Multimorbidity and overall survival among women with breast cancer: results from the South African Breast Cancer and HIV Outcomes Study.

BACKGROUND: Breast cancer survival in South Africa is low, but when diagnosed with breast cancer, many women in South Africa also have other chronic conditions. We investigated the impact of multimorbidity (≥ 2 other chronic conditions) on overall survival among women with breast cancer in South Africa. METHODS: Between 1 July 2015 and 31 December 2019, we enrolled women newly diagnosed with breast cancer at six public hospitals participating in the South African Breast Cancer and HIV Outcomes (SABCHO) Study. We examined seven chronic conditions (obesity, hypertension, diabetes, HIV, cerebrovascular diseases (CVD), asthma/chronic obstructive pulmonary disease, and tuberculosis), and we compared socio-demographic, clinical, and treatment factors between patients with and without each condition, and with and without multimorbidity. We investigated the association of multimorbidity with overall survival using multivariable Cox proportional hazard models. RESULTS: Of 3,261 women included in the analysis, 45% had multimorbidity; obesity (53%), hypertension (41%), HIV (22%), and diabetes (13%) were the most common individual conditions. Women with multimorbidity had poorer overall survival at 3 years than women without multimorbidity in both the full cohort (60.8% vs. 64.3%, p = 0.036) and stage groups: stages I-II, 80.7% vs. 86.3% (p = 0.005), and stage III, 53.0% vs. 59.4% (p = 0.024). In an adjusted model, women with diabetes (hazard ratio (HR) = 1.20, 95% confidence interval (CI) = 1.03-1.41), CVD (HR = 1.43, 95% CI = 1.17-1.76), HIV (HR = 1.21, 95% CI = 1.06-1.38), obesity + HIV (HR = 1.24 95% CI = 1.04-1.48), and multimorbidity (HR = 1.26, 95% CI = 1.13-1.40) had poorer overall survival than women without these conditions. CONCLUSIONS: Irrespective of the stage, multimorbidity at breast cancer diagnosis was an important prognostic factor for survival in our SABCHO cohort. The high prevalence of multimorbidity in our cohort calls for more comprehensive care to improve outcomes for South African women with breast cancer.

Spiritual Care, Pain Reduction, and Preferred Place of Death Among Advanced Cancer Patients in Soweto, South Africa.

CONTEXT: When religious and spiritual (R/S) care needs of patients with advanced disease are met, their quality of life (QoL) improves. We studied the association between R/S support and QoL of patients with cancer at the end of life in Soweto, South Africa. OBJECTIVES: To identify R/S needs among patients with advanced cancer receiving palliative care services and to assess associations of receipt of R/S care with patient QoL and place of death. METHODS: A prospective cohort study conducted from May 1, 2016 to April 30, 2018 at a tertiary hospital in Soweto, South Africa. Nurses enrolled patients with advanced cancer and referred them to the palliative care multidisciplinary team. Spiritual counselors assessed and provided spiritual care to patients. We compared sociodemographic, clinical, and R/S factors and QoL of R/S care recipients and others. RESULTS: Of 233 deceased participants, 92 (39.5%) had received R/S care. Patients who received R/S care reported less pain (2.82 ± 1.23 vs. 1.93 ± 1.69), used less morphine, and were more likely to die at home than patients who did not (57.5% compared with 33.7%). On multivariate logistic regression analysis, adjusting for significant confounding influences and baseline African Palliative Care Association Palliative care Outcome Scale scores, receipt of spiritual care was associated with reduced pain and family worry (odds ratio 0.33; 95% CI 0.11-0.95 and odds ratio 3.43; 95% CI 1.10-10.70, respectively). CONCLUSION: Patients with cancer have R/S needs. R/S care among our patients appeared to improve their end-of-life experience. More research is needed to determine the mechanisms by which R/S care may have improved the observed patient outcomes.

Neoadjuvant Chemotherapy Use for Nonmetastatic Breast Cancer at Five Public South African Hospitals and Impact on Time to Initial Cancer Therapy.

