Risk of Breast Cancer in Females With Hypothyroidism: A Nationwide,Population-Based,Cohort Study

ObjectivesThe results of studies investigating the relationship between breast cancer and hypothyroidism vary greatly from study to study. In this study, we analyzed a large and reliable, population-based database to gain a better understanding of the correlation.MethodsThis retrospective cohort study analyzed patients with hypothyroidism between January 1, 2000 and December 31, 2012 (hypothyroidism cohort) from the Longitudinal Health Insurance Database 2000 in Taiwan. For each woman with hypothyroidism, 1 woman without a history of breast cancer was randomly selected from the Longitudinal Health Insurance Database 2000 and frequency matched (1:4) with women without hypothyroidism by age and index year of hypothyroidism. The study outcome was the diagnosis of breast cancer during a 12-year follow-up period.ResultsIn this study, 6665 women with hypothyroidism and 26 660 women without hypothyroidism were identified. The hypothyroidism cohort had a significantly higher risk of breast cancer than the nonhypothyroidism cohort (adjusted hazard ratio [aHR] 1.69 [95% CI, 1.15-2.49]; P = .01), especially in the group aged 40 to 64 years (aHR 2.07 [95% CI, 1.32-3.23]; P = .01). Women in the hypothyroidism cohort taking levothyroxine for a duration ˃588 days showed a significantly decreased risk of breast cancer (aHR 0.37 [95% CI, 0.19-0.71]; P = .003).ConclusionWomen with hypothyroidism are at a higher risk of breast cancer than those without hypothyroidism. Levothyroxine may reduce the risk of breast cancer in a woman with hypothyroidism.     

Risk Prediction for Breast,Endometrial, and Ovarian Cancer in White Women Aged 50 y or Older: Derivation and Validation from Population-Based Cohort Studies

Background

Breast, endometrial, and ovarian cancers share some hormonal and epidemiologic risk factors. While several models predict absolute risk of breast cancer, there are few models for ovarian cancer in the general population, and none for endometrial cancer.

Methods and Findings

Using data on white, non-Hispanic women aged 50+ y from two large population-based cohorts (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [PLCO] and the National Institutes of Health–AARP Diet and Health Study [NIH-AARP]), we estimated relative and attributable risks and combined them with age-specific US-population incidence and competing mortality rates. All models included parity. The breast cancer model additionally included estrogen and progestin menopausal hormone therapy (MHT) use, other MHT use, age at first live birth, menopausal status, age at menopause, family history of breast or ovarian cancer, benign breast disease/biopsies, alcohol consumption, and body mass index (BMI); the endometrial model included menopausal status, age at menopause, BMI, smoking, oral contraceptive use, MHT use, and an interaction term between BMI and MHT use; the ovarian model included oral contraceptive use, MHT use, and family history or breast or ovarian cancer. In independent validation data (Nurses'' Health Study cohort) the breast and ovarian cancer models were well calibrated; expected to observed cancer ratios were 1.00 (95% confidence interval [CI]: 0.96–1.04) for breast cancer and 1.08 (95% CI: 0.97–1.19) for ovarian cancer. The number of endometrial cancers was significantly overestimated, expected/observed = 1.20 (95% CI: 1.11–1.29). The areas under the receiver operating characteristic curves (AUCs; discriminatory power) were 0.58 (95% CI: 0.57–0.59), 0.59 (95% CI: 0.56–0.63), and 0.68 (95% CI: 0.66–0.70) for the breast, ovarian, and endometrial models, respectively.

Conclusions

These models predict absolute risks for breast, endometrial, and ovarian cancers from easily obtainable risk factors and may assist in clinical decision-making. Limitations are the modest discriminatory ability of the breast and ovarian models and that these models may not generalize to women of other races. Please see later in the article for the Editors'' Summary     

Cancer Risk in Children and Adolescents with Birth Defects: A Population-Based Cohort Study

Objective

Birth defects are an increasing health priority worldwide, and the subject of a major 2010 World Health Assembly Resolution. Excess cancer risk may be an added burden in this vulnerable group of children, but studies to date have provided inconsistent findings. This study assessed the risk for cancer in children and young adolescents with major birth defects.

