Reduced risk of breast cancer associated with recreational physical activity varies by HER2 status.

Convincing epidemiologic evidence indicates that physical activity is inversely associated with breast cancer risk. Whether this association varies by the tumor protein expression status of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), or p53 is unclear. We evaluated the effects of recreational physical activity on risk of invasive breast cancer classified by the four biomarkers, fitting multivariable unconditional logistic regression models to data from 1195 case and 2012 control participants in the population-based Women's Contraceptive and Reproductive Experiences Study. Self-reported recreational physical activity at different life periods was measured as average annual metabolic equivalents of energy expenditure [MET]-hours per week. Our biomarker-specific analyses showed that lifetime recreational physical activity was negatively associated with the risks of ER-positive (ER+) and of HER2-negative (HER2-) subtypes (both Ptrend  ≤ 0.04), but not with other subtypes (all Ptrend  > 0.10). Analyses using combinations of biomarkers indicated that risk of invasive breast cancer varied only by HER2 status. Risk of HER2-breast cancer decreased with increasing number of MET-hours of recreational physical activity in each specific life period examined, although some trend tests were only marginally statistically significant (all Ptrend  ≤ 0.06). The test for homogeneity of trends (HER2- vs. HER2+ ) reached statistical significance only when evaluating physical activity during the first 10 years after menarche (Phomogeneity  = 0.03). Our data suggest that physical activity reduces risk of invasive breast cancers that lack HER2 overexpression, increasing our understanding of the biological mechanisms by which physical activity acts.

Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women.

INTRODUCTION: The association of breast cancer patients' mortality with estrogen receptor (ER) status (ER + versus ER-) has been well studied. However, little attention has been paid to the relationship between the quantitative measures of ER expression and mortality. METHODS: We evaluated the association between semi-quantitative, immunohistochemical staining of ER in formalin-fixed paraffin-embedded breast carcinomas and breast cancer-specific mortality risk in an observational cohort of invasive breast cancer in 681 white women and 523 black women ages 35-64 years at first diagnosis of invasive breast cancer, who were followed for a median of 10 years. The quantitative measures of ER examined here included the percentage of tumor cell nuclei positively stained for ER, ER Histo (H)-score, and a score based on an adaptation of an equation presented by Cuzick and colleagues, which combines weighted values of ER H-score, percentage of tumor cell nuclei positively stained for the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) results. This is referred to as the ER/PR/HER2 score. RESULTS: After controlling for age at diagnosis, race, study site, tumor stage, and histologic grade in multivariable Cox proportional hazards regression models, both percentage of tumor cell nuclei positively stained for ER (Ptrend = 0.0003) and the ER H-score (Ptrend = 0.0004) were inversely associated with breast cancer-specific mortality risk. The ER/PR/HER2 score was positively associated with breast cancer-specific mortality risk in women with ER + tumor (Ptrend = 0.001). Analyses by race revealed that ER positivity was associated with reduced risk of breast cancer-specific mortality in white women and black women. The two quantitative measures for ER alone provided additional discrimination in breast cancer-specific mortality risk only among white women with ER + tumors (both Ptrend ≤ 0.01) while the ER/PR/HER2 score provided additional discrimination for both white women (Ptrend = 0.01) and black women (Ptrend = 0.03) with ER + tumors. CONCLUSIONS: Our data support quantitative immunohistochemical measures of ER, especially the ER/PR/HER2 score, as a more precise predictor for breast cancer-specific mortality risk than a simple determination of ER positivity.

Estrogen-related genes and their contribution to racial differences in breast cancer risk.

Racial differences in breast cancer risk, including the risks of hormone receptor subtypes of breast cancer, have been previously reported. We evaluated whether variation in genes related to estrogen metabolism (COMT, CYP1A1, CYP1B1, CYP17A1, CYP19A1, ESR1, GSTM1, GSTP1, GSTT1, HSD17B1, SULT1A1, and UGT1A1) contributes to breast cancer risk and/or racial differences in risk within the CARE study, a multi-centered, population-based case-control study of breast cancer. Genetic variation was assessed as single nucleotide polymorphisms (SNPs), haplotypes, and SNP-hormone therapy (HT) interactions within a subset of 1,644 cases and 1,451 controls, including 949 Black women (493 cases and 456 controls), sampled from the CARE study population. No appreciable associations with breast cancer risk were detected for single SNPs or haplotypes in women overall. We detected SNP-HT interactions in women overall within CYP1B1 (rs1800440; p (het) = 0.003) and within CYP17A1 (rs743572; p (het) = 0.009) in which never users of HT were at a decreased risk of breast cancer, while ever users were at a non-significant increased risk. When investigated among racial groups, we detected evidence of an SNP-HT interaction with CYP1B1 in White women (p value = 0.02) and with CYP17A1 in Black women (p value = 0.04). This analysis suggests that HT use may modify the effect of variation in estrogen-related genes on breast cancer risk, which may affect Black and White women to a different extent.

