Stress management techniques improve long-term mood and quality of life in women diagnosed with breast cancer

A new study shows that providing women with skills to manage stress early in their breast cancer treatment can improve their mood and quality of life many years later. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings suggest that women given the opportunity to learn stress management techniques during treatment may benefit well into survivorship.

At the turn of the century, 240 women with a recent breast cancer diagnosis participated in a randomized trial that tested the effects of a stress management intervention developed by Michael Antoni, PhD, of the University of Miami. Dr. Antoni and his team found that, compared with patients who received a one-day seminar of education about breast cancer, patients who learned relaxation techniques and new coping skills in a supportive group over 10 weeks experienced improved quality of life and less depressive symptoms during the first year of treatment.

In their latest report, the researchers found that the women who received the stress management intervention had persistently less depressive symptoms and better quality of life up to 15 years later. “Women with breast cancer who participated in the study initially used stress management techniques to cope with the challenges of primary treatment to lower distress. Because these stress management techniques also give women tools to cope with fears of recurrence and disease progression, the present results indicate that these skills can be used to reduce distress and depressed mood and optimize quality of life across the survivorship period as women get on with their lives,” said lead author Jamie Stagl, who is currently at Massachusetts General Hospital, in Boston.

Stagl noted that breast cancer survivors in the stress management group reported levels of depression and quality of life at the 15-year follow-up that were similar to what is reported by women without breast cancer. Also, the intervention was helpful for women of various races and ethnic backgrounds. “This is key given the fact that ethnic minority women experience poorer quality of life and outcomes after breast cancer treatment,” said Stagl.

As survival rates increase for breast cancer, the question of how to maintain psychosocial health becomes increasingly salient. The current findings highlight the possibility that psychologists and social workers may be able to “inoculate” women with stress management skills early in treatment to help them maintain long-term psychosocial health.

Because depressive symptoms have been associated with neuroendocrine and inflammatory processes that may influence cancer progression, our ongoing work is examining the effects of stress management on depression and inflammatory biomarkers on the one hand, and disease recurrence and survival on the other,” said Dr. Antoni.

Stag et al. Long term psychological benefits of cognitive-behavioral stress management for women with breast cancer: 11-year follow-up of a randomized controlled trial. Cancer. 2015; DOI: 10.1002/cncr.29076 [Abstract]

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Detecting cancer cells in blood can give an early warning of treatment failure

A blood test that measures the number of cells shed from prostate tumours into the bloodstream can act as an early warning sign that treatment is not working, a major new study shows. Researchers showed that measuring the numbers of circulating tumour cells in the blood predicted which men were benefiting least from a prostate cancer drug after as little as 12 weeks of treatment.

They hope their work will allow doctors to switch patients to alternative treatments earlier than is currently possible, if these results are confirmed by further studies. The research could also hasten the development of cancer treatments by speeding up clinical trials, since doctors could tell much earlier whether a treatment is working.

The study was led in the UK by researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and also involved several leading international institutions. It was funded by a range of organisations including a Medical Research Council biomarkers grant, the companies Janssen Diagnostics, the Prostate Cancer Foundation in the US, and Prostate Cancer UK.

As tumours grow and progress, they shed cancer cells into the bloodstream, some of which can seed new secondary tumours elsewhere in the body. So the researchers wanted to see whether a high number of circulating tumours cells was an indication of a growing tumour that wasn’t responding to treatment, and could predict a lower chance of survival.

The study, published in the Journal of Clinical Oncology, involved the detailed analysis of blood samples from 711 men who took part in a major phase III trial of the prostate cancer drug abiraterone.

Researchers measured numbers of circulating tumour cells at four-week periods after the start of treatment with the drug, along with a range of other biomarker molecules in the blood including lactate dehydrogenase (LDH), high levels of which are a sign of general tissue damage.

The trial itself had used the standard trial end points of average overall survival and survival free of cancer progression to show abiraterone’s effectiveness in late-stage prostate cancer. But the researchers were able to cross-reference those results with data on circulating tumour cells and LDH levels in each man taking part.

They found a correlation between those men who had responded least well to treatment with abiraterone, and higher levels of cancer cells and LDH in the bloodstream, measured 12 weeks after starting treatment. They showed that levels of circulating tumour cells varied independently of a range of other biomarkers.

To prove the effectiveness of a new drug, clinical trials normally need to be run until the cancer is progressing clinically for each patient – and often until many of the patients on the trial have died. But with this new blood test, it might be possible to use circulating tumour cells as an early indicator that a drug is or is not working, and as a predictor of survival.

Study leader Professor Johann de Bono, Professor of Experimental Cancer Therapeutics at The Institute of Cancer Research, London, and Honorary Consultant at The Royal Marsden NHS Foundation Trust, said:
The past decade has seen unprecedented success in the development of new drugs for advanced, metastatic prostate cancer. One of the major challenges we face now is in optimising the use of these new treatments by making sure that the right men receive them, and only for as long as they are benefitting.
Our study showed that circulating tumour cells act as an early warning test for men who are not responding to treatment – potentially allowing doctors to switch patients early to alternative options. We hope our results will not only lead to better use of the current range of treatments, but also speed up the discovery of new drugs by providing an important new tool to the researchers trialling them.”

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:
Using a blood test to assess whether a cancer drug is working would be much easier and more convenient than other methods of monitoring treatment, and might pick up signs that a tumour is not responding weeks or months earlier than is achievable now. It could give doctors a valuable early warning that treatment is not working, and an opportunity to switch the patient promptly to an alternative drug.”

