Breast Cancer Mortality In Women Research Articles

Regional patterns and time trends in breast cancer mortality among women in China.

e12016 Background: Breast cancer is one of the leading causes of death in China. There is limited information available from large population-based cancer registries to describe the variability in breast cancer mortality in women by region and over time. Methods: The number of deaths and number of women at risk were obtained from the Third National Mortality Retrospective Sampling Survey (2004-2005). A total of 69 690 241 person-years (py) were accumulated in this study. The time trends in mortality during 1973 to 2005 were assessed using data from this survey as well as two previous surveys known as the First Survey in 1973-1975 and the Second Survey in 1990-1992. These surveys are broadly considered representative of the population in China. Results: The crude mortality rate among female breast cancer patients in China in 2004-2005 was 5.90 per 100 000 py (4112/69 690 241). This ranked the sixth most common cancer death in women, and accounted for 5.90% (4112/69 667) of all female cancer deaths. The crude mortality rates among female breast cancer patients were 6.86/100 000 py (1777/25 900 856) in Eastern China, 5.91/100 000 py (1431/24 225 738) in Central China and 4.62/100 000 py (904/19 563 647) in Western China. The age-standardized mortality rate in urban areas (4.91/100 000 py, 1899 deaths) was 1.44 fold higher than that in rural areas (3.42/100 000 py, 2213 deaths). The crude mortality doubled from 2.95/100 000 py in 1973-1975. The age-standardized mortality rate increased from 1.09/100 000 py in 1973-1975 to 3.97/100 000 py in 2004-2005. Conclusions: The mortality rate of female breast cancer in urban areas was higher than in rural areas. The mortality rate was highest in the Eastern region of China, followed by the Central then the Western regions. Breast cancer mortality in women increased substantially in China between 1973 & 2005.

Effectiveness of Mammography Screening in Reducing Breast Cancer Mortality in Women Aged 39–49 Years: A Meta-Analysis

Mammography screening of women >50 years of age significantly reduces breast cancer mortality in randomized controlled trials (RCTs). We sought to evaluate the effectiveness of mammography screening in women aged 39-49 years in reducing breast cancer mortality and to discuss previously published meta-analyses. PubMed/MEDLINE, OVID, COCHRANE, and Educational Resources Information Center (ERIC) databases were searched, and extracted references were reviewed. Dissertation abstracts and clinical trials databases available online were assessed to identify unpublished works. All assessments were independently done by two reviewers. All trials included were RCTs, published in English, included data on women aged 39-49, and reported relative risk (RR)/odds ratio (OR) or frequency data. Nine studies were identified: the Kopparberg, Ostergotland (The Two-County study), Health Insurance Plan (HIP), Canada, Stockholm, Gothenburg, Edinburgh, Age, and Malmo trials. The individual trials were quality assessed, and the data were extracted using predefined forms. Using the DerSimonian and Laird random effects model, the results from the seven RCTs with the highest quality score were combined, and a significant pooled RR estimate of 0.83 (95% confidence interval [CI] 0.72-0.97) was calculated. Post hoc sensitivity analyses excluding studies with randomization before 1980 caused a loss of statistical significance (RR 0.87, 95% CI: 0.56, 1.13). Mammography screenings are effective and generate a 17% reduction in breast cancer mortality in women 39-49 years of age. The quality of the trials varies, and providers should inform women in this age group about the positive and negative aspects of mammography screenings.

Effective biennial mammographic screening in women aged 40–49

Background The United Kingdom is currently moving the age limit for invitation in its national breast screening programme downwards from 50 to 47. In contrast, the US Preventive Services Task Force concluded that, because of borderline statistical significance on effectiveness of mammographic screening, the current evidence is insufficient to advise screening in women aged 40–49. Material and methods We designed a case-referent study to investigate the effect of biennial mammographic screening on breast cancer mortality for women in their forties. In Nijmegen, the Netherlands, screening started in 1975. A total of 272 breast cancer deaths were identified, and 1360 referents aged 40–69 were sampled from the population invited for screening. Effectiveness was estimated by calculating the odds ratio (OR) indicating the breast cancer death rate in screened versus unscreened women. Results In women aged 40–49, the effect of screening was OR = 0.50 (95% confidence interval (CI) = 0.30–0.82). This result is similar to those aged 50–59 (OR = 0.54; 95% CI = 0.35–0.85) and 60–69 (OR = 0.65; 95% CI = 0.38–1.13). Conclusion Our results add convincing evidence about the effectiveness of biennial mammographic screening in women aged 40–49.

