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Breast cancer survivors with a family history of the disease, including those who have BRCA1 and BRCA2 gene mutations, gained more weight over the course of four years than cancer-free women-especially if they received chemotherapy, according to data from a prospective study by Johns Hopkins Kimmel Cancer Center researchers, now online ahead of print in Cancer Epidemiology, Biomarkers & Prevention (doi: 10.1158/1055-9965.EPI-15-0212).


The authors noted that data from earlier studies have suggested that breast cancer survivors who gain weight may have a higher risk of recurrence, and that increases of 11 pounds or more are also associated with a higher risk of developing cardiovascular disease.


For the study, the researchers reviewed baseline questionnaires and follow-up ones completed four years later by 303 breast cancer survivors and 307 cancer-free women enrolled in an ongoing and long-term study at the Kimmel Cancer Center of women with a family history of breast or ovarian cancer. Study participants completed both questionnaires between 2005 and 2013, and 25 percent of the subjects were premenopausal.


In that four-year span, survivors gained significantly more weight-an average of 3.6 pounds-than the cancer-free women. Among 180 survivors diagnosed with cancer during the last five years of the study period, 37 (21%) gained at least 11 pounds over a four-year period compared with 35 of 307 (11%) of their cancer-free peers. The weight change findings remained the same after accounting for other factors associated with weight gain, such as increasing age, transition to menopause, and level of physical activity, the researchers said.


"Our study suggests that chemotherapy may be one of the factors contributing to weight gain among survivors," Kala Visvanathan, MBBS, MHS, Associate Professor of Epidemiology at Johns Hopkins Bloomberg School of Public Health and Director of the Clinical Cancer Genetics and Prevention Service at Kimmel Cancer Center, said in a news release. Women who completed chemotherapy within five years of the study were 2.1 times as likely as cancer-free women to have gained at least 11 pounds.


Data Has Been Limited

"There is limited data on weight change in breast cancer survivors, including those at higher risk for the disease compared with the general population," she said. "A lot of studies have focused on breast cancer survivors alone, so we don't get a sense of whether women without cancer gain more or less weight, or whether the gain is due to the cancer or the treatment."


Using information from the answers to the questionnaires, along with medical records, the researchers controlled for such factors as age, menopausal status, physical activity, the presence of cancer-linked mutations in the BRCA genes, and weight at the start of the study when they compared the gains in survivors and cancer-free women.


The results also showed a high prevalence of overweight women among the group of 303 breast cancer survivors and 307 cancer-free women with a family history or inherited predisposition for breast cancer, including those who carry BRCA1 or BRCA2 gene mutations, with about 47 percent of survivors and 55 percent of cancer-free women who were overweight or obese.


In addition, breast cancer survivors diagnosed within five years before their baseline weight measurement and who had invasive disease and cancer cells lacking receptors for estrogen gained an average of 7.26 pounds more than cancer-free women.

KALA VISVANATHAN, MB... - Click to enlarge in new windowKALA VISVANATHAN, MBBS, MHS. KALA VISVANATHAN, MBBS, MHS: "We're looking at possible biomarkers."

Statin Users

Statin users among breast cancer survivors treated with chemotherapy also gained more weight-an average of at least 10 pounds-than cancer-free women who used statins, as well as survivors and cancer-free women who did not use the cholesterol-blocking drug.


"Above and beyond age and menopausal status, there seems to be a weight gain associated with treatment of cancer, particularly in women having chemotherapy and those diagnosed with ER-negative, invasive cancers," said the first author, Amy Gross, MHS, a doctoral candidate in epidemiology at the Bloomberg School of Public Health.


Mechanism Unclear

Visvanathan noted that the study adds to an emerging body of evidence that chemotherapy can lead to weight gain in cancer survivors, but it remains unclear why that would be so. One theory is that chemotherapy increases inflammation and insulin resistance, disrupting metabolism and producing weight gain. Patients treated with chemotherapy may also be less physically active and prone to weight gain as a result.


"We're looking at biomarkers in urine and blood in our survivors and in women who are cancer-free to look for the biochemical changes that may be related to this higher weight gain."


She said that the team plans to continue following the full study group every three to four years to determine how the women's weight changes over a longer period of time, emphasizing, though that the team is not suggesting the use of any weight gain intervention at the time of chemotherapy.


"We are, though, suggesting that oncologists, internists, or anyone treating breast cancer survivors, including those with a family history of the disease, could help them monitor their weight over the long term."