Miwa Yoshida

Fusion of MRI and Sonography Image for Breast Cancer Evaluation Using Real-time Virtual Sonography with Magnetic Navigation: First Experience

OBJECTIVE We recently developed a real-time virtual sonography (RVS) system that enables simultaneous display of both sonography and magnetic resonance imaging (MRI) cutaway images of the same site in real time. The aim of this study was to evaluate the role of RVS in the management of enhancing lesions visualized with MRI. METHODS Between June 2006 and April 2007, 65 patients underwent MRI for staging of known breast cancer at our hospital. All patients were examined using mammography, sonography, MRI and RVS before surgical resection. Results were correlated with histopathologic findings. MRI was obtained on a 1.5 T imager, with the patient in the supine position using a flexible body surface coil. Detection rate was determined for index tumors and incidental enhancing lesions (IELs), with or without RVS. RESULTS Overall sensitivity for detecting index tumors was 85% (55/65) for mammography, 91% (59/65) for sonography, 97% (63/65) for MRI and 98% (64/65) for RVS. Notably, in one instance in which the cancer was not seen on MRI, RVS detected it with the supplementation of sonography. IELs were found in 26% (17/65) of the patients. Of 23 IELs that were detected by MRI, 30% (7/23) of IELs could be identified on repeated sonography alone, but 83% (19/23) of them were identified using the RVS system (P = 0.001). The RVS system was able to correctly project enhanced MRI information onto a body surface, as we checked sonography form images. CONCLUSIONS Our results suggest that the RVS system can identify enhancing breast lesions with excellent accuracy.

21-Gene expression profile assay on core needle biopsies predicts responses to neoadjuvant endocrine therapy in breast cancer patients.

This study examined postmenopausal estrogen receptor-positive breast cancer patients who received prospective neoadjuvant endocrine therapy (NAET) with tamoxifen or anastrozole to determine if the 21-gene recurrence score (RS) predicts NAET responses. RS scores were determined from pretreatment core biopsy specimens. Although half of the specimens yielded insufficient RNA, the remaining samples were highly representative. Patients with a low RS tended to respond better than those with an intermediate or high RS (n=43). Response rates by RS were similar between the tamoxifen and anastrozole groups. Patients with a low RS tended to have better relapse-free survival (RFS) than those with an intermediate or high RS (5y-RFS; 100% vs. 84% and 73%, respectively). These results suggest that RS predicts responses to NAET with tamoxifen or anastrozole. Because this pilot study examined a small sample size, these results should be validated in larger studies.

Real-Time Virtual Sonography, A Coordinated Sonography and MRI System that Uses Magnetic Navigation, Improves the Sonographic Identification of Enhancing Lesions on Breast MRI

This study verified that recently developed real-time virtual sonography (RVS) to coordinate a sonography image and the magnetic resonance imaging (MRI) multiplanar reconstruction (MPR) with magnetic navigation was useful. The purpose of this study was to evaluate the accuracy of RVS to sonographically identify enhancing lesions by breast MRI. Between December 2008 and May 2009, RVS was performed in 51 consecutive patients with 63 enhancing lesions. MRI was performed with the patients in the supine position using a 1.5-T imager with a body surface coil to achieve the same position as with sonography. To assess the accuracy of the RVS, the following three issues were analyzed: (i) The sonographic detection rate of enhancing lesions, (ii) the comparison of the tumor size measured by sonography and the MRI-MPR and (iii) the positioning errors as the distance from the actual sonographic position to the expected MRI position in 3-D. Among the 63 enhancing lesions, 42 (67%) lesions were identified by conventional B-mode, whereas the remaining 21 (33%) initial conventional B-mode occult lesions were identified by RVS alone. The sonographic size of the lesions detected by RVS alone was significantly smaller than that of lesions detected by conventional B-mode (p < 0.001). The mean tumor size provided by RVS was 12.3 mm for real-time sonography and 14.1 mm for MRI-MPR (r = 0.848, p < 0.001). The mean positioning errors for the transverse and sagittal planes and the depth from the skin were 7.7, 6.9 and 2.8 mm, respectively. The overall mean 3D positioning error was 12.0 mm. Our results suggest that RVS has good targeting accuracy to directly compare a sonographic image with MRI results without operator dependence.

