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From the Oregon Evidence-based Practice Center, Oregon Health & Science University, and Providence Cancer Center, Portland, Oregon; Group Health Research Institute, Seattle, Washington; San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California; Erasmus Medical Center, Rotterdam, the Netherlands; Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin; and Lombardi Comprehensive Cancer Center, Washington, DC.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.
Note: Each cancer registry and the Statistical Coordinating Center have received institutional review board approval for either active or passive consenting processes or a waiver of consent to enroll participants, link data, and perform analytic studies. All procedures are compliant with the Health Insurance Portability and Accountability Act, and all registries and the Statistical Coordinating Center have received a federal Certificate of Confidentiality and other protection for the identities of women, physicians, and facilities participating in this research. A list of the BCSC investigators and procedures for requesting BCSC data for research purposes is provided at http://breastscreening.cancer.gov/.
Acknowledgment: The authors thank the participating women, mammography facilities, and radiologists for the data they have provided for this study. Rose Relevo, MLIS, MS, and Robin Paynter, MA-LIS, conducted literature searches, and Katie Reitel, BA, provided assistance; all are affiliated with Oregon Health & Science University.
Grant Support: By a National Cancer Institute Activities to Promote Research Collaboration supplement (U01CA086076-10S1). Data collection was supported by the National Cancer Institute–funded BCSC cooperative agreements (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, and U01CA70040). Providence Health & Services provided additional support for Dr. Nelson, and the Veterans Affairs Fellowship in Health Issues of Women Veterans provided support for Dr. Cantor. The collection of BCSC cancer data used in this study was supported in part by several state public health departments and cancer registries throughout the United States. For a full description of these sources, please see www.breastscreening.cancer.gov/work/acknowledgement.html.
Potential Conflicts of Interest: Dr. Nelson: Grant (money to institution): NCI; Support for travel to meetings for the study or other purposes (money to institution): NCI. Dr Fu: Grant (money to institution): AHRQ. Ms. Griffin: Grant (money to institution): NCI. Dr. O'Meara: Grant (money to institution): NCI; Employment: Group Health Research Institute. Dr. Buist: Grant (money to institution): NCI. Ms. van Ravesteyn: Grant (money to institution): NCI. Dr. Trentham-Dietz: Grant (money to institution): NCI; Support for travel to meetings for the study or other purposes: NCI. Dr. Mandelblatt: Grant (money to institution): NCI; Support for travel to meetings for the study or other purposes (money to institution): NCI. Dr. Miglioretti: Grant (money to institution): NIH. Disclosures can be also viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-2350.
Requests for Single Reprints: Heidi D. Nelson, MD, MPH, Oregon Evidence-based Practice Center, Oregon Health & Science University, Mail Code BICC, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098; e-mail, mailto:firstname.lastname@example.com.
Current Author Addresses: Drs. Nelson, Zakher, Cantor, and Fu and Ms. Griffin: 3181 SW Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239.
Drs. O'Meara, Buist, and Miglioretti: 1730 Minor Avenue, Suite 1600, Seattle, WA 98101.
Dr. Kerlikowske: 4150 Clement Street, San Francisco, CA 94121.
Ms. van Ravesteyn: PO Box 2040, Rotterdam 3000, the Netherlands.
Dr. Trentham-Dietz: 307 WARF Building, 610 Walnut Street, Madison, WI 53726.
Dr. Mandelblatt: Suite 4100, 3300 Whitehaven Street NW, Washington, DC 20007.
Author Contributions: Conception and design: H.D. Nelson, D.S.M. Buist, K. Kerlikowske, N. van Ravesteyn, A. Trentham-Dietz, J. Mandelblatt, D. Miglioretti.
Analysis and interpretation of the data: H.D. Nelson, B. Zakher, A. Cantor, R. Fu, J. Griffin, E.S. O'Meara, D.S.M. Buist, K. Kerlikowske, A. Trentham-Dietz, J. Mandelblatt.
Drafting of the article: H.D. Nelson, B. Zakher, A. Cantor, R. Fu, J. Griffin, E.S. O'Meara, K. Kerlikowske, J. Mandelblatt.
Critical revision of the article for important intellectual content: H.D. Nelson, B. Zakher, A. Cantor, R. Fu, D.S.M. Buist, K. Kerlikowske, N. van Ravesteyn, A. Trentham-Dietz, J. Mandelblatt, D. Miglioretti.
Final approval of the article: H.D. Nelson, B. Zakher, R. Fu, J. Griffin, E.S. O'Meara, D.S.M. Buist, K. Kerlikowske, N. van Ravesteyn, J. Mandelblatt, D. Miglioretti.
Provision of study materials or patients: H.D. Nelson, D.S.M. Buist, K. Kerlikowske.
Statistical expertise: H.D. Nelson, R. Fu, K. Kerlikowske, D. Miglioretti.
Obtaining of funding: H.D. Nelson, D.S.M. Buist, K. Kerlikowske, J. Mandelblatt, D. Miglioretti.
Administrative, technical, or logistic support: H.D. Nelson, J. Griffin, D.S.M. Buist.
Collection and assembly of data: H.D. Nelson, B. Zakher, A. Cantor, R. Fu, J. Griffin, D.S.M. Buist, K. Kerlikowske, D. Miglioretti.
Background: Identifying risk factors for breast cancer specific to women in their 40s could inform screening decisions.
Purpose: To determine what factors increase risk for breast cancer in women aged 40 to 49 years and the magnitude of risk for each factor.
Data Sources: MEDLINE (January 1996 to the second week of November 2011), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (fourth quarter of 2011), Scopus, reference lists of published studies, and the Breast Cancer Surveillance Consortium.
Study Selection: English-language studies and systematic reviews of risk factors for breast cancer in women aged 40 to 49 years. Additional inclusion criteria were applied for each risk factor.
Data Extraction: Data on participants, study design, analysis, follow-up, and outcomes were abstracted. Study quality was rated by using established criteria, and only studies rated as good or fair were included. Results were summarized by using meta-analysis when sufficient studies were available or from the best evidence based on study quality, size, and applicability when meta-analysis was not possible. Data from the Breast Cancer Surveillance Consortium were analyzed with proportional hazards models by using partly conditional Cox regression. Reference groups for comparisons were set at U.S. population means.
Data Synthesis: Sixty-six studies provided data for estimates. Extremely dense breasts on mammography or first-degree relatives with breast cancer were associated with at least a 2-fold increase in risk for breast cancer. Prior breast biopsy, second-degree relatives with breast cancer, or heterogeneously dense breasts were associated with a 1.5- to 2.0-fold increased risk; current use of oral contraceptives, nulliparity, and age 30 years or older at first birth were associated with a 1.0- to 1.5-fold increased risk.
Limitations: Studies varied by measures, reference groups, and adjustment for confounders, which could bias combined estimates. Effects of multiple risk factors were not considered.
Conclusion: Extremely dense breasts and first-degree relatives with breast cancer were each associated with at least a 2-fold increase in risk for breast cancer in women aged 40 to 49 years. Identification of these risk factors may be useful for personalized mammography screening.
Primary Funding Source: National Cancer Institute.
Knowing which factors influence breast cancer risk for women younger than 50 years might help target screening efforts.
This review found that the following factors increased risk for breast cancer in women aged 40 to 49 years: extremely dense breasts or first-degree relatives with breast cancer (≥2-fold increase); prior breast biopsy, second-degree relatives with cancer, or heterogeneously dense breasts (1.5- to 2.0-fold increase); current oral contraceptive use, nulliparity, and age 30 years or older at first birth (1.0- to 1.5-fold increase).
Confounding may have affected some risk estimates.
Risk factor information could help personalize decisions about breast cancer screening in women aged 40 to 49 years.
—The Editors
Current practice guidelines on mammography screening differ in their recommendations for women in their 40s (1–3). The U.S. Preventive Services Task Force recommends individualized, informed decision making about when to start mammography screening based on a woman's values about benefits and harms (4). Risk-based screening has been recommended for other health conditions in the United States and may provide a similar evidence-based approach for breast cancer. However, applying this approach to clinical practice has been problematic because it is unclear how women and clinicians can effectively consider individualized risk factor information in their discussions of benefits and harms.
Microsimulation models of mammography screening developed as part of the Cancer Intervention and Surveillance Modeling Network (CISNET) indicated that women with approximately 2-fold increased risk for breast cancer who started biennial screening at age 40 years had similar benefits (life-years gained) and harms (false-positive results) as average-risk women who started screening at age 50 years (5). The risk threshold was higher when the CISNET models considered reduction in breast cancer deaths as a benefit (risk ratio [RR], 3.3) or annual rather than biennial screening (RR, 4.3). These results suggest that identifying women with at least a 2-fold increased risk for breast cancer could be useful in determining whether to initiate mammography screening before age 50 years.
