Cadmium exposure and the risk of breast cancer in Japanese women.

Non-occupational exposure to cadmium has been suspected to be a risk factor for breast cancer. The present study examined the association between urinary cadmium level and the risk of breast cancer in a case-control study among Japanese women. Cases were 153 women newly diagnosed and histologically confirmed with breast cancer at a general hospital in Gifu, Japan. A total of 431 controls individually matched to cases by age, menopausal status, and the period of urine sampling were selected from those who attended a breast cancer mass screening at this hospital. Urinary cadmium levels were measured using spot urine samples. Spot urine samples were collected from cases after surgery but before any cancer therapy. For controls, spot urine samples were obtained at the date of the screening visit. Information on known or suggested breast cancer risk factors was obtained by a self-administered questionnaire. The odds ratios (ORs) and 95 % confidence intervals (CIs) of breast cancer according to the tertile of the creatinine-adjusted cadmium level were calculated using conditional logistic regression models. Women in the highest tertile of the creatinine-adjusted cadmium level (>2.620 µg/g) had significantly elevated OR of breast cancer relative to those in the lowest tertile (<1.674 µg/g) after controlling for covariates [OR = 6.05, (95 % CI 2.90, 12.62)]. The trend of increase in risk with increasing cadmium level was also statistically significant [OR = 1.67, (95 % CI 1.39, 2.01) for every 1.0 µg/g increase in urinary cadmium level, P-trend <0.01]. These data suggested that exposure to cadmium was associated with a risk of breast cancer in Japanese women.

Causal attributions to epidemiological risk factors and their associations to later psychological adjustment among Japanese breast cancer patients.

GOALS: The objective of this study was to evaluate the causal attributions for breast cancer and their association with the subsequent psychological adjustment. MATERIALS AND METHODS: Sixty-three Japanese patients newly diagnosed with breast cancer were asked by an interviewer about risk factors and explanations for the etiology of breast cancer using a four-point scale. The General Health Questionnaire (GHQ-28) and the Center for Epidemiologic Studies Depression Scale (CES-D) were administered about 2 months later to measure psychological adjustment to the illness. The relationship between each causal attribution and measure of psychological adjustment was assessed with the Spearman rank correlation after adjusting for potential confounders (age, marital status, cancer stage at diagnosis, time between the day of diagnosis and follow-up, and physical symptoms at the follow-up). MAIN RESULTS: Attributions to several explanations, including "stress" and "personal characteristics," were positively associated with the GHQ-28 measures. Of the attributions to risk factors, "body size" was significantly inversely (r = -0.29) associated and "never having children" was insignificantly and highly inversely (r = -0.77) associated with the GHQ-28 measures, indicating better adjustment to the illness. On the other hand, the attribution to "tobacco" was significantly and positively associated with the GHQ-28 measures (r = 0.34), indicating that the attributions antagonized adjustment to the illness. CONCLUSION: The current study indicates that forming causal attributions influences the adjustment to the illness in Japanese breast cancer patients and attributions to certain risk factors for breast cancer may contribute to better adjustment.

Light exposure at night, urinary 6-sulfatoxymelatonin, and serum estrogens and androgens in postmenopausal Japanese women.

It has been hypothesized that exposure to light at night increases the risk of breast cancer by suppressing the normal nocturnal increase in melatonin production and release, thereby resulting in increased levels of circulating estrogen. We assessed associations among concentrations of serum estrogen and androgen and the principal metabolite of melatonin in urine, 6-sulfatoxymelatonin, and exposure to light at night based on information regarding the sleeping habits and history of graveyard-shift work of 206 postmenopausal Japanese women. Serum estradiol level was significantly higher in women who were not asleep at or after 1:00 a.m. (the approximate time of the melatonin peak) than those who were asleep after controlling for covariates. Significantly increased estrone levels were observed in women who had worked graveyard shift. Serum testosterone and DHEA sulfate were unrelated to sleeping habits and history of graveyard-shift work. Urinary 6-sulfatoxymelatonin was lower in women who were not asleep at or after 1:00 a.m. on weekends than those who were asleep at this time, but the difference was of borderline significance (P = 0.08). There was no significant association between urinary 6-sulfatoxymelatonin and any serum hormone levels. These data suggest that exposure to light at night has implications for the risk of breast cancer in postmenopausal women. However, the potential role of melatonin as an intervening factor between light exposure at night and the serum concentrations of estrogen was equivocal.

Dietary and lifestyle correlates of urinary excretion status of equol in Japanese women.