Evaluation of axillary status in patients with breast cancer using thin-section CT

BackgroundIn recent years, the surgical management of patients with breast cancer has shifted to a locoregional approach, and evaluating the patient’s axillary lymph node status is of the greatest importance in determining the appropriate treatment strategy. We evaluated on the efficacy of preoperative axillary staging using contrast-enhanced computed tomography (CE-CT).MethodsBetween 2000 and 2003, 235 patients with operable breast cancer who underwent CE-CT before surgery and 137 patients who received neoadjuvant chemotherapy (NAC) and underwent CE-CT before NAC and surgery were enrolled in this study. The axillary status was evaluated based on three criteria (short-axis diameter, shape, and enhancement type), and the diagnosis was correlated with the histopathological results.ResultsIn patients who did not receive NAC, the size criterion of a short-axis diameter of more than 5 mm provided a sensitivity of 78%, a specificity of 75%, and an accuracy of 76% in predicting node-positive status. According to the size criterion of a short-axis diameter of more than 5 mm and the shape criterion of the absence of intranodal fat density, the specificity and accuracy were 90% and 81%, respectively, and according to the enhancement type criterion of early enhancement, the corresponding values were 89% and 78%. Evaluation was more difficult in patients who received NAC and the sensitivity of the size-based criterion in the patients who received NAC was lower than in those who did not.ConclusionThese findings suggest that CE-CT based on size criteria is useful for evaluating the preoperative axillary status of breast cancer patients, but that evaluation is more difficult and the sensitivity is reduced in patients who have received NAC.

Prognostic Factors in Young Japanese Women with Breast Cancer: Prognostic Value of Age at Diagnosis

OBJECTIVE The primary objective of this study was to verify whether breast cancer patients aged <35 at diagnosis have poorer prognoses than those aged 35-39, in other words, to identify the prognostic value of age in younger premenopausal patients under 40 years old. The secondary objective was to assess prognostic factors specific for younger premenopausal patients. METHODS We identified 242 consecutive patients who were diagnosed with stage I-III breast cancer before the age of 40 and underwent surgery between 1990 and 2004. We compared disease-free survival and overall survival in patients aged <35 years and those aged 35-39 years, and evaluated clinicopathological factors associated with disease-free survival or overall survival in each age group and in all patients under the age of 40. RESULTS Ninety-nine (41%) patients were younger than 35 years and 143 (59%) were between 35 and 39 years. No significant difference in disease-free survival or overall survival was found between the two groups. In our cohort of patients under the age of 40, the independent factors associated with poor disease-free survival and overall survival included positive axillary lymph nodes and triple-negative status, but not age at diagnosis. Adverse prognostic factors also did not differ considerably between the two age groups. CONCLUSIONS Age at diagnosis was not an independent prognostic factor in our study. Our findings suggest that other clinicopathological features rather than age should be used to determine individualized treatment courses for breast cancer patients younger than 40 years.

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.

