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Search Results: 1 - 10 of 2210 matches for " the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) Steering Group "
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The influence of genetic variation in 30 selected genes on the clinical characteristics of early onset breast cancer
William Tapper, Victoria Hammond, Sue Gerty, Sarah Ennis, Peter Simmonds, Andrew Collins, the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) Steering Group, Diana Eccles
Breast Cancer Research , 2008, DOI: 10.1186/bcr2213
Abstract: We selected 1,001 women with early onset nonfamilial invasive breast cancer from the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) cohort and genotyped 206 single nucleotide polymorphisms (SNPs) across 30 candidate genes. After quality control, 899 cases and 133 SNPs remained. Survival analyses were used to identify SNPs associated with prognosis and determine their interdependency with recognized prognostic factors. To identify SNPs that alter breast cancer risk, association tests were used to compare cases with controls from the Wellcome Trust Case Control Consortium. To search for SNPs affecting tumour biology, cases were stratified into subgroups according to oestrogen receptor (ER) status and grade and tested for association.We confirmed previous associations between increased breast cancer risk and SNPs in CASP8, TOX3 (previously known as TNRC9) and ESR1. Analysis of prognosis identified eight SNPs in six genes (MAP3K1, DAPK1, LSP1, MMP7, TOX3 and ESR1) and one region without genes on 8q24 that are associated with survival. For MMP7, TOX3 and MAP3K1 the effects on survival are independent of the main recognized clinical prognostic factors. The SNP in 8q24 is more weakly associated with independent effects on survival. Once grade and pathological nodal status (pN stage) were taken into account, SNPs in ESR1 and LSP1 showed no independent survival difference, whereas the effects of the DAPK1 SNP were removed when correcting for ER status. Interestingly, effects on survival for SNPs in ESR1 were most significant when only ER-positive tumours were examined. Stratifying POSH cases by tumour characteristics identified SNPs in FGFR2 and TOX3 associated with ER-positive disease and SNPs in ATM associated with ER-negative disease.We have demonstrated that several SNPs are associated with survival. In some cases this appears to be due to an effect on tumour characteristics known to have a bearing on prognosis; in other cases the effect
Breastfeeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers
Joanne Kotsopoulos, Jan Lubinski, Leonardo Salmena, Henry T Lynch, Charmaine Kim-Sing, William D Foulkes, Parviz Ghadirian, Susan L Neuhausen, Rochelle Demsky, Nadine Tung, Peter Ainsworth, Leigha Senter, Andrea Eisen, Charis Eng, Christian Singer, Ophira Ginsburg, Joanne Blum, Tomasz Huzarski, Aletta Poll, Ping Sun, Steven A Narod, the Hereditary Breast Cancer Clinical Study Group
Breast Cancer Research , 2012, DOI: 10.1186/bcr3138
Abstract: We conducted a case-control study of 1,665 pairs of women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n = 422 pairs). Breast cancer cases and unaffected controls were matched on year of birth, mutation status, country of residence and parity. Information about reproductive factors, including breastfeeding for each live birth, was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the association between ever having breastfed, as well as total duration of breastfeeding, and the risk of breast cancer.Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74). Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43).These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. BRCA mutation carriers should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk.In the general population, reproductive factors, including late age at menarche, parity and breastfeeding, have been shown to protect against the development of breast cancer [1-3]. Various proposed mechanisms include reducing lifetime exposure to ovarian hormones, reducing the cumulative number of ovulatory cycles and differentiation of the breast lobules [4,5]. We and others have evaluated the impact of reproductive factors in the etiology of BRCA-associated breast cancer, although the results are conflicting and vary by BRCA1 or BRCA2 mutation [6-8]. With respect to breastfeeding and breast cancer risk in BRCA1 mutation carriers, two previous studies reported no relationship [9,10] and three studies reported a protectiv
Spontaneous and therapeutic abortions and the risk of breast cancer among BRCA mutation carriers
