Associations of the timing of sleep and meals with the presence of gastroesophageal reflux disease in community-dwelling women in Japan.

BACKGROUND: It has been suspected that circadian rhythms may play a part in the pathogenesis of gastrointestinal diseases including gastroesophageal reflux disease (GERD). The present study aimed to examine the cross-sectional association of the timing of sleep and meals with the presence of GERD in community-dwelling women in Japan. METHODS: In total, 605 women responded to a self-administered questionnaire asking for information on GERD symptoms, sleep habits, sleep disturbances and the timing of meals. GERD symptoms were evaluated using the Frequency Scale for the Symptoms of GERD, and participants with a score of more than seven points were classified as having GERD. RESULTS: In total, 104 (17.2%) women were found to have GERD. Later bedtime on both weekdays and weekends and later midpoint of sleep were significantly associated with the odds ratios (OR) of GERD after controlling for covariates: ORs for each 1 h delay were 1.31 (95% confidence interval [CI] = 1.03-1.68), 1.38 (95% CI = 1.08-1.75) and 1.43 (95% CI = 1.06-1.95). Having lunch at irregular times was significantly associated with the increased OR of GERD (1.99; 95% CI = 1.02-3.91). Longer overnight fasting duration and longer time intervals from the midpoint of sleep to breakfast and lunch were significantly associated with decreased OR of GERD (ORs for each 1 h increase were 0.73 [95% CI = 0.56-0.95], 0.64 [95% CI = 0.46-0.88] and 0.70 [95% CI = 0.51-0.96]). CONCLUSIONS: These data suggest that the timing of sleep and timing of meals relative to the sleep/wake cycle are associated with the presence of GERD.

Neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel plus trastuzumab and pertuzumab followed by epirubicin and cyclophosphamide for operable HER2-positive primary breast cancer: a multicenter phase II clinical trial (PerSeUS-BC04).

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a promising antibody partner for anti-human epidermal growth factor receptor 2 (HER2). We performed neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer (BC) using nab-PTX plus trastuzumab (T-mab) and pertuzumab (P-mab), followed by epirubicin and cyclophosphamide (EC). METHODS: In this multicenter phase II clinical trial (January 2019-July 2020), patients with stage I (T1c)-IIIB HER2-positive primary BC were treated with four cycles of nab-PTX plus T-mab and P-mab, followed by four cycles of EC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints were clinical response rate (RR), adverse events (AE), and tumor-infiltrating lymphocytes (TILs) in biopsy samples. RESULTS: In total, 43 patients were enrolled (mean age, 54 years). Twenty-two patients had HER2, and 21 patients had luminal/HER2-subtypes. The overall pCR rate was 53.5% (23/43, 95% CI: 42.6-64.1%, p = 0.184), whilst the pCR for HER2 was 68.2% (15/22, 95% CI: 45.1-86.1) and 38.1% for luminal/HER2 (8/21, 95% CI: 18.1-61.6%). The RR was 100% [clinical (c) CR:25, partial response (PR): 18]. AEs (≥ G3) included neutropenia (23.3%), leukopenia (7.0%), liver dysfunction (7.0%), and peripheral neuropathy (4.7%) when nab-PTX was administered. EC administration resulted in leukopenia (34.2%), neutropenia (31.6%), and febrile neutropenia (15.8%). The TILs in preoperative biopsy samples were significantly higher in pCR compared to non-pCR samples. CONCLUSION: Nab-PTX plus T-mab and P-mab induced a high pCR rate in HER2-positive BC, particularly in the HER2-subtype. Given that AEs are acceptable, this regimen is safe and acceptable as NAC for HER2-positive BC.

Sleep duration, nightshift work, and the timing of meals and urinary levels of 8-isoprostane and 6-sulfatoxymelatonin in Japanese women.

It has been hypothesized that disruption of circadian rhythms affects human health. Shift work and sleep deprivation are thought to disrupt the normal light-dark cycle, although the disruption due to shiftwork may be dependent on sleep deprivation. Both conditions have been suggested to be associated with an increased risk of cardiometabolic disorders. Non-photic environmental factors, such as the timing of eating, are also thought to regulate circadian rhythm and thus, may have effects on health, but the evidence from human studies is scarce. Oxidative stress is a risk factor of cardiometabolic disorders. Some laboratory studies suggest an involvement of circadian clock genes in the regulation of the redox system. The present study aimed to examine the association of sleeping habits, nightshift work, and the timing of meals with urinary levels of 8-isoprostane, a marker of oxidative stress, and 6-sulfatoxymelatonin, the principal metabolite of melatonin. Study subjects were 542 women who had previously attended a breast cancer mass screening in a community in Japan. Information on bedtimes and wake-up times, history of nightshift work, and the timing of meals was obtained by a self-administered questionnaire. The 8-isoprostane and 6-sulfatoxymelatonin were measured using the first morning void of urine and expressed per mg of creatinine. The geometric mean of 8-isoprostane levels was 12.1% higher in women with ≤6 hours of sleep than that in those with >8 hours of sleep on weekdays, and longer sleep duration on weekdays was significantly associated with lower urinary levels of 8-isoprostane after controlling for covariates (p for trend = 0.04). Women who were currently working the nightshift had a 33.3% higher geometric mean of 8-isoprostane levels than those who were not working nightshift (p = 0.03). Urinary 6-sulfatoxymelatonin levels were unrelated to sleep habits or nightshift work. Women who ate breakfast at irregular times had a 19.8% higher geometric mean of 8-isoprostane levels than those who ate breakfast at a regular time or who did not eat (p = 0.02). Women who ate nighttime snacks at irregular times had a 16.2% higher geometric mean of 8-isoprostane levels than those who did not eat nighttime snacks or who ate nighttime snacks at a regular time (p = 0.003). Among women who ate dinner at a regular time, earlier times for dinner were associated with higher 8-isoprostane and 6-sulfatoxymelatonin levels (p values for trends were 0.01 and 0.02, respectively). However, the times of dinner and nighttime snack are overlapping, and the time of last meal of the day was not associated with 8-isoprostane and 6-sulfatoxymelatonin levels. The time of breakfast or lunch was not associated with these biomarkers among women who ate the meal at regular times. Disturbing the rhythmicity of daily life may be associated with oxidative stress.

