Search

Purpose: To evaluate use of specific antiepileptic drugs (AEDs) in pregnancy in relation to specific birth defects.Methods: Using data from the National Birth Defects Prevention Study, we assessed use of AEDs and the risk of neural tube defects (NTDs), oral clefts (OCs), heart defects (HDs), hypospadias, and other major birth defects, taking specific agent, timing, and indication into consideration.Results: Drug-specific increased risks were observed for valproic acid in relation to NTDs [adjusted odds ratio (aOR), 9.7;, 95% confidence interval (CI), 3.4-27.5], OCs (aOR, 4.4; 95% CI, 1.6-12.2), HDs (aOR, 2.0; 95% CI, 0.78-5.3), and hypospadias (aOR. 2.4; 95% CI, 0.62-9.0), and for carbamazapine in relation to NTDs (aOR, 5.0; 95% CI, 1.9-12.7). Epilepsy history without AED use did not seem to increase risk.Conclusions: Valproic acid, which current guidelines suggest should be avoided in pregnancy, was most notable in terms of strength and breadth of its associations. Carbamazapine was associated with NTDs, even after controlling for folic acid use. Sample sizes were still too small to adequately assess risks of less commonly used AEDs, but our findings support further study to identify lower risk options for pregnant women. [ABSTRACT FROM AUTHOR]

Annual surveillance mammograms in older long-term breast cancer survivors are recommended, but this recommendation is based on little evidence and with no guidelines on when to stop. Surveillance mammograms should decrease breast cancer mortality by detecting second breast cancer events at an earlier stage. We examined the association between surveillance mammography beyond 5 years after diagnosis on breast cancer-specific mortality in a cohort of women aged ≥ 65 years diagnosed 1990-1994 with early stage breast cancer. Our cohort included women who survived disease free for ≥ 5 years (N = 1,235) and were followed from year 6 through death, disenrollment, or 15 years after diagnosis. Asymptomatic surveillance mammograms were ascertained through medical record review. We used Cox proportional hazards regression stratified by follow-up year to calculate the association between time-varying surveillance mammography and breast cancer-specific and other-than-breast mortality adjusting for site, stage, primary surgery type, age and time-varying Charlson Comorbidity Index. The majority (85 %) of the 1,235 5-year breast cancer survivors received ≥ 1 surveillance mammogram in years 5-9 (yearly proportions ranged from 48 to 58 %); 82 % of women received ≥ 1 surveillance mammogram in years 10-14. A total of 120 women died of breast cancer and 393 women died from other causes (average follow-up 7.3 years). Multivariable models and lasagna plots suggested a modest reduction in breast cancer-specific mortality with surveillance mammogram receipt in the preceding year (IRR 0.82, 95 % CI 0.56-1.19, p = 0.29); the association with other-cause mortality was 0.95 (95 % CI 0.78-1.17, p = 0.64). Among older breast cancer survivors, surveillance mammography may reduce breast cancer-specific mortality even after 5 years of disease-free survival. Continuing surveillance mammography in older breast cancer survivors likely requires physician-patient discussions similar to those recommended for screening, taking into account comorbid conditions and life-expectancy.

Background: Of the approximately 2.4 million American women with a history of breast cancer, 43% are aged ≥ 65 years and are at risk for developing subsequent malignancies., Methods: Women from 6 geographically diverse sites included 5-year breast cancer survivors (N = 1361) who were diagnosed between 1990 and 1994 at age ≥ 65 years with stage I or II disease and a comparison group of women without breast cancer (N = 1361). Women in the comparison group were age-matched and site-matched to breast cancer survivors on the date of breast cancer diagnosis. Follow-up began 5 years after the index date (survivor diagnosis date or comparison enrollment date) until death, disenrollment, or through 15 years after the index date. Data were collected from medical records and electronic sources (cancer registry, administrative, clinical, National Death Index). Analyses included descriptive statistics, crude incidence rates, and Cox proportional hazards regression models for estimating the risk of incident malignancy and were adjusted for death as a competing risk., Results: Survivors and women in the comparison group were similar: >82% were white, 55% had a Charlson Comorbidity Index of 0, and ≥ 73% had a body mass index ≤ 30 kg/m(2) . Of all 306 women (N = 160 in the survivor group, N = 146 in the comparison group) who developed a first incident malignancy during follow-up, the mean time to malignancy was similar (4.37 ± 2.81 years vs 4.03 ± 2.76 years, respectively; P = .28), whereas unadjusted incidence rates were slightly higher in survivors (1882 vs 1620 per 100,000 person years). The adjusted hazard of developing a first incident malignancy was slightly elevated in survivors in relation to women in the comparison group, but it was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.94-1.47)., Conclusions: Older women who survived 5 years after an early stage breast cancer diagnosis were not at an elevated risk for developing subsequent incident malignancies up to 15 years after their breast cancer diagnosis., (Copyright © 2012 American Cancer Society.)

