[Show abstract][Hide abstract] ABSTRACT: Mammographic screening with clinical breast examination has been recommended in Japan since 2000. Although mammographic screening without clinical breast examination has not been recommended, its introduction is anticipated. The efficacies of mammographic screening with and without clinical breast examination were evaluated based on the results of randomized controlled trials. PubMed and other databases for studies published between 1985 and 2014 were searched. The study design was limited to randomized controlled trials to evaluate mortality reduction from breast cancer. Five studies were eligible for meta-analysis of mammographic screening without clinical breast examination. The relative risk for women aged 40-74 years was 0.75 (95%CI: 0.67-0.83). Three studies evaluated the efficacy of mammographic screening with clinical breast examination. The relative risk for women aged 40-64 years was 0.87 (95%CI: 0.77-0.98). The number needed to invite was always lower in mammographic screening without clinical breast examination than in mammographic screening with clinical breast examination. In both screening methods, the number needed to invite was higher in women aged 40 years than in women aged 50-70 years. These results suggest that mammographic screening without clinical breast examination can afford higher benefits to women aged 50 years and over. Although evidence of the efficacy of mammographic screening without clinical breast examination was confirmed based on the results of the randomized controlled trials, a Japanese study is needed to resolve local problems. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Cancer Science 05/2015; 106(7). DOI:10.1111/cas.12693 · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aromatase inhibitors (AI) are commonly used to treat postmenopausal estrogen-receptor (ER)-positive breast carcinoma. However, resistance to AI is sometimes acquired, and the molecular mechanisms underlying such resistance are largely unclear. Recent studies suggest that AI treatment increases androgen activity during estrogen deprivation in breast carcinoma, but the role of the androgen receptor (AR) in breast carcinoma is still a matter of controversy. The purpose of this study is to examine the potential correlation between the AR- and AI-resistant breast carcinoma. To this end, we performed immunohistochemical analysis of 21 pairs of primary breast carcinoma and corresponding AI-resistant recurrent tissue samples and established two stable variant cell lines from ER-positive T-47D breast carcinoma cell line as AI-resistance models and used them in in vitro experiments. Immunohistochemical analysis demonstrated that the expression of prostate-specific antigen (PSA) and Ki-67 were significantly higher and ER and progesterone receptor (PR) were lower in recurrent lesions compared to the corresponding primary lesions. Variant cell lines overexpressed AR and PSA and exhibited neither growth response to estrogen nor expression of ER. Androgen markedly induced the proliferation of these cell lines. In addition, the expression profile of androgen-induced genes was markedly different between variant and parental cell lines as determined by microarray analysis. These results suggest that in some cases of ER-positive breast carcinoma, tumor cells possibly change from ER-dependent to AR-dependent, rendering them resistant to AI. AR inhibitors may thus be effective in a selectd group of patients.
The Journal of Steroid Biochemistry and Molecular Biology 08/2014; 144. DOI:10.1016/j.jsbmb.2014.08.019 · 3.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ScreeningFor reference: Categorization in the Japanese mammography guidelines and those of the Breast Imaging Reporting and Data SystemThe Breast Imaging Reporting and Data System (BI-RADS) developed by the American College of Radiology (ACR) as a standardized quality assessment tool for drawing up imaging findings and reports is universally recognized. In Japan, the “Guidelines for Mammography” complied on the basis of the 2nd edition of BI-RADS were published in 1999. According to those guidelines, mammogram findings are finally assessed for malignancy using 5 grading categories, i.e., category 1 or 2 requiring no additional detailed examination and categories 3–5 warranting further detailed examinations.The 4th edition of BI-RADS , on the other hand, is designed to provide a general flow of the breast cancer screening process as follows: lesions presenting screening mammographic findings based on which malignancy cannot be negated are classified into category 0 and subjected to d ...
Breast Cancer 08/2014; 22(1). DOI:10.1007/s12282-014-0557-8 · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The effectiveness of screening mammography (MMG) has mainly been demonstrated by studies in western countries. This study was conducted to evaluate cumulative survival and the risk of breast cancer death among Japanese women aged 40-69 years with screening-detected and interval breast cancer divided into three groups: MMG with clinical breast examination (CBE), CBE alone, and self-detection.
