Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma.

BACKGROUND: Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC. METHODS: A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy. RESULTS: Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P < 0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P = 0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P = 0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P = 0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis. CONCLUSION: Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.

Granular Cell Tumor Mimicking Breast Carcinoma: A Report of Two Cases.

Granular cell tumor (GCT) of the breast is a rare neoplasm that can mimic the clinical and radiological features of breast carcinoma. This paper presents two case reports - a rare male case and a more common female case - to underline the diagnostic challenges posed by GCT in the breast. The male patient was initially suspected of having a breast tumor based on mammography and ultrasound findings. The female patient also exhibited radiological signs suggestive of breast cancer. In both cases, the mammograms showed irregular lesions, while ultrasounds revealed solid masses with posterior shadowing and echogenic halos, mimicking carcinoma. Dynamic contrast-enhanced magnetic resonance imaging (MRI) suggested benign patterns in both cases, but only histopathologic examination post-core needle biopsy confirmed the diagnosis of GCT. These cases highlight the variability of GCT imaging presentations and the potential for misdiagnosis as breast carcinoma. The tumors exhibited distinct histopathological features, such as large polygonal cells with granular eosinophilic cytoplasm and S100 protein, differentiating them from breast carcinoma. However, imaging alone proved insufficient for diagnosis, emphasizing the need for histopathologic confirmation. The report discusses the importance of including GCT in differential diagnoses and utilizing core needle biopsy for accurate evaluation. Both cases had no recurrence during follow-up after wide resection, indicating a favorable prognosis for GCT when properly managed.

Granulocyte-Colony Stimulating Factor (G-CSF)-Induced Aortitis: A Case Report.

Pegylated granulocyte colony-stimulating factor (G-CSF), commonly used in chemotherapy-induced neutropenia, has been associated with rare instances of aortitis. This study describes a 67-year-old female patient with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2-positive breast cancer, undergoing chemotherapy with an epirubicin/cyclophosphamide (EC) regimen (epirubicin, cyclophosphamide) and pegylated G-CSF for neutropenia prophylaxis. Post-treatment, she developed symptoms including intermittent fever and severe arthralgia. Laboratory tests revealed an elevated white blood cell count, C-reactive protein levels, and erythrocyte sedimentation rate, while a computed tomography scan showed thickening in the aortic arch and descending aorta. Given the clinical presentation and exclusion of other potential causes, pegylated G-CSF-induced aortitis was suspected. The patient's symptoms improved significantly following the cessation of pegylated G-CSF, aiding in the differentiation from other types of aortitis. This study highlights the importance of considering pegylated G-CSF as a potential cause of aortitis in patients presenting with unexplained symptoms of fever and inflammation after chemotherapy. The rapid improvement upon discontinuation of the drug is a key feature distinguishing it from other aortitis causes. In conclusion, while rare, aortitis should be considered in the differential diagnosis of patients treated with pegylated G-CSF who exhibit relevant clinical symptoms. Early detection and management, including the discontinuation of the causative agent, are crucial for patient recovery and prognosis.

Risk factors for late recurrence and postrelapse survival in estrogen receptor (ER)-positive, human epidermal growth factor receptor (HER) 2-negative breast cancer after 5 years of endocrine therapy.

