Lung and breast cancer mortality among women in France: Future trends

Estimates of mortality in future years are crucial for communication, prevention and anticipation related to the burden of diseases and for developing scenarios studying the effects of reducing environmental exposure. The aim of this study is to project observed trends of mortality in France for lung and breast cancer among females to 2021. Projections of mortality rates are based on a Bayesian age-period-cohort model and a Poisson distribution. We used cancer mortality data from the French mortality register (period 1977–2006) and population data from population registers (estimated for 1977–2006 and projected for period 2007–2021 using five scenarios: largest, smallest, youngest, older, average population). Alternative models were tested (generalized additive model, negative binomial distribution).For the average population scenario, lung and breast cancer mortality rates age-standardized to the world population, are respectively: 11.5 per 10⁵ women (Credibility interval: 10.3–12.8) and 15.9 (14.4–17.6) in 2007–2011, 14.6 (11.7–18.1) and 14.5 (11.6–18.0) in 2012–2016, 18.2 (12.6–26.0) and 13.3 (9.1–18.9) in 2017–2021.Projections show an ongoing increase for lung cancer and decrease for breast cancer mortality rates, which are expected to be equal in 2012–2016. Compared projections of these two cancers using a similar method had not been done before. Aggressive prevention strategies targeting smoking among women are needed to control this fast growing epidemic of avoidable cancer. Planning of health care capacity for diagnosis and treatment of cancer among females is also necessary.     

Contribution of early detection and adjuvant treatments to breast cancer mortality reduction in Catalonia, Spain

Background

Reductions in breast cancer (BC) mortality in Western countries have been attributed to the use of screening mammography and adjuvant treatments. The goal of this work was to analyze the contributions of both interventions to the decrease in BC mortality between 1975 and 2008 in Catalonia.

Methodology/Principal Findings

A stochastic model was used to quantify the contribution of each intervention. Age standardized BC mortality rates for calendar years 1975–2008 were estimated in four hypothetical scenarios: 1) Only screening, 2) Only adjuvant treatment, 3) Both interventions, and 4) No intervention. For the 30–69 age group, observed Catalan BC mortality rates per 100,000 women-year rose from 29.4 in 1975 to 38.3 in 1993, and afterwards continuously decreased to 23.2 in 2008. If neither of the two interventions had been used, in 2008 the estimated BC mortality would have been 43.5, which, compared to the observed BC mortality rate, indicates a 46.7% reduction. In 2008 the reduction attributable to screening was 20.4%, to adjuvant treatments was 15.8% and to both interventions 34.1%.

Conclusions/Significance

Screening and adjuvant treatments similarly contributed to reducing BC mortality in Catalonia. Mathematical models have been useful to assess the impact of interventions addressed to reduce BC mortality that occurred over nearly the same periods.     

Regional trends in prostate cancer incidence,treatment with curative intent and mortality in Norway 1980–2007

Objectives: To compare the trends in prostate cancer incidence, treatment with curative intent and mortality across regions and counties in Norway, and to consider changes in incidence (an indicator for early diagnosis) and treatment with curative intent as explanatory factors for the decreasing prostate cancer mortality rates. Patients and methods: Prostate cancer incidence and mortality data (1980–2007) alongside treatment data (1987–2005) were obtained from the national, population-based Cancer Registry of Norway. Joinpoint regression models were fitted to age-adjusted incidence, treatment and mortality rates to identify linear changes in the trends. Results: Both age-adjusted incidence rates and rates of curative treatment of prostate cancer increased significantly in all five regions of Norway since the early 1990s. There was a strong positive correlation between increasing incidence and increasing use of curative treatment. The frequency of curative treatment in Western Norway was almost threefold that in the Northern and Central regions around year 2000. Subsequently, the regional trends converged and only minor differences in prostate cancer incidence and use of curative treatment were observed by 2005. The declines in mortality were observed earliest in the regions with the highest incidence and the most frequent use of curative treatment, while the largest decreases in mortality were found in counties where the largest increases in curative treatment were observed. Conclusions: The elucidation of the prostate cancer mortality trends is hindered by an inability to tease out the potential effects of early treatment from the more general impact of improved and more active treatment. However, it is likely that both sets of intervention have contributed to the decline in prostate cancer mortality in Norway since 1996.     

