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Leslie Bernstein

Publications and source records attributed to Leslie Bernstein.

103 records · Page 6Linked to original sources

Genetic determinants of mammographic density.

BACKGROUND: Changes in breast density are highly correlated with steroid hormone exposure. MATERIALS AND METHODS: In a cross-sectional study of 396 Caucasian and African-American women, we evaluated whether polymorphisms in genes involved in steroid hormone biosynthesis and metabolism, CYP17 (T27C), COMT (Val158Met), 17HSDB1 (Ser312Gly) and 3HSDB1 (Asn367Thr), predict mammographic density. We also evaluated whether associations vary by menopausal and hormone replacement therapy status. RESULTS: We found no strong consistent relationships between polymorphisms in these genes and breast density. African-American women homozygous for the Thr allele of 3HSDB1 had increased density (the absolute difference versus the Asn/Asn genotype was +19.7%; P trend = 0.02), while Caucasian homozygous women had decreased density (-5.1%; P trend = 0.04). Among premenopausal women, carriers of the Ser allele had (not significantly) greater density (versus Gly/Gly genotype: +7.1%; P trend = 0.07). In addition, among current users of hormone replacement therapy, we observed that women with the low-activity Met/Met genotype of COMT had greater breast density (versus the Val/Val genotype: +11.7%; P trend = 0.01). CONCLUSION: Additional large studies evaluating these and other candidate breast cancer genes will be required to determine what proportion, if any, of the interindividual differences in breast density are due to underlying genetic variation in genes involved in steroid hormone biosynthesis or metabolism.

17-Hydroxysteroid Dehydrogenases↗

Hormone replacement therapy regimens and breast cancer risk(1).

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

Adult↗

The NICHD Women's Contraceptive and Reproductive Experiences Study: methods and operational results.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The methodologic details of this large collaboration may assist researchers conducting similar investigations.

Adult↗

Lifestyle and other risk factors for thyroid cancer in Los Angeles County females.

PURPOSE AND METHODS: We conducted a population-based case-control study of thyroid cancer. Cases were 292 women, aged 15-54 when diagnosed between the years 1980 and 1983 (145 diagnosed in 1980-81 and 147 diagnosed in 1982-83). Female neighborhood controls (n = 292) were matched to each case on birth-year and race. RESULTS: Among women < 35 years, thyroid disease in first-degree relatives increased thyroid cancer risk [odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.1-3.7]. Risk was not associated with fish consumption, although high childhood consumption of shellfish decreased thyroid cancer risk (OR = 0.2, 95% CI = 0.05-0.7 for consumption at least a few times weekly). Among papillary thyroid cancers (82% of cases), frequent adult consumption of saltwater fish decreased risk. Cancer risk was reduced with consumption of certain vegetables, wine, and tea. Other dietary variables, including milk, beer and hard liquor, and coffee were not related to thyroid cancer risk. Among the papillary sample, risk increased with longer use of multivitamins (OR = 2.9, 95% CI = 1.2-7.4 for > 10 years of use). Smoking and body mass were not associated with thyroid cancer risk. CONCLUSIONS: These results suggest a role of family history of thyroid disease and certain dietary variables in the etiology of thyroid cancer in adult females.

Adolescent↗

Urinary 2-hydroxyestrone/16alpha-hydroxyestrone ratio and family history of breast cancer in premenopausal women.

