HER2-positivity rates in breast cancer: no variation over time when clinicopathological features and testing are stable.

HER2 status is essential for breast cancer subtyping and for systemic treatment decisions as patients with HER2-positive tumours can benefit from anti-HER2 targeted therapies. However, few data are available on the current HER2-positive breast cancers rate and its evolution across years. Using data from the Côte d'Or breast cancer registry, we identified, between 1998 and 2011, 3220 women with invasive breast cancer diagnosed in the same laboratory which carries out regular internal quality controls and participates in multiannual international quality control programmes. Throughout the studied period of time, despite an increase of annual breast cancer cases, HER2 positivity rate remained stable (13.1%; P = 0.495), as did the proportion of tumours with positive hormone receptor status (P = 0.467) and the proportion of SBR grade II/III tumours (P = 0.747). Other characteristics, less strongly associated with HER2-positive status, showed either no annual variation (nodal and metastatic status, tumour size) or an annual positive trend (mean age, lobular carcinomas) or an annual negative trend (ductal carcinomas). These data reveal that in a population with stable clinical and pathological characteristics, and with the use of standardised assays, HER2 positivity rate remains stable over time. These results also emphasise that current HER2 positivity rate is lower than initially reported.

Stage IV breast cancer: a population-based study about prognostic factors according to HER2 and HR status.

We aim to describe trends in net survival (NS) and to assess the prognostic factors among women with de novo metastatic breast cancer (MBC) according to human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status. Data on women suffering from de novo MBC and diagnosed from 1998 to 2009 were provided by the Côte-d'Or breast cancer registry. NS was described using the Pohar Perme estimator and prognostic factors were investigated in a generalised linear model. We identified 232 patients (mean age = 64.7). Median NS was 29.2 months, 1- and 5-year NS were 76% and 26% respectively. The survival trend in patients with HER2-positive tumours who did not receive trastuzumab was similar to that in women with triple-negative tumours. A higher relative excess risk of death by cancer was observed for high-grade tumours [RER, relative excess rates = 1.76 (95% CI, confidence intervals: 1.17-2.62) for Scarff Bloom Richardson grade 3 vs. 1 + 2], while a lower risk was observed for luminal tumours [RER = 0.49 (95% CI: 0.27-0.89)] and HER2-positive tumours treated with trastuzumab [RER = 0.28 (95% CI: 0.14-0.59)], both compared with triple-negative tumours. Surgery of the primary tumour was associated with better survival [RER = 0.43 (95% CI: 0.28-0.68)]. With half of the women dead before 29 months, stage IV breast cancer still has a bleak outlook. Progress should continue with new target therapies for both HR and HER2 receptors.

Trends in breast cancer incidence and mortality in France 1990-2008.

The objective of this work was to detail the incidence and mortality trends of invasive and in situ breast cancer (BC) in France, especially regarding the development of screening, over the 1990-2008 period. Data issued from nine population-based cancer registries were studied. The incidence of invasive BC increased annually by 0.8 % from 1990 to 1996 and more markedly by 3.2 % from 1996 to 2003, and then sharply decreased until 2006 (-2.3 % per year), especially among women aged 50-69 years (-4.9 % per year). This trend was similar whatever the introduction date of the organized screening (OS) program in the different areas. The incidence of ductal carcinoma in situ steadily increased between 1990 and 2005, particularly among women aged 50-69 years and 70 and older. At the same time, the mortality from BC decreased annually by 1.1 % over the entire study period. This decrease was more pronounced in women aged 40-49 and 50-69 and, during the 1990-1999 period, in the areas where OS began in 1989-1991. The similarity in the incidence trends for all periods of implementation of OS in the different areas was striking. This suggests that OS alone does not explain the changes observed in incidence rate. Our study highlights the importance of closely monitoring the changes in incidence and mortality indicators, and of better understanding the factors causing variation.

Impact of sentinel node biopsy on long-term quality of life in breast cancer patients.