Evaluating genetic association among ovarian, breast, and endometrial cancer: evidence for a breast/ovarian cancer relationship

The possibility of a genetic relationship between ovarian, breast, and endometrial cancer was investigated in data from a large multicenter, population-based, case-control study, the Cancer and Steroid Hormone Study conducted by the Centers for Disease Control (CDC). Age-adjusted relative risks (RRs) for mothers and sisters of 493 ovarian cancer cases, 895 breast cancer cases, and 143 endometrial cancer cases versus 4,754 controls were calculated. Significantly elevated age-adjusted RRs were found for ovarian cancer (RR = 2.8; 95% confidence interval [CI] = 1.6-4.9) and breast cancer (RR = 1.6; 95% CI = 1.1-2.1) among relatives of ovarian cancer probands and for breast cancer (RR = 2.1; 95% CI = 1.7-2.5) and ovarian cancer (RR = 1.7; 95% CI = 1.0-2.0) among relatives of breast cancer probands. Relatives of endometrial cancer probands had an elevated RR for endometrial cancer only (RR = 2.7; 95% CI = 1.6-4.8). The genetic relationship between ovarian, breast, and endometrial cancer was tested using a multivariate polygenic threshold model developed by Smith (1976), which was modified to accommodate three classes of probands. Estimates of heritability for ovarian, breast, and endometrial cancer were 40%, 56%, and 52%, respectively. There was a significant genetic correlation between ovarian and breast cancer (R12 = .484). Evidence for significant genetic overlap between endometrial cancer and either ovarian or breast cancer was not found. These results suggest the existence of a familial breast/ovarian cancer syndrome. Endometrial cancer, while heritable, appears to be genetically unrelated.     

Age-specific mortality rates in reef fishes: Evidence and implications

Abstract Mortality is a fundamental demographic rate, the nature of which has profound consequences for both the dynamics of populations and the life-history evolution of species. For example, if per capita mortality rates are age- or stage-specific, life-history traits should evolve in response to age- and stage-specific differences in selection arising from these temporally variable rates. Similarly, variation in the average mortality rate across ages and/or stages can also select for shifts in life history. Mortality rates of recently settled reef fishes can be very high and per capita mortality is commonly assumed to decrease with increasing age. A review of evidence for age-specific per capita mortality rates in reef fishes from early postsettlement up to 13 months postsettlement suggests that during this period these rates are often age invariant. The data on which these interpretations are based, however, are extremely limited both in terms of the proportion of the life cycle over which mortality rates have been sampled and the quality of these data. Nonetheless, these data do suggest that selective pressures associated with patterns of mortality may vary among species of reef fishes and that these species therefore could be more effectively used in the study of life-history evolution. At present, reef fishes are under-represented in the study of life-history evolution compared with other vertebrate taxa.     

Design of novel tyrosine-nitrogen mustard hybrid molecules active against uterine, ovarian and breast cancer cell lines

L-para-Tyrosine was linked to ortho-hydroxyaniline, meta-hydroxyaniline and para-hydroxyaniline giving three distinct tyrosinamide molecules. The new extended amino acid derivatives were constructed to imitate, in part, the estradiol (E(2), the natural female sex hormone) nucleus. The resulting tyrosinamides were then linked to chlorambucil either directly, or via a 5 and 10 carbon atoms spacer chain. This was done in an attempt to target cancerous cells expressing the estrogen receptor alpha (ERα) and to obtain a more specific chemotherapeutic agent. The tyrosinamide-chlorambucil molecules were designed and synthesized in good yields, according to two different approaches. The novel compounds were evaluated for their anticancer efficacy in hormone-dependent and hormone-independent (ER+; MCF-7 and ER-; MDA-MB-231) breast cancer cell lines. Interestingly, the meta-hydroxyphenyl-tyrosinamide-chlorambucil derivatives were more active than the ortho- and para- analogs. The molecules bearing a 5 carbon atoms spacer were selected for additional biological study using a panel of female cancerous cells; breast (ZR-75-1, MDA-MB-436, MDA-MB-468), ovarian (OVCAR-3, A2780) and uterine (Ishikawa, HEC-1A). It was discovered that for breast cancer cells, the new compounds were up to 4.2 times more active than chlorambucil itself.     

