ROC study of the effect of stereoscopic imaging on assessment of breast lesions

An observer performance study was conducted to evaluate the usefulness of assessing breast lesion characteristics with stereomammography. Stereoscopic image pairs of 158 breast biopsy tissue specimens were acquired with a GE Senographe 2000D full field digital mammography system using a 1.8x magnification geometry. A phantom-shift method equivalent to a stereo shift angle of +/- 3 degrees relative to a central axis perpendicular to the detector was used. For each specimen, two pairs of stereo images were taken at approximately orthogonal orientations. The specimens contained either a mass, microcalcifications, both, or normal tissue. Based on pathological analysis, 39.9% of the specimens were found to contain malignancy. The digital specimen radiographs were displayed on a high resolution MegaScan CRT monitor driven by a DOME stereo display board using in-house developed software. Five MQSA radiologists participated as observers. Each observer read the 316 specimen stereo image pairs in a randomized order. For each case, the observer first read the monoscopic image and entered his/her confidence ratings on the presence of microcalcifications and/or masses, margin status, BI-RADS assessment, and the likelihood of malignancy. The corresponding stereoscopic images were then displayed on the same monitor and were viewed through stereoscopic LCD glasses. The observer was free to change the ratings in every category after stereoscopic reading. The ratings of the observers were analyzed by ROC methodology. For the 5 MQSA radiologists, the average Az value for estimation of the likelihood of malignancy of the lesions improved from 0.70 for monoscopic reading to 0.72 (p=0.04) after stereoscopic reading, and the average Az value for the presence of microcalcifications improved from 0.95 to 0.96 (p=0.02). The Az value for the presence of masses improved from 0.80 to 0.82 after stereoscopic reading, but the difference fell short of statistical significance (p=0.08). The visual assessment of margin clearance was found to have very low correlation with microscopic analysis with or without stereoscopic reading. This study demonstrates the potential of using stereomammography to improve the detection and characterization of mammographic lesions.     

Improvement of mammographic mass characterization using spiculation meausures and morphological features

We are developing new computer vision techniques for characterization of breast masses on mammograms. We had previously developed a characterization method based on texture features. The goal of the present work was to improve our characterization method by making use of morphological features. Toward this goal, we have developed a fully automated, three-stage segmentation method that includes clustering, active contour, and spiculation detection stages. After segmentation, morphological features describing the shape of the mass were extracted. Texture features were also extracted from a band of pixels surrounding the mass. Stepwise feature selection and linear discriminant analysis were employed in the morphological, texture, and combined feature spaces for classifier design. The classification accuracy was evaluated using the area Az under the receiver operating characteristic curve. A data set containing 249 films from 102 patients was used. When the leave-one-case-out method was applied to partition the data set into trainers and testers, the average test Az for the task of classifying the mass on a single mammographic view was 0.83 +/- 0.02, 0.84 +/- 0.02, and 0.87 +/- 0.02 in the morphological, texture, and combined feature spaces, respectively. The improvement obtained by supplementing texture features with morphological features in classification was statistically significant (p = 0.04). For classifying a mass as malignant or benign, we combined the leave-one-case-out discriminant scores from different views of a mass to obtain a summary score. In this task, the test Az value using the combined feature space was 0.91 +/- 0.02. Our results indicate that combining texture features with morphological features extracted from automatically segmented mass boundaries will be an effective approach for computer-aided characterization of mammographic masses.     

Aromatase inhibitor-induced modulation of breast density: clinical and genetic effects

Background:

Change in breast density may predict outcome of women receiving adjuvant hormone therapy for breast cancer. We performed a prospective clinical trial to evaluate the impact of inherited variants in genes involved in oestrogen metabolism and signalling on change in mammographic percent density (MPD) with aromatase inhibitor (AI) therapy.

Methods:

Postmenopausal women with breast cancer who were initiating adjuvant AI therapy were enrolled onto a multicentre, randomised clinical trial of exemestane vs letrozole, designed to identify associations between AI-induced change in MPD and single-nucleotide polymorphisms in candidate genes. Subjects underwent unilateral craniocaudal mammography before and following 24 months of treatment.

Results:

Of the 503 enrolled subjects, 259 had both paired mammograms at baseline and following 24 months of treatment and evaluable DNA. We observed a statistically significant decrease in mean MPD from 17.1 to 15.1% (P<0.001), more pronounced in women with baseline MPD ⩾20%. No AI-specific difference in change in MPD was identified. No significant associations between change in MPD and inherited genetic variants were observed.

Conclusion:

Subjects with higher baseline MPD had a greater average decrease in MPD with AI therapy. There does not appear to be a substantial effect of inherited variants in biologically selected candidate genes.     

Neoadjuvant docetaxel and capecitabine and the use of thymidine phosphorylase as a predictive biomarker in breast cancer.

PURPOSE: Thymidine phosphorylase (TP) induction by docetaxel is a proposed mechanism for the observed preclinical synergy of docetaxel and capecitabine (DC). We evaluated whether TP protein expression is increased by docetaxel and correlates with pathologic complete response (pCR) in breast cancer patients. EXPERIMENTAL DESIGN: Women with stage II to III breast cancer were given four cycles of neoadjuvant docetaxel 36 mg/m(2) i.v. over 30 min on days 1, 8, and 15 and capecitabine 2,000 mg/d, in two divided doses, on days 5 to 21 of a 28-day cycle. Radiology-directed biopsies of the breast tumors were done at baseline and 5 days after the first dose of docetaxel to evaluate TP expression. Following DC therapy, patients had core breast biopsies, and if residual disease was present, received four cycles of standard dose-dense doxorubin and cyclophosphamide (AC). RESULTS: The pCR rate was 26.9% (95% confidence interval, 11.6-47.8). Up-regulation of TP expression was not observed by either quantitative immunofluorescence (QIF) or immunohistochemistry. Radiology-directed core biopsy after neoadjuvant chemotherapy accurately predicted pathologic response in 88% (95% confidence interval, 69.8-97.6) of the cases. Neither level of TP expression nor TP up-regulation correlated with pCR. Significant toxicity resulted in therapy discontinuation in 3 of 26 patients. CONCLUSIONS: DC chemotherapy exhibited a similar pCR rate compared with standard taxane regimens, with increased toxicity. TP expression was not up-regulated after docetaxel and did not correlate with therapeutic response. Core breast biopsy after neoadjuvant chemotherapy accurately predicted pathologic response.