BACKGROUND: The aim of this study was to assess long-term quality of life (QoL) over a period of 6 years in women with breast cancer (BC) who underwent sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), or SLNB followed by ALND. METHODS: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30 and the EORTC-QLQ-BR-23 questionnaires were used to assess QoL before surgery, just after surgery, 6, 12 and 72 months later. The longitudinal effect of surgical modalities on QoL was assessed with a mixed model analysis of variance for repeated measurements. RESULTS: Five hundred and eighteen BC patients were initially included. The median follow-up was 6 years. During the follow-up, 61 patients died. None of the patients of the SLNB group developed lymphedema during follow-up and the relapse rate was similar in the different groups (P=0.62). Before surgery, global health status (P=0.52) and arm symptoms (BRAS) (P=0.99) QoL scores were similar whatever the surgical procedure. The BRAS score (P=0.0001) was better in the SLNB group 72 months after surgery. Moreover, during follow-up, patients treated with SLNB had lower arm symptoms scores than ALND patients and there was no difference for arm symptoms between patients treated with ALND and those treated with SLNB followed by complementary ALND. CONCLUSION: Long-term follow-up showed that SLNB was associated with less morbidity than ALND.

Impact of neoadjuvant chemotherapy on survival in breast cancer patients in daily practice: a population-based study.

This population-based study aimed to describe the effects of neoadjuvant chemotherapy (NC) on survival in breast cancer (BC) patients in daily practice. BC patients treated with NC followed by surgery and radiotherapy, were retrospectively selected from 1982 to 2005 using the Côte d'Or BC registry. These patients were matched for the baseline AJCC (American Joint Committee on Cancer) stage, age at diagnosis, date of diagnosis and oestrogens receptors status to those who had undergone surgery followed by adjuvant chemotherapy and radiotherapy. The prognostic effect of NC on survival in BC patients was assessed with relative survival (RS) analyses. From 1982 to 2005, 210 patients with BC diagnosed in Côte d'Or were treated with NC followed by surgery and radiotherapy. For these patients, mean age at diagnosis was 50 (SD = 11). The main tumour characteristics were clinical AJCC stage 3 (46%) and an advanced Scarff Bloom and Richardson (SBR) stage (80%). Breast conserving surgery was performed in 84 patients (40%), 151 patients (72%) were treated with anthracyclines as the NC and the 5-year RS rate was 71%. Among these patients, 92 (37%) were matched. In this population, multivariate analyses showed that the use of NC did not independently influence RS: relative excess risk = 0.93 (0.50, 1.71).

Breast cancer in men in Cote d'Or (France): epidemiological characteristics, treatments and prognostic factors.

Breast cancer in men is rare, and clinical trials are thus not feasible. This study aimed to describe the epidemiological characteristics, treatment and prognostic factors of breast cancer in men. A population-based study was performed using data from the Cote d'Or breast and gynaecological cancer registry. Data on male breast cancer diagnosed from 1982 to 2008 were provided. Relative survival rates were estimated at 5 years according to the characteristics of the patient and tumour, and treatment. Prognostic factors of survival in men with breast cancer were identified using a generalised linear model. Seventy-five men with invasive breast cancer were registered. Mean age at diagnosis was 66 years. The use of adjuvant chemotherapy (P= 0.013) and hormone therapy (P < 0.0001) increased over time. Relative survival rate at 5 years was 69% for the whole population. Analysis of relative survival according to the treatment showed that survival was longer for patients treated with surgery + radiotherapy + hormone therapy: 89% at 5 years. Scarff, Bloom and Richardson grade was independent prognostic factor of survival. Male breast cancer is a rare disease with a poor prognosis, and diagnosis is often made at an advanced stage. Early diagnosis and better knowledge of the disease would certainly lead to improvements in the prognosis.

A multicenter cohort study to compare quality of life in breast cancer patients according to sentinel lymph node biopsy or axillary lymph node dissection.

