Survival in patients with HR+/HER2- metastatic breast cancer treated with initial endocrine therapy versus initial chemotherapy. A French population-based study.

BACKGROUND: According to international guidelines, endocrine therapy (ET) is the preferred option for hormone receptor-positive (HR+) HER2-negative (HER2-) metastatic breast cancer. In spite of clear recommendations, these are not strictly followed in daily practice. The objectives of this study were to investigate the effect of the first anti-metastatic treatment therapy choice on progression-free survival (PFS) and overall survival (OS). METHODS: In this population-based study, we included patients with HR+/HER2- metastatic breast cancer recorded in the Côte d'Or Breast Cancer Registry. Differences in PFS and OS between patients initially treated with chemotherapy (CT) or ET were analysed in Cox proportional hazards models. In a sensitivity analysis, we used a propensity score (PS) to limit the indication bias. RESULTS: Altogether, 557 cases were included, 280 received initial ET and 277 received initial CT. PFS and OS in patients initially treated with ET was improved significantly when compared to patients with initial CT (respectively, HR = 0.83 (95% CI 0.69-0.99) and HR = 0.71 (95% CI 0.58-0.86)). The results of the sensitivity analysis supported these findings. CONCLUSION: This study shows that treating patients with HR+/HER2- metastatic breast cancer with initial ET could provide a survival advantage in comparison with initial CT.

Socio-economic and occupational outcomes of long-term survivors of gynaecological cancer: A French population-based study.

OBJECTIVE: To describe socio-economic and professional outcomes in long-term survivors of cervical, endometrial or ovarian cancer, including return to work and problems related to obtaining loans and insurance. METHODS: Women with cervical, endometrial or ovarian cancers diagnosed from 2006 to 2013 were selected through the French gynaecological cancer registry of Côte d'Or, in a cross-sectional survey. Using a questionnaire established with the help of sociologists and psychologists, social and cancer-related work issues were collected among women aged less than 60 years at the time of cancer diagnosis. The socio-economic status was also assessed, at the time of the survey using the EPICES questionnaire. RESULTS: A total of 92 gynaecological cancer survivors (CS) participated in this survey. Gynaecological CS reported a decrease in income since cancer diagnosis, difficulties obtaining loans, and a decrease in ability to work, both in the short term after treatment and at the time of survey, on average 6 years after diagnosis. Fatigue, emotional and cognitive difficulties were the reasons cited to explain the decreased ability to work, both immediately after treatment and in the long term. CONCLUSIONS: Gynaecological CS experienced many problems, such as decreased work capacity, decreased income and difficulty obtaining loans.

Determinants of quality of life among long-term breast cancer survivors.

PURPOSE: To identify the impact of clinical and socio-economic determinants on quality of life (QoL) among breast cancer (BC) survivors 5 years after diagnosis. METHODS: A cross-sectional survey was conducted in women diagnosed in 2007 for primary invasive non-metastatic BC and identified through the Côte d'Or BC registry. QoL was assessed with the Medical Outcomes Study 12-item Short Form Health Survey (SF-12), the European Organization for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-C30) and the breast cancer (EORTC-QLQ-BR23) questionnaires. Social support was assessed with Sarason's social support questionnaire, and deprivation was assessed by the EPICES questionnaire. Clinical variables were collected through the registry database. Determinants of QoL were identified using multivariable mixed model analysis for each SF-12 dimension. A sensitivity analysis was conducted with multiple imputations on missing data. RESULTS: Overall, 188 patients on 319 patients (59 %) invited to participate to the survey completed the questionnaires. Five years after breast cancer diagnosis, the disease stages at diagnosis, as well as the treatment received, were not determinants of QoL. Only the age at diagnosis and comorbidities were found to be determinants of QoL. CONCLUSIONS: Five years after BC diagnosis, disease severity and the treatment received did not affect QoL.

Age-related socio-economic and geographic disparities in breast cancer stage at diagnosis: a population-based study.

