Published Research Articles
Full-text copies of these articles can usually be obtained through your local public library.
CARE [The Women's Contraceptive and Reproductive Experiences Study]
Title
The NICHD Women's Contraceptive and Reproductive Experiences Study: Methods and Operational Results
Authors
Marchbanks PA, McDonald JA, Wilson HG, Burnett NM, Daling JR, Bernstein L, Malone KE, Strom BL, Norman SA, Weiss LK, Liff JM, Wingo PA, Burkman RT, Folger SG, Berlin JA, Deapen DM, Ursin G, Coates RJ, Simon MS, Press MF, Spirtas R.
Source
Ann Epidemiol 2002; 12(4):213-221
Abstract
This paper presents methods and operational results of a population-based case-control study examining the effects of oral contraceptive use on breast cancer risk among white and black women aged 35-64 years in five U.S. locations. Cases were women newly diagnosed with breast cancer during July 1994 through April 1998. Controls were identified through random digit dialing (RDD) using unclustered sampling with automated elimination of nonworking numbers. Sampling was density-based, with oversampling of black women. In-person interviews were conducted from August 1994 through December 1998. Blood samples were obtained from subsets of cases and controls, and tissue samples were obtained from subsets of cases. A computerized system tracked subjects through study activities. Special attention was devoted to minimizing exposure misclassification, because any exposure-disease associations were expected to be small. An estimated 82% of households were screened successfully through RDD. Interviews were completed for 4575 cases (2953 whites; 1622 blacks) and 4682 controls (3021 whites; 1661 blacks). Interview response rates for cases and controls were 76.5% and 78.6%, respectively, with lower rates for black women and older women. The methodologic details of this large collaboration may assist researchers conducting similar investigations.
Title
Relation of Regimens of Combined Hormone Replacement Therapy to Lobular, Ductal, and Other Histologic Types of Breast Carcinoma
Authors
Daling JR, Malone KE, Doody DR, Voigt LF, Bernstein L, Coates RJ, Marchbanks PA, Norman SA, Weiss LK, Ursin G, Berlin JA, Burkman RT, Deapen D, Folger SG, McDonald JA, Simon MS, Strom BL, Wingo PA, Spirtas R.
Source
Cancer 2002; 95(12):2455-2464
Abstract
The incidence of invasive lobular carcinoma has been increasing among postmenopausal women in some parts of the United States. Part of this may be due to changes in classification over time. However, the use of combined (estrogen and progestin) hormone replacement therapy (CHRT) also has increased during the last decade and may account in part for the increase in invasive lobular breast carcinoma. A large, multicenter case-control study of Caucasian and African-American women who were diagnosed at age < 65 years with their first invasive breast tumor from July 1, 1994 through April 30, 1998 was conducted. In-person interviews were conducted with 1749 postmenopausal patients, and their responses were compared with the responses of 1953 postmenopausal control women identified through random-digit dialing who met the study criteria of being postmenopausal at the time of diagnosis. Polytomous logistic regression was used to calculate the odds ratio (OR) as an estimate of the relative risk and to compute the 95% confidence interval (95%CI) associated with the use of various regimens of hormone replacement therapy (HRT) among women diagnosed with ductal breast carcinoma, lobular (or mixed lobular and ductal) breast carcinoma, and a grouping of other histologic types of breast carcinoma. Ever use of unopposed estrogen therapy (ERT) was not associated with an increase in the risk of any histologic type of breast carcinoma. The risk of invasive lobular breast carcinoma and the risk of breast carcinoma of the grouping of other histologies increased among women currently using CHRT (OR, 2.2; 95%CI, 1.4-3.3; and OR, 1.9; 95%CI, 1.0-3.4, respectively). The risk increase was greater for the mixed lobular-ductal type than for the pure lobular type of breast carcinoma, although the difference was not statistically significant. There was some indication that >or= 5 years of continuous CHRT (>or= 25 days per month of progestin) was associated with a higher risk of lobular breast carcinoma (OR, 2.5; 95%CI, 1.4-4.3) compared with sequential CHRT (< 25 days per month of progestin; OR, 1.5; 95%CI, 0.8-2.6). Current use of continuous CHRT was only moderately associated with risk of ductal breast carcinoma. Postmenopausal women who take CHRT appear to be at an increased risk of lobular breast carcinoma. Data from this study suggest that neither ERT use nor CHRT substantially increase the risk of ductal breast carcinoma among women age < 65 years.
Title
Oral Contraceptives and the Risk of Breast Cancer
Authors
Marchbanks PA, McDonald JA, Wilson HG, Folger SG, Mandel MG, Daling JR, Bernstein L, Malone KE, Ursin G, Strom BL, Norman SA, Wingo PA, Burkman RT, Berlin JA, Simon MS, Spirtas R, Weiss LK.
Source
N Engl J Med 2002; 346(26):2025-2032
Abstract
It is uncertain whether the use of an oral contraceptive increases the risk of breast cancer later in life, when the incidence of breast cancer is increased. We conducted a population-based, case-control study to determine the risk of breast cancer among former and current users of oral contraceptives. We interviewed women who were 35 to 64 years old. A total of 4575 women with breast cancer and 4682 controls were interviewed. Conditional logistic regression was used to calculate odds ratios as estimates of the relative risk (incidence-density ratios) of breast cancer. The relative risk was 1.0 (95 percent confidence interval, 0.8 to 1.3) for women who were currently using oral contraceptives and 0.9 (95 percent confidence interval, 0.8 to 1.0) for those who had previously used them. The relative risk did not increase consistently with longer periods of use or with higher doses of estrogen. The results were similar among white and black women. Use of oral contraceptives by women with a family history of breast cancer was not associated with an increased risk of breast cancer, nor was the initiation of oral-contraceptive use at a young age. Among women from 35 to 64 years of age, current or former oral-contraceptive use was not associated with a significantly increased risk of breast cancer.
Title
Good News about Oral Contraceptives
Authors
Davidson NE, Helzlsouer KJ.
Source
N Engl J Med 2002; 346(26):2078-2079
Abstract
This is a editorial comment related to the previous article by Marchbanks, et al., Oral Contraceptives and the Risk of Breast Cancer.
Title
Association of Regimens of Hormone Replacement Therapy to Prognostic Factors among Women Diagnosed with Breast Cancer Aged 50-64 Years
Authors
Daling JR, Malone KE, Doody DR, Voigt LF, Bernstein L, Marchbanks PA, Coates RJ, Norman SA, Weiss LK, Ursin G, Burkman RT, Deapen D, Folger SG, McDonald JA, Simon MS, Strom BL, Spirtas R.
