Meeting News CoveragePerspective

Obesity linked to mortality in premenopausal, ER-positive early breast cancer

Obesity was an independent risk factor for breast cancer mortality among premenopausal women with ER-positive disease, according to results of a meta-analysis.

Researchers did not observe the association among postmenopausal women with ER-positive disease, or in women with ER-negative disease.

“Obesity is reportedly associated with worse prognosis in early breast cancer, but this association could depend strongly on ER positivity and ovarian activity,” Hongchao Pan, PhD, lead study author and a researcher at the University of Oxford in the United Kingdom, said during a press conference. “Previously studies of this were inconclusive.”

Pan and colleagues evaluated Early Breast Cancer Trialists’ Collaborative Group data on 80,000 women enrolled in 70 trials. The researchers compared outcomes of women who had a normal weight (BMI range, 20 to 25), those who were overweight (BMI range, 25 to 30) and those who were obese (BMI ≥30) who received the same treatment in the same clinical trial.

Mean follow-up was 8 years.

In women with ER-positive disease (n=60,000), BMI was significantly associated with breast cancer mortality among those who were pre- and postmenopausal (P˂.00001 for both). However, when researchers controlled for tumor characteristics, obesity was only significantly associated with breast cancer mortality among the 20,000 women with ER-positive disease who were premenopausal (RR=1.34; 95% CI, 1.22-1.47).

Among 40,000 postmenopausal women with ER-positive disease, researchers observed a trend toward greater breast cancer mortality among those with BMI ≥30, but this association was not statistically significant (RR=1.06; 95% CI, 0.99-1.14).

Pan and colleagues reported little association between breast cancer mortality and BMI among the 20,000 women with ER-negative disease, and they observed no association after they controlled for tumor diameter and nodal status.

When researchers evaluated BMI in analyses controlled for age in place of menopausal status, obesity was associated with breast cancer mortality in women with ER-positive disease until age 55 years.

Obesity substantially increases blood estrogen levels only in postmenopausal women, so we were surprised to find that obesity adversely impacted outcomes only in pre-menopausal women,” Pan said in a press release. “This means we don’t understand the main biological mechanisms by which obesity affects prognosis.”

For more information:

Pan H. Abstract #503. Scheduled for presentation at: 2014 ASCO Annual Meeting; May 30-June 3, 2014; Chicago.

Disclosure: The study was funded by the British Heart Foundation, Cancer Research UK and the UK Medical Research Counsel. The researchers report no relevant financial disclosures.

Obesity was an independent risk factor for breast cancer mortality among premenopausal women with ER-positive disease, according to results of a meta-analysis.

Researchers did not observe the association among postmenopausal women with ER-positive disease, or in women with ER-negative disease.

“Obesity is reportedly associated with worse prognosis in early breast cancer, but this association could depend strongly on ER positivity and ovarian activity,” Hongchao Pan, PhD, lead study author and a researcher at the University of Oxford in the United Kingdom, said during a press conference. “Previously studies of this were inconclusive.”

Pan and colleagues evaluated Early Breast Cancer Trialists’ Collaborative Group data on 80,000 women enrolled in 70 trials. The researchers compared outcomes of women who had a normal weight (BMI range, 20 to 25), those who were overweight (BMI range, 25 to 30) and those who were obese (BMI ≥30) who received the same treatment in the same clinical trial.

Mean follow-up was 8 years.

In women with ER-positive disease (n=60,000), BMI was significantly associated with breast cancer mortality among those who were pre- and postmenopausal (P˂.00001 for both). However, when researchers controlled for tumor characteristics, obesity was only significantly associated with breast cancer mortality among the 20,000 women with ER-positive disease who were premenopausal (RR=1.34; 95% CI, 1.22-1.47).

Among 40,000 postmenopausal women with ER-positive disease, researchers observed a trend toward greater breast cancer mortality among those with BMI ≥30, but this association was not statistically significant (RR=1.06; 95% CI, 0.99-1.14).

Pan and colleagues reported little association between breast cancer mortality and BMI among the 20,000 women with ER-negative disease, and they observed no association after they controlled for tumor diameter and nodal status.