Methods and Findings

This retrospective, statewide, population-based, cohort study was conducted in three US states (Utah, Arizona, Iowa). A cohort of 44,151 children and young adolescents (0 through 14 years of age) with selected major, non-chromosomal birth defects or chromosomal anomalies was compared to a reference cohort of 147,940 children without birth defects randomly sampled from each state’s births and frequency matched by year of birth. The primary outcome was rate of cancer prior to age 15 years, by type of cancer and type of birth defect. The incidence of cancer was increased 2.9-fold (95% CI, 2.3 to 3.7) in children with birth defects (123 cases of cancer) compared to the reference cohort; the incidence rates were 33.8 and 11.7 per 100,000 person-years, respectively. However, the excess risk varied markedly by type of birth defect. Increased risks were seen in children with microcephaly, cleft palate, and selected eye, cardiac, and renal defects. Cancer risk was not increased with many common birth defects, including hypospadias, cleft lip with or without cleft palate, or hydrocephalus.

Conclusion

Children with some structural, non-chromosomal birth defects, but not others, have a moderately increased risk for childhood cancer. Information on such selective risk can promote more effective clinical evaluation, counseling, and research.     

Preeclampsia as a Risk Factor for Diabetes: A Population-Based Cohort Study

Background

Women with preeclampsia (PEC) and gestational hypertension (GH) exhibit insulin resistance during pregnancy, independent of obesity and glucose intolerance. Our aim was to determine whether women with PEC or GH during pregnancy have an increased risk of developing diabetes after pregnancy, and whether the presence of PEC/GH in addition to gestational diabetes (GDM) increases the risk of future (postpartum) diabetes.

Methods and Findings

We performed a population-based, retrospective cohort study for 1,010,068 pregnant women who delivered in Ontario, Canada between April 1994 and March 2008. Women were categorized as having PEC alone (n = 22,933), GH alone (n = 27,605), GDM alone (n = 30,852), GDM+PEC (n = 1,476), GDM+GH (n = 2,100), or none of these conditions (n = 925,102). Our main outcome was a new diagnosis of diabetes postpartum in the following years, up until March 2011, based on new records in the Ontario Diabetes Database. The incidence rate of diabetes per 1,000 person-years was 6.47 for women with PEC and 5.26 for GH compared with 2.81 in women with neither of these conditions. In the multivariable analysis, both PEC alone (hazard ratio [HR] = 2.08; 95% CI 1.97–2.19) and GH alone (HR = 1.95; 95% CI 1.83–2.07) were risk factors for subsequent diabetes. Women with GDM alone were at elevated risk of developing diabetes postpartum (HR = 12.77; 95% CI 12.44–13.10); however, the co–presence of PEC or GH in addition to GDM further elevated this risk (HR = 15.75; 95% CI 14.52–17.07, and HR = 18.49; 95% CI 17.12–19.96, respectively). Data on obesity were not available.

Conclusions

Women with PEC/GH have a 2-fold increased risk of developing diabetes when followed up to 16.5 years after pregnancy, even in the absence of GDM. The presence of PEC/GH in the setting of GDM also raised the risk of diabetes significantly beyond that seen with GDM alone. A history of PEC/GH during pregnancy should alert clinicians to the need for preventative counseling and more vigilant screening for diabetes. Please see later in the article for the Editors'' Summary     

Intentional Weight Loss and Longevity in Overweight Patients with Type 2 Diabetes: A Population-Based Cohort Study

Objective

This study examined the influence of weight loss on long-term morbidity and mortality in overweight (BMI≥25kg/m²) patients with type 2 diabetes, and tested the hypothesis that therapeutic intentional weight loss supervised by a medical doctor prolongs life and reduces the risk for cardiovascular disease in these patients.

Methods

This is a 19 year cohort study of patients in the intervention arm of the randomized clinical trial Diabetes Care in General Practice. Weight and prospective intentions for weight loss were monitored every third month for six years in 761 consecutive patients (≥40 years) newly diagnosed with diabetes in general practices throughout Denmark in 1989–92. Multivariable Cox regression was used to estimate the association between weight change during the monitoring period (year 0 to 6) and the outcomes during the succeeding 13 years (year 6 to 19) in 444 patients who were overweight at diagnosis and alive at the end of the monitoring period (year 6). The analysis was adjusted for age, sex, education, BMI at diagnosis, change in smoking, change in physical activity, change in medication, and the Charlson comorbidity 6-year score. Outcomes were from national registers.

