Decrease In Breast Cancer Mortality Research Articles

What are the risks and benefits of doing mammograms in women ages 40–49 at average risk of breast cancer?

Evidence-Based Answer Mammographic screening for women 40–49 years of age at average risk of breast cancer yields a 7%-23% absolute decrease in breast cancer mortality compared with a 22% reduction in women older than 50, but its use should be balanced with the increased risk of false-positive results (20%-61%) and overdiagnosis (19% over 10 years) associated with early screening (SOR: A, based on systematic reviews of RCTs with consistent findings).

Non-normal Screening Mammography Results, Lumpectomies, and Breast Cancer Reported by California Women, 2001–2009

BackgroundAlthough screening mammography may contribute to decreases in breast cancer mortality in a population, it may also increase the risk of false positives, anxiety, and unnecessary and costly medical procedures in individuals. We report trends in self-reported non-normal screening mammography results, lumpectomies, and breast cancer in a representative sample of California women. MethodsData were obtained from the 2001, 2005, and 2009 cross-sectional California Health Interview Surveys (CHIS) and weighted to the California population. CHIS employed a multistage sampling design to administer telephone surveys in 6 languages. Our study sample was restricted to women 40 years and older who reported a screening mammogram in the past 2 years. Sample sizes were 13,974 in 2001, 12,069 in 2005, and 15,552 in 2009. Women reporting non-normal results were asked whether they had an operation to remove the lump and, if so, whether the lump was confirmed as malignant. FindingsBetween 2001 and 2009, the percent of California women who reported having been diagnosed with breast cancer was relatively stable. For each of the three age groups studied, the percentage of non-normal mammography results increased and the percentages of lumpectomies decreased and, for every woman reporting a diagnosis of breast cancer, three women reported a lumpectomy that turned out not to be cancer. This ratio was greater for younger women and less for older women. ConclusionsDespite relatively constant rates of breast cancer diagnosis from 2001 to 2009, the percentage of non-normal mammography results increased and lumpectomies declined.

Abstract P6-10-04: Statins and breast cancer stage and mortality in the Women's Health Initiative cohort

Abstract Background: Statins are the most widely prescribed cholesterol-lowering drugs in the United States, with approximately 25% of US adults using statins by 2008. The anti-carcinogenic effect of statins may reduce the metastatic potential of cancer cells leading to ‘stage migration’ with statin users more likely diagnosed with early rather than late stage cancer. We evaluated the effects of statins on breast cancer stage migration and breast cancer-specific mortality in the Women’s Health Initiative (WHI) Clinical Trial and Observational Study. Methods: The study population included 128,675 postmenopausal women aged 50 to 79 years, with 7,883 newly-diagnosed pathologically-confirmed cases of in situ (19%), local stage (61%), regional stage (19%) and distant stage (1%) breast cancer and 401 deaths due to breast cancer after an average of 11.5 (SD=3.7) years of follow-up. To reduce the possibility of detection bias, we excluded women who did not report a mammogram within 5 years of study entry, and who had no health insurance or medical care provider (n=28,237). Stage was coded using criteria implemented in the Surveillance, Epidemiology and End Results Program and stratified into early stage (in situ and local) vs. late stage (regional and distant). Information on statin use prior to breast cancer diagnosis was collected at baseline and years one, three, six, and nine years post-baseline. Self- and interviewer-administered questionnaires were used to collect risk factor information. Cause of death was based on medical record review by physician adjudicators. Cox proportional hazards regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) to evaluate the relationship between statin use as a time-dependent exposure and diagnosis of late stage breast cancer and breast cancer-specific mortality adjusting for important confounders. For these models, participants who had early stage breast cancer or who died during follow-up were censored at time of diagnosis or death, respectively. We also evaluated the effect of statins stratified by estrogen receptor (ER) status. Statistical tests were two-sided. Results: Statins were used by 10,474 women (8%) at baseline. In the multivariable-adjusted time-dependent model, statin use was associated with a marginal reduction in risk of late stage breast cancer (HR 0.84, 95% CI: 0.70-1.02, p=0.082) and a reduction in risk of late stage estrogen receptor positive breast cancer (HR 0.79, 95% CI: 0.63-0.99, p=0.044). Statin use was also associated with a marginal reduction in breast cancer-specific mortality although it did not reach statistical significance (HR 0.59, 95% CI: 0.32-1.06, p=0.075). Conclusions: In the WHI, statin use was associated with a modest reduction in risk of late stage estrogen positive breast cancer and a non-significant decrease in breast cancer mortality. We are currently performing sensitivity analyses on these models. Studies using other large data sets with longer follow-up and information on cancer-directed therapy are needed to further evaluate this possible association. Citation Format: Monica P Arun, Pinkal Desai, Amy Lehman, Marilyn L Kwan, JoAnn E Manson, Sayeh Lavasani, Sylvia Wasswertheil-Smoller, Gloria E Sarto, Meryl S LeBoff, Jane Cauley, Michele L Cote, Jennifer Beebe-Dimmer, Allison Jay, Rowan T Chlebowski, Michael S Simon. Statins and breast cancer stage and mortality in the Women's Health Initiative cohort [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-10-04.

