Time trends of breast cancer survival in Europe in relation to incidence and mortality

Increasing breast cancer survival, observed in most western countries, is not easily interpreted: it could be due to better treatment, more effective treatment due to earlier diagnosis or simply lead-time bias. Increased diagnostic activity (e.g., screening) can inflate both incidence and survival. To understand interrelations between incidence, mortality and survival trends and their consequences, we analyzed survival trends in relation to mortality and incidence. Starting with observed survival from EUROCARE, mortality from WHO and using the MIAMOD method, we estimated breast cancer incidence trends from 1970 to 2005 in 10 European countries. To smooth out peaks in incidence and survival due to early diagnosis activity, survival trends were assumed similar to those observed by EUROCARE in 1983-1994. The following patterns emerged: (1) increasing survival with increasing incidence and declining or stable mortality (Sweden, Finland); (2) slight survival increase, marked incidence increase and slight mortality decrease (Denmark, the Netherlands and France); (3) increasing survival, marked decrease in mortality and tendency to incidence stabilization (UK); (4) marked survival increase, steady or decreasing mortality and moderate increases in incidence (Spain, Italy); (5) stable survival, increasing incidence and mortality (Estonia). In most countries survival increased, indicating a real advantage for patients when accompanied by decreasing or stable mortality, and attributable to improved cancer care (Sweden, UK, France, Italy and Spain). In Finland (with high survival), the Netherlands and Denmark, increasing mortality and incidence indicate increasing breast cancer risk, probably related to life-style factors. In Estonia, low and stable survival in the context of increasing incidence and mortality suggests inadequate care.     

Cancer incidence,survival and mortality: Explaining the concepts

Cancer incidence, survival and mortality are essential population‐based indicators for public health and cancer control. Confusion and misunderstanding still surround the estimation and interpretation of these indicators. Recurring controversies over the use and misuse of population‐based cancer statistics in health policy suggests the need for further clarification. In our article, we describe the concepts that underlie the measures of incidence, survival and mortality, and illustrate the synergy between these measures of the cancer burden. We demonstrate the relationships between trends in incidence, survival and mortality, using real data for cancers of the lung and breast from England and Sweden. Finally, we discuss the importance of using all three measures in combination when interpreting overall progress in cancer control, and we offer some recommendations for their use.     

Prediagnostic body size and breast cancer survival in the E3N cohort study

Obesity has been associated with poor breast cancer prognosis, however most studies have focused on body mass index (BMI) and few have considered the distribution of adipose tissue. We investigated associations between prediagnostic adiposity and breast cancer survival, considering BMI, waist and hip circumferences (WC and HC), and waist‐to‐hip ratio (WHR). Analyses included 3,006 women from the French E3N prospective cohort study diagnosed with primary invasive breast cancer between 1995 and 2008. We investigated overall, breast cancer‐specific, and disease‐free survival, overall and according to stage, menopausal and hormonal status and year of diagnosis, using Cox proportional hazard models adjusted for tumor characteristics and lifestyle risk factors. Women with a prediagnostic HC > 100 cm were at increased risk of death from all causes (hazard ratio (HR)_{>100vs < 95 cm} = 1.38, 95% Confidence Interval (CI) = 1.02–1.86, P_trend = 0.02) and from breast cancer (HR_{>100vs < 95 cm} = 1.50, CI = 1.03–2.17, P_trend = 0.03), and of second invasive cancer event (HR_{>100vs < 95 cm} = 1.36, CI = 1.11–1.67, P_trend = 0.002), compared to those with HC <95 cm. Associations were stronger after adjustment for BMI. BMI, WC and WHR were not associated with survival after breast cancer. Our study underlines the importance of going beyond BMI when studying the association between adiposity and breast cancer survival. Further studies should be conducted to confirm our results on hip circumference.     