The first national public breast cancer screening program in Saudi Arabia

BACKGROUND AND OBJECTIVES:Despite its relatively low incidence in Saudi Arabia, breast cancer has been the most common cancer among Saudi females for the past 12 consecutive years. The objective of this study was to report the results of the first national public breast cancer screening program in Saudi Arabia.METHODS:Women 40 years of age or older underwent breast cancer screening. Mammograms were scored using the Breast Imaging-Reporting and Data System (BI-RADS). Correlations between imaging findings, risk factors and pathological findings were analyzed.RESULTS:Between September 2007 and April 2008, 1215 women were enrolled. The median age was 45 years, and median body mass index was 31.6 kg/m2. Sixteen cases of cancer were diagnosed. No cancer was diagnosed in 942 women with R1/R2 scores, and only 1 case of cancer was diagnosed in 228 women with R0/R3 scores. However, among 26 women with R4/R5 scores, 50% had malignant disease and 35% had benign lesions. No correlation was found between known risk factors and imaging score or cancer diagnosis.CONCLUSIONS:Public acceptance of the breast cancer screening program was encouraging. Longitudinal follow-up will help in better determining the risk factors relevant to our patient population.

Metabolic Syndrome and Breast Cancer in the Me-Can (Metabolic Syndrome and Cancer) Project

Few studies have assessed the metabolic syndrome (MetS) as an entity in relation to breast cancer risk, and results have been inconsistent. We aimed to examine the association between MetS factors (individually and combined) and risk of breast cancer incidence and mortality. Two hundred ninety thousand women from Austria, Norway, and Sweden were enrolled during 1974-2005, with measurements of height, weight, blood pressure, and levels of glucose, cholesterol, and triglycerides. Relative risks (RR) of breast cancer were estimated using Cox proportional hazards regression for each MetS factor in quintiles and for standardized levels (z-scores) and for a composite z-score for the MetS. There were 4,862 incident cases of breast cancer and 633 deaths from breast cancer identified. In women below age 50, there was a decreased risk of incident cancer for the MetS (per 1-unit increment of z-score; RR, 0.83; 95% confidence interval, 0.76-0.90) as well as for the individual factors (except for glucose). The lowest risks were seen among the heaviest women. In women above age 60, there was an increased risk of breast cancer mortality for the MetS (RR, 1.23; 95% confidence interval, 1.04-1.45) and for blood pressure and glucose. The strongest association with mortality was seen for increased glucose concentrations. The MetS was associated with a decreased risk of incident breast cancer in women below age 50 with high body mass index, and with an increased risk of breast cancer mortality in women above 60. Lifestyle interventions as recommended for cardiovascular disease prevention may be of value to prevent breast cancer mortality in postmenopausal women.

Use of paroxetine during tamoxifen therapy for breast cancer was associated with increased breast-cancer and all-cause mortality

Source Citation Kelly CM, Juurlink DN, Gomes T, et al. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ. 2010;3...

Mammographic screening for breast cancer: An invited review of the benefits and costs

Mammographic screening is a proven method for reducing breast cancer mortality for women 40 years of age and older, but the best method for implementation of mammographic screening, particularly in the age group 40–49, remains controversial. The author, in an invited review, summarizes the data and offers guidance based on the best information available for women at risk for breast cancer, and their care providers, with particular emphasis on costs and benefits.

