Targeting Depressive Symptoms in Younger Breast Cancer Survivors
Guest Editor’s Note: Psychological distress is highly prevalent in women diagnosed with premenopausal breast cancer and has a significant negative impact on their quality of life. Thus, effective strategies are urgently needed to reduce the symptom burden. In this installment of The ASCO Post’s Integrative Oncology series, Patricia A. Ganz, MD, FASCO, and Julienne E. Bower, PhD, both of UCLA, summarize the study conducted by their group to determine the potential of a mindfulness meditation intervention in managing psychological disturbances in young breast cancer survivors.
Patricia A. Ganz, MD, FASCO
Julienne E. Bower, PhD
Breast cancer is the most common cancer in women in the United States and around the world. Although the average age of onset for breast cancer is 61, about 19% of new cases are diagnosed in women who are younger than 50. This is a time in life where most women are working or may still be in school and have caregiving responsibilities for children or older adults. Adding a new diagnosis of cancer to a busy life, especially at a life stage when cancer is not expected, can cause substantial psychological distress. Many cancers in younger women are discovered at a more advanced stage and often require complex and toxic therapy that may compromise fertility and family planning, such as ovarian function suppression, which initiates the abrupt onset of menopause.
In addition to these facts about the epidemiology of breast cancer in younger women, depression is much more common in younger adults in the general population. Thus, the co-occurrence of a life-threatening cancer diagnosis in a psychologically vulnerable age group increases the likelihood of greater severity and persistence of depressive symptoms after a breast cancer diagnosis in these younger women.
Background to the Intervention Study
Our group has had a long-term interest in the quality-of-life impact of breast cancer treatments on women’s lives.1-3 Early on, we found that these impacts were often more severe for younger women with breast cancer.3 In a systematic review, we documented the literature that consistently noted the greater burden of psychological distress in younger women with breast cancer.4 These findings encouraged us to examine the unique issues these women faced and to design interventions that addressed their needs.
Young breast cancer survivors told us that the thing they needed most was something to help them manage their psychological distress.— Patricia A. Ganz, MD, FASCO, and Julienne E. Bower, PhD
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In a focus group we conducted prior to embarking on intervention development, young breast cancer survivors told us that the thing they needed most was something to help them manage their psychological distress. A growing body of research was documenting the beneficial effects of mindfulness-based interventions for depression, anxiety, and pain in clinical populations. With their focus on reducing distress and enhancing well-being, we thought these interventions may be a good choice for young breast cancer survivors.
The Mindful Awareness Research Center (MARC) at our institution had developed and was popularizing a program called “Mindful Awareness Practices,” which were taught in weekly group sessions over a 6-week period. We partnered with MARC to conduct an initial phase II randomized controlled trial of mindful awareness practices vs a waitlist control in 71 younger breast cancer survivors. It showed significant reductions in perceived stress after the intervention was employed, with marginally significant reduction in depressive symptoms.5 There was also evidence of reduced fatigue and insomnia, increased positive affect and meaning/purpose in life, and a significant reduction in inflammation. Based on these strong preliminary data, we moved to a larger, full-scale, multisite clinical trial.
Pathways to Wellness (PTW) Trial Details
The PTW trial was conducted at the University of California, Los Angeles (UCLA), Dana-Farber Cancer Institute, and Johns Hopkins Kimmel Cancer Center between 2017 and 2020. The three-arm trial involved younger patients (≤ age 50 at diagnosis) with early-stage breast cancer who had completed primary treatment; the three arms were designated as mindful awareness practices, survivor education, or waitlist control.6 Potential participants were required to have a minimal level of depressive symptoms to be eligible, with no previous training in mindfulness or currently practicing meditation on a regular basis. Recruitment occurred through clinical and cancer registries, as well as community organizations in each of the three study locations.
The mindful awareness practices and survivor education interventions were conducted as 2-hour group sessions weekly, for 6 weeks. The interventions were manualized and offered by local instructors who were centrally trained and whose classes were monitored for fidelity. The analytic design was a comparison of mindful awareness practices and survivor education with the waitlist control condition to see how each intervention might benefit the participants. Psychosocial assessments were done prior to randomization, immediately after the intervention, and at 3- and 6-month follow-ups. Blood was collected at baseline, after the intervention, and at 6 months for evaluation of inflammatory markers, ie, C-reactive protein, interleukin-6, and tumor necrosis factor–alpha.
