Supportive-expressive group therapy for women with metastatic breast cancer: survival and psychosocial outcome from a randomized controlled trial

BACKGROUND: Mixed reports exist about the impact of supportive-expressive group therapy (SEGT) on survival. METHODS: From 485 women with advanced breast cancer recruited between 1996-2002, 227 (47%) consented and were randomized within an average 10 months of cancer recurrence in a 2:1 ratio to intervention with 1 year or more of weekly SEGT plus three classes of relaxation therapy (147 women) or to control receiving three classes of relaxation therapy (80 women). The primary outcome was survival; psychosocial well-being was appraised secondarily. Analysis was by intention-to-treat. RESULTS: SEGT did not prolong survival (median survival 24.0 months in SEGT and 18.3 in controls; univariate hazard ratio for death 0.92 [95% CI, 0.69-1.26]; multivariate hazard ratio, 1.06 [95% CI, 0.74-1.51]). Significant predictors of survival were treatment with chemotherapy and hormone therapy (p<0.001), visceral metastases (p<0.001) and advanced disease at first diagnosis (p<0.05). SEGT ameliorated and prevented new DSM-IV depressive disorders (p = 0.002), reduced hopeless-helplessness (p = 0.004), trauma symptoms (p = 0.04) and improved social functioning (p = 0.03). CONCLUSIONS: SEGT did not prolong survival. It improved quality of life, including treatment of and protection against depression.     

Effects of supportive-expressive group therapy on survival of patients with metastatic breast cancer: a randomized prospective trial

BACKGROUND: This study was designed to replicate our earlier finding that intensive group therapy extended survival time of women with metastatic breast cancer. Subsequent findings concerning the question of whether such psychosocial support affects survival have been mixed. METHODS: One hundred twenty-five women with confirmed metastatic (n = 122) or locally recurrent (n = 3) breast cancer were randomly assigned either to the supportive-expressive group therapy condition (n = 64), where they received educational materials plus weekly supportive-expressive group therapy, or to the control condition (n = 61), where they received only educational materials for a minimum of 1 year. The treatment, 90 minutes once a week, was designed to build new bonds of social support, encourage expression of emotion, deal with fears of dying and death, help restructure life priorities, improve communication with family members and healthcare professionals, and enhance control of pain and anxiety. RESULTS: Overall mortality after 14 years was 86%; median survival time was 32.8 months. No overall statistically significant effect of treatment on survival was found for treatment (median, 30.7 months) compared with control (median, 33.3 months) patients, but there was a statistically significant intervention site-by-condition interaction. Exploratory moderator analysis to explain that interaction revealed a significant overall interaction between estrogen-receptor (ER) status and treatment condition (P = .002) such that among the 25 ER-negative participants, those randomized to treatment survived longer (median, 29.8 months) than ER-negative controls (median, 9.3 months), whereas the ER-positive participants showed no treatment effect. CONCLUSIONS: The earlier finding that longer survival was associated with supportive-expressive group therapy was not replicated. Although it is possible that psychosocial effects on survival are relevant to a small subsample of women who are more refractory to current hormonal treatments, further research is required to investigate subgroup differences.     

Locally advanced primary breast cancer: medium-term results of a randomised trial of multimodal therapy versus initial hormone therapy

We report the medium-term (median FOLLOW-UP=52 months) results of a prospective randomised trial of multimodal therapy (neoadjuvant chemotherapy, Patey mastectomy, postoperative radiotherapy and adjuvant hormone therapy) (n=56) versus initial hormone therapy (n=52) for locally advanced primary breast cancer. Compared with multimodal therapy, initial hormone therapy was associated with reduced number of therapies for disease control (mean=3.6 versus 4.9) and mastectomy rate (31%). Multimodal therapy conferred better initial locoregional control and a longer disease-free interval. Nevertheless, there was no statistically significant differences in the rates of survival, metastasis and uncontrolled locoregional disease, as well as in the time to metastasis between the two therapy groups. Regardless of the therapy groups, oestrogen receptor positivity conferred a lower metastasis rate, better survival and locoregional control. Thus, initial hormone therapy may be a reasonable option for managing locally advanced primary breast cancer, especially for oestrogen receptor-positive tumours.     

