Brief cognitive-behavioral and relaxation training interventions for breast cancer: A randomized controlled trial.

OBJECTIVE: Women with breast cancer (BCa) report elevated distress postsurgery. Group-based cognitive-behavioral stress management (CBSM) following surgery improves psychological adaptation, though its key mechanisms remain speculative. This randomized controlled dismantling trial compared 2 interventions featuring elements thought to drive CBSM effects: a 5-week cognitive-behavioral training (CBT) and 5-week relaxation training (RT) versus a 5-week health education (HE) control group. METHOD: Women with stage 0-III BCa (N = 183) were randomized to CBT, RT, or HE condition 2-10 weeks postsurgery. Psychosocial measures were collected at baseline (T1) and postintervention (T2). Repeated-measures analyses of variance (ANOVAs) tested whether CBT and RT treatments improved primary measures of psychological adaptation and secondary measures of stress management resource perceptions from pre- to postintervention relative to HE. RESULTS: Both CBT and RT groups reported reduced depressive affect. The CBT group reported improved emotional well-being/quality of life and less cancer-specific thought intrusions. The RT group reported improvements on illness-related social disruption. Regarding stress management resources, the CBT group reported increased reliability of social support networks, while the RT group reported increased confidence in relaxation skills. Psychological adaptation and stress management resource constructs were unchanged in the HE control group. CONCLUSIONS: Nonmetastatic breast cancer patients participating in 2 forms of brief, 5-week group-based stress management intervention after surgery showed improvements in psychological adaptation and stress management resources compared with an attention-matched control group. Findings provide preliminary support suggesting that using brief group-based stress management interventions may promote adaptation among nonmetastatic breast cancer patients.

Improved clinical outcomes associated with vitamin D supplementation during adjuvant chemotherapy in patients with HER2+ nonmetastatic breast cancer.

BACKGROUND: Vitamin D (VD) supplementation has pleiotropic effects that extend beyond their impact on bone health, including the disruption of downstream VD receptor signaling and human epidermal growth factor receptor 2 (HER2) signaling through the ErbB2/AKT/ERK pathway. In the present study, we examined our institutional experience with patients having nonmetastatic HER2-positive (HER(+)) breast cancer and hypothesized that those patients who received VD supplementation during neoadjuvant chemotherapy would have improved long-term outcomes. PATIENTS AND METHODS: We performed a retrospective review of all patients (n = 308) given trastuzumab-based chemotherapy between 2006 and 2012 at the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC). We identified 2 groups of patients for comparison-those who received VD supplementation during neoadjuvant chemotherapy (n = 134) and those who did not (n = 112). Univariate and multivariate Cox proportional hazard regression models were fitted to overall survival (OS) and disease-free survival (DFS). RESULTS: More than half of the patients received VD during neoadjuvant chemotherapy (54.5%), with 60% receiving a dose < 10,000 units/wk and 33.3% having a VD deficiency at the start of therapy. In our final multivariate model, VD use was associated with improved DFS (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.15-0.88; P = .026], whereas larger tumor size was associated with worse DFS (HR, 3.52; 95% CI, 1.06-11.66; P = .04). There were no differences in OS based on any of the categories, including VD use, tumor size, number of metastatic lymph nodes, age at diagnosis, or lymphovascular invasion (LVI). CONCLUSION: VD supplementation in patients with nonmetastatic HER2(+) breast cancer is associated with improved DFS.

A cost-benefit analysis of bevacizumab in combination with paclitaxel in the first-line treatment of patients with metastatic breast cancer.