Background: Clinical interpretation of health related quality of life (HRQOL) scores is challenging. The purpose of this analysis was to interpret score changes and identify minimal clinically important differences (MCID) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) before (T1) and during (T2) cancer treatment., Methods: Patients (N = 627) in stem cell transplant (SCT) and medical (MED) or radiation (RAD) oncology at two comprehensive cancer centers, enrolled in the Electronic Self-Report Assessment-Cancer study and completed the QLQ-C30 at T1 and T2. Perceived changes in five QOL domains, physical (PF), emotional (EF), social (SF), cognitive functioning (CF) and global quality of life (QOL), were reported using the Subject Significance Questionnaire (SSQ) at T2. Anchored on SSQ ratings indicating "improvement", "the same", or "deterioration", means and effect sizes were calculated for QLQ-C30 score changes. MCID was calculated as the mean difference in QLQ-C30 score changes reflecting one category change on SSQ rating, using a two-piece linear regression model., Results: A majority of SCT patients (54%) perceived deteriorating global HRQOL versus improvement (17%), while approximately equal proportions of MED/RAD patients perceived improvement (25%) and deterioration (26%). Global QOL decreased 14.2 (SCT) and 2.0 (MED/RAD) units, respectively, among patients reporting "the same" in the SSQ. The MCID ranged 5.7-11.4 (SCT) and 7.2-11.8 (MED/RAD) units among patients reporting deteriorated HRQOL; ranged 2.7-3.4 units among MED/RAD patients reporting improvement. Excepting for the global QOL (MCID =6.9), no meaningful MCID was identified among SCT patients reporting improvement., Conclusions: Cancer treatment has greater impact on HRQOL among SCT patients than MED/RAD patients. The MCID for QLQ-C30 score change differed across domains, and differed for perceived improvement and deterioration, suggesting different standards for self-evaluating changes in HRQOL during cancer treatment. Specifically, clinical attention can be focused on patients who report at least a 6 point decrease, and for patients who report at least a 3 point increase on QLQ-C30 domains., Trial Registration: The trial was registered with ClinicalTrials.gov: NCT00852852.

Background: Men diagnosed with localized prostate cancer (LPC) can choose from multiple treatment regimens and are faced with a decision in which medical factors and personal preferences are important. The Personal Patient Profile-Prostate (P3P) is a computerized decision aid for men with LPC that focuses on personal preferences. We determined whether the P3P intervention improved the concordance of treatment choice with self-reported influential side-effects compared with a control group., Methods: English/Spanish-speaking men diagnosed with LPC (2007-2009) from four US cities were enrolled into a randomized trial and followed through 6-months via mailed or online questionnaire. Men were randomized to receive the P3P intervention or standard education plus links to reputable websites. We classified choice as concordant if men were concerned with (a) sexual function and chose external beam radiotherapy or brachytherapy, (b) bowel function and chose prostatectomy, (c) sex, bowel, and/or bladder function and chose active surveillance, or (d) not concerned with any side effect and chose any treatment. Using logistic regression, we calculated odds ratios (OR) and 95% confidence intervals (CI) for the association between the P3P intervention and concordance., Results: Of 448 men, most were <65 years, non-Hispanic white, had multiple physician consultations prior to enrollment, and chose a treatment discordant with concerns about potential side effects. There was no significant difference in concordance between the intervention (45%) and control (50%) group (OR = 0.82; 95%CI = 0.56, 1.2)., Conclusions: The P3P intervention did not improve concordance between potential side effects and treatment choice. Information and/or physician consultation immediately after diagnosis was likely to influence decisions despite concerns about side effects. The intervention may be more effective before the first treatment options consultation., Trial Registration: NCT00692653 http://clinicaltrials.gov/ct2/show/NCT00692653.

