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1.
Artigo em Inglês | MEDLINE | ID: mdl-33392844

RESUMO

PURPOSE: We evaluated the association of percent mammographic density (PMD), absolute dense area (DA), and non-dense area (NDA) with risk of "intrinsic" molecular breast cancer (BC) subtypes. METHODS: We pooled 3492 invasive BC and 10,148 controls across six studies with density measures from prediagnostic, digitized film-screen mammograms. We classified BC tumors into subtypes [63% Luminal A, 21% Luminal B, 5% HER2 expressing, and 11% as triple negative (TN)] using information on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. We used polytomous logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CI) for density measures (per SD) across the subtypes compared to controls, adjusting for age, body mass index and study, and examined differences by age group. RESULTS: All density measures were similarly associated with BC risk across subtypes. Significant interaction of PMD by age (P = 0.001) was observed for Luminal A tumors, with stronger effect sizes seen for younger women < 45 years (OR = 1.69 per SD PMD) relative to women of older ages (OR = 1.53, ages 65-74, OR = 1.44 ages 75 +). Similar but opposite trends were seen for NDA by age for risk of Luminal A: risk for women: < 45 years (OR = 0.71 per SD NDA) was lower than older women (OR = 0.83 and OR = 0.84 for ages 65-74 and 75 + , respectively) (P < 0.001). Although not significant, similar patterns of associations were seen by age for TN cancers. CONCLUSIONS: Mammographic density measures were associated with risk of all "intrinsic" molecular subtypes. However, findings of significant interactions between age and density measures may have implications for subtype-specific risk models.

2.
Int J Cancer ; 148(1): 28-37, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32621751

RESUMO

Little is known about how health insurance policies, particularly in developing countries, influence breast cancer prognosis. Here, we examined the association between individual health insurance and breast cancer-specific mortality in China. We included 7436 women diagnosed with invasive breast cancer between 2009 and 2016, at West China Hospital, Sichuan University. The health insurance plan of patient was classified as either urban or rural schemes and was also categorized as reimbursement rate (ie, the covered/total charge) below or above the median. Breast cancer-specific mortality was the primary outcome. Using Cox proportional hazards models, we calculated hazard ratios (HRs) for cancer-specific mortality, contrasting rates among patients with a rural insurance scheme or low reimbursement rate to that of those with an urban insurance scheme or high reimbursement rate, respectively. During a median follow-up of 3.1 years, we identified 326 deaths due to breast cancer. Compared to patients covered by urban insurance schemes, patients covered by rural insurance schemes had a 29% increased cancer-specific mortality (95% CI 0%-65%) after adjusting for demographics, tumor characteristics and treatment modes. Reimbursement rate below the median was associated with a 42% increased rate of cancer-specific mortality (95% CI 11%-82%). Every 10% increase in the reimbursement rate is associated with a 7% (95% CI 2%-12%) reduction in cancer-specific mortality risk, particularly in patients covered by rural insurance schemes (26%, 95% CI 9%-39%). Our findings suggest that underinsured patients face a higher risk of breast cancer-specific mortality in developing countries.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33277321

RESUMO

BACKGROUND: Clinical use of breast cancer risk prediction requires simplified models. We evaluate a simplified version of the validated Rosner-Colditz model and add percent mammographic density (MD) and polygenic risk score (PRS), to assess performance from ages 45-74. We validate using prospective data from the Mayo Mammography Health Study (MMHS). METHODS: We derived the model in the Nurses' Health Study (NHS) based on: MD, 77SNP PRS and a questionnaire score (QS) (lifestyle and reproductive factors). 2799 invasive breast cancer cases were diagnosed from 1990-2000. MD (using Cumulus software) and PRS were assessed in a nested case-control study. We assess model performance using this case-control data set and evaluate 10-year absolute breast cancer risk. The prospective MMHS validation dataset includes 21.8% of women age <50, and 434 incident cases identified over 10 years of follow-up. RESULTS: In the NHS, MD has the highest odds ratio (OR) for 10-year risk prediction: OR per SD =1.48 (95% CI 1.31 - 1.68), followed by PRS, OR per SD = 1.37 (95% CI 1.21 - 1.55) and QS, OR per SD = 1.25 (95% CI 1.11 - 1.41). In MMHS, the AUC adjusted for age was 0.595; for age+MD 0.636; for age+MD+QS 0.650; for age+MD+QS+PRS 0.687. CONCLUSIONS: A simplified assessment of QS, MD and PRS performs consistently to discriminate those at high 10-year breast cancer risk. IMPACT: This simplified model provides accurate estimation of 10-year risk of invasive breast cancer that can be used in a clinic setting to identify women who may benefit from chemopreventive intervention.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33288551