It is unclear which patients with ER-positive, HER2-negative breast cancer benefit from extended endocrine therapy beyond 5 years. Prognostic factors for late-recurring breast cancer postrelapse survival have been reported. We retrospectively analyzed data from 892 patients with ER-positive and HER2-negative invasive breast cancer who were disease-free after completing a 5-year adjuvant endocrine therapy. Patients were then classified as high-risk (positive lymph nodes, large tumor size, high tumor grade) or low-risk. High-risk patients were divided into extended endocrine therapy and stop groups. Comparisons were made using propensity score matching, and the benefits of extended endocrine therapy for high-risk patients and prognostic factors for postrelapse survival were assessed. The high- and low-risk groups comprised 444 and 448 patients, respectively. The 10-year distant disease-free survival (DDFS) rates were 96.3 % (95 % confidence interval [CI] 0.912-0.985) and 86.5 % (95 % CI 0.798-0911) in the extended and stop groups, respectively (P = 0.00382). Cox proportional hazards model revealed that extended endocrine therapy promoted greater reduction in distant metastasis risk than 5-year endocrine therapy in high-risk populations (hazard ratio [HR] 0.27; 95 % CI 0.11-0.68; P = 0.0054). Postrelapse survival was significantly different in patients with DDFS ≥7 years (HR 0.24; 95 % CI 0.072-0.81; P = 0.021) and those with better response to first-line treatment (HR 0.072; 95 % CI, 0.058-0.90; P = 0.041). Patients with risk factors for late recurrence should be considered for extended endocrine therapy. Longer DDFS and response to first-line treatment may be a prognostic factor for postrelapse survival after late recurrence.

Mitochondrial dynamics as a novel treatment strategy for triple-negative breast cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC), recognized as the most heterogeneous type of breast cancer (BC), exhibits a worse prognosis than other subtypes. Mitochondria dynamics play a vital role as mediators in tumorigenesis by adjusting to the cell microenvironments. However, the relationship between mitochondrial dynamics and metabophenotype exhibits discrepancies and divergence across various research and BC models. Therefore, this study aims to explore the role of mitochondrial dynamics in TNBC drug resistance and tumorigenesis. METHODS: The Wst-8 test was conducted to assess doxorubicin sensitivity in HCC38, MDA-MB-231 (TNBC), and MCF-7 (luminal). Confocal microscopy and FACS were used to quantify the mitochondrial membrane potential (ΔφM), mitophagy, and reactive oxygen species (ROS) production. Agilent Seahorse XF Analyzer was utilized to measure metabolic characteristics. Dynamin-related protein-1 (DRP1), Parkin, and p62 immunohistochemistry staining were performed using samples from 107 primary patients with BC before and after neoadjuvant chemotherapy (NAC). RESULTS: MDA-MB-231, a TNBC cell line with reduced sensitivity to doxorubicin, reduced ΔφM, and enhanced mitophagy to maintain ROS production through oxidative phosphorylation (OXPHOS)-based metabolism. HCC38, a doxorubicin-sensitive cell line, exhibited no alterations in ΔφM or mitophagy. However, it demonstrated an increase in ROS production and glycolysis. Clinicopathological studies revealed that pretreatment (before NAC) expression of DRP1 was significant in TNBC, as was pretreatment expression of Parkin in the hormone receptor-negative group. Furthermore, low p62 levels seem to be a risk factor for recurrence-free survival. CONCLUSION: Our findings indicated that the interplay between mitophagy, linked to a worse clinical prognosis, and OXPHOS metabolism promoted chemotherapy resistance in TNBC. Mitochondrial fission is prevalent in TNBC. These findings suggest that targeting the unique mitochondrial metabolism and dynamics in TNBC may offer a novel therapeutic strategy for patients with TNBC.

Hexokinase II in breast carcinoma: a potent prognostic factor associated with hypoxia-inducible factor-1α and Ki-67.

Hypoxia-inducible factor-1α (HIF-1α) mediates adaptive responses to changes under tissue hypoxia in carcinoma cells by controlling the expression of various target genes. Previous studies have demonstrated that HIF-1α is associated with adverse clinical outcome in breast carcinoma patients, but details of HIF-1α's role have remained largely unknown. Therefore, in this study, we examined the expression profiles of HIF-1α-induced genes in 10 breast carcinoma cases using microarray data. As a result, we demonstrated that the status of hexokinase II (HKII) was associated with carcinoma recurrence in patients with these genes. The enzyme HKII is involved in the first, and rate-limiting, step of glycolysis, but its clinical significance has not yet been examined in breast carcinoma. Therefore, we immunolocalized HKII in 118 breast carcinomas, and HKII immunoreactivity was detected in 44% of the cases. It is significantly associated with histological grade, Ki-67 labeling index and HIF-1α immunoreactivity. Also, HKII status is significantly associated with increased risk of recurrence and adverse clinical outcome in breast cancer patients. Subsequent multivariate analysis demonstrated that HKII status was an independent prognostic factor for disease-free survival of patients. These results all suggest that HKII is induced by HIF-1α and plays important roles in the proliferation and/or progression of breast carcinoma possibly through increased glycolytic activity. The status of HKII is therefore considered a potent prognostic factor in human breast cancer patients.

