Amy Trentham-Dietz

Physical Activity and Survival after Diagnosis of Invasive Breast Cancer

Previous studies suggest that increased physical activity may lower the risk of breast cancer incidence, but less is known about whether levels of physical activity after breast cancer diagnosis can influence survival. We prospectively examined the relation between postdiagnosis recreational physical activity and risk of breast cancer death in women who had a previous invasive breast cancer diagnosed between 1988 and 2001 (at ages 20-79 years). All women completed a questionnaire on recent postdiagnosis physical activity and other lifestyle factors. Among 4,482 women without history of recurrence at the time of completing the questionnaire, 109 died from breast cancer within 6 years of enrollment. Physical activity was expressed as metabolic equivalent task-hours per week (MET-h/wk); hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression. After adjusting for age at diagnosis, stage of disease, state of residence, interval between diagnosis and physical activity assessment, body mass index, menopausal status, hormone therapy use, energy intake, education, family history of breast cancer, and treatment modality compared with women expending <2.8 MET-h/wk in physical activity, women who engaged in greater levels of activity had a significantly lower risk of dying from breast cancer (HR, 0.65; 95% CI, 0.39-1.08 for 2.8-7.9 MET-h/wk; HR, 0.59; 95% CI, 0.35-1.01 for 8.0-20.9 MET-h/wk; and HR, 0.51; 95% CI, 0.29-0.89 for ≥21.0 MET-h/wk; P for trend = 0.05). Results were similar for overall survival (HR, 0.44; 95% CI, 0.32-0.60 for ≥21.0 versus <2.8 MET-h/wk; P for trend <0.001) and were similar regardless of a woman’s age, stage of disease, and body mass index. This study provides support for reduced overall mortality and mortality from breast cancer among women who engage in physical activity after breast cancer diagnosis. (Cancer Epidemiol Biomarkers Prev 2008;17(2):379–86)

Socioeconomic risk factors for breast cancer: distinguishing individual- and community-level effects.

Background: Women are at higher risk of breast cancer if they have higher socioeconomic status (SES) or live in higher SES or urban communities. We examined whether women living in such communities remained at greater risk of breast cancer after controlling for individual education and other known individual-level risk factors. Methods: Data were from a population-based, breast cancer case-control study conducted in Wisconsin from 1988 to 1995 (n = 14,667). Data on community SES and urbanicity come from the 1990 census, measured at the census tract and zip code levels. We evaluated relationships between individual- and community-level variables and breast cancer risk using multilevel logistic regression models with random community intercepts. Results: After controlling for individual education and other individual-level risk factors (age, mammography use, family history of breast cancer, parity, age at first birth, alcohol intake, body mass index, hormone replacement use, oral contraceptive use, and menopausal status), women living in the highest SES communities had greater odds of having breast cancer than women living in the lowest SES communities (1.20; 95% confidence interval = 1.05–1.37). Similarly, the odds were greater for women in urban versus rural communities (1.17; 1.06–1.28). Conclusions: Community SES and urbanicity are apparently not simply proxies for individual SES. Future research should examine why living in such communities itself is associated with greater risk of breast cancer.

Risk Factors for Breast Cancer for Women Aged 40 to 49 Years: A Systematic Review and Meta-analysis

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.

Prevalence and Treatment of Menopausal Symptoms Among Breast Cancer Survivors

Women diagnosed with breast cancer often experience early menopause secondary to treatment effects, yet physicians may be reluctant to prescribe hormone replacement therapy (HRT) because of the potential increased risk of recurrence. To assess the burden of menopausal symptoms, HRT use, and alternative treatments in recent breast cancer survivors, a population-based, case-control study was conducted among breast cancer survivors and age-matched controls. Wisconsin women 18-69 years old with a new diagnosis of breast cancer 8-11 months prior to interview (n = 110) and control subjects randomly selected from population lists (n = 73) responded to a standardized telephone questionnaire that elicited information on menopausal symptoms, estrogen and alternative therapies (prescription medications, vitamins, herbal preparations, soy products, acupuncture, chiropractic) used to alleviate symptoms. We used multivariate logistic regression to obtain odds ratios and 95% confidence intervals (CI) for symptoms of menopause, use of estrogen, and use of alternative therapies. Breast cancer survivors were 5.3 (95% CI 2.7-10.2) times more likely to experience symptoms, 25 (95% CI 8.3-100) times less likely to use estrogen, and 7.4 (95% CI 2.5-21.9) times more likely to use alternatives than controls. Soy, vitamin E, and herbal remedies were the most common alternative therapies reported by participants; use was greater in cases compared to controls. Most soy users reported increasing soy products specifically to reduce the chances of a diagnosis of recurrent breast cancer. Among cases, tamoxifen users (n = 62) reported a higher prevalence of symptoms and a higher prevalence of alternative treatments. This is the first population-based survey of menopausal symptoms and treatments that compares breast cancer cases with disease-free controls. Cases are both more likely to experience menopausal symptoms and less likely to use HRT than controls. Instead, cases treat menopausal symptoms with vitamin E and soy products, even though the safety and efficacy of these therapies are unproven. The increased use of soy products in this population has not been previously documented.

