Tsuneo Imai

Reproducible Surveillance Breast Ultrasound Using an Image Fusion Technique in a Short-Interval Follow-up for BI-RADS 3 Lesions: A Pilot Study

The aim of our study was to verify the utility of surveillance ultrasound (US) using real-time virtual sonography (RVS)--to coordinate present US images with past US images reconstructed from previously acquired US volume data using an image fusion technique--for short-interval follow-up of Breast Imaging-Reporting and Data System (BI-RADS) category 3 mass lesions. We enrolled 20 women (23 lesions) with more than 24 mo of follow-up after classification as BI-RADS category 3 during initial US. US surveillance was scheduled at 6, 12 and 24 mo. Measurement of the target lesion diameter was performed after the probe was adjusted to include the maximum diameter of a past US image at each visit. RVS was technically successful in 100% of patients. All target lesions were detected, including two iso-echoic lesions. The mean target lesion diameters at baseline and at 6, 12 and 24 mo were 8.2 ± 4.2, 8.4 ± 4.5, 8.1 ± 4.5 and 8.3 ± 5.0 mm, respectively (p = 0.785). Our results suggest that RVS is a reproducible, operator-independent technique for comparison of US images of BI-RADS category 3 mass lesions obtained at different time points.

Targeted sonography using an image fusion technique for evaluation of incidentally detected breast lesions on chest CT: a pilot study

BackgroundWith increasing use of computed tomography (CT), incidentally detected breast lesions are being encountered more frequently. The aim of our study was to verify the utility of targeted sonography using an image fusion technique, real-time virtual sonography (RVS) that coordinates real-time sonography images with previously obtained CT images using a magnetic position tracking system, for evaluation of incidentally detected breast lesions on chest CT.MethodsEleven lesions in 11 women with no history of breast cancer who were referred to our unit for assessment of breast lesions incidentally detected on CT were enrolled in this study. To assess the efficacy of targeted sonography using RVS, we analyzed the frequency of sonographic detection of incidentally detected breast lesions and the difference between sonography- and CT-determined diameters.ResultsUsing RVS guidance, all 11 lesions were sonographically detected. Ten (91xa0%) of 11 lesions underwent sonography-guided biopsy, yielding a success rate of 90xa0% (9/10). The remaining sonography-guided biopsy failure lesion required surgical biopsy for definitive diagnosis; this was performed after RVS was used to mark CT imaging information onto the breast surface. Four (36xa0%) lesions subsequently proved to be malignant. The mean diameters provided by RVS were 14.9xa0±xa06.7xa0mm for sonography and 16.8xa0±xa07.5xa0mm for CT (pxa0=xa00.538).ConclusionUsing RVS, a sonographic probe was precisely guided to the lesions. Our results suggest that targeted sonography using RVS is a useful technique for identifying incidentally detected breast lesions on chest CT.

The association of cognitive fatigue with menopause, depressive symptoms, and quality of life in ambulatory breast cancer patients

BackgroundThe causes of cancer-related fatigue, which can influence patients’ activities, are multidimensional; however, little is known about the cognitive dimension. We examined the association of cognitive fatigue with menopause, depressive symptoms, and quality of life in ambulatory breast cancer patients after primary treatment.MethodsThis descriptive, cross-sectional study recruited 20–64-year-old breast cancer patients in an outpatient setting. The patients (Nxa0=xa093; mean agexa0=xa053xa0years) were divided into low (L-CogF) and high-cognitive fatigue (H-CogF) groups according to their scores on the cognitive fatigue subscale of the Cancer Fatigue Scale. We compared the groups on their sociodemographic and medical characteristics and scores on the Functional Assessment of Cancer Therapy-Breast (FACT-B) [a measure of quality of life (QOL)], Simplified Menopausal Index (SMI), and Self-Rating Questionnaire for Depression (SRQ-D).ResultsThe L-CogF (nxa0=xa055) and H-CogF (nxa0=xa038) patients did not differ in age, years since diagnosis, marital status, educational background, or treatment history. Total and subscale FACT-B scores, except for physical well-being, were significantly lower in H-CogF participants than in L-CogF participants. SMI and SRQ-D scores were significantly higher in H-CogF participants. Employed H-CogF participants were concerned about keeping their jobs (pxa0<xa00.05).ConclusionsBreast cancer patients with high-cognitive fatigue suffer from severe menopause and depressive symptoms, and deteriorating QOL. Cognitive fatigue should be considered when interpreting patients’ cognitive complaints.

Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer

AbstractBackgroundnAlthough carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are useful tumor markers (TMs) in metastatic breast cancer (MBC), circulating tumor cells (CTCs) are also detected in patients with advanced or metastatic breast cancer. We analyzed CTCs in MBC patients in order to establish the optimal cut-off value, to evaluate the prognostic utility of CTC count, and to clarify whether CTC count could provide information in addition to CEA and CA15-3.MethodsWe studied 98 MBC patients enrolled between June 2007 and March 2013. To quantify CTCs, 7.5xa0ml of blood was collected and CEA and CA15-3 were measured simultaneously. CTCs were counted using the CellSearch™ System. The CTC count was dichotomized as 0 (CTC-negative) or ≥1 (CTC-positive). The clinical significance of CTCs was evaluated in terms of its relationship with levels of CEA and CA15-3. Associations between qualitative variables were evaluated using the chi-square test. In order to evaluate the predictive value of CTCs for advanced or metastatic breast cancer, multivariate Cox proportional hazards modeling was used to calculate hazard ratios.ResultsWith a CTC cut-off value of 1, there were 53 (54.1xa0%) CTC-negative patients and 45 (45.9xa0%) CTC-positive patients. Patients in the CTC-positive group had worse survival than those in the CTC-negative group (pxa0<xa00.0001). Seventy-one patients (72.4xa0%) had TM data at the time of CTC testing. To study the relationship between CTCs and TMs, we divided patients into normal TM and high TM groups. In the normal TM group, the CTC-negative patients had statistically significant survival than the CTC-positive patients (pxa0=xa00.005). The data suggested that CTC count could provide additional prognostic information beyond TMs for advanced/metastatic breast cancer. In multivariate analysis, the only significant predictor of overall survival was CTCxa0≥xa01 (hazard ratio, 3.026; 95xa0% confidence interval 1.350–6.784).ConclusionWe found that a CTC cut-off value of 1 is appropriate in patients with advanced/metastatic breast cancer. CTCs could yield additional information beyond CEA and CA15-3.

Histopathological analysis of anaplastic thyroid carcinoma cases with long-term survival: A report from the Anaplastic Thyroid Carcinoma Research Consortium of Japan.

The aim of this study was to clarify the histopathological features of anaplastic thyroid carcinoma in patients who achieved long-term survival. We reviewed 88 anaplastic thyroid carcinoma cases in which the patient survived less than 3 months (short-term survival), and 68 anaplastic thyroid carcinoma cases in which the patient survived more than one year (long-term survival) from the database of the Anaplastic Thyroid Carcinoma Research Consortium of Japan. We examined these cases both histologically and immunohistochemically. Six (6.8%) short-term survival cases and 27 (39.7%) long-term survival cases were considered not to be anaplastic thyroid carcinoma after central review. Of these, 12 were revised to papillary carcinoma with squamous cell carcinoma. In cases without chemotherapy, long-term survival was significantly more common if there was a pre-existing tumor, epithelial growth, or lymphocytic infiltration, and short-term survival was more common if neutrophilic infiltration was present. In cases with chemotherapy, long-term survival was significantly more common if epithelial growth or a squamous cell carcinoma component was present, whereas short-term survival was more common in cases with rhabdoid cells. Immunohistochemical results were not related to survival. Some long-term survival cases showed histological findings other than those typically associated with anaplastic thyroid carcinoma. The presence of a pre-existing tumor, epithelial growth, a squamous cell carcinoma component, no neutrophilic infiltration and lymphocytic infiltration may therefore be favorable prognostic factors in anaplastic thyroid carcinoma.

