Linda Hovanessian-Larsen

Differentiation of Cancerous Lesions in Excised Human Breast Specimens Using Multiband Attenuation Profiles From Ultrasonic Transmission Tomography

This study examines the tissue differentiation capability of the recently developed high‐resolution ultrasonic transmission tomography (HUTT) system in the context of differentiating between benign and malignant tissue types in mastectomy specimens.

The role of axillary ultrasound in the detection of metastases from primary breast cancers.

BACKGROUND The value of diagnostic axillary ultrasound (AUS) in the preoperative evaluation of lymph nodes for breast cancer patients has yet to be completely clarified. METHODS Results of AUS were reviewed for all patients with invasive cancers who were clinically node negative (cN0) and had subsequent axillary lymphadenectomy. Patients with positive ultrasound-guided node core biopsies bypassed sentinel lymph node biopsy (SLNB) and had axillary lymph node dissection, whereas those with sonographically normal nodes or benign/nondiagnostic biopsy results had SLNB. RESULTS Of 128 cN0 patients with invasive cancer, 23 (18%) had abnormal axillary AUS. Of 18 core biopsies, 12 (67%) were malignant. SLNB was positive in 19 of 110 (17%) patients. ALND was performed in 32 (25%) patients. For determining axillary metastases, AUS sensitivity was 16 of 31 (52%), specificity was 90 of 97 (93%), the positive predictive value was 16 of 23 (69%), and the negative predictive value was 90 of 105 (86%). CONCLUSIONS AUS examination was a valuable method for evaluating the axilla in newly diagnosed cN0 breast cancer patients.

Double-blind randomized 12-month soy intervention had no effects on breast MRI fibroglandular tissue density or mammographic density

Soy supplementation by patients with breast cancer remains controversial. No controlled intervention studies have investigated the effects of soy supplementation on mammographic density in patients with breast cancer. We conducted a double-blind, randomized, placebo-controlled intervention study in previously treated patients with breast cancer (n = 66) and high-risk women (n = 29). We obtained digital mammograms and breast MRI scans at baseline and after 12 months of daily soy (50 mg isoflavones per day; n = 46) or placebo (n = 49) tablet supplementation. The total breast area (MA) and the area of mammographic density (MD) on the mammogram were measured using a validated computer-assisted method, and mammographic density percent (MD% = 100 × MD/MA) was determined. A well-tested computer algorithm was used to quantitatively measure the total breast volume (TBV) and fibroglandular tissue volume (FGV) on the breast MRI, and the FGV percent (FGV% = 100 × FGV/TBV) was calculated. On the basis of plasma soy isoflavone levels, compliance was excellent. Small decreases in MD% measured by the ratios of month 12 to baseline levels were seen in the soy (0.95) and the placebo (0.87) groups; these changes did not differ between the treatments (P = 0.38). Small decreases in FGV% were also found in both the soy (0.90) and the placebo (0.92) groups; these changes also did not differ between the treatments (P = 0.48). Results were comparable in patients with breast cancer and high-risk women. We found no evidence that soy supplementation would decrease mammographic density and that MRI might be more sensitive to changes in density than mammography. Cancer Prev Res; 8(10); 942–51. ©2015 AACR.

A Phase II Study of 3′-Deoxy-3′-18F-Fluorothymidine PET in the Assessment of Early Response of Breast Cancer to Neoadjuvant Chemotherapy: Results from ACRIN 6688

Our objective was to determine whether early change in standardized uptake values (SUVs) of 3′deoxy-3′-18F-fluorothymidine (18F-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAC). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAC. Methods: This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAC varied among centers. All evaluable patients underwent 18F-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAC (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAC completion (FLT3). The percentage change in maximum SUV (%ΔSUVmax) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of ΔSUVmax for pCR was determined using receiver-operating-characteristic curve analysis. The correlation between SUVmax and Ki-67 was also assessed. Results: Fifty-one of 90 recruited patients (median age, 54 y; stage IIA–IIIC) met the eligibility criteria for the primary objective analysis, with an additional 22 patients totaling 73 patients for secondary analyses. A pCR in the primary breast cancer was achieved in 9 of 51 patients. NAC resulted in a significant reduction in %SUVmax (mean Δ, 39%; 95% confidence interval, 31–46). There was a marginal difference in %ΔSUVmax_FLT1-FLT2 between pCR and no-pCR patient groups (Wilcoxon 1-sided P = 0.050). The area under the curve for ΔSUVmax in the prediction of pCR was 0.68 (90% confidence interval, 0.50–0.83; Delong 1-sided P = 0.05), with slightly better predictive value for percentage mean SUV (P = 0.02) and similar prediction for peak SUV (P = 0.04). There was a weak correlation with pretherapy SUVmax and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUVmax and Ki-67 after completion of NAC was stronger (r = 0.68, P < 0.0001). Conclusion: 18F-FLT PET imaging of breast cancer after 1 cycle of NAC weakly predicted pCR in the setting of variable NAC regimens. Posttherapy 18F-FLT uptake correlated with Ki-67 on surgical specimens. These results suggest some efficacy of 18F-FLT as an indicator of early therapeutic response of breast cancer to NAC and support future multicenter studies to test 18F-FLT PET in a more uniformly treated patient population.