Results

Overall, weight loss regardless of intention was an independent risk factor for increased all-cause mortality (P<0.01). The adjusted hazard ratio for all-cause mortality, cardiovascular mortality, and cardiovascular morbidity attributable to an intentional weight loss of 1 kg/year was 1.20 (95%CI 0.97–1.50, P = 0.10), 1.26 (0.93–1.72, P = 0.14), and 1.06 (0.79–1.42, P = 0.71), respectively. Limiting the analysis to include only those patients who survived the first 2 years after the monitoring period did not substantially change these estimates. A non-linear spline estimate indicated a V-like association between weight change and all-cause mortality, suggesting the best prognosis for those who maintained their weight.

Conclusions

In this population-based cohort of overweight patients with type 2 diabetes, successful therapeutic intentional weight loss, supervised by a doctor over six years, was not associated with reduced all-cause mortality or cardiovascular morbidity/mortality during the succeeding 13 years.     

Risks for Acquisition of Bacterial Vaginosis Among Women Who Report Sex with Women: A Cohort Study

Background

Bacterial vaginosis (BV) is common in women who have sex with women. While cross-sectional data support a role for sexual transmission, risks for incident BV have not been prospectively studied in this group.

Methodology/Principal Findings

We studied risks for BV acquisition in a prospective cohort study of women (age 16–35 years) who reported sex with other women (≥1 partner, prior year). Women were followed for one year with examinations at quarterly visits and for genital symptoms at any time. Species-specific 16S rRNA gene PCRs for BV-associated bacteria (BVAB) were applied to vaginal fluid obtained at enrollment. Sexual behaviors were ascertained by computer-assisted interview. Of 335 participants, 239 had no BV at baseline; 199 were seen in follow-up (median follow-up 355 days, 4.0 visits/subject). Forty women experienced ≥1 BV episode. Risks for incident BV were presentation ≤14 days since onset of menses (hazard ratio (HR) 2.3 (95% CI, 1.2–4.7), report of new sex partner with BV history (HR 3.63 (1.1–11.9)), change in vaginal discharge (HR 2.6 (1.3–5.2)) and detection of any of several BVAB in vaginal fluid at enrollment, including BVAB1 (HR 6.3 (1.4–28.1)), BVAB2 (HR 18.2 (6.4–51.8)), BVAB3 (HR 12.6 (2.7–58.4)), G. vaginalis (HR 3.9 (1.5–10.4)), Atopobium vaginae (HR 4.2 (1.9–9.3)), Leptotrichia spp (9.3 (3.0–24.4)), and Megasphaera-1 (HR 11.5 (5.0–26.6)). Detection of Lactobacillus crispatus at enrollment conferred reduced risk for subsequent BV (HR 0.18 (0.08–0.4)). Detailed analysis of behavioral data suggested a direct dose-response relationship with increasing number of episodes of receptive oral-vulvovaginal sex (HR 1.02 (95% CI, 1.00–1.04).

Conclusions/Significance

Vaginal detection of several BVAB in BV-negative women predicted subsequent BV, suggesting that changes in vaginal microbiota precede BV by weeks or months. BV acquisition was associated with report of new partner with BV; associations with sexual practices – specifically, receptive oral sex – require further investigation.     

Sarcoidosis in Patients with Psoriasis: A Population-Based Cohort Study

Purpose

Psoriasis is a chronic inflammatory disease characterized by a systemic immunological response which is mainly driven by activated T helper (Th) 1 and Th17 lymphocytes. Like psoriasis, sarcoidosis is a chronic inflammatory disorder with Th1/Th17-driven inflammation. Therefore, we investigated the risk of sarcoidosis in patients with psoriasis compared to the background population in a nationwide cohort.

Methods

The study included the entire Danish population aged ≥10 years followed from 1^st January 1997 until diagnosis of sarcoidosis, death or 31^st December 2011. Patients with a history of psoriasis and/or sarcoidosis at baseline were excluded. Information on comorbidity and concomitant medication was identified by individual-level linkage of administrative registers. Incidence rates of sarcoidosis were calculated and adjusted hazard ratios (HRs) were estimated by multivariable Cox regression models adjusted for age, gender, comorbidity, medications and socioeconomic status.

