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Sunday, June 2, 2019

Understanding the Impact of BMI Reduction in Primary Breast Cancer

By Catlin Nalley

CHICAGO—During the ASCO 2019 session, "Furthering Fitness: Implementing Wellness to Improve Breast Cancer Outcomes," Jennifer Bea, PhD, of The University of Arizona Cancer Center took a closer look at the impact of BMI reduction on breast cancer, including the challenges and opportunities for primary prevention.

High BMI is associated with postmenopausal breast cancer, she noted. "The median age at diagnosis is 62 years of age with a rate of prevalent breast cancer between 55 and 64. That is when they are most often diagnosed, so we are seeing the greatest prevalence in postmenopausal women.

"For every 5 minute increase in BMI there is a 12 percent increase in risk. And just overall there is a 1.5 to 2 fold increase in breast cancer risk with obesity," she explained. "So, it is critical that we try and turn the tide on the obesity epidemic in the U.S."

Bea reported that the strongest associations are seen with hormone receptor positive tumors, never users of menopausal hormone therapy, and advanced disease and death.

Additionally, Bea noted that high BMI is also associated with breast cancer in men. "However, we see the opposite, or no association, for premenopausal breast cancer," she said. "It is null if you combine the tumor types, but if you are looking at hormone receptor positive breast tumors we actually see a reduction when looking at BMI associations with breast cancer risks."

Weight Changes & Breast Cancer Risk

"Weight gain at any time in a female adult life is associated with increased postmenopausal breast cancer risk," Bea noted. "And again, we see this enhanced for hormone-receptor positive tumors, non-users of hormone therapy, and advanced disease.

Additionally, there is a dose-dependent relationship with 5 kg gained resulting in 4-8 percent increased risk in postmenopausal breast cancer, according to Bea.

"There is some inkling of racial and ethnic differences in these associations," she explained. "For example, some studies have shown that the menopausal status may not matter in Hispanic women or that increase in weight may be more important in Asian women, but there are very few studies about this and it needs to be confirmed, and we also need to look at it in a more diverse sample."

Weight cycling is another area that should be looked at as well. "Many of you have witnessed in your patient population or families that you can get a significant amount of weight off of an obese or overweight person with behavioral techniques, surgical techniques, etc., but for behavioral techniques at least, within a year about 90 percent have regained the weight and within 5 years close to 100 percent have totally regained the weight that was lost.

"So there is an interest in looking at this pattern of weight loss, regain, weight loss, regain, and we live in a society where we push a lot of weight loss strategies and medications. This has actually not been shown to be significantly associating with breast cancer risk at this time."

Weight loss has been shown to reduce the risk of postmenopausal breast cancer. According to Bea, this is seen consistently across longitudinal and case-controlled studies, though there are very few prospective studies that were planned to assess breast cancer risk with weight loss.

"However, we do get some great insight from the bariatric surgery field," she noted. "In one large study, Kaiser Permanente pulled together five different regions from the KP system, for approximately 2,500 breast cancer cases, we see a significant reduction in postmenopausal breast cancer with bariatric surgery and that is 42 percent."

While this is promising Bea advised that behavioral equivalents are needed. "Bariatric surgery is dramatic, invasive, and generally reserved for the morbidly obese," she said. "And so we need to see these effects in behavioral studies where we are not necessarily intervening surgically and for that we need to plan prospective, large, long-term studies."

Physical Activity

In addition to weight loss, higher physical activity levels have been associated with decreased risk of breast cancers. "Very interestingly, this can be independent of BMI, estrogen receptor status of the tumor, hormone therapy, and smoking," Bea noted, during her presentation. "Unfortunately, Americans are not getting adequate physical activity."

A little less than 20 percent of U.S. adults are getting the recommended physical activity. Similarly, adolescents are about 17-20 percent compliant, according to Bea. "And so, we need to turn the tide on physical activity as well, even if you can't move the needle on the scale for weight, physical activity can have an effect."

Does obesity modify the relationship between physical activity and breast cancer risk? Research suggests it does. A meta-analysis (Breast Cancer Res Treat 2017;166(2):367-381) showed that, "Overall, a significant reduction in the relative risk of breast cancer was found in postmenopausal women with high versus low levels of physical activity for women with a BMI <25 kg/m2(RR 0.85, 95% CI 0.79, 0.92) and ≥25 kg/m2 (RR 0.87, 95% CI 0.81, 0.93) but not ≥30 kg/m2 (RR: 0.93, 95% CI 0.76, 1.13)."

"Perhaps for those in the obese category of the BMI, we need both weight loss and physical activity," noted Bea.

Challenges to Be Addressed

"We have many challenges when we study obesity and breast cancer associations, one of which is understanding the complexity of the disease of obesity," Bea explained. "We still don't fully understand the endogenous and exogenous hormonal influences; there are differences between specific fat depots and we still need that practical, but concise measure of adiposity.

It is likely that we will need different treatments for different individuals and maybe combinations of treatments for obesity," she continued.

Additionally, there are very few studies prospectively set out to study weight loss for breast cancer prevention. "We need to get those going and have long term follow-up," she noted.

It is also important to consider long-term interventions. "Twelve weeks of an intervention or a year of an intervention to then look a decade down the road probably isn't going to cut it," Bea suggested. "We need to be thinking about reenrolling, booster sessions, etc., in order to address our communities.

"And lastly, in my group, we see a lot of underserved participants and patients and they have competing priorities and cancer prevention is really not at the top of their list, so how do we deal with that?"

Bea and her team are working to address this in a number of ways, including the program, "Restoring Balance in Indian Country."

"This is survivor focused in terms of outcomes, but we are taking up to two family members that don't have cancer," she explained. "So it is an opportunity for primary prevention in a group that has high levels of adiposity, diabetes, family history of cancer, etc.

"This is one way we can start to target prevention in ongoing survivor studies," she continued. "We have four sites in and around Navajo nation as well as outreach materials for primary prevention."

Guideline Adherence

The lifestyle guidelines from the WCRF/AICR project are multifaceted, according to Bea. It's not just about weight. It is also about being physically active, a diet rich in whole grains, a lower consumption of fast foods, etc.

"What we have seen overtime is adherence to five or more of these guidelines can reduce the risk of breast cancer up to 60 percent," she added. "That is on the high end, but very promising and each additional recommendation met in that study so an additional reduction."

Bea noted that a systematic review of these guidelines and others was recently done, which showed a range of 13-60 percent reduction in breast cancer risk, which is "clinically relevant and should be considered a key avenue for preventing breast cancer."

Catlin Nalley is associate editor.