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Background: Oral contraceptives (OC) are widely used in the United States. Although the relation between OC use and breast cancer incidence has been widely studied, the few studies examining associations between OC use prior to breast cancer diagnosis and survival are inconsistent., Methods: Women with invasive breast cancer participating in the Women's Contraceptive and Reproductive Experiences (CARE) Study, a population-based case-control study (4565 women ages 35-64 years), and the California Teachers Study (CTS) cohort (3929 women ages 28-91 years) were followed for vital status. A total of 1,064 women died in the CARE Study (median follow-up, 8.6 years) and 523 died in the CTS (median follow-up, 6.1 years). Cox proportional hazards regression provided hazard rate ratio estimates [(relative risk, RR)] with 95% confidence intervals (CIs) for risk of death from any cause and from breast cancer., Results: No association was observed for any OC use prior to diagnosis and all-cause mortality [CARE Study: RR = 1.01 (95% CI = 0.86-1.19); CTS: RR = 0.84 (95% CI = 0.67-1.05)]. A decreased risk of all-cause mortality was observed in the CTS among women with more than 10 years of OC use (RR = 0.67, 95% CI = 0.47-0.96); however, no trend of decreasing risk with increasing OC duration was observed (P(trend) = 0.22), and no association was observed in the CARE study. No associations were observed for breast cancer-specific mortality., Conclusions: OC use is not associated with all-cause or breast cancer-specific mortality among women with invasive breast cancer., Impact: These 2 independent studies demonstrated no overall association between OC use and survival among women with breast cancer., (©2011 AACR)

Background: Urinary bladder cancer is two to four times more common among men than among women, a difference in risk not fully explained by established risk factors. Our objective was to determine whether hormonal and reproductive factors are involved in female bladder cancer., Methods: We analyzed data from two population-based studies: the Los Angeles-Shanghai Bladder Cancer Study, with 349 female case-control pairs enrolled in Los Angeles and 131 female cases and 138 frequency-matched controls enrolled in Shanghai, and the California Teachers Study (CTS), a cohort of 120,857 women with 196 incident cases of bladder urothelial carcinoma diagnosed between 1995 and 2005. We also conducted a meta-analysis summarizing associations from our primary analyses together with published results., Results: In primary data analyses, parous women experienced at least 30% reduced risk of developing bladder cancer compared with nulliparous women (Shanghai: OR = 0.38, 95% CI: 0.13-1.10; CTS: RR = 0.69, 95% CI: 0.50-0.95) consistent with results of a meta-analysis of nine studies (summary RR = 0.73, 95% CI: 0.63-0.85). The CTS, which queried formulation of menopausal hormone therapy (HT), revealed a protective effect for use of combined estrogen and progestin compared with no HT (RR = 0.60, 95% CI: 0.37-0.98). Meta-analysis of three studies provided a similar effect estimate (summary RR = 0.65, 95% CI: 0.48-0.88)., Conclusions: A consistent pattern of reduced bladder cancer risk was found among parous women and those who used estrogen and progestin for HT., Impact: These results suggest that more research is warranted to investigate hormonal and reproductive factors as possible contributors to bladder cancer risk., (©2011 AACR.)

Background: Results from studies examining the association between hormone therapy (HT) and lung cancer risk disagree., Methods: We examined the associations between HT use and lung cancer risk among 60,592 postmenopausal women enrolled in the prospective California Teachers Study cohort. Between 1995 and 2007, a total of 727 women had a diagnosis of lung cancer. Multivariable Cox proportional hazards regression models were fit using age as the time metric., Results: No measure of HT use was associated with lung cancer risk (all P(trend) values ≥0.4). In addition, no variations in risk by smoking status (never, ever, former, current), type of HT [estrogen (E)-alone, E + progestin (P) use], type of menopause, or lung cancer histology were observed., Conclusions: Our findings do not support an association between HT and lung cancer., Impact: This large-scale, prospective study, which capitalizes on the detailed hormone use, smoking history, and type of menopause information available within this unique cohort, was unable to find any association between intake of HT and lung cancer risk., (©2011 AACR.)

Background: Although it is well established that combined estrogen-progestin therapy (EPT) increases breast cancer risk, questions remain regarding the effect of different formulations of hormones, whether certain women are at particularly high risk, and whether risk varies by tumor subtype., Methods: We investigated hormone therapy (HT) use in relation to breast cancer risk in the California Teachers Study cohort; after a mean follow-up of 9.8 years, 2,857 invasive breast cancers were diagnosed., Results: Compared with women who had never used HT, women who reported 15 or more years of estrogen therapy (ET) use had a 19% greater risk of breast cancer (95% confidence interval, 1.03-1.37), whereas women using EPT for 15 or more years had an 83% greater risk (95% confidence interval, 1.48-2.26). Breast cancer risk was highest among women using continuous combined EPT regimens. Risks associated with EPT and ET use were increased with duration of HT use for women with a body mass index (BMI) of <29.9 kg/m(2) but not for women with BMI of >or=30 kg/m(2). Elevated risks associated with EPT and ET use were confined to tumors that were positive for both estrogen and progesterone receptors and those that were HER2+ but were slightly diminished for HER2- tumors., Conclusions: Breast cancer risks increased with longer duration of ET and EPT use, and risks were highest for continuous-combined EPT use. Furthermore, risks varied by BMI and tumor subtype., Impact: These findings underscore the need for personalized risk-benefit discussions with women contemplating HT use., ((c)2010 AACR.)