BACKGROUND: In the U.S., neoadjuvant chemotherapy (NAC) for nonmetastatic breast cancer (BC) is used with extensive disease and aggressive molecular subtypes. Little is known about the influence of demographic characteristics, clinical factors, and resource constraints on NAC use in Africa. MATERIALS AND METHODS: We studied NAC use in a cohort of women with stage I-III BC enrolled in the South African Breast Cancer and HIV Outcomes study at five hospitals. We analyzed associations between NAC receipt and sociodemographic and clinical factors, and we developed Cox regression models for predictors of time to first treatment with NAC versus surgery. RESULTS: Of 810 patients, 505 (62.3%) received NAC. Multivariate analysis found associations between NAC use and black race (odds ratio [OR] 0.49; 95% confidence limit [CI], 0.25-0.96), younger age (OR 0.95; 95% CI, 0.92-0.97 for each year), T-stage (T4 versus T1: OR 136.29; 95% CI, 41.80-444.44), N-stage (N2 versus N0: OR 35.64; 95% CI, 16.56-76.73), and subtype (triple-negative versus luminal A: OR 5.16; 95% CI, 1.88-14.12). Sites differed in NAC use (Site D versus Site A: OR 5.73; 95% CI, 2.72-12.08; Site B versus Site A: OR 0.37; 95% CI, 0.16-0.86) and time to first treatment: Site A, 50 days to NAC versus 30 days to primary surgery (hazard ratio [HR] 1.84; 95% CI, 1.25-2.71); Site D, 101 days to NAC versus 126 days to primary surgery (HR 0.49; 95% CI, 0.27-0.89). CONCLUSION: NAC use for BC at these South African hospitals was associated with both tumor characteristics and heterogenous resource constraints. IMPLICATIONS FOR PRACTICE: Using data from a large breast cancer cohort treated in South Africa's public healthcare system, the authors looked at determinants of neoadjuvant chemotherapy use and time to initiate treatment. It was found that neoadjuvant chemotherapy was associated with increasing tumor burden and aggressive molecular subtypes, demonstrating clinically appropriate care in a lower resource setting. Results of this study also showed that time to treatment differences between chemotherapy and surgery varied by hospital, suggesting that differences in resource limitations were influencing clinical decision making. Practice guidelines and care quality metrics designed for low- and middle-income countries should accommodate heterogeneity of available resources.

Psychosocial factors related to non-persistence with adjuvant endocrine therapy among women with breast cancer: the Breast Cancer Quality of Care Study (BQUAL).

Non-adherence to adjuvant endocrine therapy (ET) for breast cancer (BC) is common. Our goal was to determine the associations between psychosocial factors and ET non-persistence. We recruited women with BC receiving care in an integrated healthcare system between 2006 and 2010. Using a subset of patients treated with ET, we investigated factors related to ET non-persistence (discontinuation) based on pharmacy records (≥90 days gap). Serial interviews were conducted at baseline and every 6 months. The Functional Assessment of Cancer Therapy (FACT), Medical Outcomes Survey, Treatment Satisfaction Questionnaire (TSQM), Impact of Events Scale (IES), Interpersonal Processes of Care measure, and Decision-making beliefs and concerns were measured. Multivariate models assessed factors associated with non-persistence. Of the 523 women in our final cohort who initiated ET and had a subsequent evaluation, 94 (18 %) were non-persistent over a 2-year follow-up. The cohort was primarily white (74.4 %), stage 1 (60.6 %), and on an aromatase inhibitor (68.1 %). Women in the highest income category had a lower odds of being non-persistent (OR 0.43, 95 % CI 0.23-0.81). Quality of life and attitudes toward ET at baseline were associated with non-persistence. At follow-up, the FACT, TSQM, and IES were associated with non-persistence (p < 0.001). Most women continued ET. Women who reported a better attitude toward ET, better quality of life, and more treatment satisfaction, were less likely to be non-persistent and those who reported intrusive/avoidant thoughts were more likely to be non-persistent. Interventions to enhance the psychosocial well-being of patients should be evaluated to increase adherence.

Latent class analysis suggests four distinct classes of complementary medicine users among women with breast cancer.

