Is letrozole needed for controlled ovarian stimulation in patients with estrogen receptor-positive breast cancer?

OBJECTIVE: To assess the advantages and disadvantages of using letrozole for controlled ovarian stimulation (COH) in young patients with estrogen receptor-positive (ER+) breast cancer, wishing to cryopreserve oocytes. DESIGN: Retrospective cohort analysis. SETTING: Sixteen Italian units for reproductive medicine and in vitro fertilization. METHODS: Data of 50 ER+ breast cancer patients undergoing COH to cryopreserve oocytes before gonadotoxic chemotherapy with a letrozole plus gonadotropins (Le+Gn) protocol were compared with those of 25 young women with ER- breast cancer, submitted to COH using a protocol with gonadotropins alone (Gn-only). RESULTS: The Le+Gn protocol implied a significantly lower total Gn consumption and allowed to maintain significantly lower circulating E2 levels at all checkpoints throughout stimulation (peak E2 value 446 ± 357 versus 1553 ± 908 pg/ml, respectively; p = 0.001). On the other side, the Le+Gn protocol allowed a significantly lower yield of oocytes available for cryostorage (6.6 ± 3.5 versus 8 ± 5, respectively; p = 0.038). CONCLUSIONS: In breast cancer patients, the association of letrozole to Gn significantly reduces the number of oocytes available for cryostorage in comparison with the use of Gn alone. On the other side, it is associated with significantly lower E2 levels during the whole stimulation cycle, a safety issue that has been traditionally considered advantageous in case of ER+ cancers.

Breast cancer incidence trends in European women aged 20-39 years at diagnosis.

An increase in the incidence of breast cancer in women aged<40 years has been reported in recent years. Increased incidence could be partly explained by subtle detection biases, but the role of other risk factors cannot be ruled out. The purpose of the present study was to investigate the changes in temporal trends in breast cancer incidence in European women aged 20-39 years at diagnosis. Age specific breast cancer incidence rates for 17 European Cancer Registries were retrieved for the calendar period 1995-2006. Cancer registries data were pooled to reduce annual fluctuations present in single registries and increase incidence rates stability. Regression models were fitted to the data assuming that the number of cancer cases followed the Poisson distribution. Mean annual changes in the incidence rate (AIC) across the considered time window were calculated. The AIC estimated from all European registries was 1.032 (95% CI=1.019-1.045) and 1.014 (95% CI=1.010-1.018) in women aged 20-29 and 30-39 years old at diagnosis, respectively. The major change was detected among women aged 25-29 years at diagnosis: AIC=1.033 (95% CI=1.020-1.046). The upward trend was not affected when registries with high or low AIC were removed from the analysis (sensitivity analysis). Our findings support the presence of an increase in the incidence of breast cancer in European women in their 20s and 30s during the decade 1995-2006. The interpretation of the observed increase is not straightforward since a number of factors may have affected our results. The estimated annual increase in breast cancer incidence may result in a burden of the disease that is important in terms of public health and deserves further investigation of possible risk factors.

Second-line treatment with intravenous gemcitabine and oral etoposide in platinum-resistant advanced ovarian cancer patients: results of a phase II study.

OBJECTIVE: The outcome of advanced ovarian cancer patients has not significantly improved since the introduction of platinum. One of the major reasons for this failure is the lack of an effective second-line treatment. In this phase II trial we tested the combination of gemcitabine and etoposide in 2 different groups of patients. Group 1 consisted of patients showing disease progression or relapse within 6 months of first-line platinum-based chemotherapy. Group 2 comprised heavily pretreated patients showing progression during the last chemotherapy attempt. METHODS: Thirty-four patients were enrolled. Gemcitabine was administered at a dose of 1,000 mg/m(2) on days 1 and 8 and etoposide was administered orally at 100 mg/day on days 8-12 for 6 courses. RESULTS: Eighteen patients (52.9%) had an objective response and the median duration of the response was 10.3 months. Our chemotherapy regimen showed a low toxicity and good patient compliance. In 5 patients the treatment had to be delayed and in only 2 patients it was discontinued. CONCLUSIONS: The combination of gemcitabine and oral etoposide seems to be a safe and effective second-line treatment for platinum-resistant ovarian cancer patients. Additional data on larger series are warranted to better define the activity of this combination regimen.

Early effects of low benzene exposure on blood cell counts in Bulgarian petrochemical workers.