BACKGROUND: This prospective multicenter study assessed and compared the impact of different surgical procedures on quality of life (QoL) in breast cancer patients. PATIENTS AND METHODS: The EORTC QLQ-C30 and the EORTC QLQ-BR-23 questionnaires were used to assess global health status (GHS), arm (BRAS) and breast (BRBS) symptom scales, before surgery, just after surgery and 6 and 12 months later. The Kruskal-Wallis test with the Bonferroni correction was used to compare scores. A mixed model analysis of variance for repeated measurements was then applied to assess the longitudinal effect of surgical modalities on QoL. RESULTS: Before surgery, GHS (P = 0.7807) and BRAS (P = 0.7688) QoL scores were similar whatever the surgical procedure: sentinel node biopsy (SLNB), axillary node dissection (ALND) or SLNB + ALND. As compared with other surgical groups, GHS 75.91 [standard deviation (SD) = 17.44, P = 0.041] and BRAS 11.39 (SD = 15.36, P < 0.0001) were better in the SLNB group 12 months after surgery. Whatever the type of surgery, GHS decreased after surgery (P < 0.0001), but increased 6 months later (P = 0.0016). BRAS symptoms increased just after surgery (P = 0.0329) and until 6 months (P < 0.0001) before decreasing (P < 0.0001). CONCLUSIONS: SLNB improved GHS and BRAS QoL in breast cancer patients. However, surgeons must be cautious, SLNB with ALND results in a poorer QoL.

Population-based study of breast cancer survival in Cote d'Or (France): prognostic factors and relative survival.

BACKGROUND: Few population-based studies have reported jointly analyses of relative survival according to the following prognostic factors: tumour-node-metastasis (TNM) stage, age, number of examined and positive nodes, hormonal status, histological Scarff, Bloom and Richardson (SBR) grade, tumour extension, hormone receptor status and tumour multifocal status. PATIENTS AND METHODS: Data on female invasive breast cancer were provided by the Cote d'Or breast cancer registry. The Kaplan-Meier method and log-rank test were used to estimate and compare the survival probability at 1, 5, 10 and 15 years. The effect of prognostic factors on survival was assessed with crude and relative multivariate survival analyses. RESULTS: Crude survival seemed to be worse in patients aged >60 years compared with those aged 45-60 (P > 0.0001), whereas relative survival did not differ. TNM stage, histological SBR grade, progesterone receptor status, tumour multifocal status, locoregional extension and the period of diagnosis were independent prognostic factors of crude and relative survival. CONCLUSION: Breast cancer is influenced by many factors. Despite the absence of any association between the number of examined nodes and overall survival in this study, the number of nodes removed, in conjunction with other prognostic factors, may be useful in selecting node-negative patients for systemic therapy.

Cancer incidence and mortality in France over the period 1980-2005.

BACKGROUND: The objective of this study was to provide updated estimates of national trends in cancer incidence and mortality for France for 1980-2005. METHODS: Twenty-five cancer sites were analysed. Incidence data over the 1975-2003 period were collected from 17 registries working at the department level, covering 16% of the French population. Mortality data for 1975-2004 were provided by the Inserm. National incidence estimates were based on the use of mortality as a correlate of incidence, mortality being available at both department and national levels. Observed incidence and mortality data were modelled using an age-cohort approach, including an interaction term. Short-term predictions from that model gave estimates of new cancer cases and cancer deaths in 2005 for France. RESULTS: The number of new cancer cases in 2005 was approximately 320,000. This corresponds to an 89% increase since 1980. Demographic changes were responsible for almost half of that increase. The remainder was largely explained by increases in prostate cancer incidence in men and breast cancer incidence in women. The relative increase in the world age-standardised incidence rate was 39%. The number of deaths from cancer increased from 130,000 to 146,000. This 13% increase was much lower than anticipated on the basis of demographic changes (37%). The relative decrease in the age-standardised mortality rate was 22%. This decrease was steeper over the 2000-2005 period in both men and women. Alcohol-related cancer incidence and mortality continued to decrease in men. The increasing trend of lung cancer incidence and mortality among women continued; this cancer was the second cause of cancer death among women. Breast cancer incidence increased regularly, whereas mortality has decreased slowly since the end of the 1990s. CONCLUSION: This study confirmed the divergence of cancer incidence and mortality trends in France over the 1980-2005 period. This divergence can be explained by the combined effects of a decrease in the incidence of the most aggressive cancers and an increase in the incidence of less aggressive cancers, partly due to changes in medical practices leading to earlier diagnoses.

