Anthracycline could be essential for triple-negative breast cancer: A randomised phase II study by the Kanagawa Breast Oncology Group (KBOG) 1101.

BACKGROUND: It is important to determine whether anthracycline-containing regimens or taxane-containing regimens are more effective in individual patients. The present study compared the efficacy of six cycles of docetaxel and cyclophosphamide (TC6) with that of three cycles of 5-fluorouracil, epirubicin and cyclophosphamide followed by docetaxel (FEC-D) in Japanese patients with hormone receptor (HR)-negative breast cancer (BC) to identify subtypes requiring anthracycline treatment. METHODS: The study included 103 patients with operable HR-negative BC. Of these patients 53 received FEC-D and 50 received TC6. The primary endpoint was pathological complete response (pCR). The secondary endpoints were safety, breast-conserving surgery, disease-free survival (DFS) and overall survival (OS). The predictive factors for each regimen were evaluated. RESULTS: Of the 103 patients, 97 completed the study (FEC-D, 50 patients; TC6, 47 patients). The pCR rate was higher with FEC-D (36%) than with TC6 (25.5%); however, the difference was not significant (P = 0.265). TC6 was safer than FEC-D, as the adverse events with docetaxel in the FEC-D regimen were similar to those with the TC6 regimen. Among patients with basal BC, the pCR rate was significantly higher with FEC-D (42.9%) than with TC6 (13.6%; P = 0.033). Among patients with triple-negative breast cancer (TNBC), the DFS and OS were significantly better with FEC-D than with TC6 (P = 0.016 and P = 0.034, respectively). CONCLUSION: TC6 was not as effective as FEC-D for treating HR-negative BC, as TC6 was not sufficient to treat TNBC, particularly the basal subtype. Our findings suggest that anthracyclines are better treatment options than taxanes for basal BC.

Outcomes of clinically node-negative breast cancer without axillary dissection: can preserved axilla be safely treated with radiation after a positive sentinel node biopsy?

PURPOSE: We analyzed whether axillary nodal irradiation could control clinically node-negative disease, including those patients with a positive sentinel lymph node biopsy (SLNB), most of whom received regional nodal irradiation. We also evaluated toxicity profiles that resulted from nodal irradiation. PATIENTS AND METHODS: From 1988 to 2011, 2107 patients with cT1-T2N0M0 breast cancer underwent breast conservation therapy in the absence of axillary dissection: nx group (n = 1548), without any axillary surgery; the sn(-) group (n = 518), with a negative SLNB; and sn(+) group (n = 104), with a positive SLNB. RESULTS: The median follow-up times were 88, 56, and 55 months for the nx, sn(-), and sn(+) groups, respectively. The nx group had more risk factors than did the other 2 groups in terms of age, grade, or T stage. Ninety-eight percent of the sn(-)group received only tangent irradiation, and 100% and 83% of the sn(+) and nx group, respectively, received additional regional nodal irradiation. The 5-year cumulative incidences of axillary failure and regional nodal failure were 34, 3, and 0 (2.7%, 0.7%, and 0%; P = .02, log-rank test) and 57, 4, and 0 (4.4, 1%, and 0; P = .04), respectively. Overall survival rates in 5 years were 96.4%, 98.9%, and 97.6% (P = .03), respectively. Symptomatic but transient radiation pneumonitis developed in 31, 16, and 6 (2.0%, 3.1%, and 5.7%). Mild arm edema was observed in 1, 4, and 0 (0.06%, 0.8%, and 0%) in the nx, sn(-), sn(+) groups, respectively. CONCLUSIONS: Treatment without axillary dissection showed excellent outcomes with negligible toxicity for patients with clinically node negative, including those with a positive SLNB. Regional nodal irradiation after a positive SLNB is a reasonable alternative to axillary dissection.

Axillary Irradiation with High Tangent Fields for Clinically Node-Negative Breast Cancer: Can 3-D Conformal Radiotherapy with a Field-in-Field Technique Better Control the Axilla?

