Breast cancer survivors gain more weight than cancer-free women

Breast cancer survivors with a family history of the disease, including those who carry BRCA1 and BRCA2 gene mutations, gained more weight over the course of four years than cancer-free women – especially if they were treated with chemotherapy, according to a prospective study by Johns Hopkins Kimmel Cancer Center researchers.

Data from earlier studies suggest that breast cancer survivors who gain weight may have a higher risk of having their cancer return, the researchers say, noting that gains of 11 pounds or more are also associated with a higher risk of developing cardiovascular disease.

For the study, the researchers reviewed a baseline questionnaire and a follow-up one 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 a baseline and at least one follow-up questionnaire between 2005 and 2013, and one-quarter of the subjects were premenopausal.

In the four-year span, survivors gained significantly more weight – 3.6 pounds on average – than cancer-free women. Among 180 survivors diagnosed with cancer during the last five years of the study period, 37 (21 percent) gained at least 11 pounds over a four-year period compared with 35 of 307 (11 percent) 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 say.

Our study suggests that chemotherapy may be one of the factors contributing to weight gain among survivors,” says Kala Visvanathan, M.B.B.S., M.H.S., an associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health and director of the Clinical Cancer Genetics and Prevention Service at the Kimmel Cancer Center. 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 during the study.

There is limited data on weight change in breast cancer survivors, including those at higher risk for the disease compared to the general population,” Visvanathan says. “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.”

Results of the study by Visvanathan and her colleagues appear online in Cancer Epidemiology, Biomarkers & Prevention.

Using information from study subjects’ answers in detailed questionnaires, along with their medical records, the scientists 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 gains in survivors and cancer-free women.

The researchers say they also found 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 46.9 percent of survivors and 55.1 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.

Statin users among breast cancer survivors treated with chemotherapy also gained more weight – an average of 10 pounds more – 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 estrogen receptor-negative, invasive cancers,” says Amy Gross, M.H.S., a doctoral candidate in epidemiology at the Bloomberg School of Public Health.

The Johns Hopkins study adds to an emerging body of evidence that chemotherapy can lead to weight gain in cancer survivors, Visvanathan noted, but it’s not clear why the treatment has this effect. Some scientists suggest 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,” Visvanathan says.

The researchers plan 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.

Noting the limits of the study and the need for longer follow-up, Visvanathan cautions that “we’re not yet suggesting any weight gain intervention at the time of chemotherapy.”

But we are 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,” she adds.

The scientists note that the majority of subjects in the current study are Caucasian, which limits their ability to apply their findings to women of other ethnic backgrounds. The study’s reliance on self-reported weight also can be subject to bias or error, but the scientists found a high degree of similarity between self-reported and measured weight among a subgroup of the study participants.

Gross et al. Weight Change in Breast Cancer Survivors Compared to Cancer-Free Women: A Prospective Study in Women at Familial Risk of Breast Cancer. Cancer Epidemiol. Biomarkers Prev. 2015; doi:10.1158/1055-9965.EPI-15-0212 [Abstract]

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Increased radiation offers no survival benefit for patients with low-risk prostate cancer

Increased radiation dose was only associated with higher survival rates in men with more aggressive cancers

Increased radiation dose is associated with higher survival rates in men with medium- and high-risk prostate cancer, but not men with low-risk prostate cancer, according to a new study from Penn Medicine published this week in JAMA Oncology. Already-high survival rates for men with low-risk prostate cancer were unaffected by higher radiation dosages compared to lower radiation dosages.

In 2014, low-risk prostate cancer was the most common type of prostate cancer diagnosed in the United States, affecting about 150,000 patients, many of whom undergo aggressive treatment, either complete removal of the prostate or radiation.

Our study raises the provocative question of whether radiation dose reduction for patients with low-risk prostate cancer could achieve similar cure rates while avoiding the increased risk of side effects associated with higher radiation doses,” said the study’s lead author,Anusha Kalbasi, MD, a resident in the department of Radiation Oncology at the Perelman School of Medicine at the University of Pennsylvania.

Using data from a National Cancer Database, the study employed specialized analytic methods to compare the survival rates of 42,481 men in the absence of a randomized clinical trial. Some men received standard dose of radiation while others received higher dose radiation. For men with medium- and high-risk forms of prostate cancer, the study found that for every incremental increase in radiation dose, there was a 7.8 percent and 6.3 percent reduction in the rate of death from any cause. For men with low-risk cancer, no differences in survival were found whether they received the standard dosage of radiation or a higher dosage.

The study is the first to link increased radiation dose with higher survival rates. Previous studies have linked increased radiation dose with two key measures: steady PSA scores and the absence of re-growth in tumors of the prostate following successful radiation.

The Penn-led team examined men who were diagnosed with prostate cancer between 2004 and 2006 and followed through 2012. In 2004, 56 percent of these men received higher dosages of radiation. Today, the figure is approximately 90 percent.

Kalbasi and his colleagues found that in the low-risk group of men, seven-year adjusted survival rates were 86 percent for both standard-dose and higher-dose patients. In the medium-risk group of men, seven-year adjusted survival rates were 82 percent and 78 percent for higher-dose and standard-dose patients, respectively. In the high-risk group of men, seven-year adjusted survival rates were 74 percent and 69 percent for higher-dose and standard-dose patients respectively.