BACKGROUND: This study aimed to determine the impact of socio-economic and geographic disparities on disease stage at diagnosis according to age in breast cancer (BC) patients. Secondary purpose was to describe survival METHODS: All women with primary invasive BC, diagnosed from 1998 to 2009 in the department of Côte d'Or were retrospectively selected using data from the Côte d'Or BC registry. European transnational ecological deprivation index (French European Deprivation Index) was used to measure the socio-economic environment. Relationships between socio-geographic deprivation and disease stage at diagnosis according to age were assessed by a multilevel ordered logistic regression model. Relative survival rates (RSRs) were given at 5 years according to tumour and patients characteristics. RESULTS: In total, 4364 women were included. In multivariable analysis, socio-economic deprivation was associated with disease stage at diagnosis. Women aged between 50 and 74 years and living in deprived areas were more often diagnosed with advanced tumour stages (stages II/III vs. I or stages IV vs. II/III) with odds ratio = 1.27 (1.01-1.60). RSRs were lowest in women living in the most deprived area compared with those living in most affluent area with RSR = 88.4% (85.9-90.4) and 92.6% (90.5-94.2), respectively. CONCLUSIONS: Socio-economic factors affected tumour stage at diagnosis and survival. Living in a deprived area was linked to advanced-stage BC at diagnosis only in women aged 50-74 years. This is probably due to the socio-economic disparities in participation in organized BC screening programmes. Furthermore, living in deprived area was associated with a poor survival rate.

Population-based study of breast cancer in older women: prognostic factors of relative survival and predictors of treatment.

BACKGROUND: A large proportion of women with breast cancer (BC) are elderly. However, there is a lack of information regarding BC prognostic factors and care in this population. The aims of this study were to assess the prognostic factors of relative survival (RS) among women with BC aged ≥ 75 years old and to identify the predictive factors of treatments administered to this population. METHODS: A population-based study was performed using data from the Cote d'Or breast and gynaecological cancer registry. Women aged 75 years and older with primary invasive BC and resident in Cote d'Or at the time of diagnosis made between January 1998 and December 2008 were retrospectively selected. Prognostic factors of RS were estimated in a generalized linear model with a Poisson error structure. RS rate for the whole population was given at 5 years. Logistic regression models were used to identify the predictors of the treatments administered. RESULTS: Six hundred and eighty-one women were included. Median age at diagnosis was 80. Comorbidities (p = 0.02), pT stage (p = 0.04), metastases (p =< 0.001), having a family doctor (p = 0.03) and hormone-receptor status (p = 0.006) were independent prognostic factors of RS. The RS rate at 5 years for the whole population was 78.2%, 95%CI = [72.2-83.0]. Age, pT stage, metastases, histoprognostic SBR grade, hormone receptor status and comorbidities were frequently found to be predictors of treatment with surgery alone, hormone therapy alone, breast conserving surgery plus adjuvant therapy and mastectomy plus adjuvant therapy. CONCLUSIONS: Comorbid conditions adversely affect survival in older women with breast cancer. Moreover the results of this study showed that there are numerous predictors of the type of treatment administered, and that the most important were age and comorbidities.

[The use of virtual slides in the daily practice of a pathology laboratory]. / L'utilisation des lames virtuelles en pratique quotidienne par un laboratoire de pathologie.

INTRODUCTION: We describe a first experiment in routine use of a virtual slides system within a pathology practice whose technical facilities are not located on the same geographical site as pathologists. MATERIAL AND METHODS: The samples to be analyzed were biopsies, tissues, and cytology preparations in liquid environment. They were processed through technical facilities using a slide scanner. The process is monitored by the company specialised in e@pathology solutions (CCITI) http://www.e@pathologie facility. RESULTS: From November 2008 to September 2009, 611 patient files have been processed, i.e. 1183 slides have been digitalized without selective criteria. The average digitalization time per slide was 30 seconds to 2 minutes for biopsies and 7 minutes for tissues and smears. The record of the areas examined confirms that the whole slide has been visualized. The time and space constraints were reduced in case a second reading is requested. Less than 1% of the slides had to be re-digitalized. The reports were standardized with pre-defined questions/answers or bible code. The average time for processing a file is 3 to 5 minutes. DISCUSSION: The http://www.e@pathologie facility simplifies routine second advice requests and allows the control of operating costs through the mutualisation of technical facilities of several laboratories while preserving their independence. CONCLUSION: The online virtual slide system must go beyond the experimental stage whilst remaining in perfect accord with the users needs and economic realities. It will also make it possible to enrich the patient's medical follow-up digital file.