Source
Cancer Epidemiol Biomarkers Prev 2003; 12(11):1175-1181
Abstract
This study was conducted to assess the histopathological features of breast cancers in women diagnosed with breast cancer at 50-64 years of age who have and have not used hormone replacement therapy (HRT). A case-case analysis of the tumors from women aged 50-64 years who participated in a multicenter population-based case-control study of invasive breast cancer was conducted. In-person interviews collected a detailed history of all episodes of hormone use. Information was collected on selected tumor characteristics from 2346 women with breast cancer. Polytomous logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs), contrasting the histopathological characteristics of the tumors of women who used various regimens of HRT with those of women who have never used HRT. The tumors of cases who used each regimen of HRT were smaller and of earlier stage than those of non-HRT users. Adjustment for screening diminished the magnitude of the effect, and only cases who used estrogen alone (estrogen replacement therapy) had reduced odds of being diagnosed with later-stage disease (regional or distant) than cases who never used HRT (OR, 0.7; 95% CI, 0.6-0.9). Higher proportions of estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors were seen in cases who used any regimen of HRT versus those who did not use HRT. However, after adjustment for age and race, only the tumors of cases who used continuous combined HRT remained more likely to be ER+ and PR+ [OR ER- = 0.6 (95% CI, 0.4-0.9) and OR PR- = 0.5 (95% CI, 0.4-0.7)]. The tumors of women with breast cancer who used HRT have some better prognostic factors than those of women who have not used HRT. However, with the exception of the results noted above, this advantage may be due to the racial and age differences in those who use the various regimens of HRT and the effect of more frequent screening among HRT users, leading to earlier diagnosis.
Title
Combined effect of oral contraceptive use and hormone replacement therapy on breast cancer risk in postmenopausal women
Authors
Norman SA, Berlin JA, Weber AL, Strom BL, Daling JR, Weiss LK, Marchbanks PA, Bernstein L, Voigt LF, McDonald JA, Ursin G, Liff JM, Burkman RT, Malone KE, Simon MS, Folger SG, Deapen D, Wingo PA, Spirtas R.
Source
Cancer Causes Control 2003; 14(10):933-943
Abstract
We examined breast cancer risk related to lifetime exposure to oral contraceptives (OCs) and hormone replacement therapy (HRT) in postmenopausal women. The Women's 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. Forty-five percent 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). 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.
Title
Alcohol exposure and breast cancer: results of the women's contraceptive and reproductive experiences study
Authors
McDonald JA, Mandel MG, Marchbanks PA, Folger SG, Daling JR, Ursin G, Simon MS, Bernstein L, Strom BL, Norman SA, Malone KE, Weiss LK, Burkman RT, Weber AL, Spirtas R.
Source
Cancer Epidemiol Biomarkers Prev 2004; 13(12):2106-2116
Abstract
The objective of this study was to explore associated biological outcomes and clarify the role of timing of exposure in the alcohol-breast cancer relationship. In a population-based study of 4,575 women ages 35 to 64 years diagnosed with invasive breast cancer between 1994 and 1998 and 4,682 controls, we collected details of lifetime alcohol use and factors that could confound or modify the alcohol-breast cancer relationship. We used conditional logistic regression to compute the odds of breast cancer among drinkers relative to nondrinkers at all ages and at ages 35 to 49 and 50 to 64 years separately. Recent consumption (at reference age minus two) of >/=7 drinks per week was associated with increased risk [odds ratio (OR), 1.2; 95% CI, 1.01-1.3] and evidence of dose response was observed. Most of the excess was observed among women ages 50-64 years (OR 1.3; 95% CI, 1.1-1.6), although the test for age interaction was not statistically significant. Exposure later in life seemed more important than early exposure. Excess breast cancer associated with recent consumption was restricted to localized disease. When outcome was examined according to tumor hormone receptor status, highest risks were observed for estrogen receptor-positive/progesterone receptor-negative tumors (OR 1.6; 95% CI, 1.2-2.3). The effect of timing of alcohol exposure on breast cancer risk is complicated and will require additional study focused on this one issue. Further work is needed to explain how alcohol exposure, sex hormones, and tumor receptor status interact.
Title
Absence of an effect of injectable and implantable progestin-only contraceptives on subsequent risk of breast cancer
Authors
Strom BL, Berlin JA, Weber AL, Norman SA, Bernstein L, Burkman RT, Daling JR, Deapen D, Folger SG, Malone KE, Marchbanks PA, Simon MS, Ursin G, Weiss LK, Spirtas R.
Source
Contraception 2004; 69(5):353-360
Abstract
Animal data indicate that both estrogens and progestins could be carcinogenic and that progestins could serve as tumor promoters. Human studies have not confirmed an increased risk of breast cancer from long-term use of oral contraceptives, but have shown an increased risk from hormone replacement therapy including progestins. The present study analyzed the relationship between breast cancer and use of injectable and implantable progestin-only contraceptives. Analyses were performed on data collected in a population-based, multicenter, case-control study, the Women's Contraceptive and Reproductive Experiences Study of the National Institute of Child Health and Human Development. The study involved 4575 randomly sampled cases with invasive breast cancer diagnosed between 1994 and 1998, and 4682 controls, identified using random digit dialing. We assessed the association between exposure to injectable contraceptives and risk of breast cancer. The use of injectable contraceptives was not associated with an increased risk of breast cancer [odds ratio (OR) = 0.9, 95% confidence interval (CI): 0.7, 1.2]. Risk was not increased among current users, defined as women who used injectable contraceptives within 1 year of the reference date (OR = 0.7, 95% CI: 0.4, 1.3) or those who initiated use in the 5 years immediately preceding the reference date (OR = 0.9, 95% CI: 0.5, 1.4), or with use beginning before age 35 (OR = 0.9, 95% CI: 0.6, 1.3). Among users, risk increased with increasing duration of use (p = 0.03). However, short-term users (<6 months duration) were at decreased risk relative to never users (OR = 0.6, 95% CI: 0.4, 1.0). When the short-term users were then excluded from the duration-response analysis, the slope of the duration-response became slightly (and nonsignificantly) negative. Risk was not increased among women with 24 or more months of use relative to never users (OR = 1.4, 95% CI: 0.8, 2.5). No increased risk was seen from implantable contraceptives either, although the sample sizes were small. This study does not support an increased risk of breast cancer associated with the use of injectable or implantable progestin-only contraceptives in women aged 35 to 64.
Title
Reproductive factors and risk of breast carcinoma in a study of white and African-American women
Authors
Ursin G, Bernstein L, Wang Y, Lord SJ, Deapen D, Liff JM, Norman SA, Weiss LK, Daling JR, Marchbanks PA, Malone KE, Folger SG, McDonald JA, Burkman RT, Simon MS, Strom BL, Spirtas R.
