Differences in Re-excision Rates for Breast-Conserving Surgery Using Intraoperative 2D Versus 3D Tomosynthesis Specimen Radiograph.

BACKGROUND: Intraoperative specimen radiographs performed during breast conservation surgery for cancer reduces the need for re-excision for positive margins. We studied 2D versus 3D image-guided cavity margin excision and compared it to final pathology and need for additional surgery. METHODS: We conducted a retrospective review of 657 breast-conserving operations performed for cancer from 2013 to 2018. Procedures were performed by four surgeons at a single tertiary institution with access intraoperatively to 2D and 3D radiographs. Data collected included demographics, intraoperative margin assessment, final pathology, and re-excision rates. RESULTS: A total of 466 patients had 2D and 191 had 3D specimen imaging. The 2D group had a lower mean age and a higher body mass index and proportion of minority patients than the 3D group (P < 0.01). In the 3D group, there was a higher percentage of patients with mammographically denser breasts (P < 0.06); 58% of patients in the 3D group had additional imaging-directed cavity margins excised versus 32% of patients in the 2D group (P < 0.01). In the 2D group, 44 patients (9%) had positive final margins versus 8 patients (4%) in the 3D group (P = 0.02). No difference was found on total volume of excision (P = 0.56). The re-excision rate for the 2D group was 11% versus 5% for the 3D group (P = 0.02; adjusted odds ratio = 0.41, 95% confidence interval 0.19-0.86). CONCLUSIONS: Re-excision rates using both modalities are low. A lower re-excision rate is independently associated with 3D tomosynthesis. This allows surgeons to excise additional margins at the index operation, decreasing reoperations and anxiety/costs for patients.

Germline Genetic Testing: What the Breast Surgeon Needs to Know.

PURPOSE: The American Society of Breast Surgeons (ASBrS) sought to provide educational guidelines for breast surgeons on how to incorporate genetic information and genomics into their practice. METHODS: A comprehensive nonsystematic review was performed of selected peer-reviewed literature. The Genetics Working Group of the ASBrS convened to develop guideline recommendations. RESULTS: Clinical and educational guidelines were prepared to outline the essential knowledge for breast surgeons to perform germline genetic testing and to incorporate the findings into their practice, which have been approved by the ASBrS Board of Directors. RECOMMENDATIONS: Thousands of women in the USA would potentially benefit from genetic testing for BRCA1, BRCA2, and other breast cancer genes that markedly increase their risk of developing breast cancer. As genetic testing is now becoming more widely available, women should be made aware of these tests and consider testing. Breast surgeons are well positioned to help facilitate this process. The areas where surgeons need to be knowledgeable include: (1) identification of patients for initial breast cancer-related genetic testing, (2) identification of patients who tested negative in the past but now need updated testing, (3) initial cancer genetic testing, (4) retesting of patients who need their genetic testing updated, (5) cancer genetic test interpretation, posttest counseling and management, (6) management of variants of uncertain significance, (7) cascade genetic testing, (8) interpretation of genetic tests other than clinical cancer panels and the counseling and management required, and (9) interpretation of somatic genetic tests and the counseling and management required.

Assessing, Counseling, and Treating Patients at High Risk for Breast Cancer.

Identifying patients at high risk of carrying pathogenic variants in genes is a crucial part of providing both accurate counseling and evidence-based treatment recommendations. Current risk assessment models have strengths and weaknesses that may limit their applicability to specific clinical circumstances. Clinicians must have knowledge regarding variations in available models, how they should be used, and what data they can expect from specific models. In addition, indications for genetic testing are expanding, and the adoption of next-generation sequencing has allowed the creation of multigene testing panels. Complex consequences of panel testing have included an increase in the incidence of identifying variants of uncertain significance and the identification of pathogenic variants in genes for which treatment guidelines are not available. Women diagnosed with breast cancer who carry pathogenic variants in genes with proven associations with breast cancer (BRCA1/2) or highly likely associations (PTEN, PALB2) require additional risk assessment to facilitate treatment decisions that will limit in-breast tumor recurrence and contralateral breast cancer.