Incidence,mortality, survival,and disease burden of breast cancer in China compared to other developed countries

Breast cancer was the most diagnosed malignant neoplasm and the second leading cause of cancer mortality among Chinese females in 2020. Increased risk factors and widespread adoption of westernized lifestyles have resulted in an upward trend in the occurrence of breast cancer. Up to date knowledge on the incidence, mortality, survival, and burden of breast cancer is essential for optimized cancer prevention and control. To better understand the status of breast cancer in China, this narrative literature review collected data from multiple sources, including studies obtained from the PubMed database and text references, national annual cancer report, government cancer database, Global Cancer Statistics 2020, and Global Burden of Disease study (2019). This review provides an overview of the incidence, mortality, and survival rates of breast cancer, as well as a summary of disability-adjusted life years associated with breast cancer in China from 1990 to 2019, with comparisons to Japan, South Korea, Australia and the United States.     

Diet and risk for breast cancer recurrence and survival

Dietary factors may influence the risk for breast cancer and also the prognosis following diagnosis and treatment. The aim of this study was to assess whether self-reported prediagnosis diet or other patient factors associated with breast cancer incidence were predictive of recurrence and survival. Patients (n=149) diagnosed with primary breast cancer between 1989 and 1991 were followed for five or more years. Total energy (hazard ratio (HR)=1.58, 95%, confidence interval (CI)= 1.05, 2.38) as well as total (HR = 1.46, 95% CI = 1.05, 2.01), saturated (HR = 1.79,95% CI = 1.05, 3.04), and monounsaturated (HR = 1.65, 95% CI = 1.09,2.49) fat intakes were associated with increased risk, and energy-adjusted bread and cereal consumption (HR = 0.55, 95% CI = 0.33, 0.93) with decreased risk of recurrence. Both total energy (HR = 1.58, 95% CI = 1.03, 2.43) and polyunsaturated fat (HR = 1.84, 95% CI = 1.09, 3.13) intakes were associated with an increased risk of death. All associations between dietary fat and recurrence and survival attenuated following energy adjustment. Oral contraceptive use (HR = 1.28, 95% CI = 1.03, 1.60), lymph node positive status (HR = 2.36, 95% CI = 1.01, 5.49), and tumor stage (HR = 2.22, 95% CI = 1.02, 4.81) were associated with increased risk of recurrence. Tumor stage (HR = 4.96, 95% CI = 1.86, 13.23), lymph node positive status (HR = 3.31, 95% CI = 1.38, 7.95, and estrogen receptor negative status (HR = 2.46, 95% CI = 1.02, 5.94) were associated with increased risk, and arm muscle circumference (HR = 0.27, 95% CI = 0.09, 0.86) and mammographic utilization (HR = 0.77, 95% CI = 0.61, 0.98) with decreased risk of death. Higher levels of energy, fat intakes, and selected patient characteristics (particularly disease stage and anthropometric indicators of adiposity) appear to increase risk of recurrence and/or shortened survival following the diagnosis of breast cancer.     

Severe obesity prior to diagnosis limits survival in colorectal cancer patients evaluated at a large cancer centre

Background:

In contrast to the consistent evidence for obesity and colorectal cancer (CRC) risk, the impact of obesity in CRC patients is less clear. In a well-characterised cohort of CRC patients, we prospectively evaluated class I and class II obesity with survival outcomes.

Methods:

The CRC patients (N=634) were followed from the date of diagnosis until disease progression/first recurrence (progression-free survival (PFS)) or death (overall survival (OS)). Body mass index (BMI) was calculated from reported usual weight prior to diagnosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in models adjusted for clinicopathologic, treatment, and lifestyle factors.

Results:

Over a median follow-up of 4 years, 208 (33%) patients died and 235 (37%) recurred or progressed. Class II obesity, as compared with either overweight or normal weight, was associated with an increased risk of death (HR and 95% CI: 1.55 (0.97–2.48) and 1.65 (1.02–2.68), respectively), but no clear association was observed with PFS. In analyses restricted to patients who presented as stages I–III, who reported stable weight, or who were aged <50 years, obesity was associated with a significant two- to five-fold increased risk of death.

Conclusions:

In CRC patients evaluated at a large cancer centre, severely obese patients experienced worse survival outcomes independent of many other factors.     