Much research has been published describing personal and clinical risk factors associated with breast cancer. However, studies generally included women of various ages, measured and reported risk factors in different ways, and provided wide ranges of risk estimates. Consequently, results of broad-based epidemiologic studies may not be clinically applicable to the screening decisions of individual women and in some cases may be misleading.
The purpose of this systematic review and meta-analysis is to determine what factors increase risk for invasive breast cancer, specifically for women aged 40 to 49 years, and to estimate the magnitude of risk for each factor compared with average-risk women. It focuses on women who are eligible for screening mammography under current practice guidelines in the United States and considers average-risk women to be those without the risk factor or who represent the mean or majority of women in the cohort, depending on the risk factor. This project was conducted in collaboration with development of the CISNET models of mammography screening based on increasing levels of risk and builds on previous work (6–7).
A standard protocol was developed and followed for this review. In conjunction with a research librarian, we used the National Library of Medicine's Medical Subject Headings keyword nomenclature to search MEDLINE (1996 to the second week of November 2011), the Cochrane Central Register of Controlled Trials (fourth quarter of 2011), and the Cochrane Database of Systematic Reviews (fourth quarter of 2011) for relevant English-language studies and systematic reviews. We also conducted secondary referencing by manually reviewing reference lists of papers and by using Scopus to search citations of key studies. Searches included studies published during the past 16 years to provide data that are relevant to current cohorts of women considering mammography screening and to correspond to the time frame of risk factor data collected by the Breast Cancer Surveillance Consortium (BCSC) that were also used in this study.
We developed inclusion and exclusion criteria for abstracts and articles based on the target population, risk factors, and outcome measures. We included randomized, controlled trials; observational studies; systematic reviews; and meta-analyses. After an initial review of abstracts, we retrieved full-text articles and conducted a second review by using additional inclusion criteria defined specifically for each risk factor, including eligibility of the data for statistical meta-analysis. When sufficient studies were not available for a meta-analysis, we used the best evidence as determined by consensus among the investigators on the basis of study quality, size, and applicability.
The target population consisted of women aged 40 to 49 years who were eligible for screening mammography. Studies were excluded if they enrolled women who were not candidates for routine screening because they had prior breast or ovarian cancer, ductal carcinoma in situ or other noninvasive breast cancer, current breast physical findings, presence of deleterious BRCA1/BRCA2 mutations in self or relatives, or prior chest radiation for such conditions as lymphoma. Included studies were conducted in countries with patient populations and health care services similar to those of the United States to ensure applicability. Studies that reported outcomes in age groups that differed from the 40- to 49-year age category were included if most participants were aged 40 to 49 years and all were younger than 55 years. When studies reported outcomes by menopausal status rather than age, we used results for premenopausal women as long as the group included a majority of women in their 40s.
The main outcome measure was incidence of invasive breast cancer at age 40 to 49 years or invasive and noninvasive breast cancer as a combined outcome when this was the only measure reported in a study.
Risk factors included race and ethnicity, body mass index (BMI), physical activity, alcohol use, smoking, family history of breast cancer, breast density, prior breast procedures, and reproductive factors (age at menarche; parity; age at birth of first child; breastfeeding; oral contraceptive use; menopausal age, status, and type; and menopausal hormone therapy). We included studies meeting the following criteria: studies of risk factors for recent or current status that reflected exposure within 1 year of breast cancer diagnosis; studies of physical activity that reported categories of exercise descriptively (inactive, some, or regular) or quantified by metabolic equivalents; studies of alcohol use and smoking that reported use status (current, former, or never), recency, and amounts of use (drinks per week or packs per day); and studies of oral contraceptive and menopausal hormone therapy use that investigated any formulation (combination, progestin, or estrogen only) and used various definitions of ever and never use. We excluded studies of nonoral forms of contraception and those evaluating formulations not applicable to the target population (8).
We included studies that defined parity as the number of full-term births, full-term pregnancies, live births, or pregnancies lasting 6 months or more regardless of outcome, consistent with standard medical definitions (9). We included studies of breastfeeding that used a nonbreastfeeding group of parous women as the reference category and determined breastfeeding activity (ever or never) and total duration.
We included studies that reported menopausal status and history of hysterectomy or oophorectomy if the event preceded the breast cancer diagnosis in women in their 40s. We reviewed studies of mammographic breast density that used several methods to categorize density, but we reported results only from studies that used the Breast Imaging Reporting and Data System (BI-RADS) classification (1 = almost entirely fat, 2 = scattered fibroglandular densities, 3 = heterogeneously dense, and 4 = extremely dense) because of its clinical relevance to practice in the United States (10).
For the included studies, an investigator abstracted the following data: study design, setting, participant characteristics (including age, race and ethnicity, and diagnosis), enrollment criteria, exposures (dose and duration), procedures for data collection, number enrolled and number lost to follow-up, methods of exposure and outcome ascertainment, analytic methods (including adjustment for confounders), and results for each outcome. A second investigator confirmed the accuracy of key data.
We used predefined criteria developed by the U.S. Preventive Services Task Force to assess the quality of studies (11). Two investigators independently rated the quality of each eligible study (good, fair, or poor), and final ratings were determined by consensus among raters. We used only studies rated as good or fair to determine risk estimates.
We assessed applicability of studies by using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) approach (12). In addition, applicability of case–control studies was based on the control group population. For all studies, applicability was high if participants were recruited predominantly from community populations rather than clinical populations. For each risk factor, we also determined the consistency of results (that is, the degree of similarity in the effect sizes of the different studies). Studies were considered consistent if outcomes were generally in the same direction of effect and ranges of effect sizes were narrow. Applicability and consistency were determined by consensus of the investigators who reviewed the studies and conducted the meta-analyses.
For eligible studies, we combined data in several meta-analyses to obtain more precise estimates of the relationship between risk factors and breast cancer. All included studies had cohort or case–control designs, and only studies reporting estimates that adjusted for at least 1 potential confounder in their analysis were included in the meta-analysis. To determine the appropriateness of meta-analysis, we considered clinical and methodological diversity and assessed statistical heterogeneity.
We abstracted or calculated estimates of RRs (odds ratio, rate ratio, or hazard ratio) and their SEs from each study and used them as the effect measures. Because the incidence of breast cancer was low, we considered the estimates of odds ratios to be equivalent to estimates of relative risks (rate ratio or hazard ratio). This assumed that the underlying event rates in the case–control studies, for example, reflected the low incidence rate in the population.
For most risk factors, studies reported RRs based on similar cut points across included studies and we used estimates based on the reported cut points. For BMI, the cut points were too disparate to be combined as reported in the published studies. Therefore, we combined BMI categories to correspond to the World Health Organization definitions of underweight (<18.5 kg/m2), normal weight (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2), and obese (≥30 kg/m2) (13). We combined the underweight and normal weight categories because too few women were included in the underweight group. When studies categorized BMI by using other cut points, we calculated RRs by assuming that BMI is log-normally distributed and that a linear association exists between breast cancer risk and BMI on the logit scale. We estimated distribution parameters of BMI from published information in each study.
We assessed the presence of statistical heterogeneity among the studies by using standard chi-square tests and the magnitude of heterogeneity by using the I2 statistic (14). We used a random-effects model to account for variation among studies. In general, when there is no variation among studies, the random-effects model yields the same results as a fixed-effects model without a study effect (15). To explore heterogeneity, we used meta-regression to assess the effect of the degree of adjustment for confounders in the original studies. This was quantified by the total number of adjusted variables and the number of adjusted risk factors considered in the review as well as other study-level variables, such as quality, study design, and breast cancer type. We also conducted sensitivity analyses to assess the robustness of results that considered variation from different definitions of risk factors and reference groups, inclusion of noninvasive breast cancer as an outcome, and outlying studies. The results of the sensitivity analyses indicated no major differences from the main analysis.
For specific risk factors (BMI, age at menarche, and age at birth of first child), we recalculated RRs from the meta-analysis by using reference groups that differed from the original studies to approximate average risk in the population. The new reference groups were chosen to align with the distribution or mean of risk factors in the target population to provide more clinically relevant risk estimates. Data describing distributions or means in the target population were obtained from various sources representing U.S. national samples (16–22) (Appendix Table).
Population Distribution of Risk Factors for Women Aged 40 to 49 Years
We included data from the BCSC to supplement the systematic review because some risk factors were not reported in published studies. The BCSC is a national collaboration of 5 mammography registries and 2 affiliate sites in the United States that prospectively collects data on breast imaging, risk factors, and breast cancer outcomes (23). We analyzed BCSC data collected from 1994 to 2010 for women aged 40 to 49 years at the time of screening mammography. Risk factor data were obtained at the time of each screening mammography and reported in categories similar to those defined by the systematic review. Results for 380 585 women aged 40 to 49 years were provided in proportional hazards models adjusted for age, race, family history of breast cancer, and BMI and stratified by site. We used partly conditional Cox regression (24) to incorporate multiple observations per woman (allowing her to enter the analysis at each eligible screening mammography) and accounted for multiple observations per woman by using the robust sandwich estimator of the SE (25). Women were followed until they were diagnosed with invasive breast cancer; until they were censored at the first occurrence of ductal carcinoma in situ, death, age 50 years, or end of complete cancer follow-up or eligibility for her site; or for 5 years after the examination date. Mean length of follow-up was 3.3 years.
