Steinar Thoresen

Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients.

Aims:  To determine the frequency and survival of the various types of uterine sarcoma in the total population of Norway and evaluate histopathological prognostic factors in order to identify risk groups.

A Basal Epithelial Phenotype Is More Frequent in Interval Breast Cancers Compared with Screen Detected Tumors

Interval breast cancer reduce the effectiveness of mammography screening programs. We studied 95 interval cancers, diagnosed during 1996 to 2001 as part of the population-based Norwegian Breast Cancer Screening Program. These cases were matched on size (±2.0 mm) to 95 screen-detected breast cancers, and the tumors were compared by immunohistochemical methods using tissue microarrays. Patients with interval cancers were more likely to be younger [odds ratio (OR), 4.7; P = 0.0001], to have dense breasts (OR, 3.4; P = 0.004), and to have estrogen receptor–negative tumors (OR, 2.6, P = 0.01), and p53 expression was more frequent (OR, 4.0; P = 0.001). Notably, interval cancers were more likely to have a basal epithelial phenotype, in that expression of cytokeratin 5/6 (OR, 2.3; P = 0.04) and P-cadherin (OR, 2.5; P = 0.04) was more frequent in interval cases than in size-matched, screen-detected tumors. In a logistic regression model, p53 expression, age, and breast density were independent predictors of interval cancers. Our data suggest that breast cancers with a basal epithelial phenotype are more likely than nonbasal breast cancers to present between regular mammograms.

Pregnancy outcome in women before and after cervical conisation : population based cohort study

Objectives To examine the consequences of cervical conisation in terms of adverse outcome in subsequent pregnancies. Design Population based cohort study. Data sources Data on cervical conisation derived from the Cancer Registry of Norway and on pregnancy outcome from the Medical Birth Registry of Norway, 1967-2003. 15 108 births occurred in women who had previously undergone cervical conisation and 57 136 who subsequently underwent cervical conisation. In the same period there were 2 164 006 births to women who had not undergone relevant treatment (control). Results The proportion of preterm delivery was 17.2% in women who gave birth after cervical conisation versus 6.7% in women who gave birth before cervical conisation and 6.2% in women who had not undergone cervical conisation. The relative risk of a late abortion (<24 weeks’ gestation) was 4.0 (95% confidence interval 3.3 to 4.8) in women who gave birth after cervical conisation compared with no cervical conisation. The relative risk of delivery was 4.4 (3.8 to 5.0) at 24-27 weeks, 3.4 (3.1 to 3.7) at 28-32 weeks, and 2.5 (2.4 to 2.6) at 33-36 weeks. The relative risk of preterm delivery declined during the study period and especially of delivery before 28 weeks’ gestation. Conclusion Cervical conisation influences outcome in subsequent pregnancies in terms of an increased risk of preterm delivery, especially in the early gestational age groups in which the clinical significance is highest. A careful clinical approach should be taken in the selection of women for cervical conisation and in the clinical care of pregnancies after a cervical conisation.

Histopathologic subtyping of cervical adenocarcinoma reveals increasing incidence rates of endometrioid tumors in all age groups: A population based study with review of all nonsquamous cervical carcinomas in Norway from 1966 to 1970, 1976 to 1980, and 1986 to 1990

The effect of histopathologic review and subclassification on incidence rates for nonsquamous cell carcinoma (non‐SCC) of the uterine cervix in the Norwegian population was evaluated.

Incidence of thyroid cancer in Norway 1970-1985. Population review on time trend, sex, age, histological type and tumour stage in 2625 cases

In the Norwegian population, a total of 1977 females and 648 males had a diagnosis of thyroid cancer and were reported to the Cancer Registry during 1970‐85. Most of the cases (98%) were histologically or cytologically confirmed, and 141 cases were diagnosed at autopsy (5.4%). Of the patients with information available, 13% had not been subjected to radical surgery. The actual number and annual incidence rate of thyroid cancer increased during the period, especially among females, although a possible levelling off was observed at the end. The frequency of papillary carcinoma clearly increased with time, and tumours were more often localized at presentation in later years. Improved detection of smaller tumours and differences in histopathological judgement may in part explain these results, but our findings are so notable that etiological factors must also be accounted for and researched. Associations between sex, age, histology and stage were further studied in a multivariate log‐linear model. The results confirm the importance of sex and age when exploring the observed incidence pattern and also show that various histological types are unique with respect to metastatic patterns, when confounding factors have been adjusted for.

