Size Matters: Examining Obesity's Role in Cancer Outcomes

“After a cancer diagnosis, you can go into a shell and look for what is comforting and familiar. That was food for me. I wish I had the forethought to have released my anxiety with a walk instead of overeating.” — SUSAN YANKEE - PHOTO BY ANGELA CHICOSKI

Susan Yankee, an opera singer and voice teacher in Madison, Connecticut, was diagnosed with breast cancer in February 2015 at age 48. She had a single mastectomy and reconstruction, but didn’t need chemotherapy, and today takes the hormonal drug tamoxifen daily.

Yankee admits to being overweight at the time of her diagnosis. She knew she needed to lose weight, but felt overwhelmed by her cancer and started to “stress eat” to help her cope emotionally. As a result, she gained 10 pounds over the next six months. “After a cancer diagnosis, you can go into a shell and look for what is comforting and familiar,” Yankee says. “That was food for me. I wish I had the forethought to have released my anxiety with a walk instead of overeating.”

Yankee is far from alone, oncologists report. In fact, as the obesity epidemic in the United States worsens, cancer specialists are seeing more and more patients who are either overweight or obese at the time of diagnosis. This is concerning, they say, because obesity can adversely affect treatment outcomes, influence mortality and increase a patient’s risk of recurrence.

The good news, experts say, is that it’s never too late or impossible to lose weight and, even after a cancer diagnosis, trimming down may bring many lasting health benefits. Studies show that simple, common-sense plans for healthy eating and exercise — particularly those that are supervised through programs aimed at survivors of cancer — are associated with lower cancer risks, and for those with cancer, a smaller risk of recurrence. Whether these interventions are truly responsible for this decreased risk is not proven, but experts assume it to be the case. There are several controlled trials in progress that are formally testing whether exercise or diet aimed at both conditioning and weight loss could have a favorable impact on cancer risk.

THE OBESITY/CANCER LINK

Obesity is measured using body mass index (BMI), which is calculated by dividing a person’s weight in kilograms by their height in meters squared. A BMI of 25 to 29.9 is considered overweight; 30 or higher is considered obese. According to a report in the Journal of the American Medical Association, in the years 2013-2014, 35 percent of American men and more than 40 percent of women met the clinical definition for obesity. Rates of obesity are also rising among American children, of whom around 17 percent are considered obese, reports the National Cancer Institute (NCI), quoting a 2007-08 National Health and Nutrition Examination Survey.

Excess weight can contribute to a variety of health issues, including heart disease, hypertension and diabetes. It can also increase one’s chances of developing certain types of cancers, including breast, endometrial, kidney, gallbladder, esophagus, pancreas, thyroid and colon, multiple studies show. In fact, the results of a 2003 study published in The New England Journal of Medicine estimated that the proportion of all deaths from cancer attributable to overweight and obesity in U.S. adults ages 50 or older may have been as high as 14 percent in men and 20 percent in women. Observed the authors, “Under the assumption that these relations are causal, the public health implications for the United States are profound: More than 90,000 deaths per year from cancer might be avoided if everyone in the adult population could maintain a body-mass index under 25.0 throughout life.”

The exact mechanism behind this phenomenon is not entirely understood, but researchers believe a number of factors may play a role. One of the strongest contenders is inflammation, notes Jennifer Griggs, M.D., professor of medical oncology and of health management and policy at the University of Michigan in Ann Arbor. “Obesity is considered a chronic inflammatory state,” Griggs explains, “and an inflammatory state may be pro-carcinogenic.”

Certain hormones are another suspected mechanism. The aromatase in fat tissue converts androgens to estrogen, and this elevated estrogen level has been associated with a higher risk for breast, endometrial and other forms of cancer, reports the NCI. Fat cells also produce hormones called adipokines that may stimulate tumor growth, and are suspected of directly or indirectly affecting other tumor-growth regulators.

Insulin and insulin-like growth factor-1 are also under study. Commonly found in higher levels in the blood of obese people, these compounds are suspected of promoting the development of certain tumors, including kidney and colorectal cancer, reports the American Institute for Cancer Research.

WEIGHT AFFECTS TREATMENT SUCCESS

The negative influence of obesity reaches further than increased cancer risk — excess weight can also affect treatment in a variety of ways, researchers report. One of the most important issues on this front is chemotherapy dosing. Until recently, oncologists commonly prescribed the same amounts of chemotherapy drugs to obese patients as they did to more slender patients, potentially underdosing their larger patients and negatively affecting treatment outcomes. “The concern was that the risk of toxicity associated with chemotherapy could be higher in obese patients because they were getting much larger doses than non-obese patients,” explains Joseph Sparano, M.D., associate director for clinical research at the Albert Einstein Cancer Center in New York.

The consequences of underdosing can be significant. A 2013 review by Gary H. Lyman and Alex Sparreboom, published in the journal Nature Reviews Clinical Oncology, found that a 20 percent reduction in chemotherapy dosing lowered remission and cure rates by half in animal tumor models. Another study, published in 2015 in the journal JAMA Oncology, found that a group of women with ovarian cancer, including some who were overweight and some who were not, had a 35 percent higher risk of mortality if they received less than 85 percent of the chemotherapy dose they should have gotten based on their weight, compared with women who received adequate dosing.

