Fazzio, Robert T.

Elevated intratumoral interstitial fluid pressure (IFP) can negatively impact the efficacy of neoadjuvant chemotherapy (NAC) of breast cancer. This study aims to predict breast cancer pathological complete response (pCR) to NAC based on IFP measures by 3-D subharmonic-aided pressure estimation (SHAPE). SHAPE uses the inverse linear relationship between hydrostatic pressure and subharmonic signal magnitude from intravascular ultrasound contrast agents. Thirty-eight breast cancer patients undergoing NAC from three clinical sites were enrolled for this study. SHAPE data were collected for each subject at 0%, 10%, and 30% of NAC completion using a Logiq E9 system (GE HeathCare) equipped with an RSP6-16D probe. The contrast agent used was Definity (Lantheus Medical Imaging). The subharmonic signal gradients between tumor and adjacent normal tissue were calculated and compared with patient pathological response outcome using t-test and receiver operating characteristic (ROC) curve analysis. Pressure gradients between pCR (15 patients) and non-pCR (23 patients) groups were significantly different at 0 (p = 0.02), 10 (p = 0.03), and 30% (p = 0.0003) completion of NAC. Area under the curve values of 0.69, 0.77, and 0.86 were achieved at 0%, 10%, and 30% of NAC completion, respectively. Overall, SHAPE pressure gradients may aid prediction of NAC pathological response in breast cancer patients.

Abstract Background Accurate assessment of axillary lymph nodes (ALNs) is a critical step for timely diagnosis of metastasis and proper subsequent intervention in breast cancer patients. Herein, we compare the diagnostic utility of quantitative high-definition microvasculature imaging (qHDMI), shear wave elastography (SWE) and their combination for differentiation of metastatic ALNs from reactive. Methods A total of 85 female patients with suspicious ALNs recommended for fine needle aspiration biopsy (FNAB) were included in the study, and the pathology results were used as the gold standard for labeling the status of each ALN. Three SWE metrics and ten qHDMI-derived biomarkers were used in our analyses. Additionally, age, as well as clinical ultrasound features such as nodal size and cortical thickness were included as clinical factors. The Wilcoxon rank-sum test was utilized to analyze distributional differences in biomarkers between metastatic and reactive ALNs. Multiple elastic-net logistic regression models were developed based on varying combinations of clinical, qHDMI, and SWE feature sets. A 70%/30% train/test split was adopted, and ROC curve analyses were performed to evaluate and compare classification performance. Moreover, distributional differences in qHDMI and SWE biomarkers between ALNs corresponding to breast cancer immunohistochemical subtypes luminal A and B were investigated. Results Of the total of 85 ALNs included in the analysis, 42 were metastatic. Statistically significant (p-value < 0.05) differences were observed in all but one of the qHDMI biomarkers, as well as all the SWE metrics. Test-set discrimination defined by area under ROC curve (AUC) was low for the model using only clinical features (0.62; 95% CI = [0.39,0.84]), with higher performance observed for models using SWE only (0.93; [0.82,1.00]), qHDMI only (0.97; [0.91,1.00]), qHDMI-SWE (0.97; [0.92,1.00]), and qHDMI-SWE plus clinical biomarkers (0.98; [0.94,1.00]). No statistically significant improvements were seen in the combined SWE-qHDMI and SWE-qHDMI-C classification models relative to the qHDMI-only model, although power for comparison was limited. Four qHDMI biomarkers and two SWE measures exhibited statistically significant distributions among breast cancer luminal A and B subtypes. Conclusions qHDMI classification model was able to separate metastatic from reactive ALNs with high accuracy. qHDMI, SWE, and the combined models had improved classification performance over the baseline Clinical model. qHDMI biomarkers can be valuable in determining the malignancy status of suspicious ALNs, providing helpful information regarding breast cancer prognosis.

Axillary lymph nodes (ALNs) are generally among the first to be impacted by the metastatic spread of breast tumors. Consequently, evaluating their condition is of great importance as the removal of affected ALNs can potentially curtail the further spread of cancer cells to other parts of the body. Conventional ultrasound imaging suffers from low sensitivity and specificity and does not provide a comprehensive picture of the status of the node. In this work, we utilize an ultrasound microvessel imaging technique to visualize vascular structures within ALNs and, through several image processing steps, characterize the morphology of these structures. Several morphological metrics are used as biomarkers to differentiate between reactive and metastatic lymph nodes of patients with suspicious ALNs. A group of 68 patients is included in this study. Pathology examination results are used as the gold-standard reference for data labeling. A support vector machine (SVM) model is trained, and its performance is evaluated. Statistical analysis of the discriminative potential of individual biomarkers and receiver operating characteristic (ROC) curve analysis of the trained model are presented. Preliminary results suggest that a sensitivity of 0.88, specificity of 0.88, and area under the curve of 0.94 are achievable. Work supported by NIH-R01CA239548.

