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1.
Int J Cancer ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33544892

RESUMO

Breast cancer survivors have a high risk of a second primary contralateral breast cancer (CBC), but there are few studies of CBC risk in racial/ethnic minority populations. We examined whether the incidence and risk factors for CBC differed by race/ethnicity in the United States. Women with a first invasive Stage I-IIB breast cancer diagnosis at ages 20-74 years between 2000 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) 18 registries were followed through 2016 for a diagnosis of invasive CBC ≥1 year after the first breast cancer diagnosis. We used cause-specific Cox proportional hazards models to test the association between race/ethnicity and CBC, adjusting for age, hormone receptor status, radiation therapy, chemotherapy and stage at first diagnosis, and evaluated the impact of contralateral prophylactic mastectomy, socioeconomic status, and insurance status on the association. After a median follow-up of 5.9 years, 9247 women (2.0%) were diagnosed with CBC. Relative to non-Hispanic (NH) White women, CBC risk was increased in NH Black women (hazard ratio = 1.44, 95% CI 1.35-1.54) and Hispanic women (1.11, 95% CI 1.02-1.20), with the largest differences among women diagnosed at younger ages. Adjustment for contralateral prophylactic mastectomy, socioeconomic status and health insurance did not explain the associations. Therefore, non-Hispanic Black and Hispanic women have an increased risk of CBC that is not explained by clinical or socioeconomic factors collected in SEER. Large studies of diverse breast cancer survivors with detailed data on treatment delivery and adherence are needed to inform interventions to reduce this disparity.

2.
Curr Psychiatry Rep ; 22(12): 87, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33289044

RESUMO

PURPOSE OF REVIEW: To consider various precision medicine approaches to further elucidate the relationship between inflammation and depression and to illustrate how a neurodevelopmental perspective can help in this regard. RECENT FINDINGS: Inflammation associates most strongly with phenotypes of depression that reflect illness behavior and/or metabolic dysfunction and obesity. A separate body of research has shown that maternal inflammation during pregnancy can alter brain circuitry important for mood regulation and/or reward in the developing fetus. Our research group is finding that maternal CRP levels differentially predict positive and negative affect in children assessed at age 4 years, depending on the timing of plasma sampling during pregnancy and the sex of the child. Recent authors have stressed the need to use a variety of precision medicine approaches to refine our understanding of inflammation-depression links. Adding a neurodevelopmental perspective may help to address some of the methodological challenges in this active area of study.

3.
J Natl Cancer Inst ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33301022

RESUMO

BACKGROUND: Clinical guidelines often use predicted lifetime risk from birth to define criteria for making decisions regarding breast cancer screening rather than thresholds based on absolute 5-year risk from current age. METHODS: We used the Prospective Family Cohort Study of 14,657 women without breast cancer at baseline in which, during a median follow-up of 10 years, 482 women were diagnosed with invasive breast cancer. We examined the performances of the IBIS and BOADICEA risk models when using alternative thresholds by comparing predictions based on 5-year risk with those based on lifetime risk from birth and remaining lifetime risk. All statistical tests were two-sided. RESULTS: Using IBIS, the areas under the receiver-operating characteristic curves were 0.66 (95% confidence interval = 0.63 to 0.68) and 0.56 (95% confidence interval = 0.54 to 0.59) for 5-year and lifetime risks, respectively (Pdiff<0.001). For equivalent sensitivities, the 5-year incidence almost always had higher specificities than lifetime risk from birth. For women aged 20-39 years, 5-year risk performed better than lifetime risk from birth. For women aged 40 years or more, receiver-operating characteristic curves were similar for 5-year and lifetime IBIS risk from birth. Classifications based on remaining lifetime risk were inferior to 5-year risk estimates. Results were similar using BOADICEA. CONCLUSIONS: Our analysis shows that risk stratification using clinical models will likely be more accurate when based on predicted 5-year risk compared with risks based on predicted lifetime and remaining lifetime, particularly for women aged 20-39 years.

