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Biomedical subjects

Malcolm C Pike

Publications and source records attributed to Malcolm C Pike.

At least 37 records · Page 2Linked to original sources

A controlled 2-mo dietary fat reduction and soy food supplementation study in postmenopausal women.

BACKGROUND: Low intake of dietary fat and high intake of soy foods have been suggested to partly explain the lower breast cancer rates in Asia, perhaps because of lower endogenous estrogens. OBJECTIVE: The objective was to assess the hormonal and nonhormonal effects of diets resembling an Asian diet in terms of total fat and soy food contents. DESIGN: Fifty-seven postmenopausal women participated in a randomized, controlled, dietary intervention study. The subjects consumed a very-low-fat diet (VLFD; 11% of energy as fat), a Step I diet (25% of energy as fat) supplemented with soy food (SFD; 50 mg isoflavones/d), or a control Step I diet (CD; 27% of energy as fat) with no soy food. All diets were prepared at the General Clinical Research Center of the University of Southern California. Serum hormones and other markers were measured at baseline and every 2 wk during the 8 wk of intervention. RESULTS: There were no significant differences in total estradiol and sex hormone binding globulin at the completion of the intervention between women in the SFD and VLFD groups and those in the CD group. Serum insulin decreased significantly in the SFD group, and leptin decreased significantly in the SFD and VLFD groups; however, these changes did not differ significantly from the changes in the CD group. CONCLUSIONS: This study does not provide evidence that ingestion of soy food or a VLFD significantly reduces estrogen concentrations in postmenopausal women. However, short-term changes in diet may have significant and beneficial effects on blood insulin and leptin concentrations.

Dietary Fats↗

Comparison of prostate-specific antigen and hormone levels among men in Singapore and the United States.

Prostate cancer incidence rates markedly vary between countries. The highest rates of prostate cancer are observed in Western countries such as the United States, whereas the lowest rates are seen in Asian countries such as Singapore. To gain an understanding of the difference in prostate cancer burden between low-risk and high-risk populations, we examined serum prostate-specific antigen (PSA) levels among Singapore-Chinese men (n = 315) from the Singapore Chinese Health Study and African-American (n = 440), U.S. White (n = 355), U.S. Latino (n = 523), and Japanese-American (n = 349) men from the Hawaii-Los Angeles Multiethnic Cohort Study. All men had no history of prostate cancer at the time of blood draw. PSA measurements were assayed by one centralized diagnostic facility. Testosterone and 3alpha-androstanediol glucuronide levels were examined in a subsample of men. Scheffe's multiple comparison tests were used to evaluate differences in PSA and hormone levels between groups. PSA levels among the Singapore-Chinese (geometric mean = 1.43 ng/mL) were similar to that of African-Americans (1.46 ng/mL), U.S. Whites (1.28 ng/mL), and Japanese-Americans (1.22 ng/mL) and significantly higher than U.S. Latinos (1.18 ng/mL; P = 0.038). Although there was a strong correlation (R2= 0.89) between PSA levels and U.S. ethnic group-specific prostate cancer incidence rates before PSA screening (1983-1987), the levels among the Singapore-Chinese completely failed to relate to their low incidence rate. Testosterone and 3alpha-androstanediol glucuronide levels did not reflect racial/ethnic patterns of disease. Our results highlight a potentially large group of Singapore-Chinese men with undiagnosed prostate cancer. Given that the overall mortality rate of prostate cancer in Singapore is low, these undiagnosed cancers may be of nonaggressive type. Alternatively, PSA may be a poor marker of prostate cancer in this low-risk population.

Age Distribution↗

Role of lipid peroxidation in the epidemiology and prevention of breast cancer.

We have recently proposed a common mechanistic pathway by which obesity and hypertension lead to increased renal cell cancer risk. Our hypothesis posits lipid peroxidation, which is a principal mechanism in rodent renal carcinogenesis, as an intermediate step that leads to a final common pathway shared by numerous observed risks (including obesity, hypertension, smoking, oophorectomy/hysterectomy, parity, preeclampsia, diabetes, and analgesics) or protective factors (including oral contraceptive use and alcohol) for renal cell cancer [Cancer Causes Control 2002;13:287-93]. During this exercise, we have noticed how certain risk factors for renal cell carcinoma are protective for breast cancer and how certain protective factors for renal cell carcinoma increase risk for breast cancer. Parity and oophorectomy, for example, are positively associated with renal cell carcinoma but are negatively associated with breast cancer. Similarly, obesity and hypertension are positively associated with renal cell carcinoma, but obesity is negatively associated with breast cancer in premenopausal women and hypertension during pregnancy is negatively associated with breast cancer. Furthermore, alcohol intake, negatively associated with renal cell carcinoma, is also positively associated with breast cancer. We propose here the possibility that lipid peroxidation may represent a protective mechanism in breast cancer. Although this runs counter to the conventional view that lipid peroxidation is a process that is harmful and carcinogenic, we present here the chemical and biological rationale, based on epidemiologic and biochemical data, which may deserve further consideration and investigation.