A Case of Estrogen Receptor Positive Secretory Carcinoma in a 9-Year-old Girl With ETV6–NTRK3 Fusion Gene

The patient was a 9-year-old premenarcheal pediatric female, whose chief complaint was a well-circumscribed palpable right breast mass without nipple discharge. Although the patient had noticed the lump 2 years prior to hospital admission, its size (1.5 × 1.3 cm) had been stable. There was no family history or previous history of malignancies. Physical examination showed a well-delimited, elastic-firm and movable tumor just beneath the nipple and areolar complex. Regional lymph nodes were not palpable. Ultrasonography and breast computed tomography revealed a subareolar oval-shaped tumor exhibiting homogeneous echogenicity with clear margins. Distant metastases could not be detected using whole-body computed tomographic scans. A fine-needle aspiration cytology specimen showed atypical cells with prominent nucleoli and abundant intracellular secretory material, suggesting the possibility of secretory carcinoma. Histopathological analysis of the core needle biopsy specimen revealed that the tumor was a secretory carcinoma. The patient underwent total mastectomy with sentinel lymph node biopsy. Metastases were not observed in the removed lymph nodes. Estrogen receptor was weakly positive and progesterone receptor was negative. Human epidermal growth factor receptor 2 expression was also negative. In addition, the ETV6 (exon 5) and NTRK3 (exon 13) fusion gene was detected using the reverse transcription-polymerase chain reaction method. This gene is considered specific for secretory carcinoma. Immunohistochemistry revealed weak basal differentiation [cytokeratin 5/6(CK5/6)(+), vimentin(+) and epidermal growth factor receptor(+)]. The patient has received no adjuvant therapy and is currently disease free at 12 months after surgery.

Loss of heterozygosity on chromosome 16q suggests malignancy in core needle biopsy specimens of intraductal papillary breast lesions

It is often difficult to make a definitive diagnosis of papillary breast lesions using core needle biopsy (CNB) specimens. We studied loss of heterozygosity (LOH) on chromosome 16q in order to assess its diagnostic use for papillary breast lesions in CNB specimens. Of 25 patients with intraductal papillary breast tumors, we extracted DNA from paired samples of tumor cells from CNB specimens and non-tumor cells from subsequent excision specimens and analyzed LOH at the D16S419 and D16S514 loci on chromosome 16q. LOH analysis results were compared with final diagnoses based on pathological features of the resected specimens. On the CNB specimens, 21 tumors were histologically diagnosed as indeterminate or suspicious for malignancy, while four tumors were unambiguously malignant. Of the 21 indeterminate or suspicious tumors, 11 were finally diagnosed as benign and ten as malignant, and on these, LOH analyses were informative for 8 of the 11 benign tumors and 7 of the 10 malignant tumors. LOH was also informative on two of the four tumors unambiguously malignant on CNB. None of the eight informative benign tumors showed LOH on 16q. Six of the eleven informative malignant tumors showed LOH on 16q. LOH on 16q was significantly different between CNB specimens of benign and malignant intraductal papillary tumors (P = 0.007). Analysis of LOH on 16q may be helpful in making a definitive diagnosis in cases of papillary breast lesions, in both excised and CNB specimens.

Usefulness of preoperative multidetector-row computed tomography in evaluating the extent of invasive lobular carcinoma in patients with or without neoadjuvant chemotherapy