4.
Int J Epidemiol ; 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33306803

RESUMO

BACKGROUND: Despite a clear association seen in congenitally infected children, the effect of postnatal cytomegalovirus (CMV) infection during early childhood on cognitive development has not yet been determined. METHODS: CMV-infection status was obtained based on serological measurements when children were 7 years old. Using population-based longitudinal data, we employed multivariate Poisson regression with a robust variance estimator to characterize the relationship between childhood CMV infection and adverse neurocognitive outcomes in children. Suboptimal neurocognitive outcomes were compared between CMV-positive and CMV-negative children using various cognitive assessments from 8 to 15 years of age. Children were evaluated on the cognitive domains of language, reading, memory and general intelligence, with a suboptimal score being >2 standard deviations lower than the mean score. Approximate Bayes factor (ABF) analysis was used to determine the level of evidence for the observed associations. RESULTS: With adjustment for potential confounders, we observed that early-childhood CMV infection was associated with suboptimal total intelligence quotient (IQ) at 8 years of age [incidence-rate ratio (IRR) = 2.50, 95% confidence interval (CI) 1.35-4.62, ABF = 0.08], but not with suboptimal total IQ at 15 years of age (IRR = 0.97, 95% CI 0.43-2.19, ABF = 1.68). Suboptimal attentional control at 8 years (IRR = 1.74, 95% CI 1.13-2.68, ABF = 0.18) and reading comprehension at 9 years (IRR = 1.93, 95% CI 1.12-3.33, ABF = 0.24) were also associated with CMV infection. ABF analysis provided strong evidence for the association between CMV infection and total IQ at 8 years, and only anecdotal evidence for attentional control at 8 years and reading comprehension at 9 years. All other cognitive measures assessed were not associated with CMV infection. CONCLUSION: In this large-scale prospective cohort, we observed some evidence for adverse neurocognitive effects of postnatal CMV infection on general intelligence during early childhood, although not with lasting effect. If confirmed, these results could support the implementation of preventative measures to combat postnatal CMV infection.

5.
BMC Pregnancy Childbirth ; 20(1): 771, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33308186

RESUMO

BACKGROUND: As cannabis consumption is increasing globally, including among pregnant women, there is a critical need to understand the effects of cannabis on fetal development and birth outcomes. We had two objectives: to determine 1) the factors associated with self-reported cannabis use in the pre/early-pregnancy period, and 2) whether cannabis use is associated with low birth weight, preterm birth, or small size for gestational age (GA) infants. METHODS: Maternal questionnaire and birth outcome data was gathered from 2229 women and 1778 singleton infants in the Ontario Birth Study, a hospital-based prospective cohort study (2013-2019). Women self-reported cannabis use within 3 months of learning their pregnancy status. Multivariable linear and logistic regression was conducted to 1) identify factors associated with cannabis use, and 2) determine the associations between cannabis use with the selected birth outcomes. RESULTS: Cannabis use increased in the cohort over time. Women who reported cannabis use (N = 216) were more likely to be younger and more likely to use alcohol, tobacco, and prescription pain medication, although most did not. These women had infants born at lower average birth weights and had 2.0 times the odds of being small for GA (95% confidence interval: 1.3, 3.3) after multivariable adjustment for socioeconomic factors and other substance use. CONCLUSION: Our results suggest that women who use cannabis around the time of conception have higher odds of having infants that are small for gestational age. Targeted clinical messaging may be most applicable to women actively trying to conceive.

6.
Am J Epidemiol ; 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33128063

RESUMO

Earlier pubertal development is only partially explained by childhood body mass index (BMI); the role of other factors like childhood infections is less understood. Using data from the LEGACY Girls Study (2011 - 2016), we prospectively examined the associations between childhood viral infections (Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Herpes Simplex Virus 1 (HSV1), HSV2 and pubertal timing. We measured exposures based on seropositivity in pre-menarcheal girls (n=490). Breast and pubic hair development were classified based on mother-reported Tanner Stage (TS: TS2+ compared with TS1), adjusting for age, BMI, and sociodemographic factors. The average age at first blood draw was 9.8 years (Stdev=1.9 years). The prevalences were 31% CMV+, 37% EBV+, 14% HSV1+, 0.4% HSV2+, and 16% for both CMV+/EBV+. CMV+ infection without co-infection was associated with developing breasts an average of 7 months earlier (Hazard Ratio (HR)=2.12, 95% CI 1.32, 3.40). CMV+ infection without co-infection and HSV1+ and/or HSV2+ infection were associated with developing pubic hair 9 months later (HR 0.41, 95% CI 0.24, 0.71, HR 0.42, 95% CI 0.22, 0.81, respectively). Infection was not associated with menarche. If replicated in larger cohorts with blood collection prior to any breast development, this study supports that childhood infections may play a role in altering pubertal timing.