It has been hypothesized that the ratio of urinary 2-hydroxyestrone to 16alpha-hydroxyestrone (2-OHE1/16alpha-OHE1 represents a biomarker for breast cancer risk; the lower the ratio the higher the risk. We obtained early morning urine samples from 70 'high risk' premenopausal women who had a first degree family history of breast cancer and 27 'low risk' women with no such history. Five estrogen metabolites in urine were determined: 2-OHE1, 16alpha-OHE1, estrone (E1), estradiol (E2), and estriol (E3) conjugates. We compared geometric mean levels of each metabolite adjusted for age and weight. 'High risk' women did not have elevated levels of any of these metabolites. Instead, we observed decrements of 3-27% in women with a family history of breast cancer compared with women without such history, this difference was statistically significant for E2, 2- OHE1, and 16alpha-OHE1. The ratio of 2-OHE1/16alpha-OHE1 was identical in women with and without a family history of breast cancer. These results were unchanged, when additionally adjusted for recent intake of alcohol or cruciferous vegetables. Our data suggest that among premenopausal women, family history is not associated with higher urinary estrogen levels or a lower ratio of urinary 2-OHE1/16alpha-OHE1.

Adult↗

Epidemiology of endocrine-related risk factors for breast cancer.

Ovarian and other hormones are major determinants of breast cancer risk. Particularly important is the accumulative exposure of the breast to circulating levels of the ovarian hormones estradiol and progesterone. A number of breast cancer risk factors can be understood in light of how they affect women's hormone profiles. Age is a marker for the onset and cessation of ovarian activity. Racial differences in hormone profiles correlate with breast cancer incidence patterns. Age at menarche not only serves as the chronological indicator of the onset of ovarian activity, but as a predictor of ovulatory frequency during adolescence and hormone levels in young adults, and has a long-lasting influence on risk. Age at menopause, another established breast cancer risk factor, marks the cessation of ovarian activity. Pregnancy history and lactation experience also are hormonal markers of breast cancer risk. Postmenopausal obesity, which is associated with higher levels of estrogen following cessation of ovarian activity, increases breast cancer risk, whereas physical activity, which can limit menstrual function, reduces risk. A relatively recent area of investigation is prenatal exposures like preeclampsia and low birth weight; both may be associated with lower in utero exposure to estrogen and also may predict lower breast cancer risk as an adult. Improved understanding of these exposures and their potential interactions with breast cancer susceptibility genes may, in the future, improve our prospects for breast cancer prevention.

Adult↗

High breast cancer incidence rates among California teachers: results from the California Teachers Study (United States).

OBJECTIVE: [corrected] To determine risk factor profiles and cancer incidence rates among participants in the California Teachers Study (CTS), a study designed to document high breast cancer incidence rates of California teachers and to investigate emergent hypotheses in the etiology of breast and other cancers. METHODS: The CTS is a prospective study of 133,479 California female teachers and administrators, established in 1995-1996 with members of the California State Teachers Retirement System completing a detailed mailed questionnaire regarding possible risk factors for breast and other cancers. Cancer outcomes were identified by linkage with the California Cancer Registry. RESULTS: CTS participants have a 51% higher age-standardized invasive breast cancer incidence rate and a 67% higher in-situ breast cancer incidence rate than would be expected based on race-specific statewide rates after three years of follow-up. CTS participants also have substantially elevated rates of endometrial cancer (rate ratio, RR = 1.72), ovarian cancer (RR = 1.28), melanoma (RR = 1.59), non-Hodgkin's lymphoma (RR= 1.53), and leukemia (RR = 1.28), but low rates of invasive cervix cancer (RR = 0.53) and lung cancer (RR = 0.66). CONCLUSIONS: CTS members have high rates of several major cancers, particularly breast cancer, and low rates of lung and cervix cancer. Although late age at first birth can explain a portion of the observed excess risk of breast cancer in this cohort, the unique risk factor profile of CTS members may account for much of their higher risk of breast and selected other cancers. The CTS offers a rich resource for future studies of cancer risk and of women's health, in general.

Adult↗

Medical radiation, family history of cancer, and benign breast disease in relation to breast cancer risk in young women, USA.

