Mostrando las entradas con la etiqueta Breast cancer. Mostrar todas las entradas
Mostrando las entradas con la etiqueta Breast cancer. Mostrar todas las entradas

26 junio, 2013

NICE: Guidance on familial breast cancer.

Ovarian and breast cancer patients in a pedigr...
Ovarian and breast cancer patients in a pedigree chart of a family (Photo credit: Wikipedia)
Familial breast cancer occurs in people with one or more family members affected by breast, ovarian, or a related cancer such as primary peritoneal cancer. About 5% of all breast cancers can be attributed to inherited mutations in specific high risk genes such as BRCA1, BRCA2, and TP53.
This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on the classification and care of people at risk of familial breast cancer.1 The guideline updates previous NICE guidance on familial breast cancer, published in 2004 and 2006.2 3 It also provides new guidance on men and women with a newly or previously diagnosed breast cancer who have a family history of breast and ovarian cancer, as they were excluded from previous guidance.4

Enhanced by Zemanta

30 mayo, 2013

Frequency of Mammography: Age, Breast Density, and Hormone Therapy


Practice Update

JAMA Intern Med 2013 May 01;173(8)807-816, K Kerlikowske, W Zhu, RA Hubbard, B Geller, K Dittus, D Braithwaite, KJ Wernli, DL Miglioretti, ES O'Meara



TAKE-HOME MESSAGE

This large, prospective cohort study found that biennial screening mammography for most women aged 40 to 49 and 50 to 74 years, even among those with high breast density or receiving combination hormone therapy (risk factors for breast cancer), results in similar risks of presenting with advanced-stage disease as with annual screening mammography. Most women who undergo annual mammography are at high risk of false-positive results without benefit from the more frequent screening. However, a small proportion of women aged 40 to 49 with extremely dense breasts are more likely to present with advanced-stage disease if they undergo biennial vs annual screening; this benefit is counterbalanced by a higher risk of cumulative false-positive mammography results with annual screening.
Screen all women aged 50 to 74 biennially (regardless of breast density or hormone therapy use). When counseling women aged 40-49 about breast cancer screening, those with extremely high density breasts should be informed that annual mammography may minimize their risk of presenting with advanced-stage disease but the cumulative risk of false-positive results is high.




SUMMARY
PracticeUpdate Editorial Team
Updated US guidelines recommending that women aged 50 to 74 years undergo mammography biennially, instead of every 1 to 2 years as previously recommended, do not take into account women with additional breast cancer risk factors, such as increased breast density and postmenopausal use of hormonal therapy (HT). More frequent screening may be advantageous in these women, but few studies have reported outcomes when risk factors are combined with frequency of screening mammography.
This study evaluated women aged 40 to 74 years undergoing screening mammography in a community setting to determine whether the benefits (detection of early-stage disease) and harms (false-positive result or biopsy recommendation) differed by screening frequency according to age, breast density, and postmenopausal HT use. Breast Cancer Surveillance Consortium mammography registry data from 1994 through 2008 were used to identify women with and without breast cancer who had undergone annual, biennial, or triennial screening mammography. Analyses for benefit included 11,474 women with at least two screening examinations before diagnosis with breast cancer. Most of these women were aged ≥ 50 years, and > 50% had heterogeneously dense or extremely dense breasts. Analyses for harm included 922,624 women with no previous breast cancer and no cancer within 1 year of screening. Of these women aged 40 to 49 years, 55.1% had extremely dense breasts.
The risk of presenting with advanced-stage breast cancer was similar for most women aged 40 to 49 years and 50 to 74 years screened biennially compared with those screened annually, including those women with high breast density or who were receiving combination HT. Only women aged 40 to 49 years with extremely dense breasts were at increased risk of presenting with advanced-stage rather than early-stage disease when screened biennially vs annually (adjusted odds ratio [AOR] = 1.89; 95% CI, 1.06-3.39) and of presenting with a tumor size > 20 mm (AOR = 2.39; 95% CI, 1.37-4.18). Women aged 50 to 74 years with heterogeneously dense or extremely dense breasts who were receiving combination HT had an apparent, but nonstatistically significant, increased risk of advanced-stage disease (AOR = 1.56; 95% CI, 0.88-2.80) and tumor size > 20 mm (AOR = 1.59; 95% CI, 0.97-2.61) with biennial vs annual screening.
Annual screening was associated with a high probability of a false-positive mammography result in most women, with probability decreasing as the screening interval increased. Women aged 40 to 49 years were most likely to have at least one false-positive recall after 10 years of subsequent annual mammography, with cumulative probabilities of 68.9% and 65.5% in women with heterogeneously dense or extremely dense breasts, respectively. Likewise, women aged 50 to 74 years receiving combination HT and with heterogeneously dense or extremely dense breasts had similarly high cumulative probabilities of a false-positive result with annual screening (68.1% and 65.8%, respectively). Lowest cumulative probabilities were seen in women with fatty breasts across both age groups and regardless of combination HT use (30.3%–36.3%). Cumulative probabilities of at least one false-positive biopsy recommendation after 10 years were much lower than those of a false-positive recall, although of a similar pattern.
This study found that, with the exception of women aged 40 to 49 years with extremely dense breasts, biennial screening mammography was associated with a similar risk of presenting with advanced-stage disease compared with annual screening mammography, but overall the probability of a false-positive screening result was higher.




