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Obesity ‘Clearly’ Not Tied to Worse Survival in MBC

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The relationship between obesity and overweight and breast cancer has some elements of mystery. But this is not one of them: in metastatic breast cancer (MBC), excess body weight does not negatively influence outcomes.

Multiple small studies have demonstrated this point, and now, for the first time, a large multicenter cohort analysis indicates the same.

Using medical records from 18 French comprehensive cancer centers, investigators reviewed body mass index (BMI) and overall survival (OS) data for nearly 13,000 women. The median OS was 47.4 months, and the median follow-up was about the same length of time. The team reports that obesity and overweight “were clearly not associated with prognosis.”

However, underweight was independently associated with worse OS (median, 33 months; hazard ratio [HR], 1.14, 95% CI, 1.02 – 1.27), report Khalil Saleh, MD, of Gustave Roussy in Villejuif, France, and colleagues.

In short, obesity or overweight had no effect on the primary outcome of OS, but underweight did.

“Underweight should be the subject of clinical attention at the time of diagnosis of MBC, and specific management should be implemented,” said study author Elise Deluche, MD, of CHU de Limoges, in an email to Medscape Medical News.

The study was published online December 1 in The Breast.

“It’s really wonderful to have such a large cohort to look at this question,” said Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute, Boston, Massachusetts, who was asked for comment.

Is this another case of obesity paradox in cancer (as in renal cell carcinoma and melanoma, where excess weight is tied to better cancer-specific survival)?

No, said Ligibel: “There’s no hint at all [in this study] that people with obesity and overweight did better…. They just didn’t have worse outcomes.”

The study authors point out that the opposite is true in early-stage breast cancer ― in this patient population, excess weight is associated with worse outcomes.

For example, in a 2014 meta-analysis of 82 follow-up studies in early-stage disease, obesity was associated with higher total mortality (relative risk [RR], 1.41) and breast cancer–specific mortality (RR, 1.35) as compared to normal weight.

Why is there such a contrast between early- and late-stage disease?

“I don’t think we know exactly,” answered Ligibel. “It may be that with breast cancer, as disease progresses, the pathways through which lifestyle may impact breast cancer may become less important.

“Obesity and overweight are associated with cancer risk in general,” said Ligibel, citing more than a dozen malignancies, including breast cancer.

But there is also an age element. Overweight or obesity is an independent predictor of breast cancer risk in postmenopausal women, but in premenopausal women, it appears to be protective. “Historically, there has been a lower risk of hormone receptor–positive breast cancer in women with obesity at younger ages that we don’t completely understand,” Ligibel noted.

That age-based difference is a conundrum, said Ligibel: “People have been trying to figure that out for a long time.”

Ligibel summarized as follows:

“There is a clear relationship between obesity and the risk of developing breast cancer; there is a clear relationship in early breast cancer that obesity is related to an increased risk of occurrence and mortality. What we are seeing from this study is that by the time you get to metastatic breast cancer, body weight does not seem to play as important a role.”

More Study Details

The findings come from the French National Epidemiological Strategy and Medical Economics (ESME)–Metastatic Breast Cancer observational cohort, which includes 22,000-plus consecutive patients who were newly diagnosed with metastatic disease between 2008 and 2016.

A total of 12,999 women for whom BMI data were available when they were diagnosed with metastatic breast cancer were selected for analysis. They were divided into four groups, according to World Health Organization classification: underweight (BMI <18.5 kg/m2), normal weight (18.5 – 24.9), overweight (25.0 – 29.9), and obese (≥30.0).

A total of 20% of women were obese, which is a much lower percentage than the 40% to 50% that would be expected in a comparable American cohort, said Ligibel. Also, 5% of the French cohort was underweight.

Multivariate Cox analyses were carried out for OS and for first-line progression-free survival (PFS).

As noted above, underweight was independently associated with a worse OS. It was also tied to worse first-line PFS (HR, 1.11; 95% CI, 1.01 – 1.22). Overweight or obesity had no effect.

“Patients with a low BMI had more visceral metastases and a greater number of metastatic sites,” pointed out study author Deluche. “We attribute the fat loss in patients with metastatic breast cancer to aggressive tumor behavior with a higher energy requirement.”

The study authors also observe that in early-stage breast cancer, underweight is not associated with overall or breast cancer–specific survival. “Underweight at metastatic diagnosis seems to have a different significance and impact,” they write. The French team also observes that in other cancers, underweight is also an adverse prognostic factor and has been associated with a higher risk for death.

The study authors acknowledge that BMI has limitations as a measure of body type. “BMI alone cannot estimate a woman’s muscle mass and adiposity,” they observe. The suggestion is that among women with a similar BMI, some might be muscular, whereas others might have more body fat.

Multiple study authors report financial ties to industry, including pharmaceutical companies with drugs used in breast cancer. The database used in the study receives financial support from Roche, Pfizer, AstraZeneca, MSD, Eisai, and Daiichi Sankyo. Ligibel reports no relevant financial relationships.

Breast. Published online December 1, 2020. Full text

Nick Mulcahy is an award-winning senior journalist for Medscape. He previously freelanced for HealthDay and MedPageToday and had bylines in WashingtonPost.com, MSNBC, and Yahoo. Email: [email protected] and on Twitter: @MulcahyNick.

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