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

BACKGROUND: Some 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. METHODS: In 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. RESULTS: Ductal 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. CONCLUSION: Our 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.

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

INTRODUCTION: Mammography 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. METHODS: We 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. RESULTS: We 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)). CONCLUSIONS: After nine years follow-up, at least 33% of the improved survival is attributable to improved breast cancer management through multidisciplinary medical care.

Effect of an antepartum Pap smear on the coverage of a cervical cancer screening programme: a population-based prospective study.

BACKGROUND: Almost one-third of Norwegian women aged 25-69 years invited to have a Pap smear do not attend during the recommended period, and thus constitute a population with high-risk of cervical cancer (CC). Since the incidence of precancerous lesions of the cervix peak with occurrence of pregnancies within the same decade in women aged 25 to 35 years of age, antepartum care presents an opportunity to offer a Pap smear thereby increasing the coverage of the programme. The study objective was to describe the effect of the antepartum Pap smear on the coverage of a cytological CC screening programme. METHODS: Among 2 175 762 women resident in Norway in 31.12.1996, all women who gave birth in 1996-7 were identified from the Medical Birth Registry of Norway. Attendance to the cervical cancer screening was assessed by linkage to the Cytology Registry separately for the pregnant and non-pregnant women cohorts. The results were stratified by age, history of previous Pap smear and history of invitation to the CC screening programme. Logistic regression was used to estimate the relative probabilities of having a Pap smear adjusted for age, screening history, and time since invitation, for pregnant and non-pregnant women, respectively. RESULTS: 69% of the pregnant women had a Pap smear during one year of follow-up since beginning of the pregnancy with the majority taken during the antepartum period. Irrespectively of age or history of having a Pap smear, pregnant women were 4.3 times more likely to have a Pap smear during follow-up compared to non-pregnant women. 63.2% of the pregnant women had a smear as response to the invitation letter compared to 28.7% of the non-pregnant women, OR = 2.1 (95% CI 1.9 to 2.4). As an indication of "over-screening", 5397 pregnant women (57.8%) with a smear shortly before the start of follow-up also had a new Papsmear, compared to 83 023 (32.3%) in non-pregnant. CONCLUSION: Pap smear screening during pregnancy increases the coverage of the CC screening programme. The contribution of the antepartum Pap smear to "over-screening" exists but its effect is modest in countries where women on average become pregnant after the start of recommended age of screening.

Trends in testicular cancer incidence in the Nordic countries, focusing on the recent decrease in Denmark.

Testicular cancer is the most frequent malignancy among young men, and there have been steady increases in its incidence in most western countries for many decades. Recently, a decrease was seen in some countries, including Denmark. Here, we report recent trends in testicular cancer incidence in the Nordic countries. We address the hypothesis that the causal factors for testicular cancer in Denmark are related to birth cohort and that non-seminoma and seminoma tumours have a common aetiology. An overall increase in testicular cancer incidence was found in the Nordic countries, corresponding to increases with each consecutive birth cohort in each country. In Denmark, a decline in incidence was observed during the past 5 years, and men born around 1943 and around 1968 showed lower incidences than men born just before or just after these dates. These birth-cohort effects were seen both for seminoma and non-seminoma tumours. This descriptive study confirms the hypothesis that birth cohort has a major influence on the incidence pattern of testicular tumours and suggests that seminoma and non-seminoma have common aetiological factors.

Screening histories of women with CIN 2/3 compared with women diagnosed with invasive cervical cancer: a retrospective analysis of the Norwegian Coordinated Cervical Cancer Screening Program.

OBJECTIVE: This study compares the screening history for women with cervical intraepithelial neoplasia (CIN) 2/3 or adenocarcinoma in situ (ACIS) with women with different stages and subtypes of cervical carcinoma. METHODS: An analysis of the Norwegian Coordinated Cervical Screening Program comparing all cases with a CIN 2/3/ACIS (N=8586) with all ICC (N=777) in the period 2000-2002. All Pap smears since 1992 were used to characterise detection mode and screening history. Multinominal regression models estimated the risk associated with detection mode and adequate Pap smear history. RESULTS: A wide range of age at diagnosis, from 16 to 92 years of age was observed regardless of the stage of the disease. Fifty five percentage of the women diagnosed with CIN 2/3/ACIS had an adequate screening history. Of women diagnosed with SCC, 45.1% in stage I, and 10.5% in stage IV had an adequate history. The median age of women with CIN 2/3 (34 years) and squamous cervical carcinoma (SCC) stage I (37 years) given an adequate Pap smear history was not significantly different. For women with ACC, the proportion with adequate screening history was roughly 50% for all stages. After adjustment for detection mode and age, the OR for being diagnosed with ICC stage I compared to CIN 2/3 was 1.2 (95% CI: 1.0-1.5), while the OR of being diagnosed with ICC stage II-IV was 3.4 (95% CI: 2.3-4.8). CONCLUSIONS: Women with CIN 2/3 and ICC stage I were similar with respect to screening histories, i.e. detection mode and age at diagnosis, while women with ICC stage II-IV seldom had an adequate screening history and were diagnosed at a significantly higher age.

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.

Predicting CIN2+ when detecting HPV mRNA and DNA by PreTect HPV-proofer and consensus PCR: A 2-year follow-up of women with ASCUS or LSIL Pap smear.

It has been suggested that human papillomavirus (HPV) testing improves follow-up of atypical cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) in cervical cancer screening programs. To evaluate the prognostic value of including HPV testing as an adjunct to cytology, we carried out a 2-year follow-up study of 77 women with ASCUS or LSIL Papanicolaou (Pap) smear in the Norwegian Cervical Cancer Screening Program (NCCSP) for detection of histological cervical intraepithelial neoplasia (CIN) 2+. The study includes a comparison between viral mRNA and DNA detection. PreTect HPV-Proofer was used for HPV E6/E7 mRNA detection from the 5 high-risk types 16, 18, 31, 33 and 45, and Gp5+/6+ consensus PCR was used for HPV DNA detection. Twice as many women were positive for HPV DNA (54.6%) than for HPV mRNA (23.4%). PreTect HPV-Proofer and consensus PCR had a sensitivity of 85.7% (95% confidence interval [CI] = 42.1-99.6) for detecting CIN2+ during follow-up. The specificity was significantly higher for PreTect HPV-Proofer, 84.9% (95% CI = 73.9-92.5), than for consensus PCR, 50.0% (95% CI = 37.4-62.6). PreTect HPV-Proofer positive women were 69.8 times (95% CI = 4.3-1137.3) more likely to be diagnosed with CIN2+ within 2 years than PreTect HPV-Proofer negative women. Consensus PCR-positive women were 5.7 times (95% CI = 0.6-52.0) more likely to be diagnosed with CIN2+ within 2 years than PCR-negative women. With equal sensitivity and higher specificity than consensus PCR, the PreTect HPV-Proofer might offer an improvement for the triage of women with ASCUS or LSIL Pap smear.