Abstract P1-11-06: Mammograms on-the-go: Predictors of repeat visits to mobile mammography vans in St. Louis, Missouri

Abstract Background: Among women, breast cancer is the most common noncutaneous cancer and second most common cancerous cause of death. The American Cancer Society recommends that all healthy women over age 40 have a mammogram annually because early detection and treatment of tumors has been associated with a 15% decrease in breast cancer mortality. African American women have higher mortality rates than white women and, in general, uninsured women have low rates of screening. To increase screening rates, mobile mammography has been implemented in many cities. Previous studies have investigated women’s self-reported adherence to screening guidelines at the time of participation in mobile mammography, but no study has examined if women use it as an annual screening tool. Objective: The purpose of this study was to determine if women are using mobile mammography vans as their established source of medical care for breast cancer screening and the factors that predict repeat visits to these vans. Methods: A prospective cohort study was conducted from 2006 to 2013 in which 8450 women who received a mammogram as part of Siteman Cancer Center’s Breast Health Outreach Program responded to surveys and provided access to their clinical records. Only visits on the mammography van were included. The predictor variables explored in this study were: urban status, insurance coverage, age group, race, marital status, mammography experience at baseline visit, employment status, and year of screening. Data were analyzed using chi-square tests, logistic regression, and negative binomial regression. Results: Among the study participants, 25.3% (N=2134) had multiple visits to the mobile mammography van. Of these women, 57.2% had good mammography experiences at baseline, 48.2% were from urban settings, 70.6% were uninsured, 51.2% were ages 50-65, 69.7% were Black, 76.4% were not currently married, and 63.3% were unemployed. Women who were ages 50-65, uninsured, or Black had a higher odds of a repeat visit to the mobile mammography van compared to women who were ages 40-50, insured, or White (OR=1.135, 95% CI: 1.013-1.271; OR=1.302, 95% CI: 1.146-1.479; OR=1.281, 95% CI: 1.125-1.457), respectively. However, the odds of having a repeat visit to the van was lower among women who reported a rural zip code or were unemployed compared to women who provided a suburban zip code or were employed (OR=.503, 95% CI: .411-.616; OR=.868, 95% CI: .774-.972), respectively. Conclusion: This study has identified key characteristics of women who are either more or less likely to use mobile mammography vans as their primary source of medical care for breast cancer screening and have repeat visits. It is important that mobile mammography is maintained and remains easily accessible to women who continuously use the service. Further research should be done to discover ways to make mobile mammography a more effective resource for those more likely to use it for routine screening. Citation Format: Bettina F Drake, Salmafatima S Abadin, Sarah Lyons, Su-Hsin Chang, Lauren T Steward, Susan Kraenzle, Melody S Goodman. Mammograms on-the-go: Predictors of repeat visits to mobile mammography vans in St. Louis, Missouri [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-11-06.