Rehabilitation needs and breast cancer: The first month after primary therapy

Summary Breast cancer is the most common neoplasm in occidental women, yet very little information is available about the rehabilitation needs of these patients. This report reviews in detail the physical, psychological, social, and financial problems identified by fifty women during the first month after primary surgical treatment. The most frequently reported problems were physical and psychological. Patients undergoing modified radical mastectomy (MRM) are compared with patients receiving segmental mastectomy and primary radiotherapy (SM). There were few differences between the two surgical treatment groups; however, patients in the MRM group reported more difficulty with clothing and body image, while the SM group had more disruption of recreation and social activities. Information about the rehabilitation problems of patients with this common neoplasm should be helpful to patients and to the members of the health care team who are helping them recover.     

Modulating effect of lonidamine on response to doxorubicin in metastatic breast cancer patients: Results from a multicenter prospective randomized trial

Previous results from our preclinical studies have shown that lonidamine (LND) can positively modulate the antiproliferative activity of doxorubicin (DOX) on breast cancer cell lines. To evaluate the effect of LND in a clinical setting, a multicenter randomized trial was carried out on patients with advanced breast cancer. From September 1991 to July 1993, 181 patients were enrolled in the trial and received an initial treatment of DOX at 75 mg/m² for 3 cycles. The 137 patients who reached complete remission, partial remission, or stable disease were randomized to receive either DOX alone (75 mg/m² day 1) (arm A) or DOX plus LND (600 mg orally/day) (arm B).The patients enrolled in the two arms were fairly homogeneous in terms of major clinical characteristics. Toxicity was similar in both arms except for myalgia: WHO grade 2 was observed in 57% of arm B patients. Overall response rate to DOX + LND was 50% and to DOX alone 38% in evaluable patients, and 48% vs 37% in all registered patients, as determined by an intention-to-treat analysis. The differences did not reach statistical significance. Conversely, in agreement with previous findings, we observed a significant difference in response rate in the subgroup of patients with liver metastases, regardless of the extent of hepatic involvement (DOX + LND 68% vs DOX 33%, p=0.03). This observation makes LND an important tool in association with anthracyclines in the treatment of this subgroup of patients.     

Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer

BACKGROUND: Few studies have compared primary neoadjuvant endocrine therapy with neoadjuvant chemotherapy in breast cancer patients. The need for preoperative chemotherapy with doxorubicin or taxanes may be reduced in postmenopausal patients with estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive tumors. This randomized, controlled, phase 2 study evaluated the efficacy of neoadjuvant chemotherapy compared with endocrine treatment with aromatase inhibitors in postmenopausal women with ER-positive and/or PgR-positive breast cancer. METHODS: Eligible patients were randomly assigned to receive neoadjuvant anastrozole 1 mg/day (n = 61) or exemestane 25 mg/day (n = 60) for 3 months or doxorubicin 60 mg/m(2) with paclitaxel 200 mg/m(2) (four 3-week cycles). Study end points included overall objective response determined by palpation, mammography, and ultrasound, and the number of patients who qualified for breast-conserving surgery and radiotherapy. RESULTS: Clinical objective response was 64% in the endocrine therapy and chemotherapy treatment groups. Median time to clinical response was 57 and 51 days with aromatase inhibitors and chemotherapy, respectively (P > .05). Rates of pathological complete response (3% vs 6%) and disease progression (9% vs 9%) did not differ significantly in the endocrine therapy or chemotherapy group, respectively (P > .05). Rates of breast-conserving surgery were slightly higher in the endocrine group (33% vs 24%; P = .058). The most frequent toxicities from chemotherapy were alopecia (79%), grade 3/4 neutropenia (33%), and grade 2 neuropathy (30%). Endocrine treatment was well tolerated. No deaths occurred during the preoperative treatment. CONCLUSIONS: Preoperative neoadjuvant endocrine therapy with aromatase inhibitors was well tolerated and resulted in rates similar to chemotherapy in overall objective response and breast-conserving surgery in postmenopausal women with ER-positive and/or PgR-positive tumors.     