In 2012, the American Society of Clinical Oncology published revised clinical practice guidelines that encouraged oncologists to measure chemotherapy drugs based on a patient’s actual size and weight rather than ideal weight after studies showed that this practice did not cause extra side effects.

Obesity can affect outcomes in other ways, as well. For example, a 2013 study published in the Journal of the National Cancer Institute suggests there could be a reactivation of dormant tumor cells across levels of fat, as evidenced by the fact that, in animals, where visceral fat is present, both circulating tumor cells and lung cancer metastasis are more likely to be seen. Additional evidence comes from the observation that receptors for growth factors that are elevated with obesity are commonly expressed on circulating tumor cells. The same study noted, too, that fat tissue can dramatically affect the metabolization of chemotherapy drugs, and thus influence efficacy and prognosis.

When cancers are linked to obesity, that doesn't always spell a negative impact on prognosis, however. A 2016 study published in the Journal of Clinical Oncology found that, while obesity is a risk factor for clear cell renal cell carcinoma (RCC), a high BMI is a prognostic factor for improved survival in patients with metastatic RCC who have received targeted therapy. Several hypotheses have been proposed for this paradox, including the theory that longer survival among obese patients is due to a less aggressive disease subtype.

Obesity may also play a significant role in cancer recurrence, researchers suggest. It’s an issue of particular concern for certain breast cancer patients, because a higher BMI at the time of diagnosis has been associated with poorer outcomes in terms of recurrence and survival, says Heather Greenlee, N.D., Ph.D., assistant professor of epidemiology at the Columbia University Mailman School of Public Health in New York. “It appears that if women gain a substantial amount of weight following a breast cancer diagnosis, that also is associated with poorer outcomes,” Greenlee notes. A 2012 study published in the journal Cancer affirms this concept, noting that overweight and obese women diagnosed with early-stage, hormone receptor-positive breast cancer and treated with standard chemotherapy and hormonal drugs have a higher risk of recurrence and lower survival rates.

WEIGHT GAIN DURING TREATMENT

An issue of concern often unforeseen by patients with cancer is weight gain during treatment. Patients often assume that they will lose weight during their treatment regimens, and are greatly surprised when the opposite occurs. “We tend to think of cancer chemotherapy as causing weight loss, but when that happens, it’s usually from the cancer itself,” notes Griggs.

Weight gain during treatment is fairly common, especially among breast cancer patients, but researchers are unsure of the exact mechanism behind it. “One hypothesis is that women reduce their physical activity during treatment,” Greenlee says. “It also could be an effect of the drugs themselves. Likely, it’s a combination of the two.”

There is evidence that a woman can lose lean body mass during treatment, slowing her metabolism and, thus, her ability to burn calories; if treatment induces menopause, that may also cause weight gain.

“Cancer disrupts people’s lifestyles,” adds Sarah Kiser, M.S., R.D., a clinical oncology dietician with Cancer Treatment Centers of America at Western Regional Medical Center in Goodyear, Arizona. “There can be grieving and stress involved, along with life changes. Additionally, treatment can cause side effects that might result in choosing less-than-desirable foods, such as taste changes. If a patient is experiencing taste changes, they might crave comfort foods over a well-balanced diet.”

When weight gain does occur, it can be difficult to lose, adds Griggs. “It’s not their destiny to gain weight, but when patients think they’re losing weight and people want to help by bringing them meals and taking them out, they actually put on 10 pounds,” she observes. “That 10 pounds can be very hard to lose, whereas if they lose weight on chemotherapy, they are likely to gain that back.”

FINDING WEIGHT-LOSS SUCCESS

Yankee knows how difficult post-treatment weight loss can be. Upon enrolling in the Survivorship Clinic at Smilow Cancer Hospital at Yale New Haven, in Connecticut, she was placed in the LEAN Study, which looked at how weight affects survivorship. Initially, she was part of the control group, which meant she received only a brief meeting with a nutritionist and a pamphlet on healthy eating. Yankee continued to gain weight until she was provided with ongoing nutritional counseling and weight-loss tools, such a food journal, pedometer and weight-loss program book.

“Getting up to 10,000 steps a day was difficult, especially since the first week of the program I reopened stitches from my DIEP flap revision (the breast reconstruction) and needed to be careful about my exercise,” Yankee says. “But that same week, I lost three pounds from the food journaling and portioning alone. At the end I lost 25 pounds, and have lost five additional pounds since then.”

The program worked for many others in the study too, and its authors say their findings support the idea that weight loss interventions should be used to improve diet among breast cancer survivors.

Kiser, too, encourages all cancer patients to eat with nutrition in mind as they go through their cancer journeys. She recommends a diet rich in fruits, vegetables, whole grains, nuts and seeds, and light on red and processed meat such as bacon and sausage. She also suggests limiting saturated fatty acids, which come primarily from animal foods.

“I think every patient who faces a cancer diagnosis is interested in making dietary changes of some kind,” Kiser says. “It can be a positive point of change in someone’s life.”