Eitan Friedman, Joanne Kotsopoulos, Jan Lubinski, Henry T Lynch, Parviz Ghadirian, Susan L Neuhausen, Claudine Isaacs, Barbara Weber, William D Foulkes, Pal Moller, Barry Rosen, Charmaine Kim-Sing, Ruth Gershoni-Baruch, Peter Ainsworth, Mary Daly, Nadine Tung, Andrea Eisen, Olufunmilayo I Olopade, Beth Karlan, Howard M Saal, Judy E Garber, Gad Rennert, Dawna Gilchrist, Charis Eng, Kenneth Offit, Michael Osborne, Ping Sun, Steven A Narod, the Hereditary Breast Cancer Clinical Study Group
Breast Cancer Research , 2006, DOI: 10.1186/bcr1387
Abstract: In a matched case-control study, the frequencies of spontaneous abortions were compared among 1,878 BRCA1 mutation carriers, 950 BRCA2 mutation carriers and 657 related non-carrier controls. The rates of spontaneous and therapeutic abortions were compared for carriers with and without breast cancer.There was no difference in the rate of spontaneous abortions between carriers of BRCA1 or BRCA2 mutations and non-carriers. The number of spontaneous abortions was not associated with breast cancer risk among BRCA1 or BRCA2 mutation carriers. However, BRCA2 carriers who had two or more therapeutic abortions faced a 64% decrease in the risk of breast cancer (odds ratio = 0.36; 95% confidence interval 0.16–0.83; p = 0.02).Carrying a BRCA1 or BRCA2 mutation is not a risk factor for spontaneous abortions and spontaneous abortions do not appear to influence the risk of breast cancer in carriers of BRCA1 or BRCA2 mutations. However, having two or more therapeutic abortions may be associated with a lowered risk of breast cancer among BRCA2 carriers.Germline mutations in BRCA1 (MIM # 113705) and BRCA2 (MIM # 600185) are estimated to account for about 80% of breast/ovarian cancer families and 20% to 50% of site-specific breast cancer families [1-3]. Mutation carriers face substantially increased risks of developing both breast and ovarian cancer; the lifetime risk for developing breast cancer in BRCA1/2 mutation carriers is estimated to be 40% to 85% (4 to 7-fold greater risk than the general population) and for ovarian cancer to be 16% to 64% (a 30-fold increase) [3-5]. Reproductive factors have been shown to modify the risk of breast cancer risk in both mutation carriers [6] and the general population [7,8]. However, the relationships between induced or spontaneous abortions and breast cancer risk in BRCA1 or BRCA2 carriers have not been well studied. A recent study from Israel suggested that BRCA1/2 mutation carriers might be at increased risk for recurrent spontaneous abortion
Clinical trial update: International Breast Cancer Study Group
Karen N Price, Aron Goldhirsch, the International Breast Cancer Study Group
Breast Cancer Research , 2005, DOI: 10.1186/bcr1334
Abstract: The International Breast Cancer Study Group (IBCSG) opened its first generation of trials in 1978. The IBCSG includes both participating cooperative groups and individual institutions from all over the world. The groups are from Switzerland (Swiss Group for Clinical Cancer Research, 38 centers), Sweden (West Sweden Breast Cancer Study Group, 11 centers), Australia and New Zealand (Australian New Zealand Breast Cancer Trials Group, 56 centers), and Chile (GOCCHI, a Chilean cooperative group, 23 centers). Individual centers are located in Italy (14 centers), Slovenia, Hungary (2 centers), Spain, Romania, Austria, United Kingdom, Belgium (2 centers), Brazil, Peru, Hong Kong, India, South Africa (2 centers), and Canada.The IBCSG is conducting trials of tailored treatment approaches for these subpopulations: patients with endocrine non-responsive early breast cancer; older patients with endocrine non-responsive early breast cancer who are not candidates for standard chemotherapy regimens; and younger patients with endocrine responsive early breast cancer. Because each of these three populations is somewhat rare, treatment decisions tend to be based on the findings from the largest breast cancer population: middle-aged (median age 55) women with endocrine responsive breast cancer (i.e. estrogen receptor-positive and/or progesterone receptor-positive) who were included in trials of chemotherapy and of endocrine therapy across the board. Through subgroup analyses of these large heterogeneous trials we have identified distinct responsiveness features, and the current generation of IBCSG trials investigates treatments tailored to populations based on these features (Table 1). Examples of such trials are described below.The CM-Maintenance Trial (IBCSG 22-00) studies a tailored chemotherapy approach for patients with endocrine non-responsive tumors. The role of prolonged, low-dose chemotherapy after a standard adjuvant chemotherapy regimen to reduce the risk of relapse and impr
