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Introduction: To investigate the occurrence of previous cancer diagnoses in women suffering from premature ovarian insufficiency (POI) and compare it with the general population, shedding light on the association between cancer, cancer treatments, and POI., Material and Methods: We conducted a nationwide case-control study based on registry data from various sources, including the Social Insurance Institution, Finnish Population Information System, and Finnish Cancer Registry spanning from 1953 to 2018. Our participants comprised all women in Finland who, between 1988 and 2017, received hormone replacement therapy reimbursement for ovarian insufficiency before the age of 40 years (n = 5221). Controls, matched in terms of age and municipality of residence, were selected from the Finnish Population Information System (n = 20 822). Our main exposure variable was a history of cancer diagnosis preceding the diagnosis of POI. We analyzed odds ratios (OR) to compare the prevalence of previous cancers in women with POI with that in controls, stratifying results based on cancer type, age at cancer diagnosis, and the time interval between cancer diagnosis and POI. We also assessed changes in OR for previous cancer diagnoses over the follow-up period., Results: Out of the women diagnosed with POI, 21.9% had previously been diagnosed with cancer, resulting in an elevated OR of 36.5 (95% confidence interval [CI] 30.9 to 43.3) compared with 0.8% of the controls. The risk of developing POI was most pronounced during the first 2 years following a cancer diagnosis, with an OR of 103 (95% CI 74.1 to 144). Importantly, this risk remained elevated even when the time interval between cancer and POI exceeded 10 years, with an OR of 5.40 (95% CI 3.54 to 8.23)., Conclusions: This study reveals that 21.9% of women with POI have a history of cancer, making the prevalence of cancer among these women 27.5 times higher than age-matched controls in the Finnish population. The risk of developing POI is most substantial in the first 2 years following a cancer diagnosis. These findings underscore the role of cancer treatments as an etiological factor for POI and emphasize the importance of recognizing the risk of POI in cancer survivors for early diagnosis and intervention., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Introduction: The long-term risk of cancer among first-degree relatives of ovarian cancer patients, especially their offspring, is of apparent clinical importance. Risks caused by known inherited factors such as BRCA1 or BRCA2 pathogenic variants are well established, but these account for only about 15% of ovarian cancer cases. Less is known about the possible familial risks of sporadic ovarian cancers., Material and Methods: Using registry data, we conducted a retrospective cohort study with a total of 6501 first-degree relatives of 559 epithelial ovarian cancer patients. We studied the occurrence of overall cancer and cancer in specific sites known or suspected to be associated with ovarian cancer (breast, cervix, colon, endometrium, lung and trachea, skin melanoma, ovary, pancreas, prostate, rectum, and stomach)., Results: The overall number of cancers was not increased among the first-degree relatives of epithelial ovarian cancer patients during the up to 48 years of follow up. Among female relatives, the standardized incidence ratio for ovarian cancer was 1.92 (95% CI 1.27-2.79), mostly explained by a 2.30-fold (95% CI 1.46-3.45) risk among the patients' sisters. There was a decreasing trend in the standardized incidence ratio for ovarian cancer among patients' sisters by increasing age of the index patient., Conclusions: In our study cohort, we did not observe an increase in the overall cancer risk among the first-degree relatives of epithelial ovarian cancer patients in comparison with the general population. The risk for ovarian cancer, however, was increased. Current recommendations suggest prophylactic removal of the fallopian tubes and ovaries only with identified inherited risk factors. Our results emphasize the role of genetic counseling and testing, particularly in young ovarian cancer patients and their close female relatives., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Cholangiocarcinoma (CCA) is a cancer arising from the intra- and extrahepatic bile ducts. The early stages are often asymptomatic, CCA is frequently diagnosed in an advanced stage and the prognosis of CCA is often dismal., Objective: Our objective was to estimate the incidence of CCA in Finland and to identify risk factors for CCA, with a special interest in primary sclerosing cholangitis (PSC)., Methods: We identified all CCA cases during 1974-2018 from the Finnish Cancer Registry and calculated age-standardised incidence rates. Five controls for each case were extracted from the Population Registry, matched by age, gender and municipality of residence at the time of diagnosis. Odds ratios (ORs) for risk factors were estimated with conditional logistic regression and survival estimates with the Kaplan-Meier method., Results: Incidence of CCA remained stable in both genders; the age-standardised rate (World Standard) in 2013-2017 in males and females was 1.7 per 100,000 person years and 1.3 per 100,000 person years, respectively. Primary sclerosing cholangitis carried a 30-fold risk of intrahepatic cholangiocarcinoma (iCCA) and 25-fold risk of extrahepatic cholangiocarcinoma (eCCA). Diabetes, inflammatory bowel disease and liver cirrhosis were associated with iCCA, whereas cholelithiasis and viral hepatitis C were associated with eCCA. The cumulative 5-year survival was 4.6%., Conclusions: The incidence of CCA has been stable. Known risk factors for CCA were confirmed, with PSC having the highest OR. Survival remains poor., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Purpose: Published epidemiological studies on the association between finasteride use and the risk of male breast cancer have been inconclusive due to methodological limitations including a few male breast cancer cases included. Determinants of male breast cancer have been studied, but it remains unexplored whether these are also related to finasteride use and thereby constitute potential confounders. This study aimed to assess whether there are differences between finasteride users and nonusers with regard to numerous potential confounders., Methods: In total, 246 508 finasteride users (≥35 years) were identified in the prescription registries of Denmark (1995-2014), Finland (1997-2013), and Sweden (2005-2014). An equal number of nonusers were sampled. The directed acyclic graph (DAG) methodology was used to identify potential confounders for the association between finasteride and male breast cancer. A logistic regression model compared finasteride users and nonusers with regard to potential confounders that were measurable in registries and population surveys., Results: Finasteride users had higher odds of testicular abnormalities (odds ratio [OR] 1.40; 95% confidence interval [CI] 1.36-1.44), obesity (1.31; 1.23-1.39), exogenous testosterone (1.61; 1.48-1.74), radiation exposure (1.22; 1.18-1.27), and diabetes (1.07; 1.04-1.10) and lower odds of occupational exposure in perfume industry or in high temperature environments (0.93; 0.87-0.99), living alone (0.89; 0.88-0.91), living in urban/suburban areas (0.97; 0.95-0.99), and physical inactivity (0.70; 0.50-0.99) compared to nonusers., Conclusions: Systematic differences between finasteride users and nonusers were found emphasizing the importance of confounder adjustment of associations between finasteride and male breast cancer., (© 2020 John Wiley & Sons Ltd.)