Improved breast cancer survival following introduction of an organized mammography screening program among both screened and unscreened women: a population-based cohort study.

IntroductionMammography screening reduces breast cancer mortality through earlier diagnosis but may convey further benefit if screening is associated with optimized treatment through multidisciplinary medical care. In Norway, a national mammography screening program was introduced among women aged 50 to 69 years during 1995/6 to 2004. Also during this time, multidisciplinary breast cancer care units were implemented.MethodsWe constructed three cohorts of breast cancer patients: 1) the pre-program group comprising women diagnosed and treated before mammography screening began in their county of residence, 2) the post-program group comprising women diagnosed and treated through multidisciplinary breast cancer care units in their county but before they had been invited to mammography screening; and 3) the screening group comprising women diagnosed and treated after invitation to screening. We calculated Kaplan-Meier plots and multivariable Cox proportional hazard models.ResultsWe studied 41,833 women with breast cancer. The nine-year breast cancer-specific survival rate was 0.66 (95%CI: 0.65 to 0.67) in the pre-program group; 0.72 (95%CI: 0.70 to 0.74) in the post-program group; and 0.84 (95%CI: 0.80 to 0.88) in the screening group. In multivariable analyses, the risk of death from breast cancer was 14% lower in the post-program group than in the pre-program group (hazard ratio 0.86; (95%CI: 0.78 to 0.95, P = 0.003)).ConclusionsAfter nine years follow-up, at least 33% of the improved survival is attributable to improved breast cancer management through multidisciplinary medical care.

Incidence and tumor characteristics of breast cancer diagnosed before and after implementation of a population-based screening-program

Background. Randomized controlled trials and service screening programs have shown that breast cancer screening reduces the mortality from the disease. Several years of monitoring are needed to prove such an effect. In the meantime attention should be paid to early surrogate measures, such as histopathological tumor characteristics. The Norwegian Breast Cancer Screening Program started November 1995. This study compares incidence, prognostic tumor characteristics and surgical treatment in breast cancer cases diagnosed in the pre-screening (1987–1995, n=2 618) and screening period (1996–2004, n=5 417), in women aged 50–69 years, residing in the first four counties implementing the screening program. The screening period is divided into those invited versus those not invited to the screening program, and those exposed (participants) versus those not exposed to the program (non-participants). Results. The incidence of invasive breast cancer rose from 170 per 100 000 women years (wy) in 1987 to 355 per 100 000 wy in 1997. The proportion of DCIS was 5% in the pre-screening period, and 14% in the screening period. Tumors 20 mm or less were diagnosed in 56% of the invasive cases in the pre-screening period, in 74% of the invited, and in 77% of the exposed women. The relative risk of diagnosing breast cancer with metastases was 0.85 (95% CI 0.84–0.87) for invited and 0.82 (95% CI 0.81–0.84) for exposed women, relative to those diagnosed in the pre-screening period. Ablation was performed in 85% of the invasive cases diagnosed in the pre-screening period, and in 45% of the cases in the screening period. Conclusion. Breast cancer diagnosed in the screening period had prognostically favorable tumor characteristics compared to breast cancer diagnosed in the pre-screening period. Implementation of organized population based screening and the time trend are considered possible reasons.

Histological type and grade of breast cancer tumors by parity, age at birth, and time since birth: a register-based study in Norway

