Clinical validity assessment of a breast cancer risk model combining genetic and clinical information

_Background:_ The extent to which common genetic variation can assist in breast cancer (BCa) risk assessment is unclear. We assessed the addition of risk information from a panel of BCa-associated single nucleotide polymorphisms (SNPs) on risk stratification offered by the Gail Model.

_Methods:_ We selected 7 validated SNPs from the literature and genotyped them among white women in a nested case-control study within the Women’s Health Initiative Clinical Trial. To model SNP risk, previously published odds ratios were combined multiplicatively. To produce a combined clinical/genetic risk, Gail Model risk estimates were multiplied by combined SNP odds ratios. We assessed classification performance using reclassification tables and receiver operating characteristic (ROC) curves. 

_Results:_ The SNP risk score was well calibrated and nearly independent of Gail risk, and the combined predictor was more predictive than either Gail risk or SNP risk alone. In ROC curve analysis, the combined score had an area under the curve (AUC) of 0.594 compared to 0.557 for Gail risk alone. For reclassification with 5-year risk thresholds at 1.5% and 2%, the net reclassification index (NRI) was 0.085 (Z = 4.3, P = 1.0×10^-5^). Focusing on women with Gail 5-year risk of 1.5-2% results in an NRI of 0.195 (Z = 3.8, P = 8.6×10^−5^).

_Conclusions:_ Combining clinical risk factors and validated common genetic risk factors results in improvement in classification of BCa risks in white, postmenopausal women. This may have implications for informing primary prevention and/or screening strategies. Future research should assess the clinical utility of such strategies.
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Impact of cyclooxygenase inhibitors in the Women's Health Initiative hormone trials: secondary analysis of a randomized trial.

OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials. DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6. SETTING: The Women's Health Initiative hormone trials were conducted at 40 clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did not significantly affect the Women's Health Initiative hormone trial results

Colorectal cancer in relation to postmenopausal estrogen and estrogen plus progestin in the Women’s Health Initiative clinical trial and observational study

Background: Colorectal cancer incidence was reduced among women assigned to active treatment in the Women’s Health Initiative (WHI) estrogen plus progestin randomized trial, but the interpretation was obscured by an associated later stage of diagnosis. In contrast the estrogen-alone trial showed no incidence reduction or differential stage at diagnosis. Here, data from the WHI observational study are considered, in conjunction with colorectal cancer mortality data from the hormone therapy trials, in an attempt to clarify postmenopausal hormone therapy effects. Participants and Methods: Postmenopausal women aged 50-79 at WHI enrollment. Estrogen-alone analyses include 21,552 and 10,739 women who were post-hysterectomy from the observational study and clinical trial respectively. Estrogen plus progestin analyses include 32,084 and 16,608 observational study and clinical trial women with uterus. Colorectal cancers were verified by central medical and pathology report review. Results: Hazard ratios (95% confidence intervals) from the WHI observational study were 0.80 (0.53 to 1.20) for estrogen and 1.15 (0.74 to 1.79) for estrogen plus progestin, with respectively 168 and 175 women diagnosed with colorectal cancer. Delayed diagnosis with estrogen plus progestin is not evident in the observational study. No protective effect on colorectal cancer mortality in the estrogen plus progestin trial is seen over an 8-year intervention and follow-up period. Conclusion: Hazard ratio patterns in the WHI clinical trial and observational study do not provide strong evidence of a clinically important colorectal cancer benefit with either estrogen-alone or estrogen plus progestin over 7-8 years of treatment and follow-up

Impact of cyclooxygenase inhibitors in the Women\u27s Health Initiative hormone trials: secondary analysis of a randomized trial

OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women\u27s Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials. DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6. SETTING: The Women\u27s Health Initiative hormone trials were conducted at 40 clinical sites in the United States. PARTICIPANTS: The trials enrolled 27,347 postmenopausal women, aged 50-79 y. INTERVENTIONS: We randomized 16,608 women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo, and 10,739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo. OUTCOME MEASURES: Myocardial infarction, coronary death, and coronary revascularization were ascertained during 5.6 y of follow-up in the estrogen plus progestin trial and 6.8 y of follow-up in the estrogen alone trial. RESULTS: Hazard ratios with 95% confidence intervals were calculated from Cox proportional hazard models stratified by COX inhibitor use. The hazard ratio for myocardial infarction/coronary death with estrogen plus progestin was 1.13 (95% confidence interval 0.68-1.89) among non-users of COX inhibitors, and 1.35 (95% confidence interval 0.86-2.10) among continuous users. The hazard ratio with estrogen alone was 0.92 (95% confidence interval 0.57-1.48) among non-users of COX inhibitors, and 1.08 (95% confidence interval 0.69-1.70) among continuous users. In a second analytic approach, hazard ratios were calculated from Cox models that included hormone trial assignment as well as a time-dependent covariate for medication use, and an interaction term. No significant interaction was identified. CONCLUSIONS: Use of COX inhibitors did not significantly affect the Women\u27s Health Initiative hormone trial results