Results

A total of 6,043,518 subjects were eligible for analysis. In the study period 70,125 patients with new-onset psoriasis, including 11,834 patients with severe psoriasis, were identified. The overall incidence rates of sarcoidosis were 1.18, 2.22, and 4.06 per 10,000 person-years for the reference population (9,717 cases), mild psoriasis (78 cases) and severe psoriasis (22 cases), respectively. Compared to the reference population, the age- and gender-adjusted HRs for sarcoidosis were increased in patients with psoriasis with HR 1.49 (95% confidence interval [CI] 1.18–1.87) and HR 2.51 (CI 1.64–3.85) for those with mild and severe disease, respectively.

Conclusion

In this nationwide cohort, psoriasis was associated with a disease severity-dependent increased risk of sarcoidosis.     

Breast Cancer Biology and Ethnic Disparities in Breast Cancer Mortality in New Zealand: A Cohort Study

Introduction

Indigenous Māori women have a 60% higher breast cancer mortality rate compared with European women in New Zealand. We investigated differences in cancer biological characteristics and their impact on breast cancer mortality disparity between Māori and NZ European women.

Materials and Methods

Data on 2849 women with primary invasive breast cancers diagnosed between 1999 and 2012 were extracted from the Waikato Breast Cancer Register. Differences in distribution of cancer biological characteristics between Māori and NZ European women were explored adjusting for age and socioeconomic deprivation in logistic regression models. Impacts of socioeconomic deprivation, stage and cancer biological characteristics on breast cancer mortality disparity between Māori and NZ European women were explored in Cox regression models.

Results

Compared with NZ European women (n=2304), Māori women (n=429) had significantly higher rates of advanced and higher grade cancers. Māori women also had non-significantly higher rates of ER/PR negative and HER-2 positive breast cancers. Higher odds of advanced stage and higher grade remained significant for Māori after adjusting for age and deprivation. Māori women had almost a 100% higher age and deprivation adjusted breast cancer mortality hazard compared with NZ European women (HR=1.98, 1.55-2.54). Advanced stage and lower proportion of screen detected cancer in Māori explained a greater portion of the excess breast cancer mortality (HR reduction from 1.98 to 1.38), while the additional contribution through biological differences were minimal (HR reduction from 1.38 to 1.35).

Conclusions

More advanced cancer stage at diagnosis has the greatest impact while differences in biological characteristics appear to be a minor contributor for inequities in breast cancer mortality between Māori and NZ European women. Strategies aimed at reducing breast cancer mortality in Māori should focus on earlier diagnosis, which will likely have a greater impact on reducing breast cancer mortality inequity between Māori and NZ European women.     

Risk of Second Primary Cancer among Prostate Cancer Patients in Korea: A Population-Based Cohort Study

As patients with prostate cancer have a long life expectancy, there is increasing interest in predicting the risk of development of a second primary cancer (SPC), and we therefore designed this study to estimate the overall risk of developing SPCs among Korean prostate cancer patients. We used a population-based cohort from the Korean Central Cancer Registry composed of 55,378 men diagnosed with a first primary prostate cancer between 1993 and 2011. Standardized incidence ratios (SIRs) of SPCs were analyzed by age at diagnosis, latency period, period of diagnosis, and type of initial treatment. Survival analysis was stratified by development of SPC. Men with primary prostate cancer had an overall lower risk of developing an SPC [SIR = 0.75; 95% CI, 0.72−0.78], which was significant for SPCs of the esophagus, stomach, rectum, liver, gallbladder, bile duct, pancreas, larynx, lung, and bronchus. In contrast, there were significant increases in the risk of bladder and thyroid cancers, which tended to decrease after longer follow-up. Patients who received initial radiation therapy had an increased risk of subsequent rectal cancer, although this was still lower than that of the general male population. Other urinary tract cancers including those of the kidney, renal pelvis, and ureter tended to be associated with a higher risk of developing an SPC, but this difference did not reach statistical significance. The patients with prostate cancer and SPC had lower overall survival rates than those with one primary prostate cancer. Our findings suggest that men with prostate cancer have a 25% lower risk of developing an SPC in Korea, but a higher risk of developing subsequent bladder and thyroid cancers, which suggests the need for continued cancer surveillance among prostate cancer survivors.     

Major Depressive Disorder and Stroke Risks: A 9-Year Follow-Up Population-Based,Matched Cohort Study

Background and Purpose

Major depressive disorder (MDD) is characterized by recurrent depressive episodes and one of the treatment choices is antidepressants. Patients with MDD are at greater risk of developing major metabolic diseases that may in turn lead to stroke. Moreover, both depressive symptoms and taking antidepressant medications are associated with higher risk of stroke. However, whether and how clinical depression increases stroke risk remains an unanswered question. Our aim was to provide answers to this question.