Previous studies have suggested that metabolic syndrome may be associated with an increased risk of breast cancer, particularly in postmenopausal women, but U.S. black women have not been assessed. We examined the associations of abdominal obesity, type 2 diabetes, hypertension, and high cholesterol individually and in combination with breast cancer incidence in the Black Women's Health Study. By means of Cox regression models, we estimated incidence rate ratios (IRR) and 95 % confidence intervals (CI) for the associations of baseline and time-dependent values of self-reported abdominal obesity, type 2 diabetes, hypertension, and high cholesterol with breast cancer incidence. During 516,452 person years of follow-up (mean years = 10.5; standard deviation = 2.9) from 1995 to 2007, 1,228 breast cancer cases were identified. After adjustment for age, education, body mass index at age 18, physical activity, and individual cardiometabolic factors, neither individual nor combinations of cardiometabolic factors were associated with breast cancer incidence overall; the multivariable IRR was 1.04 (95 % CI 0.86-1.25) for the combination of ≥3 factors relative to the absence of all factors, and 1.17 (0.85-1.60) for having all four factors. Among postmenopausal women, however, the comparable IRRs were 1.23 (0.93-1.62) and 1.63 (1.12-2.37), respectively. Our findings provide some support for an association between cardiometabolic factors and breast cancer incidence among postmenopausal U.S. black women.

Background: The definitive local therapy options for early-stage breast cancer are mastectomy and breast-conserving surgery followed by radiation therapy. Older women and those with comorbidities frequently receive breast-conserving surgery alone. The interaction of age and comorbidity with breast cancer severity and their impact on receipt of definitive therapy have not been well-studied., Study Design: In a cohort of 1,837 women aged 65 years and older receiving treatment for early-stage breast cancer in 6 integrated health care delivery systems in 1990-1994 and followed for 10 years, we examined predictors of receiving nondefinitive local therapy and assessed the impact on breast cancer recurrence within levels of severity, defined as level of risk for recurrence., Results: Age and comorbidity were associated with receipt of nondefinitive therapy. Compared with those at low risk, women at the highest risk were less likely to receive nondefinitive therapy (odds ratio = 0.32; 95% CI, 0.22-0.47), and women at moderate risk were about half as likely (odds ratio = 0.54; 95% CI, 0.35-0.84). Nondefinitive local therapy was associated with higher rates of recurrence among women at moderate (hazard ratio = 5.1; 95% CI, 1.9-13.5) and low risk (hazard ratio = 3.2; 95% CI, 1.1-8.9). The association among women at high risk was weak (hazard ratio = 1.3; 95% CI, 0.75-2.1)., Conclusions: Among these older women with early-stage breast cancer, decisions about therapy partially balanced breast cancer severity against age and comorbidity. However, even among women at low risk, omitting definitive local therapy was associated with increased recurrence., (Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiologic studies have yet to provide consistent evidence to support a protective effect of aspirin and other non-steroidal anti-inflammatory drugs (NSAID) on the incidence of breast cancer., Objective: We evaluated the relations of current use of aspirin, non-aspirin NSAIDs, and acetaminophen with breast cancer incidence in the Black Women's Health Study., Methods: Biennial follow-up of 59,000 study participants began in 1995. During 558,600 person-years of follow-up through 2007, 1,275 breast cancer cases were identified. Using Cox proportional hazards regression, we estimated incidence rate ratios (IRR) and 95% confidence intervals (CI) for associations of current and former use of aspirin, other NSAIDs, and acetaminophen with incident breast cancer., Results: After adjustment for age, education, body mass index at age 18, physical activity, female hormone use, current smoking, and other NSAID use, the IRRs were 0.79 (95% CI = 0.66, 0.95) for current aspirin use and 0.68 (95% CI = 0.50, 0.92) for ≥5 years of aspirin use. Similar associations were observed for acetaminophen use., Conclusions: Both aspirin and acetaminophen use were inversely associated with breast cancer incidence in the present study. Reasons for the association with acetaminophen use are unclear, given that acetaminophen has very weak anti-inflammatory effects.