Pharmacogenetic association between GSTP1 genetic polymorphism and febrile neutropenia in Japanese patients with early breast cancer

BackgroundGenetic risk factors for febrile neutropenia (FN), the major adverse event of perioperative chemotherapy for early breast cancer, remain unclear.MethodsThis study retrospectively explored pharmacogenetic associations of single nucleotide polymorphisms (SNPs) of the uridine glucuronosyltransferase 2B7 (UGT2B7, rs7668258), glutathione-S-transferase pi 1 (GSTP1, rs1695), and microcephalin 1 (MCPH1, rs2916733) genes with chemotherapy-related adverse events in 102 Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer.ResultsThe allele frequencies for all of the SNPs were in concordance with the Hap-Map data of Japanese individuals. Among the 24 patients who had FN at least once during all courses of chemotherapy, 23 had the A/A genotype, and 1 had the A/G genotype of the GSTP1 polymorphism (rs1695, Pxa0=xa00.001); 23 of the 70 patients with the A/A genotype had FN, as compared with only 1 of the 32 patients with the A/G and G/G genotypes. The genotype distributions of the UGT2B7 and MCPH1 polymorphisms did not differ between the patients who had FN or grade 3/4 neutropenia and those who did not.ConclusionAmong Japanese women who received epirubicin and cyclophosphamide as perioperative chemotherapy for early breast cancer, those with the A/A genotype of the GSTP1 polymorphism (rs1695) were more likely to have FN.

Second-look US Using Real-time Virtual Sonography, a Coordinated Breast US and MRI System with Electromagnetic Tracking Technology: A Pilot Study

Our aim was to retrospectively evaluate the utility of second-look ultrasound (US) using real-time virtual sonography (RVS) for detection of conventional B-mode (cB-mode) occult magnetic resonance imaging (MRI)-detected breast lesions. Between July 2011 and May 2015, 53 consecutive patients who underwent second-look US to identify lesions detected by prone MRI were enrolled in this study. Second-look US using RVS was performed for cB-mode occult MRI-detected breast lesions after an additional supine MRI. In the 53 patients, 59 lesions were initially detected by prone MRI, followed by second-look US. Of the 59 lesions, 20 (34%) were identified by second-look US using cB-mode. Of the 39 (66%) cB-mode occult lesions, 38 (97%) were detected in supine MRI and 33 (85%) were detected by second-look US using RVS. MRI morphology types of the 33 lesions were as follows: mass, 16; non-mass enhancement, 5; and focus, 12. US-guided biopsy under RVS or excisional biopsy demonstrated that of the 33 lesions, 8 (24%) were malignant and the remaining 25 (76%) were benign. A total of 53 (90%) MRI-detected lesions were sonographically identified using both cB-mode and RVS (pxa0<xa00.001). All five remaining US-occult lesions could be followed up under RVS after the enhancing area was marked on the breast surface using RVS. Although further prospective studies are required, the findings of our pilot study suggest that second-look US using RVS with additional supine MRI may improve the sonographic and histopathologic detection rate of cB-mode occult MRI-detected breast lesions.

Alterations in three biomarkers (estrogen receptor, progesterone receptor and human epidermal growth factor 2) and the Ki67 index between primary and metastatic breast cancer lesions

In recurrent breast cancer, the tumor phenotype, as assessed by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) status, occasionally changes. This change, in addition to the Ki67 index were evaluated at sites of recurrence and the correlation between changes in tumor phenotype and survival were assessed in breast cancer patients. Comparisons in pathological parameters between primary and metastatic lesions were drawn between ER, PR, HER2, and the Ki67 index in 70 patients with recurrent breast cancer. The association between changes in tumor phenotype and patient survival was assessed. The hormone receptor status changed from positive, in the primary lesions, to negative, in the metastatic lesions in 19.8% (ER) and 39.5% (PR) of patients, respectively. Conversion from negative to positive status was confirmed in 27.2% (ER) and 31.2% (PR) of patients, respectively. A change in HER2 status from negative (primary lesion) to positive (metastatic lesion) occurred in seven patients (10%). The mean Ki67 index of primary lesions with positive hormone receptor status was significantly lower than at sites of recurrence with any hormone receptor status, from 10.9±9.8 standard deviation (SD) to 22.9±18.6 (P=0.031) and 12.2±10.5 SD to 27.4±20.9 (P=0.023), for ER and PR, respectively. The mean overall survival of patients with ER status conversion from positive to negative was 7.4±1.2 standard error (SE) years, and 14.8±1.4 SE years for patients who retained positive ER status (P=0.005, log-rank), with a hazard ratio of 3.44 (95% confidence interval, 1.36-8.33). This difference in survival based upon change in ER status was similarly observed in patients with PR status conversion in the same direction. Thus, ER and PR status conversion at the time of recurrence strongly impact survival, particularly if the change is from positive (primary lesion) to negative (metastatic lesion). Monitoring the biological behavior of breast cancer may benefit a patient by allowing for a novel personalized treatment strategy.