Methods

A matched cohort study of 5015 subjects (1003 MDD patients and 4012 control subjects) was conducted using a nationwide database. Subjects were followed to a maximum of 9 years to determine rates of newly-developed strokes, and controls and MDD groups with different levels of antidepressant refractoriness were compared to determine the temporal relation between stroke and three major metabolic comorbidities (i.e., diabetes mellitus, hypertension and hyperlipidemia). The levels of depressive symptoms and the antidepressant medications before stroke onset were investigated.

Results

Patients with MDD had significantly higher rates of stroke (4.3% vs. 2.8%, p<0.05) during the follow-up. Mediation regression analyses revealed that the occurrence of stroke in the MDD subjects was significantly mediated by the development of major metabolic diseases. Greater severity of depression, but not greater use of antidepressants, preceded the occurrence of stroke.

Conclusions

A clinical diagnosis of major depression leads to stroke indirectly through more intense depressive symptoms and the development of major comorbidities.     

Fracture Risk and Adjuvant Therapies in Young Breast Cancer Patients: A Population-Based Study

Background

Breast cancer survivors have an increased risk of bone fracture. But the risk among young patients with adjuvant therapies remains unknown. This population-based study is aimed to assess the incidence and risk of fracture among young (age of 20 to 39 years) breast cancer patients who received adjuvant therapies.

Methods

From January 2001 to December 2007, 5,146 newly diagnosed breast cancer patients were enrolled from the National Health Insurance Research Database (NHIRD) in Taiwan. Patients were observed for a maximum of 6 years to determine the incidence of newly onset fracture. Kaplan Meier and Cox regression analyses were used to evaluate the risk of fracture in young breast cancer patients who received adjuvant treatments.

Results

Of the total 5,146 young (age of 20 to 39 years) breast cancer patients, the Cox multivariate proportional hazards analysis showed that AIs, radiotherapy, and monoclonal antibodies were significantly associated with a high risk of fracture. Moreover, patients who received AIs for more than 180 days had a high hazard ratio (HR) of 1.77 (95% CI = 0.68–4.57), and patients who received more than four radiotherapy visits had a high HR of 2.54 (95% CI = 1.07–6.06). Under the site-specific analysis, young breast cancer patients who received AIs had the highest risk of hip fracture (HR = 8.520, 95% CI = 1.711–42.432, p < 0.04), whereas patients who received radiotherapy had the highest risk of vertebral fracture (HR = 5.512, 95% CI = 1.847–16.451, p < 0.01).

Conclusion

Young breast cancer patients who are receiving AIs, radiotherapy or monoclonal antibody need to be more careful for preventing fracture events. Breast cancer treatment plans are suggested to incorporate fracture prevention interventions.     

Hospital Recorded Morbidity and Breast Cancer Incidence: A Nationwide Population-Based Case-Control Study

Introduction

Chronic diseases and their complications may increase breast cancer risk through known or still unknown mechanisms, or by shared causes. The association between morbidities and breast cancer risk has not been studied in depth.

Methods

Data on all Danish women aged 45 to 85 years, diagnosed with breast cancer between 1994 and 2008 and data on preceding morbidities were retrieved from nationwide medical registries. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression associating the Charlson comorbidity score (measured using both the original and an updated Charlson Comorbidity Index (CCI)) with incident breast cancer. Furthermore, we estimated associations between 202 morbidity categories and incident breast cancer, adjusting for multiple comparisons using empirical Bayes (EB) methods.

Results

The study included 46,324 cases and 463,240 population controls. Increasing CCI score, up to a score of six, was associated with slightly increased breast cancer risk. Among the Charlson diseases, preceding moderate to severe renal disease (OR = 1.25, 95% CI: 1.06, 1.48), any tumor (OR = 1.17, 95% CI: 1.10, 1.25), moderate to severe liver disease (OR = 1.86, 95% CI: 1.32, 2.62), and metastatic solid tumors (OR = 1.49, 95% CI: 1.17, 1.89), were most strongly associated with subsequent breast cancer. Preceding myocardial infarction (OR = 0.89, 95% CI: 0.81, 0.99), connective tissue disease (OR = 0.87, 95% CI: 0.80, 0.94), and ulcer disease (OR = 0.91, 95% CI: 0.83, 0.99) were most strongly inversely associated with subsequent breast cancer. A history of breast disorders was associated with breast cancer after EB adjustment. Anemias were inversely associated with breast cancer, but the association was near null after EB adjustment.

