The impact of breast cancer on the lives of middle-aged women: Results from the Australian longitudinal study of women's health

This article investigated the impact of breast cancer (BC) in middle-aged Australian women (45-50 years). Two waves of data collected 2 years apart from a longitudinal survey of 12,177 women identified 3 groups: (a) 11,933 (98%) who reported never having had BC, (b) 181 (1.5%) who reported a diagnosis of BC at Time 1, and (c) 63 (0.5%) who reported onset of BC between Time I and Time 2. Repeated measures analysis of variance was used to compare the 3 groups. Women with recent onset of BC experienced significant changes across a range of functioning compared with the other 2 groups. Compared with women with no BC, women with longer established onset of BC had significantly worse health and social outcomes, but these were associated with small effect sizes. Both groups of women with BC reported less impact on mental and emotional health than on other areas of functioning.

Psychosocial impact of newly diagnosed advanced breast cancer

The purpose of this study was to delineate the key emotional concerns of women newly diagnosed with recurrent or metastatic breast cancer. Sixty-six women diagnosed with metastatic breast cancer within the previous 6 months, receiving treatment at the Medical Oncology Departments of two metropolitan teaching hospitals, completed measures of HADS, IES, CARES-SF and Memorial Symptom Assessment Scale, and participated in a semistructured interview. There were high levels of psychological morbidity, 56.7% of women younger than 55 years qualifying as 'cases' on the HADS, compared with 34.5% of women aged over 55 years. The total HADS score was significantly correlated with the Global and Physical Subscales of the MSAS and CARES. Women younger than 55 years had significantly higher levels of intrusive and avoidant symptoms than women over 55 years. Women also reported high numbers of physical symptoms. Key themes which emerged during the interviews were: difficulties in communicating with doctors, perceived delay in diagnosis, the emotional impact, concerns about the family, feelings about why the cancer developed, other life stress and trauma, and use of non-prescribed treatments. Copyright (c) 2004 John Wiley & Sons, Ltd.

Molecular characterization and cancer risk associated with BRCA1 and BRCA2 splice site variants identified in multiple-case breast cancer families

Genetic screening of women from multiple-case breast cancer families and other research-based endeavors have identified an extensive collection of germline variations of BRCA1 and BRCA2 that can be classified as deleterious and have clinical relevance. For some variants, such as those in the conserved intronic splice site regions which are highly likely to alter splicing, it is not possible to classify them based on the identified DNA sequence variation alone. We studied 11 multiple-case breast cancer families carrying seven distinct splice site region genetic alterations in BRCA1 or BRCA2 (BRCA1, c.IVS6-2delA, c.IVS9-2A>C, c.IVS4-1G>T, c.IVS20+1G>A and BRCA2, c.IVS17-1G>C, c.IVS20+1G>A, c.IVS7-1G>A) and applied SpliceSiteFinder to predict possible changes in efficiency of splice donor and acceptor sites, characterized the transcripts, and estimated the average age-specific cumulative risk (penetrance) using a modified segregation analysis. SpliceSiteFinder predicted and we identified transcipts that illustrated that all variants caused exon skipping, and all but two led to frameshifts. The risks of breast cancer to age 70 yrs, averaged over all variants, over BRCA1 variants alone, and over BRCA2 variants alone, were 73% (95% confidence interval 47-93), 64% (95%CI 28-96) and 79% (95%CI 48-98) respectively (all P

Isoform specific changes in PPAR alpha and beta in colon and breast cancer with differentiation

To investigate the role of peroxisome proliferator-activated receptors (PPARs) chi and beta in the differentiation of colon cancer cells, we differentiated HT-29 cells using sodium butyrate (NaB) and culturing post-confluence and assessed differentiation using the marker intestinal alkaline phosphatase. While PPAR chi levels only changed with culturing post confluence, PPAR beta levels increased independent of the method of differentiation. To explore further the differences induced by NaB. we assessed changes in both PPAR isoforms in MCF-7 breast cancer cells cultured in the presence of NaB over 48 h. Again a very different expression pattern was observed with PPAR-1 increasing after 4 h and remaining elevated, while PPAR beta increased transiently. Our studies suggest that the expression of PPARs is dependent upon both the method of differentiation and on time. Moreover, these studies show that changes in levels are not required for the differentiation of colon cancer cell lines, whereas changes in PPAR beta are more closely associated with differentiation. (c) 2005 Elsevier Inc. All rights reserved.

