Multivariate analysis of independent roles of socioeconomic status, occupational physical activity, reproductive factors, and postmenopausal hormonal therapy in risk of breast cancer.

PURPOSE: This case-control study assesses the independent roles of reproductive history, postmenopausal hormonal therapy (HT), socioeconomic status (SES), and occupational physical activity on the risk of breast cancer (BC). METHODS: Odds ratios (OR) were estimated from conditional logistic multivariate regression model in a data set of 19,253 Finnish women diagnosed with BC between 1994 and 2013 and 96,265 age-matched population controls. RESULTS: Both pre- and postmenopausal white-collar workers had significantly increased risk of ductal and lobular BC as compared to manual workers. Moderate occupational physical activity reduced risk of lobular BC by 14%. There was a transient increase in the risk of BC observed after each birth followed by a protective effect starting some years after the delivery. As the number of children increased, the short-term excess risk was lower and protective effect was observed earlier. Continuous estrogen-progestin therapy (EPT) significantly increased the risk of both ductal and lobular BC and the magnitude of risk was directly proportional to duration of use (OR for 5+ years of use 2.26, 95% confidence interval 2.12-2.42). Monthly EPT for 5+ years increased the risk (OR 1.32, 95% CI 1.20-1.45). Users of estradiol plus levonorgestrel intrauterine system devices showed ORs of 1.56 (95% CI 1.45-1.69) and 2.18 (95% CI 1.81-2.64) for ductal and lobular BC, respectively. CONCLUSION: This study concludes that pregnancy has a dual effect on BC risk, with a transient increase in risk followed by a long-term protective effect. The SES and HT have a large effect on BC risk while occupational physical activity has only a small independent effect.

Parity, menopausal hormone therapy, and risk of ovarian granulosa cell tumor - A population-based case-control study.

OBJECTIVE: Adult-type ovarian granulosa cell tumors (AGCTs) are hormonally active neoplasms with limited epidemiological data available. We evaluated the effect of parity and postmenopausal hormone therapy (HT) use on the risk of AGCT in a population-based case-control setting. METHODS: We identified all women diagnosed with AGCT during 1994-2015 (n = 505) from the Finnish Cancer Registry. For each case, five controls matched for age were selected from the National Population Registry, which also provided data on parity and ages at deliveries. Information on postmenopausal HT by different regimens (estradiol-only, sequential estrogen-progestin and continuous estrogen-progestin) was obtained from nationwide Prescription Register. The association between parity, ages at deliveries, HT use, and AGCT incidence was evaluated by odds ratios (ORs) using a conditional logistic regression model and stratified by age at index date (<55 years or ≥ 55 years). RESULTS: Parity and age at first or last delivery had no significant effect on AGCT risk. Systemic postmenopausal HT had been used by 20.4% of women who were later diagnosed with AGCT. The risk for subsequent AGCT was significantly decreased among users of estradiol-only therapy for at least five years (OR 0.28; 95% confidence interval 0.08-0.94) and continuous estradiol-progestin therapy for 6 months to 5 years (0.23; 0.08-0.71). CONCLUSIONS: Unlike in epithelial ovarian cancer, AGCT development is not clearly associated with parity, and users of postmenopausal HT do not seem to carry an excess risk for AGCT formation.

Impact of parity on the incidence of ovarian cancer subtypes: a population-based case-control study.

BACKGROUND: Parity is known to have a protective effect as regards ovarian cancer, but its effect on the different histological subtypes of ovarian cancer is not well known. The impact of parity on the incidence of ovarian cancer subtypes was studied. MATERIAL AND METHODS: All Finnish women diagnosed 1994-2013 with ovarian cancer for the first time were included. Altogether, 5412 cases of ovarian cancer were identified in the Finnish Cancer Registry and stratified according to morphology into serous, mucinous, endometrioid, clear cell and others. Five age-matched controls were randomly selected for each case from the Finnish National Population Registry. Data on postmenopausal hormonal therapy were derived from the Registry of Prescribed drugs and used as cofactors. Multivariate conditional logistic regression for matched case-control data was used to examine the associations between parity parameters and ovarian cancer risk. RESULTS: Parous women had lower risk than nulliparous women in getting ovarian cancer of any type under age of 55 years. The odds ratio (OR) for serous cancer was 0.65 (95% confidence interval 0.56-0.77), for mucinous cancer 0.66 (0.52-0.83), for endometrioid cancer 0.52 (0.40-0.68), for clear-cell cancer 0.30 (0.19-0.46) and for other types 0.59 (0.43-0.80). In women aged 55 or older, the respective ORs were 0.86 (0.75-0.99), 0.78 (0.57-1.07), 0.61 (0.47-0.79), 0.44 (0.29-0.66) and 0.74 (0.57-0.95), adjusted for hormone therapy. Number of childbirths was associated with a trend toward reduction of risk, especially in serous and clear-cell cancers. Higher age at first birth was associated with higher risk of clear-cell cancer but otherwise age at first or last birth did not have an impact on the incidence of cancer subtypes. CONCLUSIONS: Childbirths decrease the risk of all histologic subtypes of epithelial ovarian cancer in women in premenopausal and postmenopausal age.