JAMA internal medicine
Outcomes of Screening Mammography by Frequency, Breast Density, and Postmenopausal Hormone Therapy
JAMA Intern Med 2013 May 01;173(8)807-816, K Kerlikowske, W Zhu, RA Hubbard, B Geller, K Dittus, D Braithwaite, KJ Wernli, DL Miglioretti, ES O'Meara
Enhanced by Zemanta

19 mayo, 2013

Cancer Risks for BRCA1 and BRCA2 Mutation Carriers: Results From Prospective Analysis of EMBRACE

 

Source:  http://jnci.oxfordjournals.org/content/early/2013/04/26/jnci.djt095

Cancer Risks for BRCA1 and BRCA2 Mutation Carriers: Results From Prospective Analysis of EMBRACE


  1. on behalf of EMBRACE
+ Author Affiliations
  1. Affiliations of authors: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care (NM, SP, DF, SE, RP, EF, ACA, DFE); Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK (DGE); South East Thames Regional Genetics Service, Guy’s Hospital, London, UK (LI); Oncogenetics Team, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London, UK (RAE); Yorkshire Regional Genetics Service, Leeds, UK (JA); Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Glasgow, UK (RD); Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK (DE); West Midlands Regional Genetics Service, Birmingham Women’s Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK (TC); Sheffield Clinical Genetics Service, Sheffield Children’s Hospital, Sheffield, UK (JC); Department of Clinical Genetics, Royal Devon & Exeter Hospital, Exeter, UK (CB); Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, UK (MT); Institute of Genetic Medicine, Centre for Life, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK (FD); Clinical Genetics Department, St.Georges University of London, Tooting, London, UK (SH); Oxford Regional Genetics Service, Churchill Hospital, Oxford, UK (LW); South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, UK (MEP); Northern Ireland Regional Genetics Centre, Belfast City Hospital, Belfast, UK (PJM); North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, London, UK (LES); Academic Unit of Clinical and Molecular Oncology, Trinity College Dublin and St James’s Hospital, Dublin, Ireland (MJK); Cheshire & Merseyside Clinical Genetics Service, Liverpool Women’s NHS Foundation Trust, Liverpool, UK (CH); South West Regional Genetics Service, Bristol, UK (AD); All Wales Medical Genetics Services, University Hospital of Wales, Cardiff, UK (MTR); North West Thames Regional Genetics Service, Kennedy-Galton Centre, Harrow, UK (HD); North of Scotland Regional Genetics Service, NHS Grampian & University of Aberdeen, Foresterhill, Aberdeen, UK (ZM, HG); Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, UK (JE); Leicestershire Clinical Genetics Service, University Hospitals of Leicester NHS Trust, Leicester, UK (JB); All Wales Medical Genetics Service, Glan Clwyd Hospital, Rhyl, UK (EM, AM).
  1. Correspondence to: Nasim Mavaddat, MBBS, PhD, Strangeways Research Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK (e-mail: nasim@srl.cam.ac.uk).
  • Received July 24, 2012.
  • Revision received March 20, 2013.
  • Accepted March 22, 2013.

Abstract


Background Reliable estimates of cancer risk are critical for guiding management of BRCA1 and BRCA2 mutation carriers. The aims of this study were to derive penetrance estimates for breast cancer, ovarian cancer, and contralateral breast cancer in a prospective series of mutation carriers and to assess how these risks are modified by common breast cancer susceptibility alleles.