Animals↗

Urinary estrogen metabolites and their ratio among Asian American women.

Controversy persists regarding the role of a low ratio of 2-hydroxyestone (2-OHE(1))/16alpha-hydroxyestrone (16alpha-OHE(1)) as a potential estrogen metabolism marker of increased risk for breast cancer. Most of the evidence has been provided by case-control studies, where tumor effects on hormone metabolism are not known. Studies in populations at various risk of breast cancer are not consistent, with some suggesting that levels of the ratio may be altered by changes in diet and exercise. We studied Asian American women participating as controls in a case-control study of breast cancer in which migration history--a composite of the subject's place of birth, type of residence in Asia (urban or rural), length of time living in the West, and grandparents' place of birth--was associated with a 6-fold risk gradient that paralleled the historical differences in incidence rates between the United States and Asian countries. This population offered the possibility to address whether the ratio of 2-OHE(1):16alpha-OHE(1) differs according to recognized breast cancer risk factors, including migration history. Overnight 12-hour urines were obtained from 368 premenopausal and 143 naturally postmenopausal women of Chinese, Japanese, or Filipino descent who donated urines between 1985 and 1988. The estrogen metabolites 2-OHE(1) and 16alpha-OHE(1) were measured with an ELISA kit and adjusted for creatinine levels. In each ethnic group, the ratio of 2-OHE(1):16alpha-OHE(1) was consistently lower in women born in the West than in those who had migrated from Asia. For premenopausal women, the ratio declined 20% due to lower levels of 2-OHE(1). Among postmenopausal women, the ratio was 23% lower in those born in the West, but no consistent patterns based on place of birth were observed for either 2-OHE(1) or 16alpha-OHE(1). The ratio did not vary with most recognized breast cancer risk factors, except for lower metabolite ratios in women with a younger age at first birth and more children, which runs contrary to the hypothesis, because both characteristics reduce breast cancer risk. Our study suggests that the ratio of 2-OHE(1):16alpha-OHE(1) may be a marker for lifestyle influences on estrogen metabolism associated with westernization.

Adult↗

Prevention of cancers of the breast, endometrium and ovary.

A central epidemiological feature of cancers of the breast, endometrium and ovary is the sharp slowing down in their rate of increase with age around the time of menopause. The incidence of these tumors by the age of 70 years would be between fourfold and eightfold increased if the rapid increase with age seen in young women continued into old age. These phenomena can be explained by the different effects of ovarian hormones on cell division rates in the relevant tissues. Models of these effects provide a plausible explanation of most of the known epidemiology of each of the cancers, including the increase in breast cancer risk from menopausal estrogen-progestin therapy. Some recent epidemiological findings in endometrial and ovarian cancer suggest new avenues for possible chemoprevention of these cancers.

Aged↗

Post-treatment change in serum estrone predicts mammographic percent density changes in women who received combination estrogen and progestin in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.

PURPOSE: Postmenopausal estrogen and progestin therapy (EPT) increases mammographic percent density and breast cancer risk substantially more than does estrogen therapy alone. We determined whether increases in serum estrone as a function of treatment predict increases in mammographic percent density. METHODS: We measured mammographic percent density and serum estrone levels in participants in the Postmenopausal Estrogen/Progestin Interventions Trial who were randomly assigned to receive conjugated equine estrogens (CEE) 0.625 mg/d; CEE and medroxyprogesterone acetate (MPA) 10 mg on days 1 to 12 per 28-day cycle; CEE and MPA 2.5 mg/d; or CEE and micronized progesterone (MP) 200 mg on days 1 to 12 per 28-day cycle. We used linear regression to determine whether serum estrone changes predicted mammographic percent density changes from baseline to 1 year. RESULTS: Mammographic percent density increased with increasing change in estrone level in the EPT groups, but not in the CEE group. Combined, the mammographic percent density in the three EPT groups demonstrated an absolute increase of 2.95% per 100 pg/mL increase in serum estrone level (P =.0003). The absolute increases were 4.09% (P =.0018) in the CEE + MPA continuous group, 2.79% (P =.0292) in the CEE + MPA cyclical group, and 1.40% (P =.36) in the CEE + MP group, but the differences among the EPT groups were not statistically significant. CONCLUSION: Greater increase in serum estrone level as a function of treatment is a significant predictor of increase in mammographic percent density in women randomly assigned to the combination of estrogen and progestin.