Background: Preliminary evidence suggests that metformin may decrease breast cancer risk by decreasing insulin levels and reducing cell proliferation. We evaluated the effect of metformin medication on the risk of incident breast cancer among peri- and postmenopausal women., Methods: We used Danish medical registries to conduct a nested case-control study among type 2 diabetic women 50 years or older who resided in northern Denmark from 1989 to 2008 (n = 4,323). We identified 393 diabetic cases and used risk-set sampling to select 10 diabetic controls per case (n = 3,930) matched on county of residence. Odds ratios (OR) and 95% CIs were estimated by conditional logistic regression associating metformin use with breast cancer occurrence., Results: Ninety-six cases (24%) and 1,154 controls (29%) used metformin for at least 1-year duration. Cases were slightly older on average than controls, but they were similar in distribution for parity, use of hormone replacement therapy, and history of diabetes complications. Metformin users were less likely with a diagnosis of breast cancer (OR = 0.77; 95% CI = 0.61-0.99) than nonmetformin users. Adjustment for diabetes complications, clinically diagnosed obesity, and important predictors of breast cancer did not substantially alter the association (OR = 0.81; 95% CI = 0.63-0.96)., Conclusion: Our results suggest that metformin may protect against breast cancer in type 2 diabetic peri- or postmenopausal women., Impact: This study supports the growing evidence of a role for metformin in breast cancer chemoprevention., (©2011 AACR.)

Maternal diet and nutrition have been thought to play a role in many childhood conditions. Studies using food frequency questionnaires (FFQ) have reported associations with maternal diet, but these findings are difficult to interpret because the reliability and validity of the FFQs for diet during a past pregnancy are not known. We determined the reproducibility of reported diet and supplement use during a past pregnancy in a subset of mothers interviewed for a case-control study of maternal diet in relation to the risk of childhood brain tumours. Cases were Children's Oncology Group patients, diagnosed at age <6 with medulloblastoma or primitive neuroectodermal tumour from 1991 to 1997. Area code, race/ethnicity, and birth date matched controls were selected by random-digit-dialling. Case and control mothers completed a modified Willett FFQ a mean of 5 years after the index child's birth. A mean of 3.6 months later, a subset of mothers consisting of 52 case and 51 control mothers repeated the interview; these comprise the reproducibility study population. The mean intra-class correlation was 0.59 (range 0.41, 0.69) for energy-adjusted nutrients from dietary sources only; it was 0.41 (range 0.06, 0.70) when supplements were included. Agreement for reporting multivitamin use during pregnancy by time period and pattern was good to very good (kappa = 0.66-0.85). Overall, the reproducibility of nutrient estimates and supplement use in pregnancy was good and similar to that reported for adult diet.

Objective: To evaluate the effectiveness of methods that control for confounding by indication, we compared breast cancer recurrence rates among women receiving adjuvant chemotherapy with those who did not., Study Design and Setting: In a medical record review-based study of breast cancer treatment in older women (n=1798) diagnosed between 1990 and 1994, our crude analysis suggested that adjuvant chemotherapy was positively associated with recurrence (hazard ratio [HR]=2.6; 95% confidence interval [CI]=1.9, 3.5). We expected a protective effect, so postulated that the crude association was confounded by indications for chemotherapy. We attempted to adjust for this confounding by restriction, multivariable regression, propensity scores (PSs), and instrumental variable (IV) methods., Results: After restricting to women at high risk for recurrence (n=946), chemotherapy was not associated with recurrence (HR=1.1; 95% CI=0.7, 1.6) using multivariable regression. PS adjustment yielded similar results (HR=1.3; 95% CI=0.8, 2.0). The IV-like method yielded a protective estimate (HR=0.9; 95% CI=0.2, 4.3); however, imbalances of measured factors across levels of the IV suggested residual confounding., Conclusion: Conventional methods do not control for unmeasured factors, which often remain important when addressing confounding by indication. PS and IV analysis methods can be useful under specific situations, but neither method adequately controlled confounding by indication in this study.

