Breast cancer (BC) patients diagnosed between two screenings (interval cancers) are more likely than screen-detected patients to carry rare deleterious mutations in cancer genes potentially leading ...to increased risk for other non-breast cancer (non-BC) tumors. In this study, we include 14,846 women diagnosed with BC of which 1,772 are interval and 13,074 screen-detected. Compared to women with screen-detected cancers, interval breast cancer patients are more likely to have a non-BC tumor before (Odds ratio (OR): 1.43 1.19-1.70, P = 9.4 x 10
) and after (OR: 1.28 1.14-1.44, P = 4.70 x 10
) breast cancer diagnosis, are more likely to report a family history of non-BC tumors and have a lower genetic risk score based on common variants for non-BC tumors. In conclusion, interval breast cancer is associated with other tumors and common cancer variants are unlikely to be responsible for this association. These findings could have implications for future screening and prevention programs.
There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients. This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure, ...and ischemic heart disease in women diagnosed with breast cancer.
A register-based matched cohort study was conducted including 8015 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region and followed up until 2017. Time-dependent risks of arrhythmia, heart failure, and ischemic heart disease in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model.
Time-dependent analyses revealed long-term increased risks of arrhythmia and heart failure following breast cancer diagnosis. Hazard ratios (HRs) within the first year of diagnosis were 2.14 (95% CI = 1.63-2.81) for arrhythmia and 2.71 (95% CI = 1.70-4.33) for heart failure. HR more than 10 years following diagnosis was 1.42 (95% CI = 1.21-1.67) for arrhythmia and 1.28 (95% CI = 1.03-1.59) for heart failure. The risk for ischemic heart disease was significantly increased only during the first year after diagnosis (HR = 1.45, 95% CI = 1.03-2.04). Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following locoregional radiotherapy.
Administration of systemic adjuvant therapies appears to be associated with increased risks of heart disease. The risk estimates observed in this study may aid adjuvant therapy decision-making and patient counseling in oncology practices.
This work was supported by the Swedish Research Council (grant no: 2018-02547); Swedish Cancer Society (grant no: CAN-19-0266); and FORTE (grant no: 2016-00081).
Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age.
To address this question, we undertook the world's largest ...prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic (MZ) and 30,054 dizygotic (DZ) same-sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability.
The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter for MZ than DZ pairs (median, 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability heritability = 58% (95% confidence interval, 52%-63%) of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary.
Results from the population-based twin cohort indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age.
Findings affect the search for genetic and epigenetic markers and frame prevention efforts.
Male breast cancer is a rare disease with an incidence rate less than 1% of that of female breast cancer. Given its low incidence, few studies have assessed risk and prognosis.
This population-based ...study, including 459,846 women and 2,665 men diagnosed with breast cancer in Denmark, Finland, Geneva, Norway, Singapore, and Sweden over the last 40 years, compares trends in incidence, relative survival, and relative excess mortality between the sexes.
World standardized incidence rates of breast cancer were 66.7 per 10(5) person-years in women and 0.40 per 10(5) person-years in men. Women were diagnosed at a younger median age (61.7 years) than men (69.6 years). Male patients had a poorer 5-year relative survival ratio than women (0.72 95% CI, 0.70 to 0.75 v 0.78 95% CI, 0.78 to 0.78, respectively), corresponding to a relative excess risk (RER) of 1.27 (95% CI, 1.13 to 1.42). However, after adjustment for age and year of diagnosis, stage, and treatment, male patients had a significantly better relative survival from breast cancer than female patients (RER, 0.78; 95% CI, 0.62 to 0.97).
Male patients with breast cancer have later onset of disease and more advanced disease than female patients. Male patients with breast cancer have lower risk of death from breast cancer than comparable female patients.
The proportion of women living with a diagnosis of breast cancer in developed countries is increasing. Because breast cancer-specific deaths decrease with time since diagnosis, it is important to ...assess the burden of other causes of death in women diagnosed with breast cancer.
Different causes of death within 10 years from diagnosis were assessed in 12,850 women younger than 75 years of age with stage 1 to 3 breast cancer diagnosed in Stockholm and Gotland regions 1990 to 2006. Flexible parametric survival models were used to estimate hazard ratios over time since diagnosis by tumor characteristics and age at diagnosis.
The proportion of deaths attributed to breast cancer ranged from 95.0% among women younger than age 45 years at diagnosis to 44.5% among women age 65 to 74 years. The proportions of circulatory system-specific deaths and deaths resulting from other causes increased with older age at diagnosis. Patients with one to three positive lymph nodes were more likely to die as a result of breast cancer during the first 10 years of follow-up compared with women without positive lymph nodes. Women with estrogen receptor (ER) -positive tumors had the same risk of dying as a result of breast cancer 5 years after diagnosis compared with women with ER-negative tumors.
Lymph node negativity is an important long-term predictor of more favorable prognosis. The nature of the relationship between ER status and risk of dying as a result of breast cancer after 5 years of follow-up requires further investigation. Circulatory system diseases are an important cause of death, especially in women diagnosed with breast cancer at an older age.
Despite the biological link between thyroid hormones and breast cancer cell proliferation shown in experimental studies, little is known about the association between hyperthyroidism and breast ...cancer, as well as its association with the most common mammographic and genetic risk predictors for breast cancer.
