Anita L. Weber

Hormone replacement therapy regimens and breast cancer risk

OBJECTIVE Hormone replacement therapy (HRT) has increased in the United States over the past 2 decades in response to reports of long‐term health benefits. A relationship between HRT and breast cancer risk has been observed in a number of epidemiological studies. In 2002, the Womens Health Initiative Randomized Controlled Trial reported an association between continuous combined HRT and breast cancer risk. The objective of this study was to examine the association between breast cancer risk and HRT according to regimen and duration and recency of use. METHODS A multicenter, population‐based, case‐control study was conducted in five United States metropolitan areas from 1994 to 1998. Analyzed were data from 3823 postmenopausal white and black women (1870 cases and 1953 controls) aged 35–64 years. Odds ratios (ORs) were calculated as estimates of breast cancer risk using standard, unconditional, multivariable logistic regression analysis. Potential confounders were included in the final model if they altered ORs by 10% or more. Two‐sided P values for trend were computed from the likelihood ratio statistic. RESULTS Continuous combined HRT was associated with increased breast cancer risk among current users of 5 or more years (1.54; 95% confidence interval 1.10, 2.17). Additionally, a statistically significant trend indicating increasing breast cancer risk with longer duration of continuous combined HRT was observed among current users (P = .01). There were no positive associations between breast cancer risk and other HRT regimens. CONCLUSION Our data suggest a positive association between continuous combined HRT and breast cancer risk among current, longer term users. Progestin administered in an uninterrupted regimen may be a contributing factor. Risk dissipates once use is discontinued.

Discrimination of simple and complex gratings

Abstract We investigated the discriminability of simple and complex gratings containing one or two barely detectable sinusoidal luminance modulations at 3 and 9 c/deg, which will be referred to as ƒ and 3ƒ. Our major findings were the following: (1) frequency discrimination of the simple gratings seems to be limited only by their detectability; (2) relative phase differences between components in a complex grating are essentially indiscriminable even when each component is nearly perfectly detectable in the presence of the other; (3) when the contrast of the ƒ-component is at least 4 times its threshold value, it is only the detectability of the 3ƒ-component which limits the discriminability of complex gratings differing in relative phase by π radians; (4) a high contrast 3ƒ-component hinders the detection of ƒ while a high contrast ƒ component facilitates the detection of 3ƒ It is possible to offer a plausible explanation of some of these phenomena by invoking the existence in the human visual system of broad-band, phase-sensitive channels, as well as of narrow-band channels.

Risk Factors for Lymphedema after Breast Cancer Treatment

Background: As cancer treatments evolve, it is important to reevaluate their effect on lymphedema risk in breast cancer survivors. Methods: A population-based random sample of 631 women from metropolitan Philadelphia, Pennsylvania, diagnosed with incident breast cancer in 1999 to 2001, was followed for 5 years. Risk factor information was obtained by questionnaire and medical record review. Lymphedema was assessed with a validated questionnaire. Using Cox proportional hazards models, we estimated the relative incidence rates [hazard ratios (HR)] of lymphedema with standard adjusted multivariable analyses ignoring interactions, followed by models including clinically plausible treatment interactions. Results: Compared with no lymph node surgery, adjusted HRs for lymphedema were increased following axillary lymph node dissection [ALND; HR, 2.61; 95% confidence interval (95% CI), 1.77-3.84] but not sentinel lymph node biopsy (SLNB; HR, 1.04; 95% CI, 0.58-1.88). Risk was not increased following irradiation [breast/chest wall only: HR, 1.18 (95% CI, 0.80-1.73); breast/chest wall plus supraclavicular field (+/− full axilla): HR, 0.86 (95% CI, 0.48-1.54)]. Eighty-one percent of chemotherapy was anthracycline based. The HR for anthracycline chemotherapy versus no chemotherapy was 1.46 (95% CI, 1.04-2.04), persisting after stratifying on stage at diagnosis or number of positive nodes. Treatment combinations involving ALND or chemotherapy resulted in approximately 4- to 5-fold increases in HRs for lymphedema [e.g., HR of 4.16 (95% CI, 1.32-12.45) for SLNB/chemotherapy/no radiation] compared with no treatment. Conclusion: With standard multivariable analyses, ALND and chemotherapy increased lymphedema risk whereas radiation therapy and SLNB did not. However, risk varied by combinations of exposures. Impact: Treatment patterns should be considered when counseling and monitoring patients for lymphedema. Cancer Epidemiol Biomarkers Prev; 19(11); 2734–46. ©2010 AACR.