Accuracy of Contrast‐Enhanced Ultrasound Compared With Magnetic Resonance Imaging in Assessing the Tumor Response After Neoadjuvant Chemotherapy for Breast Cancer

This pilot study compared contrast enhanced ultrasound (US) with contrast‐enhanced magnetic resonance imaging (MRI) in assessing the treatment response in patients with breast cancer receiving preoperative neoadjuvant chemotherapy (NAC).

A Phase II Study of [(18)F]-3'Deoxy-3'-Fluorothymidine Positron Emission Tomography (FLT-PET) in The Asessment of Early Response of Breast Cancer to Neoadjuvant Chemotherapy: Results From ACRIN 6688

Our objective was to determine whether early change in standardized uptake values (SUVs) of 3′deoxy-3′-18F-fluorothymidine (18F-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAC). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAC. Methods: This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAC varied among centers. All evaluable patients underwent 18F-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAC (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAC completion (FLT3). The percentage change in maximum SUV (%ΔSUVmax) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of ΔSUVmax for pCR was determined using receiver-operating-characteristic curve analysis. The correlation between SUVmax and Ki-67 was also assessed. Results: Fifty-one of 90 recruited patients (median age, 54 y; stage IIA–IIIC) met the eligibility criteria for the primary objective analysis, with an additional 22 patients totaling 73 patients for secondary analyses. A pCR in the primary breast cancer was achieved in 9 of 51 patients. NAC resulted in a significant reduction in %SUVmax (mean Δ, 39%; 95% confidence interval, 31–46). There was a marginal difference in %ΔSUVmax_FLT1-FLT2 between pCR and no-pCR patient groups (Wilcoxon 1-sided P = 0.050). The area under the curve for ΔSUVmax in the prediction of pCR was 0.68 (90% confidence interval, 0.50–0.83; Delong 1-sided P = 0.05), with slightly better predictive value for percentage mean SUV (P = 0.02) and similar prediction for peak SUV (P = 0.04). There was a weak correlation with pretherapy SUVmax and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUVmax and Ki-67 after completion of NAC was stronger (r = 0.68, P < 0.0001). Conclusion: 18F-FLT PET imaging of breast cancer after 1 cycle of NAC weakly predicted pCR in the setting of variable NAC regimens. Posttherapy 18F-FLT uptake correlated with Ki-67 on surgical specimens. These results suggest some efficacy of 18F-FLT as an indicator of early therapeutic response of breast cancer to NAC and support future multicenter studies to test 18F-FLT PET in a more uniformly treated patient population.

High-frequency ultrasound imaging for breast cancer biopsy guidance

Abstract. Image-guided core needle biopsy is the current gold standard for breast cancer diagnosis. Microcalcifications, an important radiographic finding on mammography suggestive of early breast cancer such as ductal carcinoma in situ, are usually biopsied under stereotactic guidance. This procedure, however, is uncomfortable for patients and requires the use of ionizing radiation. It would be preferable to biopsy microcalcifications under ultrasound guidance since it is a faster procedure, more comfortable for the patient, and requires no radiation. However, microcalcifications cannot reliably be detected with the current standard ultrasound imaging systems. This study is motivated by the clinical need for real-time high-resolution ultrasound imaging of microcalcifications, so that biopsies can be accurately performed under ultrasound guidance. We have investigated how high-frequency ultrasound imaging can enable visualization of microstructures in ex vivo breast tissue biopsy samples. We generated B-mode images of breast tissue and applied the Nakagami filtering technique to help refine image output so that microcalcifications could be better assessed during ultrasound-guided core biopsies. We describe the preliminary clinical results of high-frequency ultrasound imaging of ex vivo breast biopsy tissue with microcalcifications and without Nakagami filtering and the correlation of these images with the pathology examination by hematoxylin and eosin stain and whole slide digital scanning.

