Set-up of a population-based familial breast cancer registry in Geneva, Switzerland: validation of first results

Background: This article evaluates the accuracy of family history of breast and ovarian cancer among first-degree relatives of breast cancer patients, retrospectively collected during the setting up of a population-based family breast cancer registry. Patients and methods: Family histories of cancer for all women with breast cancer recorded at the Geneva Cancer Registry from 1990 to 1999 were retrospectively extracted from medical files. The accuracy of these family histories was validated among Swiss women born in Geneva: all 119 with a family history of breast (n = 110) or ovarian (n = 9) cancer and a representative sample of 100 women with no family history of breast or ovarian cancer. We identified the first-degree relatives of these women with information from the Cantonal Population Office. All first-degree relatives, resident in Geneva from 1970 to 1999, were linked to the cancer registry database for breast and ovarian cancer occurrence. Sensitivity, specificity and level of overall agreement (κ) were calculated. Results: Among 310 first-degree relatives identified, 61 had breast cancer and six had ovarian cancer recorded at the Geneva Cancer Registry. The sensitivity, specificity and κ of the reported family histories of breast cancer were 98%, 97% and 0.97, respectively. For ovarian cancer, the sensitivity, specificity and κ were 67%, 99%, and 0.66, respectively. Conclusions: This study indicates that retrospectively obtained family histories are very accurate for breast cancer. For ovarian cancer, family histories are less precise and may need additional verificatio

Breast cancer management and outcome according to surgeon's affiliation: a population-based comparison adjusted for patient's selection bias

Background Studies have reported that breast cancer (BC) units could increase the quality of care but none has evaluated the efficacy of alternative options such as private BC networks, which is our study objective. Patients and methods We included all 1404 BC patients operated in the public unit or the private network and recorded at the Geneva Cancer Registry between 2000 and 2005. We compared quality indicators of care between the public BC unit and the private BC network by logistic regression and evaluated the effect of surgeon's affiliation on BC-specific mortality by the Cox model adjusting for the propensity score. Results Both the groups had high care quality scores. For invasive cancer, histological assessment before surgery and axillary lymph node dissection when indicated were less frequent in the public sector (adjusted odds ratio (OR): 0.4, 95% confidence interval (CI) 0.3-0.7, and OR: 0.4, 95% CI 0.2-0.8, respectively), while radiation therapy after breast-conserving surgery was more frequent (OR: 2.5, 95% CI 1.4-4.8). Surgeon affiliation had no substantial effect on BC-specific mortality (adjusted hazard ratio (HR): 0.8, 95% CI 0.5-1.4). Conclusions This study suggests that private BC networks could be an alternative to public BC units with both structures presenting high quality indicators of BC care and similar BC-specific mortalit

Hormonal therapy for oestrogen receptor-negative breast cancer is associated with higher disease-specific mortality

Background: Tamoxifen has a remarkable impact on the outcome of oestrogen receptor (ER)-positive breast cancer. Without proven benefits, tamoxifen is occasionally prescribed for women with ER-negative disease. This population-based study aims to estimate the impact of tamoxifen on the outcome of ER-negative disease. Methods: We identified all women (n = 528) diagnosed with ER-negative invasive breast cancer between 1995 and 2005. With Cox regression analysis, we calculated breast cancer mortality risks of patients treated with tamoxifen compared with those treated without tamoxifen. We adjusted these risks for the individual probabilities (propensity scores) of having received tamoxifen. Results: Sixty-nine patients (13%) with ER-negative disease were treated with tamoxifen. Five-year disease-specific survival for women treated with versus without tamoxifen were 62% [95% confidence interval (CI) 48% to 76%] and 79% (95% CI 75% to 83%), respectively (PLog-rank < 0.001). For ER-negative patients, risk of death from breast cancer was significantly increased in those treated with tamoxifen compared with patients treated without tamoxifen (adjusted hazard ratio = 1.7, 95% CI 1.1-2.9, P = 0.031). Conclusion: Our results show that patients with ER-negative breast cancer treated with tamoxifen have an increased risk of death from their disease. Tamoxifen use should be avoided for these patient

Remarkable change in age-specific breast cancer incidence in the Swiss canton of Geneva and its possible relation with the use of hormone replacement therapy