The isoflavone metabolite equol has been identified in urine or blood samples in some but not all humans. In this cross-sectional study, we examined the association between lifestyle, including diet, and the urinary excretion of equol. Study subjects were 419 Japanese women who were recruited from a breast cancer screening center. Each woman responded to a self-administered questionnaire seeking information about health and lifestyle factors. Diet was assessed by a validated semiquantitative food frequency questionnaire. Urinary isoflavones were measured using spot urine samples. Equol was detected in the urine of 84 (20.0%) women. After controlling for covariates, it was found that dairy product intake was significantly lower in those who excreted detectable equol levels in urine than in those who did not. Because equol is derived from daidzein, individuals with low intake of daidzein may produce undetectable levels of equol. To account for this, the study subjects were restricted to 163 women with urinary daidzein levels of 10 nmol/mg creatinine or higher. The association of equol excretion with dairy product intake remained significant. Demographic factors, smoking status, and menstrual and reproductive factors were unrelated to equol excretion. These data suggest that dairy product intake may be associated with the production of equol.

Urinary 6-sulfatoxymelatonin and mammographic density in Japanese women.

A protective role of melatonin in the etiology of breast cancer has been suggested. The down-regulation of estrogen secretion by melatonin is thought to be a main cause of the link between melatonin and breast cancer risk. The present cross-sectional study examined whether the urinary 6-sulfatoxymelatonin (aMT6-s) level is inversely associated with mammographic density, which is regarded as a marker of breast cancer risk. The study subjects were 289 Japanese women (175 premenopausal and 123 postmenopausal women) who were recruited from participants in a mammographic breast cancer screening. The size of the total breast area and that of the dense area were measured quantitatively using an automated mammographic mass detection method. The concentration of aMT6-s was measured using first-void morning urine. In premenopausal women, the urinary aMT6-s level was significantly positively associated with percent density after controlling for covariates (P for trend=0.02). There was no significant association between urinary aMT6-s level and the percent density in postmenopausal women. We found no evidence that the melatonin level is inversely associated with mammographic density.

Fat intake is associated with serum estrogen and androgen concentrations in postmenopausal Japanese women.

A reduction in fat intake has been associated with decreased estrogen levels in dietary intervention studies. However, previous cross-sectional studies conducted mainly among Western populations did not find a positive association between fat intake and postmenopausal estrogen levels. This study examined the cross-sectional association of fat intake with serum levels of estrone, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEAS) in women. Study subjects were 324 healthy postmenopausal Japanese women. Diet including fat intake was assessed by a validated semiquantitative FFQ. After controlling for age and other potential breast cancer risk factors, serum estrone was positively associated with the percentage of energy from total fat (P = 0.04). The associations of serum estrone with monounsaturated fat and polyunsaturated fat were of borderline significance (P = 0.05). Serum DHEAS was positively associated with the percentage of energy from total fat (P = 0.007), saturated fat (P = 0.009), monounsaturated fat (P = 0.006), and polyunsaturated fat (P = 0.04). Serum estrone and DHEAS concentrations increased 11.8 and 9.3%, respectively, with a 5% increase in the percentage of energy from total fat. These data suggest that a high intake of fat is associated with higher serum levels of estrone and DHEAS in postmenopausal women.

Associations of mammographic density with dietary factors in Japanese women.

BACKGROUND: A high percentage of mammographic dense area has been strongly associated with a risk of beast cancer. The present cross-sectional study evaluated the relations of percent density with dietary factors, such as fats, protein, dietary fiber, and soy isoflavones. METHODS: Study subjects were 601 (348 premenopausal and 253 postmenopausal) Japanese women who were recruited from a mammographic screening center. The size of the total breast area and the dense area were measured quantitatively using an automated mammographic mass detection method. Intakes of nutrients were estimated with a validated semiquantitative food-frequency questionnaire. RESULTS: The crude means of the percent density were 39.2% and 18.9% in premenopausal and postmenopausal women, respectively. There were no significant associations of any dietary factors with the percent density in premenopausal women. In postmenopausal women, percent density was significantly positively associated with intakes of protein, total fat, and saturated fat after controlling for covariates; the increase in the means of percent density were 7.2%, 5.6%, and 9.2% in the highest versus lowest quartile of intakes for protein, total fat, and saturated fat, respectively (P for linear trend were 0.006, 0.04, and 0.01, respectively). Carbohydrate intake was inversely associated with percent density; the mean of percent density was 6.0% lower in the highest versus the lowest quartile of intake (P(trend) = 0.03). The associations of dietary factors with dense area were very similar to those with percent density. CONCLUSION: These dietary factors may have implications for the risk of breast cancer in postmenopausal women.

Association of vegetable intake with urinary 6-sulfatoxymelatonin level.