BACKGROUND: The target volume for postoperative breast irradiation is the remaining breast tissue, and the axillary region is not an intentional target volume. PATIENTS AND METHODS: Between 2001 and 2009, eligible women with pT1-2cN0/pN0(sn) breast cancer underwent breast-conserving therapy without axillary dissection. Treatment outcomes between 2 radiotherapy planning groups, high tangent fields with 2-dimensional (2-D) simulation-based planning and 3-dimensional (3-D) computed tomography-based planning with a field-in-field technique, were compared. The correlating factors for axillary failure were also calculated. RESULTS: In total, 678 patients were eligible. As of May 2009, the median follow-up times for the 2-D (n = 346) and 3-D (n = 332) groups were 94 and 52 months, respectively. Patient characteristics were balanced, except for a younger population in the 2-D group and more lymphovascular invasion in the 3-D group. On multivariate analysis, 2-D planning was the only risk factor for axillary failure. In the 2-D and 3-D groups, the 5-year cumulative incidences of axillary failure were 8 (3.1%) and 1 (0.3%) (log-rank p = 0.009), respectively. The respective 5-year overall survival rates were 97.4 and 98.4% (p = 0.4). CONCLUSION: High tangent irradiation with 3-D planning improved axillary control compared to that with 2-D planning, suggesting that optimizing axillary dose distribution may impact outcomes.

Clinical efficacy and value of redistributed subclavian arterial infusion chemotherapy for locally advanced breast cancer.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of redistributed subclavian arterial infusion chemotherapy (RESAIC). We have focused on the local response, quality of life (QOL), and complications. We have also investigated factors that influence the local response of RESAIC. MATERIALS AND METHODS: The subjects were patients with locally advanced breast cancer whose tumors were resistant to standard systemic chemotherapy (at least more than two regimens), those who were physically unable to tolerate systemic chemotherapy, and patients with locally recurrent breast cancer. The registration period was between April 2006 and May 2009. RESULTS: A total of 24 cases in 22 patients (mean age 59.5 years, range 36-82 years) were entered in the study. The local response rate of RESAIC was 77.3% (17/22). The QOL score showed improvement on average. There were no serious complications during catheter port implantation, and there was hematological toxicity over grade 3 in 27.3% (6/22) of patients. A significant difference between responders and nonresponders was seen in patients with a replaced type tumor (on imaging, diffuse contrast enhancement was seen in whole quadrants) (P = 0.043), and the patients underwent radiotherapy (P = 0.043). CONCLUSION: RESAIC is an effective, safe treatment for locally advanced breast cancer. Because it was reviewed in only a few cases, however, large-scale studies are warranted.

Radiologic-pathological correlation of punctate hyperechoic foci by ultrasound in stereotactic vacuum-assisted breast biopsy samples.

PURPOSE: To correlate punctate hyperechoic foci (PHF) on ultrasound (US) with microcalcifications detected by mammography (MMG) and at histopathology. MATERIALS AND METHODS: Forty-eight subjects who underwent stereotactic vacuum-assisted breast biopsy (SVABB) for evaluation of breast microcalcifications between April and December 2008 were evaluated for 191 lesions obtained after SVABB. The concordance between PHF on US with microcalcifications detected on MMG and histopathology was therefore evaluated for 191 lesions. Values for sensitivity and specificity were determined against histopathology as the reference standard. RESULTS: In 154 of 191 samples (80.6%), the PHF on US corresponded with microcalcifications on MMG and histopathology. The overall sensitivity and specificity were 85.3% and 80.0%, respectively, for US, and 89.7% and 90.7%, respectively, for MMG. There were no significant differences between values for US and MMG. At US, 12 PHF did not correlate with any microcalcifications at MMG or histopathology. Histopathology revealed collagen fibers in fatty tissue in 5 of 12 lesions and collagenization in 2 of 12 lesions. CONCLUSION: There was a general concordance between PHF on US and microcalcifications detected at MMG. However, in addition to microcalcifications, collagen fibers in fatty tissue and collagenization may account for some PHF. This possibility should be considered when interpreting US findings.

Microcalcifications of breast tissue: appearance on synchrotron radiation imaging with 6-microm resolution.