Abstract OT1-1-08: Master regulator (MR)-directed therapy in residual breast cancer patient derived xenografts (PDXs)

Abstract Background: Neoadjuvant chemotherapy (NACT) is standard of care in operable breast cancer (BC). There are no therapies that have demonstrated benefit in patients who failed to achieve a pathologic complete response (pCR). There remains an unmet need to identify appropriate targets in which to direct therapy in this high-risk population to decrease BC mortality. Computational approaches to reverse engineering of cell signaling networks from patient tumor-specific RNA expression data can identify key molecular dependencies that result in the malignant phenotype, i.e. MRs. These approaches out-perform traditional methods, such as identifying mutated or over-expressed genes, in determining true tumor dependencies. Successful targeting of MRs may be a means for rational selection of targeted drugs in the operable BC setting. Trial Design: A single center pilot study that will accrue 35 subjects with BC who will have received standard NACT and at least 1.5 cm of residual disease. At the time of definitive surgery, resected tissue will be assessed for residual disease and then allocated. After reserving required tissue for pathologic diagnosis, 0.5 cm3 will be procured for xenografting and 0.5 cm3 will be flash frozen for RNA extraction. Tissue for xenografting is immediately sent to a Champions Oncology site for implantation. We will use fresh frozen tissue to perform RNA-seq. Previously validated computational algorithms at our center, including MARINa and VIPER, will be used to interrogate the expression data and identify the top MRs in individual tumors. Upon maturation of a Champions Oncology Tumor Graft model, the second generation expansion group will be divided into four cohorts. We plan to test two drugs that target tumor-specific MRs, one vehicle control, and one negative control (paclitaxel, as these tumors have demonstrated paclitaxel resistance) in each model. Eligibility Criteria 1. Patients ≥18 years with newly diagnosed BC, deemed candidates for definitive surgery. 2. Subjects must have received standard NACT with taxane (paclitaxel or docetaxel; herceptin +/- pertuzumab if HER2+) and/or adriamycin/cytoxan. 3. Clinical or radiographic evidence of ≥1.5 cm of residual BC. 4. ECOG PS ≤2 Specific Aims: 1) To computationally infer MRs in individual patient tumors resistant to NACT 2) To determine if targeting MRs results in superior tumor growth inhibition in PDX models Statistical Methods: In the PDX model, pre- and post-treatment tumor volume (TV) is calculated: TV= width2 x length x 0.52, and is standardized as a tumor growth inhibition (TGI) percentage compared to the vehicle control. Since we anticipate the MR-directed arms will demonstrate a TGI (80%) twice that of the paclitaxel arm (40%), we have 80% power to detect a difference in 18 patients (one-sided alpha, 0.05). We assume a xenograft take-rate of 50% in the post-NACT setting and thus aim for an N of 35. Final data analysis will be adjusted using ANOVA. Present and Target Accrual: 35 patients, projected to accrue in 18-24 months. Estimate based on number of locally advanced BC patients seen, competing studies, and likelihood of participation. The study will open in Fall 2014. Citation Format: Kevin Kalinsky, Prabhjot Mundi, Dawn L Hershman, Eileen Connolly, Katherine D Crew, Hanina Hibshoosh, Andrea Calfiano, Matthew Maurer. Master regulator (MR)-directed therapy in residual breast cancer patient derived xenografts (PDXs) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-1-08.

Mammography screening in three Finnish residential areas: comprehensive population-based study of breast cancer incidence and incidence-based mortality 1976-2009.

Background:The aim of this study was to evaluate the effectiveness of a large-scale screening programme for breast cancer (BC) in Turku, Finland. Incidence and incidence-based mortality (IBM) figures were compared with the areas applying different screening policies.Methods:Deaths and person-time of women aged 40–84 were assessed for the period 1976–1986 (prescreening era) and the periods 1987–1997 and 1998–2009 (screening periods) using incidence and IBM by age at diagnosis and at death. There was a total of 40.7 million women-years, 83 497 invasive BCs obtained from the Finnish Cancer Registry; 17 508 BC deaths were linked with the data from Statistics Finland.Results:In Turku, a significant (> 20%) reduction in IBM occurred during 1987–2009 among women aged 60–74 years at diagnosis compared with Helsinki (IBMRR: 0.75, 95% CI: 0.57–1.00), and in women aged 75–84 years at death compared with the rest of Finland (IBMRR: 0.72, 95% CI: 0.53–0.96).Conclusions:The wide mammography screening programme in Turku was effective in decreasing BC mortality in the elderly age groups. These results support the implementation of BC screening from age 50 up to 74 years.