Survival of cancer patients in France: a population-based study from The Association of the French Cancer Registries (FRANCIM).

We present the main results of the first population-based cancers survival study gathering all French registry data. Survival data on 205,562 cancer cases diagnosed between 01/01/1989 and 31/12/1997 were analysed. Relative survival was estimated using an excess rate model. The evolution of the excess mortality rate over the follow-up period was graphed. The analysis emphasised the effect of age at diagnosis and its variation with time after diagnosis. For breast and prostate cancers, the age-standardised five-year relative survivals were 84% and 77%, respectively. The corresponding results in men and women were 56% versus 58% for colorectal cancer and 12% versus 16% for lung cancer. For some cancer sites, the excess mortality rate decreased to low values by five years after diagnosis. For most cancer sites, age at diagnosis was a negative prognostic factor but this effect was often limited to the first year after diagnosis.

The French National Mesothelioma Surveillance Program.

OBJECTIVES: The French National Mesothelioma Surveillance Program (NMSP) was established in 1998 by the National Institute for Health Surveillance (InVS). Its objectives are to estimate the trends in mesothelioma incidence and the proportion attributable to occupational asbestos exposure, to help improve its pathology diagnosis, to assess its compensation as an occupational disease, and to contribute to research. METHODS: The NMSP records incident pleural tumours in 21 French districts that cover a population of approximately 16 million people (a quarter of the French population). A standardised procedure of pathological and clinical diagnosis ascertainment is used. Lifetime exposure to asbestos and to other factors (man made mineral fibres, ionising radiation, SV40 virus) is reconstructed, and a case-control study was also conducted. The proportion of mesothelioma compensated as an occupational disease was assessed. RESULTS: Depending on the hypothesis, the estimated number of incident cases in 1998 ranged from 660 to 761 (women: 127 to 146; men: 533 to 615). Among men, the industries with the highest risks of mesothelioma are construction and ship repair, asbestos industry, and manufacture of metal construction materials; the occupations at highest risk are plumbers, pipe-fitters, and sheet-metal workers. The attributable risk fraction for occupational asbestos exposure in men was 83.2% (95% CI 76.8 to 89.6). The initial pathologist's diagnosis was confirmed in 67% of cases, ruled out in 13%, and left uncertain in the others; for half of the latter, the clinical findings supported a mesothelioma diagnosis. In all, 62% applied for designation of an occupational disease, and 91% of these were receiving workers' compensation. CONCLUSIONS: The NMSP is a large scale epidemiological surveillance system with several original aspects, providing important information to improve the knowledge of malignant pleural mesothelioma, such as monitoring the evolution of its incidence, of high risk occupations and economic sectors, and improving pathology techniques.

Late psychosocial sequelae in Hodgkin's disease survivors: a French population-based case-control study.

PURPOSE: To evaluate late psychosocial sequelae in long-term survivors of Hodgkin's disease (HD) in the population of Calvados, France. PATIENTS AND METHODS: Ninety-three patients issued from the Calvados General Tumor Registry, treated from 1978 to 1990, free of relapse and second malignancy since January 1991, were enrolled onto cross-sectional case-control study. One hundred eighty-six healthy controls, matched for sex, age, and residency, were selected at random from electoral rolls. Two self-administered questionnaires were mailed in the spring of 1995. RESULTS: Compared with controls, HD patients reported (1) more physical (P < .001), role (P < .001), and cognitive (P = .015) functioning impairments, as well as dyspnea (P < .001) and chronic fatigue (P = .025), while no statistical difference was found in global health status; (2) to be more often childless (P = .04), fewer divorces or separations (P = .013), fewer changes in relationships with friends (P = .012), similar proportions at work but less ambitious professional plans (P < .001), and greater difficulties in borrowing from banks (P < .001); (3) a slight increase in the number of visits to a general practitioner (P = .05) and greater consumption of medical resources (mainly thyroid extracts, P = .05). CONCLUSION: The study demonstrated that French long-term HD survivors have good global health status and good psychologic, familial, and professional status, although difficulties in borrowing from banks remain a major limitation in daily life. Although physical, role, and cognitive functioning impairments persist that might limit their activities, HD survivors seem to have learned to cope with problems related to their disease and its treatment.