By matching a list of 126,537 women (358,242 person-screenings) who participated in the Miyagi Cancer Society Screening program between 1 April 1995 and 31 December 2002 with the Miyagi Prefectural Cancer Registry, 429 MMG with CBE, 522 CBE, and 3,047 self-detected cases were included in this study. Follow-up was performed until the date of death or 31 December 2007. Survival was estimated by the Kaplan-Meier method. The Cox proportional hazards model was used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for breast cancer death.
Five-year survival for women in the MMG with CBE, CBE, and self-detection groups was 96.8, 92.7, and 86.6 %, respectively. The HR (95 % CI) for breast cancer death was 2.38 (0.72-7.94) among CBE-screened and 4.44 (1.42-13.89) among self-detected cases for women aged 40-49 years, but was 3.00 (1.63-5.50) among CBE-screened and 4.51 (2.69-7.56) among self-detected cases for women aged 50-69 years relative to cases screened by use of MMG with CBE.
In terms of the survival and risk of breast cancer death, MMG with CBE may be more effective than MMG alone or self-detection for Japanese women aged 40-69 years.
Breast Cancer 12/2012; 21(5). DOI:10.1007/s12282-012-0434-2 · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The effectiveness of screening mammography (SMG) on mortality has been established in randomized controlled trials in Western countries, but not in Japan. This study evaluated the effectiveness by comparing the survival based on detection methods. The survivals were estimated by the Kaplan-Meier method. Breast cancer patients diagnosed from 1 January 1989 to 31 December 2000 were determined using the Miyagi Prefectural Cancer Registry and follow-up was performed from the date of the diagnosis until the date of death or the end of follow-up, 31 December 2005. The hazard ratios (HR) and 95% confidence interval (CI) of breast cancer death based on the detection methods were estimated by the Cox proportional-hazard regression model. The mean age of the 7513 patients was 55.7 years (range, 15.0-99.3). The 5-year survival associated with the SMG group, the clinical breast examination (CBE) group, and the self-detection group was 98.3%, 94.3%, and 84.8%, respectively. The HR (95% CI) of deaths from breast cancer was 2.50 (1.10-5.69) for patients in the CBE group and 6.57 (2.94-14.64) for the self-detection group in comparison to the SMG group. In women aged 50-59, the HRs were 1.64 (0.58-4.62) among the CBE group and 3.74 (1.39-10.03) among the self-detection group, and the HRs for the CBE and self-detection groups in women aged 60-69 were 2.96 (0.68-12.83) and 9.51 (2.36-38.26), respectively. After adjusting for stage, the HRs dropped remarkably. Screening mammography may be more effective in the elderly group and be able to reduce the mortality of breast cancer in Japan.
Cancer Science 06/2009; 100(8):1479-84. DOI:10.1111/j.1349-7006.2009.01212.x · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The age-specific sensitivity of a screening program was investigated using a population-based cancer registry as a source of false-negative cancer cases. A population-based screening program for breast cancer was run using either clinical breast examinations (CBE) alone or mammography combined with CBE in the Miyagi Prefecture from 1997 to 2002. Interval cancers were newly identified by linking the screening records to the population-based cancer registry to estimate the number of false-negative cases of screening program. Among 112 071 women screened by mammography combined with CBE, the number of detected cancers, false-negative cases and the sensitivity were 289, 22 and 92.9%, respectively, based on the reports from participating municipalities. The number of newly found false-negative cases and corrected sensitivity when using the registry were 34 and 83.8%, respectively. In detected cancers, the sensitivity of screening by mammography combined with CBE in women ranging from 40 to 49 years of age based on a population-based cancer registry was much lower than that in women 50-59 and 60-69 years of age (40-49: 18, 71.4%, 50-59: 19, 85.8%, 60-69: 19, 87.2%). These data suggest that the accurate outcome of an evaluation of breast cancer screening must include the use of a population-based cancer registry for detecting false-negative cases. Screening by mammography combined with CBE may therefore not be sufficiently sensitive for women ranging from 40 to 49 years of age.