BACKGROUND: Breast cancer patients commonly report using >1 form of complementary and alternative medicine (CAM). However, few studies have attempted to analyze predictors and outcomes of multiple CAM modalities. We sought to group breast cancer patients by clusters of type and intensity of complementary and alternative medicine (CAM) use following diagnosis. METHODS: Detailed CAM use following breast cancer diagnosis was assessed in 2002-2003 among 764 female residents of Long Island, New York diagnosed with breast cancer in 1996-1997. Latent class analysis (LCA) was applied to CAM modalities while taking into account frequency and intensities. RESULTS: Four distinct latent classes of CAM use emerged: 1) "Low-dose supplement users" (40%), who used only common nutritional supplements; 2) "Vitamin/mineral supplement users" (39%), using an abundance of supplements in addition to other practices; 3) "Mind-body medicine users" (12%), with near-universal use of supplements, mind-body medicine techniques, and massage; and 4) "Multi-modality high-dose users" (9%), who were highly likely to use nearly all types of CAM. Predictors of membership in classes with substantial CAM use included younger age, more education, higher income, Jewish religion, ideal body mass index, higher fruit and vegetable intake, higher levels of physical activity, receipt of adjuvant chemotherapy, and prior use of oral contraceptives. CONCLUSIONS: LCA identified important subgroups of breast cancer patients characterized by varying degrees of complementary therapy use. Further research should explore the reproducibility of these classes and investigate the association between latent class membership and breast cancer outcomes.

Dietary supplement use among patients with hepatocellular carcinoma.

BACKGROUND: More than 50% of US adults, and an even larger proportion of cancer patients, use dietary supplements. Since many supplements require hepatic metabolism, they may be particularly likely to cause toxicities in patients with hepatocellular carcinoma (HCC). However, little is known about supplement use in patients with HCC. METHODS: From 2008 to 2012, we gave newly diagnosed HCC patients at our institution a standardized questionnaire about dietary supplement use, demographic factors, and clinical characteristics. We then followed patients for four years or until time to death to examine the relationship with supplement use. RESULTS: Of 146 patients, 71% had used vitamins and 45% herbal supplements. Most commonly used supplements were antioxidants (51%), multivitamins (46%), vitamin D (25%), and milk thistle (23%). People in mid-higher income brackets were more likely to use herbal supplements (19% of those earning <$30 000, 50% of those earning $30 000-60 000, and 34% of those earning >$60 000 used supplements). Hepatitis C (HCV) patients were more likely to use milk thistle than those without HCV (30% vs 13%, P = .03), and patients with hepatitis B (HBV) were more likely than non-HBV patients to use vitamin C (32% vs 14%, P = .01). Supplement use was not associated with overall survival. CONCLUSIONS: Like cancer patients in other studies, the majority of our HCC patients used dietary supplements. Supplement use was not associated with overall survival but should be studied in larger patient samples.

A phase I dose-finding study of silybin phosphatidylcholine (milk thistle) in patients with advanced hepatocellular carcinoma.

PURPOSE: To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. EXPERIMENTAL DESIGN: Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. RESULTS: Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. CONCLUSION: Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests.

Use of Self-Care and Practitioner-Based Forms of Complementary and Alternative Medicine before and after a Diagnosis of Breast Cancer.

Purpose. We examine factors associated with self-care, use of practitioner-based complementary and alternative medicine (CAM), and their timing in a cohort of women with breast cancer. Methods. Study participants were women with breast cancer who participated in the Long Island Breast Cancer Study Project. Self-care is defined as the use of multivitamins, single vitamins, botanicals, other dietary supplements, mind-body practices, special diets, support groups, and prayer. Within each modality, study participants were categorized as continuous users (before and after diagnosis), starters (only after diagnosis), quitters (only before diagnosis), or never users. Multivariable logistic regression was used for the main analyses. Results. Of 764 women who provided complete data, 513 (67.2%) initiated a new form of self-care following breast cancer diagnosis. The most popular modalities were those that are ingestible, and they were commonly used in combination. The strongest predictor of continuous use of one type of self-care was continuous use of other types of self-care. Healthy behaviors, including high fruit/vegetable intake and exercise, were more strongly associated with continuously using self-care than starting self-care after diagnosis. Conclusions. Breast cancer diagnosis was associated with subsequent behavioral changes, and the majority of women undertook new forms of self-care after diagnosis. Few women discontinued use of modalities they used prior to diagnosis.

Noninitiation of adjuvant chemotherapy in women with localized breast cancer: the breast cancer quality of care study.