Multidetector row helical computed tomography for invasive ductal carcinoma of the breast: correlation between radiological findings and the corresponding biological characteristics of patients.

The aim of this study is to evaluate the correlation between multidetector row helical computed tomography (MDCT) findings and the histopathological characteristics of patients with invasive ductal carcinoma. We retrospectively reviewed MDCT findings and the corresponding histopathological features of 442 women with invasive ductal carcinoma. We received informed consent from the patients and the protocol was approved by the Ethics Committee at Tohoku University. The median age was 53 years (26-89 years). We examined the MDCT findings based on mass shape classified into well, moderate, poorly and scattered demarcated shapes, the enhancement pattern classified into homogenous, heterogeneous, rim and poor, and mass density classified into high, intermediate or low. We subsequently compared these radiological findings with the histological characteristics and clinical outcome. Poorly demarcated types were higher in ER+/HER2- (P = 0.008), while the well-demarcated type was higher in ER-/HER2- and ER-/HER2+ (P < 0.001 and P = 0.010). Rim pattern was higher in ER-/HER2- (P < 0.001). Intermediate or low density was higher in ER-/HER2- (P < 0.001, respectively). Further analysis based on histological grade, mitotic counts and lymphovascular invasion demonstrated that the well-demarcated shape was higher in grade 2 and 3 (P = 0.006 and P < 0.001, respectively), and rim pattern was observed in grade 3 (P < 0.001). Regarding mitotic counts, poorly and scattered demarcated shapes were observed in score 1 (P = 0.008 and P = 0.014), while well-demarcated shape and rim enhancement were observed in score 3 (P < 0.001, respectively). Lymphovascular invasion correlated with a moderate demarcated shape (P = 0.029). Regarding recurrence rates, there were statistically significant differences between well and moderate, poorly or scattered demarcated shapes (P = 0.007, 0.028 and 0.035, respectively). These proposed MDCT diagnostic criteria based on biological characteristics contribute to more accurately predicting the biological behavior of breast cancer patients.

Retrospective analysis of mammographic findings for Japanese women: a potential predictor for breast malignancies.

This purpose of this study was to retrospectively stratify the risks of malignancy according to the mammographic characteristics of Japanese women. We studied the mammographic findings of 1267 Japanese women. We characterized malignant phenotypes according to mass shape, margin and mass density, and by shape and distribution of calcified foci, and to obtain possible predictors for malignancies according to age groups. Lobular and irregular mass shape, no circumscribed margin and higher density turned out to be more powerful predictors for malignancy than other radiological factors (P < 0.001, respectively). The ratio of the cases detected as a mass in those between 21 and 49 years was lower than that of other age groups. In addition, the presence of calcifications and no mammographic abnormalities were the most powerful predictors for malignancies in the young age groups (P < 0.001, respectively). The peak age of breast cancer is between 40 and 49 years in Japan. In the present study, subtle differences were found in the mammographic results for young and old women, in contrast to those of women in the USA and Europe. The results of this study might enable more accurate prediction of biological behavior of the breast lesions in Japanese women.

Development of a quantitative diagnostic method of estrogen receptor expression levels by immunohistochemistry using organic fluorescent material-assembled nanoparticles.