7.
Am J Epidemiol ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057572

RESUMO

Stressful environments have been associated with earlier menarche. We hypothesized that anxiety, and possibly other internalizing symptoms, are also associated with earlier puberty in girls. The LEGACY Girls Study (2011-2016) includes 1040 girls aged 6 to 13 years at recruitment with growth and development assessed every 6 months. Pre-pubertal maternal reports of daughter's internalizing symptoms were available for breast onset (N=447), pubic hair onset (N=456), and menarche (N=681). Using Cox Proportional Hazard Regression, we estimated prospective hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between one standard deviation of the percentiles of pre-pubertal anxiety, depression, and somatization symptoms and the timing of each pubertal outcome. Multivariable models included age, race/ethnicity, study center, maternal education, body mass index percentile, and breast cancer family history. Additional models included maternal self-reported anxiety. One standard deviation increase of maternally-reported anxiety in girls at baseline was associated with earlier subsequent onset of breast (HR 1.22, 95% CI 1.09-1.36) and pubic hair (HR 1.15, 95% CI 1.01-1.30) development, but not menarche (HR 0.94, 95% CI 0.83-1.07). The association of anxiety with earlier breast development persisted after adjustment for maternal anxiety. Increased anxiety in young girls may indicate risk for earlier pubertal onset.

8.
Breast ; 54: 62-69, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32927238

RESUMO

OBJECTIVE: To examined the impact of reproductive factors on the relationship between radiation treatment (RT) for a first breast cancer and risk of contralateral breast cancer (CBC). METHODS: The Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multi-center, population-based case-control study where cases are women with asynchronous CBC (N = 1521) and controls are women with unilateral breast cancer (N = 2211). Rate ratios (RR) and 95% confidence intervals (CI) were estimated using conditional logistic regression to assess the independent and joint effects of RT (ever/never and location-specific stray radiation dose to the contralateral breast [0, >0-<1Gy, ≥1Gy]) and reproductive factors (e.g., parity). RESULTS: Nulliparous women treated with RT (≥1Gy dose) were at increased risk of CBC compared with nulliparous women not treated with RT, although this relationship did not reach statistical significance (RR = 1.34, 95% CI 0.87, 2.07). Women treated with RT who had an interval pregnancy (i.e., pregnancy after first diagnosis and before second diagnosis [in cases]/reference date [in controls]) had an increased risk of CBC compared with those who had an interval pregnancy with no RT (RR = 4.60, 95% CI 1.16, 18.28). This was most apparent for women with higher radiation doses to the contralateral breast. CONCLUSION: Among young female survivors of breast cancer, we found some evidence suggesting that having an interval pregnancy could increase a woman's risk of CBC following RT for a first breast cancer. While sampling variability precludes strong interpretations, these findings suggest a role for pregnancy and hormonal factors in radiation-associated CBC.

9.
World J Biol Psychiatry ; 21(7): 529-538, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32462949

RESUMO

Objectives: Maternal-foetal tryptophan metabolism plays multiple roles in neurodevelopment and immunomodulation across pregnancy. Tryptophan and the immune system are both influenced by the seasons of the year. We thus compared tryptophan and kynurenine levels in subgroups of pregnant women defined by maternal seasonality and season-of-conception (SoC).Methods: Maternal plasma samples taken at 9-15 and 23-29 weeks of pregnancy were analysed in 47 women with historical full or sub-syndromal Seasonal Affective Disorder (SAD) and 144 pregnant controls. Repeated measure ANCOVAs compared tryptophan and kynurenine levels in the two study groups over the two pregnancy sampling times, using SoC as a moderator.Results: Significant differences in both plasma tryptophan and kynurenine were found across the eight subgroups defined by maternal seasonality and SoC. These results were independent of the state of depression.Conclusions: Pregnant women with a history of full or sub-syndromal SAD exhibited a different pattern of plasma tryptophan and kynurenine across the seasons compared to control mothers, independent of current mood state. Follow-up of the children will determine the implications of these findings for neurodevelopment and psychiatric risk. Maternal seasonality and SoC may be important considerations when studying tryptophan and its metabolites in human pregnancy and foetal brain development.