Trends in endocrine therapy prescription and survival in patients with non-metastatic hormone receptor positive breast cancer treated with endocrine therapy: A population based-study.

PURPOSE: To identify prognostic factors of invasive-disease free survival (iDFS) in women with non-metastatic hormone receptor positive (HR+) breast cancer (BC) in daily routine practice. METHODS: We performed a retrospective study using data from the Côte d'Or breast and gynecological cancer registry in France. All women diagnosed with primary invasive non-metastatic HR + BC from 1998 to 2015 and treated by endocrine therapy (ET) were included. Women with bilateral tumors or who received ET for either metastasis or relapse were excluded. We performed adjusted survival analysis and Cox regression to identify prognostic factors of iDFS. RESULTS: A total of 3976 women were included. Age at diagnosis, ET class, SBR grade, treatment, stage and comorbidity were independently associated with iDFS. Women who had neither surgery nor radiotherapy had the highest risk of recurrence (HR = 3.75, 95%CI [2.65-5.32], p < 0.0001). Receiving aromatase inhibitors (AI) was associated with a lower risk of recurrence (HR = 0.70, 95%CI [0.54-0.90], p = 0.055) compared to tamoxifen. Compared to women with no comorbidities, women with 1 or 2 comorbidities were more likely to receive AI (OR = 1.63, 95%CI [1.22-2.17], p = 0.0009). CONCLUSIONS: Comorbidities, age at diagnosis and previous treatment were associated with iDFS in non-metastatic HR + BC patients. This study also showed that women who received tamoxifen for their cancer experienced worse iDFS compared to women treated with AI.

Population-based study of ovarian cancer in Côte d'Or: prognostic factors and trends in relative survival rates over the last 20 years.

BACKGROUND: The aim of this population-based study was to assess independent prognostic factors in ovarian cancer using relative survival (RS) and to investigate changes in RS rates from 1982 to 2005. METHODS: Data on 748 patients with ovarian cancer were provided by the Côte d'Or gynaecologic cancer registry. The RS was estimated using a generalized linear model with a Poisson error structure. Relative survival and its 95% confidence interval (CI) were described at the following specific time points 1, 3 and 5 years. The effect of prognostic factors on survival was assessed with multivariate analyses of RS. RESULTS: The median follow-up was 12 years. The RS rates at 1, 3 and 5 years were 81%, 55% and 44%, respectively. As compared with the period 1982-1989, an improvement in survival was found for the period 1998-2005: HR = 0.52[0.40-0.67]. Women who lived in urban areas had better RS: HR = 0.82[0.67-0.99]. Patients with epithelial types of ovarian cancer other than mucinous or endometrioid cancer had worse RS than those with serous histology. Age ≥ 70 years was associated with lower survival. CONCLUSIONS: Period of diagnosis, stage at diagnosis, histology, place of residence and age were independent prognostic factors for survival in ovarian cancer. An improvement in the survival rate was observed after 1998 but a significant improvement was limited to advanced stage cancers.

What Are Young Women Living Conditions after Breast Cancer? Health-Related Quality of Life, Sexual and Fertility Issues, Professional Reinsertion.