Preoperative neoadjuvant chemotherapy using nanoparticle albumin-bound paclitaxel followed by epirubicin and cyclophosphamide for operable breast cancer: a multicenter phase II trial.

BACKGROUND: Recently, the use of taxane-based regimens before anthracycline-based regimens has been shown to achieve high pathological complete response (pCR) rates in patients with breast cancer. Nanoparticle albumin-bound paclitaxel (nab-PTX) has been reported as highly effective and less toxic compared with Cremophor-based Taxol. This phase II clinical trial evaluated the safety and efficacy of preoperative neoadjuvant chemotherapy (NAC) with nab-PTX followed by an epirubicin plus cyclophosphamide (EC)-based regimen for operable breast cancer. PATIENTS AND METHODS: From June 2012 to January 2014, four cycles of every-3-week (q3w) nab-PTX [plus q3w trastuzumab in cases of human epidermal growth factor 2 (HER2) positivity] followed by four cycles of q3w EC were administered to patients with operable breast cancer (stage IC-IIIA). The primary endpoint was the pCR rate (ypT0/TisypN0). RESULTS: A total of 55 patients were enrolled, 54 of whom received at least one nab-PTX dose. All patients underwent radical surgery after chemotherapy. The overall pCR rate was 22.2% (p = 0.006). The pCR rates for patients with the luminal B, luminal/HER2, HER2-rich, and triple-negative breast cancer subtypes were 10.5, 29.4, 60, and 15.4%, respectively. Stepwise logistic regression analysis revealed only HER2 as a significant factor for pCR (odds ratio 5.603; p = 0.024). The expression of secreted protein acidic and rich in cysteine showed no association with pCR. The clinical response rate was 70.4% (38/54), and the safety profile was tolerable. CONCLUSION: Preoperative NAC with nab-PTX followed by EC is effective and safe for operable breast cancer.

A case of carcinoma of the papilla of Vater in a young man after subtotal colectomy for familial adenomatous polyposis.

BACKGROUND: Carcinoma and adenoma of the duodenum, including the papilla of Vater, are problematic diseases in patients with familial adenomatous polyposis (FAP). CASE PRESENTATION: A 36-year-old man underwent a periodic medical examination for early colon cancer originating from FAP for which laparoscopic-assisted subtotal colectomy with a J-shaped ileal pouch-rectal anastomosis was performed 3 years earlier. A tumor was detected at the papilla of Vater along with elevation of total bilirubin and hepatobiliary enzymes. Although cytology did not determine the tumor to be an adenocarcinoma, we suspected adenocarcinoma due to its hypervascularity shown by contrast-enhanced computed tomography. Pylorus-preserving pancreaticoduodenectomy with modified Imanaga reconstruction and regional lymph node dissection (D2) was performed. The pathological study showed that the tumor was a papillary and moderately differentiated tubular adenocarcinoma. The patient is currently in good health without recurrence, weight loss, or severe diarrhea at 12 months after surgery. CONCLUSIONS: Awareness of biliary-pancreatic symptoms and periodic gastroduodenoscopy might contribute both to the early detection of duodenal or periampullary polyps and cancer and to the radical treatment of FAP. Modified Imanaga reconstruction has the potential to become one of the more effective procedures for providing good quality of life to FAP patients with duodenal or periampullary cancer.

High-dose toremifene for fulvestrant-resistant metastatic breast cancer: a report of two cases.