RESUMO

BACKGROUND: Early-life and adult anthropometrics are associated with breast density and breast cancer risk. However, little is known about whether these factors also influence breast tissue composition beyond what is captured by breast density among women with benign breast disease(BBD). METHODS: This analysis included 788 controls from a nested case-control study of breast cancer within the Nurses' Health Study BBD subcohorts. Body fatness at ages 5 and 10 years was recalled using a 9-level pictogram. Weight at age 18, current weight, and height were reported via questionnaires. A deep-learning image analysis was used to quantify the percentages of epithelial, fibrous stromal, and adipose tissue areas within BBD slides. We performed linear mixed models to estimate beta coefficients(ß) and 95% confidence intervals(CIs) for the relationships between anthropometrics and the log-transformed percentages of individual tissue type, adjusting for confounders. RESULTS: Childhood body fatness(level≥4.5 vs. 1), BMI at age 18 (≥23 vs. <19 kg/m2), and current adult BMI(≥30 vs. <21 kg/m2) were associated with higher proportions of adipose tissue(ß[95% CI]=0.34[0.03, 0.65], 0.19[-0.04, 0.42], 0.40[0.12, 0.68], respectively) and lower proportions of fibrous stromal tissue(-0.05[-0.10, 0.002], -0.03[-0.07, 0.003], -0.12[-0.16, -0.07], respectively) during adulthood(all p-trend<0.04). BMI at age 18 was also inversely associated with epithelial tissue(p-trend=0.03). Adult height was not associated with any of the individual tissue types. CONCLUSIONS: Our data suggest that body fatness have long-term impacts on breast tissue composition. IMPACT: This study contributes to our understanding of the link between body fatness and breast cancer risk.

5.
Hum Reprod ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33289027

RESUMO

STUDY QUESTION: Is pubertal timing associated with risk of premenstrual disorders (PMDs) in young adulthood? SUMMARY ANSWER: Late pubertal development is associated with decreased premenstrual symptom burden and risk of PMDs in young adulthood. WHAT IS KNOWN ALREADY: PMDs, including premenstrual syndrome and premenstrual dysphoric disorder, may begin during the teenage years. Few risk factors in early life have been identified for PMD development. STUDY DESIGN, SIZE, DURATION: A prospective cohort study of 6495 female participants during 1996-2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included participants from the Growing Up Today Study (GUTS). Pubertal development was indicated by the timing of menarche, breast and pubic hair growth. Self-reported age at menarche was longitudinally assessed at enrollment (in 1996/2004 for GUTS I/II) and onwards, and classified as early (age ≤ mean - SD, 11.64 years), normative and late menarche (age ≥ mean + SD, 13.95 years). Timing of pubic hair and breast growth were assessed multiple times during follow-up via Tanner scales, and classified into early, normative and late development according to mean ± SD. Using a validated questionnaire based on the Calendar of Premenstrual Experiences, we assessed premenstrual symptoms and identified probable cases of PMDs in 2013. We examined the associations of timing of pubertal development with premenstrual symptom score and disorders using multivariable linear and logistic regressions, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: In 2013 (mean age = 26), 1001 (15.4%) individuals met criteria for a PMD. An inverse association was found between age at menarche and premenstrual symptom z-score (ß -0.05 per year, 95% CI -0.07 to -0.03) and risk of PMDs (odds ratio (OR) 0.93 per year, 95% CI 0.88 to 0.99). Compared to individuals with normative menarche, individuals with late menarche had a lower risk of PMDs (OR 0.73, 95% CI 0.59 to 0.91), while individuals with early menarche had comparable odds (OR 0.98, 95% CI 0.81 to 1.18). Moreover, early growth of pubic hair was associated with increased premenstrual symptoms (z-score ß 0.09 per year, 95% CI 0.02 to 0.17) and PMD risk (OR 1.28, 95% CI 1.04 to 1.56), independent of age at menarche. No associations were noted for breast development. LIMITATIONS, REASONS FOR CAUTION: One major limitation is some misclassification of menarche due to recall. We, however, showed robust association among participants who were premenarcheal at baseline. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that pubertal timing, particularly timing of menarche, is inversely associated with the risk of developing premenstrual symptoms in young adulthood, and that women with later menarche have significantly lower risk of PMDs. Information on PMDs should be provided to teenage girls and their parents. If these findings are confirmed in independent populations, prevention strategies and early detection programs may be considered for women with early pubertal development. STUDY FUNDING/COMPETING INTEREST(S): The work is supported by the National Institutes of Health and Swedish Research Council. TRIAL REGISTRATION NUMBER: N/A.