Source
Cancer 2004; 101(2):353-362
Abstract
Few studies have investigated the association between reproductive factors and the risk of breast carcinoma among African-American women. The authors assessed whether the number of full-term pregnancies, age at first full-term pregnancy, and total duration of breastfeeding were associated with similar relative risk estimates in white and African-American women in a large multicenter, population-based case-control study of breast carcinoma. Case patients were 4567 women (2950 white women and 1617 African-American women) ages 35-64 years with newly diagnosed invasive breast carcinoma between 1994 and 1998. Control patients were 4668 women (3012 white women and 1656 African-American women) who were identified by random-digit dialing and were frequency matched to case patients according to study center, race, and age. Adjusted odds ratios and 95% confidence intervals were estimated using unconditional logistic regression. For white women, the reduction in risk of breast carcinoma per full-term pregnancy was 13% among younger women (ages 35-49 years) and 10% among older women (ages 50-64 years). The corresponding risk reductions for African-American women were 10% and 6%, respectively. Risk decreased significantly with increasing number of full-term pregnancies for both races and both age categories. Duration of lactation was inversely associated with breast carcinoma risk among younger parous white (trend P = 0.0001) and African-American (trend P = 0.01) women. African-American women tended to have more children compared with white women, but parity rates were lower in younger women than in older women in both racial groups. However, breastfeeding was substantially more common in young white women than in young African-American women. Overall, parity and lactation had similar effects on breast carcinoma risk in white and African-American women. If younger African-American women now are giving birth to fewer children than in the past, without a substantial increase in breastfeeding, breast carcinoma rates may continue to increase at a more rapid rate among these women compared with white women.
Title
Racial differences in the familial aggregation of breast cancer and other female cancers
Authors
Simon MS, Korczak JF, Yee CL, Daling JR, Malone KE, Bernstein L, Marchbanks PA, Folger SG, McDonald JA, Norman SA, Strom BL, Deapen D, Ursin G, Burkman RT, Press MF, Schwartz AG, Spirtas R.
Source
Breast Cancer Res Treat 2005; 89(3):227-235
Abstract
Although breast cancer familial aggregation has been studied in Caucasians, information for African-Americans is scant. We used family cancer history from the Women's Contraceptive and Reproductive Experiences study to assess the aggregation of breast and gynecological cancers in African-American and Caucasian families. Information was available on 41,825 first and second-degree relatives of Caucasian and 28,956 relatives of African-American participants. We used a cohort approach in which the relative's cancer status was the outcome in unconditional logistic regression and adjusted for correlated data using generalized estimating equations. Race-specific models included a family history indicator, the relative's age, and type. Relative risk (RR) estimates for breast cancer were highest for first-degree relatives, and the overall RR for breast cancer among case relatives was 1.96 (95% CI = 1.68-2.30) for Caucasian and 1.78 (95% CI = 1.41-2.25) for African-Americans. The effect of CARE participants' reference age on their relatives' breast cancer risk was greatest among first-degree relatives of African-American patients with RRs (95% CI) for ages <45 and > or =45 of 2.97 (1.86-4.74) and 1.48 (1.14-1.92), respectively. Among Caucasians, first-degree relatives of case subjects were at greater risk for ovarian cancer, particularly relatives younger than 45 years (RR (95% CI) = 2.06 (1.02-4.12)), whereas African-American first-degree relatives of case subjects were at increased cervical cancer risk (RR (95% CI) = 2.17 (1.22-3.85). In conclusion, these racially distinct aggregation patterns may reflect different modes of inheritance and/or environmental factors that impact cancer risk.
Title
Lifetime Recreational Exercise Activity and Breast Cancer Risk among Black Women and White Women
Authors
Bernstein L, Patel AV, Ursin G, Sullivan-Halley J, Press MF, Deapen D, Berlin JA, Daling JR, McDonald JA, Norman SA, Malone KE, Strom BL, Liff J, Folger SG, Simon MS, Burkman RT, Marchbanks PA, Weiss LK, Spirtas R.
Source
J Natl Cancer Inst 2005; 97(22):1671-1679
Abstract
Physical inactivity is a potentially modifiable breast cancer risk factor. Because few data on this relationship exist for black women, we examined the relationship between breast cancer risk and lifetime and time- or age-specific measures of recreational exercise activity among white women and among black women. The Women's Contraceptive and Reproductive Experiences Study was a multicenter population-based case-control study of black women and white women aged 35-64 years with newly diagnosed invasive breast cancer. We collected detailed histories of lifetime recreational exercise activity during in-person interviews with 4538 case patients with breast cancer (1605 black and 2933 white) and 4649 control subjects (1646 black and 3033 white). Control subjects were frequency-matched to case patients on age, race, and study site. We examined associations between exercise activity measures (metabolic equivalents of energy expenditure [MET]-hours per week per year) and breast cancer risk overall and among subgroups defined by race, other breast cancer risk factors, and tumor characteristics by use of unconditional logistic regression. All statistical tests were two-sided. Among all women, decreased breast cancer risk was associated with increased levels of lifetime exercise activity (e.g., average MET-hours per week per year, P(trend) = .002). An average annual lifetime exercise activity that was greater than the median level for active control subjects was associated with an approximately 20% lower risk of breast cancer, compared with that for inactivity (for 6.7-15.1 MET-hours/week/year, odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.71 to 0.93; for > or =15.2 MET-hours/week/year, OR = 0.80, 95% CI = 0.70 to 0.92). The inverse associations did not differ between black and white women (for MET-hours/week/year, P(trend) = .003 and P(trend) = .09, respectively; homogeneity of trends P = .16). No modification of risk was observed by disease stage, estrogen receptor status, or any breast cancer risk factor other than first-degree family history of breast cancer. This study supports an inverse association between physical activity and breast cancer among black women and among white women.
Title
Relationship between established breast cancer risk factors and risk of seven different histologic types of invasive breast cancer
Authors
Li CI, Daling JR, Malone KE, Bernstein L, Marchbanks PA, Liff JM, Strom BL, Simon MS, Press MF, McDonald JA, Ursin G, Burkman RT, Deapen D, Spirtas R.
Source
Cancer Epidemiol Biomarkers Prev 2006; 15(5):946-954
Abstract
Important differences in the contributions of certain exposures to the risks of ductal versus lobular breast carcinomas have been observed, but few studies have evaluated the relationships between established breast cancer risk factors and other histologic types. Information on family history of cancer and reproductive, hormonal, anthropometric, and lifestyle characteristics were collected in a multicenter population-based case-control study consisting of 3,463 ductal, 274 lobular, 261 ductal-lobular, 91 medullary, 77 tubular, 70 comedo, and 61 mucinous invasive breast carcinoma cases (ages 35-64 years, newly diagnosed 1994-1998) and 4,682 controls. Associations between each of these histologic types and various exposures were evaluated using polytomous regression. Heterogeneity in the risks of different histologic types of breast cancer was observed for three exposures: menopausal hormone use, body mass index (BMI), and alcohol consumption. Specifically, current use of unopposed estrogen was associated with a reduced risk of ductal carcinoma and increased risk of comedocarcinoma, and current use of estrogen and progestin was associated with elevated risks of ductal-lobular and tubular carcinomas. Among postmenopausal women, BMI was only inversely related to risk of ductal-lobular carcinoma, and alcohol use was only positively related to risk of lobular carcinoma. Variations in the associations between known breast cancer risk factors and risk of different breast cancer histologies were observed. Although these findings require confirmation, and the analyses of some histologic groups were limited by small sample sizes, they provide some insight into the different etiologies of various histologic subtypes of breast cancer.