The proteasome inhibitor Bortezomib (Velcade) as potential inhibitor of estrogen receptor-positive breast cancer

Around 70% of breast cancers express the estrogen receptor α (ERα) and depend on estrogen for growth, survival and disease progression. The presence of hormone sensitivity is usually associated with a favorable prognosis. Use of adjuvant anti-endocrine therapy has significantly decreased breast cancer mortality in patients with early-stage disease, and anti-endocrine therapy also plays a central role in the treatment of advanced stages. However a subset of hormone receptor-positive breast cancers do not benefit from anti-endocrine therapy, and nearly all hormone receptor-positive metastatic breast cancers ultimately develop resistance to anti-hormonal therapies. Despite new insights into mechanisms of anti-endocrine therapy resistance, e.g., crosstalk between ERα and Her2/neu, the management of advanced hormone-receptor-positive breast cancers that are resistant to anti-endocrine agents remains a significant challenge. In the present study, we demonstrate that the proteasome inhibitor Bortezomib strongly inhibits ERα and HER2/neu expression, increases expression of cyclin-dependent kinase inhibitors, inhibits expression of multiple genes associated with poor prognosis in ERα+ breast cancer patients and induces cell death in ER+ breast cancer cells in both the presence and absence of functional p53. Although Bortezomib increased the levels of p53 and increased the expression of pro-apoptotic target genes in ERα+ breast cancer cells harboring wild-type p53, Bortezomib also exerts anti-tumoral effects on ERα+ breast cancer cells through suppression of ERα expression and inhibition of PI3K/Akt/mammalian target of rapamycin (mTOR) and ERK signaling independently of functional p53. These findings suggest that Bortezomib might have the potential to improve the management of anti-endocrine therapy resistant ERα+ breast cancers independently of their p53 status.

Abstract 3299: Maternal embryonic leucine zipper kinase is critical for the growth and migration of triple negative breast cancer cells

Abstract Background: Breast cancer constitutes 30% of all new cancer cases in women. Despite steady decrease in breast cancer mortality, the lack of therapeutic targets is still a major problem. While the hormone-receptor positive (ER+) and human epidermal growth factor receptor 2-positive (HER2+) breast cancers respond to current targeted therapies, no targeted therapy is available for the treatment of triple negative breast cancer (TNBC), which lacks the expression of ER alpha (ER), progesterone receptor (PR), and HER2-receptor. Hence, there is an urgent need for effective targets against this sub-type of breast cancer. Previous studies in our laboratory used gene expression profiling of human breast cancers to identify kinases overexpressed in ER-negative breast cancers. One of these highly expressed kinases is the maternal embryonic leucine-zipper kinase (MELK). MELK is a serine/threonine protein kinase known to have a role in cell cycle progression, apoptosis and DNA repair. The purpose of this study was to test the hypothesis that MELK is required for the growth and migration of TNBC. Methods: RNA and protein was isolated from a panel of TNBC and ER-positive breast cancer cell lines and MELK expression was quantified by qPCR and immunoblotting. To determine whether MELK regulates cell growth, ER-positive and TNBC cell lines were transfected with siRNA targeting MELK and cell number was measured by manual counting. Anchorage-independent growth was measured using soft agar assays. Effect on migration and invasion was determined using Boyden Chamber assays. Immunostaining with actin-phalloidin was performed on MELK knockdown cells to determine effect of MELK loss on the cytoskeleton. Results: MELK mRNA and protein levels were significantly higher in TNBC cell lines compared to ER-positive breast cancers. Knockdown of MELK suppressed growth (≥50% growth inhibition) in six TNBC cell lines but had no effect on growth of six ER positive cell lines. Colony formation was also greatly reduced in TNBC cell lines but was not affected in ER positive cell lines upon siRNA knockdown of MELK. In addition, knockdown of MELK reduced migration of three TNBC cell lines (MDAMB231, MDAMB468 and Hcc70) but had no effect on the ER-positive cell line (MCF7). Decreased staining of actin filaments was observed in cell lines where migration was reduced upon MELK knockdown suggesting a role of MELK in formation of actin cytoskeleton. Current studies are focused on understanding how MELK regulates the cell growth and migration in TNBC. Conclusions: MELK is an important growth regulator of TNBC, but not of ER positive breast cancers. Our results indicate that MELK promotes cell migration in TNBC cells. These findings suggest that MELK is a promising target for the treatment of TNBC. Supported by a Susan G. Komen for the Cure Promise Grant (KG081694), and the John Charles Cain Award. Citation Format: Nidhi Batra, Corey Speers, Ivan Uray, Abhijit Mazumdar, Anna Tsimelzon, Susan Hilsenbeck, Gordon Mills, Powel Brown. Maternal embryonic leucine zipper kinase is critical for the growth and migration of triple negative breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3299. doi:10.1158/1538-7445.AM2014-3299

Unemployment, public-sector health-care spending and breast cancer mortality in the European Union: 1990-2009.