PURPOSE: For some women, adjuvant chemotherapy for nonmetastatic breast cancer decreases recurrences and increases survival; however, patient-physician decisions regarding chemotherapy receipt can be influenced by medical and nonmedical factors. PATIENTS AND METHODS: We used a prospective cohort design and multivariate modeling to investigate factors related to noninitiation of chemotherapy among women with newly diagnosed breast cancer recruited from three US sites. We interviewed patients at baseline and during treatment on sociodemographic, tumor, and treatment decision-making factors. Patients were categorized according to National Comprehensive Cancer Network guidelines as those for whom chemotherapy was definitely indicated, clinically discretionary, or discretionary based on age greater than 70 years. RESULTS: Of 1,145 patients recruited, chemotherapy was clinically indicated for 392 patients, clinically discretionary for 459 patients, discretionary because of age for 169 patients, and not indicated for 93 patients; data were insufficient for 32 patients. Chemotherapy rates were 90% for those in whom chemotherapy was clinically indicated, 36% for those in whom it was discretionary because of clinical factors, and 19% for those in whom it was discretionary based on age greater than 70 years. Nonreceipt of chemotherapy was associated with older age, more negative beliefs about treatment efficacy, less positive beliefs about chemotherapy, and more concern about adverse effects. In the two discretionary groups, clinical predictors of worse outcome (greater tumor size, positive nodes, worse grade, and estrogen receptor- and progesterone receptor-negative status) were associated with increased chemotherapy initiation. CONCLUSION: Utilization of adjuvant chemotherapy was most common among patients who, based on clinical criteria, would most likely benefit from it, patients with more positive than negative beliefs regarding treatment efficacy, and patients with few concerns about adverse effects.

Prevalence and predictors of antioxidant supplement use during breast cancer treatment: the Long Island Breast Cancer Study Project.

BACKGROUND: Although many patients take antioxidant dietary supplements during breast cancer treatment, the benefits of such supplementation are unproven. The authors of this report analyzed the prevalence of and factors associated with antioxidant supplement use during breast cancer (BC) treatment among women who participated in the Long Island Breast Cancer Study Project. METHODS: From 2002 through 2004, women with BC who had participated a case-control study from 1996 to 1997 were invited to participate in a follow-up interview. Antioxidant supplement use was defined as any self-reported intake of supplemental vitamin C, vitamin E, beta-carotene, or selenium in individual supplements or multivitamins. RESULTS: Follow-up interview participants were younger, more predominantly white, and of higher socioeconomic status than women who did not respond. Among 764 participants who completed the follow-up interview, 663 (86.8%) reported receiving adjuvant treatment for their BC. Of those 663 women, 401 (60.5%) reported using antioxidants during adjuvant treatment: One hundred twenty of 310 women (38.7%) used antioxidants during chemotherapy, 196 of 464 women (42.2%) used them during radiation, and 286 of 462 women (61.9%) used them during tamoxifen therapy. Of 401 antioxidant users, 278 women (69.3%) used high doses (doses higher than those contained in a Centrum multivitamin). The factors that were associated with high antioxidant supplement use during treatment were higher fruit and vegetable intake at diagnosis (relative risk [RR], 1.71; 95% confidence interval [CI], 1.13-2.59), tamoxifen use (RR, 3.66; 95% CI, 2.32-5.78), ever using herbal products (RR, 3.49; 95% CI, 2.26-5.38), and ever engaging in mind-body practices (RR, 1.72; 95% CI, 1.13-2.64). CONCLUSIONS: Given the common use of antioxidant supplements during BC treatment, often at high doses and in conjunction with other complementary therapies, future research should address the effects of antioxidant supplementation on BC outcomes.

Use of antioxidant supplements during breast cancer treatment: a comprehensive review.

