Improving the physical status and quality of life of women treated for breast cancer: A pilot study of a structured exercise intervention

Background and Objectives: This pilot project assessed the acceptability of a mixed-type, moderate-intensity exercise programme following breast cancer treatment, and the impact on presence of lymphoedema, fitness, body composition, fatigue, mood and quality of life. Methods: Ten women completed the programme and measures of fitness (submaximal ergometer test), body composition (bio-electrical impedance), lympoedema (bio-electrical impedance and arm circumferences), fatigue (revised Piper Fatigue Scale), mood (Hospital Anxiety and Depression Scale), quality of life (FACT-B) and general well-being, at baseline, completion of the programme, and 6-week and 3-month follow-up. Results: Participation in the programme caused no adverse effect on the presence of lymphoedema. There was a trend towards reduction in fatigue and improved quality of life across the testing phases. Women rated the programme extremely favourably, citing benefits of the support of other women, trained guidance, and the opportunity to experience different types of exercise. Conclusions: A mixed-type, moderate-intensity exercise program in a group format is acceptable to women following breast cancer treatment, with the potential to reduce fatigue and improve quality of life, without exacerbating or precipitating lymphoedema. This pilot work needs to be confirmed in larger randomised studies. (C) 2004 Wiley-Liss, Inc.

Assessing the support needs of women with early breast cancer in Australia

The purpose of the current study was to access the degree to which the support needs of women with a newly diagnosed, early invasive, primary breast cancer and their families are being met. A random sample of 544 women diagnosed with early breast cancer was recruited to participate in a telephone survey via state and territory cancer registries. Sixteen percent of women reported not receiving enough support during their diagnosis and treatment, and only 65% of these women reported that their families received enough support. The primary sources of support for women and their families were medical practitioners (eg, surgeons, oncologists, and general practitioner) with very few women or family members utilizing mental health professionals. Given the importance of adequate support when being diagnosed and treated for breast cancer, urgent attention needs to be paid to training medical professionals in providing appropriate support and referrals for their patients.

Children's and family needs of young women with advanced breast cancer: A review

This article reviews literature about the impact of advanced breast cancer on children and families. It is clear that the adjustment of the family is influenced by disease stage and maternal adjustment, the needs of the particular child relating closely to their developmental stage. Interventions with children and families to promote adjustment when a parent has advanced cancer are also discussed, including implications for clinical practice.

Ratiometric and nonratiometric Ca2+ indicators for the assessment of intracellular free Ca2+ in a breast cancer cell line using a fluorescence microplate reader

Transporters of Ca2+ are potential drug targets and Ca2+ is a useful signal in the assessment of G-protein-coupled receptor activation. Assays involving the assessment of intracellular Ca2+ using microplate readers most often use Ca2+ indicators which do not exhibit a spectra shift on Ca2+ binding (e.g. fluo-3). Indicators that do exhibit a spectral shift upon Ca2+ binding (e.g. fura-2) offer potential advantages for the calibration of intracellular Ca2+ levels. However, experimental limitations may limit the use of ratiometric dyes in microplate readers capable of screening. In this study, we compared the assessment of intracellular Ca2+ in adherent breast cancer cells using ratiometric and nonratiometric Ca2+ indicators. Our results demonstrate that both fluo-3 and fura-2 detect ATP dose-dependent increases in intracellular Ca2+ in the MCF-7 breast cancer cell line and that some of the limitations in the use of fura-2 appear to be overcome by the use of glass bottom microplates. The calibrated intracellular Ca2+ levels derived using fura-2 are consistent with those from microscopy and cuvette-based studies. Fura-2 may be useful in microplate studies, where cell lines with different properties are compared or where screening treatments lead to differences in the number of cells or dye loading. (C) 2003 Elsevier B.V. All rights reserved.

Educating readers: Breast cancer in Australian women's magazines

Women's magazines in Australia have become increasingly involved in various public health awareness campaigns. In particular, breast cancer has been targeted as an issue for attention. This disease occupies a privileged position in women's magazines, being represented as treatable and survivable with an emphasis on the advocacy of early detection through breast self-examination and screening programs. In this way, women's magazines can be seen to be proactive in serving the public interest of their readers. Information and advice about breast cancer are not limited to medical articles, advice columns and diet pages, but occur, perhaps more accessibly, in feature articles of personal accounts of experiences with breast cancer. This paper looks at coverage of the disease in Australian women's magazines over the last 3 years to see how this role in public health awareness operates. It pays particular attention to illness narratives in feature articles and to stories associated with the magazines' own breast cancer campaigns.