Pre-Operative Planning Using Real-Time Virtual Sonography, an MRI/Ultrasound Image Fusion Technique, for Breast-Conserving Surgery in Patients with Non-Mass Enhancement on Breast MRI: A Preliminary Study

The purpose of this retrospective study was to evaluate the effect of pre-operative planning using real-time virtual sonography (RVS), a magnetic resonance imaging (MRI)/ultrasound (US) image fusion technique on breast-conserving surgery (BCS) in patients with non-mass enhancement (NME) on breast MRI. Between 2011 and 2015, we enrolled 12 consecutive patients who had lesions with NME that exceeded the US hypo-echoic area, in which it was particularly difficult to evaluate the tumor margin. During pre-operative planning before breast-conserving surgery, RVS was used to delineate the enhancing area on the breast surface after additional supine breast MRI was performed. We analyzed both the surgical margin positivity rate and the re-operation rate. All NME lesions corresponded to the index cancer. In all patients, the diameter of the NME lesion was greater than that of the hypo-echoic lesion. The median diameters of the NME and hypo-echoic lesions were 24u2009mm (range: 12-39u2009mm) and 8.0u2009mm (range: 4.9-18u2009mm), respectively (pu2009=u20090.0002). After RVS-derived skin marking was performed on the surface of the affected breast, lumpectomy and quadrantectomy were conducted in 7 and 5 patients, respectively. The surgical margins were negative in 10 (83%) patients. Two patients with positive margins were found to have ductal carcinoma in situ in 1 duct each, 2.4 and 3.2u2009mm from the resection margin, respectively. None of the patients required additional resection. Although further prospective studies are required, the findings of our preliminary study suggest that it is very well possible that the use of RVS-derived skin marking during pre-operative planning for BCS in patients with NME would have resulted in surgical outcomes similar to or better than those obtained without the use of such marking.

380PCONVERSION OF THE HORMONAL RECEPTORS ON RECURRENT BREAST CANCER PATIENTS

ABSTRACT Aim: When clinicians consider the treatment strategies for the recurrent breast cancer patients, the choice of treament is generally determined with the information of the pathological diagnosis of the primaries. However, the tumor phenotype is sometimes altered when it recurs. In this study, we compared the tumor characteristics among the primaries, metastatic lymph nodes and the recurrences, and assessed the correlation with the survival. Methods: Seventy breast cancer patients whose diagnosis of the primaries and the metastases had been confirmed at Aichi Medical University Hospital were enrolled in this study. The comparative assessment of the lesions was performed on the following factors; the status of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 index. Association with those factors were assessed and the survival was etimated. Results: For ER, 19.8% of patients with the positive status in the primaries changed to the negative in the metastases (ER + /-) and the reverse conversion (from negative to positve; ER-/+) were confimed in 27.2% patients. In the similar fashion, PR + /- was recognized in 39.5% and PR-/+ in 31.2%. As for the metastatic lymph nodes, only 1 case of ER-positive in the primary converted to the negative, but 18.8% of PR-positive and 35.7% of PR-negative were altered to the each opposite receptor status. Ki-67 index increased significantly when the negative conversion occurred in the cases of the positive primaries. The overall survival was worsened significantly on the patients with negative alteration from the positive primaries. The hazard ratio for the survival was 0.29 (95% CI = 0.12-0.73) in the cases of ER + /+ vs. ER + /-, and 0.12 (95%CI = 0.03-0.43) in the cases of PR + /+ vs. PR + /-. Conclusions: The receptor conversion that occur concomitantly with the recurrence of the breast cancer, was observed in about 20 to 40% recurrent cases. On metastasizing, the breast cancer acquired more aggressive nature, especially when its receptor status was altered from positive to negative. The tumor characteristics such as receptor status can be changed so easily that the treatment strategy have to be reconsidered for making an appropriate judgement on the next therapeutic way. Disclosure: All authors have declared no conflicts of interest.