Obesity, Severe Obesity Increase Risk for Breast Cancer Recurrence

Among breast cancer survivors treated with aromatase inhibitors (AI), women with obesity were 18% more likely to experience recurrence of disease than women of average weight, according to findings published online in JAMA Network Open.

The risk was increased nearly 2-fold among survivors with severe obesity.

There is consistent evidence for the association between elevated body mass index (BMI) and poorer prognosis of early breast cancer in postmenopausal women with hormone receptor-positive (HR+) breast cancer, the researchers wrote. Although the mechanism underlying the link is still unclear, reduced efficacy of adjuvant endocrine treatment in persons with obesity has been proposed. "Obesity can affect the response to cancer treatment," authors added, an effect related to altered drug metabolism and distribution in the presence of excess adiposity.

To explore the relationship between BMI and breast cancer recurrence further, the research team, led by Sixten Harborg, BSc, of the department of oncology at Aarhus University Hospital in Denmark, tapped the clinical database of the Danish Breast Cancer Group, which covers all women in Denmark and includes information on breast cancer diagnosed since 1977. They identified all postmenopausal women with a primary diagnosis of stage I-III HR+ breast cancer from January 1, 1998, until December 31, 2016. Inclusion required receiving endocrine therapy with AIs and information on BMI.

The end point was breast cancer recurrence, defined as the time from 6 months after the date of breast cancer surgery until the earliest occurrence of any breast cancer recurrence recorded.

Investigators used “healthy” weight as the reference category for calculation of associations. BMI was recorded at the time of surgery or at the first appointment for administration of adjuvant treatment following surgery.

The final cohort comprised 13 230 postmenopausal women with primary, early-stage, HR+ breast cancer. The participants had a median age of 64.4 years at diagnosis. Distribution of BMI at the time of diagnosis was:

• 6.5% severe obesity (BMI ≥35.0 kg/m²)
• 14.4% obesity (30-34.9 kg/m²)
• 32.5% overweight (25-29.9 kg/m²)
• 44.4% normal weight (18.5-24.9 kg/m²)
• 2.2% underweight (<18.5 kg/m²)

At the median follow up of 6.2 years, there were 1587 cases of recurrence.

FINDINGS

Harborg et al reported in a multivariable analysis that the risk of breast cancer recurrence was 18% among participants with obesity (adjusted hazard ratio [aHR], 1.18; 95% CI, 1.01-1.37) and nearly double that, 32%, among those with severe obesity (aHR, 1.32; 95% CI, 1.08-1.62).

Among participants classified as overweight at baseline, the team observed a trend toward an increased risk of recurrence, but the association did not reach statistical significance (aHR, 1.10; 95% CI, 0.97-1.24).

The risk of breast cancer recurrence among participants who were underweight or had a healthy BMI was similar (aHR, 1.12; 95% CI, 0.77-1.64).

“The results of this novel, large population-based cohort study support previous research suggesting that patients with obesity treated with adjuvant AIs [aromatase inhibitors] may derive less benefit from their adjuvant endocrine therapy than patients with healthy weight,” the researchers wrote.

Harborg and team hope the findings encourage additional research “into whether women with obesity and early-stage HR+ postmenopausal breast cancer should be offered endocrine therapies other than the currently recommended AIs to improve their prognosis.” Further investigation, they added, should focus on securing equal breast cancer treatment, regardless of body composition.

Source: Harborg S, Cronin-Fenton D, Jensen M-B R, et al. Obesity and risk of recurrence in patients with breast cancer treated with aromatase inhibitors. JAMA Netw Open. 2023;6(10):e2337780.
doi:10.1001/jamanetworkopen.2023.37780