E. Dawn Fitzgibbons

Dietary and other risk factors in women having fibrocystic breast conditions with and without concurrent breast cancer: A nested case‐control study in Shanghai, China

Risk of breast cancer is increased in women with proliferative benign breast conditions. Most of these conditions, however, do not progress to breast cancer. The purpose of our study was to identify factors possibly associated with this progression. Women with proliferative fibrocystic breast conditions alone (214), and women with proliferative fibrocystic breast conditions and concurrent breast cancer (130), were compared to each other, and each of these groups of women were also compared to 1,070 controls; and 176 women with non‐proliferative benign breast conditions alone, and 155 also with breast cancer, were similarly compared. All study subjects were selected from a cohort of women enrolled in a trial of breast self‐examination in Shanghai. Women were interviewed to ascertain information on suspected risk factors for breast cancer and dietary habits. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Increased risks of both proliferative fibrocystic breast conditions alone, and with breast cancer, were associated with low parity, a prior benign breast lump and breast cancer in a first‐degree relative. Decreasing trends in the risk of both conditions with increasing intake of fruits and vegetables were observed. No factors were significantly associated with risk of breast cancer relative to risk of proliferative changes. Similar, but in some instances weaker, associations were observed for non‐proliferative fibrocystic conditions with and without breast cancer. The possible risk or protective factors that were observed in our study most likely alter the risk of breast cancer at an early stage in the carcinogenic process, and probably do not alter risk of progression from proliferative fibrocystic breast conditions to breast cancer.

Occupational exposures and breast cancer among women textile workers in Shanghai

Background: Breast cancer incidence rates have been increasing in China over the past 2 decades. Most studies have focused on reproductive, dietary, and genetic risk factors. Little is known about the contribution of occupational exposures. Methods: We conducted a case-cohort study within a cohort of female textile workers who had participated in a randomized trial of breast self-examination in Shanghai, China. We compared 1709 incident breast cancer cases with an age-stratified reference subcohort (n = 3155 noncases). Cox proportional hazards modeling, adapted for the case-cohort design, was used to estimate hazard ratios for breast cancer in relation to duration of employment in various job processes and duration of exposure to several agents. We also evaluated the associations of cotton dust and endotoxin with breast cancer. Results: Cumulative exposures to cotton dust and endotoxin demonstrated strong inverse gradients with breast cancer risk when exposures were lagged by 20 years (trend P-values <0.001). We did not observe consistent associations with exposures to electromagnetic fields, solvents, or other chemicals. Conclusion: Endotoxin or other components of cotton dust exposures may have reduced risks for breast cancer in this cohort, perhaps acting at early stages of carcinogenesis. Replication of these findings in other occupational settings with similar exposures will be needed to confirm or refute any hypothesis regarding protection against breast cancer.

Urinary equol excretion in relation to 2-hydroxyestrone and 16α-hydroxyestrone concentrations: an observational study of young to middle-aged women

Approximately one-third to one-half of individuals harbor the colonic bacteria that are capable of metabolizing the soy isoflavone daidzein to equol. Results of prior studies suggest beneficial effects of producing equol in relation to breast cancer risk, potentially through effects on endogenous hormones. High urinary excretion of 2-hydroxyestrone (2-OH E(1)) relative to 16alpha-hydroxyestrone (16alpha-OH E(1)) has been associated with a reduced risk of breast cancer. In this pilot study we examined associations between urinary excretion of equol and 2-OH E(1), 16alpha-OH E(1), and their ratio, and investigated whether excretion of these estrogen metabolites differed between two samples collected 48h apart. Isoflavones (genistein, daidzein, O-desmethylangolensin (ODMA), and equol) were measured in two overnight urines from 126 women. Excretion of 2-OH E(1) and 16alpha-OH E(1) were measured in the first overnight urine from all 126 women and in the second overnight urine from 30 of these women; there were no significant differences between samples collected 48h apart in excretion of 2-OH E(1) or 16alpha-OH E(1) (P=0.75 and 0.17, respectively). Among all women, correlations between total isoflavone excretion (sum of genistein, daidzein, ODMA, and equol) and estrogen metabolites were non-significant (P>0.05). Among women with detectable levels of equol, total isoflavone excretion was significantly positively correlated with 16alpha-OH E(1) (r=0.32, P=0.02), but was not correlated with 2-OH E(1) or 2-OH E(1):16alpha-OH E(1) ratio (r=0.21, P=0.14, and r=-0.05, P=0.70, respectively). Equol excretion (adjusted for other isoflavone excretion) was significantly positively correlated with 2-OH E(1):16alpha-OH E(1) ratio (r=0.38, P=0.005), but was not correlated with 2-OH E(1) or 16alpha-OH E(1) (r=0.15, P=0.29, and r=-0.17, P=0.24, respectively). The finding that equol excretion, but not total isoflavone excretion, correlated positively with the 2-OH E(1):16alpha-OH E(1) ratio suggests that the colonic bacterial profile associated with equol production may be involved in estrogen metabolism, and may therefore possibly influence breast cancer risk.

Occupational exposures and ovarian cancer in textile workers.