Columnar cell lesions of the breast: The missing link in breast cancer progression? A morphological and molecular analysis

Columnar cell lesions (CCLs) of the breast are a spectrum of lesions that have posed difficulties to pathologists for many years, prompting discussion concerning their biologic and clinical significance. We present a study of CCL in context with hyperplasia of usual type (HUT) and the more advanced lesions ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. A total of 81 lesions from 18 patients were subjected to a comprehensive morphologic review based upon a modified version of Schnitt's classification system for CCL, immunophenotypic analysis (estrogen receptor [ER], progesterone receptor [PgR], Her2/neu, cytokeratin 5/6 [CK5/6], cytokeratin 14 [CK14], E-cadherin, p53) and for the first time, a whole genome molecular analysis by comparative genomic hybridization. Multiple CCLs from 3 patients were studied in particular detail, with topographic information and/or showing a morphologic spectrum of CCL within individual terminal duct lobular units. CCLs were ER an PgR positive, CK5/6 and CK14 negative, exhibit low numbers of genetic alterations and recurrent 16q loss, features that are similar to those of low grade in situ and invasive carcinoma. The molecular genetic profiles closely reflect the degree of proliferation and atypia in CCL, indicating some of these lesions represent both a morphologic and molecular continuum. In addition, overlapping chromosomal alterations between CCL and more advanced lesions within individual terminal duct lobular units suggest a commonality in molecular evolution. These data further support the hypothesis that CCLs are a nonobligate, intermediary step in the development of some forms of low grade in situ and invasive carcinoma. Copyright: © 2005 Lippincott Williams & Wilkins, Inc.

Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS)

Background Women genetically predisposed to breast cancer often develop the disease at a young age when dense breast tissue reduces the sensitivity of X-ray mammography. Our aim was, therefore, to compare contrast enhanced magnetic resonance imaging (CE MRI) with mammography for screening. Methods We did a prospective multicentre cohort study in 649 women aged 35-49 years with a strong family history of breast cancer or a high probability of a BRCA1, BRCA2, or TP53 mutation. We recruited participants from 22 centres in the UK, and offered the women annual screening with CE MRI and mammography for 2-7 years. Findings We diagnosed 35 cancers in the 649 women screened with both mammography and CE MRI (1881 screens): 19 by CE MRI only, six by mammography only, and eight by both, with two interval cases. Sensitivity was significantly higher for CE MRI (77%, 95% CI 60-90) than for mammography (40%, 24-58; p=0.01), and was 94% (81-99) when both methods were used. Specificity was 93% (92-95) for mammography, 81% (80-83) for CE MRI (p

Molecular evolution of breast cancer

Molecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi-step pathways of breast cancer progression have been delineated through genotypic-phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low- and high-grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER/PgR-negative and show Her-2 over-expression/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well-differentiated/low-grade ductal and lobular carcinomas have been blurred, with changes in E-cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non-obligate precursors of atypical ductal hyperplasia (ADH) and well-differentiated ductal carcinoma in situ (DCIS). However, only through the combination of comprehensive morphological analysis and cutting-edge molecular tools can this knowledge be translated into clinical practice and patient management. Copyright (C) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.

Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype

Purpose: To investigate the proportion of breast cancers arising inpatients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients. Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin. Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls. Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.

The molecular genetics of breast cancer: The contribution of comparative genomic hybridization

Comparative genomic hybridization (CGH) has been the technique of choice over the last 10 years for mapping DNA copy number changes in human tumors. Here we review the literature to demonstrate how CGH has contributed to the comprehension of molecular aspects of breast tumorigenesis. At least two distinct molecular pathways of breast cancer have been characterized that show a strong correlation with histological grade. It seems that grade I invasive ductal carcinomas (IDCs) arise from well-differentiated ductal carcinoma in situ (DCIS), whereas grade III IDCs come from poorly differentiated DCIS. In addition, dedifferentiation from a low- to a high-grade breast cancer has proven an unlikely phenomenon. CGH has been instrumental in dissecting distinct molecular pathways toward breast malignancy and in establishing a direct relationship between genotype and clinical pathological features. (C) 2005 Elsevier GrnbH. All rights reserved.

Plasma membrane calcium-ATPase 2 and 4 in human breast cancer cell lines

There is evidence to suggest that plasma membrane Ca2+-ATPase (PMCA) isoforms are important mediators of mammary gland physiology. PMCA2 in particular is upregulated extensively during lactation. Expression of other isoforms such as PMCA4 may influence mammary gland epithelial cell proliferation and aberrant regulation of PMCA isoform expression may lead or contribute to mammary gland pathophysiology in the form of breast cancers. To explore whether PMCA2 and PMCA4 expression may be deregulated in breast cancer, we compared mRNA expression of these PMCA isoforms in tumorigenic and non-tumorigenic human breast epithelial cell lines using real time RT-PCR. PMCA2 mRNA has a higher level of expression in some breast cancer cell lines and is overexpressed more than 100-fold in ZR-75-1 cells, compared to non-tumorigenic 184135 cells. Although differences in PMCA4 mRNA levels were observed between breast cell lines, they were not of the magnitude observed for PMCA2. We conclude that PMCA2 mRNA can be highly overexpressed in some breast cancer cells. The significance of PMCA2 overexpression on tumorigenicity and its possible correlation with other properties such as invasiveness requires further study. (c) 2005 Elsevier Inc. All rights reserved.

