Dietary fat and breast cancer: contributions from a survival trial.
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Publications and source records attributed to Rachel Ballard-Barbash.
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Several polymorphisms have been identified in genes that code for enzymes involved with estrogen biosynthesis and metabolism. Little is known about the functional relevance of these polymorphisms on sex hormones in vivo. We examined the association between CYP17, CYP1B1, COMT or SHBG genotypes and serum concentrations of estrone, estradiol, free estradiol, sex hormone-binding globulin (SHBG), testosterone, free testosterone and dehyroepiandrosterone in 366 post-menopausal breast cancer survivors in New Mexico, California and Washington. Hormone levels were determined by high performance liquid chromatography and radioimmunoassay in blood drawn approximately 2 years post-diagnosis. We used generalized linear regression to calculate mean hormone levels by genotype, adjusting for age, race/ethnicity, stage, study site, tamoxifen use, number of remaining ovaries, hormone therapy use, marital status and BMI. No associations were observed between any of the genotypes and sex hormones when analyzing the main effects. In subgroup analyses, androgen levels of Hispanic women with the variant (A2) CYP17 genotype were 46-87% higher than those of women with the wild-type; androgen levels were 13-20% lower in non-Hispanic whites with the variant genotype; no difference by genotype was observed for African-American women. Current tamoxifen users with the variant asn(327) SHBG genotype had 81% higher serum SHBG and 39% lower free testosterone concentrations than women with the wild-type genotype. Non-tamoxifen users with the variant SHBG allele had elevated free estradiol levels. These results provide little evidence that the CYP17, CYP1B1, and COMT polymorphisms are associated with different sex hormone levels in post-menopausal breast cancer survivors.
BACKGROUND: Risk prediction models for breast cancer can be improved by the addition of recently identified risk factors, including breast density and use of hormone therapy. We used prospective risk information to predict a diagnosis of breast cancer in a cohort of 1 million women undergoing screening mammography. METHODS: There were 2,392,998 eligible screening mammograms from women without previously diagnosed breast cancer who had had a prior mammogram in the preceding 5 years. Within 1 year of the screening mammogram, 11,638 women were diagnosed with breast cancer. Separate logistic regression risk models were constructed for premenopausal and postmenopausal examinations by use of a stringent (P<.0001) criterion for the inclusion of risk factors. Risk models were constructed with 75% of the data and validated with the remaining 25%. Concordance of the predicted with the observed outcomes was assessed by a concordance (c) statistic after logistic regression model fit. All statistical tests were two-sided. RESULTS: Statistically significant risk factors for breast cancer diagnosis among premenopausal women included age, breast density, family history of breast cancer, and a prior breast procedure. For postmenopausal women, the statistically significant factors included age, breast density, race, ethnicity, family history of breast cancer, a prior breast procedure, body mass index, natural menopause, hormone therapy, and a prior false-positive mammogram. The model may identify high-risk women better than the Gail model, although predictive accuracy was only moderate. The c statistics were 0.631 (95% confidence interval [CI] = 0.618 to 0.644) for premenopausal women and 0.624 (95% CI = 0.619 to 0.630) for postmenopausal women. CONCLUSION: Breast density is a strong additional risk factor for breast cancer, although it is unknown whether reduction in breast density would reduce risk. Our risk model may be able to identify women at high risk for breast cancer for preventive interventions or more intensive surveillance.