10.
J Natl Cancer Inst ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32119081

RESUMO

Whether radiation therapy (RT) affects contralateral breast cancer (CBC) risk in women with pathogenic germline variants in moderate- to high-penetrance breast cancer-associated genes is unknown. In a population-based case-control study, we examined the association between RT, variants in ATM, BRCA1/2, or CHEK2*1100delC, and CBC risk. We analyzed 708 cases of women with CBC, and 1,399 controls with unilateral breast cancer, all diagnosed with first invasive breast cancer between 1985-2000, <55 years of age at diagnosis, and screened for variants in breast cancer-associated genes. Rate ratios and 95% confidence intervals were estimated using multivariable conditional logistic regression. RT did not modify the association between known pathogenic variants and CBC risk (e.g., BRCA1/2 pathogenic variant carriers without RT, RR: 3.52, 95% CI: 1.76-7.01; BRCA1/2 pathogenic variant carriers with RT, RR: 4.46, 95% CI: 2.96-6.71), suggesting that modifying RT plans for young women with breast cancer is unwarranted. Rare ATM missense variants, not currently identified as pathogenic, were associated with increased risk of RT-associated CBC (carriers of ATM rare missense variants of uncertain significance without RT, RR: 0.38, 95% CI: 0.09-1.55; carriers of ATM rare missense variants of uncertain significance with RT, RR: 2.98, 95% CI: 1.31-6.80). Further mechanistic studies will aid clinical decision-making related to RT.

11.
Cancer Res ; 80(1): 116-125, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31578201

RESUMO

Although physical activity is associated with lower breast cancer risk for average-risk women, it is not known if this association applies to women at high familial/genetic risk. We examined the association of recreational physical activity (self-reported by questionnaire) with breast cancer risk using the Prospective Family Study Cohort, which is enriched with women who have a breast cancer family history (N = 15,550). We examined associations of adult and adolescent recreational physical activity (quintiles of age-adjusted total metabolic equivalents per week) with breast cancer risk using multivariable Cox proportional hazards regression, adjusted for demographics, lifestyle factors, and body mass index. We tested for multiplicative interactions of physical activity with predicted absolute breast cancer familial risk based on pedigree data and with BRCA1 and BRCA2 mutation status. Baseline recreational physical activity level in the highest four quintiles compared with the lowest quintile was associated with a 20% lower breast cancer risk (HR, 0.80; 95% confidence interval, 0.68-0.93). The association was not modified by familial risk or BRCA mutation status (P interactions >0.05). No overall association was found for adolescent recreational physical activity. Recreational physical activity in adulthood may lower breast cancer risk for women across the spectrum of familial risk. SIGNIFICANCE: These findings suggest that physical activity might reduce breast cancer risk by about 20% for women across the risk continuum, including women at higher-than-average risk due to their family history or genetic susceptibility.See related commentary by Niehoff et al., p. 23.


Assuntos
Neoplasias da Mama , Adolescente , Adulto , Estudos de Coortes , Exercício Físico , Feminino , Humanos , Estudos Prospectivos , Fatores de Risco
12.
Pediatr Res ; 87(7): 1263-1269, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31852009

RESUMO

INTRODUCTION: Acetaminophen is the only analgesic recommended for use during pregnancy. This use has recently been linked to childhood developmental disorders, a finding that requires further investigation. Adverse birth outcomes-preterm birth, low birthweight, and small for gestational age-are associated with increased risk of developmental disorders and can serve as intermediate outcomes when examining the impact of maternal acetaminophen use. METHODS: Clinical and lifestyle-factor data were gathered from 1200 women within the Ontario Birth Study who delivered between January 2013 and June 2017. Poisson regression with robust error variance was used to estimate the relationship between acetaminophen use before and during pregnancy and low birthweight, preterm birth, and small for gestational age. RESULTS: Offspring of mothers who used acetaminophen before pregnancy had a higher risk of low birthweight and small for gestational age. Acetaminophen use

13.
J Natl Cancer Inst ; 112(4): 418-422, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31584660

RESUMO

The performance of breast cancer risk models for women with a family history but negative BRCA1 and/or BRCA2 mutation test results is uncertain. We calculated the cumulative 10-year invasive breast cancer risk at cohort entry for 14 657 unaffected women (96.1% had an affected relative) not known to carry BRCA1 or BRCA2 mutations at baseline using three pedigree-based models (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, BRCAPRO, and International Breast Cancer Intervention Study). During follow-up, 482 women were diagnosed with invasive breast cancer. Mutation testing was conducted independent of incident cancers. All models underpredicted risk by 26.3%-56.7% for women who tested negative but whose relatives had not been tested (n = 1363; 63 breast cancers). Although replication studies with larger sample sizes are needed, until these models are recalibrated for women who test negative and have no relatives tested, caution should be used when considering changing the breast cancer risk management intensity of such women based on risk estimates from these models.


