Mean Apparent Propagator MRI: Quantitative Assessment of Tumor-Stroma Ratio in Invasive Ductal Breast Carcinoma.

Purpose To determine whether metrics from mean apparent propagator (MAP) MRI perform better than apparent diffusion coefficient (ADC) value in assessing the tumor-stroma ratio (TSR) status in breast carcinoma. Materials and Methods From August 2021 to October 2022, 271 participants were prospectively enrolled (ClinicalTrials.gov identifier: NCT05159323) and underwent breast diffusion spectral imaging and diffusion-weighted imaging. MAP MRI metrics and ADC were derived from the diffusion MRI data. All participants were divided into high-TSR (stromal component < 50%) and low-TSR (stromal component ≥ 50%) groups based on pathologic examination. Clinicopathologic characteristics were collected, and MRI findings were assessed. Logistic regression was used to determine the independent variables for distinguishing TSR status. The area under the receiver operating characteristic curve (AUC) and sensitivity, specificity, and accuracy were compared between the MAP MRI metrics, either alone or combined with clinicopathologic characteristics, and ADC, using the DeLong and McNemar test. Results A total of 181 female participants (mean age, 49 years ± 10 [SD]) were included. All diffusion MRI metrics differed between the high-TSR and low-TSR groups (P < .001 to P = .01). Radial non-Gaussianity from MAP MRI and lymphovascular invasion were significant independent variables for discriminating the two groups, with a higher AUC (0.81 [95% CI: 0.74, 0.87] vs 0.61 [95% CI: 0.53, 0.68], P < .001) and accuracy (138 of 181 [76%] vs 106 of 181 [59%], P < .001) than that of the ADC. Conclusion MAP MRI may serve as a better approach than conventional diffusion-weighted imaging in evaluating the TSR of breast carcinoma. Keywords: MR Diffusion-weighted Imaging, MR Imaging, Breast, Oncology ClinicalTrials.gov Identifier: NCT05159323 Supplemental material is available for this article. © RSNA, 2024.

The Effect of Intraoperative Margin Assessment During Breast Conserving Surgery for Breast Cancer in a Dutch Cohort.

INTRODUCTION: Intraoperative specimen radiography is a routinely used procedure to ensure adequate resection of non-palpable breast tumors. Intraoperative digital specimen mammography (IDSM) is an alternative to conventional specimen radiography (CSR) which provides immediate specimen evaluation and can potentially decrease operation time. IDSM may also result in lower positive margin and re-excision rates. IDSM was implemented in our hospital in 2018. The objective of this study was to evaluate the effect of using IDSM versus CSR on operation time, margin status and re-excision rates in breast conserving surgery. METHODS: The present study is a single-center retrospective cohort study with 2 patient cohorts: one which underwent CSR (n = 532) and one which underwent IDSM (n = 475). The primary outcome was the operation time. Secondary outcomes were the margin status of the primary surgery, the cavity shaving rate, and the re-excision rate. Differences between cohorts were compared using univariate statistics and multiple regression analyses to adjust for variables that were significantly different between the groups. RESULTS: IDSM use was associated with an 8-minute reduction in surgery time (B = -8.034, 95% CI [-11.6, -4.5]; P < .001). Treatment variables independently associated with the operation time included use of IDSM, type of surgery, and performance of cavity shaving. Cavity shaves were more often performed when IDSM was used (24% for IDSM vs. 14% for CSR, P < .001), while the proportion of negative margin rates (93% for IDSM vs. 96% for CSR, P = .070) was comparable. CONCLUSION: IDSM was associated with a modest reduction in operation time. Surgeons performed more cavity shaves since the introduction of IDSM, but this increase was not reflected by difference in negative margin rates.

Nonclinical factors associated with the treatment of older women with newly diagnosed low-grade ductal carcinoma in situ.

