Lack of Sleep Linked to Breast Cancer Aggressiveness

In Postmenopausal Women Only

Nick Mulcahy

September 07, 2012

September 7, 2012 — For the first time, lack of sleep has been associated with more aggressive breast cancers, according to findings published in the August issue of Breast Cancer Research and Treatment.

The study was conducted in 101 women with early-stage estrogen-receptor-positive breast cancer who were assessed with the Oncotype DX test, which guides treatment in early-stage breast cancer by predicting the likelihood of recurrence.

The worst scores on the recurrence probability test were found in women who reported having the least sleep at night. Specifically, having fewer than 7 hours of sleep a night during the 2 years before the diagnosis was associated with a greater risk for recurrence.

However, this association between less sleep and breast cancers that are more aggressive and more likely to recur was strong only in postmenopausal women (P = .0011), not in premenopausal women (P = .80).

"This is the first study to suggest that women who routinely sleep fewer hours may develop more aggressive breast cancers than women who sleep longer hours," said lead author Cheryl Thompson, PhD, in a press statement. She and her coauthor, Li Li, MD, PhD, are from Case Western Reserve University in Cleveland, Ohio.

The study findings are limited by the "relatively modest sample size," the authors acknowledge.

Nevertheless, the study adds to the literature on sleep duration and breast cancer. Four previous studies, all of which assessed breast cancer risk and did not specifically look at breast cancer aggressiveness, have had "mixed results," according to the authors. Three of these have suggested that sleep can reduce the risk for breast cancer and 1 found no association at all.

Medscape Medical News asked Simone P. Pinheiro, ScD, from the Center for Drug Evaluation and Research at the US Food and Drug Administration (FDA), for her opinion on this study.

Before joining the FDA, Dr. Pinheiro was the lead author of the large prospective study that "did not find convincing evidence to support an association between habitual duration of sleep and subsequent development of breast cancer" (Cancer Res. 2006;66:5521-5525). However, information on habitual sleep duration was obtained prior to the development of breast cancer in that study, she emphasized.

The study by Drs. Thompson and Li "suggests" a "significant inverse correlation" between sleep duration and breast cancer aggressiveness among women diagnosed with breast cancer, Dr. Pinheiro noted.

These results could also reflect the effect of subclinical...breast cancer on sleep duration.

"These results could also reflect the effect of subclinical (not yet diagnosed) breast cancer on sleep duration," she said in an email. In other words, a woman's nascent breast cancer might have caused sleep disturbance, she explained.

So, is lack of sleep a new risk factor for aggressive breast cancers?

The authors believe it might be. "Our data suggest that lack of sufficient sleep may cause biologically more aggressive tumors," they write. But they note that "further work will need to be done to more thoroughly characterize the biology underlying this epidemiological association."

Less Sleep and Recurrence Scores Defined

All of the study participants are enrolled in a larger 412-patient case–control breast cancer study. As such, they were recruited at diagnosis and asked about lifestyle matters, including average sleep duration in the previous 2 years. Many of the breast cancer patients in the study underwent Oncotype DX testing.

The authors designated 3 levels of nightly sleep: 6 hours or less, 6 to 7 hours, and 7 or more hours.

Using previously published data on the recurrence probability test, they determined that scores below 18 predict a low risk for recurrence, scores of 18 to 30 predict an intermediate risk, and scores of 31 or higher predict a high risk.

Overall, less sleep was found to be correlated with a higher score. Risk for recurrence was intermediate in patients who slept 6 hours or less (mean recurrence score, 27.8) or 6 to 7 hours (mean recurrence score, 18.0) and low for patients who slept 7 or more hours (mean recurrence score, 16.4).

Thus, getting an average of less than 7 hours of sleep a night was associated with an intermediate risk and getting 7 or more hours was associated a with low risk. However, this finding was only statistically significant in the subset of postmenopausal women.

The lack of a strong association in premenopausal women is explainable, say the authors.

"It is well known that there are different mechanisms underlying premenopausal and postmenopausal breast cancers," they explain. "Our data suggest that sleep may affect carcinogenic pathway(s) specifically involved in the development of postmenopausal breast cancer, but not premenopausal cancer."

The positive findings in postmenopausal women remained statistically significant after adjustment for possible confounders, including age, physical activity, smoking status, and body mass index.

"Effective intervention to increase duration of sleep and improve quality of sleep could be an underappreciated avenue for reducing the risk of developing more aggressive breast cancers and recurrence," said Dr. Li in a press statement.

This study adds to the literature on lifestyle factors that can affect breast cancer and its related risk. These studied factors are increasingly diverse and include night-shift work, light in the bedroom, and more obvious variables such as obesity.

The study was supported by National Cancer Institute grants to the Case Western Reserve University School of Medicine. The authors have disclosed no relevant financial relationships.

Breast Cancer Res Treat. 2012;134:1291-1295. Abstract