Early results from a novel quality outcomes program: the American Society Of Breast Surgeons' Mastery of Breast Surgery.

BACKGROUND: In 2008, the American Society for Breast Surgeons launched its Mastery in Breast Surgery Pilot Program to demonstrate feasibility of a Web-based tool for breast surgeons to document and monitor quality outcomes. METHODS: Participating surgeons report performance of three quality measures for breast procedures: Was a needle biopsy performed to evaluate the breast lesion before the procedure? Was the surgical specimen oriented? For nonpalpable lesions localized with image guidance, was there intraoperative confirmation of removal? Data are collected through the American Society for Breast Surgeons' Web-based software using a secure server and encrypted identification numbers. Surgeon demographic/practice characteristic data were collected, and logistic regression models were used to identify factors that affected quality measures. RESULTS: From October 2008 to December 2009, a total of 696 surgeons entered data for 28,798 breast procedures. Participants were diverse in years in practice, geographic location, practice setting and type, and proportion of practice made up of breast procedures. Delivery of "optimal care" (defined as delivery of all quality measures for which there was no valid clinical reason for nonperformance) was high for all surgeon demographic/practice characteristics, ranging from 81% to 94%. Statistically significant differences in delivery of quality measures were observed within all physician demographic/practice characteristic variables, but many absolute differences were small. CONCLUSIONS: The high level of participation and volume of breast procedures for which quality measure data was entered demonstrate this is a feasible means of collecting quality performance data. Future development will include identifying/developing additional quality measures and establishing evidence-based benchmarks for care on the basis of data collected.

Cytogenetic evidence that circulating epithelial cells in patients with carcinoma are malignant.

PURPOSE: Numerous studies of circulating epithelial cells (CECs)have been described in cancer patients, and genetic abnormalities have been well documented. However, with one exception in colorectal cancer, there has been no report of matching the genetic abnormalities in the CECs with the primary tumor. The purpose of this investigation was to determine (a) whether CECs in patients including those with early tumors are aneusomic and (b) whether their aneusomic patterns match those from the primary tumor, indicating common clonality. EXPERIMENTAL DESIGN: Thirty-one cancer patients had CECs identified by immunofluorescence staining using a monoclonal anti-cytokeratin antibody. Their CECs were analyzed by enumerator DNA probes for chromosomes 1, 3, 4, 7, 8, 11, or 17 by dual or tricolor fluorescence in situ hybridization. Touch preparations of the primary tumor tissue were available from 17 of 31 patients and hybridized with the same set of probes used to genotype the CECs. RESULTS: The number of CECs from each patient ranged from 1-92 cells/cytospin. CECs showed abnormal copy numbers for at least one of the probes in 25 of 31 patients. Touch preparations from the primary tumors of 13 patients with aneusomic CECs were available. The pattern of aneusomy matched a clone in the primary tumor in 10 patients. CONCLUSIONS: We conclude that the vast majority of CECs in breast, kidney, prostate, and colon cancer patients are aneusomic and derived from the primary tumor.

Interpretive disparity among pathologists in breast sentinel lymph node evaluation.

BACKGROUND: Immunohistochemical staining on breast sentinel lymph nodes (SLN) is controversial. METHODS: Twenty-five SLN cases were reviewed by 10 pathologists (three academic, seven private) including 5 negative by both hematoxylin and eosin (H&E) and immunohistochemistry, 11 micrometastases (<2 mm) negative by H&E but positive by immunohistochemistry, and 8 micrometastases and 1 macrometastasis (>2 mm) positive for both H&E and immunohistochemistry. Answers included "positive," "negative," and "indeterminate" for each slide. RESULTS: The mean number of incorrect responses was 6.6 for immunohistochemistry and 5 for H&E. Twelve percent of cases were correct by all 10 pathologists; 80% of positive IHC cases had at least one pathologist score it incorrectly. As tumor cells decrease in number, incorrect responses increase. When tumor cells numbered less than 10, more than 30% of pathologists answered incorrectly. CONCLUSIONS: As tumor cells decrease in number pathologists' ability to recognize them decreases. We propose adding "indeterminate" to "positive" and "negative" when tumor cells number less than 10.

uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues.