Bevacizumab in combination with chemotherapy increases progression-free survival (PFS), but not overall survival when compared to chemotherapy alone in the treatment of metastatic breast cancer (MBC). Recently in November, 2011 the Food and drug administration revoked approval of bevacizumab in combination with paclitaxel for the treatment of MBC. The European Medicines Agency, in contrast, maintained its approval of bevacizumab in MBC. While neither agency considers health economics in their decision-making process, one of the greatest challenges in oncology practice today is to reconcile hard-won small incremental clinical benefits with exponentially rising costs. To inform policy-makers in the US, this study aimed to assess the cost-effectiveness of bevacizumab/paclitaxel in MBC, from a payer perspective. We created a decision analytical model using efficacy and adverse events data from the ECOG 2100 trial. Health utilities were derived from available literature. Costs were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2010 US dollars. Quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. Sensitivity analyses were performed. Bevacizumab added 0.49 years of PFS and 0.135 QALY with an incremental cost of $100,300, and therefore a cost of $204,000 per year of PFS gained and an ICER of $745,000 per QALY. The main drivers of the model were drug acquisition cost, PFS, and health utility values. Using a threshold of $150,000/QALY, drug price would have to be reduced by nearly 80% or alternatively PFS increased by 10 months to make bevacizumab cost-effective. The results of the model were robust in sensitivity analyses. Bevacizumab plus paclitaxel is not cost-effective in treating MBC. Value-based pricing and the development of biomarkers to improve patient selection are needed to better define the role of the drug in this population.

Racial differences in acute toxicities of neoadjuvant or adjuvant chemotherapy in patients with early-stage breast cancer.

BACKGROUND: Racial disparities in breast cancer outcomes are attributed to differences in baseline tumour characteristics and biology, stage, age, ethnic background and socioeconomic factors. However, little is known about racial differences in treatment-related toxicities. We hypothesised that racial/ethnic differences result in differential tolerance to chemotherapy potentially, leading to compromised dose intensity/density of chemotherapy in patients with early-stage breast cancer. METHODS: Data were collected from patients treated at five international centers for early breast cancer with the same adjuvant/neoadjuvant chemotherapy (FEC 100: fluorouracil 500mg/m(2), epirubicin 100mg/m(2), and cyclophosphamide 500mg/m(2),every 21d for 3-6 cycles). Toxicities were assessed by first episode of ⩾grade 2 toxicity. RESULTS: Toxicities were compared according to four race/ethnicity groups (103 Caucasian, 30 African American, 164 Asian, and 34 Hispanic patients). Tumour characteristics across four race/ethnicity groups were similar. Asians had a significantly higher rate of grade 3 haematologic toxicity than Caucasians, African Americans or Hispanic women (32%, 16%, 10%, and 15%, respectively; p<0.05). In multivariate analysis, only lower BMI was associated with a higher incidence of ⩾grade 3 toxicities. However, no significant differences in chemotherapy dose intensity/density were shown across the four race/ethnicity groups. CONCLUSION: Racial differences in acute toxicity were noted in women with breast cancer who were treated with FEC 100 chemotherapy, suggesting that extrapolating toxicities from chemotherapy across ethnicities is not possible and emphasising the need to validate safety of chemotherapeutic regimens in patients of different ethnicities by enhancing the participation of minorities in clinical trials.

Stress management intervention reduces serum cortisol and increases relaxation during treatment for nonmetastatic breast cancer.

OBJECTIVE: To examine the effects of a cognitive-behavioral stress management (CBSM) intervention, which was composed of relaxation, cognitive restructuring, and coping skills training on late afternoon serum cortisol and relaxation indicators in women who were undergoing treatment for nonmetastatic breast cancer. METHODS: Participants (N = 128) were randomly assigned to receive a 10-week CBSM group intervention or a 1-day psychoeducation seminar. Serum cortisol was collected and ability to relax was assessed at study entry and again at 6- and 12-month follow-up visits. Data were analyzed using latent growth curve modeling. RESULTS: There was a significant effect of study condition on change across time for both cortisol and perceived ability to relax. Women receiving CBSM had significantly greater reductions in cortisol levels across the 12 months compared with those in the control group, who had no appreciable decline. Women receiving CBSM reported greater increases in ability to relax than controls across time. Perceived ability to relax did not mediate CBSM-related reductions in cortisol. CONCLUSIONS: Women who participate in a 10-week CBSM intervention during treatment for breast cancer show decreases in physiological stress in parallel with increases in perceived relaxation skills. This is the first study demonstrating well-maintained reductions in cortisol after a CBSM intervention in cancer patients during and just after treatment.

Chemoprevention of breast cancer.

