Image-guided breast biopsy of a residual imaging abnormality or tumor bed after neoadjuvant chemotherapy (NACT) is increasingly used to assess residual cancer, facilitate risk-adaptive surgery, and potentially identify exceptional responders in whom local therapy may be de-escalated.OBJECTIVE To further assess the accuracy of post-NACT image-guided biopsy to predict residual cancer in the breast. DESIGN, SETTING, AND PARTICIPANTSThis diagnostic study analyzed multicenter patient-level data of patients with breast cancer who were treated with NACT and underwent image-guided biopsy before surgery at Royal Marsden Hospital in London,
Background: Image-guided biopsy of the residual imaging abnormality / tumor bed at the end of neoadjuvant chemotherapy (NAC) is increasingly used to assess residual disease in the breast, facilitate risk-adaptive surgery and potentially identify exceptional responders who may not require surgical intervention. The aim of this pooled analysis was to further assess the accuracy of post-NAC, image-guided biopsy to predict residual disease in the breast. The findings could help define an optimal post-NAC biopsy protocol to support trials omitting surgery in selected groups of patients. Methods: Multi-institutional, individual patient data on post-NAC image-guided biopsy was collected and pooled following Institutional Review Board (IRB) approval from each centre (Royal Marsden Hospital, Seoul National University Hospital, MD Anderson Cancer Center). Biopsy sampling accuracy was defined as representative if pathology features suggestive of tumor bed or residual cancer were identified. Pathologic complete response (pCR) was defined as no residual disease in the breast (ypT0). Biopsy predictive accuracy was calculated using final surgical pathology as the reference standard. Simple descriptive statistics and non-parametric analyses were performed. Results: Data were analyzed from 166 women who underwent post-NAC image-guided biopsy. Median age was 49 years (range: 25-76). The majority (n=160) had invasive ductal carcinoma (IDC) with phenotype distribution of 31 (18.7%), 47 (28.3%), 29 (17.5%) and 59 (35.5%) respectively for hormone receptor (HR) positive / Human Epidermal Growth Factor Receptor (HER)-2 negative, HR and HER2 positive, HR negative / HER2 positive and triple negative (TN). Median tumor size on pre-treatment imaging was 33.5 mm (range: 12-100). The overall pCR rate was 51.2% [16.1% for HR positive / HER2 negative, 44.7% for HR positive / HER2 positive, 69% for HR negative / HER2 positive and 66.1% for TN]. The majority (n=143) underwent vacuum assisted biopsy (VAB) and 23 had core cut (CC) biopsy. Median size of the biopsy needle was 10 gauge (range: 7-14) and median number of samples was 6 (range: 2-18). The biopsy was performed under ultrasound (n=129) or stereo guidance (n=37) and in 159 cases was representative of the tumor bed. When the image-guided biopsy (VAB and CC) was representative, the false negative rate (FNR) across the whole cohort was 18.7% (95% CI 9.8-26.8). Exploratory analysis of accuracy of VAB in cases with a residual imaging abnormality < 2 cm to allow adequate sampling and at least 6 representative biopsies taken (n=76) showed a FNR of 3.2% (95% CI 0-8.8), a negative predictive value (NPV) of 97.4% (95% CI 84.6-99.6) and an overall accuracy of 89.5% (95% CI: 80.3-95.3). Subgroup analysis in patients with HER2 positive or TN cancer (n=66) who are the most likely to be exceptional responders and achieve pCR showed similar accuracy of the technique with a FNR of 4.2% (95% CI 0-10.7), a negative predictive value (NPV) of 97.2% (95% CI 83.6-99.6) and an overall accuracy of 87.9% (95% CI: 77.5-94.6). Conclusions: This large pooled multicenter data suggests that a standardized protocol using image-guided VAB of a tumor bed measuring up to 2 cm with at least 6 samples allows reliable prediction of residual disease and pCR. These results should inform the design of de-escalation trials in NAC exceptional responders testing the safety of eliminating surgery. Citation Format: Marios Konstantinos Tasoulis, Han-Byoel Lee, Wei Yang, Romney Pope, Savitri Krishnamurthy, Soo-Yeon Kim, Nariya Cho, Victoria Teoh, Gaiane M Rauch, Benjamin D Smith, Vicente Valero, Wonshik Han, Royal Marsden Hospital MDT, Fiona MacNeill, Henry M Kuerer. Accuracy of post-neoadjuvant chemotherapy image-guided breast biopsy to predict the presence of residual cancer: A multi-institutional pooled analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS5-04.