All analyses for the meta-analysis and BCSC data were performed by using Stata, version 11.0 (StataCorp, College Station, Texas), and were reported as RRs with 95% CIs.
The National Cancer Institute funded this work but had no additional role in the design, conduct, or reporting of the review and analysis.
A total of 9036 abstracts were identified by search criteria; of these, 884 full-text articles were reviewed and 95 met the inclusion criteria as well as the criteria for good or fair quality (Figure). Sixty-one studies of 8 risk factors (BMI, alcohol use, smoking, age at menarche, parity, age at first birth, breastfeeding, and oral contraceptive use) provided data for meta-analysis. Two published meta-analyses of family history of breast cancer reported results specifically for women in their 40s (26–27). Single studies provided estimates for 3 risk factors because either they were the only studies that met the inclusion and quality criteria for the risk factor (prior breast procedure) or studies did not provide data that could be used in a meta-analysis (breast density and physical activity). Individual studies providing data for risk estimates are described in the Supplement . Data from the BCSC provided the only estimates for 3 risk factors that had no published studies that met the inclusion criteria (race and ethnicity, menopausal status and type, and menopausal hormone therapy). No data were available to evaluate age at menopause.
Summary of evidence search and selection.
BMI = body mass index; OC = oral contraceptive.
* Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews.
† Reference lists, Scopus, and studies suggested by experts.
‡ Some articles are included for more than 1 risk factor.
§ Published meta-analyses.
∥ No articles met inclusion criteria for race and ethnicity, menopausal stage and type (surgical or nonsurgical), age at menopause, and menopausal hormone use.
¶ Although some studies met inclusion criteria for the systematic review, they did not provide data for the meta-analysis because they used dissimilar categories or different measures from the other included studies.
Personal risk factors included race and ethnicity, BMI, physical activity, alcohol use, and smoking (Table 1). Data from the BCSC indicated no statistically significant increased risks for breast cancer by race and ethnicity when white race was used as the reference group.
Breast Cancer Risk Associated With Personal Factors for Women Aged 40 to 49 Years
For BMI, a meta-analysis of 18 studies (17, 28–44) indicated reduced risks for women in the overweight (RR, 0.86 [95% CI, 0.82 to 0.90]) and obese (RR, 0.74 [CI, 0.68 to 0.81]) categories compared with women in the normal and underweight category. Results were similar for overweight and obese categories in the BCSC, but the CI included 1.0 for overweight. Data specifically for underweight women were not provided by the published studies, although the BCSC data indicated that risk for underweight women was not significantly different from that of normal weight women.
Ten studies of physical activity met inclusion criteria (45–54) but could not be combined in the meta-analysis because they used different measures of activity and reported results in dissimilar categories. All studies reported no statistically significant differences in breast cancer risk based on physical activity. Results from a large, good-quality study designed to specifically assess the relationship between physical activity and premenopausal breast cancer provided the estimates in Table 1(46). Data on physical activity were not available from the BCSC.
Although 12 studies reporting various measures of alcohol use met inclusion criteria (31, 36, 55–64), results from only 3 studies could be combined in the meta-analysis (55, 61, 64). Using no alcohol use as the reference group, results indicated higher risk estimates with increasing amounts of alcohol consumption; however, all CIs included 1.0. Smoking use (never vs. ever) and status (never vs. current or former) had no significant associations with breast cancer based on meta-analyses of 12 studies of never versus ever use (31, 62, 65–74) and 7 studies of never versus current or former use (31, 62, 67, 70–73). No BCSC data on alcohol use or smoking were available.
In an analysis of data from 52 epidemiologic studies (26), breast cancer risk was significantly increased for women with first-degree relatives with breast cancer (RR for 1 relative, 2.14 [CI, 1.92 to 2.38]; 2 relatives, 3.84 [CI, 2.37 to 6.22]; and ≥3 relatives, 12.05 [CI, 1.70 to 85.16]) (Table 2). Data from the BCSC also showed higher risk for women with a first-degree relative with breast cancer (RR, 1.86 [CI, 1.69 to 2.06]). In both the meta-analysis and the BCSC results, risk was higher among women with first-degree relatives who were diagnosed at younger ages than those diagnosed at older ages. Risk ratios for women with relatives younger than 40 years compared with women with no first-degree relatives were 3.0 (CI, 1.8 to 4.9) in the meta-analysis (26) and 2.17 (CI, 1.86 to 2.53) for women with relatives younger than 50 years in the BCSC. Risk was lower for women with relatives diagnosed at age 60 years or older (RR, 1.7 [CI, 1.3 to 2.1]) (26). In a meta-analysis of 2 studies (27), risk was also significantly increased for women with 1 or more second-degree relatives compared with none (RR, 1.7 [CI, 1.4 to 2.0]).
Breast Cancer Risk Associated With Family History, Breast Density, and Breast Procedures for Women Aged 40 to 49 Years
A published study of BCSC data reported risk estimates for breast cancer by using BI-RADS breast density categories and defined BI-RADS category 2 (scattered fibroglandular densities) as the reference group (75). Results indicated increased risk for categories 3 (RR, 1.62 [CI, 1.51 to 1.75]) and 4 (RR, 2.04 [CI, 1.84 to 2.26]) and reduced risk for category 1 (RR, 0.46 [CI, 0.37 to 0.58]).
A published study of BCSC data reported increased breast cancer risk for women who had prior benign results on breast biopsy (RR, 1.87 [CI, 1.64 to 2.13]) (76). Additional BCSC data that included prior biopsies or fine-needle aspirations also indicated increased risk (RR, 1.51 [CI, 1.36 to 1.67]).
Reproductive factors included age at menarche, parity, age at first birth, breastfeeding, oral contraceptive use, menopausal status, and menopausal hormone therapy (Table 3). In our meta-analysis of 13 studies (31, 34, 45, 77–86), menarche at age 15 years or older was associated with reduced risk for breast cancer compared with the reference age of 13 years (RR, 0.87 [CI, 0.78 to 0.97]). Results from the BCSC were similar.
Breast Cancer Risk Associated With Reproductive Factors for Women Aged 40 to 49 Years
A meta-analysis of 17 studies of parity (31, 34, 45, 74, 77–80, 82–90) indicated that nulliparous women had a significantly higher risk for breast cancer than parous women (RR, 1.16 [CI, 1.04 to 1.26]), similar to BCSC estimates (Table 3). In a meta-analysis of 13 studies (31, 34, 74, 77–80, 82, 84–87, 90), risk was significantly reduced for women with 3 or more births compared with nulliparous women (RR, 0.73 [CI, 0.61 to 0.87]). In a meta-analysis of 5 studies of age at first birth (34, 45, 77, 83, 88), women having their first child at age 30 years or older had a higher risk for breast cancer than a reference group of women aged 25 to 29 years (RR, 1.20 [CI, 1.02 to 1.42]) but a slightly lower risk than nulliparous women (RR, 1.25 [CI, 1.08 to 1.46]). Results from the BCSC indicated no significantly increased risk for these groups but did indicate decreased risk for women aged 20 years or younger at the time of the first birth.
In a meta-analysis of 14 studies (34, 74, 78, 80, 82–83, 86, 90–96), breastfeeding was associated with reduced risk for breast cancer (RR, 0.87 [CI, 0.77 to 0.98]), particularly when it continued for 12 months or longer (RR, 0.85 [CI, 0.73 to 0.99]) (34, 78, 80, 82–83, 91–96). Breastfeeding data were not available from the BCSC.
Twelve studies of oral contraceptive use provided estimates for the meta-analysis of ever use compared with never use (31, 74, 77–78, 97–104), and 8 studies provided estimates for recency of use, with the most recent category defined as within 5 years (77–78, 99–104). None of these associations was statistically significant, although all point estimates were increased (Table 3). Data from the BCSC indicated significantly higher risk for breast cancer for current oral contraceptive use than for former or never use (RR, 1.30 [CI, 1.13 to 1.49]).
Data from the BCSC showed reduced breast cancer risk for perimenopausal and postmenopausal women (either surgical or nonsurgical menopause) compared with premenopausal women. The BCSC data also indicated that women with no uterus currently using menopausal hormone therapy had a reduced risk for breast cancer compared with nonusers (RR, 0.70 [CI, 0.52 to 0.94]), whereas those with a uterus had no significant association. Presumably, women without a uterus were using estrogen alone, whereas those with a uterus were using estrogen combined with progestin.