Title
Benefit of screening mammography in reducing the rate of late-stage breast cancer diagnoses
Authors
Norman SA, Localio AR, Zhou L, Weber AL, Coates RJ, Malone KE, Bernstein L, Marchbanks PA, Liff JM, Lee NC, Nadel MR.
Source
Cancer Causes Control 2006; 17(7):921-929
Abstract
We studied the benefit of modern mammography screening in community settings, evaluating age-related differences in rates of late-stage breast cancer detection. Our multicenter population-based case-control study included 931 black and white women with incident breast cancer (American Joint Commission on Cancer Stage IIB or higher) diagnosed 1994-1998 and 4,016 randomly sampled controls never diagnosed with breast cancer. Adjusted odds ratios (ORs) estimated the relative rate of late-stage diagnosis in screened and non-screened women. Women aged 50-64 at diagnosis with at least one screening mammogram in the previous 2 years were significantly less likely to have late-stage diagnosis (OR = 0.41, 95% CI 0.33-0.52). Results for women aged 40-49 were consistent with a screening benefit, although the confidence interval marginally overlapped the null (OR = 0.81, 95% CI 0.64-1.02). Mammography screening was associated with lower rates of late-stage breast cancer among both premenopausal (OR = 0.64, 95% CI 0.50-0.81) and postmenopausal (OR = 0.44, 95% CI 0.35-0.56) women. With modern mammography in the community, rates of late-stage breast cancer diagnoses are lower in screened compared to non-screened women ages 40 and older, but age-related differences persist.
Title
Breast cancer risk estimates for relatives of white and African American women with breast cancer in the Women's Contraceptive and Reproductive Experiences Study
Authors
Simon MS, Korczak JF, Yee CL, Malone KE, Ursin G, Bernstein L, McDonald JA, Deapen D, Strom BL, Press MF, Marchbanks PA, Burkman RT, Weiss LK, Schwartz AG.
Source
J Clin Oncol 2006; 24(16):2498-2504
Abstract
Family history is a well-recognized risk factor for breast cancer. Familial aggregation and segregation analyses have estimated breast cancer risk based on family history primarily for white women; such information is limited for African American (AA) women. The purpose of this report is to update breast cancer risk estimates associated with a family history of breast cancer for white and AA women. We used family cancer history from 2,676 white and 1,525 AA women with breast cancer (probands) in the population-based National Institute of Child Health and Human Development's Women's Contraceptive and Reproductive Experiences (CARE) Study to estimate age-specific breast cancer risks in their first degree adult female relatives. Cumulative hazard curves were calculated for relatives of all probands using Cox proportional hazards models, and were stratified by the proband's race and age at diagnosis and number of relatives affected. Breast cancer risks for white and AA women with a family history of the disease are similar through age 49 years, but diverge afterwards, with higher risks by age 79 in white women than in AA women (17.5% [SE, 0.9%] v 12.2% [SE, 1.1%]; P < .001). These risks increase as the number of affected first degree relatives increases, reaching 25.2% (SE, 3.4%) and 16.9% (SE, 4.0%) in white and AA women with more than one affected relative, respectively (P=0.3). We found age-related racial differences in breast cancer risk in women with a family history of breast cancer and have updated risk estimates for white and AA women for clinical use.
Title
Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years
Authors
Malone KE, Daling JR, Doody DR, Hsu L, Bernstein L, Coates RJ, Marchbanks PA, Simon MS, McDonald JA, Norman SA, Strom BL, Burkman RT, Ursin G, Deapen D, Weiss LK, Folger S, Madeoy JJ, Friedrichsen DM, Suter NM, Humphrey MC, Spirtas R, Ostrander EA.
Source
Cancer Research 2006;66:8297-8308
Abstract
Although well studied in families at high-risk, the roles of mutations in the BRCA1 and BRCA2 genes are poorly understood in breast cancers in the general population, particularly in Black women and in age groups outside of the very young. We examined the prevalence and predictors of BRCA1 and BRCA2 mutations in 1,628 women with breast cancer and 674 women without breast cancer who participated in a multicenter population-based case-control study of Black and White women, 35 to 64 years of age. Among cases, 2.4% and 2.3% carried deleterious mutations in BRCA1 and BRCA2, respectively. BRCA1 mutations were significantly more common in White (2.9%) versus Black (1.4%) cases and in Jewish (10.2%) versus non-Jewish (2.0%) cases; BRCA2 mutations were slightly more frequent in Black (2.6%) versus White (2.1%) cases. Numerous familial and demographic factors were significantly associated with BRCA1 and, to a lesser extent, BRCA2 carrier status, when examined individually. In models considering all predictors together, early onset ages in cases and in relatives, family history of ovarian cancer, and Jewish ancestry remained strongly and significantly predictive of BRCA1 carrier status, whereas BRCA2 predictors were fewer and more modest in magnitude. Both the combinations of predictors and effect sizes varied across racial/ethnic and age groups. These results provide first-time prevalence estimates for BRCA1/BRCA2 in breast cancer cases among understudied racial and age groups and show key predictors of mutation carrier status for both White and Black women and women of a wide age spectrum with breast cancer in the general population.
Title
Vitamin D receptor polymorphisms and breast cancer risk in a large population-based case-control study
Authors
Malone KE, Daling JR, Doody DR, Bernstein L, Ursin G, Marchbanks PA, Strom BL, Humphrey MC, Ostrander EA.
Source
Breast Cancer Research 2007;9:R84 (Epub ahead of print)
Title
Projecting individualized absolute invasive breast cancer risk in African American women
Authors
Gail MH, Costantino JP, Pee D, Bondy M, Newman L, Selvan M, Anderson GL, Malone KE, Marchbanks PA, Caskill-Stevens W, Norman SA, Simon MS, Spirtas R, Ursin G, Bernstein L.
