Women and Cancer: Psychiatric Care Makes a Difference

May 27, 2011 (Honolulu, Hawaii) — Psychiatric treatment and psychosocial support may make a significant difference to survival and quality of life in women with cancer, a patient population with high rates of depression and anxiety, according to 2 studies presented here at the American Psychiatric Association 2011 Annual Meeting.

In the first study, a secondary analysis of a randomized controlled trial (RCT) of 125 women with metastatic breast cancer, investigators found that the median survival time for those who had decreasing depression symptom scores during a 1-year period was double that of those with increasing scores (53.6 vs 25.1 months).

"We were surprised at how big this difference was. It shows that treatment of depression, both psychotherapeutic and pharmacologic, is feasible and effective even in advanced cancer," David Spiegel, MD, Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, California, and Stanford's Center on Stress and Health, told Medscape Medical News.

Dr. David Spiegel

"Although the intervention we used wasn't associated with increased survival, we were able to show that decreasing depression may improve not only the quality but also the quantity of life for these women," added Dr. Spiegel.

In the second study, which was published online March 2 in Psycho-Oncology, researchers found that women who receive a cancer diagnosis during pregnancy were at particular risk of experiencing high levels of distress.

"Physicians should pay particular attention to several early markers of distress suggesting a need for referral to psychological supports. This may lead to improved long-term quality of life for both the women and for their children," Melissa Henry, PhD, from McGill University in Montreal, Quebec, Canada, told Medscape Medical News.

Dr. Henry added that both patients and clinicians can find more information on the topic at the Pregnant with Cancer support network Web site.

Psychological Interventions 'Overlooked'

According to Dr. Spiegel's study, which was also published in the February 1 issue of the Journal of Clinical Oncology, numerous trials have examined links between depression and cancer.

"Cancer researchers increasingly find significant associations between depression and endocrine dysregulations, heart rate variability, inflammatory markers, and mortality endpoints," write the investigators.

However, they note that few studies have examined "whether changes in depression symptoms are associated with survival."

In the February 2 issue of the Journal of the American Medical Association, as reported by Medscape Medical News, Dr. Spiegel wrote in an essay that social support and psychologic/psychiatric interventions can improve survival in cancer but are often "overlooked" in treating the disease.

In the same article, Richard Sloan, PhD, from the Division of Behavioral Medicine at the Columbia University Medical Center in New York City, told Medscape Medical News that although "social support almost certainly makes people feel better," there is no strong body of evidence showing that treatments addressing social or emotional issues actually improve survival for cancer patients.

"We should treat depression because it makes patients miserable not because we think it may improve survival," said Dr. Sloan at that time.

"He's just wrong about this," answered Dr. Spiegel, noting that "7 of about 12 trials have now shown an effect of emotional support on survival.

"True, not all studies show it, but a number of them do and it's not random. Our paper is another example of something that's long been pooh-poohed — that psychosocial variables do affect cancer survival. People might not like it, but the data speak for itself."

Lingering Depression 'Toxic'

In this study, the researchers evaluated data from an RCT conducted between 1991 and 1996 that examined the effects of supportive-expressive group therapy (SET) on women in the San Francisco Bay Area with metastatic breast cancer (mean age, 52.7 years).

The participants were randomized to receive either SET for 1 year plus education materials (n = 64) or the educational materials only (n = 61). The SET consisted of weekly group sessions led by cotherapy teams.

All women completed the Center for Epidemiologic Studies–Depression Scale (CES-D) at baseline and during 4-, 8-, and 12-month follow-up visits. Survival data were obtained by either consulting the Social Security Death Index or through follow-up calls to participants, their families, or their physicians.

Results showed "a significant effect of change in CES-D over the first year on survival out to 14 years (P = .007)," report the researchers.

"When we looked at 5 years after we started the study, half of the improving population [those with higher CES-D scores] was alive compared to only a third of the worsening population," said Dr. Spiegel.

Although the women in the SET treatment group had significant improvements in trauma symptoms, mood disturbance, pain, and emotion regulation, there was no significant interaction found between specific treatment group and CES-D change on survival.

"A possible clinical implication of our study is that although becoming depressed shortly after diagnosis may be a normal, necessary, and healthy experience of grieving and adjustment, if depression lingers, it may have toxic survival consequences," write the investigators.