[Ovarian cancer: incidence and mortality in France]. / Les cancers de l'ovaire: incidence et mortalité en France.

OBJECTIVES: To describe the ovarian cancer incidence and mortality trends in France from 1980 to 2000. MATERIALS AND METHODS: Incidence data were obtained from 9 French departments covered by cancer registries which systematically record all cancers, of which those of the ovary. Mortality data has been provided by INSERM bureau in charge of the analysis of death certificates. RESULTS: With 4500 incident cases and 3500 deaths for the year 2000 in France, ovarian cancer still shows a poor prognosis. Age adjusted incidence and mortality rates are almost stable over the study period at an annual rate of 9 by 100000 for incidence and 5.5 by 100000 for mortality. However the risk of developing this cancer and the risk of dying from it, steadily decreased for the cohort born in 1930 to 1950, and the beginning of this reduction corresponds exactly to the beginning of oral contraception. We present comparisons between departments and analyze the border-line tumors in parallel with invasive cancers. CONCLUSION: The cancer of the ovary represents only a small part of female cancers (3.8%) in France and its incidence is stable over time, but its prognosis is very bad.

Age and prognosis of non-small cell lung cancer. Usefulness of a relative survival model.

The aim of our study was the comparative evaluation of a relative survival model and a Cox model to determine the prognostic factors of survival for patients with surgically cured non-small cell lung cancer (NSCLC). We focused particularly on the exact role of age in this survival. 156 patients treated between 1975 and 1988 were studied. Both univariate and multivariate analyses were performed, using the actuarial method and the Cox model for crude survival and the Hakulinen model for relative survival. This study confirmed the poor prognosis of NSCLC, even if a curative surgical procedure has been possible, with a 5-year survival of 48% for stage I tumours but only 6% for stage III tumours. The most significant prognostic factor was the postsurgical TNM staging. The relative survival method of Hakulinen dismissed age as a significant prognostic factor. Our study underlines the usefulness of relative survival methods which should be more frequently employed to allow comparisons between series of different origin and to set up multicentre therapeutic trials.

Estimation of colorectal cancer prevalence in France.

The prevalence in France of patients with colorectal cancer was estimated using data from five population-based cancer registries. At the end of 1994, the number of cases diagnosed in France no more than 5 years before was approximately 95000, of whom 12180 had suffered metastasis and 9746 a local recurrence. This type of cancer is the most common in both men and women and these results enable the need for care or surveillance to be evaluated more accurately.

Effect of cell determinant (CD)34+ cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin's lymphoma patients in front-line therapy.

The aim of this study was to assess the effect of cell determinant (CD)34+ cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin's lymphoma (NHL) patients in front-line therapy. Resource utilisation, length of aplasia, overall (OS) and event-free survival (EFS) were assessed for 63 patients. Economic data were calculated taking into account harvest, hospitalisation, blood product requirements and drugs required until discharge. The point of view of the Hospital Institution was chosen. A significantly earlier haematopoietic engraftment was achieved in patients with a count of more than 5 x 10(6) CD34+/kg. There were no differences for OS and EFS. A high CD34+ cell content resulted in a total cost saving of $4210. This was principally related to a significant reduction in the length of hospitalisation (-$3010) and platelet and red blood cell transfusions (-$815), although the latter was not significant. Several sensitivity analyses showed the robustness of our results. A CD34+ cell dose higher than 5 x 10(6)/kg appeared to be optimal for clinical and economic considerations in NHL patients undergoing transplantation in front-line therapy.

Multiple primary cancers and estimation of the incidence rates and trends.