Background: Although recent reviews have suggested active smoking to be a risk factor for breast cancer, the association with passive smoke exposure remains controversial. This risk association was explored in a large prospective study of women, the California Teachers Study., Methods: Detailed lifetime information on passive smoke exposure by setting (home, work, or social) and by age of exposure was collected in 1997 from 57,523 women who were lifetime nonsmokers and had no history of breast cancer. In the ensuing decade, a total of 1,754 women were diagnosed with invasive breast cancer. Cox proportional hazards models were fit to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) associated with several lifetime passive smoke exposure metrics., Results: For all breast cancer, measures of higher lifetime passive smoking intensity and duration were associated with nonstatistically significant HRs of 1.11 to 1.14. For postmenopausal women, HRs for lifetime low, medium, and high cumulative exposure were 1.17 (95% CI, 0.91-1.49), 1.19 (95% CI, 0.93-1.53), and 1.26 (95% CI, 0.99-1.60). For women exposed in adulthood (age > or =20 years), risk was elevated at the highest level of cumulative exposure (HR, 1.18; 95% CI, 1.00-1.40), primarily among postmenopausal women (HR, 1.25; 95% CI, 1.01-1.56). A statistically significant dose response was detected when analysis was restricted to women with moderate to high levels of passive smoke exposure., Conclusion: These results suggest that cumulative exposures to high levels of sidestream smoke may increase breast cancer risk among postmenopausal women who themselves have never smoked tobacco products.

Introduction: Long-term physical activity is associated with lower breast cancer risk. Little information exists on its association with subsequent survival., Methods: California Teachers Study cohort members provided information in 1995-1996 on long-term (high school through age 54 years) and recent (past 3 years) participation in moderate and strenuous recreational physical activities. The 3,539 women diagnosed with invasive breast cancer after cohort entry and through December 31, 2004, were followed through December 31, 2005. Of these, 460 women died, 221 from breast cancer. Moderate and strenuous physical activities were combined into low (3.0 h/wk/y), or high activity (>3.0 h/wk/y of either activity type). Multivariable relative risks (RR) and 95% confidence intervals (95% CI) for mortality were estimated using Cox proportional hazards methods, adjusting for race/ethnicity, estrogen receptor status, disease stage, and baseline information on comorbidities, body mass index, and caloric intake., Results: Women with high or intermediate levels of long-term physical activity had lower risk of breast cancer death (RR, 0.53; 95% CI, 0.35-0.80; and RR, 0.65; 95% CI, 0.45-0.93, respectively) than women with low activity levels. These associations were consistent across estrogen receptor status and disease stage, but were confined to overweight women. Deaths due to causes other than breast cancer were related only to recent activity., Conclusions: Consistent long-term participation in physical activity before breast cancer diagnosis may lower risk of breast cancer death, providing further justification for public health strategies to increase physical activity throughout the lifespan.

Previous studies on the relationship between obesity and circulating insulin-like growth factor (IGF) hormones show inconsistent findings and have not considered the possibility of racial/ethnic-specific differences that may exist. We therefore examined the relationship between obesity status [as measured by body mass index (BMI)] and plasma levels of the IGF proteins, IGF-I, IGF-binding protein 3 (IGFBP-3), and the molar ratio of IGF-I/IGFBP-3 in Whites, African Americans, Latinos, Japanese Americans, and Native Hawaiians from the ongoing Hawaii and Los Angeles Multiethnic Cohort Study. We measured plasma IGF-I and IGFBP-3 by ELISA in a random sample of 811 Multiethnic Cohort participants (53% male, age range = 47-82 at blood draw). In a multivariate regression of IGF-I levels, we found a statistically significant interaction between race/ethnicity and obesity status (P = 0.005). Plasma IGF-I levels declined with increasing BMI most dramatically in Latinos and Japanese. This decline was attenuated in Whites and absent in African-American and Native Hawaiian subjects. In Japanese, the quadratic term (BMI(2)) was statistically significant in a multivariate model (P = 0.002). In Latinos, the adjusted least-squares mean IGF-I levels in ng/mL for BMI < 25, 25 to 29.99, and >or=30 were 184.6, 147.7, and 132.7, respectively. No interaction between race/ethnicity and BMI explained the plasma IGFBP-3 levels in these data. These results may help to resolve the uncertainty in the relationship between circulating IGF levels and obesity and highlight the potential importance of racial/ethnic-specific effects among these factors in explaining ethnic disparities in obesity-related cancers.