Changes in the fucose content of haptoglobin in breast and ovarian cancer: Association with disease progression

There is increasing evidence for changes in fucosylation in cancer. Previously, we showed that the fucose-specific lectin,Lotus tetragonolobus, extracts an abnormal form of haptoglobin (Hp) from cancer sera. This study investigates the monosaccharide content of Hp obtained from women with ovarian and breast cancer at different stages of their disease. In both cancers, Hp fucose was low when the disease was benign or in remission and much higher when the disease was progressive. This occurred whether the data was expressed per mole of protein or per three mannose residues. Changes in other monosaccharides were minor compared with fucose. There were small increases in theN-acetylglucosamine and galactose content (per three mannoses) in ovarian cancer, suggesting that some glycan chains have increased branching. The latter was independent of disease activity which may be due to some indirect cause such as cytotoxic therapy or an inflammatory response. When ovarian cancer patients were in remission, the number of glycosylation sites on Hp was reduced. Hp isolated from patients with early, but not advanced breast cancer also appeared to have increased glycan branching. The increased fucosylated Hp may interfere with fucose-mediated adhesion reactions of cancer cells.Part of this work was published in abstract form,Glycoconjugate J 1993;10; 318.     

Age-specific mortality and reproduction respond to adult dietary restriction in Drosophila melanogaster

Adult dietary yeast modulates mortality rate and reproduction of the Mediterranean fruit fly, Ceratatis capitata. In the medfly, a sugar-only diet leads to low mortality rates and reduced reproduction; addition of dietary yeast increases both mortality and egg laying. In Drosophila melanogaster low availability of dietary yeast is known to increase life span and reduce the rate of reproduction. Despite these similarities, because of differences in experimental design it remains unclear whether a common physiological mechanism modulates the effect of diet on survival. Here, we investigate how mortality rate and reproduction in D. melanogaster respond to the treatment regime used to study the medfly: no-yeast versus full diet. We find that adult medfly and D. melanogaster have opposite responses to the absence of yeast: D. melanogaster have high mortality when on no-yeast diet; when switched to full diet, D. melanogaster reduce mortality rates to the level presented by females continuously maintained on yeast. This reduction in mortality is accompanied by increased fecundity. These patterns are observed in all tested wildtype stocks, but flies made sterile by mutation in the gene oo18 RNA-binding protein (orb) lack this response. D. melanogaster, unlike medflies, appear to require adult dietary yeast to maintain maximal survival, and the capacity to assimilate yeast for somatic processes is one wildtype function of the gene orb.     

Kallikrein-related peptidases in prostate, breast, and ovarian cancers: from pathobiology to clinical relevance

Tissue kallikrein (KLK1) and kallikrein-related peptidases (KLK2-15) comprise a family of 15 highly conserved secreted serine proteases with similar structural characteristics and a wide spectrum of functional properties. Both gene expression and protein activity of KLKs are rigorously controlled at various levels via diverse mechanisms, including extensive steroid hormone regulation, to exert their broad physiological role. Nevertheless, deregulated expression, secretion, and function of KLK family members has been observed in several pathological conditions and, particularly, in endocrine-related human malignancies, including those of the prostate, breast, and ovary. The cancer-related abnormal activity of KLKs upon substrates such as growth factors, cell adhesion molecules, cell surface receptors, and extracellular matrix proteins facilitate both tumorigenesis and disease progression to the advanced stages. The well-documented relationship between KLK status and the clinical outcome of cancer patients has led to their identification as promising diagnostic, prognostic, and treatment response monitoring biomarkers for these complex disease entities. The main objective of this review is to summarize the existing knowledge concerning the role of KLKs in prostate, breast, and ovarian cancers and to highlight their continually evolving biomarker capabilities that can provide significant benefits for the management of cancer patients.     