Background: Occupational risk factors for ovarian cancer have been investigated only to a limited extent. We conducted a case-cohort study to examine associations between occupational exposures and ovarian cancer in the textile industry. Methods: We compared 261 incident ovarian cancer cases diagnosed between 1989 and 1998 with an age-stratified reference subcohort (n = 3199) from a cohort of 267,400 textile workers in Shanghai, China. Occupational exposures were assessed by job-exposure matrices designed for the textile industry, and estimates of quantitative cotton dust and endotoxin. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox proportional hazards modeling adapted for the case-cohort design. Results: A decreased risk of ovarian cancer was associated with ever having worked in cotton manufacturing production (HR = 0.7; 95% CI = 0.4–1.0). An increased risk was associated with ever having worked in textile finishing (2.1; 0.9–5.0). We found an increasing risk of ovarian cancer associated with cumulative exposure to silica dust (for <10 years exposure, HR = 6.8 [CI = 0.6–76]; for ≥10 years, 5.6 [1.3–23.6]), although these results are based on only 8 exposed subcohort women (0.3%) and 4 cases (1.3%). We also detected inverse risk gradients for cumulative exposures to endotoxin when exposures were lagged by 20 years (in highest quartile, HR = 0.6 [CI = 0.4–1.1]). Conclusion: Silica dust may increase the risk of ovarian cancer, and cotton dust and endotoxin may reduce risk.

Mammographic Breast Density and Tolerance for Short-Term Postmenopausal Hormone Therapy Suspension

BACKGROUND Breast density tends to decrease when women stop taking hormone therapy (HT). Some women find HT cessation difficult to tolerate, possibly because of fluctuations in endogenous hormone levels and vasomotor symptoms. We hypothesized that women with dense breasts might have lower tolerance for short-term HT suspension than do women with fatty breasts. METHODS As part of the Radiologic Evaluation And breast Density (READ) trial, we randomly assigned 881 women aged 45-80 with a prior screening (index) mammogram to suspend HT for 1 or 2 months before their next screening (study) mammogram. We measured continuous breast density on index mammograms using computer-assisted thresholding. At study mammograms, women indicated tolerance for stopping HT from 1 (extremely difficult) to 7 (very easy). Using linear regression, we evaluated the association between index breast density and tolerance after cessation, adjusting for age, body mass index (BMI), HT type, randomization group, and vasomotor symptoms. RESULTS A higher percentage of breast density was associated with lower unadjusted mean tolerance scores (tolerance 4.27, 95% confidence interval [CI] 3.77-4.77 for women with > or =50% density, and 4.73, 95% CI 4.45-5.01 for women with <10% density, not a statistically significant difference). In adjusted analyses, neither percent breast density nor dense breast area was associated with tolerance for HT suspension. CONCLUSIONS Although HT use affects breast density, tolerance for suspending HT is not associated with breast density. Women with dense breasts have the greatest potential for decreases in density after HT cessation; they should tolerate stopping HT as well as women with fatty breasts.

Urinary equol excretion in relation to 2-hydroxyestrone and 16α-hydroxyestrone concentrations

Approximately one-third to one-half of individuals harbor the colonic bacteria that are capable of metabolizing the soy isoflavone daidzein to equol. Results of prior studies suggest beneficial effects of producing equol in relation to breast cancer risk, potentially through effects on endogenous hormones. High urinary excretion of 2-hydroxyestrone (2-OH E(1)) relative to 16alpha-hydroxyestrone (16alpha-OH E(1)) has been associated with a reduced risk of breast cancer. In this pilot study we examined associations between urinary excretion of equol and 2-OH E(1), 16alpha-OH E(1), and their ratio, and investigated whether excretion of these estrogen metabolites differed between two samples collected 48h apart. Isoflavones (genistein, daidzein, O-desmethylangolensin (ODMA), and equol) were measured in two overnight urines from 126 women. Excretion of 2-OH E(1) and 16alpha-OH E(1) were measured in the first overnight urine from all 126 women and in the second overnight urine from 30 of these women; there were no significant differences between samples collected 48h apart in excretion of 2-OH E(1) or 16alpha-OH E(1) (P=0.75 and 0.17, respectively). Among all women, correlations between total isoflavone excretion (sum of genistein, daidzein, ODMA, and equol) and estrogen metabolites were non-significant (P>0.05). Among women with detectable levels of equol, total isoflavone excretion was significantly positively correlated with 16alpha-OH E(1) (r=0.32, P=0.02), but was not correlated with 2-OH E(1) or 2-OH E(1):16alpha-OH E(1) ratio (r=0.21, P=0.14, and r=-0.05, P=0.70, respectively). Equol excretion (adjusted for other isoflavone excretion) was significantly positively correlated with 2-OH E(1):16alpha-OH E(1) ratio (r=0.38, P=0.005), but was not correlated with 2-OH E(1) or 16alpha-OH E(1) (r=0.15, P=0.29, and r=-0.17, P=0.24, respectively). The finding that equol excretion, but not total isoflavone excretion, correlated positively with the 2-OH E(1):16alpha-OH E(1) ratio suggests that the colonic bacterial profile associated with equol production may be involved in estrogen metabolism, and may therefore possibly influence breast cancer risk.