Conclusions

There was no substantial association between morbidity measured with the CCI and breast cancer risk.     

Breast Cancer Survival in Germany: A Population-Based High Resolution Study from Saarland

Population-based survival studies of breast cancer patients are commonly restricted to age- and stage-specific analyses. This study from Germany aimed at extending available population-based survival data on further prognostic cancer characteristics such as tumor grade, hormone receptor status and human epidermal growth factor receptor type 2 (HER2/neu) expression. Data from the population-based Saarland Cancer Registry including female patients diagnosed with invasive breast cancer between 2000 and 2009 were included. Period analysis methodology and regression modelling were used to obtain estimates of 5-year relative survival and tumor related excess risks in 2005-2009. Overall age standardized 5-year relative survival was 83%. In addition to age and stage, tumor grade and hormone receptor status were independent predictors of 5-year relative survival. Detailed analyses by age, stage, morphology, tumor grade, hormone receptor status and HER2/neu expression consistently revealed lower survival of patients with high grade, hormone receptor negative or HER2/neu positive cancers and patients aged 70 years or older. This high resolution study extends available population-based survival data of breast cancer patients. Particular efforts should be made to overcome the persisting large survival deficits, which were observed for elderly patients in all clinical subgroups.     

Use of Oral Bisphosphonates in Primary Prevention of Fractures in Postmenopausal Women: A Population-Based Cohort Study

Oral bisphosphonates are first-line drugs in the treatment of osteoporosis under most guidelines, and have been shown to decrease risk of first fracture only in asymptomatic vertebral fractures and in clinical trial populations that are generally very different from the general population.

Objective

To compare incidence of first osteoporotic fracture in two cohorts of postmenopausal women, one treated with bisphosphonates and the other only with calcium and vitamin D.

Design

Retrospective population cohort study with paired matching based on data from electronic health records.

Setting

Women aged 60 years and older in 2005, from 21 primary care centers in a healthcare region of Spain.

Participants

Two groups of women aged 60 years and older (n = 1208), prescribed either calcium and vitamin D (CalVitD) or bisphosphonates (BIPHOS) with or without calcium and vitamin D, were compared for the end point of first recorded osteoporotic-related fracture, with 5-years follow-up.

Main Outcome Measure

Incidence of first fracture: Vertebral fracture, osteoporosis with pathological fracture, fracture of the upper humeral epiphysis, fracture of the lower radial epiphysis, or femur fracture.

Results

Estimated 10-year risk of fracture was 11.4% (95% confidence interval: 9.6 to 13.2), 11.8% (9.2 to 14.3) in the BIPHOS group and 11.1% (8.6 to 13.6) in the CalVitD group. No significant differences were found between groups in total fractures (Hazard ratio = 0.934 (0.67 to 1.31)) or location (vertebral, femoral, radial or humeral).

Conclusions

In postmenopausal women, bisphosphonates have not been shown to better decrease risk of first fracture compared with calcium and vitamin D therapy alone.     

Barriers to and Facilitators of Compliance with Clinic-Based Cervical Cancer Screening: Population-Based Cohort Study of Women Aged 23-60 Years

Objective

This study aims to identify possible barriers to and facilitators of cervical cancer screening by (a) estimating time and travel costs and other direct non-medical costs incurred in attending clinic-based cervical cancer screening, (b) investigating screening compliance and reasons for noncompliance, (c) determining women’s knowledge of human papillomavirus (HPV), its relationship to cervical cancer, and HPV and cervical cancer prevention, and (d) investigating correlates of HPV knowledge and screening compliance.

Materials and Methods

1510 women attending the clinic-based cervical cancer screening program in Stockholm, Sweden were included. Data on sociodemographic characteristics, time and travel costs and other direct non-medical costs incurred in attending (e.g., indirect cost of time needed for the screening visit, transportation costs, child care costs, etc.), mode(s) of travel, time, distance, companion’s attendance, HPV knowledge, and screening compliance were obtained via self-administered questionnaire.