BACKGROUND: This article aims to explain the reasons for the remarkable change in age of breast cancer occurrence in the Swiss canton of Geneva. METHODS: We used population-based data from the Geneva cancer registry, which collects information on method of detection, stage and tumour characteristics since 1975. For patients diagnosed between 1997–2003, we obtained additional information on use of hormone replacement therapy from a large prospective study on breast cancer. Using generalized log linear regression analysis, we compared age-specific incidence rates with respect to period, stage, oestrogen receptor status, method of detection and use of hormone replacement therapy. RESULTS: In the periods 1975–1979 and 1985–1989, breast cancer risk increased with age, showing the highest incidence rates among women aged ≥ 85 years. From 1997, the age-specific incidence curve changed completely (p < 0.0001), showing an incidence peak at 60–64 years and a reduced incidence among elderly women. This incidence peak concerned mainly early stage and oestrogen positive cancers and was exclusively observed among women who ever used hormone replacement therapy, regardless whether the tumour was screen-detected or not. CONCLUSION: The increasing prevalence of hormone replacement therapy use during the 1990s could explain the important change in age-specific breast cancer incidence, not only by increasing breast cancer risk, but also by revealing breast cancer at an earlier age

Impact of familial risk factors on management and survival of early-onset breast cancer: a population-based study

This population-based study evaluates the impact of a strong family history of breast cancer on management and survival of women with early-onset disease. We identified all breast cancer patients ⩽50 years, recorded between 1990 and 2001 at the Geneva familial breast cancer registry. We compared patients at high familial risk and low familial risk in terms of tumour characteristics, method of detection, treatment, survival and breast cancer mortality risk. Compared to patients at low familial risk (n=575), those at high familial risk (n=58) received significantly more often systemic therapy, especially for node-negative or receptor-positive disease. Five-year disease-specific survival rates of patients at high vs low familial risk were 86 and 90%, respectively. After adjustment, there was no difference in breast cancer mortality in general. A strong family history nonsignificantly increased breast cancer mortality in patients ⩽40 years (adjusted hazard ratio (HR) 4.0, 95% CI 0.8–19.7) and in patients treated without chemotherapy (adjusted HR 2.7, 95% CI 0.6–12.5). A strong family history of breast cancer is associated with an increased use of systemic therapy in early-onset patients. Although a strong family history does not seem to affect survival in general, it may impair survival of very young patients and patients treated without adjuvant chemotherapy. Owing to the limited number of patients in this study, these results should be used only to generate hypotheses

CONTRACTILE RESPONSE OF PERITUBULAR MYOID CELLS TO PROSTAGLANDIN F2alfa

Prostaglandin (PG) F2alpha, a well known agonist of smooth muscle, is produced in the male gonad. We have investigated whether PG F2alpha stimulates seminiferous tubule contractility through direct action on peritubular myoid cells. Myoid cells from prepubertal rats were highly purified through Percoll density gradient and cultured in vitro. Stimulation with PG F2alpha was observed to induce: (i) rapid and dose-dependent production of inositol phosphates; (ii) mobilization of Ca2+ from intracellular stores and (iii) cell contraction. Moreover, at a concentration of 10 microM the agonist was found to induce immediate contractile response of peritubular tissue in freshly explanted tubular fragments from both young and adult rats; the explants were examined in whole-mount preparations and the peritubular myoid cell layer was identified by selective staining for alkaline phosphatase activity. Our observations demonstrate that myoid cells are a direct target for PG F2alpha and suggest a role of the eicosanoid in the intragonadal control of seminiferous tubule contractility

Platelet-Derived GrowthFactor-BB stimulates hypertrophy of peritubular smooth muscle cells from rat testis in primary cultures