Interpreting breast international group (BIG) 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer
Meredith M Regan, Karen N Price, Anita Giobbie-Hurder, Beat Thürlimann, Richard D Gelber, for the International Breast Cancer Study Group and BIG 1-98 Collaborative Group
Breast Cancer Research , 2011, DOI: 10.1186/bcr2837
Abstract: Clinicaltrials.gov ID: NCT00004205.Reports of large trials of breast cancer confirm the value of aromatase inhibitors as adjuvant systemic therapy for postmenopausal women with endocrine-responsive early breast cancer [1-9]. The inclusion of an aromatase inhibitor in the adjuvant treatment program for this population has been recommended by both the American Society of Clinical Oncology and St. Gallen guidelines [10,11]. Studies have shown that 5 years of adjuvant therapy with an aromatase inhibitor alone improved disease-free survival (DFS) and time to distant recurrence (TDR) in comparison with 5 years of tamoxifen in this population [1-3,12], and recently the Breast International Group (BIG) 1-98 trial showed improved overall survival (OS) with the aromatase inhibitor letrozole [13]. Other studies have shown that switching to an aromatase inhibitor after 2 years of tamoxifen improves outcome [4-8]. Results were confirmed in an overview analysis [9].The BIG 1-98 study is a double-blind, four-arm trial comparing 5 years of monotherapy with tamoxifen or with letrozole or with sequences of 2 years of one of these agents followed by 3 years of the other (Figure 1). Centers participated in one of two randomization options (two-arm or four-arm). Between 1998 and 2003, 8,010 patients were enrolled. The trial is designed to answer two questions concerning how best to use endocrine agents for the treatment of early breast cancer in postmenopausal women with hormone receptor-positive tumors, the first to compare letrozole monotherapy with tamoxifen monotherapy and the second to determine the benefit of letrozole in sequence with tamoxifen. Table 1 presents a summary of the study subpopulations contributing to various data analyses of efficacy questions. In BIG 1-98, the primary endpoint is DFS, defined as the time from random assignment to the earliest time of invasive recurrence in local, regional, or distant sites; a new invasive breast cancer in the contralateral breast;
Hormone Replacement Therapy after Prophylactic Adnexectomy
Pascale This, Rémy J Salmon, Sylvie Dolbeault, Anne de la Rochefordière, Brigitte Sigal-Zafrani, Dominique Stoppa-Lyonnet, the Institut Curie Breast and Ovarian Cancer Risk Study Group
Hereditary Cancer in Clinical Practice , 2005, DOI: 10.1186/1897-4287-3-4-181
Abstract: At the Curie Institute, we take into account the preferences of women after they have been thoroughly informed:1. We recommend PA to women at 40 years of age if they have a BRCA1 mutation, or a BRCA2 mutation and a family history of ovarian cancer, and at 50 years of age if they have a BRCA2 mutation without a family history of ovarian cancer.2. In women unaffected by breast cancer, we give very complete information on the benefits and risks of HRT and alternatives, such as symptomatic treatments for hot flushes, vaginal oestrogens, and non-hormonal treatment for osteoporosis.3. We always propose psychological support to allow each woman to estimate and anticipate the consequences of PA.4. In case of uterine diseases such as fibroma, surgeons may propose a hysterectomy as well as PA, in which case oestrogens can be prescribed alone and progestins can be avoided (4).5. After PA, a gynaecological consultation is offered: HRT is given only to thoroughly informed women who really want it and have accepted PA with the assurance that they would have HRT afterwards. HRT is also offered to women who have had a prophylactic bilateral mastectomy. For other cases, clinical follow-up is proposed, and osteodensitometry is prescribed. If menopausal problems occur, alternative treatments are proposed first. For persistent problems, HRT is prescribed at the lowest dose for as long as the woman wishes. It is strongly recommended that treatment be stopped at the natural age of menopause, around 50 years of age.We think that over-alarmist information on menopause and strongly held beliefs against HRT lead some young women to refuse or delay an intervention that may save their life. Therefore, we advocate clear information, honest dialogue, and shared decision making with each woman.
