult," she conceded.

However, if we tell women that losing weight could be "as effective as chemotherapy, they might be more motivated," said Dr. Han.

ASCO president Clifford A. Hudis, MD, FACP, pointed out that this is "yet another in the long list of potential negatives related to lifestyle and obesity."

"It could be that subsets of obese patients would benefit from specific therapeutic interventions, be it targeted diet, drugs, or food supplements — all of which may be useful in mitigating the risk," he said

"But any way we look at this, obesity is slated to replace tobacco as the leading overall modifiable risk factor for cancer," Dr. Hudis added. "We are going to have to tackle this from a public health point of view."

Study Details

Obesity, defined as a body mass index (BMI) of at least 30 kg/m², is associated with a worse prognosis in early breast cancer. But this association could be affected by ER positivity, ovarian activity, and age, the investigators note.

Dr. Han and colleagues gathered data from the Early Breast Cancer Trialists' Collaborative Group on 80,000 patients who participated in 70 early breast cancer trials. They evaluated BMI, ER status, menopausal status, age, recurrence, death, tumor diameter, and nodal status.

In this cohort, mean follow-up was 8 woman-years, 40,000 women were postmenopausal, and 20,000 women had ER-negative disease.

In patients with ER-negative disease, there was little association between BMI and breast cancer mortality. After adjustment for tumor diameter and nodal status, there was no association.

In women with ER-positive disease, BMI was associated with breast cancer mortality in pre- and perimenopausal women (2P < .00001) and in postmenopausal women (2P < .00001). After adjustment for tumor characteristics, this association was significant only in pre- and perimenopausal women.

After adjustment for tumor characteristics, the only significant mortality rate ratio — for obese pre- and perimenopausal women with ER-positive disease, compared with corresponding healthy-weight women — was 1.34 (95% confidence interval [CI], 1.22 - 1.47; 2P < .00001).

The same association was not observed for postmenopausal women with ER-positive disease (rate ratio, 1.06; 95% CI, 0.99 - 1.14; 2P = .12).

When the data for ER-positive women were analyzed by age instead of menopausal status, obesity appeared to be relevant in women up to about 55 years of age.

This study was funded by the UK Medical Research Council, Cancer Research UK, and the British Heart Foundation. The authors have disclosed no relevant financial relationships.

2014 Annual Meeting of the American Society of Clinical Oncology. Abstract 503. To be presented May 31, 2014.

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