The detection of estrogen receptors (ERs) by immunohistochemistry (IHC) using 3,3'-diaminobenzidine (DAB) is slightly weak as a prognostic marker, but it is essential to the application of endocrine therapy, such as antiestrogen tamoxifen-based therapy. IHC using DAB is a poor quantitative method because horseradish peroxidase (HRP) activity depends on reaction time, temperature and substrate concentration. However, IHC using fluorescent material provides an effective method to quantitatively use IHC because the signal intensity is proportional to the intensity of the photon excitation energy. However, the high level of autofluorescence has impeded the development of quantitative IHC using fluorescence. We developed organic fluorescent material (tetramethylrhodamine)-assembled nanoparticles for IHC. Tissue autofluorescence is comparable to the fluorescence intensity of quantum dots, which are the most representative fluorescent nanoparticles. The fluorescent intensity of our novel nanoparticles was 10.2-fold greater than quantum dots, and they did not bind non-specifically to breast cancer tissues due to the polyethylene glycol chain that coated their surfaces. Therefore, the fluorescent intensity of our nanoparticles significantly exceeded autofluorescence, which produced a significantly higher signal-to-noise ratio on IHC-imaged cancer tissues than previous methods. Moreover, immunostaining data from our nanoparticle fluorescent IHC and IHC with DAB were compared in the same region of adjacent tissues sections to quantitatively examine the two methods. The results demonstrated that our nanoparticle staining analyzed a wide range of ER expression levels with higher accuracy and quantitative sensitivity than DAB staining. This enhancement in the diagnostic accuracy and sensitivity for ERs using our immunostaining method will improve the prediction of responses to therapies that target ERs and progesterone receptors that are induced by a downstream ER signal.

Breast ultrasonographic and histopathological characteristics without any mammographic abnormalities.

OBJECTIVE: We evaluated ultrasonographic findings and the corresponding histopathological characteristics of breast cancer patients with Breast Imaging Reporting and Data System (BI-RADS) category 1 mammogram. METHODS: We retrospectively reviewed the ultrasonographic findings and the corresponding histopathological features of 45 breast cancer patients with BI-RADS category 1 mammogram and 537 controls with mammographic abnormalities. We evaluated the ultrasonographic findings including mass shape, periphery, internal and posterior echo pattern, interruption of mammary borders and the distribution of low-echoic lesions, and the corresponding histopathological characteristics including histological classification, hormone receptor and human epidermal growth factor receptor 2 status of invasive ductal carcinoma and ductal carcinoma in situ, histological grade, mitotic counts and lymphovascular invasion in individual cases of BI-RADS category 1 mammograms and compared with those of the control group. RESULTS: The ultrasonographic characteristics of the BI-RADS category 1 group were characterized by a higher ratio of round shape (P< 0.001), non-spiculated periphery (P= 0.021), non-interruption of mammary borders (P< 0.001) and non-attenuation (P= 0.011) compared with the control group. A total of 52.6% of low-echoic lesions were associated with spotted distribution in the BI-RADS 1 group, whereas 25.8% of low-echoic lesions were associated with spotted distribution in the control group (P= 0.012). As for histopathological characteristics, there was a statistically higher ratio of triple-negative subtype (P= 0.021), and this particular tendency was detected in histological grade 3 in the BI-RADS category 1 group (P= 0.094). CONCLUSION: We evaluated ultrasonographic findings and the corresponding histopathological characteristics for BI-RADS category 1 mammograms and noted significant differences among these findings in this study. Evaluation of these ultrasonographic and histopathological characteristics may provide a more accurate ultrasonographic screening system for breast cancer in Japanese women.

Development of silica-coated silver iodide nanoparticles and their biodistribution.