Little is known about the risk of recurrence >5 years after diagnosis among older breast cancer survivors. A community-based population of women >or=65 years diagnosed with early-stage breast cancer who survived disease free for 5 years was followed for 5 additional years or until a diagnosis of breast cancer recurrence, second primary, death, or loss to follow-up. These 5-year disease-free survivors (N = 1,277) had primary breast cancers that were node negative (77%) and estrogen receptor positive or unknown (86%). Five percent (n = 61) developed a recurrence between 5 and 10 years after diagnosis: 25% local, 9.8% regional, and 66% distant. Women who were node positive [hazard ratio (HR), 3.9; 95% confidence interval (95% CI), 1.5-10], had poorly differentiated tumors (HR, 2.5; 95% CI, 0.9-6.6), or who received breast conserving surgery without radiation therapy (HR, 2.4; 95% CI, 1.0-5.8) had higher recurrence rates compared with node negative, well differentiated, and receipt of mastectomy, respectively. Not receiving adjuvant tamoxifen, compared with receiving adjuvant tamoxifen, was also positively associated with late recurrence among women with estrogen receptor-positive/unknown tumors. Although relatively few women experience a late recurrence, most recurrences present as advanced disease, which is difficult to treat in older women. This study of late recurrence emphasizes that the risk, although small, is not negligible even in this group at high risk of death due to competing causes.

Background: Comorbidity indices summarize complex medical histories into concise ordinal scales, facilitating stratification and regression in epidemiologic analyses. Low subject prevalence in the highest strata of a comorbidity index often prompts combination of upper categories into a single stratum ('collapsing')., Objective: We use data from a breast cancer cohort to illustrate potential inferential errors resulting from collapsing a comorbidity index., Methods: Starting from a full index (0, 1, 2, 3, and ≥4 comorbidities), we sequentially collapsed upper categories to yield three collapsed categorizations. The full and collapsed categorizations were applied to analyses of (1) the association between comorbidity and all-cause mortality, wherein comorbidity was the exposure; (2) the association between older age and all-cause mortality, wherein comorbidity was a candidate confounder or effect modifier., Results: COLLAPSING THE INDEX ATTENUATED THE ASSOCIATION BETWEEN COMORBIDITY AND MORTALITY (RISK RATIO, FULL VERSUS DICHOTOMIZED CATEGORIZATION: 4.6 vs 2.1), reduced the apparent magnitude of confounding by comorbidity of the age/mortality association (relative risk due to confounding, full versus dichotomized categorization: 1.14 vs 1.09), and obscured modification of the association between age and mortality on both the absolute and relative scales., Conclusions: Collapsing categories of a comorbidity index can alter inferences concerning comorbidity as an exposure, confounder and effect modifier.

Background: Limb reduction deficiencies that are accompanied by amniotic bands (AB-Ls) and terminal transverse limb deficiencies (TLDs) have each been attributed to vascular disruption; for the former, however, it is not clear if amniotic bands are the primary cause of or are secondary to vascular disruption. If amniotic bands are secondary to vascular disruption, then a shared pathogenesis for each case group might be exhibited by similar risk factors., Methods: We evaluated maternal age, education, race/ethnicity, parity, pregnancy wantedness, and vasoactive exposures among 139 AB-L and 373 TLD cases, using interview data collected from mothers in 10 states by the National Birth Defects Prevention Study. Vasoactive exposures included maternal cigarette smoking and use of decongestants, nonsteroid anti-inflammatory drugs, and antihypertensive drugs in the periconceptional period., Results: Increased risk estimates were observed for Black mothers (OR 2.5; 95% CI: 1.5-4.1) and nulliparous mothers (2.1; 1.4-3.0) in relation to AB-L, while neither was associated with TLD. Hispanic women (1.4; 1.0-1.9) and those not wanting the pregnancy (1.5; 1.1-2.1) had increased risks of TLD, but not AB-L. Maternal cigarette smoking and aspirin use each increased the risk of AB-L, but not TLD; while decongestants and possibly antihypertensive medications increased the risk of TLD, but not AB-L., Conclusions: The lack of consistent findings for the two case groups suggests that AB-L and TLD may be distinct entities. The inconsistencies also suggest that these vasoactive exposures may not be markers for vascular disruption or that vascular disruption may not play a major role in the pathogenesis of these two types of limb deficiencies.