BackgroundSome studies have indicated that reproductive factors affect the risk of histological types of breast cancer differently. The long-term protective effect of a childbirth is preceded by a short-term adverse effect. Few studies have examined whether tumors diagnosed shortly after birth have specific histological characteristics.MethodsIn the present register-based study, comprising information for 22,867 Norwegian breast cancer cases (20-74 years), we examined whether histological type (9 categories) and grade of tumor (2 combined categories) differed by parity or age at first birth. Associations with time since birth were evaluated among 9709 women diagnosed before age 50 years. Chi-square tests were applied for comparing proportions, whereas odds ratios (each histological type vs. ductal, or grade 3-4 vs. grade 1-2) were estimated in polytomous and binary logistic regression analyses.ResultsDuctal tumors, the most common histological type, accounted for 81.4% of all cases, followed by lobular tumors (6.3%) and unspecified carcinomas (5.5%). Other subtypes accounted for 0.4%-1.5% of the cases each. For all histological types, the proportions differed significantly by age at diagnoses. The proportion of mucinous and tubular tumors decreased with increasing parity, whereas Paget disease and medullary tumors were most common in women of high parity. An increasing trend with increasing age at first birth was most pronounced for lobular tumors and unspecified carcinomas; an association in the opposite direction was seen in relation to medullary and tubular tumors. In age-adjusted analyses, only the proportions of unspecified carcinomas and lobular tumors decreased significantly with increasing time since first and last birth. However, ductal tumors, and malignant sarcomas, mainly phyllodes tumors, seemed to occur at higher frequency in women diagnosed <2 years after first childbirth. The proportions of medullary tumors and Paget disease were particularly high among women diagnosed 2-5 years after last birth. The high proportion of poorly differentiated tumors in women with a recent childbirth was partly explained by young age.ConclusionOur results support previous observations that reproductive factors affect the risk of histological types of breast cancer differently. Sarcomas, medullary tumors, and possible also Paget disease, may be particularly susceptible to pregnancy-related exposure.

HPV positive bronchopulmonary carcinomas in women with previous high-grade cervical intraepithelial neoplasia (CIN III)

A significant higher incidence of some cancers, especially lung cancer, has been found in women with previous HPV-related (human papillomavirus) urogenital and anal neoplasias than in individuals without this particular clinical history. The aim of our study was to investigate whether HPV is present in both CIN III (cervical intraepithelial neoplasia) lesions and bronchopulmonary second primary cancers in women with a clinical history of both diseases. Paraffin-embedded tumour tissue from 75 patients with bronchopulmonary carcinomas was examined using the polymerase chain reaction (PCR) technique and in situ hybridization for the presence of human HPV. In total, 51 primary tumours without metastases, 11 primary tumours with metastases and 13 lymph node metastases without available tissue from primary tumours were analysed. In our study 37/75 primary bronchopulmonary tumours (49%) were identified as HPV positive by the PCR method: 18 cases were purely HPV 16 positive (49%), 12 were purely HPV 6 positive (32%), 5 cases were HPV 16/6 positive (14%), 1 case was HPV 16/11 positive (2%) and 1 case was HPV 16/18 positive (2%). Fourteen metastases were HPV positive, and HPV 16, 11 and 6 were detected in both regional and distant metastases. Two of the HPV 16-positive metastases were brain metastases from two separate HPV 16-positive primary tumours; 35% of the HPV-positive cases were adenocarcinomas, 30% squamous cell carcinomas, 22% oat cell carcinomas, 5% large cell carcinomas, 3% anaplastic carcinoma, 3% low-differentiated carcinoma, and 3% malignant cylindroma. The CIN III lesions from 34 of the 37 HPV-positive bronchopulmonary carcinomas were analysed by PCR. The overall HPV positivity in the CIN III lesions was 74% (25/34 cases): 48% were purely HPV 16 positive, 24% purely HPV 6 positive, 24% HPV 16/6 positive and 4% were HPV 18 positive. Our results indicate that HPV is also involved in the development of bronchopulmonary cancers in women with a history of CIN III lesions.

Completeness of invasive cervical cancer at the Cancer Registry of Norway

The traditional function of population-based cancer registries as providers of timely and relevant information on cancer incidence has expanded in the last decades to include research on the causes of cancer and their prevention. The quality of the data collected is critical in justifying its use in epidemiological research and decision-making. Completeness is a key indicator of quality and determines the extent to which all incident cancers in the population are included in the registry [1]. The Cancer Registry of Norway has, since 1952, systematically collected notifications on cancer for the Norwegian population. Recent evaluations indicate the Registry is close to complete, partly through compulsory reporting practices and the use of multiples sources of information [2,3].