Results

Few respondents had low socioeconomic status. Mean total time and travel costs and direct non-medical cost per attendance, including companion (if any) were €55.6. Over half (53%) of the respondents took time off work to attend screening (mean time 147 minutes). A large portion (44%) of the respondents were noncompliant (i.e., did not attend screening within 1 year of the initial invitation), 51% of whom stated difficulties in taking time off work. 64% of all respondents knew that HPV vaccination was available; only 34% knew it was important to continue to attend screening following vaccination. Age, education, and income were the most important correlates of HPV knowledge and compliance; and additional factors associated with compliance were time off work, accompanying companion and HPV knowledge.

Conclusion

Time and travel costs and other direct non-medical costs for clinic-based screening can be considerable, may affect the cost-effectiveness of a screening program, and may constitute barriers to screening while HPV knowledge may facilitate compliance with screening.     

The Prescription Pattern of Chinese Herbal Products That Contain Dang-Qui and Risk of Endometrial Cancer among Tamoxifen-Treated Female Breast Cancer Survivors in Taiwan: A Population-Based Study

Purpose

The increased practice of traditional Chinese medicine worldwide has raised concerns regarding herb-drug interactions. We analyzed the usage of Chinese herbal products containing dang-qui and investigated whether dang-qui therapy increases endometrial cancer risk among tamoxifen-treated breast cancer survivors in Taiwan.

Methods

All patients newly diagnosed with invasive breast cancer who received tamoxifen treatment from January 1, 1998, to December 31, 2008 were selected from the National Health Insurance Research Database. The usage, frequency of service and type of Chinese herbal products containing dang-qui prescribed across the 31,970 survivors were evaluated. Logistic regression method was employed to estimate the odds ratios for utilization of Chinese herbal products containing dang-qui. Cox proportional hazard regression was performed to calculate the hazard ratio of endometrial cancer associated with dang-qui use within the cohort.

Results

Almost one in two study subjects had used dang-qui. Among 31,938 tamoxifen-treated breast cancer survivors, 157 cases of subsequent endometrial cancer were identified. The hazard ratio for development of endometrial cancer among breast cancer survivors aged 20–79 years who had taken dang-qui after tamoxifen treatment was decreased compared to survivors who had never used dang-qui (HR: 0.61, 95%CI: 0.44–0.84). To minimise potential confounding factors, women with breast cancer in the reproductive age were excluded from further analysis, and the negative relationship between dang-qui consumption and subsequent endometrial cancer among breast cancer survivors aged 55–79 years was still observed, although not significantly (HR: 0.74, 95%CI: 0.46–1.17).

Conclusions

Dang-qui consumption is common among breast cancer survivors aged 20–79 years and seems decrease the risk of subsequent endometrial cancer after less than a cumulative dose of 7,500 mg of tamoxifen treatment.     

Age-Related Disparity in Immediate Prognosis of Patients with Triple-Negative Breast Cancer: A Population-Based Study from SEER Cancer Registries

Background

Triple-negative breast cancer (TNBC) has been demonstrated to carry poor prognosis, but whether or not there exists any age-related variation in TNBC outcomes has yet to be elucidated. The current population-based study investigated the early survival pattern of elderly women with TNBC and identified outcome-correlated factors.

Patients and Methods

We searched the Surveillance, Epidemiology, and End Results (SEER) database and enrolled female primary non-metastatic TNBC cases. The patients were subdivided into elderly (≥70 years) and young groups (<70 years). The survival status of elderly patients was compared to that of the younger women. The primary and secondary endpoints were cancer-specific survival (CSS) and overall survival (OS) respectively.

Results

9908 female TNBC patients diagnosed from 2010 to 2011 were included in the current study (20.4% elderly). Elderly patients with relatively advanced diseases exhibited distinctly worse cancer-specific (log-rank, p<0.001) and overall survival (log-rank, p<0.001) than their young counterparts. Advanced age at diagnosis (≥70 years) was significantly predictive of poor outcome in terms of CSS (hazard ratio (HR), 2.125; 95% confidence interval (CI), 1.664 to 2.713; p<0.001) and OS (HR, 3.042; 95%CI, 2.474 to 3.740; p<0.001). Underuse of curative treatment especially radiotherapy was more prevalent in elderly women with stage II or III diseases than in younger patients.

Conclusion

Elderly patients with TNBC displayed elevated early mortality within the first two years of diagnosis compared to the younger individuals. The observed lower rate of loco-regional treatment might be associated with worse cancer-specific outcome for these patients.     