The global economic crisis has been associated with increased unemployment, reduced health-care spending and adverse health outcomes. Insights into the impact of economic variations on cancer mortality, however, remain limited. We used multivariate regression analysis to assess how changes in unemployment and public-sector expenditure on health care (PSEH) varied with female breast cancer mortality in the 27 European Union member states from 1990 to 2009. We then determined how the association with unemployment was modified by PSEH. Country-specific differences in infrastructure and demographic structure were controlled for, and 1-, 3-, 5- and 10-year lag analyses were conducted. Several robustness checks were also implemented. Unemployment was associated with an increase in breast cancer mortality [P < 0.0001, coefficient (R) = 0.1829, 95% confidence interval (CI) 0.0978-0.2680]. Lag analysis showed a continued increase in breast cancer mortality at 1, 3, 5 and 10 years after unemployment rises (P < 0.05). Controlling for PSEH removed this association (P = 0.063, R = 0.080, 95% CI -0.004 to 0.163). PSEH increases were associated with significant decreases in breast cancer mortality (P < 0.0001, R = -1.28, 95% CI -1.67 to -0.877). The association between unemployment and breast cancer mortality remained in all robustness checks. Rises in unemployment are associated with significant short- and long-term increases in breast cancer mortality, while increases in PSEH are associated with reductions in breast cancer mortality. Initiatives that bolster employment and maintain total health-care expenditure may help minimize increases in breast cancer mortality during economic crises.

Disparities in cervical and breast cancer mortality in Brazil.

OBJECTIVE To analyze cervical and breast cancer mortality in Brazil according to socioeconomic and welfare indicators.METHODS Data on breast and cervical cancer mortality covering a 30-year period (1980-2010) were analyzed. The data were obtained from the National Mortality Database, population data from the Brazilian Institute of Geography and Statistics database, and socioeconomic and welfare information from the Institute of Applied Economic Research. Moving averages were calculated, disaggregated by capital city and municipality. The annual percent change in mortality rates was estimated by segmented linear regression using the joinpoint method. Pearson’s correlation coefficients were conducted between average mortality rate at the end of the three-year period and selected indicators in the state capital and each Brazilian state.RESULTS There was a decline in cervical cancer mortality rates throughout the period studied, except in municipalities outside of the capitals in the North and Northeast. There was a decrease in breast cancer mortality in the capitals from the end of the 1990s onwards. Favorable socioeconomic indicators were inversely correlated with cervical cancer mortality. A strong direct correlation was found with favorable indicators and an inverse correlation with fertility rate and breast cancer mortality in inner cities.CONCLUSIONS There is an ongoing dynamic process of increased risk of cervical and breast cancer and attenuation of mortality because of increased, albeit unequal, access to and provision of screening, diagnosis and treatment.

Highlights from the ninth European breast cancer conference, glasgow, 19-21 march 2014.

The Ninth European Breast Cancer Conference (EBCC-9), one of the largest breast cancer conferences in the world, was held in Glasgow in March 2014, and brought together the voices of doctors, researchers, nurses, and patients. All the major breast cancer advocacy groups and institutions were united in one forum (Europa Donna, the EORTC Breast Cancer group, and EUSOMA).The Scientific Programme for EBCC-9 highlighted a holistic picture of breast cancer, including research, prevention, treatment, advocacy, and care. Participants were able to discover the most up-to-date developments and findings within the field for implementation into daily practice. Improvements in treatment, as well as enhanced access to care, underlie the sustained decreases in breast cancer mortality seen in 30 European countries from 1989 to 2010.