Methods Prospective cancer risks were estimated using a cohort of 978 BRCA1 and 909 BRCA2 carriers from the United Kingdom. Nine hundred eighty-eight women had no breast or ovarian cancer diagnosis at baseline, 1509 women were unaffected by ovarian cancer, and 651 had been diagnosed with unilateral breast cancer. Cumulative risks were obtained using Kaplan–Meier estimates. Associations between cancer risk and covariables of interest were evaluated using Cox regression. All statistical tests were two-sided.

Results The average cumulative risks by age 70 years for BRCA1 carriers were estimated to be 60% (95% confidence interval [CI] = 44% to 75%) for breast cancer, 59% (95% CI = 43% to 76%) for ovarian cancer, and 83% (95% CI = 69% to 94%) for contralateral breast cancer. For BRCA2 carriers, the corresponding risks were 55% (95% CI = 41% to 70%) for breast cancer, 16.5% (95% CI = 7.5% to 34%) for ovarian cancer, and 62% (95% CI = 44% to 79.5%) for contralateral breast cancer. BRCA2 carriers in the highest tertile of risk, defined by the joint genotype distribution of seven single nucleotide polymorphisms associated with breast cancer risk, were at statistically significantly higher risk of developing breast cancer than those in the lowest tertile (hazard ratio = 4.1, 95% CI = 1.2 to 14.5; P = .02).
Conclusions Prospective risk estimates confirm that BRCA1 and BRCA2 carriers are at high risk of developing breast, ovarian, and contralateral breast cancer. Our results confirm findings from retrospective studies that common breast cancer susceptibility alleles in combination are predictive of breast cancer risk for BRCA2 carriers.

Management of hereditary breast and ovarian cancer syndrome and patients with BRCA mutations

Ovarian and breast cancer patients in a pedigr...
Ovarian and breast cancer patients in a pedigree chart of a family (Photo credit: Wikipedia)
Via: Alfonso Casi en grupo https://www.facebook.com/groups/informacionmedica/
Salud Juntos  RIESGO FAMILIAR DEL CANCER DE MAMA, el primer paso es conocer, en mujeres con intensa historia familiar de cáncer de mama, su situación de portadora o no de la mutación BRCA.

Sólo alrededor del 5% al 10% de los cánceres de mama que se diagnostican son causados por mutaciones BRCA 1 y 2; la mayoría son causados por otros factores.
Ciertas características señalan a las mujeres que tienen mayor riesgo de ser portadoras de la mutación, como una menor edad en el momento del diagnóstico, una intensa historia familiar y ciertos grupos étnicos. En estos casos se recomienda un asesoramiento genético para las mutaciones BRCA 1 y 2.
Las portadoras de la mutación BRCA tienen un 80% a 90% riesgo de cáncer de mama durante su vida (estudio retrospectivo), así como un 40% a 50% riesgo de cáncer de ovario. (Riesgo prospectivo de 1/200 aproximadamente).
Las principales opciones para el riesgo de cáncer de mama son la vigilancia, el tratamiento médico preventivo con tamoxifeno u otros agentes quimioterapéuticos, o la doble mastectomía profiláctica - la forma más eficaz de prevención pero con importantes implicaciones.
Para información exhaustiva ->http://ow.ly/lbr4s
http://ow.ly/lbrck
 Read More

16 mayo, 2013

Bandolier: Genewatch: BRCA genes - potential and problems

Ovarian and breast cancer patients in a pedigr...
Ovarian and breast cancer patients in a pedigree chart of a family (Photo credit: Wikipedia)

 

Genewatch: BRCA genes - potential and problems


Potential and Problems

The New England Journal of Medicine had a headline back in May of which Bandolier would be proud - "BRCA genes - Bookmaking, Fortunetelling, and Medical care" [1]. It pulled together information in four papers in that issue which examined new research on these genes involved with breast and ovarian cancer. The correspondence published in September is also interesting for those contemplating how to make the best use of new genetic information.

Statistical prophecies

The discovery of the so-called breast cancer genes, BRCA 1 in 1994 and BRCA 2 in the following year, were clearly landmarks in the study of breast cancer. It was naturally hoped, indeed almost assumed, that such important discoveries would quickly be followed by rationally designed improvements in prevention and treatment of this dread disease. The message that a woman with a strong family history of breast and/or ovarian cancer who carries a germ line mutation in one of these genes carries a lifetime risk of breast cancer of about 85%, and about 60% for ovarian cancer, is a very frightening one. Not surprisingly the pressure created for the practical application of these discoveries was almost immediate and very great.
The situation was further complicated by the potential economic returns of genetic testing and the speed with which commercial companies were able to offer their services. Although the ethical and socio-economic problems raised by this were quickly appreciated, ongoing discussions between well informed representatives of the public, patient groups and the relevant professions will be required before any consensus can be reached. It is at least of some comfort to note that government regards the situation as sufficiently important to have set up (even if only after severe pressure from the professions!) both a Human Genetic Commission and a Genetics Testing Advisory Group.

