High body fat, even with normal BMI, increases breast cancer risk

Issue: March 10, 2018

Neil Iyengar

Higher body fat levels appeared associated with increased breast cancer risk among postmenopausal women with normal BMI, according to study results scheduled for presentation at the American Association for Cancer Research’s special conference, Obesity and Cancer: Mechanisms Underlying Etiology and Outcomes.

Perspective from Christina M. Dieli-Conwright, PhD, MPH

“It was previously unknown whether individuals who have a normal BMI but increased body fat have an increased risk [for] developing cancer,” Neil Iyengar, MD, medical oncologist at Memorial Sloan Kettering Cancer Center, said in a press release. “Our findings show that the risk [for] invasive breast cancer is increased in postmenopausal women with normal BMI and higher levels of body fat, meaning that a large proportion of the population has an unrecognized risk [for] developing cancer.”

BMI — widely used to estimate body fat levels — often informs individual health recommendations. Postmenopausal women with obesity, defined as a BMI greater than 30 kg/m², are known to have increased risk for ER-positive breast cancer.

However, it is unknown whether body fat levels contribute to breast cancer risk among women with normal BMI.

“[Although] BMI may be a convenient method to estimate body fat, it is not an exact way to determine whole body fat levels, as muscle mass and bone density cannot be distinguished from fat mass,” Thomas Rohan, MBBS, PhD, DHSc, professor and chair of the department of epidemiology and population health at Albert Einstein College of Medicine, said in the release.

Instead, researchers used dual energy X-ray absorptiometry — a technology that specifically measures fat content — to evaluate the association between body fat levels and breast cancer risk among 3,460 postmenopausal women with normal BMI (18.5 kg/m² to < 25 kg/m²) enrolled in the Women’s Health Initiative.

Over a median follow-up of 16 years, 182 incidence invasive breast cancers occurred, 146 of which were ER positive.

Multivariable-adjusted analyses showed the risk for invasive breast cancer increased among women with the highest vs. lowest quartile of whole body fat mass (HR = 1.7; 95% CI, 1.06-2.72) and trunk fat mass (HR = 1.75; 95% CI, 1.09-2.81).

This risk increased when researchers evaluated ER-positive breast cancer associated with the highest quartile of whole body fat mass (HR = 2.1; 95% CI, 1.23-3.58) and trunk fat mass (HR = 1.91; 95% CI, 1.12-3.23).

Adjusting for waist-hip ratio did not impact the results.

Circulating levels of metabolic and inflammatory factors — including insulin, C-reactive protein, Interluekin-6, leptin and triglycerides — appeared higher after adjustment for age and race/ethnicity among women in the higher quartiles of trunk fat mass (P < .01 for each). Conversely, levels of HDL-cholesterol and sex hormone binding globulin were lower among women with greater trunk fat mass (P < .01 for each).

Andrew Dannenberg

Researchers noted they could not analyze how changes in body fat over time impact breast cancer risk.

“These findings will probably be surprising to many doctors and patients alike, as BMI is the current standard method to assess the risks for diseases related to body weight,” Andrew Dannenberg, MD, associate director of cancer prevention at Sandra and Edward Meyer Cancer Center of Weill Cornell Medicine, said in the release. “We hope that our findings will alert women to the possibility of increased breast cancer risk related to body fat, even if they have a healthy weight.” – by Alexandra Todak

Reference:

Iyengar N, et al. Abstract PR06. Presented at: Obesity and Cancer: Mechanisms Underlying Etiology and Outcomes. Jan. 27-30, 2018; Austin, Texas.

Disclosures: The authors report no relevant financial disclosures.

Perspective

Christina M. Dieli-Conwright, PhD, MPH

The association between obesity and risk for postmenopausal breast cancer, recurrence and mortality is well established. These associations have been namely derived from large epidemiological studies that have assessed obesity as a measure of BMI. Although BMI is an inexpensive, convenient assessment of obesity, it has significant limitations that may disguise potential health risks among women with a normal BMI. For example, BMI does not account for tissue composition, such as fat or lean mass. Examining measurements of fat mass using technologies, such as DXA, provides direct assessments of obesity that can unmask health risks among women with normal BMI. Therefore, perhaps a more relevant research question is whether fat mass and fat mass depots are associated with breast cancer risk.

The abstract by Iyengar and colleagues supports this notion. To date, this appears to be the first study of body fat, assessed by DXA, and risk for invasive breast cancer among women with normal BMI. Although the results may appear striking, the fact that high body fat is associated with increased risk for breast cancer seems scientifically logical, as we know excess fat mass plays a driving force in the development of breast cancer.

What is more surprising is that the women with higher body fat actually had a normal BMI. Excess body fat in an adult with normal BMI is often referred to in lay terms as “skinny fat” — a concept that has circulated the exercise science community for years and now may prove clinically relevant to breast cancer risk. The medical term for this, “MONW” — or metabolically obese but normal weight — represents a population of adults who are increasingly studied. Therefore, the abstract findings highlight the need to derive future investigations examining cancer risk in MONW populations. It is plausible that this relation may exist in other cancer types whereby obesity is a risk factor.

Possibly the greater quandary at hand is a question of how we modify our global approach to capture obesity and/or body composition in such a way that we can measure body fat and other clinically relevant tissue compartments, such as visceral and trunk fat. Despite potential limitations — such as inclusion of only postmenopausal women and small number of incident invasive breast cancers — this study emphasizes the need to move beyond BMI for body fat assessment. This includes consideration of standardized yet cost-effective tools to assess body fat in a clinical setting, perhaps such as bioelectrical impedance.

The authors also found that women who participated in lower levels of physical activity had higher amounts of body fat. Although this is intuitive, it further emphasizes the need for women to participate in physical activity despite their normal BMI status. Clinically, health care providers should be cognizant of promoting physical activity to patient populations regardless of BMI, given that BMI will likely mask excess fat in an individual with normal BMI.

Overall, this important study sets the precedence for exploring the association of obesity and cancer risk beyond BMI and reinforces the need to measure body fat composition. Future scientific inquiries should seek to examine breast cancer risk for MONW women and identify validated, cost-effective resources that can be utilized in clinics worldwide to capture body composition data for cancer risk.

Christina M. Dieli-Conwright, PhD, MPH

University of Southern California

Disclosures: Dieli-Conwright reports no relevant financial disclosures.