6.
Cancer ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33259061

RESUMO

BACKGROUND: Many young women with newly diagnosed breast cancer are interested in future pregnancies. Prospective data regarding fertility interest and reproductive patterns after diagnosis are needed to counsel patients. METHODS: The Young Women's Breast Cancer Study is a multicenter, prospective cohort of women who were diagnosed with breast cancer at age ≤40 years between 2006 and 2016. Women complete surveys at baseline, every 6 months for 3 years, then annually. Here, the authors describe fertility interest and pregnancies within 5 years of diagnosis for women with stage 0 through III breast cancer. RESULTS: Of 1026 eligible participants, 368 (36%) reported interest in future biologic children at least once within 5 years after diagnosis, including 16% at 5 years after diagnosis. Among 130 women who attempted to become pregnant, 90 (69.2%) conceived; and, among 896 women who did not attempt to conceive, 18 (2.0%) became pregnant, with a total of 152 pregnancies resulting in 91 live births. Factors associated with pregnancy included younger versus older age at diagnosis (aged ≤30 vs 36-40 years: odds ratio [OR], 6.63; 95% CI, 3.18-13.83; P < .0001; aged 31-35 vs 36-40 years: OR, 5.86; 95% CI, 3.37-10.17; P < .0001) and being nulliparous versus parous (OR, 2.66; 95% CI, 1.56-4.53; P = .001). The receipt of endocrine therapy versus no endocrine therapy (OR, 0.35; 95% CI, 0.20-0.59; P = .001) was inversely associated with pregnancy. CONCLUSIONS: Many women remain interested in future fertility in the 4 years after a breast cancer diagnosis, indicating that longitudinal fertility discussions are needed. Although a minority of those interested in having children attempted to become pregnant in the first 5 years, most who attempted to conceive did so and had live births.

7.
NPJ Breast Cancer ; 6(1): 62, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33298921

RESUMO

Immunohistochemical (IHC) staining in breast cancer shows both gain and loss of COX2 expression with disease risk and progression. We investigated four common COX2 antibody clones and found high specificity for purified human COX2 for three clones; however, recognition of COX2 in cell lysates was clone dependent. Biochemical characterization revealed two distinct forms of COX2, with SP21 recognizing an S-nitrosylated form, and CX229 and CX294 recognizing non-nitrosylated COX2 antigen. We found S-nitrosylated and non-nitrosylated COX2 occupy different subcellular locations in normal and breast cancer tissue, implicating distinct synthetic/trafficking pathways and function. Dual stains of ~2000 breast cancer cases show early-onset breast cancer had increased expression of both forms of COX2 compared to postmenopausal cases. Our results highlight the strengths of using multiple, highly characterized antibody clones for COX2 IHC studies and raise the prospect that S-nitrosylation of COX2 may play a role in breast cancer biology.

8.
NPJ Breast Cancer ; 6(1): 61, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33298962

RESUMO

Adolescent drinking is associated with higher risks of proliferative benign breast disease (BBD) and invasive breast cancer (BC). Furthermore, adolescent nut and fiber consumptions are associated with lower risks of benign lesions and premenopausal BC. We hypothesize that diet (nuts, fiber) may mitigate the elevated BBD risk associated with alcohol. A prospective cohort of 9031 females, 9-15 years at baseline, completed questionnaires in 1996-2001, 2003, 2005, 2007, 2010, 2013, and 2014. Participants completed food frequency questionnaires in 1996-2001. In 2005, participants (>=18 years) began reporting biopsy-confirmed BBD (N = 173 cases). Multivariable logistic regression estimated associations between BBD and cross-classified intakes (14-17 years) of alcohol and peanut butter/nuts (separately, total dietary fiber). Only 19% of participants drank in high school; drinking was associated with elevated BBD risk (OR = 1.75, 95% CI: 1.20-2.56; p = 0.004) compared to nondrinkers. Participants consuming any nuts/butter had lower BBD risk (OR = 0.64, 95% CI: 0.45-0.90; p = 0.01) compared to those consuming none. Participants in top 75% fiber intake had lower risk (OR = 0.57, 95% CI: 0.40-0.81; p = 0.002) compared to bottom quartile. Testing our hypothesis that consuming nuts/butter mitigates the elevated alcohol risk, analyzing alcohol and nuts combined found that those who consumed both had lower risk (RR = 0.47, 95% CI: 0.24-0.89; p = 0.02) compared to drinkers eating no nuts. Our analysis of alcohol and fiber together did not demonstrate risk mitigation by fiber. For high school females who drink, their BBD risk may be attenuated by consuming nuts. Due to modest numbers, future studies need to replicate our findings in adolescent/adult females. However, high school students may be encouraged to eat nuts and fiber, and to avoid alcohol, to reduce risk of BBD and for general health benefits.