BACKGROUND: Obesity, defined by a body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) of 30.0 or more, is associated with an increased risk of death, but the relation between overweight (a BMI of 25.0 to 29.9) and the risk of death has been questioned. METHODS: We prospectively examined BMI in relation to the risk of death from any cause in 527,265 U.S. men and women in the National Institutes of Health-AARP cohort who were 50 to 71 years old at enrollment in 1995-1996. BMI was calculated from self-reported weight and height. Relative risks and 95 percent confidence intervals were adjusted for age, race or ethnic group, level of education, smoking status, physical activity, and alcohol intake. We also conducted alternative analyses to address potential biases related to preexisting chronic disease and smoking status. RESULTS: During a maximum follow-up of 10 years through 2005, 61,317 participants (42,173 men and 19,144 women) died. Initial analyses showed an increased risk of death for the highest and lowest categories of BMI among both men and women, in all racial or ethnic groups, and at all ages. When the analysis was restricted to healthy people who had never smoked, the risk of death was associated with both overweight and obesity among men and women. In analyses of BMI during midlife (age of 50 years) among those who had never smoked, the associations became stronger, with the risk of death increasing by 20 to 40 percent among overweight persons and by two to at least three times among obese persons; the risk of death among underweight persons was attenuated. CONCLUSIONS: Excess body weight during midlife, including overweight, is associated with an increased risk of death.
OBJECTIVES: The increasing number of cancer survivors brings greater attention to the biopsychosocial impact of surviving cancer. Instruments exist that measure quality of life (QOL), symptoms, and specific types of functioning after cancer; however, a reliable and valid assessment of the perceived impact of cancer (IOC) on the life plans and activities of cancer survivors has been missing. This study evaluated the psychometric properties of the 16-item Brief Cancer Impact Assessment (BCIA). METHODS: Factor analysis with Promax oblique rotation established the factor structure of the BCIA in 783 ethnically diverse breast cancer survivors, >or=2 years after diagnosis. Construct validity was assessed by comparing factor-based scale means by demographic and treatment characteristics, and correlating scales with psychosocial and health-related QOL scales. RESULTS: Factor analysis revealed four factors measuring the IOC on caregiving and finances, exercise and diet behaviors, social and emotional functioning, and religiosity. Scale scores differed by demographic and treatment characteristics according to expectations, and the pattern of correlations with psychosocial and health-related QOL generally supported the construct validity of the scales. CONCLUSION: Including the BCIA with measures of QOL, symptoms, and functioning will allow researchers to gain a more comprehensive assessment of the biopsychosocial IOC in survivors.
Insulin receptor substrate-1 (IRS-1) is a key downstream signaling molecule common to both the insulin and IGF signaling pathways that can interact with the estrogen pathway to regulate breast cell growth. We investigated whether a putative functional variant for IRS-1 (G972R) influences circulating levels of sex hormones, sex hormone binding globulin (SHBG), C-peptide, and insulin-like growth factor 1 (IGF-1) levels among post-menopausal African-American and non-Hispanic white breast cancer patients enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study. Circulating levels of sex hormones and growth factors can influence breast cancer recurrence and survival. Serum estrone, estradiol, testosterone, SHBG, IGF-1 and C-peptide were measured in 468 patients at 30+ months post diagnosis. Non-protein bound hormone levels (free estradiol, free testosterone) were calculated. In African-American patients, the IRS-1 variant was associated with increased serum levels of estrone (p = 0.02), free estradiol (p = 0.04), total testosterone (p = 0.04), free testosterone (p = 0.006) and decreased levels of sex hormone-binding globulin (p = 0.02). No association was present for white patients. Our findings provide suggestive evidence that IRS-1 G972R variant may be associated with circulating levels of sex hormones and SHBG in African American breast cancer survivors.