Benefit of adjuvant chemotherapy in elderly ER-negative breast cancer patients: benefits and pitfalls

Approximately 50% of breast cancer (BC) cases occur in women aged 65 and older, and more than 30% occur in those aged over 70, yet very old (older than 70) patients are under-represented in clinical trials. In the Oxford meta-analysis, the hazard ratios for recurrence and BC mortality in women aged over 70 were 0.88 and 0.87, respectively, suggesting a benefit from chemotherapy in this group of patients as well; however, the large confidence intervals surrounding reductions in this subgroup reflect the small number of older patients recruited in randomized trials in Early Breast Cancer Trialists’ Collaborative Group meta-analyses. If we consider the tumor biology of BC in older adults, we will see that they are more likely to develop a tumor with high estrogen receptor (ER)- and/or progesterone receptor-positive status and a lower proliferative index. However, the biology of these tumors appears to change according to chronological age into aggressive forms diagnosed in these patients as well. This subgroup analysis for the benefit of adjuvant chemotherapy in elderly patients (at least 65 years) is reported in a few studies, even though a limited statistical significance has been revealed. Retrospective evidences suggest that even more aggressive treatments such as taxanes and dose-dense schedule appear feasible (but probably more toxic) in the elderly. Age is no longer considered the only criterion for choosing the right treatment for patients with BC; in fact, functional status and comorbidity have to be taken into consideration as well. Fit elderly patients with more aggressive forms (node-positive and ER-poor disease) seem to obtain the same benefits as younger patients, and thus have to be treated in the same manner.

Benefits of Screening Mammography

Breast cancer is a leading cause of premature death for women in their forties, and mammographic screening significantly reduces the risk of death due to breast cancer. The latter was the conclusion of the United States Preventive Services Task Force (USPSTF) meta-analysis of the randomized controlled trials (RCTs) of screening mammography1. The USPSTF concluded, however, that the absolute benefit from routine mammographic screening of women in their forties was too low to offset the harms. As a woman in her forties, and a radiologist specializing in breast imaging, I find their conclusions puzzling. RCTs underestimate the true benefits of mammographic screening2. RCTs assess mortality reduction among women randomized to the group invited to be screened rather than those who actually participated in screening. In an RCT, an invited woman who never has a mammogram and dies of breast cancer is counted as having been screened, just as a woman in the control group who decides to have a mammogram outside the trial is counted as having not been screened. In several RCTs, mammographic quality was quite poor or only a single mammographic view was obtained, both of which reduce cancer detection. Two observational studies among women who underwent screening mammography (with the current standard of two views of each breast), comprising millions of person-years of observation of both screened and unscreened populations, reported a 30 to 40% reduction in breast cancer mortality for women in their forties3, 4. However, these high-quality observational data were not considered by the USPSTF, which limited its focus to RCTs. For women aged 40 to 49 in a screening program, on average, about 1 in 460 will be diagnosed with breast cancer in any given year; during that decade of life, one in 69 women will be diagnosed with invasive breast cancer2. The incidence of breast cancer increases with age, particularly above age 40, with the rates at ages 45 to 49 virtually identical to those at ages 50 to 54, and no abrupt change at age 502. At least a third of potential years of life lost to breast cancer occur among women who died of breast cancer after being diagnosed in their forties5. Over 40,000 women die from breast cancer each year, of whom 18% were diagnosed during their forties (personal communication, Carol DeSantis, MPH, American Cancer Society, December 10, 2009); assuming a 30% reduction in breast cancer deaths due to screening, annual mammography prevents over 2000 deaths per year among women diagnosed in their forties in the United States. Mammographic screening also increases the chance of detecting breast cancer small enough to be treated by lumpectomy instead of mastectomy and decreases the need for chemotherapy. Harms of treating more advanced disease and the increased risk of recurrence for women not screened by mammography were not considered by the USPSTF.

Disparities in breast cancer mortality trends between 30 European countries: retrospective trend analysis of WHO mortality database

Objective To examine changes in temporal trends in breast cancer mortality in women living in 30 European countries.Design Retrospective trend analysis.Data source WHO mortality database on causes of deathsSubjects reviewed...

Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study

Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study

Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study

Objective To characterise whether some selective serotonin reuptake inhibitor (SSRI) antidepressants reduce tamoxifen’s effectiveness by inhibiting its bioactivation by cytochrome P450 2D6 (CYP2D6).Design Population based cohort study.Participants Women living in...