National and regional breast cancer incidence and mortality trends in Mexico 2001–2011: Analysis of a population-based database

IntroductionBreast cancer is the most common malignancy in Mexican women since 2006. However, due to a lack of cancer registries, data is scarce. We sought to describe breast cancer trends in Mexico using population-based data from a national database and to analyze geographical and age-related differences in incidence and mortality rates.MethodsAll incident breast cancer cases reported to the National Epidemiological Surveillance System and all breast cancer deaths registered by the National Institute of Statistics and Geography in Mexico from 2001 to 2011 were included. Incidence and mortality rates were calculated for each age group and for 3 geographic regions of the country. Joinpoint regression analysis was performed to examine trends in BC incidence and mortality. We estimated annual percentage change (APC) using weighted least squares log-linear regression.ResultsWe found an increase in the reported national incidence, with an APC of 5.9% (95% CI 4.1–7.7, p < 0.05). Women aged 60–65 had the highest increase in incidence (APC 7.89%; 95% CI 5.5 −10.3, p < 0.05). Reported incidence rates were significantly increased in the Center and in the South of the country, while in the North they remained stable. Mortality rates also showed a significant increase, with an APC of 0.4% (95% CI 0.1–0.7, p < 0.05). Women 85 and older had the highest increase in mortality (APC 2.99%, 95% CI 1.9–4.1; p < 0.05).ConclusionsThe reporting of breast cancer cases in Mexico had a continuous increase, which could reflect population aging, increased availability of screening, an improvement in the number of clinical facilities and better reporting of cases. Although an improvement in the detection of cases is the most likely explanation for our findings, our results point towards an epidemiological transition in Mexico and should help in guiding national policy in developing countries.     

Incidence,mortality and receptor status of breast cancer in African Caribbean women: Data from the cancer registry of Guadeloupe

BackgroundGeographical disparities in breast cancer incidence and outcomes are reported worldwide. Women of African descent show lower incidence, higher mortality rates and earlier age of onset. We analyzed data from the cancer registry of Guadeloupe for the period 2008–2013.MethodsWe describe breast cancer characteristics by molecular subtype, as well as estimated observed and net survival. We used Cox proportional hazard models to determine associations between cancer subtypes and death rate, adjusted for variables of interest.ResultsOverall, 1275 cases were recorded with a mean age at diagnosis of 57(±14) years. World standardized incidence and mortality were respectively 71.9/100,000 and 14.1/100,000 person-years. Age-specific incidence rates were comparable to European and US populations below the age of 45, and higher in Guadeloupean women aged between 45 and 55 years. Overall, 65.1% of patients were hormone receptor (HR)+ and 20.1% were HR-. Triple negative breast cancers (TNBC) accounted for 14% of all cases, and were more frequent in patients under 40 (21.6% vs. 13.4%, p = 0.02). Five-year net survival was 84.9% [81.4-88.6]. It was higher for HR+/Her2+ and HR+/Her2- subtypes, and lower for HR-/Her2+ and TNBC patients.ConclusionWe found high age-specific incidence rates of breast cancer in women aged 45 to 55 years, which warrants further investigation in our population. However, this population of mainly African descent had good overall survival rates, and data according to subtypes are consistent with those reported internationally. These results may suggest that poorer survival in other African descent populations may not be an inherent feature of the disease but may be amenable to improvement.     

Temporal and regional trends of cancer mortality in West Germany

Age-specific and cumulative mortality rates are presented for different cancer sites from 1970 until 1988 for the 11 individual federal states of West Germany (FRG). Sex- and age-specific evaluations are performed and tempora and regional trends in mortality from different cancer sites are revealed. In the FRG there is no comprehensive cancer registry with national coverage for recording cancer patients of all ages (nationwide incidence rates are available only for childhood cancers). Therefore, in view of the lack of a nationwide cancer registry the importance of long-term cancer mortality studies for health policy is emphasized. Methodological aspects of certification regulations and classification of cancer sites are discussed.