The primary outcome was reduction in depressive symptoms at the postintervention assessments, with secondary outcomes including change in depressive symptoms over the 6-month follow-up and impact of the interventions on fatigue, insomnia, vasomotor symptoms, psychological function, and inflammation. The Patient Health Questionnaire for Depression (PHQ-8) was used for eligibility screening, and the Center for Epidemiologic Studies Depression Scale (CES-D) was the primary measure of depression used in the trial outcome analysis.
Key Results of the PTW Trial
Across the three sites, we enrolled 247 women (median age, 46 years) who were randomly assigned to mindful awareness practices (n = 85), survivor education (n = 81), or waitlist control (n = 81). Mindful awareness practices and survivor education led to significant decreases in depressive symptoms from before to after the intervention relative to the waitlist control (mean change relative to the waitlist control [95% confidence interval (CI)]: mindful awareness practices, –4.7 [–7.5 to –1.9]; survivor education, –4.0 [–6.9 to –1.1]), which persisted at the 6-month follow-up for mindful awareness practices (mean change relative to the waitlist control [95% CI]: mindful awareness practices, –3.7 [–6.6 to –0.8]; survivor education, –2.8 [–5.9 to 0.2]).
Jun J. Mao, MD, MSCE
Mindful awareness practices, but not survivor education, also had beneficial effects on fatigue, insomnia, and vasomotor symptoms that persisted at the 6-month follow-up (P < .05).6 We also found that mindful awareness practices significantly decreased intrusive thoughts and worry after the intervention and at the 3-month follow-up relative to the waitlist control (P < .027) and significantly increased positive affect and meaning and peace after the intervention, with positive affect persisting at the 3-month follow-up (P < .027). Survivor education significantly decreased intrusive thoughts at the 3-month follow-up and significantly increased positive affect at the 6-month follow-up relative to the waitlist control (P < .01). Proinflammatory gene expression increased in the waitlist control relative to mindful awareness practices (P = .016) but did not differ from survivor education. There were no intervention effects on other outcomes.7
The 6-week education program on mindful awareness practices showed a benefit in younger breast cancer survivors who in addition to having symptoms of depression also suffered from concurrent fatigue, insomnia, and vasomotor symptoms. Our next steps are to evaluate two alternative means of delivering mindful awareness practices using the Zoom digital platform with a live instructor or a digital app that delivers the same educational content. There is clearly a need for addressing the psychological distress in this vulnerable population of cancer survivors.
DISCLOSURE: Dr. Ganz has received royalties from UpToDate for her role as editor of its section on cancer survivorship and consulting fees from InformedDNA, Blue Note Therapeutics, and Roche. Dr. Bower reported no conflicts of interest.
1. Ganz PA, Hirji K, Sim MS, et al: Predicting psychosocial risk in patients with breast cancer. Med Care 31:419-431, 1993.
2. Ganz PA, Rowland JH, Desmond K, et al: Life after breast cancer: Understanding women’s health-related quality of life and sexual functioning. J Clin Oncol 16:501-514, 1998.
3. Ganz PA, Greendale GA, Petersen L, et al: Breast cancer in younger women: Reproductive and late health effects of treatment. J Clin Oncol 21:4184-4193, 2003.
4. Howard-Anderson J, Ganz PA, Bower JE, et al: Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: A systematic review. J Natl Cancer Inst 104:386-405, 2012.
5. Bower JE, Crosswell AD, Stanton AL, et al: Mindfulness meditation for younger breast cancer survivors: A randomized controlled trial. Cancer 121:1231-1240, 2015.
6. Bower JE, Partridge AH, Wolff AC, et al: Targeting depressive symptoms in younger breast cancer survivors: The Pathways to Wellness randomized controlled trial of mindfulness meditation and survivorship education. J Clin Oncol 39:3473-3484, 2021.
7. Bower JE, Partridge AH, Wolff AC, et al: Improving biobehavioral health in younger breast cancer survivors: Pathways to Wellness trial secondary outcomes. J Natl Cancer Inst 115:83-92, 2023.