9.
J Natl Cancer Inst ; 2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33367714

RESUMO

BACKGROUND: Increased body mass index (BMI) is associated with higher postmenopausal breast cancer risk and lower premenopausal breast cancer risk. Less is known about the central adiposity-breast cancer risk association, particularly for tumor subtypes. METHODS: We used prospective waist (WC) and hip circumference (HC) measures in the Nurses' Health Studies. We examined associations of WC, HC and waist-to-hip ratio (WHR) with breast cancer independent of BMI, by menopausal status. Cox proportional hazards models estimated the hazard ratio (HR) and 95% confidence intervals (CI) adjusting for breast cancer risk factors, with and without BMI. RESULTS: Adjusting for BMI, WC, and HC were not associated and WHR was positively associated with premenopausal breast cancer risk (WHR, quintile 5 vs. 1: HRQ5vQ1, BMI-adjusted=1.27, 95%CI = 1.04-1.54, p-trend = 0.01); particularly for, estrogen receptor-negative (ER-)/ progesterone receptor-negative (PR-) and basal-like breast cancers. Premenopausal WC, HC, and WHR were not associated with postmenopausal breast cancer risk, with or without BMI adjustment. Postmenopausal WC, HC, and WHR were each positively associated with postmenopausal breast cancer (eg, WC HRQ5vsQ1=1.59, 95%CI = 1.36-1.86); after adjustment for BMI, only WC remained statistically significant (HRQ5vsQ1, BMI-adjusted=1.38, 95%CI = 1.15-1.64, p-trend = 0.002). In postmenopausal women, associations were stronger among never users of hormone therapy and for ER+/PR+ breast cancers. CONCLUSIONS: Central adiposity was positively associated with pre- and postmenopausal breast cancers independent of BMI. This suggests that mechanisms other than estrogen may also play a role in the relationship between central adiposity and breast cancer. Maintaining a healthy waist circumference may decrease pre- and postmenopausal breast cancer risk.

10.
Cancer Res ; 80(22): 5134-5143, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33188079

RESUMO

Fruits and vegetables contain many bioactive components that may contribute to improved survival after diagnosis of breast cancer, however, evidence to date is insufficient. We prospectively assessed the associations of postdiagnostic fruit and vegetable consumption with breast cancer-specific and all-cause mortality among 8,927 women with stage I-III breast cancer identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and NHSII (1991-2011), using a validated food frequency questionnaire completed every 4 years after diagnosis. We prospectively documented 2,521 deaths, including 1,070 from breast cancer through follow-up until 2014 in the NHS and 2015 in the NHSII. Total fruit and vegetable and total vegetable consumption was related to lower all-cause [HRQ5vsQ1, 0.82; 95% confidence interval (CI), 0.71-0.94; P trend = 0.004, and HRQ5vsQ1, 0.84; 95% CI, 0.72-0.97; P trend = 0.001, respectively], but not breast cancer-specific mortality. Total fruit consumption was not related to breast cancer-specific or all-cause mortality. Greater intake of green leafy and cruciferous vegetables was associated with lower all-cause mortality. Each 2 servings/week of blueberries was associated with a 25% (HR, 0.75; 95% CI, 0.60-0.94) lower breast cancer-specific and a 17% (HR, 0.83; 95% CI, 0.72-0.96) lower all-cause mortality. In contrast, higher fruit juice consumption was associated with higher breast cancer-specific (HRQ5vsQ1, 1.33; 95% CI, 1.09-1.63; P trend = 0.002) and all-cause mortality (HRQ5vsQ1, 1.19; 95% CI, 1.04-1.36; P trend = 0.003). Apple juice largely accounted for these higher risks and orange juice was not associated with risk. Higher postdiagnostic fruit and vegetable consumption among breast cancer survivors was not associated with breast cancer-specific mortality. However, our findings suggest that higher vegetable consumption, particularly green leafy and cruciferous vegetables, was associated with better overall survival among patients with breast cancer. Higher fruit juice consumption, but not orange juice, was associated with poorer breast cancer-specific and all-cause survival. SIGNIFICANCE: A large-scale study shows that high fruit and vegetable consumption may be associated with better overall survival among breast cancer patients, while high fruit juice consumption may be associated with poorer porgnosis.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33219162