Breast↗

Does mammographic density reflect ethnic differences in breast cancer incidence rates?

Breast cancer incidence rates in the United States are substantially lower among Asian-American women than among White or African-American women. The authors determined whether mammographic density reflects these ethnic differences by evaluating mammograms from 442 White, African-American, and Asian-American women without breast cancer who served as controls in one of two population-based, breast cancer case-control studies conducted in Los Angeles, California, in 1994-1998. Absolute and percent mammographic densities were determined with a previously developed and validated computer-assisted method. Data were analyzed using multiple regression methods. Mean age-adjusted percent mammographic density was significantly higher in Asian Americans (35.9%) than in African Americans (27.8%, p < 0.05) but was no longer significant after further adjustment for body mass index. After adjustment for age, body mass index, selected menstrual/reproductive factors, and family history, absolute mammographic density was statistically significantly lower in Asian Americans than in African Americans (p < 0.05) but not than in Whites. The ethnic difference in absolute mammographic density was particularly evident among women older than age 50 years. Additional adjustment for breast size reduced these ethnic differences. This study suggests that absolute but not percent mammographic density reflects the lower breast cancer incidence rates of Asian Americans in relation to those of African Americans and Whites.

Adult↗

Hormonal factors and the risk of invasive ovarian cancer: a population-based case-control study.

OBJECTIVE: To examine the influence of hormone-related factors on the risk of invasive epithelial ovarian cancer (ovarian cancer). DESIGN: Population-based case-control study using in-person interviews. SETTING: Academic department of preventive medicine. PATIENT(S): Four hundred seventy-seven ovarian cancer patients and 660 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Numbers of and ages at births, oral contraceptive use, and use of menopausal hormone therapy. RESULT(S): Compared with nulliparous women, women whose only (last) birth was after age 35 years had an estimated 51% (95% confidence interval: 21%-70%) reduction in risk. If this birth occurred earlier, the reduction in risk was progressively less. Additional (earlier) births reduced the risk further. Oral contraceptive use also reduced risk. Increased body mass index increased risk, but this effect was confined to localized disease and is likely to be a diagnostic bias, as a consequence of other problems associated with being overweight and in itself having no etiological significance. CONCLUSION(S): If the major protective effect of a late birth can be confirmed, our most challenging task will be to understand the mechanism to develop a chemoprevention approach to exploit this finding.

Adult↗

Maternal risk factors for testicular cancer: a population-based case-control study (UK).

OBJECTIVE: To investigate the role of a range of maternal and pre-natal characteristics as potential risk factors for testicular cancer. METHODS: A population-based case-control study of testicular cancer. Mothers of participants completed a questionnaire about their reproductive and obstetric history. RESULTS: The risk of testicular cancer was approximately doubled for sons of mothers aged 15-19 years at conception compared with mothers with older ages at conception. Nausea or vomiting during the first trimester of pregnancy was associated with a reduced risk of testicular cancer (odds ratio of 0.73, 95% confidence interval 0.53-1.00). There was also a borderline reduction in risk in men who had been breastfed for 6 months or more (odds ratio 0.65, 95% confidence interval 0.41-1.04). Men who had low birthweights (< 2500 g) or had been born two or more weeks early had slightly increased risks, as did men whose mothers had used oral contraception in the 12 months before their conception. CONCLUSIONS: These findings support previous reports of increased risks in men born early or with low birthweight, but the direction of the association with maternal age is contrary to some other studies. The suggestion of a protective effect of breastfeeding requires further confirmation.

Adolescent↗

IL-6 levels and genotype are associated with risk of young adult Hodgkin lymphoma.