Laxative use and incident falls, fractures and change in bone mineral density in postmenopausal women: results from the Women\u27s Health Initiative

BACKGROUND: Laxatives are among the most widely used over-the-counter medications in the United States but studies examining their potential hazardous side effects are sparse. Associations between laxative use and risk for fractures and change in bone mineral density [BMD] have not previously been investigated. METHODS: This prospective analysis included 161,808 postmenopausal women (8907 users and 151,497 nonusers of laxatives) enrolled in the WHI Observational Study and Clinical Trials. Women were recruited from October 1, 1993, to December 31, 1998, at 40 clinical centers in the United States and were eligible if they were 50 to 79 years old and were postmenopausal at the time of enrollment. Medication inventories were obtained during in-person interviews at baseline and at the 3-year follow-up visit on everyone. Data on self-reported falls (\u3e/=2), fractures (hip and total fractures) were used. BMD was determined at baseline and year 3 at 3 of the 40 clinical centers of the WHI. RESULTS: Age-adjusted rates of hip fractures and total fractures, but not for falls were similar between laxative users and non-users regardless of duration of laxative use. The multivariate-adjusted hazard ratios for any laxative use were 1.06 (95% confidence interval [CI], 1.03-1.10) for falls, 1.02 (95% CI, 0.85-1.22) for hip fractures and 1.01 (95% CI, 0.96-1.07) for total fractures. The BMD levels did not statistically differ between laxative users and nonusers at any skeletal site after 3-years intake. CONCLUSION: These findings support a modest association between laxative use and increase in the risk of falls but not for fractures. Its use did not decrease bone mineral density levels in postmenopausal women. Maintaining physical functioning, and providing adequate treatment of comorbidities that predispose individuals for falls should be considered as first measures to avoid potential negative consequences associated with laxative use

The Iowa Homemaker vol.17, no.6

Genuinely “Big” Business by Grace McIlrath Ellis, page 1 Every Gram of Jam by Ruth Kunerth, page 2 Confessions of Shoe Salesman and Florist by Paul Montgomery and Paul Buehler, page 3 What Would You Do If by Harriet Beyer, page 4 Food Shots Are Not So Candid by Ruth Dahlberg, page 5 Yumph Invades the Formal Field by Lois Swenson, page 6 Just Skin Deep by Donna Button, page 7 On Your Own Toes by Jane Helser, page 8 Resolve to Charm by Frances Dickerson, page 9 What’s New in Home Economics edited by Marjorie Pettinger, page 10 No Peacock Tongues by Daisy Mary Kimberley, page 12 She Knows Her Turkeys by Mary Ellen Lynch, page 13 On the Airwaves by Grace Strohmeier, page 13 Science in the Kitchen, page 14 Radiation Ratings by Kay Dodds, page 15 The Gavel Strikes by Donna Button, page 16 What Goal Posts? By Jean Metcalf and Rachel Roewe, page 17 Alums Make News by Faithe Danielson, page 18 Up With the Dawn by the editor, page 2

The Iowa Homemaker vol.18, no.4

A Queen of Homemakers by Harriet Beyer, page 2 Dining Midst Drama by Daisy Mary Kimberley, page 3 Scientific Fun by Ruth Stultz, page 4 A Recipe for Life by Helen Greene, page 5 Fashions Are Fancy Free by Polly Towne, page 6 On a European Honeymoon by Gaynold Carroll, page 7 Home Economics for Homemakers by Daisy Mary Kimberley, page 8 Designs for Richer Living by Marie Larson, page 9 What’s New in Home Economics edited by Marjorie Pettinger, page 10 Food for the Masculine Taste by Ida Halpin, page 12 Behind Bright Jackets edited by Winnifred Cannon, page 13 Help Yourself to Manners by Winnifred Cannon, page 14 Personality in Bloom by Edith Wahrenbrock, page 15 Notes for Music Lovers by Jean Metcalf, page 16 Alums in the News by Grace Strohmeier, page 18 Grooming Guide by Ruth Jensen, page 20 Keeping Posted by the editor, page 2