Significantly greater reduction in breast cancer mortality from post‐diagnosis running than walking

The purpose of these analyses is to test prospectively whether post-diagnosis running and walking differ significantly in their association with breast cancer mortality. Cox proportional hazard analyses were used to compare breast cancer mortality to baseline exercise energy expenditure (METs, 1 MET-hour ≅1 km run) in 272 runners and 714 walkers previously diagnosed with breast cancer from the National Runners' and Walkers' Health Studies when adjusted for age, race, menopause, family history, breastfeeding and oral contraceptive use. Diagnosis occurred (mean ± SD) 7.9 ± 7.3 years before baseline. Forty-six women (13 runners and 33 walkers) died from breast cancer during 9.1-year mortality surveillance. For the 986 runners and walkers combined, breast cancer mortality decreased an average of 23.9% MET-hours/day [95% confidence interval (CI): 7.9-38.3%; p = 0.004]. There was a significantly greater decrease in risk for running than walking (risk per MET-hours/day run vs. walked: p = 0.03). For the 272 runners analyzed separately, breast cancer mortality decreased an average of 40.9% per MET-hours/day run (95% CI: 19.3-60.0%, p = 0.0004). When analyzed by categories of running energy expenditure, breast cancer mortality was 87.4% lower for the 1.8-3.6 MET-hours/day category (95% CI: 41.3-98.2% lower, p = 0.008) and 95.4% lower for the ≥3.6 MET-hours/day category (95% CI: 71.9-100% lower, p = 0.0004) compared to the <1.07 MET-hours/day category. In contrast, the 714 walkers showed a nonsignificant 4.6% decrease in breast cancer mortality per MET-hours/day walked (95% CI: 27.3% decreased risk to 21.3% increased risk, p = 0.71). These results suggest that post-diagnosis running is associated with significantly lower breast cancer mortality than post-diagnosis walking.

Breast cancer follow-up strategies in randomized phase III adjuvant clinical trials: a systematic review

The effectiveness of different breast cancer follow-up procedures to decrease breast cancer mortality are still an object of debate, even if intensive follow-up by imaging modalities is not recommended by international guidelines since 1997. We conducted a systematic review of surveillance procedures utilized, in the last ten years, in phase III randomized trials (RCTs) of adjuvant treatments in early stage breast cancer with disease free survival as primary endpoint of the study, in order to verify if a similar variance exists in the scientific world. Follow-up modalities were reported in 66 RCTs, and among them, minimal and intensive approaches were equally represented, each being followed by 33 (50%) trials. The minimal surveillance regimen is preferred by international and North American RCTs (P = 0.001) and by trials involving more than one country (P = 0.004), with no relationship with the number of participating centers (P = 0.173), with pharmaceutical industry sponsorship (P = 0.80) and with trials enrolling > 1000 patients (P = 0.14). At multivariate regression analysis, only geographic location of the trial was predictive for a distinct follow-up methodology (P = 0.008): Western European (P = 0.004) and East Asian studies (P = 0.010) use intensive follow-up procedures with a significantly higher frequency than international RCTs, while no differences have been detected between North American and international RCTs. Stratifying the studies according to the date of beginning of patients enrollment, before or after 1998, in more recent RCTs the minimal approach is more frequently followed by international and North American RCTs (P = 0.01), by trials involving more than one country (P = 0.01) and with more than 50 participating centers (P = 0.02). It would be highly desirable that in the near future breast cancer follow-up procedures will be homogeneous in RCTs and everyday clinical settings.

Long-term surveillance mammography and mortality in older women with a history of early stage invasive breast cancer