RESUMO

BACKGROUND: We investigated the associations of post-diagnostic dietary glycemic index (GI), glycemic load (GL), insulin index (II), and insulin load (IL) with breast cancer-specific and all-cause mortality. METHODS: Among 8,932 women with stage I-III breast cancer identified in the Nurses' Health Study (NHS) (1980-2010) and NHSII (1991-2011), we prospectively evaluated the associations between post-diagnostic GI, GL, II, and IL, and breast cancer-specific and all-cause mortality. Participants completed a validated food frequency questionnaire every four years after diagnosis. RESULTS: During follow-up by 2014 in the NHS and 2015 in the NHSII, 2,523 deaths, including 1,071 from breast cancer were documented. Higher post-diagnostic GL was associated with higher risk of both breast cancer-specific mortality (HRQ5vsQ1=1.33, 95%CI=1.09-1.63; Ptrend=0.008) and all-cause mortality (HRQ5vsQ1=1.26, 95%CI=1.10-1.45; Ptrend=0.0006). Higher all-cause mortality was also observed with higher post-diagnostic GI (HRQ5vsQ1=1.23, 95%CI=1.08-1.40; Ptrend=0.001), II (HRQ5vsQ1=1.20, 95%CI=1.04-1.38; Ptrend=0.005), and IL (HRQ5vsQ1=1.23, 95%CI=1.07-1.42; Ptrend=0.0003). The associations were not modified by insulin receptor or estrogen receptor status of the tumor, or body mass index. CONCLUSION: We found that higher dietary GL, reflecting postprandial glucose response, after a breast cancer diagnosis was associated with higher risk of breast cancer-specific mortality. Higher dietary GI, GL, II, and IL after a breast cancer diagnosis were associated with higher risk of death from any cause. IMPACT: These results suggest that carbohydrate quantity and quality may be important in breast cancer prognosis.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33150547

RESUMO

PURPOSE: The 21-gene Breast Recurrence Score test predicts benefit from adjuvant chemotherapy in estrogen receptor-positive, HER2-negative (ER+/HER2-) breast cancer (BC). We examined whether the 21-gene assay predicts response to neoadjuvant chemotherapy (NCT). METHODS: We identified patients with stage I-III ER+/HER2- BC treated with NCT from the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with BC at age ≤40 years. The 21-gene assay was performed on tumor specimens removed prior to NCT either as part of clinical care or retrospectively for research. Pathological complete response (pCR) was defined as ypT0/is ypN0. The relationship between Recurrence Score result and pCR was evaluated using logistic regression modeling. RESULTS: 76 women received NCT for ER+/HER2- BC and were eligible for this analysis. Median age at diagnosis was 37 years (range 24-40). Scores ranged between 5 and 77 with 50% >25 and 5% <11. Median Recurrence Score result was significantly higher among tumors achieving pCR vs. non-pCR response (61.5 vs. 23, pwilcoxon = 0.0005). pCR rate in patients with scores >25 was 21% (8/38) vs. 5% in patients with scores <25 (2/38) (p = 0.09), with both pCRs in the <25 group in patients with scores between 21 and 25. In multivariable analysis, only Recurrence Score result was significantly associated with pCR (OR: 1.07, 95%CI 1.01-1.12, p = 0.01). CONCLUSIONS: In young women with ER+/HER2- BC who received NCT, higher pretreatment Recurrence Score result was associated with an increased likelihood of pCR. Gene expression profile assays may have a role in decision making in young women in need of neoadjuvant therapy.