The tunica propria of seminiferous tubules contains a particular type of smooth muscle cell (myoid cells) arranged in a contractile epithelioid layer that is responsible for sperm and tubular fluid flow. Unlike other types of smooth muscle (SM) cells, highly purified populations of peritubular smooth muscle cells (PSMC) survive and maintain their contractile phenotype in primary cultures in controlled conditions. We used this culture model to investigate the response of the SM contractile phenotype to prolonged exposure to platelet-derived growth factor (PDGF), one of the main factors involved in vascular SM pathologies. We observed that 4-day continuous exposure of PSMC to PDGF-BB at nanomolar concentrations in plain medium enhances contractile phenotype traits and induces cell hypertrophy without inducing proliferation. In Northern and Western blotting experiments, SM-alpha-actin transcript and protein were found to be markedly increased in the PDGF-BB-treated samples, which is in line with the formation of conspicuous SM-alpha-actin-containing stress fibers. Moreover, binding sites for endothelin-1 were increased, and the calcium response to the contractile agonist, determined in single fura-2-loaded cells, was enhanced. In response to PDGF-BB, the cells underwent immediate, transient contraction, as seen in a scanning electron microscope, followed by a gradual increase in size, as evaluated by cytofluorometry, and enhancement of protein synthesis. The observed pattern of response to PDGF-BB was not accompanied by cell proliferation, as assessed by [3H]thymidine incorporation and direct cell counts. Unlike other SM cell types, in which proliferation and loss of contractile traits are induced by PDGF, chronic treatment of PSMC with this growth factor results in hypertrophy rather than hyperplasia

Pure Sertoli Cell Cultures: A New Model for the Study of Somatic-Germ Cell Interactions

A new technique involving a brief hypotonic treatment was developed for obtaining pure rat Sertoli cell cultures. This method forthe selective removal of the germ cells present in Sertoli cell enriched cultures (SCEC) is based on the differential response of the two cell types to changes in osmolarity. It was found that the optimal conditions for germ cell detachment without Sertoli cell impairment consist of incubation for 2.5 minutes at 20 C in 20 mM TRIS-HCl. When compared with SCEC, the Sertolicell-onlycultures (SCOC) thus obtained retain unaltered morphologic features and responsiveness to FSH stimulation (morphologic modifications and 17 -estradiol secretion). The availability of pure Sertoli cell cultures (ie, free of contaminating germ cells) provides an advantage in the study of their metabolic activity. Moreover, with this technique it is feasible to compare Sertoli cell function in association with germ cells to function in the absence of germ cells.A new technique involving a brief hypotonic treatment was developed for obtaining pure rat Sertoli cell cultures. This method for the selective removal of the germ cells present in Sertoli cell enriched cultures (SCEC) Is based on the differential response of the two cell types to changes in osmolarity. It was found that the optimal conditions for germ cell detachment without Sertoli cell impairment consist of incubation for 2.5 minutes at 20 C in 20 m TRISHCI. When compared with SCEC, the Sertolicell-only cultures (SCOC) thus obtained retain unaltered morphologic features and responsiveness to FSH stimulation (morphologic modifications and 17 β-estradiol secretion). The availability of pure Sertoli cell cultures (Ie, free of contaminating germ cells) provides an advantage in the study of their metabolic activity. Moreover, with this technique it is feasible to compare Sertoli cell function in association with germ cells to function in the absence of germ cells

Gastric emptying and dyspeptic symptoms in patients with gastroesophageal reflux [see comments]

OBJECTIVES. To clarify 1) whether gastric emptying of a mixed meal is delayed in patients with gastroesophageal reflux and 2) the relationship between dyspeptic symptoms and delayed gastric emptying in refluxers. METHODS. Gastric emptying of a solid meal was studied by ultrasound in 25 patients with pathological esophageal acid exposure. Gastric emptying was then assessed in relation to upper digestive endoscopy, esophageal manometry, 24-h pH monitoring and quantification of symptoms of reflux- and dysmotility-like dyspepsia. RESULTS. Fifteen of 25 refluxers had esophagitis, and 15 were "dyspeptic". Refluxers exhibited a significant delay in gastric emptying compared with controls [307.6 (21.0) vs. 209 (10.4) min, p < 0.001). Patients with delayed emptying had low LES pressure [11.9 (2.1) vs. 18.6 (2.1) mm Hg, p < 0.05]. There was no correlation between delayed emptying and either pH monitoring or presence of esophagitis. There were no differences in any of the pH monitoring parameters between refluxers with and without coexisting dysmotility-like symptoms. CONCLUSIONS. Gastric emptying of a solid meal is markedly delayed in patients with gastroesophageal reflux. However, no direct causal link was found between delayed emptying and reflux. Our data suggest the presence of a motility disorder in gastroesophageal reflux which is not confined to the esophagogastric junction