Patterns and risk of first and subsequent recurrences in women within ten years after primary invasive breast cancer

Background: Previous studies suggest a distinct pattern and a number of predictive factors for breast cancer recurrence. However, only few studies include data on recurrence site and no study provides data regarding second and third breast cancer recurrence after local and regional recurrence. The aim of this study was to analyse the occurrence, timing and predictive factors of first and subsequent local (LR), regional (RR) or distant (DM) recurrence during the first 10 years after treatment for primary invasive breast cancer in women. Methods: Women with stage I-III invasive breast cancer diagnosed in 2003 and treated with curative intent were selected from the Netherlands Cancer Registry (N = 9797). Median follow-up was 10 years. Multivariable cox proportional hazards regression was used to model the hazard of recurrence over time for site-specific first recurrence and for subsequent recurrences after LR or RR. Predictive factors were identified for first and for subsequent recurrences. All tests were two-sided and probability values of <0.05 were considered statistically significant. Results: In total 379 patients had LR, 156 patients had RR and 1412 patients had DM as first recurrence. The risk of first recurrence was highest around 2 years post-diagnosis (HR 0.040 95% CI 0.036–0.044) with a similar pattern for LR, RR and DM. Multivariable analysis showed that lower age and negative estrogen-receptor (ER) status were predictive factors for first LR. Tumour size >2 cm, grade III and negative ER were predictive factors for first RR and tumour size >2 cm, grade II or III, increasing number of involved lymph nodes and negative progesterone-receptor (PR) status were predictive factors for first DM. After a LR 109/379 patients (28.7%) developed subsequent recurrence: 11 patients had another LR (2.9%), 13 patients had RR (3.4%) and 85 patients (22.4%) had DM. Median time to second recurrence was 1.1 year (IQR 0.3–2.5 year). Tumour size >2 cm, grade III, primary tumour histology (other vs invasive ductal), >3 positive lymph nodes and negative PR-status were predictive factors for a second recurrence after LR. After a first RR 79/156 patients (50.6%) developed subsequent recurrence: 8 patients had LR (5.1%), 3 patients had RR (1.9%) and 68 patients (43.6%) had DM. Median time to second recurrence was 1.1 year (IQR 0.5–2.1 year). In multivariable analysis, no predictive factor for a second recurrence after RR was identified. After previous LR or RR a third subsequent recurrence occurred in 18 patients (9.6%). Conclusions: The pattern of first recurrence was similar for LR, RR and DM. To improve personalized follow-up, predictive factors could be taken into account. However, this study showed no explicit predictive factor for site specific recurrence and subsequent recurrences after LR and RR. Future studies that take treatment characteristics into account are needed

Patterns and risk of first and subsequent recurrences in women within ten years after primary invasive breast cancer

Background: Previous studies suggest a distinct pattern and a number of predictive factors for breast cancer recurrence. However, only few studies include data on recurrence site and no study provides data regarding second and third breast cancer recurrence after local and regional recurrence. The aim of this study was to analyse the occurrence, timing and predictive factors of first and subsequent local (LR), regional (RR) or distant (DM) recurrence during the first 10 years after treatment for primary invasive breast cancer in women. Methods: Women with stage I-III invasive breast cancer diagnosed in 2003 and treated with curative intent were selected from the Netherlands Cancer Registry (N = 9797). Median follow-up was 10 years. Multivariable cox proportional hazards regression was used to model the hazard of recurrence over time for site-specific first recurrence and for subsequent recurrences after LR or RR. Predictive factors were identified for first and for subsequent recurrences. All tests were two-sided and probability values of 2 cm, grade III and negative ER were predictive factors for first RR and tumour size >2 cm, grade II or III, increasing number of involved lymph nodes and negative progesterone-receptor (PR) status were predictive factors for first DM. After a LR 109/379 patients (28.7%) developed subsequent recurrence: 11 patients had another LR (2.9%), 13 patients had RR (3.4%) and 85 patients (22.4%) had DM. Median time to second recurrence was 1.1 year (IQR 0.3–2.5 year). Tumour size >2 cm, grade III, primary tumour histology (other vs invasive ductal), >3 positive lymph nodes and negative PR-status were predictive factors for a second recurrence after LR. After a first RR 79/156 patients (50.6%) developed subsequent recurrence: 8 patients had LR (5.1%), 3 patients had RR (1.9%) and 68 patients (43.6%) had DM. Median time to second recurrence was 1.1 year (IQR 0.5–2.1 year). In multivariable analysis, no predictive factor for a second recurrence after RR was identified. After previous LR or RR a third subsequent recurrence occurred in 18 patients (9.6%). Conclusions: The pattern of first recurrence was similar for LR, RR and DM. To improve personalized follow-up, predictive factors could be taken into account. However, this study showed no explicit predictive factor for site specific recurrence and subsequent recurrences after LR and RR. Future studies that take treatment characteristics into account are needed