Introduction: The association between endometriosis and breast cancer is unclear. We assessed the risk of breast cancer in women with surgically verified endometriosis, with special focus on the age at cancer diagnosis, time from endometriosis diagnosis and breast cancer histology., Material and Methods: All women with first endometriosis-associated diagnoses occurring concomitantly with relevant surgical codes during 1987-2012 were retrieved from the Finnish Hospital Discharge Register in Finland. Breast cancers diagnosed after the endometriosis diagnosis were identified from the Finnish Cancer Registry. The Finnish female population served as the reference. The endometriosis cohort consisted of 49 933 women (23 210 cases of ovarian, 20 187 peritoneal and 2372 deep infiltrating endometriosis). The outcome measure was the standardized incidence ratio (SIR) with 95% confidence interval (95% CI) of breast cancer calculated for the whole cohort and for the subtypes of endometriosis, stratified by the age at breast cancer diagnosis, histology and time from endometriosis diagnosis., Results: The overall risk of breast cancer (1555 cases) was similar to the reference population (SIR 0.99; 95% CI 0.94-1.03), did not differ in types of endometriosis, and was similar for ductal and lobular breast cancer. However, the SIR of breast cancer was increased in the age group of 20-29 years (SIR 4.44; 95% CI 2.22-7.94) and in the age group of 30-39 years (SIR 1.28; 95% CI 1.03-1.57). The risk of in situ breast cancer (170 cases) was increased in the entire endometriosis cohort (SIR 1.25; 95% CI 1.07-1.44)., Conclusions: The overall risk of breast cancer in women with surgically verified endometriosis was similar to that of general population. However, the risk of breast cancer at young age was increased. Young women with surgically verified endometriosis represent highly symptomatic patients with more frequent surgeries and additional therapies that might also contribute to the risk of breast cancer., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Introduction: Women with a history of placental abruption have an increased later morbidity, but not much is known of the later mortality., Material and Methods: Data on women with placental abruption (index cohort) between 1969 and 2005 (n = 7805) were collected from the Finnish Hospital Discharge Register and the Finnish Medical Birth Register. A matched reference cohort consisted of women without placental abruption (n = 23 523). The causes of death were retrieved from the Cause-of-Death Register. Cause-specific mortality was compared by hazard ratios (HR). Standardized mortality ratios were calculated to compare both cohorts with the general female population. The main outcome measure was subsequent mortality., Results: By the end of 2013 there were 395 deaths in the index cohort and 863 deaths in the reference cohort. The overall mortality was increased in the index cohort compared with the reference cohort [HR 1.39, 95% confidence interval (CI) 1.24-1.57]. The index cohort had an increased risk of death from respiratory tract malignancies (HR 1.72, 95% CI 1.05-2.82), alcohol-related causes (HR 1.84, 95% CI 1.25-2.72), and external causes (HR 1.63, 95% CI 1.19-2.22), especially suicide (HR 1.71, 95% CI 1.07-2.74). The mortality from cardiovascular diseases did not differ. The standardized mortality ratio was increased in the index cohort compared with the general Finnish female population (HR 1.13, 95% CI 1.02-1.24), especially for respiratory tract malignancies (HR 1.79, 95% CI 1.16-2.64). The index cohort women tended to die younger than referent women (p < 0.001)., Conclusions: Overall mortality among women with a history of placental abruption is increased. These women tend to die younger than referent women do., (© 2017 Nordic Federation of Societies of Obstetrics and Gynecology.)