PURPOSE: An estimated 45-80% of breast cancer patients use antioxidant supplements after diagnosis, and use of antioxidant supplements during breast cancer treatment is common. Dietary supplements with antioxidant effects include vitamins, minerals, phytonutrients, and other natural products. We conducted a comprehensive review of literature on the associations between antioxidant supplement use during breast cancer treatment and patient outcomes. METHODS: Inclusion criteria were: two or more subjects; clinical trial or observational study design; use of antioxidant supplements (vitamin C, vitamin E, antioxidant combinations, multivitamins, glutamine, glutathione, melatonin, or soy isoflavones) during chemotherapy, radiation therapy, and/or hormonal therapy for breast cancer as exposures; treatment toxicities, tumor response, recurrence, or survival as outcomes. RESULTS: We identified 22 articles that met those criteria. Their findings did not support any conclusions regarding the effects of individual antioxidant supplements during conventional breast cancer treatment on toxicities, tumor response, recurrence, or survival. A few studies suggested that antioxidant supplements might decrease side effects associated with treatment, including vitamin E for hot flashes due to hormonal therapy and glutamine for oral mucositis during chemotherapy. Underpowered trials suggest that melatonin may enhance tumor response during treatment. CONCLUSION: The evidence is currently insufficient to inform clinician and patient guidelines on the use of antioxidant supplements during breast cancer treatment. Thus, well designed clinical trials and observational studies are needed to determine the short- and long-term effects of such agents.

Change in quality of life and immune markers after a stay at a raw vegan institute: a pilot study.

OBJECTIVE: The purpose of this study was to explore changes in quality of life (QOL), anxiety, stress, and immune markers after a stay at a raw vegan institute. DESIGN: Prospective observational study. SETTING: English-speaking attendees at Hippocrates Health Institute (Florida, US), a raw vegan institute, were recruited on arrival and typically stayed 1-3 weeks. MAIN OUTCOME MEASURES: Participants completed questionnaires assessing overall QOL (SF-36), dietary QOL (QOL related to dietary change), perceived stress (Perceived Stress Scale), anxiety, and depression (Hospital Anxiety and Depression Scale) upon arrival and 12 weeks later. C-reactive protein (CRP), lymphocytes, T cells, CD4 cells, CD8 cells, B cells, and NK cells were measured at baseline and 12 weeks in participants living in North America. RESULTS: Of 107 attendees eligible for the questionnaire study and 82 for the blood marker substudy, 51 and 38 participants, respectively, provided complete follow-up data. Overall QOL improved 11.5% (p=0.001), driven mostly by the mental component. Anxiety decreased 18.6% (p=0.009) and perceived stress decreased 16.4% (p<0.001). Participants' ratings of the food's taste were unchanged, but their ratings of how well they were taking care of themselves improved. CRP, lymphocytes, T cells, and B cells did not change significantly, but CD4, CD8, and NK cells decreased slightly. CONCLUSIONS: A stay at a raw vegan institute was associated with improved mental and emotional QOL. Studies are needed to determine the feasibility of conducting a clinical trial of the raw vegan diet among healthy people, and subsequently among patients with specific diseases.

Factors affecting adherence to a raw vegan diet.

The purpose of this study was to evaluate adherence and identify predictors of adherence to a raw vegan diet (i.e., uncooked plant foods) following a stay at a raw vegan institute. In this cohort study of guests at a raw vegan institute, subjects completed written questionnaires upon arrival and 12 weeks later. Of 107 eligible guests, 84 participated. Mean age was 54 years, 23 were male, and 73 white. Fifty-one completed the 12-week follow-up. Eight (16%) reported their diet to be 80% raw vegan at baseline and 14 (28%) at follow-up. Based on a raw vegan dietary adherence score (range 0-42) created for this study, mean adherence (SD) increased from 15.1 (5.4) to 17.0 (5.8) over 12 weeks (p=0.03). Baseline predictors of adherence included: education (beta=0.95), severity of disease (beta=0.98), and self-efficacy to adhere (beta=0.72). Future interventions that evaluate this diet should address self-efficacy, an important, potentially remediable predictor of adherence.

Surgeon characteristics and receipt of adjuvant radiotherapy in women with breast cancer.