Employment in the Ecuadorian cut-flower industry and the risk of spontaneous abortion

<p>Abstract</p> <p>Background</p> <p>Research on the potentially adverse effects of occupational pesticide exposure on risk of spontaneous abortion (SAB) is limited, particularly among female agricultural workers residing in developing countries.</p> <p>Methods</p> <p>Reproductive histories were obtained from 217 Ecuadorian mothers participating in a study focusing on occupational pesticide exposure and children's neurobehavioral development. Only women with 2+ pregnancies were included in this study (n = 153). Gravidity, parity and frequency of SAB were compared between women with and without a history of working in the cut-flower industry in the previous 6 years. Logistic regression analysis was conducted to assess the relation between SAB and employment in the flower industry adjusting for maternal age.</p> <p>Results</p> <p>In comparison to women not working in the flower industry, women working in the flower industry were significantly younger (27 versus 32 years) and of lower gravidity (3.3 versus 4.5) and reported more pregnancy losses. A 2.6 (95% CI: 1.03-6.7) fold increase in the odds of pregnancy loss among exposed women was observed after adjusting for age. Odds of reporting an SAB increased with duration of flower employment, increasing to 3.4 (95% CI: 1.3, 8.8) among women working 4 to 6 years in the flower industry compared to women who did not work in the flower industry.</p> <p>Conclusion</p> <p>This exploratory analysis suggests a potential adverse association between employment in the cut-flower industry and SAB. Study limitations include the absence of a temporal relation between exposure and SAB, no quantification of specific pesticides, and residual confounding such as physical stressors (i.e., standing). Considering that approximately half of the Ecuadorian flower laborers are women, our results emphasize the need for an evaluating the reproductive health effects of employment in the flower industry on reproductive health in this population.</p

The Organophosphate Chlorpyrifos Interferes with the Responses to 17β-Estradiol in the Digestive Gland of the Marine Mussel Mytilus galloprovincialis

BACKGROUND: Many pesticides have been shown to act as endocrine disrupters. Although the potencies of currently used pesticides as hormone agonists/antagonists are low compared with those of natural ligands, their ability to act via multiple mechanisms might enhance the biological effect. The organophosphate Chlorpyrifos (CHP) has been shown to be weakly estrogenic and cause adverse neurodevelopmental effects in mammals. However, no information is available on the endocrine effects of CHP in aquatic organisms. In the digestive gland of the bivalve Mytilus galloprovincialis, a target tissue of both estrogens and pesticides, the possible effects of CHP on the responses to the natural estrogen 17β-estradiol (E(2)) were investigated. METHODOLOGY/PRINCIPAL FINDINGS: Mussels were exposed to CHP (4.5 mg/l, 72 hrs) and subsequently injected with E(2) (6.75 ng/g dw). Responses were evaluated in CHP, E(2) and CHP/E(2) treatment groups at 24 h p.i. by a biomarker/transcriptomic approach. CHP and E(2) induced additive, synergistic, and antagonistic effects on lysosomal biomarkers (lysosomal membrane stability, lysosome/cytoplasm volume ratio, lipofuscin and neutral lipid accumulation). Additive and synergistic effects were also observed on the expression of estrogen-responsive genes (GSTπ, catalase, 5-HTR) evaluated by RT-Q-PCR. The use of a 1.7K cDNA Mytilus microarray showed that CHP, E(2) and CHP/E(2), induced 81, 44, and 65 Differentially Expressed Genes (DEGs), respectively. 24 genes were exclusively shared between CHP and CHP/E(2), only 2 genes between E(2) and CHP/E(2). Moreover, 36 genes were uniquely modulated by CHP/E(2). Gene ontology annotation was used to elucidate the putative mechanisms involved in the responses elicited by different treatments. CONCLUSIONS: The results show complex interactions between CHP and E(2) in the digestive gland, indicating that the combination of certain pesticides and hormones may give rise to unexpected effects at the molecular/cellular level. Overall, these data demonstrate that CHP can interfere with the mussel responses to natural estrogens

Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer

Introduction Cardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Some breast cancer treatments including anthracyclines, trastuzumab and radiotherapy can increase the risk of CVD, especially for patients with pre-existing CVD risk factors. Early identification of patients at increased CVD risk may allow switching to less cardiotoxic treatments, active surveillance or treatment of CVD risk factors. One of the strongest independent CVD risk factors is the presence and extent of coronary artery calcifications (CAC). In clinical practice, CAC are generally quantified on ECGtriggered cardiac CT scans. Patients with breast cancer treated with radiotherapy routinely undergo radiotherapy planning CT scans of the chest, and those scans could provide the opportunity to routinely assess CAC before a potentially cardiotoxic treatment. The Bragatston study aims to investigate the association between calcifications in the coronary arteries, aorta and heart valves (hereinafter called ‘cardiovascular calcifications’) measured automatically on planning CT scans of patients with breast cancer and CVD risk. Methods and analysis In a first step, we will optimise and validate a deep learning algorithm for automated quantification of cardiovascular calcifications on planning CT scans of patients with breast cancer. Then, in a multicentre cohort study (University Medical Center Utrecht, Utrecht, Erasmus MC Cancer Institute, Rotterdam and Radboudumc, Nijmegen, The Netherlands), the association between cardiovascular calcifications measured on planning CT scans of patients with breast cancer (n≈16 000) and incident (non-)fatal CVD events will be evaluated. To assess the added predictive value of these calcifications over traditional CVD risk factors and treatment characteristics, a case-cohort analysis will be performed among all cohort members diagnosed with a CVD event during follow-up (n≈200) and a random sample of the baseline cohort (n≈600). Ethics and dissemination The Institutional Review Boards of the participating hospitals decided that the Medical R

Occupational exposure to potential endocrine disruptors: Further development of a job exposure matrix

OBJECTIVES: The aim was to develop a new up-to-date and comprehensive job exposure matrix (JEM) for estimating exposure to potential endocrine disruptors in epidemiological research. METHODS: Chemicals with endocrine disrupting properties were identified from the literature and classified into 10 chemical groups: polycyclic aromatic hydrocarbons (PAHs), polychlorinated organic compounds, pesticides, phthalates, organic solvents, bisphenol A, alkylphenolic compounds, brominated flame retardants, metals and a miscellaneous group. Most chemical groups were divided into three to six subgroups. Focusing on the years 1996-2006, three experts scored the probability of exposure to each chemical group and subgroup for 353 job titles as "unlikely" (0), "possible" (1) or "probable" (2). Job titles with positive exposure probability scores were provided with exposure scenarios that described the reasoning behind the scores. RESULTS: Exposure to any chemical group was unlikely for 238 job titles (67%), whereas 102 (29%) job titles were classified as possibly (17%) or probably (12%) exposed to one or several endocrine disruptors. The remaining 13 job titles provided too little information to classify exposure. PAHs, pesticides, phthalates, organic solvents, alkylphenolic compounds and metals were often linked to a job title in the JEM. The remaining chemical groups were found to involve very few occupations. CONCLUSIONS: Despite some important limitations, this JEM could be a valuable tool for exposure assessment in studies on the health risks of endocrine disruptors, especially when task specific information is incorporated. The documented exposure scenarios are meant to facilitate further adjustments to the JEM to allow more widespread use

Adverse reproductive outcomes among male painters with occupational exposure to organic solvents

Contains fulltext : 50551.pdf (publisher's version ) (Closed access)OBJECTIVES: To assess the risks of reproductive disorders and birth defects in offspring of male painters with exposure to organic solvents, and to determine the shape of the dose-response relationship. METHODS: Random samples of painters and carpenters were drawn from workers affiliated with the Dutch Trade Union for Construction Workers, the Netherlands, 2001. Information on reproductive outcomes, occupational exposures, and lifestyle habits was retrospectively obtained through self-administered questionnaires filled in by 398 painters exposed to organic solvents in paints, thinners, and cleansers in the period of three months before the last pregnancy, and 302 carpenters with little or no exposure to solvents. A statistical model was used to estimate quantitative exposure measures. RESULTS: Workers employed as painters at three months before pregnancy had an increased risk (odds ratio 6.2, 95% CI 1.4 to 27.9) of congenital malformations in offspring compared to carpenters. There was a positive exposure-response trend with increasing exposure to organic solvents based on quantitative model predicted exposure estimates using toluene as a marker. There was some indication of an increased risk of functional developmental disorders in offspring among painters with intermediate and high model predicted exposure. The risk of low birth weight children seemed to be slightly increased among painters as well. Results for other reproductive outcomes (time to pregnancy, spontaneous abortion, and preterm birth) did not show increased risks. CONCLUSION: This study showed a positive association between paternal occupational exposure to organic solvents and congenital malformations in offspring. However, the small numbers of cases, especially when examining different exposure levels, as well as the self-reported nature of exposure and outcome variables, may hamper interpretation of the results