Source
Journal of the National Cancer Institute 2007;99:1782-1792
Abstract
The Breast Cancer Risk Assessment Tool of the National Cancer Institute (NCI) is widely used for counseling and determining eligibility for breast cancer prevention trials, although its validity for projecting risk in African American women is uncertain. We developed a model for projecting absolute risk of invasive breast cancer in African American women and compared its projections with those from the Breast Cancer Risk Assessment Tool. Data from 1607 African American women with invasive breast cancer and 1647 African American control subjects in the Women's Contraceptive and Reproductive Experiences (CARE) Study were used to compute relative and attributable risks that were based on age at menarche, number of affected mother or sisters, and number of previous benign biopsy examinations. Absolute risks were obtained by combining this information with data on invasive breast cancer incidence in African American women from the NCI's Surveillance, Epidemiology and End Results Program and with national mortality data. Eligibility screening data from the Study of Tamoxifen and Raloxifene (STAR) trial were used to determine how the new model would affect eligibility, and independent data from the Women's Health Initiative (WHI) were used to assess how well numbers of invasive breast cancers predicted by the new model agreed with observed cancers. Tables and graphs for estimating relative risks and projecting absolute invasive breast cancer risk with confidence intervals were developed for African American women. Relative risks for family history and number of biopsies and attributable risks estimated from the CARE population were lower than those from the Breast Cancer Risk Assessment Tool, as was the discriminatory accuracy (i.e., concordance). Using eligibility screening data from the STAR trial, we estimated that 30.3% of African American women would have had 5-year invasive breast cancer risks of at least 1.66% by use of the CARE model, compared with only 14.5% by use of the Breast Cancer Risk Assessment Tool. The numbers of cancers predicted by the CARE model agreed well with observed numbers of cancers (i.e., it was well calibrated) in data from the WHI, except that it underestimated risk in African American women with breast biopsy examinations. The CARE model usually gave higher risk estimates for African American women than the Breast Cancer Risk Assessment Tool and is recommended for counseling African American women regarding their risk of breast cancer.
Title
Protection of mammography screening against death from breast cancer in women aged 40-64 years
Authors
Norman SA, Russell LA, Weber AL, Coates RJ, Zhou L, Bernstein L, Malone KE, Marchbanks PA, Weiss LK, Lee NC, Nadel MR.
Source
Causes & Control 2007;18:909-918
Abstract
This study assessed the efficacy of community-based screening mammography in protecting against breast cancer death, asking whether age differences in efficacy persisted in the 1990s. In a case-control study with follow-up, odds ratios (OR) were used to estimate the relative mortality rates from invasive breast cancer among women with at least one screening mammogram in the two years prior to a baseline reference date compared to non-screened women, adjusting for potential confounding. The multicenter population-based study included 553 black and white women diagnosed during 1994-1998 who died in the following five years, and 4016 controls without breast cancer. Efficacy for reducing the rate of breast cancer death within five years after diagnosis was greater at ages 50-64 years (OR = 0.47, 95% confidence interval (CI) 0.35-0.63) than at ages 40-49 (OR = 0.89, 95% CI 0.65-1.23), and greater among postmenopausal (OR = 0.45, 95% CI 0.33-0.62) than premenopausal women (OR = 0.74, 95% CI 0.53-1.04). Estimates of efficacy were conservative, as shown by sensitivity analyses addressing whether cancer was discovered by a screening mammogram, age at which screening was received, the length of the screening observation window, and years of follow-up after diagnosis. Despite the persistence of age differences in efficacy of mammography screening, with greater observed benefit for women aged 50-64 years, these findings support current screening recommendations for women 40-64 years old.
PACE [Puget Sound Area Breast Cancer Surveillance]
Title
Relation between Use of Antihypertensive Medications and Risk of Breast Carcinoma among Women Ages 65-79 Years
Authors
Li CI, Malone KE, Weiss NS, Boudreau DM, Cushing-Haugen KL, Daling JR.
Source
Cancer 2003; 98(7):1504-1513
Abstract
Limited data are available regarding the incidence of breast carcinoma among users of relatively recently introduced forms of antihypertensive therapy. Although it has been suggested that women who have taken calcium channel blockers (CCBs) have an increased risk and that women who have taken angiotensin-I-converting enzyme (ACE) inhibitors have a decreased risk, currently, no conclusions can be drawn. A population-based case-control study of women ages 65-79 years was conducted in western Washington State. The responses of 975 women who were diagnosed with invasive breast carcinoma during 1997-1999 were compared with the responses of 1007 women in a control group. Associations between use of different types of antihypertensive medications and breast carcinoma incidence were evaluated using logistic regression. Overall, women who had ever used CCBs, beta-blockers, or ACE inhibitors did not have an altered risk of breast carcinoma relative to women who had never used antihypertensive medications. Although the use of immediate-release CCBs, thiazide diuretics, and potassium-sparing diuretics was associated with modestly increased risks of breast carcinoma (odds ratio [OR], 1.5; 95% confidence interval [95% CI], 1.0-2.1; OR, 1.4; 95% CI, 1.1-1.8; and OR, 1.6; 95% CI, 1.2-2.1, respectively), the absence of any trend in the size of excess risk with increasing duration or with current versus former use of these agents argues for a cautious interpretation. The use of particular types of antihypertensive medications, including immediate-release CCBs and certain diuretics, may increase the risk of breast carcinoma among older women. Additional studies are warranted to clarify these potential associations.
Title
The Relationship between Alcohol Use and Risk of Breast Cancer by Histology and Hormone Receptor Status among Women 65-79 Years of Age
Authors
Li CI, Malone KE, Porter PL, Weiss NS, Tang MT, Daling JR.
Source
Cancer Epidemiol Biomarkers Prev 2003; 12(10):1061-1066
Abstract
Alcohol consumption is associated with a moderate increase in breast cancer risk, possibly because alcohol increases estrogen levels in blood. Certain types of breast carcinomas are more hormonally responsive than others, including those that have a lobular histology or are hormone receptor positive, but few studies evaluating alcohol use and breast cancer risk have stratified results by histology or estrogen receptor (ER)/progesterone receptor (PR) status. We conducted a population-based case-control study of women 65-79 years of age in western Washington State. Women (975) diagnosed with invasive breast cancer during 1997-1999 were compared with 1007 controls. Ever-use of alcohol over the past 20 years was associated with a 1.3-fold [95% confidence interval (CI), 1.0-1.5] increased risk of breast cancer, although this increase was primarily limited to women who consumed > or =30.0 g/day of alcohol [odds ratio (OR), 1.7; 95% CI, 1.1-2.6]. Differences in risk by histology were observed: ever-use of alcohol was associated with a 1.8-fold (95% CI, 1.3-2.5) increased risk of lobular cancer but only a 1.2-fold (95% CI, 0.9-1.4) increased risk of ductal cancer. Ever-users of alcohol had an increase in risk of ER+/PR+ tumors (OR, 1.3; 95% CI, 1.1-1.7), but no change in their risks of ER+/PR- or ER-/PR- tumors. Alcohol use appears to be more strongly associated with risk of lobular carcinomas and hormone receptor-positive tumors than it is with other types of breast cancer. These results are consistent with there being an underlying hormonal basis for the known association between alcohol use and breast cancer incidence.
Title
Reproductive and Anthropometric Factors in Relation to the Risk of Lobular and Ductal Breast Carcinoma among Women 65-79 Years of Age
Authors
Li CI, Malone KE, Porter PL, Weiss NS, Tang MT, Daling JR.