The use of different registration rules from one registry to another, both generally and also for paired organs, leads to variations in the proportion of multiple primary cancers: in men, from 0.4 to 4.9% for the colon, 0.1 to 2.7% for the lung, and 4.1 to 8.6% for the mouth and pharynx. Subjective factors, often impossible to verify, contribute to these variations. The impact on the estimation of incidence rates and trends is not negligible for cancers of the mouth and the pharynx and for all the cancers taken together. The trend towards an increase of cancers of the mouth and pharynx in the Bas-Rhin disappeared when the incidence was expressed taking only the first cancer (incidence by individual) into consideration, and the differences in incidence between the Calvados and the Bas-Rhin registries for the same site also disappeared. In the absence of harmonisation of the rules and methods followed for registration, incidence by individual is the only approach which makes it possible to compare incidence rates and trends between registries.

Incidence of thyroid cancer in adults recorded by French cancer registries (1978-1997).

This article analyses time trends and geographical variations of thyroid cancer by histological type. Incidence data were provided by 8 French cancer registries over the period 1978-1997, with 3853 adult cases reported. To assess the effects of age, period, cohort and area on incidence, log-linear Poisson regression models were used. Thyroid cancer increased exponentially from the cohort born in 1925. This increase was essentially due to papillary cancer, which increased by 6.2% per year in men and 8.1% per year in women over the entire period (1978-1997). In women, the recent trends were significantly different between the studied geographical areas. The analysis shows that the increase in thyroid cancer, essentially of the papillary type, is not recent. It may be attributed to a possible screening effect or to an increase in the number of "incidentally" discovered cases linked to the use of modern diagnostic tools.

Are alcohol intake and smoking associated with mycosis fungoides? A European multicentre case-control study.

The incidence of mycosis fungoides (MF) is low, and the aetiology of the disease is unknown. The aim of this study was to investigate whether wine consumption protects against the disease and whether smoking constitutes a risk factor. This paper is part of the European Rare Cancers Study that tries to determine the risk factors for seven selective rare cancers, including mycosis fungoides, involved in the development of cancer. A multicentre case-control study was conducted in six European countries. Only incident cases with confirmed histology were included in the analysis which include a total of 76 cases of MF and 2899 controls. Wine intake had no protective effect; on the contrary the consumption of more than 24 g of alcohol per day was associated with a high risk of MF (odds ratio (OR)=3.02, 95% confidence interval (CI), 1.34-6.79), after adjusting for centre, country, age, sex and education. There was a dose-dependent increase in the risk of MF with increased smoking habits, albeit the observed trend was not statistically significant. A combined exposure to high tobacco and alcohol use yielded a significantly increased risk factor for MF (P=0.0073). Alcohol intake was associated with MF.

Viral infection, atopy and mycosis fungoides: a European multicentre case-control study.

Mycosis fungoides (MF) is a rare disease with an unknown aetiology, although it has been suggested that infections may play a role. The present study investigates whether infections, atopic disorders and some other diseases are risk indicators for MF. A European multicentre case-control study involving seven rare cancers, including MF, was conducted from 1995 to 1998. Patients between 35 and 69 years of age diagnosed with MF (n = 140) were recruited, and the diagnoses were verified by a reference pathologist, who classified 83 cases as definitive and 35 cases as possible; 22 cases were not accepted. Of the 118 accepted cases, 104 patients were interviewed (including 76 definitive cases and 28 possible cases). These 76 definitive cases were used for this study. A common set of controls to serve all case groups were interviewed, representing a total of 4574 controls. The latter included 1008 colon cancer patients and 3566 subjects selected from population registers. Information on infections, skin pathology and clinical history 5 years before the diagnosis of MF was used to estimate odds ratios (ORs) derived from logistic regression-modelling, which included gender, age and country. The highest ORs for MF were found in patients who reported a history of psoriasis 5 years before MF was diagnosed (OR 7.2, 95% CI: 3.6-14.5). Urticaria had an OR of 1.4 (95% CI: 0.6-3.6). Infections and atopic diseases were not closely associated with MF. Some diseases correlated to MF. Whether this has a causal background or reflects early diagnostic uncertainty is not known.