The authors determined the validity and reliability of their Past Year Total Physical Activity Questionnaire (PYTPAQ), which assesses the frequency, duration, and intensity of occupational, household, and recreational activities performed over the past year. The PYTPAQ was completed twice at baseline, 9 weeks apart (on average), by 154 healthy Canadian men and women aged 35-65 years for assessment of reliability. The PYTPAQ was completed again 1 year later as a self-administered questionnaire. Four times during the year, participants wore an accelerometer for 7 days and completed 7-day physical activity logs. The authors assessed validity by comparing PYTPAQ summary values with 1-year averages of the physical activity logs and accelerometer data and with physical fitness and anthropometric data measured at baseline and 1 year. Spearman correlations for reliability (metabolic equivalent-hours/week) were 0.64 for total activity, 0.70 for occupational activity, 0.73 for recreational activity, and 0.65 for household activity. For total activity, the intraclass correlation coefficient for correlation between the PYTPAQ and the 7-day physical activity logs was 0.42 (95% confidence interval: 0.28, 0.54), and for the accelerometer data it was 0.18 (95% confidence interval: 0.03, 0.32). Spearman correlations between PYTPAQ hours/week of vigorous activity and maximal oxygen uptake were 0.37 and 0.32 at baseline and follow-up, respectively. In general, the PYTPAQ has acceptable reliability and validity for measurement of past-year physical activity that is comparable to that of similar questionnaires.
BACKGROUND: Results of 2 trials of postmenopausal hormone therapy (HT) challenged established practice patterns; 1 was not associated with changes in HT use, whereas the other was associated with substantial decline. Differential coverage by lay newspapers may have contributed to the differential impact. OBJECTIVE: To examine newspaper coverage of HT before and after the publication of the Heart and Estrogen Replacement Study (HERS) in August 1998, and the main findings of the estrogen plus progestin therapy arm of the Women's Health Initiative (EPT-WHI) in July 2002. DESIGN: Longitudinal review of newspaper articles, 1998 to 2003 (n=663). SETTING: Twenty local and 6 regional/national newspapers. MEASUREMENTS: Number and content of articles about HT. RESULTS: The average number of articles about HT published during the month of the publication of the EPT-WHI was at least 8-fold greater than the number of articles published on the topic during any prior period. While the majority of articles in all periods presented information about the potential benefits of HT, information about harms became more common than information about benefits during the 2 months before the publication of the EPT-WHI, when the trial participants were notified of the early termination of the study. The presentation of specific health harms was more common after the publication of the EPT-WHI than after the publication of HERS. Few articles in any period used visual aids. CONCLUSIONS: The publication of the EPT-WHI was associated with a change in both the volume and content of newspaper coverage about HT.
PURPOSE: We describe trends in the use of chemotherapy and hormonal therapy by nodal and estrogen receptor (ER) status in women with early-stage breast cancer. METHODS: Cases were randomly sampled from the population-based Surveillance, Epidemiology and End Results (SEER) program and physician verified treatment was examined. A total of 9,481 women, aged 20 years and older, diagnosed with early-stage breast cancer in 1987 to 1991, 1995, and 2000 were included in the study. RESULTS: The use of chemotherapy plus tamoxifen increased between 1995 and 2000 for women with node-negative, ER-positive breast cancer > or = 1 cm (8% to 21%). Nearly 23% of women with node-negative and ER-positive tumors > or = 1 cm received no adjuvant therapy. The use of chemotherapy alone increased to nearly 60% in women with node-negative, ER-negative tumors > or = 1 cm (48% to 59%). However, in 2000, 16% of women with node-positive and ER-negative tumors received no adjuvant therapy and an additional 6% received tamoxifen alone. The influence of age can clearly be seen. Chemotherapy is given much less often in women 70 years or older. CONCLUSION: The results from SEER areas across the United States suggest that physicians quickly responded to publications and guidelines regarding breast cancer therapy. The lack of definitive findings from clinical trials on the use of adjuvant therapy in women 70 years and older may explain the lower use in this group of women.