BackgroundThe present study was conducted to assess the clinical usefulness of multidetector-row CT (MDCT) in determining the extent of invasive lobular carcinoma (ILC) and especially the extent of residual tumor after neoadjuvant chemotherapy (NAC).Patients and methodsThe subjects were 24 patients with primary ILC who underwent surgery without NAC and 17 patients with ILC who underwent surgery after NAC at National Cancer Center Hospital (NCCH) between April 1999 and December 2005. The extent of primary ILC was assessed by ultrasound, mammography, and MDCT before surgery, and the results obtained using each modality were compared with the results of pathological examination after surgery. In addition, the characteristic findings of ILC obtained by MDCT were assessed. Similarly, the extent of residual tumor after NAC was evaluated using ultrasound, mammography, and MDCT before surgery in the subjects who underwent NAC, and the results obtained by each modality were compared with the results of pathological examination after surgery.ResultsThe findings of primary ILC obtained by MDCT showed that the carcinoma was the non-localized type rather than the localized type in 63% of the subjects. In addition, with regard to the pattern of time-sequential contrast enhancement, the persistent pattern (in which tumor enhancement is strong in the late phase rather than in the early phase) was observed in 46% of the subjects, and the plateau pattern (in which contrast enhancement is weak in both the early phase and the late phase) was observed in 38% of the subjects. These trends were significant in the subjects who underwent NAC and in whom tumor enhancement could not be clearly observed by MDCT. Assessment of the extent of carcinoma showed that the diagnostic accuracy of MDCT was 79%, as compared with 71% for either ultrasound or mammography. Assessment of the extent of carcinoma after NAC also showed that the diagnostic accuracy of MDCT was 71%, as compared with 48% for ultrasound and 53% for mammography, indicating that MDCT provided the highest accuracy. It should be noted that for all modalities, the extent of ILC was not overestimated as compared with the tumor diameter measured during pathological examination.ConclusionAssessment by MDCT showed that ILC tends to be diffuse, tumor enhancement tends to be very weak, and the rate of enhancement tends to be low. In addition, MDCT was found to be useful for determining the extent of carcinoma, and the diagnostic accuracy of MDCT, especially in determining the extent of carcinoma after NAC, was much higher than that of ultrasound or mammography.

Abstract P3-13-17: A multi-center prospective study of radiofrequency ablation therapy for small breast carcinomas

Background: As the management of breast carcinoma evolves toward less invasive treatments, the next step is the possibility of removing the primary tumor without surgery. The most promising noninvasive ablation technique is radiofrequency ablation (RFA), which can effectively kill tumor cells with a low complication rate. Our preliminary studies of RFA followed by standard surgical resection have indicated that this technique is effective for surgical ablation of small (≤ 2cm) breast tumors without extensive intraductal components (EIC). Methods: To determine if RFA is oncologically and cosmetically appropriate for the local treatment of primary breast carcinoma, this multi-center prospective study used RFA as the sole local treatment of breast tumors ≤ 1.5cm in size on ultrasound and MRI. Exclusion criteria include receiving of preoperative chemotherapy, or the presence of invasive lobular carcinoma or invasive ductal carcinoma with suspicious EIC. After confirmation that the standard baseline core biopsy for diagnosis and measurement of tumors markers (ER, PgR, HER-2/neu expression and the presence of the Ki-67 proliferative marker) have been obtained, consent will be obtained and the patient scheduled RFA. All patients received adjuvant radiation therapy. The use and choice of systemic therapy will be based on the information from the baseline core biopsy. The first primary endpoints of this study is successful tumor ablation, as evidenced by negative findings on vacuum-assisted or core biopsies and imaging studies after RFA. The second primary endpoints is the incidence of procedure related adverse events. Forty patients with small tumors that are clearly identifiable and measurable by ultrasound and MRI were enrolled. The response to ablation was evaluated with both vacuum-assisted or core biopsies and imaging studies every 3 months during the first year. The long-term outcomes were assessed using quality of life measurement scales and imaging studies every 6 months thereafter through year 5. Results: Of the 58 patients who participated in this study, 55 completed the protocol. In 48 of the 55 (87%) treated patients, successful tumor ablation, as determined by negative findings on vacuum-assisted or core biopsies and imaging studies, was confirmed. The remaining 7 patients with biopsies positive for residual tumor underwent surgical resection. There were no local or distant recurrences in treated 55 patients with a median follow up of 47 (range 36-73) months. Conclusions: RFA can be safely used alone in patients with small breast tumors, provided that local tumor control must be regularly assessed by image-guided vacuum-assisted or core biopsies after ablation. RFA has several potential advantages over lumpectomy for the treatment of early stage breast cancer. Citation Format: Kinoshita T, Ohtani S, Doihara H, Yamamoto N, Takahashi M, Fujisawa T, Aogi K, Hojo T, Asaga S, Yoshida M, Tsuda H. A multi-center prospective study of radiofrequency ablation therapy for small breast carcinomas [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-17.