Sixty-six studies identified in the systematic review contributed data for breast cancer risk estimates for 13 unique risk factors, whereas data from the BCSC provided estimates for 11 risk factors, 3 of which were not included in published studies. Both sources provided estimates for some risk factors that were expressed in alternate ways, such as in dichotomous as well as ordinal categories. A summary of evidence for the systematic review describes the number and design of included studies; breast cancer outcomes; and ratings for quality, consistency, and applicability for each risk factor (Table 4). Overall, studies were consistent and applicability was high, largely because conditions of the study population were incorporated into inclusion criteria.
Summary of Evidence for Studies Providing Data for Risk Estimates
Results indicated that women in their 40s with extremely dense breasts on mammography or at least 1 first-degree relative with breast cancer had at least a 2-fold increased risk for breast cancer (Table 5). This level of risk corresponds to the risk threshold of the CISNET models, which demonstrated similar benefits and harms for increased-risk women starting biennial screening at age 40 years and average-risk women starting at age 50 years (5). Risk was even higher among women with 2 or more first-degree relatives with breast cancer or first-degree relatives diagnosed before age 40 years.
Factors Significantly Associated With Increased Breast Cancer Risk for Women Aged 40 to 49 Years
The following 3 factors were associated with a 1.5- to 2.0-fold increased risk: a prior benign breast biopsy result, a second-degree relative with breast cancer, and heterogeneously dense breast tissue. Current use of oral contraceptives, nulliparity, and first birth at age 30 years or older were associated with a 1.0- to 1.5-fold increased risk, although some results differed by data sources, which suggests inconsistency. Several factors were associated with lower-than-average risk, including BMI of 25 kg/m2 or higher; low breast density; age 15 years or older at menarche; birth of 3 or more children; breastfeeding; perimenopausal or postmenopausal status; and use of menopausal, estrogen-only hormone therapy.
Although the results of this review are consistent with previous research, our estimates of risk are unique and relevant to current clinical dilemmas about mammography screening for women in their 40s. Although most women who develop breast cancer have no known risk factors, information about risk may be particularly useful when making decisions about screening. Of note, several risk factors identified in single studies or in studies of women of various ages were not statistically significant in our analysis. These findings may be useful to women, clinicians, and health systems considering risk-based screening who find a long list of potential risk factors difficult to navigate. Focusing on high breast density and first-degree family history of breast cancer may be a more clinically feasible approach to personalized screening.
Family history is an important, well-established risk factor for breast cancer, and its role in breast cancer screening and prevention extends beyond mammography. Current recommendations from the U.S. Preventive Services Task Force for women with family histories of breast cancer include genetic counseling and mutation testing if appropriate (105) and consideration of medications to reduce risk for primary breast cancer (106).
Several studies have reported associations between mammographic breast density and breast cancer (107–111), but only 1 met inclusion criteria for this review because it reported results with BI-RADS classifications that are used in U.S. clinical practice and provided risk estimates specific to the target population (75). The use of breast density in screening and prevention is currently unclear, although research suggests that it may be important for estimating risk (111–114) and for determining the age at which screening should begin and appropriate screening intervals (115). However, clinical trials of these strategies have not been done and use of breast density in current practice poses such challenges as variability of reporting among radiologists (116).
Our risk estimates were derived from epidemiologic data, and their application in predicting individual risk has not been evaluated. They may be particularly useful for developing more complex risk prediction models. Although several such models exist (for example, the Gail model), they were not developed specifically for women in their 40s, were not based on recent research, and have low discriminatory accuracy in predicting individual risk (117). Improving risk models and demonstrating their effectiveness in clinical applications are necessary future steps in this work.
Although our risk estimates may be useful in informing clinical practice, effective methods to modify risk factors to reduce breast cancer incidence are largely untested. Our results indicated reduced breast cancer risk for women with BMIs in the overweight and obese categories. However, an inverse association has been found in postmenopausal women (118). Given the higher incidence of breast cancer in postmenopausal women, an appropriate clinical recommendation would be to modify weight gain after menopause rather than at a younger age. Some risk factors may reflect underlying biological effects that cannot be modified for disease prevention purposes, such as parity. In contrast, breast density was reduced in high-risk women receiving tamoxifen in clinical trials (119). How to apply this information to individual patients is currently unclear.
This evidence review and meta-analysis is limited in several ways. Studies reported different measures, dissimilar categories for exposures and outcomes, and reference groups that did not represent average risk in the target population. Studies also varied in the degree of adjustment for confounders in their risk estimates. All of these variations could lead to potential bias in the combined estimates of RRs. In addition, some women outside the targeted age group were included because studies provided data in categories that did not align with ours. Publication bias and selective reporting are also potential limitations but are difficult to assess.
To address these issues, we developed inclusion criteria that considered the quality and applicability of studies consistently across risk factors, included only fair- or good-quality studies, selected best-evidence estimates for risk factors that lacked estimates from a meta-analysis, and redefined reference groups to approximate the mean or distribution of the target population. In addition, we analyzed primary BCSC data to supplement or support the meta-analysis results. To address concerns of heterogeneity, we performed several sensitivity analyses, including an analysis based on the degree of adjustment for confounders, and we found no important differences in results.
Data in the meta-analysis and the BCSC were derived from observational studies that were subject to inherent potential biases, such as unmeasured and uncontrolled confounders. Our analysis was limited to the effects of individual risk factors, and we did not assess the risk associated with multiple concurrent factors. Our inclusion criteria led to the selection of studies enrolling a specifically defined population, and results may not be applicable to different populations. Also, we focused on factors that increase risk for breast cancer in collaboration with the development of the CISNET models. Clinical application of our estimates of factors associated with reduced risk is limited because the CISNET models were not designed for similar reduced-risk scenarios.
This comprehensive systematic review and meta-analysis of risk factors for breast cancer in women aged 40 to 49 years, as well as a primary analysis of the same risk factors using BCSC data, indicated that having either extremely dense breast tissue on mammography or first-degree relatives with breast cancer is associated with at least a 2-fold increased risk for breast cancer. Identification of these risk factors may be useful for personalized mammography screening.
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Screening is more effective when the incidence of the target disease is high, that is, more deaths will be prevented while a lower proportion of positive screening tests will be false positives. The idea of optimizing screening effectiveness in women 40 to 49 years of age by targeting women with greater risk to develop a breast cancer is appealing. The review of breast risk factors among by Nelson and Colleagues (1) may provide guidance on how to provide personalized counseling to pre- menopausal women about the likely benefits and side-effects of mammography screening. The review found that breast radiological density, family history, reproductive history, use of oral contraceptives and prior benign breast biopsy were factors associated with higher breast cancer incidence in women aged 40-49 years. However, since the primary goal of breast screening being to decrease the risk to die from breast cancer, screening would be more effective for women at higher risk to die from this cancer, and not just a higher risk to be diagnosed with that cancer. The caveat that risk factors for breast cancer occurrence would have a similar influence on the risk of breast cancer death is not correct. Few studies have been done on risk factors associated with breast cancer death, but they show that reproductive factors have little influence on the risk to die from breast cancer (2). High breast density is associated with more aggressive cancer and this factor is thus relevant to both incidence and mortality (3). Adiposity is associated with reduced breast cancer risk in pre-menopausal women, and therefore, this factor was not selected by the review. However, the risk of breast cancer death in pre-menopausal women increases with adiposity (4) and obese women would probably benefit more from screening than lean women. Women giving birth in their forties become increasingly common, and breast cancers occurring in the two years following childbirth are known to be more lethal (5). So, these women should probably be offered screening shortly after discontinuation of breast feeding. The risk of breast cancer death associated with use of oral contraceptives and prior benign breast biopsy are not known. In conclusion, compared to risk factors for breast cancer occurrence, personalized screening counseling based on risk factors for breast cancer mortality may be more effective and identify different women likely to benefit from screening.
1. Nelson HD, Zakher B, Cantor A, Fu R, Griffin J, OMeara ES, et al. Risk factors for breast cancer for women aged 40 to 49 years. Ann Int Med. 2012; 156: 635-48.
2. Barnett GC, Shah M, Redman K, Easton DF, Ponder BAJ, Pharoah PDP Risk factors for the incidence of breast cancer: Do they affect survival from the disease? J Clin Oncol. 2008; 26:3310-6.
3. Chiu SY, Duffy S, Yen AF, Tab?r L, Smith RA, Chen H. Effect of baseline breast density on breast cancer incidence, stage, mortality, and screening parameters: 25-year follow-up of a swedish mammographic screening. Cancer Epidemiol Biomarkers Prev. 2010; 19; 1219-28.
4. Loi S, Milne RL, Friedlander ML, McCredie MRE, Giles GG, Hopper JL, Phillips K. Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev. 2005; 14:1686-91.