OBJECTIVE: The purpose of this study was to use synchrotron radiation imaging with 6-microm resolution to evaluate amorphous and pleomorphic breast tissue microcalcifications. CONCLUSION: Synchrotron radiation imaging depicted microcalcifications as small as 24 microm. Imaging with this technique revealed that most amorphous and pleomorphic calcifications on conventional mammograms are clusters of fine specks and that in addition to the shape or density of a speck, the distribution density of clustered specks is a factor determining the apparent shape.

Diagnostic accuracy of high-resolution MRI using a microscopy coil for patients with presumed DCIS following mammography screening.

PURPOSE: To prospectively evaluate the accuracy of high-resolution (HR)-MRI as a secondary examination in women with abnormal calcifications detected on mammography. MATERIALS AND METHODS: We used a 4.7-cm microscopy coil to acquire HR-MRI signal data. We examined 52 women with breast lesions preoperatively using HR-MRI and vacuum-assisted core needle biopsy. The lesions were suspicious of malignancy, classified as category 3-5 on mammography (Breast Imaging Reporting and Data System [BI-RADS]), and without a palpable mass. All visualized suspicious lesions were correlated with histological findings. We compared the HR-MRI and pathological findings and calculated the sensitivity, specificity, and accuracy. RESULTS: We compared the breast HR-MRI results with the gold standard of pathological results for studies of malignancy (DCIS and invasive cancer), and found a sensitivity of 88.5%, specificity of 92.3%, and accuracy of 90.4%. The positive predictive value (PPV) was 92%, and the negative predictive value (NPV) was 88.9%. When breast MRI was compared with pathological results for studies that diagnosed DCIS only, the results revealed a sensitivity of 88.6%, specificity of 88.2%, accuracy of 88.5%, PPV of 93.9%, and NPV of 78.9%. CONCLUSION: HR-MRI using a microscopy coil is a useful, reliable, safe, and minimally invasive procedure that is a good choice for secondary assessment of abnormal calcification in the breast.

Effects of ultrasonic intensity and reactor scale on kinetics of enzymatic saccharification of various waste papers in continuously irradiated stirred tanks.

Based on the enzymatic saccharification of the various pulps in the previous 0.8 l ultrasonic stirred tank reactor, the ultrasound-enhanced saccharification of waste papers such as newspaper, carton paper, office paper etc. was carried out in the same reactor as well as larger scale stirred tank reactors of size 3.2 and 6.4 l. The saccharification of each waste paper was less enhanced in the larger reactor at a given ultrasonic intensity. This could be attributed to the decrease in the ultrasonic intensity per reaction volume, i.e., the specific ultrasonic intensity. Most waste papers were more efficiently hydrolyzed with increasing specific ultrasonic intensities, although newspaper was less efficiently done for a too high specific intensity. Such an adverse effect might be due to the fact that some impurities in the newspaper such as lignin were activated by an intensive ultrasonic irradiation to form a rigid and closed network, which inhibited the access and adsorption of cellulase on to the substrate surface. The previous kinetic model was found to be applicable to analyze and simulate the saccharification of each waste paper in the different ultrasonic reactors. The ultimate conversion of a substrate based on the total sugar concentration estimated for an infinite reaction time could be correlated as a function of the ratio of initial substrate to enzyme concentrations at a fixed specific ultrasonic intensity. Either the apparent rate constant or the ultimate conversion increased and tended to approach a constant with an increase in the specific ultrasonic intensity except for the case of newspaper, while neither the apparent Michaelis constant, product inhibition constant nor glucose formation equilibrium constant was influenced by the specific ultrasonic intensity.

Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase.