Oral contraceptive formulation and risk of breast cancer.

BACKGROUND: While evidence on the association between oral contraceptive (OC) use and breast cancer generally suggests little or no increased risk, the question of whether breast cancer risk varies by OC formulation remains controversial. Few studies have examined this issue because large samples and extensive OC histories are required. STUDY DESIGN: We used data from a multicenter, population-based, case-control investigation. Women aged 35-64 years were interviewed. To explore the association between OC formulation and breast cancer risk, we used conditional logistic regression to derive adjusted odds ratios, and we used likelihood ratio tests for heterogeneity to assess whether breast cancer risk varied by OC formulation. Key OC exposure variables were ever use, current or former use, duration of use and time since last use. To strengthen inferences about specific formulations, we restricted most analyses to the 2282 women with breast cancer and the 2424 women without breast cancer who reported no OC use or exclusive use of one OC. RESULTS: Thirty-eight formulations were reported by the 2674 women who used one OC; most OC formulations were used by only a few women. We conducted multivariable analyses on the 10 formulations that were each used by at least 50 women and conducted supplemental analyses on selected formulations of interest based on recent research. Breast cancer risk did not vary significantly by OC formulation, and no formulation was associated with a significantly increased breast cancer risk. CONCLUSIONS: These results add to the small body of literature on the relationship between OC formulation and breast cancer. Our data are reassuring in that, among women 35-64 years of age, we found no evidence that specific OC formulations increase breast cancer risk.

Breast cancer risk and ovariectomy, hysterectomy, and tubal sterilization in the women's contraceptive and reproductive experiences study.

Removal or impairment of ovaries before menopause may affect a woman's breast cancer risk by altering her cumulative exposure to ovarian hormones. The Women's Contraceptive and Reproductive Experiences Study, a population-based, multicenter case-control study of incident invasive breast cancer, recruited women aged 35-64 years (4,490 cases and 4,611 controls) who provided data on ovariectomy, hysterectomy, and tubal sterilization during in-person interviews. Controls were frequency-matched to cases by age, race, and study site. Unconditional logistic regression analysis was used. Women who had not undergone premenopausal reproductive surgery were the referent group. Bilateral ovariectomy was associated with reduced breast cancer risk overall (odds ratio (OR) = 0.59, 95% confidence interval (CI): 0.50, 0.69) and among women <45 years of age (ORs ranged from 0.31 to 0.52), but not among those who were older at surgery. It was also associated with a reduced risk for estrogen and progesterone receptor-positive tumors (OR = 0.63, 95% CI: 0.52, 0.75) but not receptor-negative tumors. Hysterectomy with ovarian conservation (OR = 0.83, 95% CI: 0.72, 0.96) and hysterectomy with partial ovary removal (OR = 0.73, 95% CI: 0.59, 0.91) were also associated with lower risk. No association with breast cancer risk was observed with tubal sterilization only or partial ovariectomy without hysterectomy. Reproductive organ surgeries may alter ovarian hormone levels, thereby affecting breast cancer risk.

A case-control study of body mass index and breast cancer risk in white and African-American women.

OBJECTIVE: Large body size has been associated with decreased risk of breast cancer in premenopausal women but with increased risk in postmenopausal women. Limited information is available about African-American women and differences by estrogen and progesterone receptor status. METHODS: We analyzed data from the Women's Contraceptive and Reproductive Experiences Study among 3,997 white and African-American breast cancer case patients diagnosed in 1994 to 1998 and 4,041 control participants ages 35 to 64 years. We calculated multivariate odds ratios (OR) as measures of relative risk of breast cancer associated with self-reported body mass index (BMI) at age 18 and 5 years before diagnosis (recent BMI). RESULTS: Risk tended to decrease with increasing BMI at age 18 years in all women [OR(BMI > or = 25 kg/m(2) versus < 20 kg/m(2)) = 0.76; 95% confidence interval (CI), 0.63-0.90; P(trend) = 0.005] and with recent BMI in premenopausal women (OR(BMI > or = 35 kg/m(2) versus < 25 kg/m(2)) = 0.81; 95% CI, 0.61-1.06; P(trend) = 0.05), unmodified by race. Among postmenopausal white but not African-American women, there was an inverse relation between recent BMI and risk. High recent BMI was associated with increased risk of estrogen receptor- and progesterone receptor-positive tumors among postmenopausal African-American women (OR(BMI > or = 35 kg/m(2) versus < 25 kg/m(2)) = 1.83; 95% CI, 1.08-3.09; P(trend) = 0.03). CONCLUSION: Among women at age 35 to 64 years, BMI at age 18 years is inversely associated with risk of breast cancer, but association with recent BMI varies by menopause status, race, and hormone receptor status. IMPACT: Our findings indicate that studies of BMI and breast cancer should consider breast cancer subtypes.