Promoter methylation and the detection of breast cancer

Mammographic screening has been shown to reduce breast cancer mortality in women over the age of 50 years, and to a lesser extent in younger women. The sensitivity of mammography, however, is reduced in some groups of women. There remains a need for a minimally invasive, cost-effective procedure that could be used along side mammography to improve screening sensitivity. Silencing of tumor suppressor genes through promoter hypermethylation is known to be a frequent and early event in carcinogenesis. Further, changes in methylation patterns observed in tumors are also detectable in the circulation of women with breast cancer. This makes these alterations candidate markers for early tumor detection. In this paper, we review the current literature on promoter hypermethylation changes and breast cancer and discuss issues that remain to be addressed in order for the potential of these markers to augment the sensitivity of screening mammography. In general, studies in well-defined populations, including appropriate controls and larger numbers are needed. Further, focus on the optimization of methods of methylation detection in small amounts of DNA is needed.

Age-specific breast, uterine and ovarian cancer mortality trends in Spain: Changes from 1980 to 2006

Introduction: Cancers of the breast, uterus and ovary are responsible for 30% of the cancer deaths in Spanish women. In recent decades, Spain has experienced important socioeconomic transformations, which may have affected mortality trends. We present the current situation of mortality in Spain due to cancers of the breast, uterus and ovary, as well as trends over 1980–2006. Methods: Data on population and deaths due to cancers of the breast, uterus and ovary were obtained from records of the National Statistics Institute. Overall and age-specific changes in mortality of these tumors were studied using change-point Poisson regression models. Results: Breast cancer was responsible for more than 140,000 deaths of females in 1980–2006. Trend analysis of breast cancer mortality of women of all ages showed that rates increased 2.9% annually until 1992 (95% confidence interval (CI) = 2.5, 3.3). After 1992, mortality declined steadily at a rate of −2.1% per year (95% CI = −2.4, −1.8). The number of deaths due to cancers of the uterus was 49,287 between the years 1980 and 2006. Uterine cancer mortality registered a steady decrease of −1.9% every year since 1980 (95% CI = −2.1, −1.8). Ovarian cancer caused 36,157 deaths during the same period, with rates in women older than 50 years more than ten-fold those of younger women. Trend analysis showed a sharp increase of mortality up to 1998 (4.4% annually; 95% CI = 3.9, 4.8) followed by a stabilization. Conclusion: The downturn observed in mortality for these tumors mainly reflects improved survival as a result of earlier diagnosis and better cancer treatments. Cancer management is moving in the right direction in Spain.

How effective are breast cancer screening programmes by mammography? Review of the current evidence

Randomised controlled trials showed that breast cancer screening by mammography reduces breast cancer mortality in women over age 50 by 25–30%. However, it was not clear if this effect would persist outside the controlled trial environment or even could be enhanced. We review the current evidence of the impact of long-standing breast cancer screening programmes (Australia, Canada, Denmark, Finland, Iceland, Italy, the Netherlands, Spain, Sweden and the United Kingdom) on breast cancer mortality. The decrease observed in women invited to screening ranges from 16% to 36%. Breast cancer mortality reductions range from 24% to 48% in women having attended at least one screen after correcting for selection bias. Although evaluation design, time period studied, participation rates achieved differ, the trend in mortality reduction is consistent. Adjuvant therapy is estimated to contribute about one third to this decrease. We conclude that mammography screening programmes implemented for at least 10 years achieve a similar, but not greater mortality reduction as the randomised controlled trials. However, it may take some more years before the full impact of these mammography screening programmes can be assessed.

Patient and tumor characteristics associated with increased mortality in young women (< or =40 years) with breast cancer.