Annual surveillance mammograms in older long-term breast cancer survivors are recommended, but this recommendation is based on little evidence and with no guidelines on when to stop. Surveillance mammograms should decrease breast cancer mortality by detecting second breast cancer events at an earlier stage. We examined the association between surveillance mammography beyond 5 years after diagnosis on breast cancer-specific mortality in a cohort of women aged ≥ 65 years diagnosed 1990-1994 with early stage breast cancer. Our cohort included women who survived disease free for ≥ 5 years (N = 1,235) and were followed from year 6 through death, disenrollment, or 15 years after diagnosis. Asymptomatic surveillance mammograms were ascertained through medical record review. We used Cox proportional hazards regression stratified by follow-up year to calculate the association between time-varying surveillance mammography and breast cancer-specific and other-than-breast mortality adjusting for site, stage, primary surgery type, age and time-varying Charlson Comorbidity Index. The majority (85 %) of the 1,235 5-year breast cancer survivors received ≥ 1 surveillance mammogram in years 5-9 (yearly proportions ranged from 48 to 58 %); 82 % of women received ≥ 1 surveillance mammogram in years 10-14. A total of 120 women died of breast cancer and 393 women died from other causes (average follow-up 7.3 years). Multivariable models and lasagna plots suggested a modest reduction in breast cancer-specific mortality with surveillance mammogram receipt in the preceding year (IRR 0.82, 95 % CI 0.56-1.19, p = 0.29); the association with other-cause mortality was 0.95 (95 % CI 0.78-1.17, p = 0.64). Among older breast cancer survivors, surveillance mammography may reduce breast cancer-specific mortality even after 5 years of disease-free survival. Continuing surveillance mammography in older breast cancer survivors likely requires physician-patient discussions similar to those recommended for screening, taking into account comorbid conditions and life-expectancy.

Breast cancer screening: Controversy of impact

Few medical issues have been as controversial—or as political, at least in the United States—as the role of mammographic screening for breast cancer. The advantages of finding a cancer early seem obvious. Indeed, randomized trials evaluating screening mammography demonstrate a reduction in breast cancer mortality, but the benefits are less than one would hope. Moreover, the randomized trials are themselves subject to criticism, including that they are irrelevant in the modern era because most were conducted before chemotherapy and hormonal therapy became widely used.In this article I chronicle the evidence and controversies regarding mammographic screening, including attempts to assess the relative contributions of screening and therapy in the substantial decreases in breast cancer mortality that have been observed in many countries over the last 20–25 years. I emphasize the trade-off between harms and benefits depending on the woman's age and other risk factors. I also discuss ways for communicating the associated risks to women who have to decide whether screening (and what screening strategy) is right for them.

Joinpoint Regression Analysis of Female Breast Cancer Mortality in Serbia 1991–2010

The aim of this descriptive epidemiologic study was to analyze the mortality trends of female breast cancer in Serbia (excluding Kosovo and Metohia) from 1991 to 2010. Average annual percentage of change and the corresponding 95% confidence interval (CI) was computed for trend using linear models assuming a Poisson distribution. The Serbian female population showed an increase in breast cancer mortality continuously from 1991 to 2010 (average annual percentage of change = + 0.9, 95% CI = 0.6–1.1). Breast cancer mortality declined in women aged 30–49 years but increased in women ≥50 years old. Decline in breast cancer mortality in young women was observed during the entire period and was significant in those 35–49 years old. In women 50–54 years old, a significant increase in breast cancer mortality during the period 1991–1997 was followed by significant decrease until 2010. In all older age groups, mortality rates significantly increased during all periods observed. The only exception was among women aged 65–69 years old in whom a small, non-significant decrease in breast cancer mortality was observed in the period 1991–1998, followed by significant increase until 2010. According to a comparability test, breast cancer mortality trends in 30–49, 50–69, and 70+ year age groups differed significantly (p < 0.01).

Breast Intervention: How I Do It

Breast imaging has undergone many changes since the early years of mammography. Screening mammography is credited with contributing to the substantial decrease in breast cancer mortality through early detection. Screening mammography programs allow depiction of nonpalpable, suspicious findings requiring histologic evaluation, but most of which eventually are proved benign. Widespread acceptance of percutaneous breast biopsy techniques represents the most important practice-changing development in breast imaging. The radiologist now plays a vital role not only in the detection and evaluation of breast disease, but also in the diagnosis and management of breast cancer. Descriptions of the advantages of percutaneous breast biopsy and the techniques of performing breast intervention are the focus of this review.

Breast cancer mortality among users of cholesterol-lowering drugs.