In recent decades, the living conditions of young breast cancer (BC) survivors have garnered increasing attention. This population-based study aimed to identify the clinical, social and economic determinants of Health-Related Quality of Life (HRQoL), and to describe other living conditions of young long-term BC survivors. Women with non-metastatic BC diagnosed between 2006 and 2015, aged 45 years and younger at the time of diagnosis, were identified through the Breast and Gynecologic Cancer Registry of the Côte d'Or, France. Participants completed self-report questionnaires including standardized measures of HRQoL, anxiety, depression, social deprivation, social support and sexuality. Fertility and professional reintegration issues were also assessed. The determinants of HRQoL were identified using mixed regression model. In total, 218 BC survivors participated in the survey. The main determinants of poor HRQoL were anxiety, depression, comorbidities, social deprivation and menopausal status. Among 72% of women who did not receive information about fertility preservation, 38% of them would have liked to have been informed. Finally, 39% of survivors reported a negative impact of BC on their professional activity. This study showed that BC stage or treatments did not have an impact on HRQOL of young long-term BC survivors. Fertility, sexuality and professional reintegration remained the main concerns for survivors. Specific interventions in these population should focus on these issues.

Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of colon cancers.

The RAS-MAPK, PI (3)K signaling pathways form a network that play a central role in tumorigenesis. The BRAF, KRAS and PI3KCA genes code 3 partners of this network and have been found to be activated by mutation in colorectal cancer; these mutations lead to unrestricted cell growth. We evaluated the clinicopathological features and the prognosis of patients with activated-network colon cancers in a population-based study. A total of 586 colon adenocarcinomas were evaluated using sequencing for mutations of KRAS and PI3KCA, and allelic discrimination for mutation of BRAF. Clinicopathological characteristics were correlated to the risk of bearing a mutation of the network using logistic regression. Three-year survival rates were compared with the Log rank test. A multivariate survival analysis using the Cox model was performed. After adjustment for age and microsatellite instability, activation of the network by mutation of at least 1 of the 3 genes was significantly associated with female sex (p = 0.02) and proximal location (p < 0.001). Lower levels of 3-year survival were associated with activation of the network by mutation of at least 1 of the 3 genes (59.4 and 69.4%, respectively; p = 0.009). These results remained significant in a multivariate analysis adjusted for sex, age, location, stage and microsatellite instability (HR = 1.48; CI CI(95%) = [1.07-2.04]). Our study is the first report to underline the potential role of RAS-MAPK, PI (3)K network mutations on survival in colon cancers. Because of the role of this signaling network on anticancer agents, the evaluation of its mutations could have clinical implications.

Breast cancer subtype of French women is not influenced by socioeconomic status: A population-based-study.

CONTEXT: The molecular subtype of breast tumours plays a major role in cancer prognosis and treatment options. Triple negative tumours (TN) carry the worst prognosis and affects most frequently women of low socioeconomic status (SES). Studies have shown that non-biologic factors, such as the socioeconomic status could have an influence on tumour biology. To this date no study has been done investigating this association in French women. The objective is to study the association between the SES and the molecular tumour subtype of breast cancer patients in the French county of Côte d'Or. This study benefits from the population data from the Côte d'Or breast cancer registry known for its strict quality control policy. METHODS: Invasive breast cancer cases between 2003 and 2013 were extracted from the Breast cancer registry database in Côte d'Or. A multivariate analysis was conducted using a hierarchical polytomous regression for the multinomial outcomes for the cancer subtype with HR+/HER2 as reference category. RESULTS: A total of 4553 cases were included in our study. There was no significant association found between SES and tumour subtype in French women at diagnosis. Women older than 75 years were less likely to have a TN and HR+/HER2+ breast cancer (OR = 0.66; CI95% = [0.46-0.94] and OR = 0.51; CI95% = [0.37-0.70] respectively). Women with TN tumour subtype had significantly less lymph node invasion when compared to HR+/HER2- subtype (OR = 0.71; CI95% = [0.54-0.92]). CONCLUSION: No significant association was found between socioeconomic status and molecular subtype. Further studies are needed to clarify the mechanisms associated with developing each tumour subtype.

Clinical value of mitochondrial mutations in colorectal cancer.