Assuntos
Neoplasias da Mama/epidemiologia , Modelos Estatísticos , Adulto , Idoso , Austrália/epidemiologia , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Canadá/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Risco , Estados Unidos/epidemiologia , Adulto Jovem
14.
JNCI Cancer Spectr ; 3(4): pkz066, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31853515

RESUMO

Background: iPrevent is an online breast cancer (BC) risk management decision support tool. It uses an internal switching algorithm, based on a woman's risk factor data, to estimate her absolute BC risk using either the International Breast Cancer Intervention Study (IBIS) version 7.02, or Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm version 3 models, and then provides tailored risk management information. This study assessed the accuracy of the 10-year risk estimates using prospective data. Methods: iPrevent-assigned 10-year invasive BC risk was calculated for 15 732 women aged 20-70 years and without BC at recruitment to the Prospective Family Study Cohort. Calibration, the ratio of the expected (E) number of BCs to the observed (O) number and discriminatory accuracy were assessed. Results: During the 10 years of follow-up, 619 women (3.9%) developed BC compared with 702 expected (E/O = 1.13; 95% confidence interval [CI] =1.05 to 1.23). For women younger than 50 years, 50 years and older, and BRCA1/2-mutation carriers and noncarriers, E/O was 1.04 (95% CI = 0.93 to 1.16), 1.24 (95% CI = 1.11 to 1.39), 1.13 (95% CI = 0.96 to 1.34), and 1.13 (95% CI = 1.04 to 1.24), respectively. The C-statistic was 0.70 (95% CI = 0.68 to 0.73) overall and 0.74 (95% CI = 0.71 to 0.77), 0.63 (95% CI = 0.59 to 0.66), 0.59 (95% CI = 0.53 to 0.64), and 0.65 (95% CI = 0.63 to 0.68), respectively, for the subgroups above. Applying the newer IBIS version 8.0b in the iPrevent switching algorithm improved calibration overall (E/O = 1.06, 95% CI = 0.98 to 1.15) and in all subgroups, without changing discriminatory accuracy. Conclusions: For 10-year BC risk, iPrevent had good discriminatory accuracy overall and was well calibrated for women aged younger than 50 years. Calibration may be improved in the future by incorporating IBIS version 8.0b.

15.
Breast Cancer Res ; 21(1): 128, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779655

RESUMO

BACKGROUND: Alcohol consumption and cigarette smoking are associated with an increased risk of breast cancer (BC), but it is unclear whether these associations vary by a woman's familial BC risk. METHODS: Using the Prospective Family Study Cohort, we evaluated associations between alcohol consumption, cigarette smoking, and BC risk. We used multivariable Cox proportional hazard models to estimate hazard ratios (HR) and 95% confidence intervals (CI). We examined whether associations were modified by familial risk profile (FRP), defined as the 1-year incidence of BC predicted by Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), a pedigree-based algorithm. RESULTS: We observed 1009 incident BC cases in 17,435 women during a median follow-up of 10.4 years. We found no overall association of smoking or alcohol consumption with BC risk (current smokers compared with never smokers HR 1.02, 95% CI 0.85-1.23; consuming ≥ 7 drinks/week compared with non-regular drinkers HR 1.10, 95% CI 0.92-1.32), but we did observe differences in associations based on FRP and by estrogen receptor (ER) status. Women with lower FRP had an increased risk of ER-positive BC associated with consuming ≥ 7 drinks/week (compared to non-regular drinkers), whereas there was no association for women with higher FRP. For example, women at the 10th percentile of FRP (5-year BOADICEA = 0.15%) had an estimated HR of 1.46 (95% CI 1.07-1.99), whereas there was no association for women at the 90th percentile (5-year BOADICEA = 4.2%) (HR 1.07, 95% CI 0.80-1.44). While the associations with smoking were not modified by FRP, we observed a positive multiplicative interaction by FRP (pinteraction = 0.01) for smoking status in women who also consumed alcohol, but not in women who were non-regular drinkers. CONCLUSIONS: Moderate alcohol intake was associated with increased BC risk, particularly for women with ER-positive BC, but only for those at lower predicted familial BC risk (5-year BOADICEA < 1.25). For women with a high FRP (5-year BOADICEA ≥ 6.5%) who also consumed alcohol, being a current smoker was associated with increased BC risk.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Fumar Cigarros/efeitos adversos , Adolescente , Adulto , Idoso , Suscetibilidade a Doenças , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Vigilância em Saúde Pública , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
16.
JAMA Netw Open ; 2(9): e1912259, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31560388