BACKGROUND: Adjuvant radiotherapy following breast conservation surgery (BCS) is considered to be an indicator of quality of care for the majority of women with breast cancer, but many women do not receive adjuvant radiotherapy. We investigated the association of surgeon-related factors with receipt of adjuvant radiotherapy after BCS. METHODS: We used the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database to identify women aged 65 years or older with stage I/II breast cancer who were diagnosed between 1991 and 2002 and underwent BCS. We collected demographic and clinical data from SEER and treatment information from Medicare claims data. The American Medical Association Masterfile was used to obtain information on surgeons' characteristics, including sex, medical school location (United States or elsewhere), and type of degree (MD or Doctorate in Osteopathic Medicine [DO]). The associations of patient (age, race, rural vs urban residence, comorbidities, marital status), tumor (hormone receptor status, grade, stage), and surgeon-related factors with receipt of adjuvant radiotherapy were analyzed using Generalized Estimating Equations to control for clustering. All statistical tests were two-sided. RESULTS: Of 29,760 women in our sample, 22,207 (75%) received radiotherapy. Patients who received adjuvant radiotherapy were younger, had fewer comorbidities, and were more likely to be white, married, from an urban area, and diagnosed in a later year compared with those who did not. They were also more likely to have a surgeon who was female (79% vs 73%), had an MD degree (75% vs 68%), or was US trained (75% vs 70%). The multivariable analysis confirmed the association of radiotherapy with having a surgeon who was female (odds ratio [OR] = 1.13; 95% confidence interval [CI] = 1.06 to 1.27), had an MD degree (OR = 1.55; 95% CI = 1.24 to 1.91), was US trained (OR = 1.12; 95% CI = 1.01 to 1.25), or had more than 15 patients (OR = 1.18; 95% CI = 1.10 to 1.28). CONCLUSIONS: Surgeon characteristics were associated with patients' receipt of adjuvant radiotherapy after BCS after controlling for patient and tumor characteristics, although the individual effect sizes were small for surgeon sex, location of training, and type of medical degree. More research is warranted to confirm the associations to determine whether they reflect surgeon behavior, patient response, or physician-patient interactions.

Pilot study of acupuncture for the treatment of joint symptoms related to adjuvant aromatase inhibitor therapy in postmenopausal breast cancer patients.

INTRODUCTION: Aromatase inhibitors (AIs) have become the standard of care for the adjuvant treatment of postmenopausal, hormone-sensitive breast cancer. However, patients receiving AIs may experience joint symptoms, which may lead to early discontinuation of this effective therapy. We hypothesize that acupuncture is a safe and effective treatment for AI-induced arthralgias. METHODS: Postmenopausal women with early-stage breast cancer who had self-reported musculoskeletal pain related to adjuvant AI therapy were randomized in a crossover study to receive acupuncture twice weekly for 6 weeks followed by observation or vice-versa. The intervention included full body and auricular acupuncture, and a joint-specific point prescription. Outcome measures included the Brief Pain Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index, the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life measure, and serum levels of inflammatory markers, IL-1 beta and TNF-alpha. RESULTS: Twenty-one women were enrolled and two discontinued early. From baseline to the end of treatment, patients reported improvement in the mean BPI-SF worst pain scores (5.3 to 3.3, p = 0.01), pain severity (3.7 to 2.5, p = 0.02), and pain-related functional interference (3.1 to 1.7, p = 0.02), as well as the WOMAC function subscale and FACT-G physical well-being (p = 0.02 and 0.04, respectively). No adverse events were reported. DISCUSSION/CONCLUSIONS: In this pilot study, acupuncture reduced AI-related joint symptoms and improved functional ability and was well-tolerated. IMPLICATIONS FOR CANCER SURVIVORS: Musculoskeletal side effects are common among breast cancer survivors on adjuvant AI therapy, therefore, effective treatments are needed for symptom relief and to improve adherence to these life-saving medications.

Exceptional disease courses after the use of CAM: selection, registration, medical assessment, and research. an international perspective.

OBJECTIVES: To describe the different approaches that investigators in several countries have used to obtain, register, assess, and research exceptional case histories after the use of complementary and alternative medicine (CAM). METHODS: Searches have been carried out currently in the databases PubMed and MEDLINE((R)) using the keywords: exceptional disease course/best and worst cases/best-case series + use of CAM. We have only found a few papers limited to best-case series and cancer. Furthermore, we have used the "snowball method" by contacting researchers in different countries starting with with the National Cancer Institute in the United States in order to get information about ongoing approaches to obtain, register, assess, and research exceptional case histories after the use of CAM. RESULTS: There appears to be a gap between "evidence-based" knowledge drawn from randomized controlled trials, systematic reviews, and meta-analyses and experience-based knowledge of treatment outcomes reported by patients and CAM providers. Several research groups in different countries have initiated studies on patients experiencing exceptional treatment outcomes after the use of CAM. Four different approaches to collecting and assessing such case histories have been identified. Three of the approaches collect histories from the treatment providers, whereas the fourth recruits case histories mainly from patients themselves. The medical assessments are generally similar, and seek to document whether the course of disease is different than would have been expected in a conventional treatment situation. CONCLUSIONS: Given differences in the current procedures, the establishment of an international formal collaboration for the recruitment, assessment, and study of exceptional patients is likely to take time. Comparative studies may, however, generate new knowledge about exceptional disease courses across disease categories, cultural contexts, and national boundaries. Our recommendations are that therapeutic approaches that show promising results should warrant prospective study and randomized clinical trials. In addition we recommend that there be (1) agreement on the definition of an exceptional patient, (2) agreement on the interpretation of treatment results, (3) agreement on content requirements of medical records, (4) more consideration of worst cases, (5) more international exchange of experience with registration procedures, and (6) more international exchange of experience with medical assessment procedures.

