A systematic review of published results from 203 randomized clinical trials, involving more than 80 different integrative therapies, has yielded evidence-based recommendations for clinicians and their patients with breast cancer about which of these therapies may be most helpful to manage their symptoms.
Heather Greenlee, ND, PhD
A systematic review of published results from 203 randomized clinical trials, involving more than 80 different integrative therapies, has yielded evidence-based recommendations for clinicians and their patients with breast cancer about which of these therapies may be most helpful to manage their symptoms. The recommendations also identify complementary interventions for which not enough evidence of benefit currently exists, as well as those deemed unlikely to provide any help.
This research forms the basis of newly published guidelines appearing online in the Journal of the National Cancer Institute Monographs and issued by the Society of Integrative Oncology (SIO).1 The goal of the new guidelines is to provide an evidence base for shared decision-making between clinicians and patients with breast cancer—the majority of whom studies show use complementary therapies (between 48% and 80% in North America). Worldwide and for all types of cancer, approximately 33% to 47% of patients use these therapies to complement standard care.
“Most breast cancer patients have experimented with integrative therapies to manage symptoms and improve quality of life,” noted lead author and SIO president, Heather Greenlee, ND, PhD, “but of the dozens of products and practices marketed to patients, we found that only a handful currently have a strong evidence base.”
To develop the new guidelines, researchers searched nine databases (EMBASE, MEDLINE, PubMed, CINAHL, PsychINFO, Web of Science, SCOPUS, AMED, and Accutrial) for studies published between 1990 and 2013 which evaluated the safety and effectiveness of integrative approaches used in the context of supportive cancer care.
The search generated 4900 unique articles and was then refined to include only those based on results from randomized clinical trials and those in which the patient cohort included at least 50% with a breast cancer diagnosis and/or trials reporting breast cancer—specific results; 203 articles met the criteria for final review. A panel of multidisciplinary experts in oncology and integrative medicine was convened to prepare the clinical practice guidelines, and the group used the Institute of Medicine’s guideline development process to direct its work.
Greenlee, an assistant professor of epidemiology at Columbia University’s Mailman School of Public Health, noted that the new science-based guidelines should serve as an important tool to support clinicians and their patients in assessing the risk—benefit ratio for each therapy. The expert panel also organized the therapies around specific symptoms to make them more practical for use in the clinic, eg, anxiety, depression, sleep quality, pain, and lymphedema—assigning a grade to various complementary interventions commonly used to manage these symptoms, based on the evidence.
Complementary therapies which showed demonstrable benefit in randomized clinical trials include meditation, yoga, and relaxation with imagery. These interventions received an A grade based on a modified version of the US Preventive Services Task Force grading system which was used to develop the SIO guidelines, and these approaches are recommended for routine use for anxiety and mood disorders. These same practices also received a B grade for reducing stress, depression, and fatigue. Massage also received a B grade for improving mood disturbance in posttreatment survivors.
The authors also noted promising evidence on the use of acupuncture for nausea, fatigue, anxiety, pain, and quality of life, although the modality did not achieve grade A or B on the scale. Similarly, the use of acupressure and ginseng for fatigue, and ginger for chemotherapy-induced nausea and vomiting (CINV), show potential for verification of benefit through further study.
Although 30 interventions received a C grade and did not have sufficient evidence to support specific recommendations, “this does not mean that they don’t work,” stressed Greenlee. “This means that we don’t yet know if they work, in what form, or what dose is most effective.” Other complementary therapies in this category include healing touch and hypnosis for pain, manual lymph drainage and low-frequency laser therapy for lymphedema, especially for survivors who are unable to tolerate compression bandaging, and acupuncture for improving depressive symptoms in women experiencing hot flashes.
Seven therapies were deemed unlikely to provide any benefit, and one therapy which has been marketed to prevent chemotherapy-related neuropathy, acetyl-l-carnitine, was found to be harmful and actually increased the risk for the condition.
The researchers stressed the importance of ongoing assessment of the impact of the complementary interventions, even those which their scientific review deemed beneficial. Included in the published guidance is a recommendation that patients using these therapies be monitored for “efficacy and toxicity, including futility and adverse effects.” They also recommended that patients be encouraged to maintain symptom logs.
SIO intends to update the breast cancer guidelines every 3 years. It has previously issued and updated general practice guidelines for integrative therapies, as well as those specific to patients with lung cancer.
Guideline authors, among them, Debu Tripathy, MD, professor and chair of Breast Medical Oncology at MD Anderson Cancer Center, see integrative oncology as an area ripe for further research to address unmet patient needs.
“A challenge in assessing the safety and effectiveness of complementary therapies was the lack of standardization of interventions across trials using similar therapeutic approaches,” said Tripathy. The authors suggest incorporating assessment of integrative therapies as part of conventional treatment trials.
"The vast majority of therapies require further investigation through well-designed controlled clinical trials,” said Greenlee.