OBJECTIVES: Only few studies have examined early hematological effects in human populations exposed to low benzene levels and their findings are controversial. We evaluated hematological outcomes (WBC, neutrophils, lymphocytes, monocytes, eosinophils, basophils, RBC, Hb, HCT MCV, platelets and MPV) in a population of 153 Bulgarian petrochemical workers exposed to benzene (range 0.01-23.9 ppm) and 50 unexposed subjects. METHODS: Written informed consent was obtained and a self-administered questionnaire used to collect information on current smoking habits, lifestyle, and occupational activities. Exposure assessment was based on personal monitoring sampling the day before phlebotomy. Urinary trans-trans-muconic acid (t,t-MA) was determined at the beginning and end of the work shift. Based on individual airborne benzene measurements, study subjects were categorized in three exposure categories (referents, <1 and > or =1 ppm). Mean values of each hematologic outcomes in each exposure category were compared with the referent group using a multiple linear regression model adjusted for age, gender, current smoking habits and environmental toluene level. The influence of the CYP2E1 (RsaI and DraI) and NQO1 609C>T genetic polymorphisms on differential hematological parameters was also investigated. RESULTS: No dose-response effect was observed for most of the examined hematological outcomes (WBC, lymphocytes, neutrophils, monocytes, RBC, Hb, HCT, MCV, platelets and MPV). The eosinophil count was inversely related to benzene exposure only among smokers. Conversely, basophils increased with increasing exposure. No effect on benzene hematotoxicity was found for any of the investigated polymorphisms. CONCLUSION: In our study we did not find a decline in WBC and lymphocytes related to benzene exposure. A myeloproliferative effect of benzene is highly unlikely to explain the observed reduction in eosinophils and increase in basophils as it would lead to a concordant depression in all granulocyte subpopulations. Whether benzene effects at low doses are present in Caucasian populations remains uncertain, thus warranting further investigations.

Cancer incidence in pet dogs: findings of the Animal Tumor Registry of Genoa, Italy.

BACKGROUND: The occurrence of spontaneous tumors in pet animals has been estimated in a few European and North American veterinary cancer registries with dissimilar methodologies and variable reference populations. OBJECTIVES: The Animal Tumor Registry (ATR) of Genoa, Italy, was established in 1985 with the aim of estimating the occurrence of spontaneous tumors in dogs. METHODS: Six thousand seven hundred and forty-three tumor biopsy specimens were received from local veterinarians in the Municipality of Genoa between 1985 and 2002. Three thousand and three hundred and three (48.9%) biopsy specimen samples were diagnosed as cancer and were coded according to the International Statistical Classification of Diseases (ICD-9). RESULTS: Mammary cancer was the most frequently diagnosed cancer in female dogs, accounting for 70% of all cancer cases. Incidence of all cancers was 99.3 per 100,000 dog-years (95% CI: 93.6-105.1) in male dogs and 272.1 (95% CI: 260.7-283.6) in female dogs. The highest incidence rates were detected for mammary cancer (IR = 191.8, 95% CI: 182.2-201.4) and for non-Hodgkin's lymphoma (IR = 22.9, 95% CI: 19.7-26.5) in bitches and for non-Hodgkin's lymphoma (IR = 19.9, 95% CI: 17.4-22.7) and skin cancer (IR = 19.1, 95% CI: 16.6-21.8) in male dogs. All cancer IR increased with age ranging between 23.7 (95% CI: 18.4-30.1) and 763.2 (95% CI: 700.4-830.1) in bitches and between 16.5 (95% CI: 12.8-21.1) and 237.6 (95% CI: 209.1-269.0) in male dogs aged < or =3 years and >9-11 years. CONCLUSION: This study summarizes the work done by the ATR of Genoa, Italy, between 1985 and 2002. All cancer incidence was 3 times higher in female than in male dogs, a difference explained by the high rate of mammary cancer observed in bitches. Because a biopsy specimen was required to make a cancer diagnosis, cancer rates for internal organs cancers, such as respiratory and digestive tract cancers may have been underestimated in the study population.

Genomic damage in children accidentally exposed to ionizing radiation: a review of the literature.

During the last decade, our knowledge of the mechanisms by which children respond to exposures to physical and chemical agents present in the environment, has significantly increased. Results of recent projects and programmes focused on children's health underline a specific vulnerability of children to environmental genotoxicants. Environmental research on children predominantly investigates the health effects of air pollution while effects from radiation exposure deserve more attention. The main sources of knowledge on genome damage of children exposed to radiation are studies performed after the Chernobyl nuclear plant accident in 1986. The present review presents and discusses data collected from papers analyzing genome damage in children environmentally exposed to ionizing radiation. Overall, the evidence from the studies conducted following the Chernobyl accident, nuclear tests, environmental radiation pollution and indoor accidental contamination reveals consistently increased chromosome aberration and micronuclei frequency in exposed than in referent children. Future research in this area should be focused on studies providing information on: (a) effects on children caused by low doses of radiation; (b) effects on children from combined exposure to low doses of radiation and chemical agents from food, water and air; and (c) specific effects from exposure during early childhood (radioisotopes from water, radon in homes). Special consideration should also be given to a possible impact of a radiochemical environment to the development of an adaptive response for genomic damage. Interactive databases should be developed to provide integration of cytogenetic data, childhood cancer registry data and information on environmental contamination. The overall aim is to introduce timely and efficient preventive measures, by means of a better knowledge of the early and delayed health effects in children resulting from radiation exposure.

Ethics in studies on children and environmental health.