The impact of rehabilitation support services on health-related quality of life for women with breast cancer

As the number of women surviving breast cancer increases, with implications for the health system, research into the physical and psychosocial sequelae of the cancer and its treatment is a priority. This research estimated self-reported health-related quality of life (HRQoL) associated with two rehabilitation interventions for breast cancer survivors, compared to a non-intervention group. Women were selected if they received an early home-based physiotherapy intervention (DAART, n = 36) or a group-based exercise and psychosocial intervention (STRETCH, n = 31). Questionnaires on HRQoL, using the Functional Assessment of Cancer Therapy - Breast Cancer plus Arm Morbidity module, were administered at pre-, post-intervention, 6- and 12-months post-diagnosis. Data on a non-intervention group (n = 208) were available 6- and 12-months post-diagnosis. Comparing pre/post-intervention measures, benefits were evident for functional well-being, including reductions in arm morbidity and upper-body disability for participants completing the DAART service at one-to-two months following diagnosis. In contrast, minimal changes were observed between pre/post-intervention measures for the STRETCH group at approximately 4-months post-diagnosis. Overall, mean HRQoL scores (adjusted for age, chemotherapy, hormone therapy, high blood pressure and occupation type) improved gradually across all groups from 6- to 12-months post-diagnosis, and no prominent differences were found. However, this obscured declining HRQoL scores for 20-40% of women at 12 months post-diagnosis, despite receiving supportive care services. Greater awareness and screening for adjustment problems among breast cancer survivors is required throughout the disease trajectory. Early physiotherapy after surgery has the potential for short-term functional, physical and overall HRQoL benefits.

Randomized controlled trial of an educational intervention for managing fatigue in women receiving adjuvant chemotherapy for early-stage breast cancer

Purpose To evaluate the efficacy of a psychoeducational intervention in improving cancer-related fatigue. Patients and Methods This randomized controlled trial involved 109 women commencing adjuvant chemotherapy for stage I or II breast cancer in five chemotherapy treatment centers. Intervention group patients received an individualized fatigue education and support program delivered in the clinic and by phone over three 10- to 20-minute sessions 1 week apart. Instruments included a numeric rating scale assessing confidence with managing fatigue; 11-point numeric rating scales measuring fatigue at worst, average, and best; the Functional Assessment of Cancer Therapy-Fatigue and Piper Fatigue Scales; the Cancer Self-Efficacy Scale; the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30; and the Hospital Anxiety and Depression Scale. For each outcome, separate analyses of covariance of change scores between baseline (T1) and the three follow-up time points (T2, T3, and T4) were conducted, controlling for the variable's corresponding baseline value. Results Compared with the intervention group, mean difference scores between the baseline (T1) and immediate after the test (T2) assessments increased significantly more for the control group for worst and average fatigue, Functional Assessment of Cancer Therapy-Fatigue, and Piper fatigue severity and interference measures. These differences were not observed between baseline and T3 and T4 assessments. No significant differences were identified for any pre- or post-test change scores for confidence with managing fatigue, cancer self-efficacy, anxiety, depression, or quality of life. Conclusion Preparatory education and support has the potential to assist women to cope with cancer-related fatigue in the short term. However, further research is needed to identify ways to improve the potency and sustainability of psychoeducational interventions for managing cancer-related fatigue.

A cost-effectiveness analysis of two rehabilitation support services for women with breast cancer

The purpose of this research was to estimate the cost-effectiveness of two rehabilitation interventions for breast cancer survivors, each compared to a population-based, non-intervention group (n = 208). The two services included an early home-based physiotherapy intervention (DAART, n = 36) and a group-based exercise and psychosocial intervention (STRETCH, n = 31). A societal perspective was taken and costs were included as those incurred by the health care system, the survivors and community. Health outcomes included: (a) 'rehabilitated cases' based on changes in health-related quality of life between 6 and 12 months post-diagnosis, using the Functional Assessment of Cancer Therapy - Breast Cancer plus Arm Morbidity (FACT-B+4) questionnaire, and (b) quality-adjusted life years (QALYs) using utility scores from the Subjective Health Estimation (SHE) scale. Data were collected using self-reported questionnaires, medical records and program budgets. A Monte-Carlo modelling approach was used to test for uncertainty in cost and outcome estimates. The proportion of rehabilitated cases was similar across the three groups. From a societal perspective compared with the non-intervention group, the DAART intervention appeared to be the most efficient option with an incremental cost of $1344 per QALY gained, whereas the incremental cost per QALY gained from the STRETCH program was $14,478. Both DAART and STRETCH are low-cost, low-technological health promoting programs representing excellent public health investments.