Nanomaterials have great potential in the field of medicine and have been studied extensively. In a previous study, we addressed the potential of silver iodide (AgI) as X-ray contrast media, because it possessed high imaging ability in the measurement by X-ray computed tomography (X-CT) in vitro, and its surface can be modified with many functional groups. We developed the method of silica coating to make AgI nanoparticles more stable and uniform in size. However, the safety and metabolism of nanoparticles in vivo remains to be determined. The objective of the present study was to evaluate the in vivo biodistribution of silica-coated AgI nanoparticles (SAgINPs). X-CT, transmission electron microscopy (TEM), and inductively coupled plasma atomic emission spectrometry (ICP-AES) were performed prior to and at intervals following the intravenous administration of SAgINPs to rats and rabbits. ICP-AES is a spectral technique that can determine the presence and concentrations of metal samples. The X-CT study showed long-period enhancement in the liver and spleen, but not in the bladder of rats. The TEM study demonstrated that SAgINPs were found in hepatocytes. Using ICP-AES, Ag was detected in the bile juice of rabbits, but not found in the urine of these animals, suggesting that SAgINPs are excreted via the liver. This study shows the quantitative biodistribution of silica-coated nanoparticles for the first time, indicating that our silica coating technique is useful for development of nanoparticles with hepatic excretion. In conclusion, the SAgINPs may provide X-ray contrast media with high imaging ability and biocompatibility.

Correlation between mammographic findings and corresponding histopathology: potential predictors for biological characteristics of breast diseases.

The present study retrospectively evaluated the mammographic findings of 606 Japanese women with breast cancer (median age 50 years; range 27-89 years) and correlated them with histopathological characteristics. Mammographic findings were evaluated with an emphasis on mass shape, margin, density, calcification, and the presence of architectural distortion; these findings were correlated with histopathological characteristics such as intrinsic subtype, histological grade, lymphovascular invasion, and the Ki-67 labeling index. An irregular mass shape and masses with a spiculated margin were significantly higher in the group of patients with luminal A breast cancer than in patients with masses that were lobular or round, or in tumors with an indistinct or microlobulated periphery (P = 0.017, P = 0.024, P < 0.001, and P = 0.001, respectively). Irregular mass shape and spiculated periphery were significantly lower in patients with Grade 3 cancer (P < 0.001 for both). In terms of lymphovascular invasion, there were significant differences between oval and irregular or round mass shape (P = 0.008 and P = 0.034), between tumors with a microlobulated and indistinct periphery (P = 0.014), between tumors with a punctate and amorphous or pleomorphic calcification shape (P = 0.030 and 0.038), and between the presence and absence of architectural distortion (P = 0.027). Equivalent or low-density masses were also higher in Grade 1 breast cancers (P = 0.007). There were significant differences in the Ki-67 labeling index between irregular and lobular or round tumors (P < 0.001 and P = 0.014), as well as between spiculated and indistinct or microlobulated tumors (P < 0.001 for both). Significant differences were noted in the mammographic features of different primary breast cancer subtypes. These proposed mammographic diagnostic criteria based on biological characteristics may contribute to a more accurate prediction of biological behavior of breast malignancies.

L-type amino acid transporter 1 is associated with chemoresistance in breast cancer via the promotion of amino acid metabolism.

18F-FDG PET/CT has been used as an indicator of chemotherapy effects, but cancer cells can remain even when no FDG uptake is detected, indicating the importance of exploring other metabolomic pathways. Therefore, we explored the amino acid metabolism, including L-type amino acid transporter-1 (LAT1), in breast cancer tissues and clarified the role of LAT1 in therapeutic resistance and clinical outcomes of patients. We evaluated LAT1 expression before and after neoadjuvant chemotherapy and examined the correlation of glucose uptake using FDG-PET with the pathological response of patients. It revealed that LAT1 levels correlated with proliferation after chemotherapy, and amino acid and glucose metabolism were closely correlated. In addition, LAT1 was considered to be involved in treatment resistance and sensitivity only in luminal type breast cancer. Results of in vitro analyses revealed that LAT1 promoted amino acid uptake, which contributed to energy production by supplying amino acids to the TCA cycle. However, in MCF-7 cells treated with chemotherapeutic agents, oncometabolites and branched-chain amino acids also played a pivotal role in energy production and drug resistance, despite decreased glucose metabolism. In conclusion, LAT1 was involved in drug resistance and could be a novel therapeutic target against chemotherapy resistance in luminal type breast cancer.