13.
J Natl Cancer Inst ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33136151

RESUMO

BACKGROUND: Cumulative epidemiologic evidence has shown that early-life adiposity is strongly inversely associated with breast cancer risk throughout life, independent of adult obesity. However, the molecular mechanisms remain poorly understood. METHODS: We assessed the association of early-life adiposity, defined as self-reported body size during ages 10-20 years from a validated 9-level pictogram, with the transcriptome of breast tumor (N = 835) and tumor-adjacent histologically-normal tissue (N = 663) in the Nurses' Health Studies. We conducted multivariable linear regression analysis to identify differentially expressed genes in tumor and tumor-adjacent tissue, respectively. Molecular pathway analysis using Hallmark gene sets (N = 50) was further performed to gain biological insights. Analysis was stratified by tumor estrogen receptor (ER) protein expression status (N = 673 for ER+ and 162 for ER- tumors). RESULTS: No gene was statistically significantly differentially expressed by early-life body size after multiple comparison adjustment. However, pathway analysis revealed several statistically significantly (FDR < 0.05) up or down regulated gene sets. In stratified analyses by tumor ER status, larger body size during ages 10-20 years was associated with decreased cellular proliferation pathways, including MYC target genes, in both ER+ and ER- tumors. In ER+ tumors, larger body size was also associated with upregulation in genes involved in TNFα/NFkB signaling. In ER- tumors, larger body size was additionally associated with downregulation in genes involved in IFNα and IFNγ immune response and PI3K/ATK/mTOR signaling; the INFγ response pathway was also downregulated in ER- tumor-adjacent tissue though at borderline statistical significance (FDR = 0.1). CONCLUSION: These findings provide new insights into the biological and pathological underpinnings of the early-life adiposity and breast cancer association.

14.
Am J Clin Nutr ; 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33236056

RESUMO

BACKGROUND: Carotenoids represent 1 of few modifiable factors to reduce breast cancer risk. Elucidation of interactions between circulating carotenoids and genetic predispositions or mammographic density (MD) may help inform more effective primary preventive strategies in high-risk populations. OBJECTIVES: We tested whether women at high risk for breast cancer due to genetic predispositions or high MD would experience meaningful and greater risk reduction from higher circulating levels of carotenoids in a nested case-control study in the Nurses' Health Studies (NHS and NHSII). METHODS: This study included 1919 cases and 1695 controls in a nested case-control study in the NHS and NHSII. We assessed both multiplicative and additive interactions. RR reductions and 95% CIs were calculated using unconditional logistic regressions, adjusting for matching factors and breast cancer risk factors. Absolute risk reductions (ARR) were calculated based on Surveillance, Epidemiology, and End Results incidence rates. RESULTS: We showed that compared with women at low genetic risk or low MD, those with higher genetic risk scores or high MD had greater ARRs for breast cancer as circulating carotenoid levels increase (additive P-interaction = 0.05). Among women with a high polygenic risk score, those in the highest quartile of circulating carotenoids had a significant ARR (28.6%; 95% CI, 14.8-42.1%) compared to those in the lowest quartile of carotenoids. For women with a high percentage MD (≥50%), circulating carotenoids were associated with a 37.1% ARR (95% CI, 21.7-52.1%) when comparing the highest to the lowest quartiles of circulating carotenoids. CONCLUSIONS: The inverse associations between circulating carotenoids and breast cancer risk appeared to be more pronounced in high-risk women, as defined by germline genetic makeup or MD.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33242164

RESUMO

PURPOSE: Synchronous bilateral breast cancer is uncommon, and its pattern and incidence among younger women is unknown. Here we report the incidence, phenotypes, and long-term oncologic outcomes of bilateral breast cancer in women enrolled in the Young Women's Breast Cancer Study (YWS). METHODS: The YWS is a multi-center, prospective cohort study of women with breast cancer diagnosed at age ≤ 40 years. Those with synchronous bilateral breast cancer formed our study cohort. Tumor phenotypes were categorized as luminal A (hormone receptor (HR)+/HER2-/grade 1/2), luminal B (HR+ /HER2+ or HER2- and grade 3), HER2-enriched (HR-/HER2+), or basal-like (HR-/HER2-). Descriptive statistics were used to evaluate tumor phenotypes of bilateral cancers for concordance. RESULTS: Among 1302 patients enrolled in the YWS, 21 (1.6%) patients had synchronous bilateral disease. The median age of diagnosis was 38 years (range 18-40 years). Seventeen (81.0%) underwent genetic testing with 6 found to have pathogenic germline mutations in BRCA1, BRCA2, or TP53. The majority of patients (76.2%) underwent bilateral mastectomy. On pathology, 2 patients had bilateral in-situ disease, 6 had unilateral invasive and contralateral in-situ disease, and 13 had bilateral invasive disease. Of those with bilateral invasive disease, 10 (76.9%) had bilateral luminal tumors and, when fully characterized, 6 were of the same luminal subtype. Only 1 patient had bilateral basal-like breast cancer. At median follow-up of 8.2 years, 14 patients are alive with no recurrent disease. CONCLUSIONS: Bilateral breast cancer is uncommon among young women diagnosed with breast cancer at age ≤ 40. In our cohort, the majority of invasive tumors were of the luminal phenotype, though some differed by grade or HER2 status. These findings support the need for thorough pathologic workup of bilateral disease when it is found in young women with breast cancer to determine risk and tailor treatment.