Colorectal cancer survival in the Nordic countries and the United Kingdom: excess mortality risk analysis of 5 year relative period survival in the period 1999 to 2000

A deficit in colorectal cancer survival in Denmark and in the UK compared to Sweden, Norway and Finland was found in the EUROCARE studies. We set out to explore if these differences still exist. Patients diagnosed with colorectal cancer as their first invasive cancer at age 15-89 in the period 1994-2000 were identified using data from 11 cancer registries in the UK and from four Nordic countries. Five-year relative period survival using deaths in 1999-2000 following cancers diagnosed in 1994-2000 was analysed with excess mortality risk modelling. Follow-up time since diagnosis with age as an effect-modifier in the first half year was the most important factor with the highest excess risk of death immediately after diagnosis and with higher age and decreasing with length of follow-up. Variations between countries were bigger in the first half year following diagnosis than in the interval 0.5-5 years with about 30% higher risk in UK and Denmark. The differences between countries are still substantial and the order has not changed, even if the five year relative survival has improved since the EUROCARE studies. Patient management, diagnostics, and comorbidity likely explain the excess deaths in UK and Denmark during the first 6 months. The effect of stage and quality of management and treatment should be examined in population based studies with detailed patient information. Use of more detailed age-intervals than conventionally applied in survival studies proved to be important in statistical modelling and is recommended for future studies.     

Selection bias influences reported contralateral breast cancer incidence and survival in high risk non-BRCA1/2 patients

Summary Purpose The results of studies comparing survival in familial and sporadic breast cancer (BC) are inconsistent. A higher incidence of contralateral breast cancer (CBC) has been reported in familial BC. Ascertainment bias may influence both the reported familial CBC and survival. Design We assessed CBC incidence, distant disease free (DDFS) and overall survival (OS) in 327 BC patients who had ≥3 breast and/or ovarian cancers in the family but no BRCA1/2 gene mutation (non-BRCA1/2). They were matched to 327 sporadic controls for year and age at detection. To correct for ascertainment bias, we analyzed also separately the results (1) Of the 250 non-BRCA1/2 patients with DNA testing performed before diagnosis or within 2 years (‘unselected’) and (2) Of the 77 with testing ≥2 years after diagnosis (late-tested). Results Median follow-up of non-BRCA1/2 patients was 6.1 yrs. Ten years CBC incidence was 11% in non-BRCA1/2 versus 6% in sporadic patients (p=0.002). At multivariate analysis CBC incidence was increased in late-tested non-BRCA1/2 (HR 4.6; p=0.001) not in ‘unselected’ (HR 1.8; p=0.1). Increased CBC occurred in non-BRCA1/2 patients mainly before genetic testing, suggesting ascertainment bias. Tumors were ≤T1 in 62% of non-BRCA1/2 versus 50% of sporadic patients (p=0.003), node-negative in 55% versus 52% respectively (p=0.5). After correction for stage and therapy, OS did not differ between ‘unselected’ non-BRCA1/2 and sporadic patients (HR 0.8; p=0.3), but was improved in late-tested non-BRCA1/2. Conclusion Overall survival and contralateral breast cancer incidence were similar in ‘unselected’ non-BRCA1/2− and sporadic patients. Reports of higher CBC incidence and better survival in non-BRCA1/2 patients may substantially be caused by DNA testing selection-bias.     

Physical activity and sedentary behavior in relation to lung cancer incidence and mortality in older women: The Women's Health Initiative

Physical activity has been associated with lower lung cancer incidence and mortality in several populations. We investigated these relationships in the Women's Health Initiative Observational Study (WHI‐OS) and Clinical Trial (WHI‐CT) prospective cohort of postmenopausal women. The WHI study enrolled 161,808 women aged 50–79 years between 1993 and 1998 at 40 U.S. clinical centers; 129,401 were eligible for these analyses. Cox proportional hazards models were used to assess the association of baseline physical activity levels [metabolic equivalent (MET)‐min/week: none <100 (reference), low 100 to <500, medium 500 to <1,200, high 1,200+] and sedentary behavior with total lung cancer incidence and mortality. Over 11.8 mean follow‐up years, 2,148 incident lung cancer cases and 1,365 lung cancer deaths were identified. Compared with no activity, higher physical activity levels at study entry were associated with lower lung cancer incidence [p = 0.009; hazard ratios (95% confidence intervals) for each physical activity category: low, HR: 0.86 (0.76–0.96); medium, HR: 0.82 (0.73–0.93); and high, HR: 0.90 (0.79–1.03)], and mortality [p < 0.0001; low, HR: 0.80 (0.69–0.92); medium, HR: 0.68 (0.59–0.80); and high, HR: 0.78 (0.66–0.93)]. Body mass index (BMI) modified the association with lung cancer incidence (p = 0.01), with a stronger association in women with BMI < 30 kg/m². Significant associations with sedentary behavior were not observed. In analyses by lung cancer subtype, higher total physical activity levels were associated with lower lung cancer mortality for both overall NSCLC and adenocarcinoma. In conclusion, physical activity may be protective for lung cancer incidence and mortality in postmenopausal women, particularly in non‐obese women.     