Exploring cancer register data to find risk factors for recurrence of breast cancer – application of Canonical Correlation Analysis
Amir R Razavi, Hans Gill, Olle St?l, Marie Sundquist, Sten Thorstenson, Hans ?hlfeldt, Nosrat Shahsavar, the South-East Swedish Breast Cancer Study Group
BMC Medical Informatics and Decision Making , 2005, DOI: 10.1186/1472-6947-5-29
Abstract: One essential outcome after breast cancer treatment is recurrence of the disease. It is important to understand the relationship between different predictors and recurrence, including the time interval until recurrence. This study describes the application of CCA to find important predictors for two different outcomes for breast cancer patients, loco-regional recurrence and occurrence of distant metastasis and to decrease the number of variables in the sets of predictors and outcomes without decreasing the predictive strength of the model.Data for 637 malignant breast cancer patients admitted in the south-east region of Sweden were analyzed. By using CCA and looking at the structure coefficients (loadings), relationships between tumor specifications and the two outcomes during different time intervals were analyzed and a correlation model was built.The analysis successfully detected known predictors for breast cancer recurrence during the first two years and distant metastasis 2–4 years after diagnosis. Nottingham Histologic Grading (NHG) was the most important predictor, while age of the patient at the time of diagnosis was not an important predictor.In cancer registers with high dimensionality, CCA can be used for identifying the importance of risk factors for breast cancer recurrence. This technique can result in a model ready for further processing by data mining methods through reducing the number of variables to important ones.Breast cancer is the most common type of cancer diagnosed in women in Western countries. Sweden has had a high incidence of breast cancer for several decades, although mortality rates have been lower than in most other Western countries [1].Breast cancer prognosis is influenced by many factors such as morphological and pathological tumor specifications and biological tumor markers. Studying these predictors and finding those of most importance can give clinicians better insight regarding the prognosis.As a rule, data on cancer patients h
PRACTICE POINTS: Breast cancer guidelines for Uganda
The Uganda Breast Cancer Working Group
African Health Sciences , 2003,
Abstract: INTRODUCTION Breast cancer in Uganda is the third commonest cancer in women coming only next to cancer of the cervix and Kaposi's sarcoma. The incidence of breast cancer in Uganda has doubled from 11:100,000 in 1961 to 22:100,000 in 1995. Unfortunately the cases are often seen in late stages thus the outcome of treatment is inevitably unsatisfactory. The present day knowledge of this disease does not have any effective primary prevention. It is thus imperative that efforts should be made to detect the disease in its early stages. Mammography has been found to be useful but it is not applicable as a means of mass screening in Uganda (there are only 2 mammography units in Uganda. Public education towards Breast Self Examination (BSE) should be propagated because it is practical and affordable. African Health Sciences 2003 3(1); 47-52
Results from the tube versus trabeculectomy study
Gedde Steven,the Tube Versus Trabeculectomy Study Group
Middle East African Journal of Ophthalmology , 2009,
Abstract: The Tube Versus Trabeculectomy (TVT) Study is a multicenter randomized clinical trial comparing the safety and efficacy of tube shunt surgery to trabeculectomy with mitomycin (MMC) in eyes with previous cataract and/or failed glaucoma surgery. Tube shunt surgery was more likely to maintain intraocular pressure (IOP) control and avoid persistent hypotony, reoperation for glaucoma, or loss of light perception vision than trabeculectomy with MMC during the first year of follow-up. Both surgical procedures had similar IOP reduction at 1 year, but less supplemental medical therapy was used following trabeculectomy. The incidence of postoperative complications was higher after trabeculectomy with MMC relative to tube shunt surgery, but serious complications associated with vision loss and/or reoperation developed with similar frequency after both of the procedures. There was no significant difference in the rate of vision loss following trabeculectomy with MMC and tube shunt surgery after 1 year of follow-up. Cataract progression was common, but occurred with similar frequency with both of the surgical procedures.
Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH): study protocol
Diana Eccles, Sue Gerty, Peter Simmonds, Victoria Hammond, Sarah Ennis, Douglas G Altman, the POSH steering group
BMC Cancer , 2007, DOI: 10.1186/1471-2407-7-160
Abstract: The study is a prospective cohort study recruiting 3,000 women aged 40 years or younger at breast cancer diagnosis; the recruiting period covers 1st June 2001 to 31st December 2007. Written informed consent is obtained at study entry. Family history and known epidemiological risk data are collected by questionnaire. Clinical information about diagnosis, treatment and clinical course is collected and blood is stored. Follow up data are collected annually after the first year. An additional recruitment category includes women aged 41 to 50 years who are found to be BRCA1 or BRCA2 gene carriers and were diagnosed with their first breast cancer during the study recruiting period.Power estimates were based on 10% of the cohort carrying a BRCA1 gene mutation. Preliminary BRCA1 and BRCA2 mutation analysis in a pilot set of study participants confirms we should have 97% power to detect a difference of 10% in event rates between gene carriers and sporadic young onset cases. Most of the recruited patients (>80%) receive an anthracycline containing adjuvant chemotherapy regimen making planned analyses more straightforward.Less than 5% of breast cancers diagnosed in the UK are diagnosed in women aged 40 years or younger although there is a rapid increase in the incidence from about 35 years of age[1].Published retrospective studies suggest that early age at onset of breast cancer (below 35 years) is a poor prognosis factor; high grade and oestrogen receptor (ER) negative tumours appear to be more frequent in younger women[2,3]. Breast cancer arising due to a high penetrance genetic predisposition gene such as BRCA1 or BRCA2 occurs at younger average age than breast cancer in the general population and a higher proportion of young onset cases will have a genetic predisposition than breast cancer cases in general. Family history is still the most important indicator of an underlying inherited predisposition [4]. However BRCA1 and BRCA2 may account for less than 40% of all familia
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