Cost-effectiveness of screening with contrast enhanced magnetic resonance imaging vs X-ray mammography of women at a high familial risk of breast cancer

Contrast enhanced magnetic resonance imaging (CE MRI) is the most sensitive tool for screening women who are at high familial risk of breast cancer. Our aim in this study was to assess the cost-effectiveness of X-ray mammography (XRM), CE MRI or both strategies combined. In total, 649 women were enrolled in the MARIBS study and screened with both CE MRI and mammography resulting in 1881 screens and 1-7 individual annual screening events. Women aged 35-49 years at high risk of breast cancer, either because they have a strong family history of breast cancer or are tested carriers of a BRCA1, BRCA2 or TP53 mutation or are at a 50% risk of having inherited such a mutation, were recruited from 22 centres and offered annual MRI and XRM for between 2 and 7 years. Information on the number and type of further investigations was collected and specifically calculated unit costs were used to calculate the incremental cost per cancer detected. The numbers of cancer detected was 13 for mammography, 27 for CE MRI and 33 for mammography and CE MRI combined. In the subgroup of BRCA1 (BRCA2) mutation carriers or of women having a first degree relative with a mutation in BRCA1 (BRCA2) corresponding numbers were 3 (6), 12 (7) and 12 (11), respectively. For all women, the incremental cost per cancer detected with CE MRI and mammography combined was 28 pound 284 compared to mammography. When only BRCA1 or the BRCA2 groups were considered, this cost would be reduced to 11 pound 731 (CE MRI vs mammography) and 15 pound 302 (CE MRI and mammography vs mammography). Results were most sensitive to the unit cost estimate for a CE MRI screening test. Contrast-enhanced MRI might be a cost-effective screening modality for women at high risk, particularly for the BRCA1 and BRCA2 subgroups. Further work is needed to assess the impact of screening on mortality and health-related quality of life.

A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells

Phytochemicals have provided an abundant and effective source of therapeutics for the treatment of cancer. Here we describe the characterization of a novel plant toxin, persin, with in vivo activity in the mammary gland and a p53-, estrogen receptor-, and Bcl-2-independent mode of action. Persin was previously identified from avocado leaves as the toxic principle responsible for mammary gland-specific necrosis and apoptosis in lactating livestock. Here we used a lactating mouse model to confirm that persin has a similar cytotoxicity for the lactating mammary epithelium. Further in vitro studies in a panel of human breast cancer cell lines show that persin selectively induces a G(2)-M cell cycle arrest and caspase-dependent apoptosis in sensitive cells. The latter is dependent on expression of the BH3-only protein Bim. Bim is a sensor of cytoskeletal integrity, and there is evidence that unique structure of the compound, persin could represent a novel class of microtubule-targeting agent with potential specificity for breast cancers.

Calcium transport and signaling in the mammary gland: Targets for breast cancer

The mammary gland is subjected to extensive calcium loads during lactation to support the requirements of milk calcium enrichment. Despite the indispensable nature of calcium homeostasis and signaling in regulating numerous biological functions, the mechanisms by which systemic calcium is transported into milk by the mammary gland are far from completely understood. Furthermore, the implications of calcium signaling in terms of reaulating proliferation, differentiation and apoptosis in the breast are currently uncertain. Deregulation of calcium homeostasis and signaling is associated with mammary gland pathophysiology and as such, calcium transporters, channels and binding proteins represent potential drug targets for the treatment of breast cancer. (c) 2005 Elsevier B.V. All rights reserved.

Progressive resistance training and stretching following surgery for breast cancer: study protocol for a randomised controlled trial

Background: Currently 1 in 11 women over the age of 60 in Australia are diagnosed with breast cancer. Following treatment, most breast cancer patients are left with shoulder and arm impairments which can impact significantly on quality of life and interfere substantially with activities of daily living. The primary aim of the proposed study is to determine whether upper limb impairments can be prevented by undertaking an exercise program of prolonged stretching and resistance training, commencing soon after surgery. Methods/design: We will recruit 180 women who have had surgery for early stage breast cancer to a multicenter single-blind randomized controlled trial. At 4 weeks post surgery, women will be randomly assigned to either an exercise group or a usual care ( control) group. Women allocated to the exercise group will perform exercises daily, and will be supervised once a week for 8 weeks. At the end of the 8 weeks, women will be given a home-based training program to continue indefinitely. Women in the usual care group will receive the same care as is now typically provided, i.e. a visit by the physiotherapist and occupational therapist while an inpatient, and receipt of pamphlets. All subjects will be assessed at baseline, 8 weeks, and 6 months later. The primary measure is arm symptoms, derived from a breast cancer specific questionnaire (BR23). In addition, range of motion, strength, swelling, pain and quality of life will be assessed. Discussion: This study will determine whether exercise commencing soon after surgery can prevent secondary problems associated with treatment of breast cancer, and will thus provide the basis for successful rehabilitation and reduction in ongoing problems and health care use. Additionally, it will identify whether strengthening exercises reduce the incidence of arm swelling. Trial Registration: The protocol for this study is registered with the Australian Clinical Trials Registry (ACTRN012606000050550).