BACKGROUND: Ductal carcinoma in situ (DCIS) is the most common form of noninvasive breast cancer and is associated with an excellent prognosis. As a result, there is concern about overdiagnosis and overtreatment of DCIS because most patients with DCIS are treated as though they have invasive breast cancer and undergo either breast-conserving surgery (BCS)-most commonly followed by radiation therapy (RT)-or mastectomy. Little research to date has focused on nonclinical factors influencing treatments for DCIS. METHODS: Population-based data were analyzed from five state cancer registries (California, Florida, New Jersey, New York, and Texas) on women aged 65 years and older newly diagnosed with DCIS during the years 2003 to 2014 using a retrospective cohort design and multinominal logistic modeling. The registry records with Medicare enrollment data and fee-for-service claims to obtain treatments (BCS alone, BCS with RT, or mastectomy) were merged. Surgeon practice structure was identified through physician surveys and internet searches. RESULTS: Patients of surgeons employed by cancer centers or health systems were less likely to receive BCS with RT or mastectomy than patients of surgeons in single specialty or multispecialty practices. There also was substantial geographic variation in treatments, with patients in New York, New Jersey, and California being less likely to receive BCS with RT or mastectomy than patients in Texas or Florida. CONCLUSIONS: These findings suggest nonclinical factors including the culture of the practice and/or financial incentives are significantly associated with the types of treatment received for DCIS. Increasing awareness and targeted efforts to educate physicians about DCIS management among older women with low-grade DCIS could reduce patient harm and yield substantial cost savings.

Digital breast tomosynthesis versus X-ray of the breast specimen for intraoperative margin assessment: A randomized trial.

BACKGROUND: Involved resection margins after breast conserving surgery (BCS) often require a re-operation with increased patient anxiety and risk of impaired cosmesis. We investigated the number of re-operations due to involved resection margins after BCS comparing digital breast tomosynthesis(DBT) with X-ray for intraoperative margin evaluation. Furthermore, we assessed the diagnostic accuracy of these methods to predict histopathological margin status. Finally, we evaluated risk factors for re-operation. METHODS: In this randomized, non-blinded study, 250 invasive breast cancer patients were randomized (1:1), whereof 241 were analyzed intraoperatively with either DBT (intervention, n = 119) or X-ray (standard, n = 122). Pearson's chi-squared test, Fisher's exact test, t-test, logistic and ordinal regression analysis was used as appropriate. RESULTS: No difference was found in the number of re-operations between the DBT and X-ray group (16.8 % vs 19.7 %, p = 0.57), or in diagnostic accuracy to predict histopathological margin status (77.5 %, CI: 68.6-84.9 %) and (67.3 %, CI: 57.7-75.9 %), respectively. We evaluated 5 potential risk factors for re-operation: Ductal carcinoma in situ (DCIS) outside tumor, OR = 9.4 (CI: 4.3-20.6, p < 0.001); high mammographic breast density, OR = 6.1 (CI: 1.0-38.1, p = 0.047); non-evaluable margins on imaging, OR = 3.8 (CI: 1.3-10.8, p = 0.016); neoadjuvant chemotherapy, OR = 3.0 (CI: 1.0-8.8, p = 0.048); and T2 tumor-size, OR = 2.6 (CI: 1.0-6.4, p = 0.045). CONCLUSIONS: No difference was found in the number of re-operations or in diagnostic accuracy to predict histopathological margin status between DBT and X-ray groups. DCIS outside the tumor showed the highest risk of re-operation. Intraoperative methods with improved visualization of DCIS are needed to obtain tumor free margins in BCS.

Cytomorphological Assessment in Aspirates of Ductal Carcinoma in situ: Correlations with Histopathologic Grade, Architectural Pattern, and Invasion.

INTRODUCTION: Fine-needle aspiration biopsy (FNAB) of the breast is an effective and widely adopted diagnostic technique. Histopathologic grading of ductal carcinoma in situ (DCIS) has prognostic significance. In this current study, FNAB of DCIS was reviewed to identify parameters that predict grading, histopathologic architecture, and presence of invasion in DCIS. METHODS: Aspirates from histopathology-proven cases of DCIS were retrieved and reviewed for cytomorphologic parameters including cellularity, composition, epithelial fragment architecture cellular/nuclear features. RESULTS: In total 104 aspirates were reviewed. Cytopathologic cellular features - large nuclear size (p = 0.005), prominent nucleoli (p = 0.011), increased nuclear membrane irregularity (p = 0.043), high variation in nuclear size (p = 0.025), and presence of apoptotic figures in epithelial structures (p < 0.001); and background debris (p = 0.033) correlated with a high-grade diagnosis. Cytoplasmic vacuolation (p = 0.034) was seen exclusively in non-high-grade aspirates. Epithelial fragment architecture did not correlate with grading. A predominance (≥50%) of solid aggregates and papillary fragments on FNAB correlated with histopathologically solid (p = 0.039, p = 0.005) and papillary (p = 0.029, < p = 0.001) patterns. No parameter showed correlation with invasion. CONCLUSION: FNAB is effective in predicting DCIS grading. Epithelial fragment architecture assessment is limited to papillary or solid types, and FNAB cannot predict focal invasion in DCIS.