Cancer Science 10/2008; 99(11):2264-7. DOI:10.1111/j.1349-7006.2008.00926.x · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the introduction of screening mammography in Japan would be expected to reduce mortality from breast cancer, the optimal screening modality in terms of cost-effectiveness remains unclear. We compared the cost-effectiveness ratio, defined as the cost required for a life-year saved, among the following three strategies: (1) annual clinical breast examination; (2) annual clinical breast examination combined with mammography; and (3) biennial clinical breast examination combined with mammography for women aged 30-79 years using a hypothetical cohort of 100 000. The sensitivity, specificity and early breast cancer rates were derived from studies conducted from 1995 to 2000 in Miyagi Prefecture. The treatment costs were based on a questionnaire survey conducted at 13 institutions in Japan. We used updated parameters that were needed in the analysis. Although the effectiveness of treatment in terms of the number of expected survival years was highest for annual combined modality, biennial combined modality had a higher cost-effectiveness ratio, followed by annual combined modality and annual clinical breast examination in all age groups. In women aged 40-49 years, annual combined modality saved 852.9 lives and the cost/survival duration was 3 394 300 yen/year, whereas for biennial combined modality the corresponding figures were 833.8 and 2 025 100 yen/year, respectively. Annual clinical breast examination did not confer any advantages in terms of effectiveness (815.5 lives saved) or cost-effectiveness (3 669 900 yen/year). While the annual combined modality was the most effective with respect to life-years saved among women aged 40-49 years, biennial combined modality was found to provide the highest cost-effectiveness.
Cancer Science 12/2006; 97(11):1242-7. DOI:10.1111/j.1349-7006.2006.00296.x · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In Japan, mammography was endorsed for breast cancer screening in women aged 40 and over by the Ministry of Health, Labor and Welfare in 2004. The spread of mammographic screening has caused an increase in the incidence of non-palpable breast cancer. Precision reading for mammography is necessary to detect non-palpable breast cancer. When mass and focal asymmetric density is noted, it is important to analyze the density, density gradient, internal structure, margin and associated findings. Calcifications are classified by morphology and distribution mainly. It is necessary to distinguish secretor-type calcifications from necrotic-type calcifications. The Iwate Cancer Association performed a population-based screening program for breast cancer using mammography combined with clinical breast examination of 42,065 women in Iwate Prefecture from 1999 to 2003. A total of 2,329(5.7%)women were recalled and the 112 cases(0.27%) of cancer were detected in 114 breasts. Of 114 breast cancers, 40 (35%) were non-palpable and 74(65%) were palpable. The early breast cancer (stage 0 and I) rate of the non-palpable group was significantly higher than that of the palpable group (90% and 47%, p = 0.0003). The node-negative rate of the non-palpable group was significantly higher than that of the palpable group (92% and 68%, p = 0.011). It is expected that mammographic screening will be expanded and that the mortality rate from breast cancer in Japan will decrease, as in Europe and the United States.
Breast Cancer 02/2005; 12(4):258-66. DOI:10.2325/jbcs.12.258 · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ductal carcinoma in situ (DCIS) of the breast is known to possess characteristics of the pre-invasive stage of breast cancer and is the precursor to invasive ductal carcinoma (IDC). However, the natural history of the progression from DCIS to IDC remains unknown at the molecular level.
We investigated the loss of heterozygosities (LOHs) in tumors of seven patients with a history of breast biopsy. The seven specimens were diagnosed as DCIS on histopathological re-examination. These patients were diagnosed with ipsilateral breast cancer a few years after biopsy. We used thirteen selected microsatellite markers that were mapped to and/or very close to the tumor suppressor genes or regions with frequent LOHs in breast cancer. DNA isolated from microdissected formalin-fixed, paraffin-embedded tissues was subjected to a PCR-LOH analysis for these chromosome loci, and the pattern of LOHs was compared between the two asynchronous lesions for the seven cases.
In all patients except one, the LOHs were concordant at 91% as the informative chromosome loci in cases 1 to 6 were 56, and the concordance in LOH pattern between DCIS and IDC was detected at 50 loci. The LOHs had accumulated in accordance with the tumor progression from DCIS to IDC. The recurrent lesion occurred at or near the site of the primary biopsy and had similar or identical histopathologic features.
These recurrences observed were probably residual disease rather than true recurrences. Our results suggest the following: (i) genetic alternations accumulate during cancer progression from DCIS to IDC, (ii) DCIS is a lesion that has a high risk of developing invasive transformation and (iii) after approximately 5 years without treatment, DCIS may develop into IDC.