The goal of the current study is to identify predictors responsible for mortality disparities between young (< or =40 years) and older (>40 years) women with breast cancer. From 1998 to 2006, 344 patients < or =40 years were treated for breast cancer. Cox regression models calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) to determine differences in breast cancer mortality in women < or =40 years versus >40 years (n = 3,252), controlling for potential confounders in univariate tests. From 1998 to 2006, 3,596 patients were treated for breast cancer; 9.6% were < or =40 years and 90.4% were >40 years. Young women were more likely to be African-American, with a family history of breast cancer, diagnosed at advanced stage, and treated by mastectomy (P < 0.05). Tumors in young women were more likely to be bilateral, T2/T3, grade III, ER/PR negative, and lymph-node positive (P < 0.01). Overall, young women (< or =40 years) with breast cancer were more likely to die compared with older women (>40 years) (aHR 1.52, CI 1.37-1.74). Young women (< or =40 years) with breast cancer are diagnosed at a more advanced stage and have tumors with poor prognostic features. Young women (< or =40 years) are 52% more likely to die from breast cancer compared to older women (>40 years).

EphB6 receptor significantly alters invasiveness and other phenotypic characteristics of human breast carcinoma cells

Breast cancer mortality in women is largely attributed to the metastasis of primary breast tumors. We have analysed the function of EphB6, a kinase-deficient receptor, in the invasive phenotype of breast cancer cell lines. We have demonstrated the loss of EphB6 protein in invasive breast carcinoma cell lines and absence of EphB6 transcript in a metastatic breast tumor specimen. The function of EphB6 in invasiveness was confirmed by the ability of EphB6 protein to decrease the in vitro invasiveness of MDA-MB-231, MDA-MB-435 and BT549 cells transfected with an EphB6 expression construct. In MDA-MB-231 cells, the decreased invasiveness appeared to be mediated by decreased transcript levels of matrix metalloproteinase (MMP)7 and MMP19, and increased transcript levels of tissue inhibitors of metalloproteinase 2. In addition to affecting invasiveness phenotype, EphB6 overexpression was also responsible for altering the growth rate and colony-forming efficiency of MCF-7 and MDA-MB-231 cells in a cell-line-specific manner. We suggest that the significant decrease in the invasiveness of MDA-MB-231 and other cell lines transfected with EphB6 is likely occurring by the ability of EphB6 to transduce signals to the nucleus and altering relevant gene expression.

Elevated Breast Cancer Mortality in Women Younger than Age 40 Years Compared with Older Women Is Attributed to Poorer Survival in Early-Stage Disease

We investigated differences in breast cancer mortality between younger (younger than 40 years of age) and older (40 years of age and older) women by stage at diagnosis to identify patient and tumor characteristics accounting for disparities. We conducted a retrospective study of women diagnosed with breast cancer in the 1988 to 2003 Surveillance, Epidemiology, and End Results Program data. Multivariate Cox regression models calculated adjusted hazard ratios (aHR) and 95% confidence intervals to compare overall and stage-specific breast cancer mortality in women younger than 40 years old and women 40 years and older, controlling for potential confounding variables identified in univariate tests. Of 243,012 breast cancer patients, 6.4% were younger than 40 years old, and 93.6% were 40 years of age or older. Compared with older women, younger women were more likely to be African American, single, diagnosed at later stages, and treated by mastectomy. Younger women had tumors that were more likely to be higher grade, larger size, estrogen receptor/progesterone receptor-negative, and lymph-node positive (p < 0.001). Younger women were more likely to die from breast cancer compared with older women (crude HR = 1.39; CI, 1.34 to 1.45). Controlling for confounders, younger women were more likely to die compared with older women if diagnosed with stage I (aHR = 1.44; CI, 1.27 to 1.64) or stage II (aHR = 1.09; CI, 1.03 to 1.15) disease and less likely to die if diagnosed with stage IV disease (aHR = 0.85; CI, 0.76 to 0.95). Higher breast cancer mortality in younger women was attributed to poorer outcomes with early-stage disease. Additional studies should focus on specific tumor biology contributing to the increased mortality of younger women with early-stage breast cancer.