Hormone therapy and fatal breast cancer.

PURPOSE: Among unanswered questions is whether menopausal use of estrogen therapy (ET) or estrogen-plus-progestin therapy (CHT) increases risk of developing fatal breast cancer i.e., developing and dying of breast cancer. Using a population-based case-control design, we estimated incidence rate ratios of fatal breast cancer in postmenopausal hormone therapy (HT) users compared to non-users by type, duration, and recency of HT use. METHODS: HT use prior to breast cancer diagnosis in 278 women who died of breast cancer within 6 years of diagnosis (cases) was compared with use in 2224 controls never diagnosed with breast cancer using conditional logistic regression. Measures taken to address potential bias and confounding inherent in case-control studies included collecting and adjusting for detailed data on demographic and other factors potentially associated both with HT use and breast cancer. RESULTS: Fifty-six per cent of cases and 68% of controls reported HT use. Among current 3+ year HT users, odds ratios and 95% confidence intervals for death were 0.83 (0.50, 1.38) and 0.69 (0.44, 1.09), respectively, for exclusive use of CHT or of ET, and were 0.94 (0.59, 1.48) and 0.70 (0.45, 1.07) for any use of CHT or of ET regardless of other hormone use. CONCLUSION: Point estimates suggest no increased risk of fatal breast cancer with HT use, although 50% increases in risk in longer-term current CHT users cannot be ruled out.

Protection of mammography screening against death from breast cancer in women aged 40-64 years.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Risk of breast cancer associated with short-term use of oral contraceptives.

OBJECTIVE: To estimate breast cancer risk associated with short-term (<6 months) oral contraceptive use, and explore variation in estimates by use characteristics and medical, menstrual, and reproductive history. METHODS: We analyzed data from the Women's Contraceptive and Reproductive Experiences Study. Case subjects were white women and black women, 35-64 years old, diagnosed with invasive breast cancer in July 1994-April 1998. Control subjects identified by random-digit dialing were matched to case subjects by age, race, and study site. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Overall, short-term oral contraceptive use was not associated with breast cancer risk (OR = 1.0; 95% CI = 0.8-1.1). However, significant interaction between short-term use and menopausal status led to an observed increased breast cancer risk in pre-menopausal women (OR = 1.3; 95% CI = 1.0-1.7) and a reduced risk in post-menopausal women (OR = 0.8; 95% CI = 0.6-1.0) associated with short-term use. The association was more pronounced in women with non-contraceptive reasons for use and underlying risk factors for breast cancer. CONCLUSIONS: These associations may result from underlying characteristics of users or unmeasured factors influencing duration of use and breast cancer risk.

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.

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.

Breast cancer risk estimates for relatives of white and African American women with breast cancer in the Women's Contraceptive and Reproductive Experiences Study.

PURPOSE: 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. METHODS: 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. RESULTS: 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 = .3). CONCLUSION: 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.

Body size and risk of epithelial ovarian cancer (United States).

OBJECTIVE: We conducted a population-based case-control study of epithelial ovarian cancer in relation to measures of body size and adult weight change. In particular, we sought to characterize the independent relation of body weight at particular ages with risk. METHODS: In-person interviews were sought with 35-54 year-old female residents of metropolitan Atlanta, Seattle or Detroit diagnosed with ovarian cancer during 1994-1998, and with controls sampled from these populations. Information provided by 355 cases and 1,637 controls was analyzed using unconditional logistic regression. RESULTS: The risk among women in the top tenth, relative to women in the lowest fourth, of the distribution of body weight at age 18 years was 1.5 (95% confidence interval, 1.0-2.2); at age 30, 1.9 (1.2-2.9); and 5 years before the reference date, it was 2.1 (1.4-3.3). While our results did not substantiate risk elevations reported in previous studies among subsets of women (e.g., with particular histologic tumor subtypes or according to past oral contraceptive use), we noted a particularly increased risk among women who reported 10 or more pounds gained during their first year of oral contraceptive use. CONCLUSIONS: Our findings suggest that risk of epithelial ovarian cancer may be most closely linked with body weight in the relatively recent past (but before the time in which the disease may manifest as weight loss) among women who develop this disease during the years before or shortly after menopause.