Identical twins of young adult Hodgkin lymphoma case subjects are much more likely to develop the disease compared with fraternal twins of case subjects, suggesting a genetic determinant. Interleukin 6 (IL-6) levels are increased in patients with Hodgkin lymphoma and are correlated with a poor prognosis. We hypothesized that a heritable abnormality in IL-6 regulation may predispose to young adult Hodgkin lymphoma. We obtained blood specimens from 88 young adult Hodgkin lymphoma case subjects and their twins as well as from 87 matched control subjects. IL-6 was measured from unstimulated peripheral blood mononuclear cell (PBMC) supernatant with enzyme-linked immunosorbent assays (ELISAs) and compared by using analysis of covariance. Unaffected identical twins of case subjects (surrogate case subjects) had a 87.8% higher IL-6 level compared with matched control subjects (mean difference, +483.7 pg/mL, P =.04). Analysis of the IL-6 174G>C promoter polymorphism genotypes showed that risk decreased with an increasing number of C alleles (P =.01). The CC (low secreting) genotype was associated with a decreased risk of young adult Hodgkin lymphoma relative to the GG (high secreting) genotype (odds ratio [OR] =.29; P =.03). Risk was decreased for both nodular sclerosis and other subtypes. Persons with genetically determined lower IL-6 levels may be less susceptible to young adult Hodgkin lymphoma.

Adolescent↗

Green tea and risk of breast cancer in Asian Americans.

There is substantial in vitro and in vivo evidence implicating tea polyphenols as chemopreventive agents against various cancers. However, epidemiologic data obtained from mainly Western populations are not supportive of a protective role of tea, mainly black tea, in the etiology of breast cancer. Much less is known about the relationship between green tea and breast cancer risk. During 1995-1998, we conducted a population-based, case-control study of breast cancer among Chinese, Japanese and Filipino women in Los Angeles County and successfully interviewed 501 breast cancer patients and 594 control subjects. Detailed information on menstrual and reproductive factors; dietary habits, including intake of black and green tea; and other lifestyle factors was collected. Risk of breast cancer was not related to black tea consumption. In contrast, green tea drinkers showed a significantly reduced risk of breast cancer, and this was maintained after adjusting for age, specific Asian ethnicity, birthplace, age at menarche, parity, menopausal status, use of menopausal hormones, body size and intake of total calories and black tea. Compared to women who did not drink green tea regularly (i.e., less than once a month), there was a significant trend of decreasing risk with increasing amount of green tea intake, adjusted odds ratios being 1.00, 0.71 (95% confidence interval [CI] 0.51-0.99) and 0.53 (95% CI 0.35-0.78), respectively, in association with no, 0-85.7 and >85.7 ml of green tea per day. The significant inverse association between risk of breast cancer and green tea intake remained after further adjustment for other potential confounders, including smoking; alcohol, coffee and black tea intake; family history of breast cancer; physical activity; and intake of soy and dark green vegetables. While both green tea and soy intake had significant, independent protective effects on breast cancer risk, the benefit of green tea was primarily observed among subjects who were low soy consumers. Similarly, the protective effect of soy was primarily observed among subjects who were nondrinkers of green tea. In summary, our results point to an important role of both green tea and soy intake in relation to breast cancer risk in Asian-American women.

Adult↗

A comprehensive haplotype analysis of CYP19 and breast cancer risk: the Multiethnic Cohort.

The CYP19 gene encodes for aromatase (P450arom), a key steroidogenic enzyme that catalyzes the final step of estrogen biosynthesis. Apart from rare mutations in CYP19 which result in severe phenotypes associated with estrogen insufficiency, little is known about whether common variation in CYP19 is associated with risk of hormone-related diseases. In this study, we employed a haplotype-based approach to search for common disease-associated variants in this candidate breast cancer susceptibility gene among African-American, Hawaiian, Japanese, Latina and White women in the Multiethnic Cohort Study (MEC). We utilized 74 densely spaced single-nucleotide polymorphisms (SNPs) (one every approximately 2.6 kb) spanning 189.4 kb of the CYP19 locus to characterize linkage disequilibrium (LD) and haplotype patterns among 69-70 individuals from each ethnic population. We detected four regions of strong LD (blocks 1-4) that were quite closely conserved across populations. Within each block there was a limited diversity of common haplotypes (5 to 10 with a frequency >/=5%) and most haplotypes were observed to be shared across populations. Twenty-five haplotype-tagging SNPs (htSNPs) were selected to predict the common haplotypes with high probability (average Rh2=0.92) and genotyped in a breast cancer case-control study in the MEC (cases, n=1355; controls, n=2580). We first performed global tests for differences in risk according to the common haplotypes and observed significant haplotype-effects in block 2 [P=0.01; haplotypes 2b (OR=1.23; 95% CI, 1.07-1.40), 2d (OR=1.28; 95% CI, 1.01-1.62)]. We also found a common long-range haplotype comprised of block-specific haplotypes 2b and 3c to be associated with increased risk of breast cancer (haplotype 2b-3c: OR=1.31; 95% CI, 1.11-1.54). Our findings suggest the hypothesis that women with the long-range CYP19 haplotype 2b-3c may be carriers of a predisposing breast cancer susceptibility allele.