The breast and ovarian tumor suppressor BRCA1 forms a heterodimeric RING-type ubiquitin ligase with BARD1 to catalyze untraditional Lys-6-linked polyubiquitin chains. It is not clear how the BRCA1-BARD1 ligase regulates various cellular processes such as DNA repair, cell-cycle progression, transcriptional regulation, and centrosome duplication. Here we report that BRCA1-BARD1 catalyzes the polyubiquitination of nucleolar phosphoprotein nucleophosmin/B23 (NPM). Two different mass spectrometry screens for protein ubiquitinated by BRCA1-BARD1 both identified NPM. NPM interacts with N-terminal fragments of BRCA1 and BARD1 in a manner dependent upon BRCA1-BARD1 heterodimer formation. NPM colocalizes with BRCA1 and BARD1 in mitotic cells suggesting the possibility of NPM regulation by BRCA1-BARD1 during mitosis. BRCA1-BARD1 catalyzes the ubiquitination of NPM in vitro and in vivo, and BRCA1-BARD1 co-expression in cells causes NPM stabilization rather than degradation. This is consistent with the notion that this ligase catalyzes untraditional polyubiquitin chains. Given the many overlapped functions between NPM and BRCA1, we propose that NPM is a strong candidate as a substrate of the BRCA1-BARD1 ubiquitin ligase.

[Breast cancer].

In Japan the mortality and incidence rates of breast cancer have been increasing. In 2000, the number of breast cancer deaths in female was 9,171. In 1996, the aged adjusted incidence rate of breast cancer was 38.9, top among all of female cancers and the estimated number of female breast cancer patients was 29,448 in Japan. Therefore, efficient breast cancer screening system is urgently needed. In April 2000, breast screening using biennial mammography in combination with clinical breast examination instead of annual clinical breast examination alone was introduced for women aged 50 and over in Japan. However, the compliance of screening using mammography was less than 1% in the fiscal 2000 year. On the other hand, the compliance of screening with clinical breast examination alone was 6.5% in same period. These compliances were significantly lower than that of about 65% in the USA. Given the importance of the control of quality in screening mammography, a central committee for the quality control of mammographic screening has been established in order to educate doctors and radiographers and to assess image apparatus in each facility. As of April 2002, 1,409 out of 1,978 doctors that participated in the training program had obtained either grade A (instructor level) or grade B (adequate level). Gøtzche and Olsen reassessed previous meta-analyses of screening mammography and concluded that screening for breast cancer with mammography was unjustified. Subsequently, reviews by U. S. Preventive Services Task Forces and the WHO reconfirmed the effectiveness of screening mammography in reducing breast cancer mortality. These controversies show the importance of assessment of screening mammography effectiveness in Japan.

[Breast-conserving surgery: quadrantectomy].

The surgical techniques and clinical results of quadrantectomy as a form of breast-conserving surgery are described. A quadrantectomy is a breast-conserving technique including wide resection and tumorectomy. A quadrantectomy is designed to remove an anatomic segment of breast tissue (duct-lobular system). It has the advantage of greater surgical curability than other conserving techniques in cases with ductal spread, because breast cancer arising in the terminal duct often spreads in the duct-lobular system. However, quadrantectomy poses some cosmetic problems due to the large volume of breast tissue excised. Additionally, quadrantectomy has failed to show better results in local recurrence rates compared with wide resection. Therefore quadrantectomy should be limited to breast cancer with segmental and wide ductal spread. It is important to determine the surgical technique that compromises between local curability and cosmetic results for each patient with breast cancer.

Defects of a mammography quality control phantom visualized by synchrotron radiation imaging.

Synchrotron radiation (SR) imaging of an RMI 156 mammography quality control phantom, serial number 156-15330, revealed some defects which degraded the visibility of calcification specks. SR imaging was performed at SPring-8, in Harima, Japan by using a monochromatic energy of 20 KeV with a field-of-view of 24 X 24 mm. Different kinds of images were obtained by changing sample-to-detector distances; absorption images and refraction-enhanced images. Specks were embedded in a wax matrix and were imaged as black in an absorption image. In a refraction-enhanced image, they were imaged as a black region with white margins. Foreign objects with opposite contrast were detected near, or overlapped with, some specks. As they were depicted as white in the absorption images and as white with a black margin in the refraction-enhanced image, it seemed that they had low X-ray attenuation and a low refraction index compared with the surrounding wax. They might presumably be air bubbles. Visibility of specks in an absorption image was seriously interfered with when those object(s) overlapped with specks. This kind of defect may cause a difficulty in meeting quality assurance specifications when a facility inadvertently purchases defective phantoms.