5. Daling JR, Malone KE, Doody DR, Anderson BO, Porter PL. The relation of reproductive factors to mortality from breast cancer. Cancer Epidemiol Biomarkers Prev. 2002;11: 235-41.
None declared
We agree with comments from Dr. Autier that identifying factors associated with increased risk of breast cancer mortality, not just breast cancer incidence, to guide breast cancer screening for women in their forties would be useful. However, it is also correct that few studies have reported these associations.
Our systematic review focused on the many published studies of risk factors for breast cancer incidence specifically for women in their forties who would be candidates for mammography screening under current U.S. guidelines (1). Our results indicated that extremely dense breasts on mammography and first-degree relatives with breast cancer were each associated with at least a 2-fold increase in risk; prior benign breast biopsy, second-degree relatives with breast cancer, and heterogeneously dense breasts with 1.5 to 2.0 fold increase; and current oral contraceptive use, nulliparity, and age at first birth 30 years and older with 1.0 to 1.5 increase. Several other risk factors were not statistically significantly associated with breast cancer incidence. Increased BMI was associated with reduced breast cancer risk, an inverse relationship that reverses for women above age 50. We did not emphasize risk factors related to reduced risk because this project was intended to identify risks above general population levels in collaboration with the development of population screening models that did not consider reduced-risk scenarios (2).
Although our risk estimates may help inform clinical decision making about screening, they were derived from epidemiologic data and their application in predicting risks for individual women has not been evaluated. Next steps in this work would be to improve risk models and demonstrate their effectiveness in clinical applications. Mortality estimates would also contribute to this effort.
Heidi D. Nelson, MD, MPH
Bernadette Zakher, MBBS
Amy Cantor, MD, MPH
Oregon Health & Science UniversityPortland, Oregon 97239
1. Nelson HD, Zakher B, Cantor A, Fu R, Griffin J, O'Meara ES, et al. Risk factors for breast cancer for women aged 40 to 49 years. Ann Intern Med. 2012; 156: 635-48.
2. van Ravesteyn NT, Miglioretti DL, Stout NK, Lee SJ, Schechter CB, Buist DSM, et al. What level of risk tips the balance of benefits and harms to favor screening mammography starting at age 40 years? Ann Intern Med. 2012;156:609-617.
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PROG21 Plus
User Stats
Profile Images
User Bio
Hello, I'm Paul.
Creative Director. Art Director. Designer. Filmmaker. Yup, that's me.
For the past 15 years, I've had a blast honing my craft, working on high-level brands and solving creative problems across many categories. But what I really pride myself on is excelling at multiple mediums. One dimensional? Me? Never. I love having my finger in all of the pies. Design, advertising, motion graphics, film – I do it all. Add in strategic thinking, and you have a good sense about what I bring to the table.
Like what you see? I'd love to talk. Give me a shout and I can tell you more about myself and my work.
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- prog21.com - To see all of my design work please visit me here.

subset: commoncrawl


text:
West Chester Area School District officials announced the cancellation of today's classes after negotiations between the district's 900-member teachers union and the school board failed to reach an agreement by 9 p.m. last night, a deadline set by the district to decide whether to hold school.
While discussions with a mediator were still going on late last night, a strike appeared likely.
"I'm expecting that . . . teachers will be picketing," said Jeffrey Sultanik, a negotiator for the school board. "The teachers have not withdrawn their strike notice."


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I'm in my last week or two of pregnancy and suddenly my appetite has completely changed - I want VERY little protein and a ton of carbs. If I have any cravings, it is for carbs (not bad carbs necessarily - fruit will satisfy it).
Anyone know why this would be? I've been primal since my 2nd trimester and have had a healthy appetite for protein/fat up until now (I'd say I was getting 70-80g protein per day but could be slightly more depending on how many eggs I ate). But at this point, honestly, I can only take a little bit of meat/egg at a time without feeling completely full, but could eat an entire bowl of fruit like it's going out of style. I also have huge cravings for green vegetables - saute an entire bag of spinach, a whole bunch of kale, etc... and I will devour it. I really think my body needs what's in those leafy greens right now more than ever. Fat intake has remained about the same and I don't have an aversion or craving either way with it.
Anyone have guesses as to why my body has shifted into "Fill me up with carbs!!!!!!!" overdrive all of a sudden? I'm guessing there is some energy shifting needed as my body prepares to give birth?
Thanks for any insight .


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A project of People For the American Way dedicated to monitoring and exposing the activities of the right-wing movement. Learn More >
The Great and Powerful ACORN
When President Barack Obama announced his nomination of David Hamilton to a seat on the United States 7th Circuit Court of Appeals yesterday, Wendy Long of the Judicial Confirmation Network was first out of the gate to blast the nomination because Hamilton reportedly had ties to the ACLU as well as the Right's favorite bogeyman, ACORN:
Hamilton has a history as a hard-left political activist, and his choice signals that Obama does intend to push extreme liberals onto the bench and politicize the courts as we've never seen before.
Hamilton was a fundraiser for ACORN (nice ACORN payback, Mr. President) and served as vice president for litigation and a board member of the Indiana ACLU.
Hamilton's purported ties to ACORN immediately worked its way into right-wing commentary on the nomination, being highlighted by Newbusters, Powerline, Curt Levey of the Committee for Justice, and the Family Research Council … twice, which complained that ACORN was getting it very own judge.
The idea that President Obama's nomination of Hamilton was "payback" to ACORN quickly became the right-wing talking point of the day, with people claiming that he was "a big shot at ACORN" and leading to posts like this one written by Matthew Vadum at "The American Spectator" entitled "ACORN's Federal Judge":
Giving the term judicial activism new meaning, President Obama has nominated an ACORN loyalist to the U.S. Court of Appeals for the Seventh Circuit, the Chicago Tribune reports … The Judicial Confirmation Network notes that Hamilton previously worked as a fundraiser for ACORN, the radical direct-action group that not only resurrects the dead and gets them to the polls every election but also shakes down banks and pressures them to make home loans to people who can't afford to pay them back.
In nearly every instance, Hamilton's ties to ACORN can be tracked back to Long and the Judicial Confirmation Network yet, oddly, when the group issued its own release on his nomination, it made no mention of his work with ACORN.
Wendy Long, counsel for the Judicial Confirmation Network, labeled Judge Hamilton a "hard-left political activist," noting his work with the Indiana ACLU and suggesting he had an affiliation with the community organizing group ACORN.
"After college as a young man, he served one month as a canvasser for ACORN, helping them raise money door to door.
Hamilton graduated from college in 1979.
I knew that ACORN was influential, but I had no idea it was so powerful that the President of the United States was obligated to pay it back by giving a federal judgeship to someone who worked for it for one whole month some thirty years ago.
Filed Under
Organizations:ACLU, Judicial Confirmation Network , Judicial Crisis Network, Family Research Council, American Spectator
People:Barack Obama, Wendy Long , David Hamilton
Topics:ACORN, Legal, Activism, seventh circuit, judicial activism, polls, choice
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We are a cell biology and bioengineering laboratory within the Department of Cardiac Surgery at Boston Children's Hospital. We are affiliated with the Harvard Medical School. We specialize in the biology and therapeutic potential of human Endothelial Progenitor Cells (EPCs) and Endothelial Colony-Forming Cells (ECFCs).
Stem cells and tissue engineering hold great promise in Regenerative Medicine. However, engrafting stem cells and generating tissues with stable functional vascular beds remain major challenges. Our laboratory is interested in understanding how vascular networks are formed and the mechanisms by which the vasculature modulates the activity of various human stem cells. Current projects in the lab are focused on:
Adventures in gene therapy: Getting your own blood vessels to make drugs
June 18, 2014. Juan Melero-Martin, VECTOR blog
Read more...
Human endothelial colony-forming cells serve as trophic mediators for mesenchymal stem cell engraftment via paracrine signaling
Lin RZ, Moreno-Luna R, Li D, Jaminet SCS, Greene AK, Melero-Martin JM
Proc Natl Acad Sci USA 2014; 111(28):10137-10142
Transdermal regulation of vascular network bioengineering using a photopolymerizable methacrylated gelatin hydrogel
Lin RZ, Chen YC, Moreno-Luna R, Khademhosseini A, Melero-Martin JM
Biomaterials 2013; 34(28):6785-96
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Lin RZ, Dreyzin A, Aamodt K, Li D, Jaminet SC, Dudley AC, Melero-Martin JM
Blood 2011; 118(20):5420-8
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HSCI/Children's researcher wins prestigious Bayer Hemophilia Award
May 19, 2014. Harvard Stem Cell Institute (HSCI)


text:
Free guide offers Pike Place Market holiday information
Learn about special foods and other holiday treats in the Pike Place Market Holiday Food Guide.
The free publication includes chocolate gateau, gingerbread muffins, five types of caviar, fresh Italian white truffles, and tips for holiday shopping.