Adenosquamous carcinoma of the breast is a rare subtype of metaplastic carcinoma, which accounts for <1% of invasive breast malignancy. Metaplastic carcinoma is usually high grade and aggressive with typically reported benign imaging features when compared to invasive ductal carcinoma. However, the adenosquamous variant is a subtype with a more favorable prognosis. Within the literature, there is limited imaging description with case studies focusing on metaplastic carcinoma. Herein, we report seven cases of the adenosquamous subtype describing the imaging findings with correlation to clinical history and pathology. The majority of patients (n = 6) presented with palpable breast masses. One patient was identified through screening mammography. Mammographically (n = 6), tumors appeared as irregular masses. Sonographically (n = 7), tumors appeared as irregular masses ranging from solid to mixed solid/cystic masses. On MRI (n = 1), one tumor appeared as an irregular rim enhancing mass. FDG PET/CT (n = 2) and whole-body bone scan (n = 1) were also available for review. The majority of tumors were low-grade (n = 6) with only one high-grade tumor. This case series of seven patients demonstrated predominantly suspicious imaging features despite the majority being low-grade tumors.

86 Background: Phyllodes tumors (PT) are rare breast neoplasms confounding their systematic study and evidence-based management guidelines. There is little data on the sensitivity of preoperative core needle biopsy (CNB) and imaging findings in establishing a correct preoperative diagnosis. We undertook this study to evaluate the sensitivity of CNB histologic findings and imaging findings in preoperatively categorizing tumors as benign or borderline/malignant. Methods: We identified 47 patients who underwent surgical resection of a PT at our institution after a preoperative CNB between 6/2000-3/2012. Statistical analysis utilized Wilcoxon rank-sum, chi-square or Fisher’s exact tests, and 95% confidence intervals (CI) are reported. Results: 30 patients had a final diagnosis of benign and 17 of borderline/malignant PT. The latter were significantly more often palpable (76.5% vs 36.7%, p=0.01). No other clinical or radiologic feature predicted borderline/malignant subtype, although irregular shape on US was suggestive (70.6% vs 44.8%, p= 0.09). CNB diagnosis by tumor type is summarized in the table. No benign PT had ≥10 mitoses, necrosis or marked stromal atypia on CNB. No case with absent mitoses on preoperative CNB was a borderline/malignant PT; however 77% of benign PT did exhibit mitoses on CNB. Sensitivity of CNB for PT overall was 48.9% (95% CI: 35.3-62.8%) while it was 40% (24.6-57.7%) for benign PT and 17.6% (6.2-41.0%) for borderline/malignant PT. Conclusions: Marked stromal atypia, ≥10 mitoses and necrosis were rare on CNB, but suggestive of malignancy. No imaging or histology feature reliably distinguished between tumor types. Over one-third of borderline/malignant PT had a preoperative CNB diagnosis of fibroadenoma or cellular fibroepithelial lesion emphasizing the low sensitivity of CNB and the need for judicious consideration of definitive surgical excision. [Table: see text]

3 Background: Atypical ductal hyperplasia (ADH) is a high-risk breast lesion usually diagnosed with core needle biopsy. Although upgraded to cancer at surgical excision in ~15 to 25% of cases, routine excision is questioned due to cost and overtreatment. We evaluated clinical, imaging, and histologic features associated with cancer upgrade and developed a multivariate model to predict risk of upgrade. Methods: With IRB approval a single institution retrospective review was performed of patients who underwent surgical excision of ADH diagnosed by core biopsy from 06/2005 to 06/2013. Review was performed of electronic records, breast imagin,g and biopsy slides. Multiple imputations were used for missing data. Association of cancer upgrade with various features was assessed with logistic regression. Results: 409 biopsies with ADH on core biopsy, with later surgical excision, were included. The overall upgrade rate was (16.1%, 95% CI:12.9-20.0%); 10 patients had invasive cancer at excision and 56 DCIS only. Features on core biopsy most strongly associated with upgrade were imaging estimated percent of lesion removed (upgrade 9% for 90% removed, 14% for 50 to 75%, and 27% for < 50% removed), individual cell necrosis (upgrade 34% with necrosis vs. 9.5% without), and # foci of ADH (22% for >1 focus vs 8% for 1 focus). A multivariate predictive model (see Table) showed an average C-statistic of 0.77. Women with no necrosis and either 1 focus with ≥ 50% removal or >1 focus with 90% removal (36% of the sample) have low risk of upgrade (5.0%, 95% CI:1.3-8.7%). Conclusions: ADH on core biopsy with low risk of upgrade to cancer is defined by percent of imaging lesion removed, # of foci of ADH, and lack of individual cell necrosis. If findings are validated, women whose biopsies meet low-risk criteria might be considered for chemoprevention and surveillance rather than surgical excision.[Table: see text]