Statin use and breast cancer survival and risk: a systematic review and meta-analysis

The purpose of this study is to determine the associations between statin use and breast cancer survival and risk by performing a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science up to August 2015 for identifying relevant prospective or case-control studies, or randomized clinical trials. Five prospective studies involving 60,911 patients reported the association between statin use and breast cancer mortality. Eleven prospective studies, 12 case-control studies and 9 randomized clinical trials involving 83,919 patients reported the association between statin use and breast cancer risk. After pooling estimates from all available studies, there was a significantly negative association between pre-diagnosis statin use and breast cancer mortality (for overall survival (OS): hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.54–0.84; for disease specific survival (DSS): HR = 0.72, 95% CI 0.53–0.99). There was also a significant inverse association between post-diagnosis statin use and breast cancer DSS (HR = 0.65, 95% CI 0.43–0.98), although the association with breast cancer OS did not reach statistical significance (HR = 0.71, 95% CI 0.48–1.07). Additionally, there was a non-linear relationship for the duration of post-diagnosis statin use with breast cancer specific mortality. On the other hand, with regards to the relationship between statin use and breast cancer risk, no significant association was detected. Our analyses suggest that although statin use may not influence breast cancer risk, the use of statin may be associated with decrease mortality of breast cancer patients. Further large-scale studies are warranted to validate our findings.     

Obesity,body size,and risk of postmenopausal breast cancer: the Women's Health Initiative (United States)

OBJECTIVE: Body size is an important modifiable risk factor for breast cancer. Although obesity has generally been found to be associated with increased risk for postmenopausal breast cancer, there remain questions concerning the role of body fat distribution, lifetime weight history, and effects within specific subgroups of women.METHODS: We assessed the relationship of several anthropometric measures and risk of postmenopausal breast cancer in 85,917 women aged 50–79 at entry in the Women's Health Initiative Observational Study. Women were enrolled during 1993–1998 at 40 clinics in the US and 1030 developed invasive breast cancer by April 2000. Upon entry, trained clinical center staff measured each woman's height, weight, and waist and hip circumference.RESULTS: Anthropometric factors were not associated with breast cancer among women who had ever used hormone replacement therapy (HRT). Among HRT non-users, heavier women (baseline body mass index (BMI) > 31.1) had an elevated risk of postmenopausal breast cancer (relative risk (RR) = 2.52; 95% confidence interval (CI) = 1.62–3.93), compared to slimmer women (baseline BMI 22.6). The elevation in risk associated with increasing BMI appeared to be most pronounced among younger postmenopausal women. Change in BMI since age 18, maximum BMI, and weight were also associated with breast cancer in HRT non-users. While both waist and hip circumference were associated with breast cancer risk, their ratio, a measure of fat distribution, was not (RR = 1.33; 95% CI = 0.88–2.01).CONCLUSIONS: Our study confirms previously reported findings that generalized obesity is an important risk factor for postmenopausal breast cancer, but only among women who have never taken HRT. Lifetime weight gain is also a strong predictor of breast cancer. Waist to hip ratio, a measure of weight distribution, does not appear to be related to postmenopausal breast cancer risk.     