Early onset of breast cancer in British black women

British Journal of Cancer (2008) 98, 2011. doi:10.1038/sj.bjc.6604415 www.bjcancer.comPublished online 10 June 2008& 2008 Cancer Research UKSir,We read with interest the article by Bowen et al (2008) reportingdifferences between age of onset, type of breast cancer and survivalin British black and white women in East London. They reportedthat, compared to white women, black women presented onaverage 21 years younger, that tumours in younger black womenwere more likely to be aggressive and that survival was pooreramong black women despite similar treatment and socioeconomicstatus.However, we were surprised by the authors’ statement that therehave been no previous published data on the patterns of breastcancer in British black women. We recently reported data in thisjournal on mortality from various cancers including breast cancerby country of birth in the United Kingdom (Wild et al, 2006). Weused country of birth in our analysis because death certificates inthe United Kingdom do not specify ethnicity. Although werecognise that country of birth does not necessarily reflectethnicity, it is a reasonable proxy. For example 85% of womenborn in the Caribbean and West Indies identified themselves as‘Black Caribbean’ in the 2001 Census (Office for National Statistics,2001).We reported higher breast cancer mortality, with standardisedmortality ratios (SMR) and 95% confidence intervals (CI) amongwomen born in West Africa of 132 (105–163) and in North Africaof 132 (96–176). This was an unexpected finding not reported inprevious similar analyses of mortality by country of birth and wewere interested to see the potential explanations offered by thefindings of Bowen et al.Secondly, we would like to offer an additional explanation forthe observed age difference at presentation in the British blackwomen. The national Census indicates that the British blackpopulation in the United Kingdom is younger in comparison to thewhite population (Office for National Statistics, 2001). This mayinfluence the mean age at presentation of disease. The authorshave sought to compare the age structure in the two populations;however, because broad age groups (16–59 years and 60 years ormore) were used, important variations in age structure mayremain unnoticed. It is a common mistake to deduce from themean age of presentation that the disease occurs earlier. Estimatesof age-specific rates are essential to assess whether true differencesexist in age at presentation.Finally, in our study (Wild et al, 2006) we did not find asignificant excess of breast cancer mortality for women born in theWest Indies (SMR 92 [80–106]), the majority of whom are likely tobe black. There was a much larger number of breast cancer deaths(208) for women born in the West Indies over the 3-year period ofthe study than the 85 and 43 breast cancer deaths among womenborn in West and North Africa respectively. This suggests thatthere may be heterogeneity of breast cancer risk among Britishblack women. ‘British black’ is likely to be too broad a term for thestudy of ethnic differences and ethnicity should be further definedwhere possible (Agyemang et al, 2005).

Prediagnostic Use of Hormone Therapy and Mortality After Breast Cancer

A few studies have observed reduced breast cancer mortality in women who used hormone therapy before diagnosis. Due to the high prevalence of past and current hormone use, it is important to investigate whether these preparations are related to breast cancer mortality. To evaluate the influence of prediagnostic use of hormone therapy on breast cancer mortality, a prospective cohort of 12,269 women ages 50 years or more diagnosed with incident invasive breast cancer and residents of Wisconsin, Massachusetts, or New Hampshire were enrolled in three phases beginning in 1988. They were followed for death until December 31, 2005, using the National Death Index. Cumulative mortality and multivariable adjusted hazard rate ratios for breast cancer and other mortality causes were calculated for women according to any hormone therapy use, and for exclusive use of estrogen or estrogen-progestin (EP). During an average 10.3 years of follow-up, 1,690 deaths from breast cancer were documented. Cumulative mortality from breast cancer was lower among hormone therapy users, specifically current users at the time of diagnosis, and EP users, compared with nonusers. Adjusted survival varied by type and duration of hormone therapy before diagnosis. A reduced risk of death from breast cancer was associated with EP preparations (hazard rate ratio, 0.73; 0.59-0.91) and with > or =5 years of EP use (0.60; 0.43-0.84). No association was observed for women who were former or current users of E-alone preparations. Although use of combined EP preparations increases breast cancer risk, in this study, use of these hormones before diagnosis was associated with reduced risk of death after a breast cancer diagnosis. The better survival among users, particularly of EP, persisted after adjustment of screening, stage, and measured confounders.