We explored the impact of cancer diagnosis on the employment status of 46 312 working-aged people with cancer, alive on 31 December 1997 in Finland, and an equal number of age- and gender-matched referents. In general, 50% of the cancer patients were employed, in comparison to 55% of their referents. People with cancer were slightly less often employed, mainly because of their higher retirement rate: 34% of the cancer patients and 27% of the referents had retired. People with lung cancer as well as those with cancer of the nervous system were less likely to be employed. Our results suggest that cancer diagnosis does not usually lead to unemployment or early retirement, even though the employment rate of the people with cancer varied greatly according to the cancer site. Early retirement is common among people with highly disabling cancer or poor prognosis, but in general, the employment of cancer survivors seems optimistic., (Copyright 2004 John Wiley & Sons, Ltd.)

Background: The purpose of the study was to estimate subsequent incidence of cervical cancer among women with positive cytology followed by negative histology., Methods: This was a longitudinal cohort study involving about 80,000 women with class II, III, IV or V cytology at the organized mass screening in Finland in 1971 1990. Follow-up through the Finnish Cancer Registry started from the fifth month following the initial screening and ended on December 31, 1995., Results: Standardized incidence ratios (SIR) of invasive cervical cancer varied from 2.2 (class II) to 19 (class V), and SIRs of preinvasive lesion varied from 3.0 (class II) to 20 (class V) compared to the risk among the total Finnish female population of same age and calendar period. The relative risk was greatest during first years of follow-up for both preinvasive and invasive cervical lesions, and it remained significantly high over 5 years of follow-up. For women with class II cytology there were peaks in relative risk in the years of subsequent rescreenings., Conclusion: Women with positive cytology have a high relative risk of cervical cancer even when excluding the cancers found at screening; the high relative risk is persistent for more than 5 years, and therefore these women should be kept under close surveillance and repeated smears should be taken with relatively short intervals.