Patterns and predictors of first and subsequent recurrence in women with early breast cancer

PURPOSE: Little is known about the occurrence, timing and prognostic factors for first and also subsequent local (LR), regional (RR) or distant (DM) breast cancer recurrence. As current follow-up is still consensus-based, more information on the patterns and predictors of subsequent recurrences can inform more personalized follow-up decisions. METHODS: Women diagnosed with stage I-III invasive breast cancer who were treated with curative intent were selected from the Netherlands Cancer Registry (N = 9342). Extended Cox regression was used to model the hazard of recurrence over ten years of follow-up for not only site-specific first, but also subsequent recurrences after LR or RR. RESULTS: In total, 362 patients had LR, 148 RR and 1343 DM as first recurrence. The risk of first recurrence was highest during the second year post-diagnosis (3.9%; 95% CI 3.5-4.3) with similar patterns for LR, RR and DM. Young age (2 cm, tumour grade II/III, positive lymph nodes, multifocality and no chemotherapy were prognostic factors for first recurrence. The risk of developing a second recurrence after LR or RR (N = 176) was significantly higher after RR than after LR (50 vs 29%; p < 0.001). After a second LR or RR, more than half of the women were diagnosed with a third recurrence. CONCLUSIONS: Although the risk of subsequent recurrence is high, absolute incidence remains low. Also, almost half the second recurrences are detected in the first year after previous recurrence and more than 80% are DM. This suggests that more intensive follow-up for early detection subsequent recurrence is not likely to be (cost-)effective

Inflammatory breast cancer in the Netherlands; improved survival over the last decades

PURPOSE: Locally advanced breast cancer (LABC) includes inflammatory breast cancer (IBC) as well as non-inflammatory LABC (NI-LABC). The aim of this population-based study was to compare the tumour characteristics, treatment and relative survival of IBC and NI-LABC patients. METHODS: Patients with either IBC (cT4d) or NI-LABC (cT4a-c) were identified from the nationwide Netherlands Cancer Registry from the period 1989-2015. In each group, patients are divided into three time periods in order to perform a trend analysis: 1989-1997, 1998-2006, and 2007-2015. RESULTS: IBC comprised 1.1% and NI-LABC 4.6% of all diagnosed breast cancer patients. IBC patients showed more nodal metastases (77.8 vs. 69.7%, P < 0.001) and distant metastases (39.7 vs. 34.1%, P < 0.001). IBC tumours were more often triple negative (23.2 vs. 12.8%, P < 0.001) and poorly differentiated (69.8 vs. 53.8%, P < 0.001). Trimodality therapy (neoadjuvant chemotherapy, surgery and adjuvant radiotherapy) was more often applied over time in both groups (IBC: 23.7%-56.0%-68.6%; NI-LABC: 3.7%-25.9%-43.6%; P trend < 0.001). In IBC patients, relative 5-year survival was significantly shorter than in patients with NI-LABC (30.2 vs. 45.1%, P < 0.001). The relative survival significantly improved for IBC from 17.2% (1989-1997) to 30.0 and 38.9% for the last two time periods (1998-2006: P < 0.001; 2007-2015: P < 0.001). In contrast, survival did not significantly improve in NI-LABC breast cancer: from 44.7% (1989-1997) to 44.0 and 48.4% (1998-2006: P = 0.483; 2007-2015: P = 0.091). CONCLUSIONS: IBC has tumour characteristics that determine its aggressive biology compared to NI-LABC. Trimodality therapy was increasingly applied in both groups, but did not improve survival in NI-LABC. Although relative survival in IBC patients has improved during the last decades, it remains a disease with a dismal prognosis