RESUMO

Importance: Radiation therapy for breast cancer is associated with increased risk of a second primary contralateral breast cancer, but the genetic factors modifying this association are not well understood. Objective: To determine whether a genetic risk score comprising single nucleotide polymorphisms in the nonhomologous end-joining DNA repair pathway is associated with radiation-associated contralateral breast cancer. Design, Setting, and Participants: This case-control study included a case group of women with contralateral breast cancer that was diagnosed at least 1 year after a first primary breast cancer who were individually matched to a control group of women with unilateral breast cancer. Inclusion criteria were receiving a first invasive breast cancer diagnosis prior to age 55 years between 1985 and 2008. Women were recruited through 8 population-based cancer registries in the United States, Canada, and Denmark as part of the Women's Environment, Cancer, and Radiation Epidemiology Studies I (November 2000 to August 2004) and II (March 2010 to December 2012). Data analysis was conducted from July 2017 to August 2019. Exposures: Stray radiation dose to the contralateral breast during radiation therapy for the first breast cancer. A novel genetic risk score comprised of genetic variants in the nonhomologous end-joining DNA repair pathway was considered the potential effect modifier, dichotomized as high risk if the score was above the median of 74 and low risk if the score was at or below the median. Main Outcomes and Measures: The main outcome was risk of contralateral breast cancer associated with stray radiation dose stratified by genetic risk score, age, and latency. Results: A total of 5953 women were approached for study participation, and 3732 women (62.7%) agreed to participate. The median (range) age at first diagnosis was 46 (23-54) years. After 5 years of latency or more, among women who received the first diagnosis when they were younger than 40 years, exposure to 1.0 Gy (to convert to rad, multiply by 100) or more of stray radiation was associated with a 2-fold increased risk of contralateral breast cancer compared with women who were not exposed (rate ratio, 2.0 [95% CI, 1.1-3.6]). The risk was higher among women with a genetic risk score above the median (rate ratio, 3.0 [95% CI, 1.1-8.1]), and there was no association among women with a genetic risk score below the median (rate ratio, 1.3 [95% CI, 0.5-3.7]). Among younger women with a high genetic risk score, the attributable increased risk for contralateral breast cancer associated with stray radiation dose was 28%. Conclusions and Relevance: This study found an increased risk of contralateral breast cancer that was attributable to stray radiation exposure among women with a high genetic risk score and who received a first breast cancer diagnosis when they were younger than 40 years after 5 years or more of latency. This genetic risk score may help guide treatment and surveillance for women with breast cancer.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias Induzidas por Radiação/patologia , Segunda Neoplasia Primária/induzido quimicamente , Radioterapia/efeitos adversos , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/genética , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco
17.
BMC Cancer ; 19(1): 631, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31242899

RESUMO

BACKGROUND: Mammographic density is one of the strongest risk factors for breast cancer. In the general population, mammographic density can be modified by various exposures; whether this is true for women a strong family history is not known. Thus, we evaluated the association between reproductive, hormonal, and lifestyle risk factors and mammographic density among women with a strong family history of breast cancer but no BRCA1 or BRCA2 mutation. METHODS: We included 97 premenopausal and 59 postmenopausal women (age range: 27-68 years). Risk factor data was extracted from the research questionnaire closest in time to the mammogram performed nearest to enrollment. The Cumulus software was used to measure percent density, dense area, and non-dense area for each mammogram. Multivariate generalized linear models were used to evaluate the relationships between breast cancer risk factors and measures of mammographic density, adjusting for relevant covariates. RESULTS: Among premenopausal women, those who had two live births had a mean percent density of 28.8% vs. 41.6% among women who had one live birth (P=0.04). Women with a high body weight had a lower mean percent density compared to women with a low body weight among premenopausal (17.6% vs. 33.2%; P=0.0006) and postmenopausal women (8.7% vs. 14.7%; P=0.04). Among premenopausal women, those who smoked for 14 years or longer had a lower mean dense area compared to women who smoked for a shorter duration (25.3cm2 vs. 53.1cm2; P=0.002). Among postmenopausal women, former smokers had a higher mean percent density (19.5% vs. 10.8%; P=0.003) and dense area (26.9% vs. 16.4%; P=0.01) compared to never smokers. After applying the Bonferroni correction, the association between body weight and percent density among premenopausal women remained statistically significant. CONCLUSIONS: In this cohort of women with a strong family history of breast cancer, body weight was associated with mammographic density. These findings suggest that mammographic density may explain the underlying relationship between some of these risk factors and breast cancer risk, and lend support for the inclusion of mammographic density into risk prediction models.