16.
BMC Public Health ; 20(1): 1514, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023562

RESUMO

BACKGROUND: Young women with breast cancer tend to report lower quality of life and higher levels of stress than older women with breast cancer, and this may have implications for other psychosocial factors including finances. We sought to determine if stress, anxiety, and depression at diagnosis were associated with changes in household income over 12-months in young women with breast cancer in the United States. METHODS: This study was a prospective, longitudinal cohort study comprised of women enrolled in the Young and Strong trial. Of the 467 women aged 18-45 newly diagnosed with early-stage breast cancer enrolled in the Young and Strong trial from 2012 to 2013, 356 (76%) answered income questions. Change in household income from baseline to 12 months was assessed and women were categorized as having lost, gained, maintained the same household income <$100,000, or maintained household income ≥$100,000. Patient-reported stress, anxiety, and depression were assessed close to diagnosis at trial enrollment. Adjusted multinomial logistic regression models were used to compare women who lost, gained, or maintained household income ≥$100,000 to women who maintained the same household income <$100,000. RESULTS: Although most women maintained household income ≥$100,000 (37.1%) or the same household income <$100,000 (32.3%), 15.4% lost household income and 15.2% gained household income. Stress, anxiety, and depression were not associated with gaining or losing household income compared to women maintaining household incomes <$100,000. Women with household incomes <$50,000 had a higher risk of losing household income compared to women with household incomes ≥$50,000. Women who maintained household incomes ≥$100,000 were less likely to report financial or insurance problems. Among women who lost household income, 56% reported financial problems and 20% reported insurance problems at 12 months. CONCLUSIONS: Baseline stress, anxiety, and depression were not associated with household income changes for young women with breast cancer. However, lower baseline household income was associated with losing household income. Some young survivors encounter financial and insurance problems in the first year after diagnosis, and further support for these women should be considered. TRIAL REGISTRATION: Clinicaltrials.gov , NCT01647607 ; date registered: July 23, 2012.

17.
Public Health Nutr ; : 1-8, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33023713

RESUMO

OBJECTIVE: Evaluate associations between orange juice (OJ) consumption and anthropometric parameters. DESIGN: Prospective cohort study assessing the association between OJ intake and changes in BMI and height-for-age Z-score (HAZ) using mixed linear regression. SETTING: 2004-2008, USA. PARTICIPANTS: Children from the Growing Up Today Study II (n 7301), aged 9-16 years at enrollment. RESULTS: OJ consumption was positively associated with 2-year change in HAZ in girls (mean (se)): 0·03 (0·01) for non-consumers, 0·03 (0·02) for 1-3 glasses/month, 0·06 (0·01) for 1-6 glasses/week and 0·09 (0·02) for ≥1 glass/d after full adjustment (Ptrend = 0·02). However, OJ consumption was not associated with 2-year change in BMI percentile (kg/m2, mean (se)): -0·44 (0·36) for non-consumers, 0·20 (0·41) for 1-3 glasses/month, -0·04 (0·34) for 1-6 glasses/week and -0·77 (0·62) for ≥1 glass/d in girls, Ptrend = 0·81; -0·94 (0·53) for non-consumers, -1·68 (0·52) for 1-3 glasses/month, -0·81 (0·38) for 1-6 glasses per week and -1·12 (0·61) for ≥1 glass/d in boys, Ptrend = 0·49. CONCLUSION: OJ consumption was favourably associated with height growth but unrelated to excess weight gain. OJ may be a useful alternative to whole fruit in the event that whole fruit intake is insufficient.

18.
Nat Commun ; 11(1): 4637, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32934226

RESUMO

An association between schizophrenia and subsequent breast cancer has been suggested; however the risk of schizophrenia following a breast cancer is unknown. Moreover, the driving forces of the link are largely unclear. Here, we report the phenotypic and genetic positive associations of schizophrenia with breast cancer and vice versa, based on a Swedish population-based cohort and GWAS data from international consortia. We observe a genetic correlation of 0.14 (95% CI 0.09-0.19) and identify a shared locus at 19p13 (GATAD2A) associated with risks of breast cancer and schizophrenia. The epidemiological bidirectional association between breast cancer and schizophrenia may partly be explained by the genetic overlap between the two phenotypes and, hence, shared biological mechanisms.