Comparison of 2D versus 3D mammography with screening cases: an observer study

Breast cancer is the most common type of non-skin cancer in women. 2D mammography is a screening tool to aid in the early detection of breast cancer, but has diagnostic limitations of overlapping tissues, especially in dense breasts. 3D mammography has the potential to improve detection outcomes by increasing specificity, and a new 3D screening tool with a 3D display for mammography aims to improve performance and efficiency as compared to 2D mammography. An observer study using human studies collected from was performed to compare traditional 2D mammography with this new 3D mammography technique. A prior study using a mammography phantom revealed no difference in calcification detection, but improved mass detection in 2D as compared to 3D. There was a significant decrease in reading time for masses, calcifications, and normals in 3D compared to 2D, however, as well as more favorable confidence levels in reading normal cases. Data for this current study is currently being obtained, and a full report should be available in the next few weeks.

A phase II study of 3′-Deoxy-3′- 18 F-fluorothymidine PET in the assessment of early response of breast cancer to neoadjuvant chemotherapy

Our objective was to determine whether early change in standardized uptake values (SUVs) of 3′deoxy-3′-18F-fluorothymidine (18F-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAC). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAC. Methods: This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAC varied among centers. All evaluable patients underwent 18F-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAC (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAC completion (FLT3). The percentage change in maximum SUV (%ΔSUVmax) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of ΔSUVmax for pCR was determined using receiver-operating-characteristic curve analysis. The correlation between SUVmax and Ki-67 was also assessed. Results: Fifty-one of 90 recruited patients (median age, 54 y; stage IIA–IIIC) met the eligibility criteria for the primary objective analysis, with an additional 22 patients totaling 73 patients for secondary analyses. A pCR in the primary breast cancer was achieved in 9 of 51 patients. NAC resulted in a significant reduction in %SUVmax (mean Δ, 39%; 95% confidence interval, 31–46). There was a marginal difference in %ΔSUVmax_FLT1-FLT2 between pCR and no-pCR patient groups (Wilcoxon 1-sided P = 0.050). The area under the curve for ΔSUVmax in the prediction of pCR was 0.68 (90% confidence interval, 0.50–0.83; Delong 1-sided P = 0.05), with slightly better predictive value for percentage mean SUV (P = 0.02) and similar prediction for peak SUV (P = 0.04). There was a weak correlation with pretherapy SUVmax and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUVmax and Ki-67 after completion of NAC was stronger (r = 0.68, P < 0.0001). Conclusion: 18F-FLT PET imaging of breast cancer after 1 cycle of NAC weakly predicted pCR in the setting of variable NAC regimens. Posttherapy 18F-FLT uptake correlated with Ki-67 on surgical specimens. These results suggest some efficacy of 18F-FLT as an indicator of early therapeutic response of breast cancer to NAC and support future multicenter studies to test 18F-FLT PET in a more uniformly treated patient population.

Modified Bi-Rads Scoring of Breast Imaging Findings Improves Clinical Judgment.

In contrast with the reporting requirements currently mandated under the Federal Mammography Quality Standards Act (MQSA), we propose a modification of the Breast Imaging Reporting and Data System (Bi‐Rads) in which a concluding assessment category is assigned, not to the examination as a whole, but to every potentially malignant abnormality observed. This modification improves communication between the radiologist and the attending clinician, thereby facilitating clinical judgment leading to appropriate management. In patients with breast cancer eligible for breast conserving therapy, application of this modification brings to attention the necessity for such patients to undergo pretreatment biopsies of all secondary, synchronous ipsilateral lesions scored Bi‐Rads 3‐5. All contralateral secondary lesions scored Bi‐Rads 3‐5 also require pretreatment biopsies. The application of this modification of the MSQA demonstrates the necessity to alter current recommendations (“short‐interval follow‐up”) for secondary, synchronous Bi‐Rads 3 (“probably benign”) image‐detected abnormalities prior to treatment of the index malignancy.