1514 Background: Breast cancer is a common malignancy and cause of cancer death. Recent studies have suggested that statins, an established cholesterol-lowering drug group used in the prevention of cardiovascular mortality, could have beneficial effects against recurrence and progression of breast cancer. We evaluated breast cancer-specific mortality among users of statins and other cholesterol-lowering drugs (fibrates and bile-acid binding resins) in a cohort of breast cancer patients. Methods: Our study cohort included all newly diagnosed breast cancer patients in Finland during 1995-2003 (31,236 cases), identified from the Finnish Cancer Registry. Information on cholesterol-lowering medication use was obtained from a national prescription database.We used Cox proportional hazards regression method to estimate mortality among medication users. Results: A total of 4,169 participants had used statins, while 313 had used fibrates or resins. Despite similar median age, tumor and treatment characteristics, only statin use was associated with decreased breast cancer mortality (participants with localized tumors: HR 0.33, 95% CI 0.24-0.42; metastatic tumors: HR 0.52, 95% CI 0.31-0.86). Fibrate and resin use were associated with increased overall mortality (HR 1.70, 95% CI 0.96-2.99 for participants with localized disease, HR 2.65, 95% CI 1.18-5.96 for participants with metastatic disease). Conclusions: Decreased breast cancer mortality among users of statins, but not other cholesterol-lowering drugs despite similar population characteristics suggests that this drug group may have benefit in prevention of cancer progression. Clinical trials testing statins’ efficacy in breast cancer patients are warranted.

Population-based service mammography screening: the Icelandic experience

This study analyzes the efficacy of the Icelandic population-based service mammography screening. Women aged 40-69 were invited for screening at 2-year intervals starting in November 1987. The study evaluates: (A) attendance and other screened performance parameters during 1998-2010; (B) trends in age-standardized and age-specific incidence rates during 1969-2010 and mortality rates during 1969-2010; and (C) distribution of risk factors and disease specific death rates according to mode of detection. (A) In the age group of 40-69, the average 2-year attendance was 62%, recall rate was 4.1%, needle biopsy rate was 1.3%, surgery rate was 0.6%, invasive cancer rate was 0.4%, and ductal carcinoma in situ (DCIS) rate was 0.06%. (B) The linear incidence trend after the start of screening decreased significantly in the age group 40-49, increased significantly in the age group 50-69, but decreased non-significantly in the age group 70-79. The decreased age-specific incidence in the 70-79 age group was, however, greater than the increased age-specific incidence at the ages 50-69. The mortality rate decreased 41% for all age groups and the linear mortality trend decreased significantly at ages 40-49, 50-69, and 70-79. In the age group 40-74 years, the age-specific mortality decreased by 6.9 cases per 2000 during a 10-year period. (C) Screen-detected women had significantly smaller tumors, more favorable tumor grade, fewer axillary metastases and, after correction for other risk factors, the likelihood of dying from cancer decreased 54% (hazard ratio: 0.46; 95% confidence interval: 0.31-0.69) for these patients compared to cases of nonparticipators. The study results confirm acceptable rates of recalls and referrals for further diagnosis and treatment, and significantly decreased breast cancer mortality rate after starting screening.

Linking of Environmental and Health Indicators by Neural Networks: Case of Breast Cancer Mortality, Slovak Republic

This study deals with the analysis of relationship between 67 environmental indicators in geological environment and breast cancer mortality in Slovakia. Primary data comprises a database of 67 environmental indicators for groundwater and soils as a mean value for every Slovak municipality and the data on relative mortality from breast cancer for Slovak municipalities (about 2900) collected for the period of 22 years. The training neural network was used as a mathematical model for data analysis. The top 200 networks have identified 12 environmental indicators (8 for soils: pHKCl, carbonates, Ca, Mg, Na, Co, Sr and 4 for groundwater: Ba, SiO2, Zn, Fe) with high rate of influence. As the most influential environmental indicator was identified pHKCl in soil that should be within the range of acids, definitely under the neutral point. Most of environmental indicators were unambiguously identified as negative (Mg, Ca, Sr, carbonates, Ba, SiO2, Zn and Fe). These indicators should be at the lowest level of their concentration in related geological component. Three environmental indicators, Ce, Na and Co had parabolic function where certain essential concentration levels of these elements are presumed with protective effect on human health. For all influential indicators limit values with respect to the lowest mortality were proposed. The verification of achieved results was performed through regressive model of breast cancer mortality for 12 calculated influential environmental indicators for all municipalities in the Slovak Republic. The revealed difference between real mortality levels and the model values was found for 6 environmental indicators (pHKCl, Mg, Ca, Sr, Ba, Zn). Each executed limit has decreased breast cancer mortality for about 0.79 cases per 100,000 inhabitants.