The ENERGY trial

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Published: 20 Jun 2011
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Prof Cheryl Rock - University of California, USA
The Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) trial has been designed to assess the effect of weight loss in cancer survivors. Both premenopausal and postmenopausal women have a worse prognosis if they are overweight and this randomised controlled 4-year study will try to determine if weight loss after treatment increases survival rates. Prof Cheryl Rock discusses the possible reasons for the link between weight and survival and explains how the women in the investigative arm of this trial will be encouraged to lose weight and maintain that weight loss. If the researchers can show sustained weight loss and favourable effects of weight loss on psychosocial factors and comorbidities, it will be the first step toward a larger clinical trial to address cancer outcomes.

ASCO 2011 Annual Meeting, June 3-7 2011. Chicago

The ENERGY trial

Professor Cheryl Rock – University of California, USA

 

This is very exciting because we have literally hundreds of papers that have explored the relationship between being overweight and survival after the diagnosis of breast cancer; there are fewer data on colon cancer and prostate that suggest it, but with breast cancer the majority of the observational studies have shown that, all other things being equal, a woman who is heavier when she is diagnosed has about a 78% greater likelihood of having a recurrence. 

And that’s nothing whatsoever to do with the etiology of the primary breast cancer?

That’s right. It’s a different picture because, even though being overweight in a post-menopausal woman is associated with greater likelihood of a primary breast cancer diagnosis, with regard to recurrence, both pre-menopausal and post-menopausal women have a worse prognosis if they are overweight. The exciting thing about this is that there are several possible mechanisms but historically the most commonly cited mechanism is it might be due to the reproductive hormone status because particularly we would know with the ER positive tumours, that they’re more likely to have a greater risk of recurrence with higher oestrogen levels. In the older woman, most of the oestrogen in the body is actually produced in the adipose tissue because of ovarian failure. The other possibility is that we know that when someone is overweight, they have more insulin resistance, they’ve got higher levels of insulin which in turn reduces the synthesis of the sex hormone binding globulin and so insulin in itself might be a mitotic factor but it also might interact with the reproductive hormones. 

The exciting thing about the ENERGY trial is that this is the first large study that seeks to answer the question can we address this issue, can we test it in women who are breast cancer survivors who are overweight? The primary outcome from this four year trial is to demonstrate that we can promote weight loss that’s sustained for at least two years and then we’re also collecting a lot of information about cancer outcomes and also biological samples, with the idea that this could, if we can show this effect and show improvements in quality of life, that we’ll be able to be funded to do an actual cancer outcome study to answer the question if a woman loses weight after she is diagnosed, does that improve her prognosis and improve her risk for recurrence?

All other things being considered. This is a randomised trial?

Yes, it’s a randomised controlled trial.

What do the control group get?

The control group get what we would call usual care – they meet with the dietician a couple of times.

That’s not usual in most parts of the world, to see a dietician. If you get a piece of paper with a diet on it, you’re very lucky.

And that’s a good point because, especially in women in the United States who have a comorbidity if they have diabetes or heart disease risk factors, would be sent to a dietician and that individual would also give them a lot of publically available information – how to lose weight and how to exercise. They also are contacted on a monthly basis and invited to seminars on things that are not weight loss but yet helpful, like skin care and dietary supplement use, what’s appropriate. So they work as a good control group. If we didn’t provide anything then we would not be able to recruit people because no-one wants to be randomised to a group where they get nothing.

And how do you get the women to lose weight?

We have an intervention that has been developed through some prior studies. It’s basically cognitive behavioural group therapy, that they meet weekly for sixteen weeks. We teach them the skills to maintain weight in the long run, like eating a reduced calorie diet. We also have a huge emphasis on increasing physical activity because in the long run we know that’s crucial for maintenance of weight loss and it also may be of particular importance in the breast cancer survivor because studies have shown that during the diagnosis and initial treatment that most women will lose a lot of lean muscle mass and that’s the point at which their metabolic rate requirements for calories then goes down. So they’ll have greater struggles to maintain a healthy weight and eat enough food that they feel satisfied unless they increase that physical activity and restore the lean mass.

There are some cynics who would say that it’s only the exercise that matters.

Actually I hear arguments on both ends of it because if you just look at calories alone, it would take at least an hour walking briskly to burn the calories in one slice of pie. So it would make more sense to just say skip the pie, but we know in the long run that if you don’t do the exercise part too then it’s a lot more difficult to keep the weight off.

How are you getting on with the trial?

We’re really only one year into the trial and so at this point we’ve got groups at all four of the sites, we have four clinical sites in the United States, and we’ve recruited almost a quarter of the number of women that we need at this point. So with everything set up we’re fully functional and still recruiting at this point.

Compliance?

We aim to have a compliance rate of 90% which sounds high for a weight loss trial but because we build in so many retention activities like contacts and seminars and little freebies and every time we ask people to come we’ve got a goodie bag that they can take away from the clinic, so in our past experience we’ve ranged… the worst drop-out rate I’ve ever seen was about 18%. Otherwise we’ve got a pretty good track record of keeping it to that 8-10%.

And what do the groups look like? Are they all upper-middle class, intelligent, educated, white women, to be provocative?

What you describe is what often happens with a clinical trial and we’re doing our best to not have that be the picture. At least in each of the sites we’re targeting minority groups that are often under-represented. For example, in San Diego and Denver we have a pretty good Hispanic population that we can get involved in studies and in Birmingham and St Louis, those two sites have quite a large African-American population. We do recruit using those media and TV and general population routes so that we end up not just recruiting from the specialty breast cancer clinics. We have an outreach that goes to everybody and so with that effect we hope that we can have a group that’s more disparate than the typical clinical trial.

Are you confident you’re getting to everybody? I don’t know of any technique that gets to all socially deprived people.

We’re doing everything we can to do so. Fortunately all four of these sites have cancer centres that are NCI designated and each one of those sites has a community outreach arm that they actually then have routes to those community groups that can get the word out. For example, in San Diego we have a good relationship with the Filipino American community groups and Filipino Americans actually have higher rates of breast cancer than other Asian American groups. They also tend to gain weight more readily, they tend to be heavier, and so at each one of the communities we have different ways that we have community interactions through our cancer centres.