Assuntos
Peso Corporal , Densidade da Mama/genética , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Saúde da Família , Mamografia , Adulto , Idoso , Estudos Transversais , Ex-Fumantes/estatística & dados numéricos , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Estilo de Vida , Modelos Lineares , Pessoa de Meia-Idade , Paridade , Pós-Menopausa , Pré-Menopausa , Saúde Reprodutiva , Fatores de Risco , Fumantes/estatística & dados numéricos
18.
Breast Cancer Res ; 21(1): 52, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30999962

RESUMO

BACKGROUND: The use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced breast cancer risk, but it is not known if this association extends to women at familial or genetic risk. We examined the association between regular NSAID use and breast cancer risk using a large cohort of women selected for breast cancer family history, including 1054 BRCA1 or BRCA2 mutation carriers. METHODS: We analyzed a prospective cohort (N = 5606) and a larger combined, retrospective and prospective, cohort (N = 8233) of women who were aged 18 to 79 years, enrolled before June 30, 2011, with follow-up questionnaire data on medication history. The prospective cohort was further restricted to women without breast cancer when medication history was asked by questionnaire. Women were recruited from seven study centers in the United States, Canada, and Australia. Associations were estimated using multivariable Cox proportional hazards regression models adjusted for demographics, lifestyle factors, family history, and other medication use. Women were classified as regular or non-regular users of aspirin, COX-2 inhibitors, ibuprofen and other NSAIDs, and acetaminophen (control) based on self-report at follow-up of ever using the medication for at least twice a week for ≥1 month prior to breast cancer diagnosis. The main outcome was incident invasive breast cancer, based on self- or relative-report (81% confirmed pathologically). RESULTS: From fully adjusted analyses, regular aspirin use was associated with a 39% and 37% reduced risk of breast cancer in the prospective (HR = 0.61; 95% CI = 0.33-1.14) and combined cohorts (HR = 0.63; 95% CI = 0.57-0.71), respectively. Regular use of COX-2 inhibitors was associated with a 61% and 71% reduced risk of breast cancer (prospective HR = 0.39; 95% CI = 0.15-0.97; combined HR = 0.29; 95% CI = 0.23-0.38). Other NSAIDs and acetaminophen were not associated with breast cancer risk in either cohort. Associations were not modified by familial risk, and consistent patterns were found by BRCA1 and BRCA2 carrier status, estrogen receptor status, and attained age. CONCLUSION: Regular use of aspirin and COX-2 inhibitors might reduce breast cancer risk for women at familial or genetic risk.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Suscetibilidade a Doenças , Adolescente , Adulto , Idoso , Proteína BRCA1/genética , Neoplasias da Mama/metabolismo , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Mutação , Modelos de Riscos Proporcionais , Vigilância em Saúde Pública , Medição de Risco , Fatores de Risco , Adulto Jovem
19.
JAMA Netw Open ; 2(2): e190083, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30794303