Comparison of core needle biopsy (CNB) and surgical specimens for accurate preoperative evaluation of ER, PgR and HER2 status of breast cancer patients.

The roles of core needle biopsy (CNB) have become well established as an important preoperative diagnostic method for breast lesions. We examined the concordance of histological types, nuclear grades, hormone receptors, and human epidermal growth factor receptor 2 (HER2) status between CNB and surgical specimens in 353 cases. In addition, we analyzed the correlation between the number of CNB specimens obtained and accuracy of histological factors in order to explore the optimal number of CNB specimens. Between CNB and surgical specimens, concordance rates of histological type, nuclear grade, estrogen receptor (ER), and progesterone receptor (PgR) status (cut-off 0-<1%, 1-10%, and 10%<), and HER2 were 84.4%, 81.3%, 92.9%, and 89.3%, respectively. In 52 of 353 patients who were histopathologically diagnosed as ductal carcinoma in situ (DCIS) by CNB, final diagnosis was changed in to invasive ductal carcinoma (IDC) in surgical specimens. Statistically significant differences were detected in the discrepancy of the following factors between CNB and subsequent surgical specimens: histological types, nuclear grade, and PgR, between patients who received four or more cores and those who had received three or less cores. In addition, a similar tendency was also detected in estrogen receptor (ER) and HER2 as in the above, and the cases that received four cores reached to 100% concordance in diagnosis between CNB and surgical specimens. Therefore, the optimal numbers of CNB were considered four at least in assessing the histological type, invasion, nuclear grade, hormone receptor status, and HER2 status of individual patients in the preoperative setting.

Capecitabine monotherapy is efficient and safe in all line settings in patients with metastatic and advanced breast cancer.

OBJECTIVE: Capecitabine is effective and well tolerated in patients with anthracycline- and/or taxane-pre-treated metastatic breast cancer. We compared the efficacy and safety of capecitabine monotherapy between 1st, 2nd, 3rd and > or =4th line settings for advanced and metastatic breast cancer pre-treated with/without anthracycline and taxanes. METHODS: Subjects comprised 84 patients with histologically confirmed advanced or metastatic breast cancer and at least one measurable metastatic lesion. We evaluated time to disease progression (TTP), response rate (RR) and clinical benefit rate (CBR) for 1st (n = 17), 2nd (n = 28), 3rd (n = 23) and > or =4th (n = 16) line setting treatments of capecitabine monotherapy. RESULTS: Median number of cycles of capecitabine monotherapy was 12 cycles in 1st line, 11 cycles in 2nd line, 9 cycles in 3rd line and 11 cycles in > or =4th line. RR and CBR were 23.5% and 58.8% in 1st line, 21.4% and 53.6% in 2nd line, 21.7% and 52.2% in 3rd line, and 18.8% and 50.0% in > or =4th line, respectively. No significant differences in TTP were seen between each line setting (P = 0.843). CONCLUSIONS: Capecitabine monotherapy is effective and well tolerated in all line settings of chemotherapy in patients with metastatic or advanced breast cancer, and is suitable for outpatient therapy.

The correlation between ultrasonographic findings and pathologic features in breast disorders.