Maternal Overweight and Obesity and Risks of Severe Birth-Asphyxia-Related Complications in Term Infants: A Population-Based Cohort Study in Sweden

Background

Maternal overweight and obesity increase risks of pregnancy and delivery complications and neonatal mortality, but the mechanisms are unclear. The objective of the study was to investigate associations between maternal body mass index (BMI) in early pregnancy and severe asphyxia-related outcomes in infants delivered at term (≥37 weeks).

Methods and Findings

A nation-wide Swedish cohort study based on data from the Medical Birth Register included all live singleton term births in Sweden between 1992 and 2010. Logistic regression analyses were used to obtain odds ratios (ORs) with 95% CIs for Apgar scores between 0 and 3 at 5 and 10 minutes, meconium aspiration syndrome, and neonatal seizures, adjusted for maternal height, maternal age, parity, mother''s smoking habits, education, country of birth, and year of infant birth. Among 1,764,403 term births, 86% had data on early pregnancy BMI and Apgar scores. There were 1,380 infants who had Apgar score 0–3 at 5 minutes (absolute risk  = 0.8 per 1,000) and 894 had Apgar score 0–3 at 10 minutes (absolute risk  = 0.5 per 1,000). Compared with infants of mothers with normal BMI (18.5–24.9), the adjusted ORs (95% CI) for Apgar scores 0–3 at 10 minutes were as follows: BMI 25–29.9: 1.32 (1.10–1.58); BMI 30–34.9: 1.57 (1.20–2.07); BMI 35–39.9: 1.80 (1.15–2.82); and BMI ≥40: 3.41 (1.91–6.09). The ORs for Apgar scores 0–3 at 5 minutes, meconium aspiration, and neonatal seizures increased similarly with maternal BMI. A study limitation was lack of data on effects of obstetric interventions and neonatal resuscitation efforts.

Conclusion

Risks of severe asphyxia-related outcomes in term infants increase with maternal overweight and obesity. Given the high prevalence of the exposure and the severity of the outcomes studied, the results are of potential public health relevance and should be confirmed in other populations. Prevention of overweight and obesity in women of reproductive age is important to improve perinatal health. Please see later in the article for the Editors'' Summary     

Total and Differential Leukocyte Counts in Relation to Incidence of Diabetes Mellitus: A Prospective Population-Based Cohort Study

Objective

High concentrations of leukocytes in blood have been associated with diabetes mellitus. This prospective study aimed to explore whether total and differential leukocyte counts are associated with incidence of diabetes. A missense variant R262W in the SH2B3 (SH2B adaptor protein 3) gene, coding for a protein that negatively regulates hematopoietic cell proliferation, was also studied in relation to incidence of diabetes.

Methods and Results

Leukocyte count and its subtypes (neutrophils, lymphocytes and mixed cells) were analyzed in 26,667 men and women, 45–73 years old, from the population-based Malmö Diet and Cancer study. Information about the R262W polymorphism (rs3184504) in SH2B3 was genotyped in 24,489 subjects. Incidence of diabetes was studied during a mean follow-up of 14 years. Cox proportional hazards regression was used to examine incidence of diabetes by total and differential leukocyte counts. Mendelian randomization analysis using R262W as an instrumental variable was performed with two-stage least squares regression. A total of 2,946 subjects developed diabetes during the follow-up period. After taking several possible confounders into account, concentrations of total leukocyte count, neutrophils and lymphocytes were all significantly associated with incidence of diabetes. The adjusted hazard ratios (95% confidence interval; quartile 4 vs quartile 1) were 1.37 (1.22–1.53) for total leukocytes, 1.33 (1.19–1.49) for neutrophils and 1.29 (1.15–1.44) for lymphocytes. The R262W polymorphism was strongly associated with leukocytes (0.11x10⁹ cells/l per T allele, p = 1.14 x10^-12), lymphocytes (p = 4.3 x10^-16), neutrophils (p = 8.0 x10^-6) and mixed cells (p = 3.0 x10^-6). However, there was no significant association between R262W and fasting glucose, HbA_1c or incidence of diabetes.

Conclusions

Concentrations of total leukocytes, neutrophils and lymphocytes are associated with incidence of diabetes. However, the lack of association with the R262W polymorphism suggests that the associations may not be causal, although limitations in statistical power and balancing pleiotropic effects cannot be excluded.