PURPOSE: Prognostic factors that could select high-risk recurrence colorectal cancer patients and predict chemosensitivity are needed. Since mutations of mitochondrial DNA (mtDNA) have been described in different types of cancers and since they may play a role in response to anticancer agents, we investigated in a population-based series of colorectal cancer patients the clinical value of mtDNA mutations. PATIENTS AND METHODS: The displacement loop (D-loop) region of mtDNA was sequenced on a series of 365 patients recorded in the Digestive Cancer Registry of Côte-d'Or (France) between 1998 and 2000. Clinicopathologic characteristics were correlated to the presence of a D-loop mutation. Survival rates were compared with the log-rank test. A multivariate survival analysis was performed. RESULTS: D-loop mutations were found in 38.3% of the tumors. The 3-year survival rate was 53.5% in patients with D-loop mutation versus 62.1% in patients without (P = .05). After adjustment for age, stage, and microsatellite instability status, the relative risk of death in patients with D-loop mutation was 1.40 (95% CI, 1.02 to 1.93; P = .034) as compared with those without. In stage III colon cancers, adjuvant chemotherapy was beneficial only for patients without D-loop mutation (3-year survival, 78.3% v 45.4%, P < .02). In those with D-loop mutation who received adjuvant chemotherapy, the relative risk of death was 4.30 (95% CI, 1.23 to 15.00; P < .02). CONCLUSION: The D-loop region is a hotspot for somatic mutations in colorectal tumors. Moreover, presence of tumor D-loop mutation appears to be a factor of poor prognosis in colorectal patients and a factor of resistance to fluorouracil-based adjuvant chemotherapy in stage III colon cancers.

Impact of age-related socio-economic and clinical determinants of quality of life among long-term breast cancer survivors.

OBJECTIVES: The main purpose of this study was to identify age-related socioeconomic and clinical determinants of quality of life among breast cancer survivors five years after the diagnosis. The secondary objective was to describe quality of life in the studied population according to age. STUDY DESIGN: A cross-sectional survey in five-year breast cancer survivors was conducted in women diagnosed with breast cancer in 2007 and 2008 in Côte d'Or. MAIN OUTCOME MEASURES: Quality of life was assessed with the SF-12, the EORTC-QLQ-C30 and the EORTC-QLQ-BR23 questionnaires. Socio-economic deprivation was assessed by the EPICES questionnaire. Social support was assessed by the Sarason questionnaire and clinical features were collected through the Côte d'Or breast cancer registry. Age-related determinants of quality of life were identified using multivariate mixed model analysis for each SF-12 dimension. RESULTS: Overall 396 women completed the questionnaires. Women aged <65 years had a better quality of life and a greater availability of social support than did women aged ≥65 years. Body mass index, relapse and EPICES were found to be determinants of quality of life in younger women (p<0.006). For older women, comorbidities and EPICES deprivation scores were predictors of low quality of life scores (p<0.006). CONCLUSIONS: Five years after breast cancer diagnosis, disease severity did not affect quality of life. The major determinants of quality of life in younger women were disease relapse and EPICES deprivation scores while those in older women were comorbidities and EPICES deprivation scores.

About invasive cervical cancer: a French population based study between 1998 and 2010.

OBJECTIVES: The new French cancer plan provides the implementation of organized screening. To make an assessment of the situation, we aim to describe clinical, tumor and survival characteristics of patients with invasive cervical cancer. STUDY DESIGN: Data on women suffering from invasive cervical cancer and diagnosed from 1998 to 2010 were provided by the Cote d'Or breast cancer registry. Survival was described using the Kaplan-Meier method and prognostic factors of survival were estimated in a Cox proportional hazard model. RESULTS: On the whole, 1019 cancers have been collected including 311 (30.5%) invasive ones. The peak incidence was between 40 and 49 years, with an average age of 52 years (SD=16.4). Cancers were mostly squamous cell carcinoma (80.1%) and diagnosed at a localized stage (53.7%). Only 49% (71/145) of our population were up to date on their Pap smear follow up with lower rates in deprived women. The 5-year survival rate was 62% (15% for women with FIGO stage IV and 91% for women with FIGO stage I) with a median survival of 12.3 years [95% CI: 6.6-NR]. Multivariate analysis showed that risk of death was the highest for group age 50-59 (OR=4.93; 95% CI: [1.55-15.70]) compared to women aged less than 40, advanced stage (OR=3.12; 95% CI [1.82-5.35]), and non accurate follow up (OR=2.81; 95% CI [1.32-5.97]). After cancer diagnosis, no impact of the deprivation index on survival was found. CONCLUSION: This study confirms the poor outcome of advanced invasive cervical cancer and the importance of early detection of cervical cancer. Preventive communication should be even more developed and the implementation of a screening program may go through the provision of improved screening tools.