Although the emerging information is of great scientific value and interest, it does have a great potential for misunderstanding and misapplication. The editorial [1] refers to the making of gene-based statistical prophecies - but not necessarily with all the evidence yet in.

Inappropriate optimism

One of the papers in the NEJM issue was a study of the prevalence of BRCA1 mutations in a population of women with breast cancer. Clinical information, family histories and blood was given by 263 women, and DNA sequencing was used to identify BRCA1 mutations. Women were consecutive referrals who were referred either because there was a strong familial risk factor for breast cancer (169 women) or breast cancer was diagnosed before 40 years of age (94 women). There was an average of 4 breast cancers per family and 1.5 cases of ovarian cancer in the women with a family history.


BRCA 1 mutations were identified in 9/124 (7%) women where there was a family history of breast cancer without ovarian cancer, 10/57 (18%) where family members had bilateral breast cancer, 28/60 (47%) with family members with both breast and ovarian cancer or a single member with both cancers.

Implication for screening

This suggests that even when subjects are selected from families with a strong history of breast cancer only about 7 in 100 will be found to have BRCA 1 mutations. So more than 9 out of 10 tests would be negative, with 10% or fewer positive, if screening for BRCA1 mutations were instituted. The implication is that BRCA1 mutations may account for fewer than half of hereditary cases of breast cancer, not much higher figures suggested previously (see Bandolier 18 ). Routine screening, even where there is a family history, will be wasteful in that it will require enormous back up, both scientific and medical, including counselling, to undertake responsibly. Furthermore, women who do not have a mutation have to be cautioned to prevent a false sense of security, because, in the striking words of the article, "negative tests are not truly negative". That is, women with negative results for BRCA1 mutation are still at risk of cancer.

BRCA1 gene

Scientists have already identified more than 200 different mutations in the two BRCA genes. But we do not know how these different mutations differ in their relative contributions to breast, ovarian and other cancers. Clearly some mutations are responsible for the very high risks identified in some families, but others are likely to be within the normal variations found in many genes (polymorphisms) and not be relevant to cancer. It is also likely that different mutations will determine different types of cancers with different pathologies and different outcomes. There are some very preliminary indications that mutations towards one end of the BRCA1 gene are more likely to lead to breast cancer while those towards the other end of the gene are more likely to give ovarian cancer. It is also suggested that mutations in the BRCA2 gene are less likely to be found in early onset breast cancer than are BRCA1 mutations.
Moreover the same mutations may behave differently in different populations of women. This emphasises the importance of modifying factors in determining the final outcome (eg, reproductive history, hormone therapy, diet, smoking and other genes which, for example, control the metabolism of hormones). We must not forget that all cancers are ultimately determined by a combination of genetic and environmental factors and the interplay of these is one of our most urgent subjects for research.

Statistical prediction



The problem of statistical prediction becomes especially worrying when irreversible decisions are based on it. The question of whether to have prophylactic mastectomies or oophorectomies for carriers of BRCA mutations is a particularly difficult one. A theoretical model [3], based on a number of statistical assumptions, estimated that prophylactic mastectomies would add 2.9 to 5.3 years of life expectancy for a 30 year old carrier of a mutation and an oophorectomy would add 0.3 to 1.7 years. Estimated gains in life expectancy decline with age, however. Gains would be minimal for a 60 year old, less than one year on average, very little more than the estimated gain in life expectancy of 8 months for a woman without a mutation.

But as correspondence suggests [4], even this reported gain in life expectancy may overstate the benefit of prophylactic surgery to the patients for several reasons:

  • The effects of surgery on quality of life are ignored.
  • Risks associated with surgery are immediate. Benefits (prevention of cancer) accrue over time.
  • The reported gain in life expectancy applies only to women who already know they have the gene mutations. Screening to find the mutation would carry its own demerits - not least those of false positive or false negative results in circumstances where prevalence may not be high.


So this information should encourage a conservative approach to prophylactic surgery. But patients are individuals rather than units of a statistical study and each needs to be given individual consideration. Where this involves changes in genes which predispose to breast cancer this means access to experts who themselves are in possession of the latest information and are able to communicate this in a digestible form to worried people who do not understand the science or statistics.