INTRODUCTION: Hormone receptor (HR)-positive metastatic breast cancer (MBC) is usually treated with hormone therapy. In postmenopausal females, aromatase inhibitors (AIs) are usually used as first-line therapy, and fulvestrant is used subsequently. The optimal treatment beyond fulvestrant has not been established. We experienced two cases in which high-dose toremifene (hdTOR) was effective after the failure of AIs and fulvestrant. CASE 1: A 73-year-old female with HR-positive left breast cancer (T2N1M0) underwent preoperative chemotherapy and mastectomy with axillary dissection. Computed tomography (CT) revealed liver tumors in S7 (23 mm) and S8 (25 mm) during adjuvant letrozole therapy, so fulvestrant was started. The tumors initially decreased in size (23 and 22 mm), but then progressed (36 and 25 mm). Treatment was changed to hdTOR, and the tumors shrunk to 26 mm (S7) and 24 mm (S8), and she was stable for 6 months while receiving hdTOR. CASE 2: An 81-year-old female with HR-positive left breast cancer (T2N1M0) underwent left mastectomy and axillary dissection. CT revealed liver tumors in S7 (20 mm) and S8 (11 mm) during adjuvant letrozole therapy, so fulvestrant treatment was started. The tumor in S7 shrunk (13 mm), but the tumor in S8 slightly progressed (13 mm), and both tumors progressed (14 and 18 mm) after 6 months. Treatment was changed to hdTOR, and the tumors slightly shrunk (12 and 14 mm) after 6 months. hdTOR has been continued for 9 months. CONCLUSION: hdTOR was effective for MBC after multiple hormone therapies, likely because it acts via a different mechanism of action.

Two cases of mastectomy after Paclitaxel + bevacizumab therapy for locally advanced breast cancer.

INTRODUCTION: Locally advanced breast cancer (LABC) deteriorates the quality of life (QOL) of the affected patients. Combination chemotherapy or extended chemotherapy is considered to help to shrink local lesions. CASE 1: A 71-year-old female with a history of tympanitis and cystitis with methicillin-resistant Staphylococcus aureus (MRSA) visited our hospital. There was a tumor of 7 cm in diameter in her right breast with skin ulceration. Paclitaxel + bevacizumab therapy was started, and after five cycles of therapy, a mastectomy with axillary dissection was performed. Chemotherapy with anthracycline was avoided for fear of activating the MRSA. After the operation, the patient's wound opened. However, it naturally epithelialized. CASE 2: A 41-year-old female visited our hospital due to a tumor of 8 cm in diameter in her right breast with skin ulceration. Four cycles of paclitaxel + bevacizumab therapy were started, and her tumor almost disappeared during the first cycle. Then, doxorubicin + cyclophosphamide therapy was performed for four cycles, and a mastectomy with axillary dissection was performed. Her postoperative course was good. DISCUSSION: Chemotherapy with bevacizumab or extended chemotherapy is generally not considered to contribute to a survival improvement. However, such therapy contributes in increasing the response to chemotherapy, and should be considered for patients with LABC to shrink the local lesions and improve the QOL.

The efficacy of second-line hormone therapy for recurrence during adjuvant hormone therapy for breast cancer.

OBJECTIVES: The recurrence of breast cancer during adjuvant hormone therapy is often targeted by second-line hormone therapy. However, there has been a lack of prior success with such treatments. We retrospectively investigated the efficacy of subsequent hormone therapy. METHODS: Patients who underwent breast cancer surgery between 2006 and 2012 at our institution were investigated. RESULTS: A total of 20 patients developed recurrence during adjuvant hormone therapy. There were four patients with luminal A, seven with luminal B and six with luminal HER2 tumors, respectively. Twelve patients received subsequent hormone therapy, and eight patients received chemotherapy. Subsequent hormone therapy produced one partial response (PR), two long stable disease (SD), one SD and five progressive disease (PD). A clinical benefit (CB) was obtained by 33%. Subsequent chemotherapy produced one complete response (CR), two PRs, one long SD and two PD, resulting in a CB in 66%. Among those who received any hormone therapy, the best responses were two PR, three long SD and one SD. A CB was obtained by 38%, while seven patients did not have any CB from hormone therapy. Meanwhile, the best responses to chemotherapy were two CRs, four PRs, three SD and two PD, thus resulting in a CB in 72%. All luminal A cases obtained a long SD or SD with hormone therapy. However, the CB of hormone therapy for non-luminal A cases was only 30%. CONCLUSIONS: The efficacy of hormone therapy for recurrence during adjuvant hormone therapy is poor, and when selecting therapy for such patients, the breast cancer subtype should be taken into account.

Efficacy of chemotherapy after hormone therapy for hormone receptor-positive metastatic breast cancer.

OBJECTIVE: According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor-positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy-effective and hormone therapy-ineffective cases. METHODS: Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. RESULTS: A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+) status, while 7 patients had human epidermal growth factor receptor 2-positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy-ineffective patients (52.6%). A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%). The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085). However, there were no significant differences in the response to or duration of chemotherapy. CONCLUSION: The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype, and clinicians should administer chemotherapy in all cases of hormone receptor-positive metastatic breast cancer, if needed.

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.

Multiple bone metastases detected 10 years after mastectomy with silicone reconstruction for DCIS and contralateral augmentation.

KEY CLINICAL MESSAGE: The patient developed multiple bone metastases following mastectomy with silicone reconstruction and contralateral augmentation for ductal carcinoma in situ (DCIS) of the breast. She was diagnosed with contralateral invasive cancer. Distant metastasis of DCIS is rare, and other metastatic origins must be screened. However, screening of augmented breasts is difficult.

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.