RESUMO

Importance: Early breast development is a risk factor for breast cancer, and girls with a breast cancer family history (BCFH) experience breast development earlier than girls without a BCFH. Objectives: To assess whether prepubertal androgen concentrations are associated with timing of breast development (analysis 1) and to compare serum androgen concentrations in girls with and without a BCFH (analysis 2). Design, Setting, and Participants: Prospective cohort study of 104 girls aged 6 to 13 years at baseline using data collected between August 16, 2011, and March 24, 2016, from the Lessons in Epidemiology and Genetics of Adult Cancer From Youth (LEGACY) Girls Study, New York site. Exposures: Analysis 1 included serum concentrations of dehydroepiandrosterone sulfate, androstenedione, and testosterone (free and total) measured before breast development and divided at the median into high and low categories. Analysis 2 included the degree of BCFH: first-degree was defined as having a mother with breast cancer and second-degree was defined as having a grandmother or aunt with breast cancer. Main Outcomes and Measures: Analysis 1 included age at onset of breast development measured using the Pubertal Development Scale (scores range from 1-4; scores ≥2 indicate breast development), and analysis 2 included serum androgen concentrations. We also assessed breast cancer-specific distress using the 8-item Child Impact of Events Scale. Results: Our analyses included 36 girls for the prospective model, 92 girls for the cross-sectional model, and 104 girls for the longitudinal model. Of the 104 girls, the mean (SD) age at baseline was 10.3 (2.5) years, and 41 (39.4%) were non-Hispanic white, 41 (39.4%) were Hispanic, 13 (12.5%) were non-Hispanic black, and 9 (8.7%) were other race/ethnicity. Forty-two girls (40.4%) had a positive BCFH. Girls with prepubertal androstenedione concentrations above the median began breast development 1.5 years earlier than girls with concentrations below the median (Weibull survival model-estimated median age, 9.4 [95% CI, 9.0-9.8] years vs 10.9 [95% CI, 10.4-11.5] years; P = .001). Similar patterns were observed for dehydroepiandrosterone sulfate (1.1 years earlier: age, 9.6 [95% CI, 9.1-10.1] years vs 10.7 [95% CI, 10.2-11.3] years; P = .009), total testosterone (1.4 years earlier: age, 9.5 [95% CI, 9.1-9.9] years vs 10.9 [95% CI, 10.4-11.5] years; P = .001), and free testosterone (1.1 years earlier: age, 9.7 [95% CI, 9.2-10.1] years vs 10.8 [95% CI, 10.2-11.4] years; P = .01). Compared with girls without BCFH, girls with a first-degree BCFH, but not a second-degree BCFH, had 240% higher androstenedione concentrations (geometric means: no BCFH, 0.49 ng/mL vs first-degree BCFH, 1.8 ng/mL vs second-degree, 1.6 ng/mL; P = .01), 10% higher total testosterone concentrations (12.7 ng/dL vs 14.0 ng/dL vs 13.7 ng/dL; P = .01), and 92% higher free testosterone concentrations (1.3 pg/mL vs 2.5 pg/mL vs 0.3 pg/mL; P = .14). The dehydroepiandrosterone sulfate concentration did not differ between BCFH-positive and BCFH-negative girls but was elevated in girls with breast cancer-specific distress. Conclusions and Relevance: Our findings suggest that androgen concentrations may differ between girls with and without a BCFH and that elevated hormone concentrations during adolescence may be another factor to help explain the familial clustering of breast cancer.


Assuntos
Androgênios/sangue , Neoplasias da Mama/epidemiologia , Mama/crescimento & desenvolvimento , Puberdade , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Anamnese , New York/epidemiologia , Estudos Prospectivos , Puberdade/sangue , Puberdade/fisiologia
20.
Int J Cancer ; 145(2): 370-379, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-30725480

RESUMO

Benign breast disease (BBD) is an established breast cancer (BC) risk factor, but it is unclear whether the magnitude of the association applies to women at familial or genetic risk. This information is needed to improve BC risk assessment in clinical settings. Using the Prospective Family Study Cohort, we used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of BBD with BC risk. We also examined whether the association with BBD differed by underlying familial risk profile (FRP), calculated using absolute risk estimates from the Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model. During 176,756 person-years of follow-up (median: 10.9 years, maximum: 23.7) of 17,154 women unaffected with BC at baseline, we observed 968 incident cases of BC. A total of 4,704 (27%) women reported a history of BBD diagnosis at baseline. A history of BBD was associated with a greater risk of BC: HR = 1.31 (95% CI: 1.14-1.50), and did not differ by underlying FRP, with HRs of 1.35 (95% CI: 1.11-1.65), 1.26 (95% CI: 1.00-1.60), and 1.40 (95% CI: 1.01-1.93), for categories of full-lifetime BOADICEA score <20%, 20 to <35%, ≥35%, respectively. There was no difference in the association for women with BRCA1 mutations (HR: 1.64; 95% CI: 1.04-2.58), women with BRCA2 mutations (HR: 1.34; 95% CI: 0.78-2.3) or for women without a known BRCA1 or BRCA2 mutation (HR: 1.31; 95% CI: 1.13-1.53) (pinteraction = 0.95). Women with a history of BBD have an increased risk of BC that is independent of, and multiplies, their underlying familial and genetic risk.


Assuntos
Doenças Mamárias/epidemiologia , Neoplasias da Mama/epidemiologia , Adulto , Idoso , Proteína BRCA1/genética , Proteína BRCA2/genética , Doenças Mamárias/complicações , Doenças Mamárias/genética , Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Mutação , Linhagem , Estudos Prospectivos , Adulto Jovem
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