Background: The aim of this study was to evaluate the cost-effectiveness, from a societal perspective, of the Finnish nationwide breast carcinoma screening program., Methods: The effects were measured in life-years saved from 1987 to 2020, using data from the nationwide program to the end of 1992. A total of 90,000 women ages 50-59 were invited for screening during the years 1987-89. The total number of participants screened was 76,000. The screening interval was 24 months, with follow-up to the end of 1992. From the beginning of 1993, the estimation model used parameters based on published studies and national cancer statistics. Data on health care and non-health care costs and time costs were obtained from internal accounts of screening units, published studies, national statistics, health market sources, and a questionnaire completed by a sample of 1400 screening attendees. The discount rate, the annual rate of time preference over future costs and life-years saved, was 3%. The main outcome measure was the cost per life-year saved., Results: The estimated number of life-years of life saved was 578, of which 8% occurred 1987-1992. The estimated life-years saved per 1000 screenings was 3.2. The total costs were $11 million in U.S. dollars, i.e., $14.3 million per 100,000 participants., Conclusions: The cost of breast carcinoma mammographic screening per life-year saved was $18,955 in the base case, ranging from $15,502 to $40,308 according to the different models used in analysis., (Copyright 1999 American Cancer Society.)

Six statistics are compared in a simulation study for their ability to identify geographical areas with a known excess incidence of a rare disease. The statistics are the standardized incidence ratio, the empirical Bayes method of Clayton and Kaldor, Poisson probability, a statistic based on the 'Breslow T' test (BT) and two statistics based on the 'Potthoff-Whittinghill' test (PW) for extra-Poisson variance. Two alternative processes of clustering are simulated in which high-risk locations could be caused by environmental sources or could be sites of microepidemics of an infectious agent contributing to a rare disease such as childhood leukaemia. The simulation processes use two parameters (proportion of cases found in clusters and mean cluster size) which are varied to embrace a variety of situations. Real and artificial data sets of small area populations are considered. The most extreme of the artificial sets has all areas of equal population size. The other data sets use the small census areas (municipalities) in Finland since these have extremely heterogeneous population size distribution. Subset selection allows examination of this variability. Receiver operator curve methodology is used to compare the efficacy of the statistics in identifying the cluster areas; statistics are compared for the proportion of true high-risk areas identified in the top 1 per cent and 10 per cent of ranked areas. One of the PW statistics performed consistently well under all circumstances, although the results for the BT statistic were marginally better when only the top 1 per cent of ranked areas was considered. The standardized incidence ratio performed consistently worst., (Copyright 1999 National Radiological Protection Board.)

Background: The purpose of our study was to find out whether bleeding symptoms are predictive factors of subsequent gynecological or urinary cancers among women screened negative., Methods: The data stemmed from the Finnish Mass Screening Registry, and were linked to the National Cancer Registry: 37,596 screening negative women in the nationwide population-based mass screening program for cervical cancer were classified by their bleeding symptom (bloody discharge, coital bleeding, irregular bleeding, postmenopausal bleeding) at the time of screening (1985-1990) and followed up (1985-1994) in order to assess the subsequent risk of cancer., Results: Bleeding symptoms with prevalence of 5.9% were more likely to be signs of preinvasive than invasive cervical cancer with the exception of coital bleeding, nevertheless relative risk of cervical cancer (SIR 1.1, 95% CI 0.8-1.4) was not significantly increased during the total follow-up of maximum 10 years. Women with any bleeding symptom had increased risk of cancer of the corpus uteri (SIR 2.1, 95% CI 1.6-2.6), postmenopausal bleeding was the strongest symptom (RR 3.6, 95% CI 2.0-6.0). None of the bleeding symptoms increased subsequent risk of ovarian, vaginal or vulvar carcinoma. The risk of kidney cancer was increased (SIR 1.7, 95% CI 1.0-2.6)., Conclusions: The prevalence of bleeding symptoms was small and relative risks for cancers were low for them to be suitable as predictive factors of cancer neither in clinical practice nor for public health purposes, e.g. in developing selective screening based on this high risk group. Only 34 gynecological cancers during 220,000 person-years in women with bleeding symptoms were attributable to bleeding. Relative risks remained increased only for a short time after screening. Therefore, short term surveillance is important, but due to the fact that relative risks approached unity during the follow-up, reassurance of a woman that she is cancer-free should be emphasized more in the long term after the bleeding symptoms.