Conventional specimen radiography in breast-conserving therapy: a useful tool for intraoperative margin assessment after neoadjuvant therapy?

PURPOSE: A previous study in our breast unit showed that the diagnostic accuracy of intraoperative specimen radiography and its potential to reduce second surgeries in a cohort of patients treated with neoadjuvant chemotherapy were low, which questions the routine use of Conventional specimen radiography (CSR) in this patient group. This is a follow-up study in a larger cohort to further evaluate these findings. METHODS: This retrospective study included 376 cases receiving breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) of primary breast cancer. CSR was performed to assess potential margin infiltration and recommend an intraoperative re-excision of any radiologically positive margin. The histological workup of the specimen served as gold standard for the evaluation of the accuracy of CSR and the potential reduction of second surgeries by CSR-guided re-excisions. RESULTS: 362 patients with 2172 margins were assessed. The prevalence of positive margins was 102/2172 (4.7%). CSR had a sensitivity of 37.3%, a specificity of 85.6%, a positive predictive value (PPV) of 11.3%, and a negative predictive value (NPV) of 96.5%. The rate of secondary procedures was reduced from 75 to 37 with a number needed to treat (NNT) of CSR-guided intraoperative re-excisions of 10. In the subgroup of patients with clinical complete response (cCR), the prevalence of positive margins was 38/1002 (3.8%), PPV was 6.5% and the NNT was 34. CONCLUSION: This study confirms our previous finding that the rate of secondary surgeries cannot be significantly reduced by CSR-guided intraoperative re-excisions in cases with cCR after NACT. The routine use CSR after NACT is questionable, and alternative tools of intraoperative margin assessment should be evaluated.

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscopy 'Histolog® scanner' for breast margin assessment in comparison with conventional specimen radiography.

PURPOSE: The Histolog® Scanner (SamanTree Medical SA, Lausanne, Switzerland) is a large field-of-view confocal laser scanning microscope designed to allow intraoperative margin assessment by the production of histological images ready for assessment in the operating room. We evaluated the feasibility and the performance of the Histolog® Scanner (HS) to correctly identify infiltrated margins in clinical practice of lumpectomy specimens. It was extrapolated if the utilization of the HS has the potential to reduce infiltrated margins and therefore reduce re-operation rates in patients undergoing breast conserving surgery (BCS) due to a primarily diagnosed breast cancer including ductal carcinoma in situ. METHODS: This is a single-center, prospective, non-interventional, diagnostic pilot study including 50 consecutive patients receiving BCS. The complete surface of the specimen was scanned using the HS intraoperatively. The surgery and the intraoperative margin assessment of the specimen was performed according to the clinical routine consisting of conventional specimen radiography as well as the clinical impression of the surgeon. Three surgeons and an experienced pathologist assessed the scans produced by the HS for cancer cells on the surface. The potential of the HS to correctly identify involved margins was compared to the results of the conventional specimen radiography alone as well as the clinical routine. The histopathological report served as the gold standard. RESULTS: 50 specimens corresponding to 300 surfaces were scanned by the HS. The mean sensitivity of the surgeons to identify involved margins with the HS was 37.5% ± 5.6%, the specificity was 75.2% ± 13.0%. The assessment of resection margins by the pathologist resulted in a sensitivity of 37.5% and a specificity of 81.0%, while the local clinical routine resulted in a sensitivity of 37.5% and a specificity of 78.2%. CONCLUSION: Acquisition of high-resolution histological images using the HS was feasible in clinical practice. Sensitivity and specificity were comparable to clinical routine. With more specific training and experience on image interpretation and acquisition, the HS may have the potential to enable more accuracy in the margin assessment of BCS specimens.

Annual cost-savings with the implementation of estrogen-receptor-only testing on Ductal Carcinoma in Situ specimens.