Japanese Journal of Clinical Oncology 12/2003; 33(11):556-62. · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Distant metastases, including supraclavicular and parasternal lymph node metastases, were observed in about 23% of primary breast cancers in our institute. The liver was the primary site of metastasis in about 8% of cases. This rate was low compared with metastases to the bone, lung, and pleura. As treatment for metastatic lesions to other organs fails, metastatic frequency to the liver increases. As treatment, whole-body control with chemoendocrine therapy is fundamental. In chemotherapy, anthracyclines are the first choice and taxanes are the second, but the use of herceptin for herceptest-positive patients should be considered. Endocrine therapy should be adopted for patients with hormone receptor-positive tumors. Achieving a temporary partial response is possible, although cure is almost impossible. The prognosis of patients with metastasis to the liver is poor; the 3- and 5-year survival rates are 22% and 11%, respectively. We must emphasize the prevention of liver metastases by early detection using mass screening with mammography and neoadjuvant/adjuvant chemoendocrine therapy.
[Show abstract][Hide abstract] ABSTRACT: Many serological markers have been utilized to indicate the status, risk, or presence of breast cancer. In May 1996, the American Society of Clinical Oncology (ASCO) convened a Tumor Marker Panel and determined clinical practice guidelines for the use of tumor markers in breast cancer. Eight markers containing carcinoembryonic antigen (CEA) and CA15-3 were evaluated and assigned by expert reviewers to be valuable markers of breast cancer. CA15-3 recognizes a mucin-like glycoprotein, MUC-1, which is frequently expressed in breast cancer tissues. BCA225, which may recognize antigens similar to MUC-1 glycoprotein, are sensitive and specific markers for breast cancer. However, it is not recommended to measure the 2 markers in combination. The measurement of carboxy-terminal telopeptide of type I collagen (I CTP) is worthwhile as a serological diagnostic method of bone metastasis from breast cancer. Other markers such as erbB-2, CYFRA 21-1 and PTHrP are candidates for clinical utilization as tumor markers in breast cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 08/2001; 28(7):1035-40.
[Show abstract][Hide abstract] ABSTRACT: Docetaxel (TXT) has been shown to be an up-regulator of human pyrimidine nucleoside phosphorylase (PyNPase) in tumors. We have tried to use the combination of low-dose weekly TXT with 5'-DFUR (LD + D) in patients with advanced or metastatic breast cancer. In this study, we compared the clinical efficacy of LD + D with that of conventional full-dose TXT (FD) and that of low-dose weekly TXT (LD). Twenty-one patients received 3 or 4 cycles of FD 60 mg/m2 every 3 or 4 weeks (group I), 14 patients received 8 cycles of LD 20-30 mg/m2 every week (group II) and 25 patients received 8 cycles of LD 20-30 mg/m2 weekly with oral 5'-DFUR 600-1,200 mg per day (group III). The overall response rates of groups I, II and III were 29%, 29% and 52% (p = 0.24), respectively. Grade 3-4 neutropenia was observed in 91% of group I, 6% of group II and 3% of group III. Nausea was present in 27% of group I, 28% of group II and 40% of group III. Higher incidence of gastrointestinal symptoms was found in LD + D, but the symptoms abated when the doses of 5'-DFUR were reduced. Low-dose weekly TXT with oral 5'-DFUR produced a higher response rate, but less hematologic toxicity than full-dose TXT, suggesting that this combination therapy is clinically useful and may be effective for patients with advanced or metastatic breast cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 05/2000; 27(4):579-84.
[Show abstract][Hide abstract] ABSTRACT: A case-control study was conducted in Miyagi and Gunma prefectures, Japan, to evaluate the effectiveness of breast cancer screening by clinical breast examination (CBE) alone in reducing breast cancer mortality. Case subjects, who were female and had died of breast cancer, were collected from residential registry files and medical records. Control subjects matched in sex, age and residence were randomly selected from residential registry files. The screening histories during 5 years prior to the cases having been diagnosed as breast cancer were surveyed using the examinee files of the screening facilities. Finally, the data of 93 cases and 375 controls were analyzed. The odds ratio (OR) of breast cancer death for participating in screening at least once during 5 years was 0.93 (95% confidence interval (95% CI) 0.48-1.79). The cases were more symptomatic than the controls when screened. If the participants who had had symptoms in their breasts were classified as not screened, the OR decreased to 0.56 (95% CI 0.27-1.18). The case control study suggests that the current screening modality (CBE) lacks effectiveness (OR = 0.93), although it might be effective for an asymptomatic population (OR = 0.56). The number of cases was small, and a larger case-control study is desirable to define whether CBE is effective or not. However, it is necessary to consider the introduction of mammographic screening to reduce breast cancer mortality in Japan.
Japanese journal of cancer research: Gann 07/1999; 90(6):607-13. DOI:10.1111/j.1349-7006.1999.tb00790.x