Adaptation to square-wave gratings: In search of the elusive third harmonic

Abstract Blakemore and Campbell (1969) found that a square-wave adapting grating, unlike a sinewave grating of the same period, elevates threshold contrast for test gratings whose frequency is in the vicinity of the third harmonic in the square-wave. Because of its important bearing on the frequency-specificity of adaptation to gratings, we attempted to replicate this finding. Our attempt was successful with one of two observers when the method of adjustment was used to determine thresholds. With the temporal two alternative, forced-choice method, individual differences in this regard disappeared. For all three observers a 3 c/deg adapting square-wave and a 3 c/deg sinewave were equally ineffective in raising the contrast threshold for a 9 c/deg test grating, whereas a 9 c/deg adapting grating, matched to the 3rd harmonic in the square-wave, raised the test gratings threshold by 0.2 log units. Our failure to find consistent evidence that the third harmonic in a square-wave does any adapting whatever casts doubt on the frequency-specificity of adaptation to gratings.

Impact of Raloxifene or Tamoxifen Use on Endometrial Cancer Risk: A Population-Based Case-Control Study

PURPOSE Raloxifene reduces breast cancer risk in women with osteoporosis, and both tamoxifen and raloxifene prevent breast cancer in high-risk women. However, in vitro, raloxifene does not share the pro-estrogenic effects of tamoxifen on the endometrium. Randomized trials of these agents have provided limited information about endometrial cancer risk in the general population. We sought to compare endometrial cancer risks associated with raloxifene, tamoxifen, and nonusers of a selective estrogen receptor modulator (SERM) in the general population and characterize the endometrial tumors occurring in these groups. METHODS We performed a case-control study of white and African American women age 50 to 79 years in the Philadelphia area. Patients were diagnosed with endometrial cancer between July 1999 and June 2002. Controls were identified through random-digit dialing. RESULTS We analyzed 547 cases and 1,410 controls. Among cases, 3.3% had taken raloxifene; 6.2% had taken tamoxifen. Among controls, 6.6% had taken raloxifene; 2.4% had taken tamoxifen. After adjustment for other risk factors, the odds of endometrial cancer among raloxifene users was 50% that of nonusers (odds ratio [OR] = 0.50; 95% CI, 0.29 to 0.85), whereas tamoxifen users had three times the odds of developing endometrial cancer compared with raloxifene users (OR = 3.0; 95% CI, 1.3 to 6.9). Endometrial tumors in raloxifene users had a more favorable histologic profile and were predominantly International Federation of Gynecology and Obstetrics stage I and low grade. CONCLUSION Raloxifene users had significantly lower odds of endometrial cancer compared with both tamoxifen users and SERM nonusers, suggesting a role for raloxifene in endometrial cancer prevention and individualization of SERM therapy.

Combined effect of oral contraceptive use and hormone replacement therapy on breast cancer risk in postmenopausal women

Objective: We examined breast cancer risk related to lifetime exposure to oral contraceptives (OCs) and hormone replacement therapy (HRT) in postmenopausal women. Methods: The Womens Contraceptive and Reproductive Experiences (CARE) Study was a population-based case–control study that included 1847 postmenopausal women with incident invasive breast cancer, and 1932 control subjects, identified using random digit dialing. Results: 45% of cases and 49% of controls used both OCs and HRT. OC users were not at increased risk regardless of subsequent HRT exposure. HRT users who had used OCs previously did not have a higher risk of breast cancer than women with no exposure to OCs. We observed a negative interaction (p-value: 0.032) of combined hormone replacement therapy (CHRT) and past OC use. The increase in risk with CHRT was stronger in women who had never used OCs in the past (odds ratio: 1.05; 95% confidence interval: 1.01–1.10 per year of exclusive CHRT use) than in women who had used OCs (odds ratio: 1.00; 95% confidence interval: 0.97–1.03). Conclusions: We found no indication that adverse effects of exposure to OCs or HRT appeared only in the presence of the other hormone or were exacerbated by exposure to the other hormone.