Psychosocial and physical outcomes of primary breast cancer therapy: Mastectomy vs excisional biopsy and irradiation

Summary Thirty-eight patients treated for primary breast cancer as part of a prospective randomized clinical trial were questioned retrospectively as to their psychosocial adaptation to treatment. Twenty patients had received mastectomy and eighteen had received excisional biopsy plus radiation of the intact breast. Aside from body image concerns, there were no marked psychosocial differences detected between these groups. Previous studies emphasizing serious psychological problems in mastectomy patients and fewer such problems in nonmastectomy patients may be influenced by biases that are not present in a randomized study design.     

Development and evaluation of a culturally sensitive support group programme for Chinese-Australian women with breast cancer: a pilot study

Cancer support groups are an important vehicle for providing informational and psychosocial support to cancer survivors. Studies suggest that people from minority cultures are underrepresented in cancer support groups. The aims of this study were to report the development and evaluation of a culturally sensitive support group programme for Chinese-Australian women with breast cancer and to evaluate the informational and psychosocial impact of the programme. In collaboration with a Chinese cancer support organisation, 29 women were enrolled in the programme which was evaluated by a combination of quantitative and qualitative approaches. The results indicated that the programme was well received by the participants who suggested that the content was useful and relevant. In addition, the findings indicated that the programme, designed to be culturally sensitive and linguistically appropriate, was effective in providing informational support and psychosocial support for the participants. A methodology for giving breast cancer survivors a sense of interconnectedness and thus minimising their feelings of isolation and helplessness, were also among the chief outcomes of this study. The study provided some insight into the development of supportive cancer survivorship care for women being treated for breast cancer in the Australian-Chinese community.     

Internet of things-based lifestyle intervention for prostate cancer patients on androgen deprivation therapy: a prospective,multicenter, randomized trial

Androgen deprivation therapy (ADT) has several adverse effects including loss of libido, osteoporosis, and metabolic complications. We aim to examine whether the Smart After-Care (SAC) service, an Internet of Things (IoT)-based lifestyle intervention, affects clinical outcomes in prostate cancer (PCa) patients on ADT. A prospective, multicenter, randomized trial including 172 patients randomly assigned to the SAC or control group was conducted. The SAC group was provided with a smartphone application providing a personalized exercise program, daily activity monitoring, and diet counselling. The control group was briefly educated on the exercise program using a paper brochure. The primary endpoint was increase in cardiorespiratory endurance assessed using the 2-minute walking test (2MWT). Secondary endpoints included improved muscle strength (hand grip strength test and 30-second chair stand test), short physical performance battery, body composition, and health-related quality of life (EORTC-QLQ-C30 and PR25). Participants in both groups showed significant improvement in the 2MWT and 30-second chair stand test after 12 weeks of intervention. Greater improvement in the 2MWT was observed in the SAC group than in the control group. Significantly increased body fat ratio was observed in both groups; however, decreased skeletal muscle mass was observed only in the control group. Marginal improvement in skeletal muscle mass was observed over time in the SAC group when compared with that in the control group. Both groups showed improvement in all physical scales in the EORTC-QLQ-C30 questionnaire, and the SAC group showed a significant interaction of group and time for social functioning scales. SAC improved cardiorespiratory endurance, sarcopenic obesity, and health-related quality of life in patients with PCa on ADT.     