Duration of adjuvant chemotherapy for colon cancer and survival among the elderly.

PURPOSE: In randomized trials, patients with stage III colon cancer who received 6 months of fluorouracil (FU)-based adjuvant chemotherapy had better survival than patients who did not. However, little is known about the predictors of, or the survival associated with, duration of chemotherapy in the community. PATIENTS AND METHODS: The linked Surveillance, Epidemiology, and End Results-Medicare database was used to identify individuals > or = 65 years of age diagnosed with stage III colon cancer between 1995 and 1999. We used logistic and Cox proportional hazards regression models to analyze factors associated with early discontinuation of FU-based chemotherapy among these elderly colon cancer patients. RESULTS: Among 1,722 patients who received 1 to 7 months of FU-based chemotherapy, older age, being unmarried, and having comorbid conditions were associated with receiving less than 5 months of treatment. Among the 1,579 patients who survived > or = 8 months, the 1,091 (69.1%) who received 5 to 7 months of treatment had lower overall (hazard ratio [HR], 0.59; 95%, CI 0.49 to 0.71) and colon cancer-specific (HR, 0.53; 95% CI, 0.43 to 0.66) mortality than the 488 (30.9%) who received 1 to 4 months of treatment. CONCLUSION: More than 30% of elderly patients who initiated FU-based chemotherapy for stage III colon cancer and survived for at least 8 months discontinued treatment early. Mortality rates among such patients were nearly twice as high as among patients who completed 5 to 7 months of treatment. If the association we observed between duration of treatment and survival is confirmed, additional investigation is warranted to determine whether dose-intensity, cumulative dose, or other factors related to receipt of full adjuvant treatment are responsible.

Outcomes of Prolonged Parent-Child Embrace Therapy among 102 children with behavioral disorders.

A growing body of research in neuroscience points to the impact of variations in maternal nurturing on child development and provides a rationale for interventions that target stress adaptation conditioning through natural family nurturing. This pilot study was collected within the course of private practice to assess the progress of children with severe behavioral disorders who were treated effectively with a multiple family therapy prototype, Prolonged Parent-Child Embrace (PPCE) Therapy. Subjects were a consecutive series of 102 patient children aged 4-18 years and their families. Children and their family members were guided for 16h over two consecutive days through intense PPCE Therapy. Families were instructed to continue PPCE Therapy at home for at least 1 year. Scores were compared statistically using t-tests and analysis of variance. For 96 children scores declined on two written measures by approximately 50% between baseline and follow-up (P<0.001). Results showed that PPCE Therapy resulted in significant and prolonged improvements in symptomatic behavior in a majority of children.

Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study.

PURPOSE: Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged > or = 65 years with long-term follow-up. PATIENTS AND METHODS: In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women > or = 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. RESULTS: Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. CONCLUSION: When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.

The future of complementary and alternative medicine for cancer.

This article explores why cancer patients use complementary and alternative medicine (CAM), why CAM use should be of interest to physicians who treat cancer patients, and how physicians may appropriately support their patients' quest for comfort, quality of life, and healing. We use the term "CAM" to refer to substances and practices that have been available primarily outside of the American medical mainstream, that have sources other than medical doctors and allied health care providers, and that are not commonly recommended by medical doctors as treatments for a given condition. Alternative treatments are those used instead of conventional medicine; complementary treatments are those used in addition to conventional medicine.