Researchers found that obesity may make locally advanced breast cancer behave more aggressively and worsen women’s prognosis.

by Crystal Phend, Staff Writer, MedPage Today 

Houston, Texas, March 14 — Obesity may make locally advanced breast cancer behave more aggressively and worsen women’s prognosis, researchers found.

Obese and overweight women had lower breast cancer survival rates and a greater likelihood of breast cancer recurrence (P=0.001 for both) compared with normal weight or underweight women, reported Massimo Cristofanilli, M.D., of the University of Texas M.D. Anderson Cancer Center, and colleagues in the March 15 issue of Clinical Cancer Research.

In the retrospective study, obese women with breast cancer were also more likely to have inflammatory breast cancer (P=0.01), which has been associated with poor prognosis.

The findings suggest that adipose tissue increases inflammation, leading to more aggressive disease, but more importantly, the researchers said, “they highlight the need for dietary interventions as part of a multidisciplinary approach to the disease.”

Obesity has been linked to risk of developing breast cancer, but evidence for its impact on prognosis has differed by type of disease.

To see the impact in locally advanced breast cancer, the researchers reviewed outcomes for patients at M.D. Anderson by body mass index (BMI).

The study included 606 women with stage III locally advanced disease treated in clinical trials of anthracycline-based primary systemic treatment from 1974 to 2000 who had body mass index data available. All patients were treated in clinical trials at a single institution.

Among the women, 82% had nonmetastatic, non-inflammatory, locally advanced disease; the rest had inflammatory breast cancer.

Women were evenly divided by BMI with 34% classified as normal or underweight (24.9 kg/m2 or less), 32% as overweight (25.0 to 29.9 kg/m2), and 34% as obese (30 kg/m2 or higher).

Obese patients were significantly more likely to have inflammatory breast cancer than overweight and normal or underweight patients (24.5% versus 17% and 13.5%, P=0.01).

Obese and overweight patients also presented at an older age and with more adverse prognostic factors, including higher T stage tumors, higher nodal involvement, and higher grade tumors, than women with breast cancer who were normal weight or underweight at baseline.

Over a median follow-up of six years, 56% of patients died and 54% had recurrence of the disease.

As expected, inflammatory breast cancer was associated with worse outcomes compared with non-inflammatory disease for five-year overall survival (49.7% versus 62.4%, P=0.08) and recurrence-free survival (39.9% versus 54.8%, P=0.01).

The findings for obese and overweight women compared with normal or underweight women included:

Worse overall survival at five years (56.8% and 56.3% versus 67.4%).

Lower overall survival rates at 10 years (42.7% and 41.8% versus 56.5%).

Worse recurrence-free survival at five years (49.2% and 45.2% versus 61.5%).

Lower recurrence-free survival rates at 10 years (42% and 40.9% versus 54.6%).

For both inflammatory and non-inflammatory breast cancer subgroups, increasing BMI was associated with worse outcomes for recurrence and survival.

However, breast cancer type did not remain significant in the multivariate analysis (P=0.22 for overall survival and P=0.27 for recurrence-free survival).

“This may indicate a similar prognostic effect of BMI between the two subgroups,” the researchers said.

BMI, though, remained significantly associated with both outcomes in multivariate analysis after adjustment for year of diagnosis, menopausal status, number of lymph nodes removed, number of positive lymph nodes, presence or absence of taxanes in the treatment regimen, and pathologic complete response.

Increased recurrence risk with higher BMI among postmenopausal women has traditionally been attributed to excessive estrogen production through peripheral aromatization of adrenal steroids in fat, the researchers said. But in the study there was no significant interaction between BMI and menopausal status.

Another explanation may be that the hormone leptin, produced mainly in adipose tissue, promotes tumor growth, invasion, and angiogenesis, “thereby promoting a more aggressive tumor,” Dr. Cristofanilli and colleagues said.

Their group is now prospectively recording leptin levels for patients with locally advanced breast cancer. Preliminary analysis suggested baseline leptin levels were higher among patients with newly diagnosed inflammatory breast cancer, but no prognostic information is yet available, they said.

The study was limited by lack of data on BMI changes during and after treatment, on dietary habits after disease diagnoses, and on hormone receptor status and grade, which are important markers of prognosis and were not available for many of the patients treated in the 1970s and ’80s.

Systematic, prospective study is needed on endocrine and immune factors in these patients, the researchers concluded.

The study was funded by the Susan G. Komen Foundation, the Nellie B. Connally Fund for Breast Cancer Research.


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Published: March 14, 2008

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.