An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer

Background:

The cancer stem cell (CSC) hypothesis has important clinical implications for cancer therapeutics because of the proposed role of CSCs in chemoresistance. The aim of this study was to investigate changes in the CSC populations before and after primary systemic therapy (PST) and their prognostic role in human breast cancer.

Methods:

Paired samples (before and after PST) of breast cancer tissue were obtained from clinical stage II or III patients (n=92) undergoing PST with the regimen of doxorubicin plus docetaxel (AD) (n=50) or doxorubicin plus cyclophosphamide (AC) (n=42) and subsequent breast resection. The proportions of putative CSCs with CD44+/CD24− or aldehyde dehydrogenase 1+ (ALDH1+) phenotypes were determined by immunohistochemistry.

Results:

A higher proportion of CD44+/CD24− tumour cells and ALDH1 positivity in pre-chemotherapy tissue was correlated with higher histologic grade, oestrogen receptor (ER) negativity, high Ki-67 proliferation index and basal-like subtype of breast cancer. Aldehyde dehydrogenase 1 positivity in pre-chemotherapy biopsy was also associated with a higher rate of pathologic complete response following PST. In comparisons of putative CSC populations before and after PST, the proportions of CD44+/CD24− and ALDH1+ tumour cells were significantly increased after PST. The cases with increased CD44+/CD24− tumour cell populations after PST showed high Ki-67 proliferation index in post-chemotherapy specimens and those with increased ALDH1+ tumour cell population after PST were associated with ER negativity and p53 overexpression. Furthermore, cases showing such an increase had significantly shorter disease-free survival time than those with no change or a reduced number of CSCs, and the survival difference was most notable with regard to the changes of ALDH1+ tumour cell population in the patients who received AC regimen.

Conclusion:

The present study provides the clinical evidence that the putative CSCs in breast cancer are chemoresistant and are associated with tumour progression, emphasising the need for targeting of CSCs in the breast cancer therapeutics.     

Cost-effectiveness of switching to exemestane versus continued tamoxifen as adjuvant therapy for postmenopausal women with primary breast cancer

BACKGROUND: Sequential tamoxifen/exemestane therapy reportedly improves disease-free survival in women with primary breast cancer compared with continued tamoxifen therapy. The objective of the current study was to assess the cost-effectiveness of switching to exemestane after 2 to 3 years of tamoxifen versus continued tamoxifen in postmenopausal women with primary breast cancer for a total of 5 years of adjuvant therapy. METHODS: A Markov model based on the Intergroup Exemestane Study (IES) population compared switching to exemestane versus continued tamoxifen for 2.5 years of therapy and 5 years of postadjuvant therapy follow-up. Disease progression and hazards ratios (HR) for recurrence and survival were determined from datasets (IES and the Surveillance, Epidemiology, and End Results program of the National Cancer Institute) and from the published literature. An expert panel validated treatment patterns, outcomes, and resource utilization. Direct medical costs were included based on published sources. Cost-effectiveness ratios were determined, and extensive sensitivity analyses were conducted. RESULTS: Exemestane was found to be more effective than tamoxifen alone with regard to disease-free survival (2.6% absolute improvement), life-years gained (0.1028 LY), and quality-adjusted life-years gained (0.1195 QALY), at an additional cost of 2,889 Can dollars per person over 7.5 years. Incremental cost-effectiveness ratios were 28,119 Can dollars/LY gained and 24,185 Can dollars/QALY gained. The model was most sensitive to distant recurrence HR but was robust to variations in clinical, cost, and utility parameters. CONCLUSIONS: Switching to adjuvant exemestane after 2 to 3 years of tamoxifen is cost-effective in postmenopausal women with primary breast cancer.     

Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study

Objective: The primary purpose of this study was to evaluate the cognitive effects of adjuvant hormonal therapies in breast cancer patients. Participants and Methods: Post‐menopausal breast cancer patients scheduled to receive tamoxifen (n=31) or anastrozole (n=14) completed neuropsychological testing around the time of commencement of treatment (T1), and again 5–6 months later (T2). A sample of healthy female volunteers (n=28) was tested at comparable intervals. A standardized regression‐based approach was used to assess cognitive change. This method uses test/retest scores of the healthy control group to generate an equation that predicts T2 scores from T1 scores. The difference between the predicted and obtained T2 scores divided by the standard error of the estimate produces a deviation score that reflects the discrepancy from the T1–T2 difference scores that would be expected on the basis of practice and error alone. Results: Analysis of individual deviation scores revealed that both the patients taking tamoxifen and those taking anastrozole were more likely than healthy controls to show reliable cognitive decline from T1 to T2 (39, 64, and 7%, respectively). Processing speed and verbal memory were the cognitive domains most affected. Conclusion: These data suggest that hormonal therapies exert a subtle negative influence on cognition in breast cancer patients. Further analyses indicated that this effect was not fully accounted for by demographic factors or fatigue. Methodological limitations of the current study are addressed, along with recommendations for future studies in this area. Copyright © 2008 John Wiley & Sons, Ltd.     

Timing of radiotherapy in breast-conserving therapy: a large prospective cohort study of node-negative breast cancer patients without adjuvant systemic therapy

Background:

To investigate the issue of timing of radiation therapy (RT) after lumpectomy in relation to recurrences and outcome.

Methods:

Analysis was done on 1107 breast-conserving therapies (BCT) with 1070 women, all without lymph node metastasis and without any adjuvant systemic therapy. Timing was defined as time from lumpectomy till RT. Patients were categorised into tertiles: <45 days, 45–56 days, and 57–112 days.

Results:

Local control did not show a difference between the tertiles. The distant metastasis-free survival as well as the disease-specific survival showed a decreased outcome starting the RT to early after the lumpectomy.

Conclusion:

The results of this cohort study further refines the hypothesis that timing of RT in BCT might have an impact on outcome. It suggests that a randomised trial in timing of RT in BCT seems necessary to give a definite answer.     

Group cognitive behavioural therapy interventions with cancer patients: a review of the literature

At present there is considerable evidence that suggests cancer patients, once diagnosed, experience significant and long-term psychosocial problems. Several studies have evaluated group interventions, but only a few have used group cognitive behavioural therapy (GCBT) with cancer patients. The following paper represents a review of the literature of GCBT, illustrating the key findings from these studies.     

Cost-effectiveness of new guidelines for adjuvant systemic therapy for patients with primary breast cancer.

BACKGROUND: In this study, the potential impact of a new national guideline for adjuvant systemic therapy in breast cancer (introduced in The Netherlands in 1998) was assessed, as well as the modifications of this guideline, issued in 2001. Both the change in total number of patients eligible for adjuvant therapy, as well as the cost-effectiveness of the changed clinical management of these patients were analysed. PATIENTS AND METHODS: Percentages of patients who would be eligible for adjuvant therapy in 1994, 1998 and 2001 were estimated, based on clinical data from 127 patients, who were operated on in 1994. Ten-year overall survival rates were used as a measure of effectiveness, based on the two most recent EBCTCG meta-analyses. Actual resource costs were calculated. With a decision analytic model, the incremental cost-effectiveness ratios (1998 versus 1994, and 2001 versus 1998) were calculated. RESULTS: The introduction of the 1998 guideline resulted in a relative increase of 80% in the total number of patients eligible for adjuvant therapy, compared with 1994 (from 40% to 72% of all patients with primary breast cancer). With an estimated absolute increase of 10-year overall survival of 2%, the 1998 guideline was found to have an expected incremental cost-effectiveness ratio of about 4837 per life-year gained. CONCLUSIONS: Introduction of the new guideline considerably affected the number of patients eligible for adjuvant systemic therapy for breast cancer. The associated incremental cost-effectiveness ratio is well within the range of values that are generally considered acceptable.