A population-based study of the quality of life of cancer survivors and their family caregivers.

Although survival rates for all cancers continue to increase, few studies have examined the quality of life of both cancer survivors and family caregivers during the survivorship period after treatment has ended. Information is lacking on the stressors, resources, meaning, and quality of life reported by survivors and family caregivers and the interrelationship between survivors' and family caregivers' quality of life. A stratified, random sample of 123 cancer survivors and 123 family caregivers (N = 246) were interviewed in an exploratory, cross-sectional design 1-6 years after cancer treatment had ended. Approximately half (N = 62) of the dyads were white and half (N = 61) were African American. Results indicated that cancer survivors reported significantly higher quality of life, less fear of cancer recurrence, and more support than their family caregivers. The strongest predictors for cancer survivors' quality of life were family stressors, social support, meaning of the illness, and employment status, whereas the strongest predictors for family caregivers' quality of life were fear of recurrence and social support. Both the survivor's and family caregiver's quality of life independently contributed to the other's quality of life. Findings from this study suggest the importance of including both survivors and family caregivers in programs of care.

Lifetime recreational exercise activity and breast cancer risk among black women and white women.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: This study supports an inverse association between physical activity and breast cancer among black women and among white women.

Alcohol exposure and breast cancer: results of the women's contraceptive and reproductive experiences study.

OBJECTIVES: To explore associated biological outcomes and clarify the role of timing of exposure in the alcohol-breast cancer relationship. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

A case-control study of ovarian cancer in relation to infertility and the use of ovulation-inducing drugs.

The authors conducted a population-based, case-control study among women aged 35-54 years to assess the influence of infertility and use of ovulation-inducing drugs on ovarian cancer risk. The study was conducted from 1994 to 1998 in three regions (metropolitan Atlanta, Georgia, Detroit, Michigan, and Seattle, Washington) and included 378 cases and 1,637 controls. Data were obtained through in-person interviews, and analysis was conducted using unconditional logistic regression. Among parous women, the authors observed no association of cancer risk with a history of infertility, medical evaluation for infertility, specific types of infertility, or use of ovulation-inducing drugs. Among nulliparous women, risk was increased among women with a history of infertility (odds ratio = 1.6, 95% confidence interval: 1.0, 2.6), particularly when infertility first became manifest relatively late in reproductive life (for first infertility at > or =30 years of age: odds ratio = 2.2, 95% confidence interval: 1.1, 4.5); risk was not associated with medical evaluation for infertility, specific types of infertility, or use of ovulation-inducing drugs. Findings were similar when borderline and invasive epithelial tumors were considered separately. While the results of this study support the hypothesis that a subset of nulliparous women who experience infertility may be at increased risk of ovarian cancer, the reasons for this increase in risk remain unclear.

Reproductive factors and risk of breast carcinoma in a study of white and African-American women.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Absence of an effect of injectable and implantable progestin-only contraceptives on subsequent risk of breast cancer.

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.

Cancer among Arab Americans in the metropolitan Detroit area.

Detroit is home to one of the largest populations of Arab Americans outside of the Middle East, yet little is known about the cancer distribution in this ethnic group. The authors of this study created an Arab/Chaldean surname list and matched it with the Detroit SEER Registry to identify cancer cases of probable Arabic descent. We then determined proportional incidence ratios (PIR) for specific cancer sites among metropolitan Detroit Arab Americans as compared to non-Arab Whites, and contrasted the results with Middle Eastern data. Arab/Chaldean men had greater proportions of leukemia (29%), multiple myeloma (46%), liver (64%), kidney (33%), and urinary bladder (26%) cancers. Arab/Chaldean women had greater proportions of leukemia (23%), thyroid (57%), and brain (35%) cancers as compared with non-Arab White men and women. The cancers with significantly increased PIRs in the Detroit Arab/Chaldean population also are frequently diagnosed in Middle Eastern countries.

Association of regimens of hormone replacement therapy to prognostic factors among women diagnosed with breast cancer aged 50-64 years.

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.