Breast cancer remains the second leading cause of malignancy-related death in women in the USA, regardless of advances in novel therapeutic agents. High priority should be given to research aimed at the study of pharmacological and natural compounds that could potentially prevent the development of breast cancer in susceptible patients. Tamoxifen has been shown to reduce the incidence of estrogen receptor-positive invasive breast cancer in women with a high risk of developing this condition by nearly 50%, and studies in osteoporosis have revealed a similar protective effect of raloxifene in postmenopausal women. The aromatase inhibitors are superior to tamoxifen in reducing the recurrence of breast cancer in postmenopausal women; large clinical trials are currently evaluating the chemopreventive effect of these agents. The list of agents with the potential for chemoprevention in breast cancer is extensive and continues to expand. There is an immense need to develop drugs that will decrease the incidence of estrogen receptor-negative breast cancer in women at high risk of developing the disease. Herein, we review the most important chemopreventive agents in breast cancer and clinical trials that have evaluated their efficacy.

Randomized trial of high-dose chemotherapy with autologous peripheral-blood stem-cell support compared with standard-dose chemotherapy in women with metastatic breast cancer: NCIC MA.16.

PURPOSE: We conducted a multicenter, randomized trial to compare progression-free survival (PFS), overall survival (OS), and quality of life in women with metastatic breast cancer (MBC) receiving high-dose chemotherapy plus autologous stem-cell transplantation (ASCT; HDCT) compared with standard-dose therapy. PATIENT AND METHODS: Between April 1997 and December 2000, 386 women with MBC and no prior chemotherapy for metastatic disease were registered. After initial response to anthracycline- or taxane-based induction chemotherapy, 224 patients were randomly assigned: 112 to high-dose cyclophosphamide, mitoxantrone, and carboplatin chemotherapy and ASCT (HDCT), and 112 to standard therapy (ST). Median age was 47 years (range, 25 to 67 years). Thirty two percent of women randomly assigned had estrogen and progesterone receptor-negative breast cancer, 42% had visceral metastases, and 58% had bone metastases. Complete remission rates before random assignment were 11% for those receiving HDCT and 12% for those receiving ST. RESULTS: After a median follow-up of 48 months, 79 deaths were observed in the HDCT arm and 77 deaths were observed in the ST arm; seven patients (6%) in the HDCT arm died as a result of toxicity. The median OS was 24 months for the HDCT arm (95% CI, 21 to 35 months) and 28 months for ST (95% CI, 22 to 33 months; hazard ratio [HR], 0.9; 95% CI, 0.6 to 1.2; P = .43). PFS was 11 months for HDCT and 9 months for ST (HR, 0.6 in favor of HDCT; 95% CI, 0.5 to 0.9; P = .006). CONCLUSION: HDCT did not improve OS in women with MBC when used as consolidation after response to induction chemotherapy.

How stress management improves quality of life after treatment for breast cancer.

The range of effects of psychosocial interventions on quality of life among women with breast cancer remains uncertain. Furthermore, it is unclear which components of multimodal interventions account for such effects. To address these issues, the authors tested a 10-week group cognitive-behavioral stress management intervention among 199 women newly treated for nonmetastatic breast cancer, following them for 1 year after recruitment. The intervention reduced reports of social disruption and increased emotional well-being, positive states of mind, benefit finding, positive lifestyle change, and positive affect for up to 12 months (indeed, some effects strengthened over time). With respect to mechanisms tested, the intervention increased confidence in being able to relax at will. There was also evidence that effects of the intervention on the various outcomes examined were mediated by change in confidence about being able to relax. Thus, this intervention had beneficial effects on diverse aspects of quality of life after treatment for breast cancer, which appear linked to a specific stress management skill taught in the intervention.

The expanding role of epirubicin in the treatment of breast cancer.

Adjuvant treatment of early breast cancer has experienced major changes in the last 25 years. Since the mid 1970s, when cyclophosphamide, methotrexate and fluorouracil (CMF) resulted in statistically significant and clinically meaningful improvements in disease-free and overall survival, the use of adjuvant chemotherapy has become common practice worldwide. Anthracyclines are considered to be among the most active available agents to treat breast cancer and have become core components of adjuvant regimens. Anthracycline-containing polychemotherapy regimens provide a significant benefit over CMF. Regimens containing epirubicin are generally associated with prolongation in relapse-free and overall survival rates compared with standard therapies including CMF. Epirubicin-taxane combinations are active in treating metastatic breast cancer and do not appear to be associated with any pharmacokinetic interactions. Ongoing research is focusing on combining anthracyclines with taxanes in an effort to continue to improve outcomes following adjuvant therapy.