Source
Int J Cancer 2003; 107(4):647-651
Abstract
Use of combined estrogen-progestin hormone replacement therapy appears to be associated with an increased risk of invasive lobular breast carcinomas (ILC) and, to a lesser degree, with risk of invasive ductal carcinoma (IDC). Conceivably, ILCs are more hormonally responsive and so may be more strongly associated than IDCs with reproductive and anthropometric characteristics that can influence hormone levels. However, few epidemiologic studies of breast cancer have evaluated these factors by histologic type. We conducted a population-based case-control study of women aged 65-79 years in western Washington State. Responses from 975 women diagnosed with breast cancer during 1997-1999 were compared to those of 1,007 controls. Associations between various reproductive and anthropometric factors and risks of IDC (n = 656) and ILC (n = 196) were evaluated using polytomous logistic regression. Earlier age at menarche, later age at menopause and obesity were more strongly associated with elevated risks of IDC than ILC. Alternatively, oral contraceptive use was associated with an increased risk of ILC but not IDC. Thus, the pattern of results that we observed suggest that factors influencing endogenous hormones and duration of ovarian function may be more strongly associated with IDC risk, while exogenous hormones may be more strongly associated with ILC risk.
Title
Relationship Between Long Durations and Different Regimens of Hormone Therapy and Risk of Breast Cancer
Authors
Li CI, Malone KE, Porter PL, Weiss NS, Tang MT, Cushing-Haugen KL, Daling JR
Source
JAMA 2003; 289(24):3254-3263
Abstract
Women using combined estrogen and progestin hormone replacement therapy (CHRT) have an increased risk of breast cancer; however, data on use for long durations and on risk associated with patterns of use are lacking. The objective of this study was to evaluate relationships between durations and patterns of CHRT use and risk of breast cancer by histological type and hormone receptor status. This population-based, case-control study was conducted in three counties of western Washington State. The participants were 975 women 65-79 years of age diagnosed with invasive breast cancer from April 1, 1997, through May 31, 1999 (histology: 196 lobular cases, 656 ductal cases, 114 cases with other histological type, and 9 cases with an unspecified histological type; estrogen receptor (ER)/progesterone receptor (PR) status: 646 ER+/PR+ cases, 147 ER+/PR- cases, and 101 ER-/PR- cases [6 ER-/PR+ cases and 75 cases with unknown ER/PR status were not included in the analyses herein]) and 1007 population controls. The main outcome measures were fisks of invasive lobular, ductal, ER+/PR+, ER+/PR-, and ER-/PR- breast carcinomas. Women using unopposed estrogen replacement therapy (ERT) (exclusive ERT use), even for 25 years or longer, had no appreciable increase in risk of breast cancer, although the associated odds ratios were not inconsistent with a possible small effect. Ever users of CHRT (includes CHRT users who also had used ERT) had a 1.7-fold (95% confidence interval [CI], 1.3-2.2) increased risk of breast cancer, including a 2.7-fold (95% CI, 1.7-4.3) increased risk of invasive lobular carcinoma, a 1.5-fold (95% CI, 1.1-2.0) increased risk of invasive ductal carcinoma, and a 2.0-fold (95% CI, 1.5-2.7) increased risk of ER+/PR+ breast cancers. The increase in risk was greatest in those using CHRT for longer durations (users for 5-14.9 years and >or=15 years had 1.5-fold [95% CI, 1.0-2.3] and 1.6-fold [95% CI, 1.0-2.6] increases in risk of invasive ductal carcinoma, respectively, and 3.7-fold [95% CI, 2.0-6.6] and 2.6-fold [95% CI, 1.3-5.3] increases in risk of invasive lobular carcinoma, respectively. Associations of similar magnitudes were seen among users of both sequential and continuous CHRT. Risks of ER+/PR- and ER-/PR- tumors were not increased by use of any form of hormone replacement therapy; however, small numbers of these tumors limited power to detect possible associations. These data suggest that use of CHRT is associated with an increased risk of breast cancer, particularly invasive lobular tumors, whether the progestin component was taken in a sequential or in a continuous manner.
Title
A Validation Study of Patient Interview Data and Pharmacy Records for Antihypertensive, Statin, and Antidepressant Medication use among Older Women
Authors
Boudreau DM, Daling JR, Malone KE, Gardner JS, Blough DK, Heckbert SR.
Source
Am J Epidemiol 2004; 159(3):308-317
Abstract
A validation study evaluated the accuracy of self-reported use of commonly used medications among older women. Within a case-control study of breast cancer, drug information was ascertained by interview. Pharmacy records from 1990 to 1999 were obtained from a Washington State health maintenance organization (66% of subjects) and retail pharmacies (34% of subjects) on a sample of subjects (212 cases, 191 controls) and used as the "gold standard." Recall accuracy was assessed for 6-month, 2-year, and 8-year time windows. Sensitivity of antihypertensive use was 92% (95% confidence interval (CI): 85, 96) for cases and controls in the 6-month period and slightly lower for the 2-year (90% (95% CI: 82, 94) and 87% (95% CI: 78, 92)) and 8-year (80% (95% CI: 69, 88) and 79% (95% CI: 68, 88)) periods. For statins, sensitivity was 83% (95% CI: 64, 93) for cases and 93% (95% CI: 69, 99) for controls in the 6-month period, 75% (95% CI: 55, 88) and 86% (95% CI: 60, 96) in the 2-year period, and 67% (95% CI: 42, 85) and 75% (95% CI: 41, 93) in the 8-year period. For self-report of antidepressants, sensitivities ranged from 66% (95% CI: 47, 80) in the 6-month period to 44% (95% CI: 30, 60) in the 8-year period. Specificity was high among all drug classes, ranging from 91% to 100%. Recall did not differ by case-control status. Trivial changes in estimates were observed when health maintenance organization records alone were used as the gold standard. Self-reported use of antihypertensives and statins appears to be relatively accurate among older women.
Title
The Association between 3-hydroxy-3-methylglutaryl Coenzyme A Inhibitor Use and Breast Carcinoma Risk among Postmenopausal Women: A Case-Control Study
Authors
Boudreau DM, Gardner JS, Malone KE, Heckbert SR, Blough DK, Daling JR
Source
Cancer 2004; 100(11):2308-2316
Abstract
Statin use has increased dramatically in the U.S. in the past decade. Animal and mechanistic studies suggested that statins may have an inhibitory effect on cancer proliferation, including breast carcinoma. However, statins have been found to be carcinogenic in rodents and one clinical trial found an excess of breast carcinoma cases in the treatment group. The current study assessed whether the use of statins altered the risk of breast carcinoma in older women. The population-based, case-control study comprised female residents from three western Washington State counties. Cases included 975 women identified from the Cancer Surveillance System who were diagnosed with primary invasive breast carcinoma between 1997-1999, whose names appeared on a list of Social Security recipients provided by the Centers for Medicare and Medicaid Services. The cases were ages 65-79 years at the time of diagnosis. The comparison group was comprised of 1007 women without breast carcinoma who were randomly selected from the same list of Social Security recipients. Information pertaining to statin use, medical history, and health behaviors was ascertained through an in-person interview. Compared with nonusers, women who were currently using statins or had ever used statins were not found to be at an increased risk for breast carcinoma (odds ratios [OR] = 0.9; 95% confidence interval [95% CI], 0.7-1.2). There was some indication that long-term statin use (> 5 years) was related to a slight decrease in breast carcinoma risk (OR = 0.7; 95% CI, 0.4-1.0). The results of the current study provided some degree of reassurance to the increasing numbers of women using statins that such use is not associated with an increased risk of breast carcinoma. Although the data gave some support to a reduced risk of breast carcinoma among long-term users of statins, further research is needed to confirm this association.