Adult↗

Postmenopausal hormone therapy and change in mammographic density.

BACKGROUND: Mammographic density is an independent risk factor for breast cancer. Postmenopausal hormone use is associated with an increase in mammographic density, but the magnitude of the density increase is unknown. METHODS: Baseline and 12-month mammograms were obtained for 571 (65%) of the 875 women, aged 45-64 years, who were enrolled in the Postmenopausal Estrogen/Progestin Interventions Trial and randomly assigned to receive placebo, daily conjugated equine estrogens at 0.625 mg/day (CEE), daily CEE and medroxyprogesterone acetate (MPA) at 10 mg/day on days 1-12 (CEE+MPA-cyclic), daily CEE and MPA at 2.5 mg/day (CEE+MPA-continuous), or daily CEE and micronized progesterone (MP) at 200 mg/day on days 1-12 (CEE+MP). We analyzed digitized mammograms to determine the percentage of the left breast that was composed of dense tissue (i.e., mammographic percent density). Linear regression analysis was used to examine the effects of treatments on the change in mammographic percent density between baseline and 12 months, before and after adjustment for possible confounders. All statistical tests were two-sided. RESULTS: The adjusted absolute mean changes in mammographic percent density over 12 months were 4.76% (95% confidence interval [CI] = 3.29% to 6.23%), 4.58% (95% CI = 3.19% to 5.97%), and 3.08% (95% CI = 1.65% to 4.51%) for women in the CEE+MPA-cyclic, CEE+MPA-continuous, and CEE-MP groups, respectively. Each of those absolute mean changes was statistically significantly different from the adjusted absolute mean change in mammographic percent density for women in the placebo group, which was -0.07% (95% CI = -1.50% to 1.38%). CONCLUSION: Greater mammographic density was associated with the use of estrogen/progestin combination therapy, regardless of how the progestin was given, but not with the use of estrogen only.

Breast↗

Choosing haplotype-tagging SNPS based on unphased genotype data using a preliminary sample of unrelated subjects with an example from the Multiethnic Cohort Study.

We describe an approach for picking haplotype-tagging single nucleotide polymorphisms (htSNPs) that is presently being taken in two large nested case-control studies within a multiethnic cohort (MEC), which are engaged in a search for associations between risk of prostate and breast cancer and common genetic variations in candidate genes. Based on a preliminary sample of 70 control subjects chosen at random from each of the 5 ethnic groups in the MEC we estimate haplotype frequencies using a variant of the Excoffier-Slatkin E-M algorithm after genotyping a high density of SNPs selected every 3-5 kb in and surrounding a candidate gene. In order to evaluate the performance of a candidate set of htSNPS (which will be genotyped in the much larger case-control sample) we treat the haplotype frequencies estimate above as known, and carry out a formal calculation of the uncertainty of the number of copies of common haplotypes carried by an individual, summarizing this calculation as a coefficient of determination, R2h. A candidate set of htSNPS of a given size is chosen so as to maximize the minimum value of R2h over the common haplotypes, h.

Aromatase↗

Correlation of dietary intake and colorectal cancer incidence among Mexican-American migrants: the multiethnic cohort study.