Background: The pattern of second cancers after treatment for cervical cancer provides important information on the risk of radiation-induced malignancies. Large numbers of women survive many years and can be studied for late effects., Methods: Incident second cancers in 86,193 patients with cervical cancer reported to 13 population-based cancer registries in 5 countries were evaluated to estimate the risk of second cancer among very long term survivors., Results: Overall, 7543 second cancers were observed versus 6015 cancers expected based on population rates (observed/expected = 1.2). Lung cancer accounted for nearly half of the excess cancers. Among the 49,828 women treated with radiation, 3750 survived 30 or more years and a two-fold risk of cancers of heavily irradiated organs was seen. Most of the excess cancers were of the rectum, vagina, vulva, ovary, and bladder. Patterns of risk over time since treatment were consistent with a radiation etiology. Significant increases of nonchronic lymphocytic leukemia and cancers of the bone and kidney were also linked to radiotherapy. Women treated surgically were also at significant risk of second cancers, in all likelihood related to cigarette smoking and risk factors similar to those of cervical cancer., Conclusions: Curative therapy for cervical cancer results in large numbers of long term survivors who develop second cancers very late in life. Radiation is an important cause of this increase and there is no evidence that risk returns to normal levels.

Background: A cohort of women enrolled in the Mama breast self-examination-(BSE) containing breast screening program in Finland from 1973 through 1975 (with BSE used for screening and mammography for diagnosis) was studied., Methods: Twenty-eight thousand seven hundred eighty-five women who returned calendars recording their practice of BSE over a 2-year period have been followed by linkage with the records of the Finnish Cancer Registry through 1986. The incidence of and mortality from breast cancer was compared with that expected in the Finnish population based on a model incorporating Finnish national data for breast cancer incidence and case fatality., Results: Breast cancer incidence was higher than expected (a rate ratio of 1.19 over all ages). The stage distribution of cases was not different from that expected from Finnish cancer registry data for 1980, but the breast cancer mortality was lower than expected (a rate ratio of 0.75). The latter difference occurred mainly in Years 3-6 of the follow-up period. The effect seemed similar in women under and over the age of 50 years. The cohort was of higher educational status than the Finnish population, and the mortality from all causes was lower than the general Finnish population, an effect seen in previous studies of compliers with breast screening., Conclusions: The reduction in mortality from breast cancer in the study cohort is consistent with an effect of the BSE-containing Mama program, though selection bias, inherent in any observational study of screening, provided an alternative explanation for the findings.

The effect of social class on survival of female breast cancer patients was studied by linking the patient files of the Finnish Cancer Registry (FCR) with the information on patient's social status, obtained from the 1970 Population Census of Finland. The material consisted of 10,181 patients 25 to 69 years of age at diagnosis, whose cancer was diagnosed between 1971 and 1980. The classification of social class was based on occupation. The effects of social class, age, period of diagnosis, and stage of disease on survival were evaluated using the Cox proportional hazards model; mortality from causes of death other than breast cancer was taken into account using the exact causes of death. Those in the lowest social class had about 1.3 times higher relative excess risk of dying than those in the highest social class. The older the patients, the greater was the difference in survival by social class. Differences in stage distribution explained only a minor proportion of the variation in survival by social class. The Finnish legislation guarantees everyone fairly equal accessibility to health care. The results suggest that more determined efforts should be undertaken to reduce inequity in survival.