BACKGROUND: In DCIS, ER status is an important marker. The utility of concomitant PR testing remains unclear. METHODS: A single-institution retrospective cohort study was performed with a comparative analysis of the NCDB to assess annual cost-savings with omission of routine PR testing. National Medicare payment standards determined PR staining costs to be $124.92. RESULTS: 150 institutional DCIS cases with receptor data were identified. 104 (69%) were ER+/PR+, 16 (11%) were ER+/PR-, and none were ER-/PR+. Omission of routine PR testing would have resulted in $18,738 saved annually. Within the NCDB, 34,100 DCIS cases had receptor data: 29,277 (85.9%) patients were ER+, and 26,008 (76%) were both ER/PR+. 211 (0.6%) patients were ER-/PR+. Annual national cost-savings with omission of routine PR-testing would have been $4.3 million. CONCLUSION: PR testing for DCIS should be reserved only for patients with ER- DCIS undergoing breast conservation to determine the utility of adjuvant endocrine therapy.

Intraoperative Lymph Node Assessment (Touch Preparation Only) for Metastatic Breast Carcinoma in Neoadjuvant and Non-neoadjuvant Settings.

CONTEXT.­: Touch preparation (TP) alone is discouraged for intraoperative lymph node (LN) assessment in the neoadjuvant setting (NAS) owing to overall low sensitivity in detecting metastatic breast cancer. OBJECTIVE.­: To compare the sensitivity, specificity, and negative predictive value of intraoperative LN assessment via TP and examine potential causes of discrepancies along with the clinical, radiologic, and pathologic parameters in the NAS and non-neoadjuvant setting (NNAS). DESIGN.­: A total of 99 LNs from 47 neoadjuvant patients and 108 LNs from 56 non-neoadjuvant patients were identified. Discordant cases were reviewed retrospectively to reveal the discrepancy reasons. Clinical, radiologic, and pathologic data were obtained from chart review and the pathology CoPath database. RESULTS.­: The sensitivity, specificity, and negative predictive value of TP in NAS and NNAS were 34.2% versus 37.5%, 100% versus 100%, and 70.9% versus 90.2%, respectively. In NAS, discrepancy reasons were interpretation challenge due to lobular histotype, poor TP quality secondary to therapy-induced histomorphologic changes, and undersampling due to small tumor deposits (≤2 mm); the latter was the major reason in NNAS. More cases with macrometastasis were missed in NAS compared to NNAS (14 of 25 versus 1 of 10). The parameters associated with discrepancy were lobular histotype, histologic grade 2, estrogen receptor positivity, HER2 human epidermal growth factor receptor 2 negativity, multifocality, and pathologic tumor size greater than 10 mm in NAS; and lymphovascular space involvement and pathologic tumor size greater than 20 mm in NNAS. CONCLUSIONS.­: In NAS, intraoperative TP alone should be used very cautiously owing to a high false-negative rate of macrometastasis, especially for patients with invasive lobular carcinoma and known axillary LN metastasis before neoadjuvant therapy.

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscope for intraoperative margin assessment - POLARHIS study.