Overexpression of urokinase plasminogen activator system or HER-2 (erbB-2) in breast cancer is associated with a poor prognosis. HER-2 overexpression is caused by HER-2 gene amplification. The anti-HER-2 antibody trastuzumab significantly improves clinical outcome for HER2-positive breast cancer. Drugs that target the uPA system are in early clinical trials. The aims of this study were to determine whether urokinase plasminogen activator receptor (uPAR) gene amplification occurs and whether analysis of individual tumor cells (TCs) in the blood or tissue can add information to conventional pathological analysis that could help in diagnosis and treatment. Analysis of individual TCs indicates that uPAR amplification occurs in a significant portion of primary breast cancers and also circulating tumor cells (CTCs) from patients with advanced disease. There was complete concordance between touch preps (TPs) and conventional pathological examination of HER-2 and uPAR gene status in primary tumors. There was also excellent concordance of HER-2 gene status between primary tumors and CTCs provided that acquisition of HER-2 gene amplification in CTCs was taken into account. Unexpectedly, gene amplification of HER-2 and uPAR occurred most frequently in the same TC and patient, suggesting a biological bias and potential advantage for coamplification. Expression of HER-2 and uPAR in primary tumors predicted gene status in 100 and 92% of patients, respectively.

Intraoperative cytologic diagnosis of breast sentinel lymph nodes in the routine, nonacademic setting: a highly specific test with limited sensitivity.

Intraoperative determination of metastatic breast carcinoma in sentinel lymph nodes (SLNs) by cytologic methods has been proposed as highly specific and sensitive. Much of these data are derived from academic institutes with highly trained personnel and without axillary dissection occurring as a direct result of the intraoperative interpretation. This prospective study was undertaken to assess the sensitivity and specificity of cytology in the routine, private-practice, intraoperative setting. A total of 207 SLNs from 96 breast carcinoma patients were evaluated by intraoperative cytologic preparations by general surgical pathologists; positive results led to axillary lymphadenectomy. Ten nodes were positive by intraoperative cytology (IC). Permanent section analysis confirmed the presence of carcinoma in the IC-positive cases and documented carcinoma in 19 of the IC-negative cases. IC sensitivity and specificity were 34% and 100%, respectively. False-negative IC interpretations occurred in nodes with occult micrometastases (12 of 19 nodes) and lobular carcinoma (6 of 19 nodes). Only one of eight grossly positive sentinel nodes resulted in a false-negative IC. While near-perfect specificity and high sensitivity can be achieved with grossly positive sentinel nodes by IC, sensitivity is quite low in cases with micrometastatic and lobular carcinoma.

HER-2 gene amplification can be acquired as breast cancer progresses.

Amplification and overexpression of the HER-2 oncogene in breast cancer is felt to be stable over the course of disease and concordant between primary tumor and metastases. Therefore, patients with HER-2-negative primary tumors rarely will receive anti-Her-2 antibody (trastuzumab, Herceptin) therapy. A very sensitive blood test was used to capture circulating tumor cells (CTCs) and evaluate their HER-2 gene status by fluorescence in situ hybridization. The HER-2 status of the primary tumor and corresponding CTCs in 31 patients showed 97% agreement, with no false positives. In 10 patients with HER-2-positive tumors, the HER-2/chromosome enumerator probe 17 ratio in each tumor was about twice that of the corresponding CTCs (mean 6.64 +/- 2.72 vs. 2.8 +/- 0.6). Hence, the ratio of the CTCs is a reliable surrogate marker for the expected high ratio in the primary tumor. Her-2 protein expression of 10 CTCs was sufficient to make a definitive diagnosis of the HER-2 gene status of the whole population of CTCs in 19 patients with recurrent breast cancer. Nine of 24 breast cancer patients whose primary tumor was HER-2-negative each acquired HER-2 gene amplification in their CTCs during cancer progression, i.e., 37.5% (95% confidence interval of 18.8-59.4%). Four of the 9 patients were treated with Herceptin-containing therapy. One had a complete response and 2 had a partial response.