An example of the guide's information: There is free 30-minute parking at the Public Market Parking garage on Western Avenue Monday through Friday. That's enough time to pick up a few gifts or ingredients, especially if you call ahead.
Phone numbers of markets and stands are provided in the guide. For a free copy, call 682-7453.


text:
Tuner. A tuner is a device found inside set top boxes, DVRs,
TVs anything designed to receive TV signals. A tuner is what
lets you watch a specific channel or video on demand show. It
picks a show or channel to display; and it tunes to it. Your
TiVo Mini does not have its own tuner inside. Instead, when you
want to watch TV or video on demand, your TiVo Mini
borrows a tuner from the host DVR. Your installer will set up
the host to share a tuner when he/she installs your TiVo Mini.


text:
Now in its third year, Fashion's Night Out — that annual retail party night, where stores in a multitude of global cities stay open late, offer discounts, and play host to DJs, celebs, and crowds — seems to have become a verifiable institution in New York. The latest evidence are the city's hotels, which have added packages and perks specifically meant to appeal to out-of-town FNO attendees.
Makes sense, given the fact that 20% of FNO event-goers last year came from somewhere other than New York. The packages various hotels have come up are geared toward a fashion-focused clientele. The city's four W Hotels are offering guests portraits of themselves by the fashion photographer Annemarieke van Drimmelen, while The InterContinental's deals includes sending a hairstylist to your room for a pre-event blowout. The Algonquin's FNO-oriented guest package offers breakfast (okay, that's standard enough) along with two cocktails at the hotel's bar (now sounds like a pre-game to us).
If we didn't already live in New York, we'd totally get in on one of these deals for the third Fashion's Night Out coming up on September 8th. We'd love to hear about any out-of-towners exploring one of the evening's many hotel options, though — and in the meantime, we'll just get involved with some of the other fun new attendant FNO activities that have cropped up.


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Interest Level
Grades K - 2
Reading Level
Grade level Equivalent: 1.4
Lexile® Measure: 290L
Guided Reading: H
- Informational
- Archaeology and Anthropology
- Paleontology and Fossils
About This Book
Bones. Bones. We look for bones.
We look for the bones of dinosaurs.
Six small paleontologists search for bones. When they find them, they dig them up, wrap them, and load them on a truck, bound for the museum. There, they carefully put together the bones of a giant dinosaur.
In bright, bold, exuberant pictures, with a text that is just right for reading or chanting aloud, Byron Barton looks at just what happens to the bones left behind by dinosaurs of long, long ago.
Items Added to Cart:
1 Paperback
2 Hardcover
1 Teacher's Edition
$48.99 Subtotal


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BM-Causeway Bay Cinema
19 Yee Wo Street, Lok Sing Centre,
Hong Kong
No one has favorited this theater yet
The Tokyo Cinema was a small cinema on the ground floor of the podium of the Lok Sing Centre in Causeway Bay on the Hong Kong Island. Lok Sing Centre was built on the site of the former Roxy Theatre and an adjacent hotel. Its 93-seat auditorium with a small lobby and a ticket booth was converted from a shop by the Yee Wo Street.
The Tokyo Cinema opened to business in 1993 and showed adult films until it was renamed as the BM-Causeway Bay Cinema under a new management in the late-1990's. The renamed cinema showed first run Chinese dialect films until it closed in early-2000. The former cinema has been converted back into a shop and selling Indonesian goods currently.
Recent comments (view all 2 comments)
The shop[Chandra] as shown in this photograph had closed.
The guy holding a camera is Raymond Lo/Suwanti. At that day,I accompanied Mr.Ken Roe to visit the remaining theatre buildings on the Hong Kong Island.
Just login to your account and subscribe to this theater


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Blessing of the animals
WOOLRICH - Woolrich Community United Methodist Church will hold a blessing of the animals at 9 a.m. in the Woolrich parking lot. Animals must be on a leash or in a carrying cage. Each owner will receive a certificate of Blessing, showing the animal's name. The event will be held rain or shine.
Concert scheduled
Jim and Wendy Allshouse will perform in concert at 7:30 p.m. at Lairdsville Faith Church, 6786 Route 118. Call Pastor Max L. Walters Jr. for more information at 584-2765.
Labor of Love
SHAMOKIN - Mother Cabrini Youth Center will hold its eighth annual picnic at the Ranshaw Civic Association grounds fro 3-10 p.m. Saturday and 1-9 p.m. Sunday. In addition to food, entertainment will be provided. The picnic replaces the center's food stand at the Bloomsburg Fair and is used as a fund-raiser to support the operation of the youth center building and its programs.
Single service set
WOOLRICH - Woolrich Community United Methodist Church will hold one service at 10:30 a.m. in Woolrich Park at pavilion 2. Communion will be served. Bring lawn chairs. Special music will be provided by the Woolrich Women's Chorus. A picnic will following the service with barbecue, rolls and beverage provided. Everyone bring their own table service and a dish to share.
Hymn sing
CALVERT - The Beech Valley United Methodist Church will hold a hymn sing at 6:30 p.m. In addition to congregational singing, there will be special music by the Beech Valley Choir and other groups. Refreshments will be served after the program.
Yankee Stadium trip
CANTON - The Church of Christ (Disciples of Christ) of Canton will sponsor a trip led by Bonnie L. Browning, minister, and David B. Morris, retired minister, to New York City on Sept. 1 for the New York Yankees vs. Baltimore Orioles Major League Baseball game at 1:05 p.m. Cost for the baseball game and transportation (round trip coach) and breakfast is $150.00 per person. The bus will be stopping at the following locations: Mansfield, Troy, Canton, Roaring Branch, Ralston, Williamsport and Danville. The deadline for reservations is Aug. 31. For more information, call 250-3057, 673-5796 or 673-3156.
CROP Rally scheduled
The CROP Rally, to distribute materials to individuals and organizations interested in participating in the 2012 Greater Lycoming County CROP Walk to combat hunger locally and globally, will be held from 4-6 p.m. Sept. 6 at New Covenant United Church of Christ, 202 E. Third St. Sponsor forms and many types of promotional materials will be available. The Walk itself will take place at 1 p.m. on Oct. 14, embarking from St. Mark's Lutheran Church, 142 Market St. This will be the second CROP Walk at the new location, the River Walk, and the first under the direction of the new chairperson, Rev. Kenneth E. Wagner-Pizza of Trinity Episcopal Church.
Proof of Your Love Tour
WATSONTOWN - The Proof of your Love Tour, featuring For King and Country, Jason Castro and Dare Maclean will be held at 7 p.m. at Revival Tabernacle, 960 Susquehanna Trail. Tickets are $20 gold, $15 advance $18 at the door and $14 for groups of 10 or more. For more information, call WGRC at 1-800-546-9472.


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Big Bad Booty Daddy
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Comments Thread For: Tyson Fury Eyes Klitschko Fight in May, June in Germany
TYSON FURY claims Wladimir Klitschko has agreed to fight him next year and the *British boxer has vowed to knock him out in Germany.
The Morecambe heavyweight must first get past American Kevin Johnson in Belfast on Saturday but says his team has already had talks with the Ukrainian world No.1.
Fury, 24, is chasing a scrap with Wladimir the WBA, WBO and IBF champion rather than his elder brother Vitali, the WBC king.
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Whoever he chooses to fight, he's screwed anyway. No hope for Fury in either fight IMO.
Gf you tried
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He has a decent shot, it will be wlads 2nd toughest fight after haye
Fury is sloppy but he has huge power and uses his height very well
Wlad should win it but with heavyweights you can win with 1 big punch
wlad will not be able to hold him much, so it will be interesting to see this fight
average joe
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is he ready for wladimir?
he's beaten some good journeymen like rogan, maddalone & firtha. he survived a scare vs the tough pajkic(although the fight was stopped way too early imo)& has a solid win vs chisora. he is talking klitschko & he hasn't even gotten past kevin johnson yet. kingpin is big, has a great jab & can box. he is like a big version of chris byrd. he was nowhere near ready to fight a klitschko when he did but fury is not at that level yet so this will be a tough fight for fury. kingpin is defensive & can take a punch. i rate chisora higher then kingpin due to level of opposition but a win over johnson is a great step forward but i still don't think he is ready. fury can take out all the C+ level fighters & a win over kingpin would add a 2nd B level fringe contender to his resume but i think he needs a win over a legit top contender like pulev, helenius, adamek, haye or arreola before i will actually consider him ready. povetkin, haye, helenius, pulev are the top contenders while arreola & adamek are just outside the door. i'm not sure fury beats any of them. until he does i won't lift him past B level fringe contender status.
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"Fury is sloppy but he has huge power and uses his height very well"??? - There´s one major error in that sentence..