Does HPA Dysregulation Predict Survival?

Dr. Spiegel added that he has found that the patients who try to suppress emotion are actually more depressed and more anxious than those who don't.

"My goal is to convert anxiety into fear and depression into sadness so that they know what they are anxious or sad about and don't feel so overwhelmed. We also encourage people to face their fears of death, calling it 'detoxifying dying,'" he explained.

"The challenge is redefining hope and redefining priorities. And we hope that patients will be transformed from feeling damaged by their disease to transcending it and living with it as best they can."

Although he noted that causation cannot be assumed from this study, Dr. Spiegel reported that his team is now doing research on how stress and depression affect the hypothalamic-pituitary-adrenal axis (HPA) in these patients.

"There's reason to think that HPA dysregulation is a factor in predicting cancer mortality. We found that in a breast cancer sample, both at earlier stage and at metastatic stage, many did not have a normal cortisol pattern; it actually did not go down as much during the day. And this also predicted shorter survival."

More Anxious Than Depressed

Dr. Melissa Henry

In the second study, the investigators examined data from 231 women (mean age at diagnosis, 34 years; average gestation time, 14 weeks) from the Cancer and Pregnancy Registry, which was developed by coinvestigator Elyce Cardonick, MD, from Cooper University Hospital in Camden, New Jersey.

All participants completed questionnaires, including the Impact of Event Scale (IES) and the Brief Symptom Inventory 18 (BSI-18). The registry also included data on follow-up after delivery over several years.

Results showed that 74 of the women completed the IES and BSI-18 measures a mean of 3.8 years after diagnosis. A total of 52% and 21% of the women had acute levels of distress on the 2 measures, respectively.

"Interestingly, these women were more anxious overall than depressed," said Dr. Henry.

Markers of significantly increased risk for long-term psychological distress, as shown on the IES, included not receiving fertility treatments (P = .02), disregarding advice to terminate their pregnancy (P = .02), undergoing postpregnancy surgery (P = .01), and having a preterm infant (P = .005).

Significant risk markers for stress from the BSI-18 included having insufficient milk production (P = .02) and currently experiencing a cancer recurrence (P = .03). Having a caesarean delivery was also a trending factor.

"We don't know if increased distress decreases milk production or the motivation to breastfeed or if it’s the decrease in milk production that increases distress. For those diagnosed as having cancer of the breast and have a mastectomy without reconstructive surgery, it can also be very upsetting to try to breastfeed with only 1 breast," noted Dr. Henry.

"Overall, it's very difficult to know in which way the direction goes in terms of the associations between the different variables we found. It would be interesting to now do a follow-up study that is qualitative to better understand the context of the findings," she added.

'Incredible' Clinical Impact

"I treat women in pregnancy and although I don't recall any of my patients being diagnosed with cancer during that time, I absolutely agree with this paper that the psychological impact in this situation is incredible from a clinical perspective," Linda Gruenberg, DO, assistant professor at Rush University Medical Center in Chicago, Illinois, told Medscape Medical News.

"Now, is a patient coming to you after they've been diagnosed or have you been seeing them and then they become diagnosed? Your treatment relationship with them is also going to have an impact, especially if you're already treating them with psychopharmacology because of an Axis 1 disorder vs psychotherapy. It's very complex," added Dr. Gruenberg, who was not involved in the research.

She noted that in addition to the variables mentioned in the study, others that come into play include whether it is a wanted or unwanted pregnancy, if there are other children at home, what type of cancer the patient has, and what the various treatment options are for that cancer.

"The bottom line is you've got to take every case on an individual basis and look at the individual circumstances, including what the prognosis is for their situation. Presentations like this are very helpful, especially for people who don't typically think about cancer and pregnancy in the same sentence," concluded Dr. Gruenberg.

Dr. Spiegel's study was funded by grants from the National Institute of Mental Health, the National Cancer Institute, the National Institute on Aging, and the American Cancer Society and by the John D. and Catherine T. MacArthur Foundation and the Fetzer Institute. Dr. Spiegel, Dr. Henry, and Dr. Gruenberg have disclosed no relevant financial relationships.

American Psychiatric Association (APA) 2011 Annual Meeting: Scientific and Clinical Report Session 18, No. 1: Presented May 15, 2011; and Session 29, No. 1: Presented May 18, 2011.

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