Causes of death among women with breast cancer: A follow-up study of 50 481 women with breast cancer in Finland.

Our study aims to assess mortality from causes other than breast cancer among women with breast cancer with focus on indications of joint aetiology. Data on female breast cancer patients were obtained from the Finnish Cancer Registry and their underlying causes of death in 54 categories from the Statistics Finland. Standardised mortality ratios (SMR) and their 95% confidence intervals (CIs) were calculated for 50 481 patients diagnosed between 1971 and 2000 and followed until December 2012, stratified by histology, age at diagnosis and time since diagnosis. The expected numbers of deaths were based on respective mortality rates among the Finnish general population. Hazard ratio (HR) was estimated from Poisson regression model to compare risks of cause of death by histology. 41% of 30 841 deaths were due to causes other than breast cancer. Significant excess mortality was observed for stomach cancer (SMR 1.43, 95% CI 1.26-1.62), circulatory system diseases (SMR 1.17, 95% CI 1.14-1.20) and suicide (SMR 1.51, 95% CI 1.28-1.78). In an age-adjusted analysis, significantly higher relative risk of stomach cancer mortality was observed for lobular vs ductal subtype (HR 2.00, 95% CI 1.32-3.02). Significantly increased SMRs were observed for cancers of respiratory organs among premenopausal women, and for other respiratory system diseases, dementia and Alzheimer disease among postmenopausal women. We conclude that female breast cancer patients are at increased risk of death from causes other than the breast cancer diagnosis including circulatory and respiratory system diseases and cancer of stomach, ovary and respiratory systems. The excess mortality because of different causes varies based on menopausal status and histology. There might be shared aetiological factors between the diagnosis of breast cancer and the causes of death among these patients.

The effect of length of birth interval on the risk of breast cancer by subtype in grand multiparous women.

BACKGROUND: The length of interval between successive childbirths (birth interval) might influence the incidence of breast cancer, either by stimulating or by inhibiting the factors that are responsible for the initiation of breast cancer or its early development. METHODS: This is a case-control study nested in a cohort of 47,479 Finnish grand-multiparous (GM) women born after 1934, and registered as having had at least five births before 2013. The 1354 women with breast cancer diagnosis were compared with controls (1:5) matched by parity and date of birth of the mother. Conditional logistic regression was used to estimate odds ratios of the risk of ductal and lobular breast cancer subtypes associated with each of the intervals between the 1st and 5th birth, stratified by age at diagnosis. Age at first and last birth before index date were used as covariates. RESULTS: Increased intervals between the 1st and 5th births were associated with an increased risk of lobular breast cancer. In contrast, regarding ductal cancer, premenopausal women with shorter length of interval (< 2 years) between the 1st and 2nd birth had greater risk and longer intervals (3+ years) were associated with reduced risk. Spacing between the 2nd and 5th birth did not influence the risk of ductal breast cancer. CONCLUSION: The findings of our study suggest that the effect of the length of birth interval on breast cancer depends on the age and histology. The protective effect of shorter birth intervals on lobular breast among postmenopausal women and the opposite effect on ductal cancer in premenopausal women may reflect distinct differentiation and functional roles of lobular and ductal cells, and possibly also different response to hormonal exposure.

Occupational variation in the risk of female breast cancer in the Nordic countries.

OBJECTIVE: This study aimed to determine occupational variations in the incidence of breast cancer in the population-based cohort of Nordic Occupational Cancer Study (NOCCA). METHODS: The study included long-term follow-up data from almost 7.5 million Nordic women. Participants were assigned to one of the 54 occupational categories based on census records at the ages of 30-64 years. Sixty-two thousand cases of breast cancer were identified through record linkages between nationwide cancer registries in Finland, Sweden, Norway, Denmark, and Iceland, followed up between 1961 and 2005. Country-specific standardized incidence ratios (SIRs) with 95% confidence intervals were estimated. RESULTS: Overall, the highest risk elevations were seen among military personnel (SIR 1.58, 95% CI 1.03-2.32), dentists (SIR 1.43, 95% CI 1.31-1.56), and physicians (SIR 1.35, 95% CI 1.26-1.46). The lowest risks were observed among gardeners (SIR 0.76, 95% CI 0.74-0.78), farmers (SIR 0.80, 95% CI 0.78-0.82), and woodworkers (SIR 0.75, 95% CI 0.70-0.81). Welders, tobacco workers, and painters had higher SIRs for breast cancer diagnosed at age < 50. A reduced risk was observed among forestry workers, welders, and fishery workers for breast cancers diagnosed both before and after age 50. The SIRs for breast cancer did not vary substantially by histology. A significantly increased risk of breast cancer was observed among laboratory workers in the latest calendar period (1991-2005) compared with earlier periods (1976-1990 and 1961-1975). Occupations such as farming, forestry, driving, and gardening had low SIRs during all periods. CONCLUSIONS: The study suggests that the risk of breast cancer varies by occupation. Heterogeneity is also observed in some occupational categories according to age (before or after 50), histology, and calendar period.