Weight loss decreases breast cancer risk in postmenopausal women

October is breast cancer awareness month, which an annual campaign to increase the awareness about the deadly disease. With over 2 million new cases every year, it is the most prevalent cancer in women. Although breast cancer runs in families, there are other lifestyle and environmental factors which increase the risk of breast cancer.

Obesity increases the risk of postmenopausal breast cancer; the risk is 1.5 times higher in overweight women and about 2 times in obese women than healthy weight women. The association between weight loss and incidence of breast cancer is inconsistent, and few studies have evaluated the association between the two.

 A recent observational study by Chlebowski RT et al. published in Cancer, the peer-reviewed journal of the American Cancer Society reported that women decreased the risk of breast cancer by 12% if they lost weight in 3 years as compared to the ones whose weight remained stable.

“Obesity is associated with increased risk of incident postmenopausal breast cancer,” Rowan T. Chlebowski, MD, Ph.D., research professor in the department of medical oncology and therapeutics research at City of Hope National Medical Center, and colleagues wrote. “Because approximately one-third of postmenopausal women in the United States are obese, obesity represents a common and potentially modifiable factor related to breast cancer outcome. However, it has not been established that weight loss in postmenopausal women decreases breast cancer incidence or breast cancer mortality.”

The researchers from the Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California used data from the Women’s Health Initiative (WHI) Observational Study to study the association.

The study included 61,335 postmenopausal women with no prior history of breast cancer and normal mammogram with body weight and height measured and body mass index (BMI) calculated at baseline and after 3 years.

At the end of 3 years, the analysis was based on 3 weight categories: stable, 5% increase or 5% decrease.

The study participants were between 50 to 79 years, and the mean follow-up duration was 11.4 years, during which the researchers observed 3,061 cases of breast cancer.

Women (n = 8175) who lost weight faced a 12% decreased risk of breast cancer as compared to women whose weight remained stable (n = 41,139) (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.78‐0.98; P = .02). The association remained the same even after adjustment for mammography.

The mean time to develop breast cancer was 6.5 years after the 3-year weight determination.

Women who gained (≥5%) weight (n = 12,021) were not associated with increased risk of breast cancer (HR, 1.02; 95% CI, 0.93‐1.11) but did show a slightly higher incidence of triple‐negative breast cancer (HR, 1.54; 95% CI, 1.16‐2.05).

“Our study indicates that moderate, relatively short-term weight reduction was associated with a statistically significant reduction in breast cancer risk for postmenopausal women,” said Dr. Chlebowski in Wiley press release. “These are observational results, but they are also supported by randomized clinical trial evidence from the Women's Health Initiative Dietary Modification trial where, in a randomized clinical trial setting, adopting a low-fat dietary pattern that was associated with a similar magnitude of weight loss resulted in a significant improvement in breast cancer overall survival. These findings, taken together, provide strong correlative evidence that a modest weight loss program can impact breast cancer.”

Here is the visual abstract of the study.

Abstract

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Higher Topiramate dose in early pregnancy linked to increased risk of oral cleft

Use of Topiramate in early pregnancy for treating epilepsy is associated with nearly 8 times higher risk of oral clefts in newborn reports the results of a large population based cohort study published December 27, 2017 in journal Neurology.

The observed association was not very strong for lower doses of topiramate used for treating migraines and bipolar disorder.

A diagnosis of oral cleft includes cleft lip and cleft palate.

Previous studies have demonstrated a 5-fold increased risk of oral cleft in women taking around 200 mg of topiramate daily for epilepsy, but the association was unclear about consumption of lower dose.

To assess the risk of oral dose, the investigators analyzed a large cohort of 1,360,101 pregnant women with a live-born infant enrolled in Medicaid from 3 months before conception through 1 month after delivery over a period of 10 years. 

The prescription information was obtained from nationwide Medicaid Analytic eXtract (MAX) which keeps a record of all diagnoses and procedures and prescription filled outside hospitals.

The analyses of data identified 2425 women who were exposed to topiramate in early pregnancy as shown by atleast one filled prescription of the drug in first trimester.

The neonatal outcome for this cohort was compared to a reference group of 1,322,955 pregnant women who did not fill prescription for topiramate or other anticonvulsant drugs.

The multivariate analysis included many potential confounders like maternal age, race, topiramate indication (epilepsy, migraine, bipolar disorder, pain condition), obesity, smoking, comorbidities, concomitant medications, and overall health status.

Regression analysis showed that women with topiramate consumption in early pregnancy are 3 times increased risk of giving birth to a baby with oral cleft, as compared to women who have never taken the drug for any indication.

Risk was also assessed for consumption of another anticonvulsant medication, lamotrigine in first trimester. The risk with lamotrigine was only slightly more as compared to non-exposed population and the patients using topiramate were nearly 2.5 times at increased risk of oral clefts as compared to lamotrigine.

Women with epilepsy were nearly 8 times increased risk of oral cleft as compared to non-exposed.

Lead author, Dr Hernandez-Diaz, MD, professor of epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts said, "Our best estimate is that women with epilepsy using 200 mg or more of topiramate have around an 8-fold increased risk, and those using lower doses had a twofold or lower risk. The results suggest that the risk with lower doses, if it is there, is much less than for higher doses."

The researchers carried out multiple sensitivity analyses, with different doses of topiramate and window of exposure, but the association between topiramate and oral clefts remained the same.

The study confirms the results of earlier studies and stress upon the fact that “dose does matter.” The risk ratio for oral clefts for > 100 mg of topiramate was nearly 5 times more than that of < 100 mg.

In addition, topiramate does interfere with oral contraceptives and may be responsible for many unplanned pregnancies because of contraceptive failures. Hence, women who are on topiramate and do not want to conceive should additionally use a barrier method of contraception.

The study limitations include poor socioeconomic status of women (which itself is a risk for oral clefts), and not controlling for folic acid use.

Women with anti-epileptic medication should take folic acid which reduces the chances of oral clefts. 

But sometimes it is prescribed off-label to treat obesity and control weight gain.  In 2012, the United States Food and Drug Administration (FDA) approved topiramate in combination with phentermine (Qsymia) to treat weigh gain issues. 

Abstract

FDA press release