Title
The relationship between various measures of cigarette smoking and risk of breast cancer among older women 65-79 years of age
Authors
Li CI, Malone KE, Daling JR.
Source
Cancer Causes Control 2005; 16(8):975-985
Abstract
Results from studies evaluating the relationship between cigarette smoking and breast cancer have been inconsistent. Though most studies have found that smoking does not alter risk, others have observed both increased and decreased risks associated with smoking. The reasons for these inconsistencies are unclear, but they may be related to differences in study populations, designs, and exposure definitions. In particular, this relationship may vary by age, and few studies have focused on older women many of whom have smoked for very long durations. We conducted a population-based case-control study (975 cases/1007 controls) of women 65-79 years of age in western Washington State. Women who were current smokers, smoked for > or =40 years, had > or =11 pack-years of lifetime smoking, or started smoking before their first full-term birth each had 30-40% elevated risks of breast cancer (p < 0.05). Recency, length, and intensity of smoking are all associated with modest increased risks of breast cancer. A further understanding of the timing of smoking, and its interaction with other factors, may enhance our knowledge of whether and by what mechanisms smoking alters breast cancer risk.
Title
Antidepressant use and breast cancer risk
Authors
Chien C, Li CI, Heckbert SR, Malone KE, Boudreau DM, Daling JR.
Source
Breast Cancer Res Treat 2006; 95(2):131-140
Abstract
Antidepressants are among the most commonly prescribed drugs in the United States. Laboratory studies suggest that because certain antidepressants increase prolactin levels that they may also increase breast cancer risk. However, human studies evaluating use of antidepressants in relation to breast cancer risk have yielded inconsistent results. A population-based case-control study consisting of 975 breast cancer cases 65-79 years of age diagnosed from 1997-1999 and 1007 age and residence-matched controls was conducted in western Washington State. Detailed information on antidepressant use was obtained through structured in-person interviews. Logistic regression was performed to analyze the relationship between antidepressant use and breast cancer risk. Overall, there was no association between ever use of antidepressants and breast cancer risk (odds ratio [OR] = 1.2, 95% confidence interval [95% CI]: 0.9-1.6). When evaluated separately, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), and triazolopyridines were each not associated with breast cancer risk. However, risk varied by hormone receptor status. Compared to never users, ever users of SSRIs had elevated risks of progesterone receptor (PR) negative and estrogen receptor (ER) positive/PR-negative breast cancers (OR = 1.8, 95% CI: 1.1-3.6 and OR = 2.0, 95% CI: 1.1-3.8, respectively), but not of tumors with other hormone receptor profiles. Based on these results and those of previous studies, there is limited evidence that any type of antidepressant use is associated with breast cancer risk overall. SSRIs may elevate risks of PR- and ER+/PR- tumors, though further studies are needed to confirm these associations.
Title
Interactions between body mass index and hormone therapy and postmenopausal breast cancer risk
Authors
Li CI, Malone KE, Daling JR.
Source
Cancer Causes Control 2006; 17(5):695-703
Abstract
To assess interactions between use of estrogen plus progestin hormone therapy (EPHT) and body mass index (BMI) in relation to risks of different types of breast cancer, based on histology and hormone receptor status, we conducted a population-based case-control study that compared 975 postmenopausal breast cancer cases to 1,007 controls. Interactions between menopausal hormone therapy (HT) and BMI in relation to risk of different breast cancer types were evaluated using logistic regression. Obese (BMI > or = 30.0 kg/m2) never users of HT had 1.7-fold to 2.3-fold elevated risks of ductal and ER+/PR+ tumors, respectively, compared to thinner women. BMI was not related to breast cancer risk among current HT users. Current EPHT users for > or = 5 years had 2.1 to 9.6-fold elevated risks of lobular and ER+/PR+ tumors compared to never users of HT regardless of BMI. Current EPHT users for > or = 5 years with a BMI < or = 24.9 kg/m2 also had a 2.6-fold elevated risk of ductal carcinoma. However, none of the interactions between BMI and HT use evaluated reached statistical significance. While interactions between HT and BMI are well established, they appear to only be present among certain breast cancer types. Since obesity is related to breast cancer risk only among never users of HT, as HT use declines the relative impact of obesity on breast cancer incidence may grow.
EMF [Electric Power and the Risk of Breast Cancer]
Title
Night Shift Work, Light at Night, and Risk of Breast Cancer
Authors
Davis S, Mirick DK, Stevens RG
Source
J Natl Cancer Inst 2001; 93(20):1557-1562
Abstract
Exposure to light at night may increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin by the pineal gland, which, in turn, could increase the release of estrogen by the ovaries. This study investigated whether such exposure is associated with an increased risk of breast cancer in women. Case patients (n = 813), aged 20-74 years, were diagnosed from November 1992 through March 1995; control subjects (n = 793) were identified by random-digit dialing and were frequency matched according to 5-year age groups. An in-person interview was used to gather information on sleep habits and bedroom lighting environment in the 10 years before diagnosis and lifetime occupational history. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by use of conditional logistic regression, with adjustment for other potential risk factors. Breast cancer risk was increased among subjects who frequently did not sleep during the period of the night when melatonin levels are typically at their highest (OR = 1.14 for each night per week; 95% CI = 1.01 to 1.28). Risk did not increase with interrupted sleep accompanied by turning on a light. There was an indication of increased risk among subjects with the brightest bedrooms. Graveyard shiftwork was associated with increased breast cancer risk (OR = 1.6; 95% CI = 1.0 to 2.5), with a trend of increased risk with increasing years and with more hours per week of graveyard shiftwork (P =.02, Wald chi-squared test). The results of this study provide evidence that indicators of exposure to light at night may be associated with the risk of developing breast cancer.
Title
Residential magnetic fields, light-at-night, and nocturnal urinary 6-sulfatoxymelatonin concentration in women
Authors
Davis S, Kaune WT, Mirick DK, Chen C, Stevens RG.
