Abstract

Numerous large trials involving more than 100000 patients have documented that adjuvant chemotherapy (AC) leads to considerable reductions inbreastcancer–relatedmortality.1Despite the well-documented survival benefits, a proportion of women for whom AC is indicated may delay or completely fail to initiateAC.This is a cause for considerable concern, as supported by the results of a systematic reviewandmeta-analysis of 7 studies involvingmore than34000women treated surgically for breast cancer, indicating that overall and disease-free survival is reduced by 15% and 16%, respectively, for every 4-week delay in initiation of AC.2 It is therefore of urgent interest to determine the factors associatedwith noninitiation of AC.With respect to patient decisions to delay or ultimately reject AC all together, a complex interaction of sociodemographic, clinical, and psychosocial patient characteristics, as well as oncologist factors, are likely to be at play. In this issueof JAMAOncology, Greenlee et al3 explore the possible role of patients’ use of complementary and alternative medicine (CAM) in noninitiation of AC in a cohort of 685 women with nonmetastatic, invasive breast cancer. Selfreport data collected 12 months after baseline indicated that 11%of thewomen forwhomACwas indicatedaccording toNational ComprehensiveCancerNetwork guidelines didnot initiate AC. A considerable proportion of the participants (87%) reported use of 1 or several types of CAM, and, after adjusting for anumberofdemographic andclinical variables, thehigher thenumberofCAMmodalitiesused, themore likely thewomen were tohavenoninitiatedAC.Amongthestrengthsof thestudy is that not only did the authors prospectively investigate the associationofoverallCAMusewithnoninitiation,but theyalso explored the use of several CAMmodalities. Users of dietary supplements seemed to be particularly at risk of not initiatingAC,whereas use of variousmind-bodypractices (eg, yoga, meditation, and acupuncture) seemed to be unrelated to AC initiation. Greenlee and colleagues3 did not explore patients’ motivations or their perceptions of CAM efficacy, but they do discuss the possibility that the benefits patients hope to obtain differ between these 2 categories of CAM. This finds support in a study4 of CAM use in a nationwide prospective cohort of 3343 Danish women treated for primary breast cancer. A considerable proportion of CAM users (23.7%) were absolutely or relatively certain that the CAM used would have a beneficial effect on their breast cancer, and, when exploring differences between use of various types of CAM, women who used herbal medicines or dietary and/or exercise counseling emerged as more likely than women who used various mind-body practices to perceive the CAM used as effective in treating their cancer. It thus seems quite possible that similar differences in perceived efficacy could explain the findings of the Greenlee et al3 study that users of dietary supplements were less likely to initiate AC and underscores the necessity to investigate the various characteristics associated with use of different CAM modalities rather than treating CAM use as one homogenous category. Additional findings from the cohort of Danish women treated for breast cancer could indicate that this particular groupofCAMusersmaybeparticularly vulnerable.5 TheCAM users thus reported more depressive symptoms than nonusers at both 3 and 15 months after surgery, with further analyses showing that having used CAM during the 12-month follow-upperiodwas associatedwithhigher levels of depressive symptoms at follow-up, even after adjusting for baseline depressive symptoms and sociodemographic, disease-related, and treatment-related variables, including comorbidity and previous psychiatric history.When comparing different CAM modalities, theuseofdietarysupplementsemergedas theonly independentpredictorof experiencingmoredepressive symptoms at both time points. The results described by Greenlee et al3 and others emphasize theneedto improveourunderstandingof thedecisionmaking process of patientswith cancer in their choice of conventionaloralternativetreatments.Arecentsystematic review6 of 35 studies suggests that CAM-related decision-making by patients with cancer occurs as a complex, nonlinear, dynamicprocess of information-seeking andevaluation. The results suggest a wide range of motivations behind the choice to use various types of CAMas patientsmove through the different phases of cancer treatment and recovery. In the early phase,whenpatients receive their initial cancerdiagnosis, the choice touseCAMseems tobeparticularly associatedwith the need to copewith the sense of loss of control. In later phases, the use of CAM seems to be directed toward perceived ends, such asmaintainingwell-being, controlling the spreadof cancer cells, boosting the immune system, and preventing or delaying recurrence. To provide the best evidence-based decision support regardingCAMuse—includingwhether touseCAMas a complementary or alternative treatment to AC—oncologists need to be actively involved in discussing CAM use with their patients.Onlybyacknowledging that communicationaboutCAM use is an important part of cancer carewill oncologists be able to help patients to make sufficiently informed choices about CAM use. However, as shown in a systematic review of the Related article page 1170 Complementary and Alternative Medicine and Chemotherapy Initiation Original Investigation Research

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