This study estimates the incidence rate ratios (IRRs) of breast cancer among women diagnosed with hyperthyroidism, compared to those who are not, using two cohorts: a Swedish national cohort of the general female population (n = 3,793,492, 2002-2011) and the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA, n = 69,598, 2002-2017). We used logistic regression to estimate the odds ratios (ORs) of hyperthyroidism according to the mammographic and genetic risk predictors for breast cancer.
An increased risk of breast cancer was observed in patients in the national cohort with hyperthyroidism (IRR = 1.23, 95% CI = 1.12-1.36), particularly for toxic nodular goiter (IRR = 1.38, 95% CI = 1.16-1.63). Hyperthyroidism was associated with higher body mass index, early age at first birth, and lower breastfeeding duration. Higher mammographic density was observed in women with toxic nodular goiter, compared to women without hyperthyroidism. Additionally, among genotyped women without breast cancer in the KARMA cohort (N = 11,991), hyperthyroidism was associated with a high polygenic risk score (PRS) for breast cancer overall (OR = 1.98, 95% CI = 1.09-3.60) and for estrogen receptor-positive specific PRS (OR = 1.90, 95% CI = 1.04-3.43).
Hyperthyroidism is associated with an increased risk of breast cancer, particularly for patients with toxic nodular goiter. The association could be explained by higher mammographic density among these women, as well as pleiotropic genetic variants determining shared hormonal/endocrine factors leading to the pathology of both diseases.
Abstract
Background. The objective of this study was: 1) to compare health-related quality of life (HRQoL) scores of breast cancer survivors to matched controls; and 2) to examine the relative impact ...(explained variance) of the type and number of co-morbidities on HRQoL.
Material and methods. Data from the KARMA project was used in this cross-sectional study. For each woman diagnosed with breast cancer (n = 2552) there were two healthy age- and geographically matched females (n = 5104). Breast cancer survivors were categorized according to time since diagnosis: recently diagnosed (0-1 year), short- (2-5 years), mid- (6-10 years), and long-term survivors (> 10 years). Women completed a questionnaire addressing demographics (age, educational level, and geographical location), lifestyle factors (body mass index (BMI) and smoking), co-morbidities, and HRQoL. The difference in explained variance in six HRQoL-domains between demographics, lifestyle factors, and co-morbidity in women with breast cancer and matched controls was examined by hierarchical regression analyses.
Results and conclusion. Women recently diagnosed (n = 63), reported the worst HRQoL followed by short-term survivors (2-5 years, n = 863). Thereafter, HRQoL scores further improved (6-10 years, n = 726), and were comparable to healthy females after 10 years (n = 893). Co-morbidity has a negative impact on HRQoL, which increased with time after diagnosis. Cardiovascular disease and depression were the strongest associates. Breast cancer survivors report clinically significant improvement in HRQoL scores six years after diagnosis. Co-morbidity has a negative impact on HRQoL, which increases with time after diagnosis, even though the number of co-morbidities remains stable. In long-term survivors there should be increasing awareness of co-morbidity and its impact on HRQoL.
We analyzed data from twins to determine how much the familial risk of colorectal cancer can be attributed to genetic factors vs environment. We also examined whether heritability is distinct for ...colon vs rectal cancer, given evidence of distinct etiologies.
Our data set included 39,990 monozygotic and 61,443 same-sex dizygotic twins from the Nordic Twin Study of Cancer. We compared each cancer's risk in twins of affected co-twins relative to the cohort risk (familial risk ratio FRR). We then estimated the proportion of variation in risk that could be attributed to genetic factors (heritability).
From earliest registration in 1943 through 2010, there were 1861 individuals diagnosed with colon cancer and 1268 diagnosed with rectal cancer. Monozygotic twins of affected co-twins had an FRR for colorectal cancer of 3.1 (95% confidence interval CI, 2.4-3.8) relative to the cohort risk. Dizygotic twins of affected co-twins had an FRR for colorectal cancer of 2.2 (95% CI, 1.7-2.7). We estimated that 40% (95% CI, 33%-48%) of the variation in colorectal cancer risk could be attributed to genetic factors; unique environment only accounted for the remaining liability. For colon cancer, the FRR was 3.3 (95% CI, 2.1-4.5) for monozygotic twins and 2.6 (95% CI, 1.7-3.5) for dizygotic twins. For rectal cancer, comparable estimates were 3.3 (95% CI, 1.5-5.1) for monozygotic twins and 2.6 (95% CI, 1.2-4.0) for dizygotic twins. Heritability estimates for colon and rectal cancer were 16% (95% CI, 0-46%) and 15% (95% CI, 0-50%), common environment estimates were 15% (95% CI, 0-38%) and 11% (95% CI, 0-38%), and unique environment estimates were 68% (95% CI, 57%-79%) and 75% (95% CI, 61%-88%), respectively.
Interindividual genetic differences could account for 40% of the variation in susceptibility to colorectal cancer; risk for colon and rectal cancers might have less of a genetic component than risk for colorectal cancer. Siblings, and particularly monozygotic co-twins, of individuals with colon or rectal cancer should consider personalized screening.
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