Source
Am J Epidemiol 2001; 154(7):591-600
Abstract
Exposure to 60-Hz magnetic fields may increase breast cancer risk by suppressing the normal nocturnal rise in melatonin. This 1994-1996 Washington State study investigated whether such exposure was associated with lower nocturnal urinary concentration of 6-sulfatoxymelatonin in 203 women aged 20-74 years with no history of breast cancer. Each woman was interviewed and provided data on the following for a 72-hour period at two different seasons of the year: 1) magnetic field and ambient light measured every 30 seconds in her bedroom, 2) personal magnetic field measured at 30-second intervals, and 3) complete nighttime urine samples on three consecutive nights. Lower nocturnal urinary 6-sulfatoxymelatonin level was associated with more hours of daylight, older age, higher body mass index, current alcohol consumption, and current use of medications classified as beta blockers, calcium channel blockers, or psychotropics. After adjustment for these factors, higher bedroom magnetic field level was associated with significantly lower urinary concentration of 6-sulfatoxymelatonin during the same night, primarily in women who used these medications and during times of the year with the fewest hours of darkness. These results suggest that exposure to nighttime residential 60-Hz magnetic fields can depress the normal nocturnal rise in melatonin.
Title
Residential Magnetic Fields and the Risk of Breast Cancer
Authors
Davis S, Mirick DK, Stevens RG
Source
Am J Epidemiol 2002; 155(5):446-454
Abstract
Chronic exposure to 60-Hz magnetic fields may increase the risk of breast cancer by suppressing the normal nocturnal production of melatonin. This population-based case-control study investigated whether such exposure is associated with an increased risk of breast cancer in women aged 20-74 years from the greater Seattle, Washington, area. Cases were diagnosed between November 1992 and March 1995 (n = 813); controls were identified by random digit dialing and were frequency matched by 5-year age groups (n = 793). Exposure was estimated using magnetic field measurements in the home at diagnosis, wiring configuration of all homes occupied in the 10 years prior to diagnosis, and self-reported measures of at-home electric appliance use. Odds ratios and 95% confidence intervals were estimated using conditional logistic regression with adjustment for other potential risk factors. Risk did not increase with measured nighttime bedroom magnetic field level, wiring configuration of the home at diagnosis, weighted summary wire codes of all homes occupied 5 and 10 years prior to diagnosis, or reported use of common household appliances, including bed-warming devices. These data do not support the hypothesis that exposure to residential magnetic fields is associated with an increased risk of developing breast cancer.
Title
Circadian disruption, shift work and the risk of cancer: a summary of the evidence and studies in Seattle
Authors
Davis S, Mirick DK.
Source
Cancer Causes Control 2006; 17(4):539-545
Abstract
There is increasing interest in the possibility that disruption of normal circadian rhythm may increase the risk of developing cancer. Persons who engage in nightshift work may exhibit altered nighttime melatonin levels and reproductive hormone profiles that could increase the risk of hormone-related diseases, including breast cancer. Epidemiologic studies are now beginning to emerge suggesting that women who work at night, and who experience sleep deprivation, circadian disruption, and exposure to light-at-night are at an increased risk of breast cancer, and possibly colorectal cancer as well. Several studies have been conducted in Seattle recently to investigate the effects of factors that can disrupt circadian rhythm and alter normal nocturnal production of melatonin and reproductive hormones of relevance to breast cancer etiology. Studies completed to date have found: (1) an increased risk of breast cancer associated with indicators of exposure to light-at-night and night shift work; and (2) decreased nocturnal urinary levels of 6-sulphatoxymelatonin associated with exposure to 60-Hz magnetic fields in the bedroom the same night, and a number of other factors including hours of daylight, season, alcohol consumption and body mass index. Recently completed is an experimental crossover study designed to investigate whether exposure to a 60-Hz magnetic field under controlled conditions in the home sleeping environment is associated with a decrease in nocturnal urinary concentration of 6-sulphatoxymelatonin, and an increase in the urinary concentration of luteinizing hormone, follicle stimulating hormone, and estradiol in a sample of healthy women of reproductive age. Presently underway is a study to determine whether working at night is associated with decreased levels of urinary 6-sulphatoxymelatonin, and increased urinary concentrations of the reproductive hormones listed above in a sample of healthy women of reproductive age, and to elucidate characteristics of sleep among night shift workers that are related to the hormone patterns identified. A proposal is under review to extend these studies to a sample of healthy men to investigate whether working at night is associated with decreased levels of urinary 6-sulphatoxymelatonin, and increased concentrations of urinary cortisol and cortisone, urinary levels of a number of androgen metabolites, and serum concentrations of a number of reproductive hormones. Secondarily, the proposed study will elucidate characteristics of sleep among night shift workers that are related to the hormone patterns identified, as well as investigate whether polymorphisms of the genes thought to regulate the human circadian clock are associated with the ability to adapt to night shift work. It is anticipated that collectively these studies will enhance our understanding of the role of circadian disruption in the etiology of cancer.
Title
Medication use and the risk of breast cancer
Authors
Davis S, Mirick DK.
Source
European Journal of Epidemiology 2007;22:319-325
Abstract
The purpose of the study was to investigate whether the use of commonly-prescribed medications, primarily antihypertensives and antidepressants, is associated with an increased risk of breast cancer. Participants from a population-based case-control study were re-contacted 5-8 years after the original study regarding prescription and non-prescription medication use during the 10 years prior to diagnosis. Controls (n = 647) were frequency-matched to the cases (n = 600) by 5-year age groups. Medication use information was obtained during a telephone interview, and participants were sent the questionnaire in advance to facilitate recall. Odds ratios and 95% confidence intervals were estimated using conditional logistic regression. A slightly increased risk of breast cancer was associated with use of calcium channel blockers (CCBs), but there was no trend with increasing duration or recency of use. Breast cancer risk was not associated with use of antidepressants, beta blockers, corticosteroids, or non-steroidal anti-inflammatory drugs. Results were similar when analyses were restricted to cases with localized disease. These results support previous findings that CCBs may be associated with modest increases in breast cancer risk, but not findings that non-steroidal anti-inflammatory use reduces risk.
Title
Residential magnetic fields, medication use, and the risk of breast cancer
Authors
Davis S, Mirick DK.
Source
Epidemiology 2007;18:266-269
Abstract
Exposure to 60-Hz magnetic fields may increase breast cancer risk by suppressing the nocturnal production of melatonin. The use of medications associated with reduced melatonin levels could modify this relationship. We recontacted participants in a population-based case-control study of residential magnetic field exposure and breast cancer risk and interviewed them regarding medication use during the 10 years before diagnosis. Cases were diagnosed between November 1992 and March 1995, and magnetic field levels were measured in the home at diagnosis. We obtained medication use information by telephone interview from 558 cases and 588 controls. Breast cancer risk was not associated with exposure to residential magnetic fields, regardless of medication use. These results support previous findings that magnetic field exposure does not increase breast cancer risk.
1100 Fairview Ave. N. PO Box 19024 Seattle, WA 98109
©2009 Fred Hutchinson Cancer Research Center, a nonprofit organization.
Terms of Use & Privacy Policy.