References:

  1. B Healy. BRCA genes - Bookmaking, Fortunetelling, and Medical Care. New England Journal of Medicine 1997 336: 1449-9.
  2. FJ Couch, ML DeShano, A Blackwood et al. BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. New England Journal of Medicine 1997 336: 1409-15.
  3. D Schrag, KM Kuntz, JE Garber, JC Weeks. Decision analysis - effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 or BRCA2 mutations. New England Journal of Medicine 1997 336: 1465-71.
  4. JD Birkmeyer, HG Welch. Risk of breast cancer in carriers of BRCA gene mutations. New England Journal of Medicine 1997 337: 787.

Enhanced by Zemanta

03 mayo, 2013

Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence

heredity and cancer, breast cancer, inherited ...
heredity and cancer, breast cancer, inherited factors vs. other factors (Photo credit: Wikipedia)
 Despite substantial increases in the number of cases of early-stage breast cancer detected, screening mammography has only marginally reduced the rate at which women present with advanced cancer. Although it is not certain which women have been affected, the imbalance suggests that there is substantial overdiagnosis, accounting for nearly a third of all newly diagnosed breast cancers, and that screening is having, at best, only a small effect on the rate of death from breast cancer.

Más datos sobre el cribado del cáncer de mama -> Este estudio examina las tendencias entre 1976 y 2008 en la incidencia de cáncer de mama en estadio temprano (carcinoma ductal in situ y enfermedad localizada) y la fase final del cáncer de mama (enfermedad regional ya distancia) entre las mujeres de 40 años o más. Los investigadores interpretan que el cribado, a pesar del aumento del diagnóstico precoz,  en el mejor de los casos, sólo tiene un pequeño efecto en la tasa de muerte por cáncer de mama.
N Engl J Med, 22/11/2012, "Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence".
Para reducir la mortalidad, la detección debe detectar una enfermedad potencialmente mortal en una etapa más temprana y curable. Por lo tanto, los programas eficaces de detección de cáncer aumentan la incidencia de cáncer detectado en una etapa temprana y disminuyen la incidencia de cáncer en etapas tardías. Este estudio ha utilizado los datos del Surveillance, Epidemiology, and End Results para examinar las tendencias entre 1976 y 2008 en la incidencia de cáncer de mama en estadio temprano (carcinoma ductal in situ y enfermedad localizada) y la fase final del cáncer de mama (enfermedad regional y distante) entre las mujeres de 40 años de edad o más. Resultados: La introducción de la mamografía de cribado en los Estados Unidos se ha asociado con una duplicación en el número de casos de cáncer de mama en fase inicial que se detectan cada año, de 112 a 234 casos por cada 100.000 mujeres - un incremento absoluto de 122 casos por cada 100.000 mujeres . Al mismo tiempo, el ritmo en el que las mujeres alcanzan las etapas avanzadas de cáncer disminuyó en un 8%, de 102 a 94 casos por cada 100.000 mujeres - una disminución absoluta de 8 casos por cada 100.000 mujeres-. Asumiendo una carga de enfermedad subyacente constante, sólo 8 de cada 122 cánceres adicionales diagnosticados en una etapa temprana se espera que progresen a enfermedad avanzada. Después de excluir el exceso de incidencia transitoria asociado con la terapia de reemplazo hormonal y el ajuste de las tendencias en la incidencia de cáncer de mama entre las mujeres menores de 40 años de edad, se estima que el cáncer de mama se diagnosticó en exceso (es decir, los tumores que fueron detectados en el cribado que nunca habrían dado lugar a síntomas clínicos) en 1,3 millones de mujeres estadounidenses en los últimos 30 años. Se estimó que en 2008, el cáncer de mama fue diagnosticado en exceso en más de 70.000 mujeres, lo que representó el 31% de todos los cánceres de mama diagnosticados. Los autores concluyen que a pesar de un aumento sustancial en el número de casos de cáncer de mama detectados en una etapa temprana, la mamografía sólo ha reducido marginalmente la velocidad a la que las mujeres alcanzan un cáncer avanzado. Aunque no es cierto que las mujeres han sido afectadas, el desequilibrio sugiere que hay considerable exceso de diagnóstico, lo que representa casi un tercio de todos los cánceres de mama recién diagnosticados, y que el cribado, en el mejor de los casos, sólo tiene un pequeño efecto en la tasa de muerte por cáncer de mama.