OBJECTIVE: In previous studies breast cancer risk has been increased among women who received high doses (above 100-200 cGy) of ionizing radiation or those exposed to lower doses prior to age 20. Some evidence suggests that such risk may be distinctly elevated among women with a family history of breast or ovarian cancer (probably only carriers of specific gene mutations) and women with benign breast disease (BBD). METHODS: A population-based case-control study in Los Angeles County obtained interview data from 744 women who were aged 40 or younger and diagnosed with breast cancer during 1983-1988, and from 744 matched controls. Women with a positive family history of breast or ovarian cancer reported cancer in a mother, sister, or grandmother. Women with BBD reported a physician diagnosis. Radiation exposure was defined as a history of either radiation therapy or moderate exposure to medical radiography. RESULTS: Breast cancer risk was elevated among women exposed to medical radiation prior to age 20 years (odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.2-1.8), relative to unexposed women. This increased risk was observed only among women with a history of BBD (OR = 2.4, 95% CI = 1.6-3.7). Overall, risk was not associated with exposure to medical radiation after age 20 years, although among women with a positive family history of breast or ovarian cancer, exposed women had an increased risk (OR= 1.8, 95% CI = 1.0-3.1). Breast cancer risk was not increased among women with a family history of breast/ovarian cancer exposed to medical radiation before age 20 years or those with BBD exposed to medical radiation after age 20 years. DISCUSSION: Study participants may have received radiation doses that are no longer common, hampering study generalizability. Although differences in recall between cases and controls cannot be completely excluded, women with BBD or a family history of breast cancer appear to have greater breast cancer risk following relatively low ionizing radiation exposure than other women in this study.

Adult↗

Do thyroid disorders increase the risk of breast cancer?

The objective of this study was to determine whether thyroid disorders or treatment of such disorders affects the risk of breast cancer. Subjects aged 35-64 years were participants in the National Institute of Child Health and Human Development Women's Contraceptive and Reproductive Experiences Study, a population-based, case-control study of invasive breast cancer that was carried out at five sites in the United States. In-person interviews were completed for 4575 women (cases) with breast cancer (2953 white and 1622 black) and 4682 control women (3021 white and 1661 black). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multiple logistic regression methods. Models included adjustment for age (5-year age groups), race (white or black), and site. A history of any thyroid disorder (OR = 1.1, 95% CI = 0.9-1.2) was not associated with breast cancer risk. Only women with a history of thyroid cancer had an increased risk, but this was restricted to parous women (parous OR = 3.4, 95% CI = 1.5-8.1; nulliparous OR = 0.5, 95% CI = 0.04-5.1). Breast cancer risk was not associated with treatment for thyroid disorders. There was no statistical interaction between thyroid disorders, thyroid treatments, and race, menopausal status, or parity. We found no association between thyroid disorders or their associated treatments and the risk of breast cancer.

Adult↗

Evaluation of the efficacy of a nonlatex condom: results from a randomized, controlled clinical trial.

CONTEXT: To reduce unintended pregnancy and HIV infection, it is critical to develop reliable male condoms that will attract consumers who reject conventional latex condoms. METHODS: In a prospective clinical trial conducted in 1998-2000, 830 monogamous couples were randomized in equal numbers to use either a nonlatex condom or a commercial natural latex condom for six months as their only method of birth control. Couples completed detailed reports for the first five condom uses and recorded intercourse and condom use in coital diaries. Pregnancy rates associated with typical and consistent condom use were calculated using life-table analysis. Rates of clinical failure (condom breakage or slippage) were determined for the first five condom uses. RESULTS: During the first five uses, the nonlatex condom had a higher frequency of breakage or slippage during intercourse or withdrawal (4.0%) than latex condoms (1.3%); the breakage rate for the nonlatex condom was about eight times that of latex condoms. The six-cycle typical-use pregnancy rate did not differ significantly between users of nonlatex (10.8%) and latex condoms (6.4%). The six-cycle consistent-use pregnancy rate was higher for nonlatex condom users than for latex condom users (4.9% vs. 1.0%). CONCLUSIONS: The data present strong indirect support for public health messages that promote the use of latex condoms and, for individuals who cannot or are unwilling to use latex condoms, the use of nonlatex condoms for prevention of pregnancy and disease.

Adult↗