Rationale and ObjectivesTo retrospectively investigate the effect of flip angle (FA) and k-space sampling on the performance of dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) breast sequences.Materials and MethodsFive DCE-MRI breast sequences were evaluated (10°, 14°, and 18° FAs; radial or linear k-space sampling), with 7–10 patients in each group (n = 45). All sequences were compliant with current technical breast screening guidelines. Contrast agent (CA) uptake curves were constructed from the right mammary artery for each examination. Maximum relative enhancement, Emax, and time-to-peak enhancement, Tmax, were measured and compared between protocols (analysis of variance and Mann–Whitney). For each sequence, calculated values of maximum relative enhancement, Ecalc, were derived from the Bloch equations and compared to Emax. Fat suppression performance (residual bright fat and chemical shift artifact) was rated for each examination and compared between sequences (Fisher exact tests).ResultsSignificant differences were identified between DCE-MRI sequences. Emax increased significantly at higher FAs and with linear k-space sampling (P < .0001; P = .001). Radial protocols exhibited greater Tmax than linear protocols at FAs of both 14° (P = .025) and 18° (P < .0001), suggesting artificially flattened uptake curves. Good correlation was observed between Ecalc and Emax (r = 0.86). Fat suppression failure was more pronounced at an FA of 18° (P = .008).ConclusionsThis retrospective approach is validated as a tool to compare and optimize breast DCE-MRI sequences. Alterations in FA and k-space sampling result in significant differences in CA uptake curve shape which could potentially affect diagnostic interpretation. These results emphasize the need for careful parameter selection and greater standardization of breast DCE-MRI sequences.
Axillary ultrasound provides clinically useful information post-NACT, which will guide surgical decision-making. Patients with aUS-negative axillae are likely to have a lower false negative rate of SLNB after NACT (Boughey et al.). However, aUS does not replace the need to identify and biopsy the nodes which were proven to be positive prior to NACT.
PurposeTo propose a method to quantify T1 and contrast agent uptake in breast dynamic contrast‐enhanced (DCE) examinations undertaken with standard clinical fat‐suppressed MRI sequences and to demonstrate the proposed approach by comparing the enhancement characteristics of lobular and ductal carcinomas.MethodsA standard fat‐suppressed DCE of the breast was performed at 1.5 T (Siemens Aera), followed by the acquisition of a proton density (PD)‐weighted sequence, also fat suppressed. Both sequences were characterized with test objects (T1 ranging from 30 ms to 2,400 ms) and calibration curves were obtained to enable T1 calculation. The reproducibility and accuracy of the calibration curves were also investigated. Healthy volunteers and patients were scanned with Ethics Committee approval. The effect of B0 field inhomogeneity was assessed in test objects and healthy volunteers. The T1 of breast tumors was calculated at different time points (pre‐, peak‐, and post‐contrast agent administration) for 20 patients, pre‐treatment (10 lobular and 10 ductal carcinomas) and the two cancer types were compared (Wilcoxon rank‐sum test).ResultsThe calibration curves proved to be highly reproducible (coefficient of variation under 10%). T1 measurements were affected by B0 field inhomogeneity, but frequency shifts below 50 Hz introduced only 3% change to fat‐suppressed T1 measurements of breast parenchyma in volunteers. The values of T1 measured pre‐, peak‐, and post‐contrast agent administration demonstrated that the dynamic range of the DCE sequence was correct, that is, image intensity is approximately directly proportional to 1/T1 for that range. Significant differences were identified in the width of the distributions of the post‐contrast T1 values between lobular and ductal carcinomas (P < 0.05); lobular carcinomas demonstrated a wider range of post‐contrast T1 values, potentially related to their infiltrative growth pattern.ConclusionsThis work has demonstrated the feasibility of fat‐suppressed T1 measurements as a tool for clinical studies. The proposed quantitative approach is practical, enabled the detection of differences between lobular and invasive ductal carcinomas, and further enables the optimization of DCE protocols by tailoring the dynamic range of the sequence to the values of T1 measured.
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