OBJECTIVE: Breast ultrasonography has gained widespread acceptance as a diagnostic tool for the evaluation of human breast disorders. It is important to evaluate the correlation of ultrasonography findings with the corresponding histopathological features. METHOD: We retrospectively reviewed the 154 cases of breast disorders. We evaluated the correlation the ultrasonography findings and carcinoma cells extension with their corresponding histopathological findings. In addition, we also studied the information on estimation of histological types and cancer extension used by the other modalities such as computed tomography and magnetic resonance imaging. RESULTS: The concordance rate for margins between ultrasonography findings and histopathological features was 91.6% (P < 0.001) and that for boundary zone was 87.0% (P < 0.001). Histopathological correlation of internal and posterior echoes demonstrated that internal low echo masses were composed of fibroblastic cells with marked collagenization in the stroma, or the cases in which carcinoma cells proliferated in a monotonous, solid and/or expanding manners. Attenuation of posterior echo was detected in the cases associated with hyperplasia of collagenized fibroblastic stroma. An increased cellularity in the mass with prominent large tumor nests and little fibrous stroma demonstrated the accentuation or no alterations of the posterior echo. The concordance rate of borders was 84.4% (P < 0.001). The correlation between estimated histological type by ultrasonography diagnosis and actual histological types was 87.0%. An overall detection rate of carcinoma extension by ultrasonography was 86.4%. In addition, an overall detection rate of carcinoma extension by ultrasonography, magnetic resonance imaging and computed tomography was 93.8%. CONCLUSION: These results demonstrated correlation between histopathological and ultrasonographic findings of the breast lesions is cardinal for quality control or improving the quality of ultrasonography.

Effect of screening mammography on breast cancer survival in comparison to other detection methods: a retrospective cohort study.

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.

Usefulness of lesion image mapping with multidetector-row helical computed tomography using a dedicated skin marker in breast-conserving surgery.

To investigate the usefulness of computed tomography (CT) with skin-marker placement in determining the excision area and decreasing the positive or close margin rates in breast-conserving surgery (BCS). Multidetector-row helical computed tomography (MDCT) mapping images were reconstructed in subjects (n = 117) diagnosed with primary breast cancer who had undergone MDCT using CT skin markers. Serial 5-mm-thick slices prepared from the surgical specimen were used for pathological analyses. A "positive margin" was defined as the presence of malignant cells at the surgical margin, and a "close margin" as a tumor within 5 mm of the surgical margin. The rates of positive and close margins were calculated. We identified the lesions in 111 of 117 cases (94.9%) on MDCT. Of these, 93 underwent BCS under the guidance of MDCT mapping and the remaining 18 underwent mastectomy. Among the 93 cases, 6 (6.5%) had positive or close margins and were diagnosed with ductal carcinoma in situ of low nuclear grade. MDCT mapping with a CT skin marker is feasible for simulating surgical positioning and determining the excision area. MDCT mapping could decrease the positive and close margin rates in BCS.

Age-specific interval breast cancers in Japan: estimation of the proper sensitivity of screening using a population-based cancer registry.

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.

Reliability of prognostic factors in breast carcinoma determined by core needle biopsy.

OBJECTIVE: The aim of this study was to evaluate the reliability of information obtained by core needle biopsy (CNB). METHODS: We studied 111 women (112 lesions) with breast cancer who underwent CNB and subsequent surgical excision. Six factors (histological type, nuclear grade, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status, and human epidermal growth factor receptor-2 (HER2) status) were evaluated in a blinded fashion at CNB and at surgical excision. RESULTS: The histological type at CNB correlated exactly with that of the excisional specimen in 83% (87/105) of the cases. Of the 45 in situ lesions at CNB, 16 (36%) were found to have invasive carcinoma at surgical excision. The difference between the specimens from CNB and those from surgery in terms of the absolute concordance rate and kappa statistic value were 61% with a fair kappa value (0.26) in the nuclear grade, 75% with a moderate kappa value (0.55) in the histological grade, 95% with an almost perfect kappa value (0.84) in ER, 88% with a substantial kappa value (0.70) in PR and 88% with a substantial kappa value (0.65) in HER2. Regarding the evaluation of nuclear and histological grades, a trend toward greater accuracy was observed when thicker specimens were used. CONCLUSIONS: CNB provided reliable information on the histological type of invasive carcinoma. It also evaluated ER, PR and HER2 (only in cases where the score was 3+) accurately in spite of the limited quantity of the specimen obtained with the thin (16-gauge) needle.