Studies of migrants, along with geographic and temporal variations in incidence, indicate that colorectal cancer is especially sensitive to changes in environmental factors, including, most importantly, diet. The goal of this research was to examine the changes in dietary practices that may be consistent with the changing incidence of colorectal cancer in the Los Angeles Mexican-American population. Cancer incidence and dietary intake data were available for over 35,000 Latinos of Mexican national origin currently participating in the prospective Multiethnic Cohort Study, representing the largest sample of Mexican-origin Latinos of any such study in the United States. The dataset is unique in that changes in cancer rates and in dietary behaviors across three generations could be examined. Most of the change in colorectal cancer rates occurred between the first and second generations, and, correspondingly, nearly all the dietary change also occurred between the first and second generations. Although some food traditions were retained by Mexican Americans, the dietary changes due to acculturation were significant and support an association between colorectal cancer risk and certain dietary components, notably, alcohol as a risk factor and nonstarch polysaccharides and vegetables as protective factors.

Acculturation↗

Mammographic density and breast cancer in three ethnic groups.

The extent of radiodense tissue on a mammogram (mammographic densities) is strongly associated with breast cancer risk among (non-Latina) white women, but few data exist for African-American and Asian-American women. We collected prediagnostic mammograms from 622 breast cancer patients and 443 control subjects ages 35-64 years from three different ethnic groups (whites, African Americans, and Asian Americans) who participated as cases and controls in one of two ongoing breast cancer studies. Percent and absolute mammographic density were assessed using a previously validated computer-assisted method. In all three ethnic groups combined, breast cancer risk increased with increasing percent mammographic density. After adjustment for ethnicity, age, body mass index, age at menarche, breast cancer family history, age at and number of full-term pregnancies, menopausal status, and hormone replacement therapy use, women with the highest percent density had 5-fold greater breast cancer risk than women with no density (P(trend) = 0.0001). The impact of percent density on risk was stronger for older than for younger women (>/=50 versus <50 years; P = 0.05). Risk estimates did not differ significantly by ethnicity, with breast cancer risk (95% confidence interval) increasing 15% (4-27%) in whites, 30% (5-61%) in Asian Americans, and 11% (-2-26%) in African Americans for each 10% increase in density. The trends were similar for absolute density. Our results confirm that increases in computer-assisted mammographic density measurements are associated with a strong gradient in breast cancer risk. Furthermore, our findings suggest that mammographic density is as strong a predictor of risk for African-American and Asian-American women as for white women.

Adult↗

Estrogen-progestin replacement therapy: regulatory action needed.

It is now established that the most commonly prescribed estrogen-progestin replacement therapy regimen significantly increases breast cancer risk. What are the risks associated with other regimens? Studies with breast cancer as the outcome cannot answer these questions in the right timeframe. It is incumbent on us to agree that some intermediate marker of risk must be used to show the probable effect of a regimen. We should then act as if the effect on the marker is a quantitative guide to the probable effect on breast cancer risk. Regulatory authorities need to require such studies on all current regimens.

Breast Neoplasms↗

Does menopausal hormone replacement therapy interact with known factors to increase risk of breast cancer?

PURPOSE: We and other investigators have previously shown that postmenopausal combined estrogen and progestin replacement therapy (EPRT) increases the risk of breast cancer and that the risk associated with EPRT is substantially higher than for estrogen replacement therapy (ERT) alone. The present study was conducted to determine whether any particular subgroup of women are at particularly high risk of breast cancer if they use EPRT and whether tumor characteristics in women who develop cancer while on ERT or EPRT are different from those in women not using ERT or EPRT. PATIENTS AND METHODS: We conducted a population-based case-control study in Los Angeles, CA, with patients diagnosed with breast cancer in the late 1980s and early 1990s. Control subjects were matched to patients on age, ethnicity, and neighborhood of residence. We present data on 1,897 postmenopausal patients and 1,637 controls aged 55 to 72 years who had not undergone a simple hysterectomy. RESULTS: Relative risk of breast cancer associated with EPRT use did not vary with body mass index (body mass index at or below v above median [24.6 kg/m(2)]; P =.98), alcohol intake (> or + one v < one drink per week; P =.16), parity (nulliparous v parous; P =.45), history of benign breast disease (yes v no; P =.99), or family history of breast cancer (first degree v none; P =.57). All of these results were compatible with our previously reported estimate of an increased risk of breast cancer of 5% per year of use of EPRT. Hormone users, principally EPRT users, were more likely to have hormone receptor--positive, especially progesterone-positive, tumors. CONCLUSION: We found no evidence that the risk of breast cancer associated with EPRT is limited to subgroups of women with specific cofactors. Tumors in EPRT users are more often hormone receptor--positive, indicating that they may have a better prognosis than breast cancer overall.

Aged↗