Scher et al. Circulating tumor cell biomarker panel as an individual-level surrogate for survival in metastatic castration-resistant prostate cancer. J Clin Oncol. 2015;  doi: 10.1200/JCO.2014.55.3487 [Abstract]

Researchers change human leukemia cells into harmless immune cells

Researchers at the Stanford University School of Medicine have discovered that when a certain aggressive leukemia is causing havoc in the body, the solution may be to force the cancer cells to grow up and behave.

After a chance observation in the lab, the researchers found a method that can cause dangerous leukemia cells to mature into harmless immune cells known as macrophages.The findings  will be published  in the Proceedings of the National Academy of Sciences.

B-cell acute lymphoblastic leukemia with a mutation called the Philadelphia chromosome is a particularly aggressive cancer with poor outcomes, said Ravi Majeti, MD, PhD, an assistant professor of medicine and senior author of the paper. So finding potential treatments is particularly exciting.

Majeti and his colleagues made the key observation after collecting leukemia cells from a patient and trying to keep the cells alive in a culture plate. “We were throwing everything at them to help them survive,” said Majeti, who is also a member of the Stanford Cancer Institute and the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

An unusual metamorphosis

Postdoctoral scholar Scott McClellan MD, PhD, a lead author of the paper, mentioned that some of the cancer cells in culture were changing shape and size into what looked like macrophages. Majeti concurred with that observation, but the reasons for the changed cells were a mystery until he remembered an old research paper, which showed that early B-cell mouse progenitor cells could be forced to become macrophages when exposed to certain transcription factors — proteins that bind to certain DNA sequences.

B-cell leukemia cells are in many ways progenitor cells that are forced to stay in an immature state,” Majeti said. So he, McClellan and student Christopher Dove, an MD/PhD student and the paper’s other lead author, did more experiments and confirmed that methods shown to have altered the fate of the mouse progenitor cells years ago could be used to transform these human cancer cells into macrophages, which can engulf and digest cancer cells and pathogens.

Majeti and his colleagues have some reason to hope that when the cancer cells become macrophages they will not only be neutralized, but may actually assist in fighting the cancer. Like a bloodhound owner who gives the dog a sniff of an object that was associated with the person or animal he wants to track, macrophage cells present recognizable bits of abnormal cells to other immune cells so that they can launch an attack. “Because the macrophage cells came from the cancer cells, they will already carry with them the chemical signals that will identify the cancer cells, making an immune attack against the cancer more likely,” Majeti said.

The hope for a therapy

The researchers’ next steps will be to see if they can find a drug that will prompt the same reaction and that could serve as the basis for a therapy for the leukemia. There is some precedent for such a treatment. Retinoic acid is commonly used to treat another cancer called acute promyelocytic leukemia. In that case, retinoic acid is used to turn cancer cells into mature cells called granulocytes. This treatment is the only well-established therapy that matures, or “differentiates,” cancer cells, but researchers around the world are hopeful of finding many more. “There’s big-time interest in differentiation therapies for cancer,” Majeti said.

Oncologists reveal reasons for high cost of cancer drugs in the US and recommend solutions

Increasingly high prices for cancer drugs are affecting patient care in the U.S. and the American health care system overall, say the authors of a special article published online in the journal Mayo Clinic Proceedings.

Americans with cancer pay 50 percent to 100 percent more for the same patented drug than patients in other countries,” says S. Vincent Rajkumar, M.D., of Mayo Clinic Cancer Center, who is one of the authors. “As oncologists we have a moral obligation to advocate for affordable cancer drugs for our patients.”

Dr. Rajkumar and his colleague, Hagop Kantarjian, M.D., of MD Anderson Cancer Center, say the average price of cancer drugs for about a year of therapy increased from $5,000 to $10,000 before 2000 to more than $100,000 by 2012. Over nearly the same period the average household income in the U.S. decreased by about 8 percent.

In the paper, the authors rebut the major arguments the pharmaceutical industry uses to justify the high price of cancer drugs, namely, the expense of conducting research and drug development, the comparative benefits to patients, that market forces will settle prices to reasonable levels, and that price controls on cancer drugs will stifle innovation.

One of the facts that people do not realize is that cancer drugs for the most part are not operating under a free market economy,” says Dr. Rajkumar. “The fact that there are five approved drugs to treat an incurable cancer does not mean there is competition. Typically, the standard of care is that each drug is used sequentially or in combination, so that each new drug represents a monopoly with exclusivity granted by patent protection for many years.”

Drs. Rajkumar and Kantarjian say other reasons for the high cost of cancer drugs include legislation that prevents Medicare from being able to negotiate drug prices and a lack of value- based pricing, which ties the cost of a drug to its relative effectiveness compared to other drugs.

The authors recommend a set of potential solutions to help control and reduce the high cost of cancer drugs in the U.S. Some of their recommendations are already in practice in other developed countries. Their recommendations include:

  • Allow Medicare to negotiate drug prices.
  • Develop cancer treatment pathways/guidelines that incorporate the cost and benefit of cancer drugs.
  • Allow the Food and Drug Administration or physician panels to recommend target prices based on a drug’s magnitude of benefit (value-based pricing).
  • Eliminate “pay-for-delay” strategies in which a pharmaceutical company with a brand name drug shares profits on that drug with a generic drug manufacturer for the remainder of a patent period, effectively eliminating a patent challenge and competition.
  • Allow the importation of drugs from abroad for personal use.
  • Allow the Patient-Centered Outcomes Research Institute and other cancer advocacy groups to consider cost in their recommendations.
  • Create patient-driven grassroots movements and organizations to advocate effectively for the interests of patients with cancer to balance advocacy efforts of pharmaceutical companies, insurance companies, pharmacy outlets and hospitals.