Gf you tried
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why? because he knew haye was very dangerous and was a good boxer, he played it incredibly safe
as I said before, anyone can get lucky with one shot at heavyweight, what happened to wlad happened to lewis, a stupid mistake that guys like peter made wlad pay
in terms of quality, haye has been wlads toughest fighter, I know you hate him but think of it subjectively mate
fury is a good heavyweight, he will give wlad a test, I promise you that. He can win because he has huge power but most likely wlad will win a decision
Just want to add, wlad fought the perfect fight vs Haye, if he was not ultra defensive, he could have very well and in my opinion would have been knocked out. But he fought smart, used his advantages, hit and then got in a very safe position, if haye got in, he grabbed him.
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Wladimir will take him apart, unfortunatly for Tyson.
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Instructors sought for NIC center located in Bonners Ferry
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The North Idaho College center located in Bonners Ferry is scheduled to open this summer and qualified individuals are needed as instructors.
Instructors are sought to teach courses in a variety of subjects, including communications, art, psychology, sociology, creative writing, English, economics, history, math, accounting, human anatomy and physiology, medical terminology, medical transcription, medical software applications, legal issues in health care and medical coding.
"We are seeking instructors from the Bonners Ferry area to teach several face-to-face classes this fall," said NIC Director of Distance Education Candace Wheeler. "We can rely on using interactive video conferencing technology to utilize NIC instructors on the main campus if we have to, but our preference would be to start the center off on the right foot by offering face-to-face instruction for students."
Five credit classes will be offered fall semester of 2006 and a total of seven credit classes will be offered in the spring. A master's degree is required for most academic disciplines with different criteria for some skills curriculum. Part-time faculty with a bachelor's degree will be considered in some circumstances. An NIC department chair will review the candidate's qualifications.
To apply, visit the NIC Human Resources
and follow the application instructions.
Several noncredit workforce training classes and community education classes will also be held in fall of 2006 and spring of 2007.
Individuals with knowledge in a particular subject area and a willingness and ability to teach in a group setting are welcome to apply to teach personal interest classes through NIC's community education department. Many community education instructors enjoy sharing their talents and hobbies and do not need a degree, special training or certification to do so.
Individuals applying to teach a for-credit course should call the NIC Human Resources Office at (208) 769-3304. Those wishing to apply to teach a personal interest class should call the Workforce Training Center at (208) 769-3333.
For More Information
NIC Director of Distance Education Candace Wheeler, (208) 769-5906
Posted: Thursday, Feb. 23, 2006
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Star Tracks: Monday, May 16, 2016 42 years, 2,191 covers and 55,436 stories from PEOPLE magazine's history for you to enjoy
Latest News!
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People Top 5
LAST UPDATE: Tuesday February 10, 2015 01:10PM EST
PEOPLE Top 5 are the most-viewed stories on the site over the past three days, updated every 60 minutes
- May 02, 1988
- Vol. 29
- No. 17
For the Love of Money
They Have Each Other and More Than a Billion Dollars, but Harry and Leona Helmsley Wanted More
They lived luxuriously, and the press dutifully reported their extravagances: the $45,000 silver clock in the shape of the Helmsley Building, which Leona gave Harry as a birthday present; the 28-room, 26-acre estate, Dunellen Hall, that they purchased for $8 million in Greenwich, Conn.; the condo in Palm Beach; the closets stuffed with handbags and rows of designer gowns.
The ad campaign for their flagship Helmsley Palace hotel was also regal. "The only palace in the world where the queen stands guard," trumpeted the copy, accompanied by photos of the immaculately coiffed Leona scrutinizing a hotel room or overseeing the chef. Alas, now it has been charged that Queen Leona was doing more than supervising the kitchen staff—she and her consort, it was alleged, had also been cooking the books.
As the result of a 16-month investigation by state and federal authorities, the Helmsleys were hauled into court in Manhattan two weeks ago and arraigned for allegedly evading more than $4 million in income taxes. The indictment claimed that they listed as business expenses such personal fripperies as a $130,000 indoor-outdoor stereo system for their home. It said they even listed that $45,000 silver clock Leona bought Harry for his birthday as an expense for the Park Lane Hotel. A pink satin dress and jacket, the indictment said, was charged to the same hotel, described as "uniforms." And $500,000 worth of jade ob-jets that now adorn Dunellen Hall, were falsely charged off to four different hotels. Leona was also indicted separately for extorting money from suppliers and for defrauding Helmsley stockholders by paying herself $83,333.34 a month in undisclosed "consulting fees."
The Helmsleys pleaded innocent to all charges and have refused to be interviewed. Their lawyer has insisted that they will be exonerated. But the feeling around New York is that the couple's goose might be cooked, their reputations permanently damaged even if they were legally cleared. Many were confounded by the spectacle of billionaires who lacked for nothing allegedly risking jail—the charges carry penalties of four to 20 years—for small change. But people who know the couple well expressed little surprise. They say the Helmsleys have always been compulsive—even obsessive—about money, and the more they had, the worse the compulsion got. Their behavior was erratic. They could be generous with family and extravagant with charities, one year giving a breathtaking $33 million to New York Hospital. But they also seemed to suffer bouts of mind-boggling stinginess and a corrosive paranoia, believing that everyone was out to cheat them. When Leona's only son, Jay Panzirer, died of a heart attack at age 40 in 1982, Harry sued his estate to recover the cost of shipping the body to New York. Then Leona stepped in, trying to claim the lion's share of her son's small patrimony. In the end, his four children got only $432 each.
"Money triggered a hot button with Leona," said one former employee, "Once, a secretary who had spilled something on her dress sent her clothes to be cleaned at the Helmsley Palace's dry-cleaning service. Leona became enraged, said she'd cheated her, and fired her. The secretary had worked there eight years."
Few Helmsley staffers lasted so long after Leona became lady of the mansion. "The Helmsley house in Greenwich is a boot camp for servants," says one employee. "If you last six months working for her, you can get a job anywhere because people figure you must be the best." Meanwhile, back in town, Leona tyrannized the hotel staff. "I remember walking to her office and saying, 'Hail Mary, full of grace, please let her not yell at me,' " says one ex-employee. "She was so icy and without compassion. Harry's oldest and dearest employees, mostly men who had been with him for 30 to 40 years—she would pick at them and pick at them until Harry would say, 'Yes, Leona, I will fire them.' She was remorseless. A bird of prey."
Indeed, it's popular around the city—where Leona once made the 10 Pushiest Women in New York list of a local newspaper—to blame the missus for all the pettiness, double-dealing and animosity that now threaten to bring down the house of Helmsley. In this view, Harry Helmsley was a decent man before this tough little Brooklyn broad came into his life.
"I think Harry's a different person. He married a different type of wife," says Harry's ex-wife, Eve, a Quaker who throughout their quiet 33-year marriage devoted herself to charitable work. She says she's never met Leona, but adds, "I've heard she's hated."
Others blame them equally. "Harry was just as bad as she was. He permitted her to fire people—he permitted her to run rampant. It was 'Get rid of this one'; 'Get rid of that one.' And he permitted it." Helmsley, after all, is the man once dubbed by a writer 'Hungry Harry,' famous for the shrewdness with which he snapped up properties with other people's money, but also for his tightfistedness when it came to upkeep on his buildings. "I would have included him on the Village Voice's 10 Worst Landlords list," says investigative reporter Jack Newfield. "But he was so infamous, there was no point. This goes back before Leona."
It was Harry's mother who first steered him into real estate. (The daughter of a successful landlord, she had married a notions buyer.) His first job, at age 16, was not cushy, and it was not pretty: He made $18 a week collecting rents in the rough-and-tumble Manhattan neighborhood of Hell's Kitchen. By age 27, Harry had scraped together the $1,000 needed to buy his first building.
For 20 years Helmsley worked his way up through the real estate management firm and steadily acquired commercial properties. But he didn't really begin to make his mark in New York City real estate, reported the Wall Street Journal, until the age of 40, when he joined forces with real estate attorney Lawrence Wien. In their partnership, now dissolved, Wien got the funding, Harry found and made the deals. Their first big splash was buying the Empire State Building in 1961 for the then-record sum of $65 million.
Helmsley, says Wien, "was the best negotiator I've ever known." But he had other skills, too, which are of particular note in light of his current problems: With Wien, Helmsley pioneered a method of buying leases, rather than buying properties outright, that eased investors' tax burdens. And he could be an inspired penny-pincher. When Helmsley bought the New York Central Building, according to the Wall Street Journal, and was contractually obligated to change the name, he settled, after much thought, on the New York General Building. That way, he figured, he would only have the expense of chiseling two new letters, rather than an entire new name, onto the building's façade.