BACKGROUND: To the authors' knowledge, a comprehensive analysis of pathology outcomes after screening mammography, as it is practiced clinically in the U.S. general population, has not been performed. METHODS: Breast Cancer Surveillance Consortium data from 1996-2001 were used to identify pathology specimens that were obtained within 1 year of screening mammograms performed on 786,846 women ages 40-89 years. The pathology results were classified as invasive carcinoma, ductal carcinoma in situ (DCIS), or benign. The associations between overall pathology outcomes and invasive tumor size and lymph node status were analyzed by age and mammography assessment category. RESULTS: The rates of both recommending and performing a biopsy varied little with age. The 1,664,032 screening mammograms were followed by 26,748 known biopsies (1.6%) and 8815 diagnoses of breast carcinoma (0.53%). Overall, 81% of carcinomas were invasive, and 78% of those were pathologically lymph node-negative tumors, in contrast to the 66% prevalence observed in the Surveillance, Epidemiology, and End Results (SEER) data during the same period. Most invasive tumors measured between 0 mm and 10 mm (35%) or between 11 mm and 20 mm (36%) in greatest dimension, and 92% and 78% were lymph node-negative tumors, respectively: Biopsy results that were classified as malignant increased with age (P < 0.0001) and were most likely to follow Breast Imaging, Reporting, and Diagnosis System Category 5 and 4 assessments, respectively. Ductal hyperplasia (19.6%), fibroadenoma (18.5%), and other benign findings (56.1%) were the most common benign diagnoses. CONCLUSIONS: Pathologically negative lymph nodes were more prevalent in this mammographically screened population than in the overall SEER population. The prevalence of invasive carcinoma, DCIS, and benign findings presented herein establish a range of expected biopsy outcomes for women after screening mammography in the general U.S. population.
Hormone-related symptoms are common in breast cancer survivors and many aspects of these symptoms are currently under study. Reliable and valid assessment tools are needed to successfully study hormone-related symptoms in breast cancer survivors; however, no gold standard currently exists for measuring these symptoms. This study evaluated the psychometric properties of a shortened version of the Breast Cancer Prevention Trial (BCPT) symptom checklist in a sample of 803 breast cancer survivors. Principal factor analysis with Promax oblique rotation revealed a five-factor structure, identifying five separate hormone-related symptoms scales: vasomotor symptoms, urinary incontinence, cognitive/mood changes, vaginal symptoms, and weight gain/appearance concern. Hormone-related symptom scale scores differed by demographic and clinical characteristics according to expectations, suggesting that these five scales from the shortened BCPT checklist are reasonably reliable and valid. Symptom scale scores were only weakly correlated with health-related quality of life scores; however, the pattern of results generally supported the validity of the symptom scales. This study adds to the evidence that breast cancer survivors experience a significant number of hormone-related symptoms. Future clinical trials and quality of life and symptom management intervention studies would benefit from accurate assessment of hormone-related symptoms with the five scales from the shortened BCPT checklist.
PURPOSE: To determine whether there is a direct relationship between diet quality and quality of life in breast cancer survivors. METHODS: Subjects (n = 714) were members of the Health, Eating, Activity, and Lifestyle study, a study of breast cancer prognosis conducted in three areas of the western United States. Approximately 2 years after entry to this study, diet data were collecting using food frequency questionnaires. These data were used to classify diet quality using the Diet Quality Index. Approximately 10 months later, data on quality of life were gathered using the Medical Outcomes Study 36-Item short form health survey. RESULTS: After controlling for age, education, race/ethnicity, body mass index, stage of disease, and time from diagnosis to quality of life measurement, women with excellent diet quality had significantly better scores than women with poor diet quality for overall mental health functioning and for 3 of 4 mental health subscale scores and 2 of 4 physical health subscale scores. CONCLUSION: Post-diagnosis diet quality is directly associated with subsequent mental and physical functioning in breast cancer survivors. This association is stronger for mental functioning than for physical functioning. The association remains strong after control for potential confounding variables.