The Iowa Homemaker vol.18, no.3

Inside Information, page 1 Our Heritage by Daisy Mary Kimberley, page 2 Welcome by Genevieve Fisher, Dean, Home Economics Division, page 3 We Wondered “How?” – So We Asked by Berniece Williams, page 4 Behind the Kitchen Door by Myrtle Marie Campbell, page 5 Shopper Sally at Your Service by Barbara Field, page 6 Conventioning from Coast to Coast by Alvina Iverson, page 7 All Aboard for Mortar Board by Jane Currie, page 7 Dear Freshman, by Winnifred Cannon, page 8 Equipment Economics by Gwen Griffith, page 9 What’s New in Home Economics edited by Marjorie Pettinger, page 10 Coed Training for Football by Ida Halpin, page 12 “This Is the Way We Wash Our Clothes” by Marian Abbott, page 13 Alums in the News by Faithe Danielson, page 14 How Do You Rate? by Dorothy Evans, page 16 Behind Bright Jackets, page 18 To Your Dresser by Eunice Anderson, page 20 Keeping Posted by the editor, page 2

Optimism may moderate screening mammogram frequency in Medicare: A longitudinal study

Higher trait optimism and/or lower cynical hostility are associated with healthier behaviors and lower risk of morbidity and mortality, yet their association with health care utilization has been understudied. Whether these psychological attitudes are associated with breast cancer screening behavior is unknown. To assess the association of optimism and cynical hostility with screening mammography in older women and whether sociodemographic factors acted as mediators of these relationships, we used Women\u27s Health Initiative (WHI) observational cohort survey data linked to Medicare claims. The sample includes WHI participants without history of breast cancer who were enrolled in Medicare Parts A and B for \u3e /=2 years from 2005-2010, and who completed WHI baseline attitudinal questionnaires (n = 48,291). We used survival modeling to examine whether screening frequency varied by psychological attitudes (measured at study baseline) after adjusting for sociodemographic characteristics, health conditions, and healthcare-related variables. Psychological attitudes included trait optimism (Life Orientation Test-Revised) and cynical hostility (Cook Medley subscale), which were self-reported at study baseline. Sociodemographic, health conditions, and healthcare variables were self-reported at baseline and updated through 2005 as available. Contrary to our hypotheses, repeated events survival models showed that women with the lowest optimism scores (i.e., more pessimistic tendencies) received 5% more frequent screenings after complete covariate adjustment (p \u3c .01) compared to the most optimistic group, and showed no association between cynical hostility and frequency of screening mammograms. Sociodemographic factors did not appear to mediate the relationship between optimism and screenings. However, higher levels of education and higher levels of income were associated with more frequent screenings (both p \u3c .01). We also found that results for optimism were primarily driven by women who were aged 75 or older after January 2009, when changes to clinical guidelines lead to uncertainty about risks and benefits of screening in this age group. The study demonstrated that lower optimism, higher education, and higher income were all associated with more frequent screening mammograms in this sample after repeated events survival modeling and covariate adjustment

The Iowa Homemaker vol.17, no.7

Beauty from Beauty by Peggy Schenk, page 1 Through Masculine Eyes by Jim Henderson and E. L. Anderson, page 2 Use Angles and Lights for Snappy Shots by Jane Helser, page 4 Faces in Focus by Gaynold Carroll and Harriett Graves, page 5 New Style Loves by Sally, page 6 Beds for Beauty by Ruth Dahlberg, page 7 Gems in Pottery by Katherine Taube, page 8 Room for Improvement by Leah Scott, page 9 What’s New in Home Economics edited by Marjorie Pettinger, page 10 In the Still of the Night by Helen Greene, page 12 Short but Sweet by Harriet Beyer, page 13 Dessert Course, a poem by Ronny Ronningen, page 14 Controlled Curves by Gertrude E. Hendriks, page 14 First Ladies by Ruth Sawin, page 15 Complaints of Shopworn Clerks by Ruth Dahlberg, page 16 Behind Bright Jackets, page 18 Alumnae News by Faithe Danielson, page 19 Lamp Light by Mary Bush, page 20 To Whom It May Concern, a poem by Ronny Ronningen, page 20 Heart to Heart by the editor, page 2