Leona Helmsley, as befits a woman who loves both Charlotte Brontë and Julio Iglesias, embellishes her own rags-to-riches tale with enough romantic flourishes to make Scarlett O'Hara trip on her hoops. The daughter of a milliner, she was raised in Brooklyn in a family that she says "was very, very close." She modeled briefly after high school to make a living and then married lawyer Leo Panzirer, she says, at her parents' urging. They had one son, divorced after the war, and then Leona went to work as an apartment broker. "I was the best," she says. Usually un-mentioned in this American success story is a second husband, a garment industry executive named Joseph Lu-bin, whom Leona Rosenthal Panzirer married—and divorced—twice.
By 1970 Leona had a thriving career as a hard-charging real estate broker whose tenacity caught the attention of Harry Helmsley. She was working for one of Helmsley's brokerage firms on the conversion to cooperative apartments of a rental building on exclusive Sutton Place when her overzealous efforts to persuade tenants to buy their apartments resulted in her being charged with "fraudulent practices." That conversion was eventually halted. But Helmsley kept Leona—by now a millionaire in her own right—on in a high-paying job. In 1972 they were married.
Suddenly money was no impediment to the fulfillment of dreams. "All my life I wanted to go on a cruise in a chiffon dress with my hair blowing," Leona has said. For a romantic honeymoon the Helmsleys cruised to Cannes on a 136-foot yacht and then launched a lavish new life in New York. A quiet 6'3" man with a soft chin and prominent eyes who was once described as a large, white-haired rabbit, Harry underwent a dramatic change. Leona once said Helmsley "had two suits when I met him, one for winter, one for summer, both black. Now he's having fun." The couple hit the party circuit, and even detractors admit they seemed very much in love.
In 1980 Harry made Leona president of his hotel domain, and her passion for detail became a legend. But it was no myth. "We saw her pick up the phone and call somebody in Iowa and say, 'I'm Leona Helmsley, the president of Helmsley hotels, and I'm sorry the air-conditioning in your room was noisy. It will never happen again,' " said the woman who ran her ad campaign. "She really would read every complaint."
But the obsessiveness that endeared her to weary travelers grated on the staff. Chauffeurs at her home estate were put on beepers, according to one worker, the better to be at Leona's beck and call. "Mrs. Helmsley," said one, when he called in response to a beep, "I'm in church." To which she replied, "You work for me now. You don't go to church."
For the press, Leona would put on her grand mask. When CBS' 60 Minutes came to call some years ago at the couple's Connecticut mansion, the TV crew was treated to a bucolic Fragonard tableau worthy of Marie-Antoinette—Leona was gamboling on the great lawn with four sheep.
"The only thing Harry ever indulged me with is sheep," said a flirtatious Leona to Mike Wallace. "One is Bo, one is Pete, one is Baa, one is Baa-Baaa. Come here, Bo! It's your mother!" Alas, shortly after Wallace went bye-bye, so did Baa and Bo and the entire fleecy family. They were ordered slaughtered, according to a former estate employee, and the chops parceled out among the servants, in true manorial style.
Leona came to think that paying bills was beneath her, ex-associates charge. "One time Leona felt her electric bill was too high at their house in Connecticut," says one, "and she said to Joe Licari, their financial adviser [who has been indicted along with the Helmsleys], 'Don't pay it.' Then he went to Harry and Harry paid. When she heard this, she said, 'He wants to pay the electric bill? Then let him sleep with Licari.' "
Leona's mercurial streak was especially evident in her relationship with her only son, Jay R. Panzirer, and Jay's family. Three times married, with four children from his first two marriages, Jay had worked as a salesman in New York and Los Angeles before creating a company that handled purchases for hotels—including the Helmsley chain. After Jay suffered two heart attacks, Harry and Leona, concerned about his health, reportedly asked him to drop his other clients and handle only Helmsley projects. The company he headed, Deco Purchasing and Distributing Co., was a subsidiary of Helmsley Enterprises and would later figure prominently in state and federal indictments of the Helmsleys.
Before Jay's sudden death, says his third wife, Mary "Mimi" Panzirer (now remarried), Harry and Leona were model in-laws. Jay's children by earlier marriages often visited at his home near Orlando, and the Helmsleys, who had a condo in Palm Beach, spent a good amount of time with them. Leona was also very generous with Mimi. "If I bought a pair of shoes that she liked, she'd get me [pairs] in every color," says Mimi. "When we came to New York, they always had a dinner for us and always had our special favorite foods—a particular champagne Jay liked and for me raspberries."
Indeed, Mimi says, Leona's affection sometimes seemed excessive. "You've made my son very happy, which makes me joyous," she remembers Leona writing in one of her "gushy" little notes. "If I could pluck a star from the sky, I would give it to you."
But when Jay died, Mimi says, Leona's feelings for her changed dramatically—and frighteningly. After the memorial service in New York, Leona "looked at me and said, 'I will destroy you,' " recalls Mimi, who had absolutely no warning of this mood swing. Then, she says, "Leona turned to Craig [her eldest grandson] and said, 'You killed your father.' He was 14. He went into hysterics."
Leona was true to her word. Jay Panzirer had died intestate, which under Florida law meant that half of his small estate went to his widow, with the rest to be divided up among his four children. But within months, Leona had filed lawsuits against both the estate and Mimi to recover various valuables and money she claimed Jay had borrowed. Earlier, Harry Helmsley had served an eviction notice on his former daughter-in-law. Deco, it turned out, owned the home where she was living with Craig, then a ninth grader at the local school.
"I asked Harry why he was doing this," recalls Mimi. "He went into great detail about how he could no longer amortize the cost of the house against Jay's salary. His last comment was, 'So you can see I need the money.' " Bending to Mimi's pleas, Harry did agree to stay the eviction until Craig could finish the school year. But, she says, "They did a complete inventory of my home, including my underwear. There's a list on file somewhere of the number of bras and panties, the sizes and colors."
The legal battle between Mimi and the Helmsleys dragged on for five years. (Leona withdrew one suit to recover a topaz ring when Mimi produced a news clip in which Mrs. Helmsley had described the bauble as a gift to her daughter-in-law.) When it was over, the Helmsleys got most of the estate, which totaled less than $200,000. Each of Leona's four grandchildren got $432 and Mimi was awarded $2,020, which was immediately garnished by Deco to cover court costs. Though Mimi won some points on appeal, "I was totally, 100 percent wiped out," by the legal costs, she says. "To this day I don't know why they did it." When her own time of troubles began, the queen wore red to her arraignment. Her consort wore a brown suit. Harry Helmsley had been such a power in New York real estate for so long that a reporter who caught him on the steps of the courthouse was moved to ask him what he considered his greatest accomplishment. And without a moment's hesitation Helmsley glanced at his devoted wife and said, "I married her."
—By Joyce Wadler, with Victoria Balfour and Ned Geeslin in New York and Sandra Hinson in Orlando
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In Brief: Researchers look for adults with diabetes
California researchers are seeking overweight adults with type 2 diabetes -- including some in Erie -- for an online study designed to test two types of well-established diets.
The University of California, San Francisco's Osher Center for Integrative Medicine wants to determine which of the diets would be most effective for controlling the disease and easiest for patients to stick with.
Researchers at the UCSF clinic are looking for adults with type 2 diabetes who do not take insulin to participate in the study. Participants will be divided into two groups, assigned to either a low-carbohydrate diet or the "Create your plate" diet from the American Diabetes Association, which emphasizes higher fiber and lower fat foods.
For more information or to sign up for the study, go to www.succeedstudy.org.
Former McDowell teacher honored as physician
Former McDowell High School teacher Ronald L. Thomas, M.D., has been chosen as the March of Dimes Western Pennsylvania Medical Honoree of the year for his work promoting the organization's goal of giving all babies a healthy start.
The director of the division of maternal-fetal medicine at Allegheny Health Network was honored Tuesday at the Wyndham Grand Pittsburgh Downtown.
Thomas serves on the Pennsylvania chapter of the March of Dimes Programs/Public Affairs board and has spoken on behalf of the organization with numerous media outlets.
He began his career teaching physics and mathematics at McDowell and developed an interest in medicine through tutoring hospital-bound students.
Thomas was honored in Pittsburgh Magazine as a "Top Doctor" for 2010-13, and additional awards include Most Compassionate Doctor (2010), and Patient's Choice Award (2008-10).
Saint Vincent receives stroke treatment award
Saint Vincent Hospital has earned top recognition from the American Heart Association in the treatment of strokes.
The Erie hospital recently received the AHA Get With The Guidelines -- Stroke Gold Plus Quality Achievement Award. It recognized Saint Vincent's commitment and success in implementing a higher standard of care by ensuring that stroke patients receive treatment according to nationally accepted guidelines.
The program provides hospitals with a web-based patient-management tool, best practice discharge protocols and standing orders, along with a robust registry and real-time benchmarking capabilities to track performance.
The quick and efficient use of guideline procedures can improve the quality of care for stroke patients and may reduce disability.
-- from staff reports


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