BACKGROUND: Levels of physical activity (PA) contribute to health status and outcomes directly and indirectly via the effects of PA on obesity and other risk factors. Much past surveillance has focused on leisure-time physical activity (LTPA), but this may bias estimates of prevalence. This study explores inclusion of non-leisure-time walking and bicycling (NLTWB) used for transportation on the prevalence of adherence to PA recommendations and the magnitude of apparent disparities in adherence for California adults. METHODS: Results of the 2001 California Health Interview Survey, a large (n = 55,151) telephone survey were analyzed in 2005 using tabulation and logistic regression. RESULTS: Higher levels of LTPA were associated with youth, males, education, income, Pacific Islanders, and non-Hispanic (NH) whites. Inclusion of NLTWB reduced these differences for all five variables. The largest decreases in disparities in adherence occurred for race/ethnicity, education, and income, with decreases in adherence differences from approximately 18% to 7% for NH white vs Latino, approximately 27% to 16% for more than high school versus less than high school, and approximately 25% to 11% for more than 300% versus less than 100% of poverty level. Logistic regression comparing adherence gives similar results. For example, in respondents with more than high school education versus less than high school education (referent), the odds ratio changed from 2.23 (95% confidence interval [CI] = 2.0-2.4) to 1.7 (1.6-1.9) after the inclusion of NLTWB. CONCLUSIONS: Assessment of PA in multiple domains is required to understand differences in total levels of PA for people with different incomes, education levels, and racial/ethnic backgrounds. Inclusion of NLTWB reduces but does not eliminate disparities in adherence to recommended levels of PA.
OBJECTIVE: To profile and compare the content and presentation of written communications related to informed decision-making about mammography. METHODS: Materials from 16 screening programs organized at the national or regional level were analyzed according to five major information domains suggested by the international literature. RESULTS: A majority of countries provided information on the program (interval, cost and quality). There was considerable variability in comprehensiveness of elements in the domains, e.g., test characteristics (false positive/negative) and pros and cons of screening. The majority noted the likelihood of recall for further tests, few commented on the risks of additional tests or finding unimportant tumors. The audit also found variation in presentation (words and pictures). CONCLUSIONS: Presentation of comprehensive, but balanced information on screening benefits and risks is complex and daunting. Issues such as framing effects, coupled with debate about screening efficacy are challenging to the design of effective information tools. The objective of increasing screening prevalence at the population level must be balanced with objectively presenting complete and clear information. Additional research is needed on how information (and mode of presentation) impact screening decisions. PRACTICE IMPLICATIONS: Public health officials need to articulate their objectives and review written communication according to important decision-making domains.
Understanding the prevalence and demographic correlates of physical activity is important for public health and epidemiological research. This analysis examines the association between acculturation and physical activity in a large (approximately 5,000) sample of Hispanic adults from the 2000 National Health Interview Survey. Scores for eight questions concerning language use were summed to produce an acculturation index. Factor analysis indicated that these questions assessed a single underlying construct. Self-reported adherence to recommendations concerning leisure time physical activity increased from 22. 6% in the least acculturated tertile to 47% in the most acculturated tertile. In contrast, prevalence of walking or bicycling for errands decreased from 25.2 to 18.2%, and prevalence of standing or walking during most of the day decreased from 82.8 to 65.6% as acculturation increased. Thus, patterns of physical activity associated with leisure versus nonleisure time differed among Hispanics with varying acculturation levels. Alternatively, cultural factors may have differential effects on responses to questions concerning leisure and nonleisure time physical activity. In either case, assessing both types of activity is important for monitoring and understanding Hispanic health behaviors and interpreting epidemiological studies that involve physical activity in Hispanics.