When researchers evaluated BMI in analyses controlled for age in place of menopausal status, obesity was associated with breast cancer mortality in women with ER-positive disease until age 55 years.

Obesity substantially increases blood estrogen levels only in postmenopausal women, so we were surprised to find that obesity adversely impacted outcomes only in pre-menopausal women,” Pan said in a press release. “This means we don’t understand the main biological mechanisms by which obesity affects prognosis.”

For more information:

Pan H. Abstract #503. Scheduled for presentation at: 2014 ASCO Annual Meeting; May 30-June 3, 2014; Chicago.

Disclosure: The study was funded by the British Heart Foundation, Cancer Research UK and the UK Medical Research Counsel. The researchers report no relevant financial disclosures.

    Perspective
    Clifford A. Hudis

    Clifford A. Hudis

    This study is part of the growing body of evidence showing that patients who are obese generally fare worse with cancer — in this case, younger women with breast cancer. With some two-thirds of our nation’s adult population now obese or overweight, there’s simply no avoiding obesity as a complicating factor in cancer care. ASCO is working to support physicians and patients in addressing this challenge, and we urge researchers to examine new strategies for reducing obesity’s cancer-related toll.

    What we’ve known in the past is that obesity and overweight have been associated with elevated risk, and they’ve been especially associated with elevated risk in postmenopausal, ER-positive breast cancer. Obesity is often associated with a low grade, chronic inflammation of the white adipose, including the white adipose of the breast. People who have this low-grade inflammation will have increased aromatase activity, increased local production of estrogen, and that provides an explanation for the paradox of elevated ER-positive cancer with obesity after menopause when the ovaries have stopped their production of estrogen.

    That’s where we were coming in to this study. This study addresses the backend of the disease, not the initiation of the disease, but rather the follow-up and outcome. I am surprised that the effect was less clear in postmenopausal than premenopausal patients. I think this is something we’re going to have to explore further.

    Now from a practical point of view, realistically, there is no argument in favor of obesity. And, globally, obesity is a health problem in the context of heart disease, arthritis, diabetes and so forth. I don’t really believe anybody is waiting for a cancer link as the justification to stay lean throughout adult life, or to exercise more or to change diet. I think we have to be humble about that. This is yet another in the long list of potential negatives from life style and obesity.

    In terms of specific interventions, this is being studied. For example, it could be that subsets of obese patients would benefit from specific therapeutic interventions, be it targeted diet weight loss, drugs or food supplements. All of these might be effective at mitigating some of the risks, but this is an area that needs to be studied, and frankly this is why ASCO has picked up the charge, because no matter how we look at it, obesity is slated to replace tobacco as the leading, overall modifiable risk factor for cancer. We are going to have to tackle this one, and I expect to see more stories like this, that continue to dissect the problem.

    When we plan a study that actually asks about weight loss, on the one hand many people will say, ‘Why do that study? You already know that being lean or losing weight is advantageous. You already know that gaining weight after diagnosis is disadvantageous. So why do you need to prove it?’ Even if it isn’t true for breast cancer, it’s generally true overall. We’re struggling with this, because we do want to understand whether everybody needs to lose weight, or just a subset of people, and the best way to do it. Of course, this study doesn’t address that. This study only looks at the association of weight and outcome. It can’t look at the impact of the intervention aimed at losing weight.

    The big issue is despite everyone knowing the truth of this, the levels of overweight and obesity in the US continue to climb. According to the Robert Wood Johnson Foundation, about 65% of the population will be in the obese category in many parts of the US by 2030. So, knowing that it’s a negative health factor in so many domains is not yet an effective weight-changing behavior. I’m optimistic that as we focus on this we can achieve the kinds of gains we saw with tobacco control, and I’m hoping that we can do it much faster with better information and knowledge.

    In the US, only about 4% of people have any doubt about the association between tobacco and cancer. Conversely, only about 10% of the general population yet understands the association between obesity and cancer. We have a lot of progress that we can make, and a lot of good can be done with education in this regard.

    • Clifford A. Hudis, MD, FACP
    • Chief, Breast Cancer Medicine Service Memorial Sloan Kettering Cancer Center ASCO President

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