Risk factors for mortality despite early protocolized resuscitation for severe sepsis and septic shock in the emergency department.

PURPOSE The purpose was to identify risk factors associated with in-hospital mortality among emergency department (ED) patients with severe sepsis and septic shock managed with early protocolized resuscitation. METHODS This was a retrospective, observational cohort study in an academic, tertiary care ED. We enrolled 411 adult patients with severe sepsis and lactate ≥4.0 mmol/L (n = 203) or septic shock (n = 208) who received protocolized resuscitation from 2005 to 2009. Emergency department variables, microbial cultures, and in-hospital outcomes were obtained from the medical record. Multivariable regression was used to identify factors independently associated with in-hospital mortality. RESULTS Mean age was 59.5 ± 16.3 years; 57% were male. Mean lactate was 4.8 mmol/L (3.5-6.7), 54% had positive cultures, and 27% received vasopressors in the ED. One hundred and five (26%) patients died in-hospital. Age, active cancer, do-not-resuscitate status on ED arrival, lack of fever, hypoglycemia, and intubation were independently associated with increased in-hospital mortality. Lactate clearance and diabetes were associated with a decreased risk of in-hospital death. CONCLUSIONS We identified a number of factors that were associated with in-hospital mortality among ED patients with severe sepsis or septic shock despite treatment with early protocolized resuscitation. These findings provide insights into aspects of early sepsis care that can be targets for future intervention.

Hormone therapy and fatal breast cancer

Among unanswered questions is whether menopausal use of estrogen therapy (ET) or estrogen‐plus‐progestin therapy (CHT) increases risk of developing fatal breast cancer i.e., developing and dying of breast cancer. Using a population‐based case‐control design, we estimated incidence rate ratios of fatal breast cancer in postmenopausal hormone therapy (HT) users compared to non‐users by type, duration, and recency of HT use.

Gender- and Ethnic-Specific Associations with Obesity: Individual and Neighborhood-Level Factors

OBJECTIVES Gender- and ethnicity-specific groups face different risks for obesity, but little is understood about the factors that predict group-specific risks. We evaluated individual and neighborhood factors in relation to obesity. DESIGN Cross-sectional surveys of adults (ages 18-100 years) from southeastern Pennsylvania were analyzed. Individual- and neighborhood-level factors were included in fully-adjusted regression models to estimate relationships with obesity for specific gender-ethnic groups. The study included 679 Asian women, 655 Asian men, 4190 African-American women, 1568 African-American men, 1248 Hispanic women, 586 Hispanic men, 11791 European American women, and 6547 European American men. RESULTS There were significant differences in the predictors of obesity by gender-ethnic groups. Obesity was differentially associated with age (p < 0.001, positively associated with middle age in African-American men and in all women except Asian; positively associated with older age in European American women but inversely in African-American men and European American men), employment (p < 0.01, positively associated in African-American men and European American men) and poverty (p < 0.001, positively associated in Asian men, African-American women, and European American women). Reporting good/excellent health was differentially associated with less obesity (p < 0.01, no association for African-American men and Asians). Interestingly, neighborhood-level effects, however, did not differ significantly by gender-ethnic group. Inverse neighborhood effects on obesity prevalence were observed in most groups for higher neighborhood education and family income. Direct associations with obesity were observed for neighborhood poverty and neighborhood smoking. CONCLUSIONS We observed that individual- and neighborhood-level variables are associated with obesity. Several individual-level effects differ by gender-ethnic group.

Telephone-based care management for older adults initiated on psychotropic medication

This study aimed to explore the longitudinal, 6‐month symptom course of older adults newly started on an antidepressant or anxiolytic by non‐psychiatrist physicians and enrolled in a care management program.