Assuntos
Neoplasias da Mama/genética , Fatores de Transcrição GATA/genética , Esquizofrenia/genética , Idoso , Cromossomos Humanos Par 19/genética , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Suécia
19.
JAMA Surg ; 155(11): 1035-1042, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32936216

RESUMO

Importance: Young women with breast cancer are increasingly choosing bilateral mastectomy (BM), yet little is known about short-term and long-term physical and psychosocial well-being following surgery in this population. Objective: To evaluate the differential associations of surgery with quality of life (QOL) and psychosocial outcomes from 1 to 5 years following diagnosis. Design, Setting, and Participants: Cohort study. Setting: Multicenter, including academic and community hospitals in North America. Participants: Women age ≤40 when diagnosed with Stage 0-3 with unilateral breast cancer between 2006 and 2016 who had surgery and completed QOL and psychosocial assessments. Exposures (for observational studies): Primary breast surgery including breast-conserving surgery (BCS), unilateral mastectomy (UM), and BM. Main Outcomes and Measures: Physical functioning, body image, sexual health, anxiety and depressive symptoms were assessed in follow-up. Results: Of 826 women, mean age at diagnosis was 36.1 years; most women were White non-Hispanic (86.7%). Regarding surgery, 45% had BM, 31% BCS, and 24% UM. Of women who had BM/UM, 84% had reconstruction. While physical functioning, sexuality, and body image improved over time, sexuality and body image were consistently worse (higher adjusted mean scores) among women who had BM vs BCS (body image: year 1, 1.32 vs 0.64; P < .001; year 5, 1.19 vs 0.48; P < .001; sexuality: year 1, 1.66 vs 1.20, P < .001; year 5, 1.43 vs 0.96; P < .001) or UM (body image: year 1, 1.32 vs 1.15; P = .06; year 5, 1.19 vs 0.96; P = .02; sexuality: year 1, 1.66 vs 1.41; P = .02; year 5, 1.43 vs 1.09; P = .002). Anxiety improved across groups, but adjusted mean scores remained higher among women who had BM vs BCS/UM at 1 year (BM, 7.75 vs BCS, 6.94; P = .005; BM, 7.75 vs UM, 6.58; P = .005), 2 years (BM, 7.47 vs BCS, 6.18; P < .001; BM, 7.47 vs UM, 6.07; P < .001) and 5 years (BM, 6.67 vs BCS, 5.91; P = .05; BM, 6.67 vs UM, 5.79; P = .05). There were minimal between-group differences in depression levels in follow-up. Conclusions and Relevance: While QOL improves over time, young breast cancer survivors who undergo more extensive surgery have worse body image, sexual health, and anxiety compared with women undergoing less extensive surgery. Ensuring young women are aware of the short-term and long-term effects of surgery and receive support when making surgical decisions is warranted.

20.
Cancer Epidemiol Biomarkers Prev ; 29(11): 2358-2368, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32917665

RESUMO

BACKGROUND: Manual qualitative and quantitative measures of terminal duct lobular unit (TDLU) involution were previously reported to be inversely associated with breast cancer risk. We developed and applied a deep learning method to yield quantitative measures of TDLU involution in normal breast tissue. We assessed the associations of these automated measures with breast cancer risk factors and risk. METHODS: We obtained eight quantitative measures from whole slide images from a benign breast disease (BBD) nested case-control study within the Nurses' Health Studies (287 breast cancer cases and 1,083 controls). Qualitative assessments of TDLU involution were available for 177 cases and 857 controls. The associations between risk factors and quantitative measures among controls were assessed using analysis of covariance adjusting for age. The relationship between each measure and risk was evaluated using unconditional logistic regression, adjusting for the matching factors, BBD subtypes, parity, and menopausal status. Qualitative measures and breast cancer risk were evaluated accounting for matching factors and BBD subtypes. RESULTS: Menopausal status and parity were significantly associated with all eight measures; select TDLU measures were associated with BBD histologic subtype, body mass index, and birth index (P < 0.05). No measure was correlated with body size at ages 5-10 years, age at menarche, age at first birth, or breastfeeding history (P > 0.05). Neither quantitative nor qualitative measures were associated with breast cancer risk. CONCLUSIONS: Among Nurses' Health Studies women diagnosed with BBD, TDLU involution is not a biomarker of subsequent breast cancer. IMPACT: TDLU involution may not impact breast cancer risk as previously thought.

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