Impressive time-related influence of the Dutch screening programme on breast cancer incidence and mortality, 1975-2006

The aim of this study was to assess changes in the trends in breast cancer mortality and incidence from 1975 to 2006 among Dutch women, in relation to the implementation of the national breast cancer screening programme. Screening started in 1989 for women aged 50-69 and was extended to women aged 70-75 years in 1998 (attendance rate approximately >80%). A joinpoint Poisson regression analysis was used to identify significant changes in rates over time. Breast cancer mortality rates increased until 1994 (age group 35-84), but thereafter showed a marked decline of 2.3-2.8% per annum for the age groups 55-64 and 65-74 years, respectively. For the age group of 75-84 years, a decrease started in the year 2001. In women aged 45-54, an early decline in breast cancer mortality rates was noted (1971-1980), which is ongoing from 1992. For all ages, breast cancer incidence rates showed an increase between 1989 and 1993, mainly caused by the age group 50-69, and thereafter, a moderate increase caused by age group 70-74 years. This increase can partly be explained by the introduction of screening. The results indicate an impressive decrease in breast cancer mortality in the age group invited for breast cancer screening, starting to show quite soon after implementation.     

Breast cancer incidence and prevalence estimated from survival and mortality

Survival probability for female breast cancer patients was used to estimate incidence rates from breast cancer mortality data in Italy. The female breast cancer survival curve from the Lombardy Cancer Registry (LCR) was used to test the method on data from four local cancer registries, covering areas in different regions of Italy. In spite of the well known geographic variability of female breast cancer incidence and mortality, the results support the idea that survival probability does not change across the country and that the survival probability from the LCR is a good estimate of that in the country as a whole. Female breast cancer incidence and prevalence rates were then estimated for Italy, making use of a mathematical model specifically developed for chronic diseases. In 1985, crude incidence and prevalence rates of female breast cancer, for ages up to 74 years, were estimated as 71 and 701 per 100,000 women, respectively. Estimated incidence rates show a complex trend with age, increasing to a temporary pronounced peak at the age of 52. A marked cohort effect was found to increase significantly the risk of the disease from the 1886 to the 1930 birth cohorts by a factor of 2.9. After the 1930 cohort, risks have continued at a constant high level.Drs Capocaccia and Verdecchia are with the Department of Epidemiology and Biostatistics, Istituto Superiore di Sanità, Rome, Italy. Drs Micheli, Sant, Gatta, and Berrino are with the Lombardy Cancer Registry, Istituto Nazionale dei Tumori, Milan, Italy. Reprint requests should be addressed to Dr Capocaccia at Viale Regina Elena 299, Rome, Italy.     

Evidence for an age-related influence of microsatellite instability on colorectal cancer survival

It is well established that microsatellite instability (MSI), the hallmark of defective DNA mismatch repair (MMR), is associated with prolonged survival in colorectal cancer compared with tumours that are microsatellite stable (MSS). MSI in sporadic colorectal tumours is primarily due to epigenetic silencing of MLH1. However, there are no prospective population-based studies of survival in patients with germline MMR gene mutations who develop cancer. Although MSI is almost universal in tumours from HNPCC family members, there is a potential confounding effect of ascertainment and other biases that could explain the apparent survival benefit in HNPCC families. Resolving whether germline MMR gene mutations impact on survival is important because it potentially undermines the rationale for surveillance of mutation carriers. Here, we report an investigation of the influence of MSI on survival in cohorts of cancer patients (aged < 30 years at diagnosis, n = 118; non-age-selected, n = 181) in the context of clinicopathologic variables. There was a substantial age-related influence of tumour MSI status on survival. In young patients with tumour MSI, 65% of patients with MSI tumours had germline MSH2 or MLH1 mutations. Clinicopathologic variables and tumour MSI of the cohort were studied with respect to survival and compared with control groups. Young patients had excess MSI tumours (p < 0.000001), mucinous tumours (p < 0.01), advanced disease (p approximately 0.001) and poorer 5-year survival compared with older cases. Cox proportional hazard analysis identified Dukes' stage, age at diagnosis and calendar year of treatment as independent predictors of survival. There was no detectable association between tumour MSI and survival in young patients, although we confirmed previous observations that MSI is associated with better prognosis in later onset cohorts. These findings underscore the rationale for surveillance and early identification of tumours in MMR gene carriers as well as refining understanding of the influence of MSI on cancer progression.