Melatonin is present in plants consumed as vegetables; however, only a limited number of vegetables have been tested for melatonin. The antiproliferative, antioxidative, and immunostimulatory effects of melatonin have been reported from laboratory studies. The potential protective effects of vegetable against cancer and cardiovascular disease may be partially attributable to an increased melatonin intake from vegetables. As a first step to test this hypothesis, we evaluated whether vegetable intake is associated with an increased urinary melatonin in 289 community-dwelling Japanese women. Diet, including vegetable consumption, was assessed with a validated 169-item semiquantitative food-frequency questionnaire. Urinary 6-sulfatoxymelatonin (aMT6-s) was measured in the first-void morning urines. There was a significant positive association between vegetable intake and urinary aMT6-s levels. The mean urinary aMT6-s was 16% higher in women with the highest quartile of vegetable intake than it was in those with the lowest quartile of intake. This association may be explained by the melatonin contained in vegetables. However, data should be regarded as preliminary because it is impossible to estimate dietary melatonin intake from vegetables and or from the entire diet because of incomplete data for melatonin in plants.

Urinary cadmium and serum levels of estrogens and androgens in postmenopausal Japanese women.

BACKGROUND: Recent laboratory studies have suggested that cadmium is an estrogenic compound and may be a potential risk factor for breast cancer. METHODS: We investigated the relationship between urinary cadmium concentrations and serum concentrations of estrone, testosterone, and dehydroepiandrosterone sulfate in 164 postmenopausal Japanese women. RESULTS: There was a significant positive association between the urinary cadmium and serum testosterone levels after controlling for age and body mass index. The mean testosterone level was 28% higher in women with high urinary cadmium (> or = 3.00 microg/g creatinine) than in those with low urinary cadmium (< 2.00 microg/g creatinine). Urinary cadmium was not significantly associated with serum estrone and dehydroepiandrosterone sulfate levels. Additional adjustment for smoking, alcohol and reproductive factors including known risk factors for breast cancer did not substantially alter the results. CONCLUSION: Data suggested that cadmium exposure is associated with increased testosterone levels. As high testosterone levels have been associated with the risk of breast cancer, the involvement of cadmium exposure in breast cancer risk should be evaluated in future studies.

Relationship between mammographic density and the risk of breast cancer in Japanese women: a case-control study.

BACKGROUND: The relationship between mammographic density and the risk of breast cancer was examined in Japanese women. The study was a matched case-control study comparing the mammographic densities of both breast cancer cases and healthy controls. MATERIALS AND METHODS: We selected 237 women who were diagnosed with a histologically verified breast cancer, and who underwent surgery at Gihoku General Hospital in Gifu, from January, 1998 to December, 1999. During the time of this study, 3,650 people participated in breast cancer screening with mammography and ultrasound together. We selected 742 women as a control group from the screening participants and matched them by age and the number of deliveries with the cancer patients. The same mammography machine was used for both cases and controls. For evaluation, we used a visual method (Wolfe's classification) and a computer assisted method to classify the mammograms based on mammographic density. RESULTS: (1) According to Wolfe's classification, the DY group had a significantly increased breast cancer risk compared with the N1 group (Relative risk (RR)=2.20, 95% confidence interval (95%CI) (1.02-4.77). (2) The group showing a high mammographic density had a significantly increased risk of breast cancer compared with the group with low mammographic density (RR=2.83, 95%CI=1.33-5.98) as classified by the computer assisted method. CONCLUSION: It is suggested that women with high mammographic densities, classified visually or by computer, have an elevated risk of breast cancer compared with those with low mammographic densities.

Comparison of mammographic densities and their determinants in women from Japan and Hawaii.

Breast cancer incidence increases considerably in women who migrate from Japan to the United States. Based on the hypothesis that mammographic density in healthy mammograms reflects differences in breast cancer risk, we compared mammographic density in 3 groups of women at different levels of risk: Caucasian and Japanese women in Hawaii and Japanese women in Japan. In a cross-sectional design, pre- and postmenopausal women without a history of breast cancer and with a mammogram free of suspicious lesions were recruited in mammography clinics and completed a self-administered questionnaire. Cranio-caudal mammograms were scanned into a computer and the densities measured using a computer-assisted method. Statistical analyses included ANOVA and multiple linear regression. Breast size among women of Japanese ancestry was similar in Hawaii and Japan but 50% smaller than that among Caucasian women. Dense areas were smallest among women in Japan, intermediate among Japanese women in Hawaii and largest among Caucasian women. Percent densities were greater in Japanese women than Caucasian women because of the larger breast sizes in Caucasians. However, percent densities were significantly higher among Japanese women in Hawaii than in Japan. These results indicate that the size of the total breast differs primarily by ethnicity and the size of the dense areas differs mainly by place of residence. Therefore, when comparing ethnic groups with distinct physical proportions, the absolute size of the dense areas appears to be a better measure of breast cancer risk than the relative density.

[Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer].

Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.