Children, because of age-related reasons, are a vulnerable population, and protecting their health is a social, scientific and emotional priority. The increased susceptibility of children and fetuses to environmental (including genotoxic) agents has been widely discussed by the scientific community. Children may experience different levels of chemical exposure than adults, and their sensitivity to chemical toxicities may be increased or decreased in comparison with adults. Such considerations also apply to unborn (fetal exposure) and newborn (neonatal exposure) children. Therefore, research on children is necessary in both clinical and environmental fields, to provide age-specific relevant data regarding the efficacy and safety of medical treatments, and regarding the assessment of risk from unintended environmental exposure. In this context, the stakeholders are many, including children and their parents, physicians and public health researchers, and the society as a whole, with its ethical, regulatory, administrative and political components. The important ethical issues are information of participants and consent to participate. Follow-up and protection of data (samples and information derived from samples) should be discussed in the context of biobanks, where children obtain individual rights when they become adults. It is important to realise that there are highly variable practices within European countries, which may have, in the past, led to differences in practical aspects of research in children. A number of recommendations are provided for research with children and environmental health. Environmental research with children should be scientifically justified, with sound research questions and valid study protocols of sufficient statistical power, ensuring the autonomy of the child and his/her family at the time of the study and later in life, if data and samples are used for follow-up studies. When children are enrolled, we recommend a consent dyad, including (1) parental (or legal guardian) informed consent and (2) the child's assent and/or informed consent from older minors. For evaluation of the studies including children, a paediatrician should always be involved in the research ethics committee.

Retrospective mortality cohort study of Italian workers compensated for silicosis.

OBJECTIVES: To estimate cause specific mortality in a large cohort of Italian workers compensated for silicosis. METHODS: The cohort included 14 929 subjects (14,098 men and 831 women) compensated for silicosis between 1946 and 1979, alive on 1 January 1980, and resident in Tuscany (a region of central Italy with 3,547,000 inhabitants). Mortality follow up ranged from 1980 to 1999. Vital status and the causes of death were determined by linkage with the regional mortality registry and with the national mortality database. The cohort mortality rates were compared to the rates of the local reference population. SMRs and their 95% confidence intervals were computed assuming a Poisson distribution of the observed deaths. Specific SMR analyses were performed according to the level of disability, the year of compensation assignment, and the job type. RESULTS: A significant excess mortality was observed in male silicotics for cancer of the lung, trachea, and bronchus and cancer of the liver, respiratory diseases (silicosis, asbestosis, antracosilicosis, and other pneumoconiosis), and for tubercolosis. Statistically significant mortality excess was observed in female silicotics for respiratory diseases (specifically silicosis and other pneumoconiosis) and tuberculosis. Analyses for period of compensation assignment showed a twofold increased SMR for biliary tract cancer among female workers and for liver cancer among male workers compensated before 1970. CONCLUSIONS: The excess mortality from respiratory tract cancers and respiratory tract diseases detected in Italian compensated silicotics are in agreement with previous epidemiological studies. Although the twofold increased risk for liver cancer among males is suggestive of a possible association with silica dust exposure, the finding needs to be confirmed.

A mortality cohort study among workers in a graphite electrode production plant in Italy.

BACKGROUND: Graphite electrode manufacturing workers are exposed to coal tar and its volatiles containing a variety of polycyclic aromatic hydrocarbons (PAH), silica and graphite dusts, and asbestos. AIMS: To investigate mortality from cancer and other diseases among workers in a graphite electrode production plant in Italy. METHODS: A total of 1291 males actively employed between 1 January 1950 and 31 December 1989 who had worked at the plant for at least one year were studied. The follow up extended from 1950 to 1997. Standardised mortality ratios (SMR) and their 95% confidence intervals (CI) were computed using mortality rates for the Italian and regional male population. RESULTS: Excess mortality was observed for all causes (SMR 1.44, CI 1.32 to 1.56), all cancers (SMR 1.27, CI 1.07 to 1.50), liver cancer (SMR 4.19, CI 2.68 to 6.23), silicosis (SMR 66.39, CI 52.56 to 82.7), and cirrhosis and other chronic diseases of the liver (SMR 1.87, CI 1.31 to 2.59) in comparison with the national male population. When regional rates were used to calculate the number of expected deaths, SMRs remained higher for silicosis (SMR 57.32, 42.11 to 76.22), and liver cancer (SMR 2.57, 1.57 to 3.97). Mortality from silicosis was increased in workers hired at young ages (<25 years, SMR 81.79; 25-34 years, SMR 82.73), and in workers aged <45 at death (SMR 333.3, CI 159.8 to 613). Mortality from liver cancer increased threefold (SMR 3.11, CI 1.78 to 5.05) in workers with more than 10 years of employment at the plant during the manufacture of Karbate products. CONCLUSIONS: Results support the association between excess mortality from silicosis and occupational exposure to siliceous sands experienced during graphite electrode manufacturing. The observed excess mortality from liver cancer is compatible, to some extent, with exposures that may have occurred during the manufacture of phenolic and furfuryl resins treated products, although a role of lifestyle factors and viral infections cannot be excluded.