In breast cancer, are treatments and survival the same whatever a patient's age? A population-based study over the period 1998-2009.

AIM: The present study aimed to describe treatments, relative survival and prognostic factors in breast cancer patients according to age. METHODS: All women with primary invasive breast cancer, diagnosed from 1998 to 2009 in the department of Côte d'Or, were retrospectively selected. Variations in treatments administered according to age (<50 years, 50-74 years, >74 years) and period were assessed using Cochran-Armitage trend tests and χ(2) -tests, respectively. Prognostic factors according to age were estimated using a generalized linear model with a Poisson error structure. RESULTS: Overall, 4305 women were included. The oldest women (aged >74 years) were more likely than the youngest women to have comorbidities, advanced stage tumors, hormone receptor-positive tumors and be human epidermal growth factor receptor 2-negative. The use of breast conserving surgery plus adjuvant therapy decreased in older women (>74 years), whereas the proportions of women without treatments and with adjuvant hormone therapy increased with age. Multivariate relative survival analyses according to age showed an increased risk of death in women aged 50-74 years and >74 years with comorbidities compared with those without comorbidities; relative excess risks were 1.85 (1.13-3.02) and 3.23 (1.26-8.31), respectively. In contrast, a decreased risk of death was observed in women aged 50-74 years diagnosed by medical imaging compared with those diagnosed by clinical signs; relative excess risks 0.44 (0.22-0.89). CONCLUSION: Elderly women compared with the youngest women were diagnosed with more favorable tumor biology (hormone receptor-positive tumors, human epidermal growth factor receptor 2-negative). However, survival was poor in elderly women who had comorbid conditions, did not attend screening mammography examinations and were undertreated.

Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases.

The CpG island methylator phenotype (CIMP) is a distinct phenotype in colorectal cancer, associated with specific clinical, pathologic, and molecular features. However, most of the studies stratified methylation according to two subgroups (CIMP-High versus No-CIMP/CIMP-Low). In our study, we defined three different subgroups of methylation (No-CIMP, CIMP-Low, and CIMP-High) and evaluated the prognostic significance of methylation status on a population-based series of sporadic colon cancers. A total of 582 colon adenocarcinomas were evaluated using methylation-specific PCR for 5 markers (hMLH1, P16, MINT1, MINT2, and MINT31). No-CIMP status was defined as no methylated locus, CIMP-Low status as one to three methylated loci, and CIMP-High status as four or five methylated loci. Clinicopathologic and molecular characteristics were correlated to the methylation status. Crude and relative survival was compared according to methylation status. In the microsatellite-stable (MSS) group, CIMP-High was significantly associated with proximal location (P = 0.011) and BRAF mutation (P < 0.001). KRAS mutations were more associated with CIMP-High and CIMP-Low status (P = 0.008). A shorter 5-year survival was observed in MSS cancer patients with CIMP-Low or CIMP-High status. These results remained significant in multivariate analysis adjusted for age, stage, and BRAF and KRAS mutational status [CIMP-Low: hazard ratio (HR), 1.85; 95% confidence interval (95% CI), 1.37-2.51; CIMP-High, HR, 2.90; 95% CI, 1.53-5.49 compared with No-CIMP]. Within the high-level microsatellite instability group, no difference in survival was observed between the different CIMP groups. Our results show the interest of defining three subgroups of patients according to their methylation status (No-CIMP/CIMP-Low/CIMP-High). Methylation is an independent prognostic factor in MSS colon cancer.