Doctors divide localized prostate cancer (prostate cancer that is only in the prostate gland and which has not spread outside of the prostate) into three risk groups. Low-risk prostate cancers are unlikely to grow or spread for many years. Medium-risk cancers are unlikely to grow or spread for a few years. High-risk cancers may grow or spread within a few years. Three criteria are generally used for classifying prostate cancer risk: PSA level, Gleason score, and T stage. PSA is a protein produced by both normal and cancerous prostate cells; a high level of PSA can be a sign of cancer. The Gleason score is a qualitative assessment of any cancer cells that may be present. T stage refers to the size and extension of tumors.

Radiation therapy is associated with side effects and those side effects have been shown to increase with radiation dose, said Kalbasi. For patients undergoing prostate radiation, side effects include, fatigue, urinary frequency and urgency, changes in bowel habits, and erectile dysfunction.

Prostate cancer is the most common cancer diagnosed among American men, and causes more deaths annually among men than any other tumor except lung cancer. However, a large majority of men found to have prostate cancer ultimately die of other causes, prompting researchers to conduct studies to identify who benefits most from treatment and what those treatments should be.

Our findings show that the dose of radiation should be personalized to the specific characteristics of the prostate tumor,” said Justin Bekelman, MD, an associate professor of Radiation Oncology at Penn, and the study’s senior author. “For some patients, personalized treatment will lower the chances of toxicity while maintaining similar survival rates; for other patients, personalized treatment will mean escalating radiation dose to achieve the highest survival while protecting normal tissues, like the bladder and rectum.

Kalbasi et al. Dose-escalated irradiation and overall survival in men with nonmetastatic prostate cancer.JAMA Oncol. Published online July 16, 2015; doi:10.1001/jamaoncol.2015.2316 [Abstract]

Patients with lowest body mass index have shortest survival in metastatic colorectal cancer treated with bevacizumab

Patients with the lowest body mass index (BMI) had the shortest overall survival in an analysis of bevacizumab studies in metastatic colorectal cancer (mCRC) presented for the first time at the ESMO 17th World Congress on Gastrointestinal Cancer 2015 in Barcelona.

There is good evidence that obesity increases the risk of getting colorectal cancer and that it increases the risk of colorectal cancer recurrence after curative therapy,” said lead study author Dr Yousuf Zafar, associate professor of medicine at Duke Cancer Institute in Durham, North Carolina. “What we did not know prior to these results is whether there is a relationship between obesity and survival in patients with metastatic colorectal cancer.”

He continued: “There is evidence that, at least in the US, obese patients may be at risk to receive lower doses of chemotherapy, so we hypothesised that obesity would be associated with worse survival in patients with colorectal cancer.”

The current study analysed overall survival and progression-free survival according to four categories of BMI (<25, 25-<30, 30-35, >35 kg/m2) in patients treated with bevacizumab in the first line for mCRC. The researchers used a pooled dataset of patients with previously untreated mCRC who received bevacizumab with chemotherapy in four large prospective US and European registry studies, namely BEAT, BRiTE, AWB and CONCERT.

A total of 6,128 patients were included in the analysis, which showed that patients with the lowest BMI (<25 kg/m2) had a significantly shorter overall survival than patients in the other BMI categories (see table). Progression-free survival was similar across all BMI subgroups.

Zafar said: “Our primary finding was that obesity was not associated with worse survival in mCRC. Contrary to our hypothesis, patients who had the lowest BMI were at risk of having the shortest survival. This effect persisted after adjusting for study, age, ECOG performance status, gender, and hypertension. We did not see any relationship between BMI and progression-free survival.”

With regard to how the findings might be explained, Zafar said: “When it comes to obesity and colorectal cancer incidence and recurrence, there is likely some biologic mechanism that increases that risk, which may be related to factors including insulin or insulin-like growth factor. However, in the relationship between obesity and survival in metastatic colorectal cancer, it’s likely that cancer-related cachexia overwhelmed any potential biologic harm from obesity or any potential inadequate dosing that obese patients may experience.”

He added: “These results suggest that cachexia is a fairly strong predictor of poor outcomes in these patients. This could be a biologic effect or a treatment pattern issue. Cachexia by itself is a poor prognostic indicator but there also may be a relationship between cachexia and how much treatment patients can tolerate. I would hypothesise that the lowest weight patients in our analysis received or tolerated less treatment.

Patients with the lowest BMI had similar progression-free survival to those in the other BMI categories. Zafar explained: “It’s possible that the lowest weight patients may receive adequate first-line treatment but then are too sick to receive subsequent lines of therapy. That may be where we can focus more attention on improving their outcomes.”

Looking to the future of this research area, Zafar said: “An important next step in this work would be a closer study of how cachexia worsens patient outcomes in mCRC. We need to understand whether it is the biology of cachexia that harms these patients more, or whether their outcome is worsened by receipt of sub-par treatment. Or it could be a combination of both.”

Commenting on the data, Dr Roberto Labianca, Director of the Cancer Centre, Ospedale Giovanni XXIII in Bergamo, Italy, ESMO spokesperson, said: “This study is important because we can now consider BMI as a prognostic factor for patients with metastatic colorectal cancer. The clinical implication could be that patients with low BMI should be considered similar to patients with more aggressive cancer and probably they should be given more active treatment. For example, polychemotherapy instead of monotherapy or a biological plus chemotherapy instead of chemotherapy alone.”

We need more follow up of course,” continued Labianca. “The next step could be to design a prospective clinical trial using BMI to stratify patients for treatment.”

ESMO 17th World Congress on Gastrointestinal Cancer 2015 in Barcelona