PURPOSE: To retrospectively evaluate the range of performance outcomes of the radiologist in an audit of screening mammography by using a representative sample of U.S. radiologists to allow development of performance benchmarks for screening mammography. MATERIALS AND METHODS: Institutional review board approval was obtained, and study was HIPAA compliant. Informed consent was or was not obtained according to institutional review board guidelines. Data from 188 mammographic facilities and 807 radiologists obtained between 1996 and 2002 were analyzed from six registries from the Breast Cancer Surveillance Consortium (BCSC). Contributed data included demographic information, clinical findings, mammographic interpretation, and biopsy results. Measurements calculated were positive predictive values (PPVs) from screening mammography (PPV(1)), biopsy recommendation (PPV(2)), biopsy performed (PPV(3)), recall rate, cancer detection rate, mean cancer size, and cancer stage. Radiologist performance data are presented as 50th (median), 10th, 25th, 75th, and 90th percentiles and as graphic presentations by using smoothed curves. RESULTS: There were 2 580 151 screening mammographic studies from 1 117 390 women (age range, <30 to >/=80 years). The respective means and ranges of performance outcomes for the middle 50% of radiologists were as follows: recall rate, 9.8% and 6.4%-13.3%; PPV(1), 4.8% and 3.4%-6.2%; and PPV(2), 24.6% and 18.8%-32.0%. Mean cancer detection rate was 4.7 per 1000, and the median [corrected] mean size of invasive cancers was 13 mm. The range of performance outcomes for the middle 80% of radiologists also was presented. CONCLUSION: Community screening mammographic performance measurements of cancer outcomes for the majority of radiologists in the BCSC surpass performance recommendations. Recall rate for almost half of radiologists, however, is higher than the recommended rate.
PURPOSE: To investigate the association between physical activity (PA) and mammographic density in the year before diagnosis in a population-based sample of 474 women diagnosed with stage 0-IIIA breast cancer and enrolled in the Health, Eating, Activity, and Lifestyle Study. METHODS: We collected information on PA during an interview administered at a baseline visit scheduled within the first year after diagnosis. Participants recalled the type, duration, and frequency of different PAs for the year prior to their diagnosis. Dense area and percent density were estimated, from mammograms imaged approximately 1 year before diagnosis, as a continuous measure using a computer-assisted software program. Analysis of covariance methods were used to obtain mean density across PA tertiles adjusted for confounders. We stratified analyses by menopausal status and body mass index (BMI) because these factors strongly influence density. RESULTS: We observed a statistically significant decline in mammographic dense area (p for trend = 0.046) and percent density (p for trend = 0.026) with increasing level of sports/recreational PA in postmenopausal women with a BMI > or = 30 kg/m2. Conversely, in premenopausal women with a BMI < 30 kg/m2, we observed a statistically significant increase in percent density with increasing level of sports/recreational PA (p for trend = 0.037). CONCLUSIONS: Both mammographic dense area and percent density are inversely related to level of sports/recreational PA in obese postmenopausal women. Increasing PA among obese postmenopausal women may be a reasonable intervention approach to reduce mammographic density.
BACKGROUND: The diagnosis of ductal carcinoma in situ (DCIS) is increasing, although to the authors' knowledge there is no consensus regarding optimal treatment. This analysis of women treated with breast-conserving surgery (BCS) evaluated the impact of radiation therapy (RT) in patient outcomes. METHODS: The current study included a population-based sample of 1103 women residing in selected Surveillance, Epidemiology, and End Results (SEER) registries who were diagnosed with DCIS between 1991-1992. Data were obtained from the registry, physician follow-up, and pathology reports. Physicians were contacted in 1999 to determine whether the patient had developed a second event in the ipsilateral breast. For second events, pathology reports were reviewed to determine the presence of in situ or invasive disease. Registry data through 2001 were used to assess death rates and cause of death. Cox proportional hazards and logistic regression models were used to evaluate the rates of second events and breast carcinoma deaths between women treated with and without RT. RESULTS: Over an average of 91 months, 13.2% of women developed a second event. Rates of second events were 11% for women treated with BCS and RT compared with 15% for women treated with BCS only (adjusted hazards ratio, 0.64; 95% confidence interval, 0.44-0.92). Women receiving RT were significantly less likely to develop invasive breast carcinoma in the ipsilateral breast (adjusted odds ratio, 0.40). By 2001, the rate of death from breast carcinoma was 2.7%; in the group of women treated with BCS only compared with 0.8% in the group of women treated with BCS with RT. CONCLUSIONS: Among a population-based cohort, RT was found to significantly reduce the risk of second events in the ipsilateral breast, particularly invasive tumors, although not to the extent reported in clinical trials.