Body mass index before and after breast cancer diagnosis: Associations with all-cause, breast cancer, and cardiovascular disease mortality

Background: Factors related to improving outcomes in breast cancer survivors are of increasing public health significance. We examined postdiagnosis weight change in relation to mortality risk in a cohort of breast cancer survivors. Methods: We analyzed data from a cohort of 3,993 women with ages 20 to 79 years living in New Hampshire, Massachusetts, or Wisconsin with invasive nonmetastatic breast cancers diagnosed in 1988 to 1999 identified through state registries. Participants completed a structured telephone interview 1 to 2 years after diagnosis and returned a mailed follow-up questionnaire in 1998 to 2001 that addressed postdiagnosis weight and other factors. Vital status information was obtained from the National Death Index through December 2005. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models and adjusted for prediagnosis weight, age, stage, smoking, physical activity, and other important covariates. Results: During an average 6.3 years of follow-up from the postdiagnosis questionnaire, we identified 421 total deaths, including 121 deaths from breast cancer and 95 deaths from cardiovascular disease. Increasing postdiagnosis weight gain and weight loss were each associated with greater all-cause mortality. Among women who gained weight after breast cancer diagnosis, each 5-kg gain was associated with a 12% increase in all-cause mortality (P = 0.004), a 13% increase in breast cancer–specific mortality (P = 0.01), and a 19% increase in cardiovascular disease mortality (P = 0.04). Associations with breast cancer mortality were not modified by prediagnosis menopausal status, cigarette smoking, or body mass index. Conclusion: These findings suggest that efforts to minimize weight gain after a breast cancer diagnosis may improve survival. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1403–9)

Weight change and risk of postmenopausal breast cancer (United States)

AbstractObjective: Although many studies have shown that higher weight increases the risk of postmenopausal breast cancer, some aspects of this association are unclear. In order to examine the risk associated with different patterns of weight change, we analyzed data from a large case–control study of postmenopausal breast cancer. Methods: Participants included women aged 50–79 years (n = 5031) who are newly diagnosed with invasive breast cancer in Massachusetts, New Hampshire, and Wisconsin. Similarly-aged population controls (n = 5255) were selected at random from drivers license files and Medicare beneficiary lists. Height, weight, and information on other breast cancer risk factors were ascertained by structured telephone interviews from 1992 to 1995, and logistic regression was used to estimate multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Women in the top quintile groups for height at age 20, recent weight, and recent body mass index had significantly increased risks of breast cancer. Among women who reached their highest adult weight at younger ages (≤45 years), increasing weight loss since that age was associated with a reduced risk of postmenopausal breast cancer (OR 0.90, CI 0.84–0.98, per 5 kg). However, weight loss among women whose highest weight occurred after age 45 was not associated with risk (OR 1.00, CI 0.95–1.05, per 5 kg). Weight gain since the lowest adult weight increased risk by 8% for each 5 kg of gain (OR 1.08, CI 1.06–1.11). Temporary weight cycling (weight loss followed by weight gain) was not associated with increased risk. Conclusions: Weight gain clearly increased risk of postmenopausal breast cancer. These data lend further support to efforts aimed at helping women avoid weight gain as they age.

Geocoding addresses from a large population-based study: lessons learned.

Background Geographic information systems (GIS) and spatial statistics are useful for exploring the relation between geographic location and health. The ultimate usefulness of GIS depends on both completeness and accuracy of geocoding (the process of assigning study participants’ residences latitude/longitude coordinates that closely approximate their true locations, also known as address matching). The goal of this project was to develop an iterative geocoding process that would achieve a high match rate in a large population-based health study. Methods Data were from a study conducted in Wisconsin using mailing addresses of participants who were interviewed by telephone from 1988 to 1995. We standardized the addresses according to US Postal Service guidelines, used desktop GIS geocoding software and two versions of the Topologically Integrated Geographic Encoding and Referencing street maps, accessed Internet mapping engines for problematic addresses, and recontacted a small number of study participants’ households. We also tabulated the project’s cost, time commitment, software requirements, and brief notes for each step and their alternatives. Results Of the 14,804 participants, 97% were ultimately assigned latitude/longitude coordinates corresponding to their respective residences. The remaining 3% were geocoded to their zip code centroid. Conclusion The multiple methods described in this work provide practical information for investigators who are considering the use of GIS in their population health research.

Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk

Background:Bisphosphanates are used primarily for the prevention and treatment of osteoporosis, and are also indicated for osseous complications of malignancy. In addition to their bone resorption properties, the most commonly used nitrogen-containing bisphosphonate compounds also inhibit protein prenylation, and thus may exert anti-tumour properties.Methods:To evaluate whether the use of these drugs may be associated with cancer, specifically breast cancer, we conducted a population-based case–control study in Wisconsin from 2003 to 2006. Participants included 2936 incident invasive breast cancer cases and 2975 population controls aged <70 years. Bisphosphonate use and potential confounders were assessed by interview.Results:Using multivariable logistic regression, the odds ratio for breast cancer in current bisphosphonate users compared with non-users was 0.67 (95% confidence interval 0.51–0.89). Increasing duration of use was associated with a greater reduction in risk (P-trend=0.01). Risk reduction was observed in women who were not obese (P-interaction=0.005).Conclusion:These results are suggestive of an additional benefit of the common use of bisphosphonates, in this instance, the reduction in breast cancer risk.

Obesity, diabetes, and other factors in relation to survival after endometrial cancer diagnosis

Endogenous and exogenous sources of estrogen and characteristics altering these hormone levels have been related to endometrial cancer risk; however, their relationship to survival following diagnosis is less clear. In a population-based study, we examined whether mortality after endometrial cancer diagnosis was affected by prediagnosis obesity, diabetes, smoking, oral contraceptive use, parity, or postmenopausal hormone (PMH) use. Eligible women, aged 40–79 years, diagnosed from 1991–1994 with incident invasive endometrial cancer and identified through the Wisconsin statewide mandatory cancer registry were invited to participate. Of 745 eligible cases, 166 women were deceased after 9.3 years of follow-up, with 43 attributable to endometrial cancer, based upon vital records linkage. Hazard rate ratios (HRR) and 95% confidence intervals were adjusted for age at diagnosis, menopausal status, stage of disease, and other exposures of interest. Obese women (body mass index [BMI] ≥30 kg/m2) prior to endometrial cancer diagnosis had an increased risk of both all-cause (HRR = 1.6, 95% CI 1.0–2.5) and endometrial cancer (HRR = 2.0, 95% CI 0.8–5.1) mortality, compared with nonoverweight women (BMI < 25 kg/m2). Endometrial cancer cases with diabetes also had an increased risk of all-cause mortality compared with nondiabetic women (HRR = 1.7, 95% CI 1.1–2.5), although there was no association with endometrial cancer mortality. There were no associations between PMH use, oral contraceptive use, parity, or smoking and mortality from any cause. The results suggest that history of obesity and diabetes may increase risk of mortality after endometrial cancer diagnosis; modification of these characteristics may improve survival after endometrial cancer diagnosis.

A Sustained Decline in Postmenopausal Hormone Use: Results From the National Health and Nutrition Examination Survey, 1999–2010

OBJECTIVE: Short-term declines in postmenopausal hormone use were observed after the Womens Health Initiative trial results in 2002. Although concerns about the trials generalizability have been expressed, long-term trends in hormone use in a nationally representative sample have not been reported. We sought to evaluate national trends in the prevalence of hormone use and to assess variation by type of formulation and patient characteristics. METHODS: We examined postmenopausal hormone use during 1999–2010 using cross-sectional data from 10,107 women aged 40 years and older in the National Health and Nutrition Examination Survey. RESULTS: In 1999–2000, the prevalence of oral postmenopausal hormone use was 22.4% (95% confidence interval [CI] 19.0–25.8) overall, 13.3% (95% CI 11.0–15.5) for estrogen only, and 8.3% (95% CI 6.2–10.4) for estrogen plus progestin. A sharp decline in use of all formulations occurred in 2003–2004, when the overall prevalence decreased to 11.9% (95% CI 9.6–14.2). This decline was initially limited to non-Hispanic whites; use among non-Hispanic blacks and Hispanics did not decline substantially until 2005–2006. Hormone use continued to decline through 2009–2010 across all patient demographic groups, with the current prevalence now at 4.7% (95% CI 3.3–6.1) overall, 2.7% (95% CI 1.9–3.4) for estrogen only, and 1.7% (95% CI 0.7–2.7) for estrogen plus progestin. Patient characteristics currently associated with hormone use include history of hysterectomy, non-Hispanic white race or ethnicity, and income. CONCLUSION: Postmenopausal hormone use in the United States has declined in a sustained fashion to low levels across a wide variety of patient subgroups. LEVEL OF EVIDENCE: II