INTRODUCTION: Breast-conserving surgery (BCS) in case of breast cancer and/or in-situ-carcinoma lesions (DCIS) intends to completely remove breast cancer while saving healthy tissue as much as possible to achieve better aesthetic and psychological outcomes for the patient. Such modality should result in postoperative tumor-free margins of the surgical resection in order to carry on with the next therapeutical steps of the patient care. However, 10-40% of patients undergo more than one procedure to achieve acceptable cancer-negative margins. A 2nd operation or further operation (re-operation) has physical, psychological, and economic consequences. It also delays the administration of adjuvant therapy, and has been associated with an elevated risk of local and distant disease relapse. In addition, a high re-operation rate can have significant economic effects - both for the service provider and for the payer. A more efficient intraoperative assessment of the margin may address these issues. Recently, a large field-of-view confocal laser scanning microscope designed to allow real-time intraoperative margin assessment has arrived on the market - the Histolog Scanner. In this paper, we present the first evaluation of lumpectomy margins assessment with this new device. MATERIALS AND METHODS: 40 consecutive patients undergoing BCS with invasive and/or DCIS were included. The whole surface of the surgical specimens was imaged right after the operation using the Histolog Scanner (HLS). The assessment of all the specimen margins was performed intraoperatively according to the standard-of-care of the center which consists of combined ultrasound (IOUS) and/or conventional specimen radiography (CSR), and gross surgical inspection. Margin assessment on HLS images was blindly performed after the surgery by 5 surgeons and one pathologist. The capabilities to correctly determine margin status in HLS images was compared to the final histopathological assessment. Furthermore, the potential reduction of positive-margin and re-operation rates by utilization of the HLS were extrapolated. RESULTS: The study population included 7/40 patients with DCIS (17.5%), 17/40 patients with DCIS and invasive ductal cancer (IDC NST) (42.5%), 10/40 patients with IDC NST (25%), 4/40 with invasive lobular cancer (ILC) (10%), and 1/40 patients with a mix of IDC NST, DCIS, and ILC. Clinical routine resulted in 13 patients with positive margins identified by final histopathological assessment, resulting in 12 re-operations (30% re-operation rate). Amongst these 12 patients, 10 had DCIS components involved in their margin, confirming the importance of improving the detection accuracy of this specific lesion. Surgeons, who were given a short familiarization on HLS images, and a pathologist were able to detect positive margins in 4/12 and 7/12 patients (33% and 58%), respectively, that were missed by the intraoperative standard of care. In addition, a retrospective analysis of the HLS images revealed that cancer lesions can be identified in 9/12 (75%) patients with positive margins. CONCLUSION: The present study presents that breast cancer can be detected by surgeons and pathologists in HLS images of lumpectomy margins leading to a potential reduction of 30% and 75% of the re-operations. The Histolog Scanner is easily inserted into the clinical workflow and has the potential to improve the intraoperative standard-of-care for the assessment of breast conserving treatments. In addition, it has the potential to increase oncological safety and cosmetics by avoiding subsequent resections and can also have a significant positive economic effect for service providers and cost bearers. The data presented in this study will have to be further confirmed in a prospective phase-III-trial.

Lack of Clinical Value for Immunohistochemistry for Sentinel Lymph Node Assessment in Invasive Lobular Carcinoma.

BACKGROUND: The distinct histologic appearance of invasive lobular carcinoma (ILC) may pose diagnostic challenges for sentinel lymph node (SLN) analysis. We evaluated the impact of cytokeratin immunohistochemistry (IHC) on SLN assessment in ILC and its contribution to pathologic nodal upstaging. METHODS: We identified ILC patients treated with SLN surgery at our institution between September 2008 and August 2021. IHC for SLN assessment was employed at the discretion of the pathologist. Differences between groups evaluated with and without IHC were compared using Chi-square tests. RESULTS: Overall, 608 cases of ILC were identified in patients who underwent SLN surgery. IHC was used in 301 cases (49.5%) and was not associated with cT category, pT category, or tumor grade. Use of IHC increased detection of SLN+ disease when isolated tumor cells (ITCs) were included in the analysis (35.9% with IHC vs. 21.2% without IHC; p < 0.001). There was no effect on nodal upstaging to micrometastatic disease (pN1mi) or greater (21.9% with IHC vs. 21.2% without IHC; p = 0.82). IHC did not increase the number of positive SLNs detected (median 1 with and without IHC) nor did it increase axillary lymph node dissection (ALND) rates (11.6% with IHC vs. 15.3% without IHC; p = 0.18). CONCLUSION: IHC improved detection of pN0(i+) disease among ILC patients undergoing SLN surgery. IHC did not increase upstaging to pN1mi or higher categories of nodal disease, detection of a greater number of positive SLNs, or ALND rates. Our data suggest routine use of IHC for SLN assessment in ILC patients does not add clinical utility.

Economic Impact of Reducing Reexcision Rates after Breast-Conserving Surgery in a Large, Integrated Health System.

BACKGROUND: Reexcision after breast-conserving surgery (BCS) is costly for patients, but few studies have captured the economic burden to a healthcare system. We quantified operating room (OR) charges as well as OR time and then modeled expected savings of a reexcision reduction initiative. METHODS: We performed a retrospective cohort review of all breast cancer patients with BCS between January 1, 2016 and December 31, 2020. Operating room charges of disposable supplies and implants as well as operative time were calculated. RESULTS: During the 5-year period, the 8804 patients who underwent BCS, 1628 (18.5%) required reexcision. The reexcision cohort was younger (61 vs. 64 years, p < 0.001), more likely to have ductal carcinoma in situ (DCIS) (23.7% vs. 15.2%, p < 0.001), and had larger tumors (T1+T2 73.2% vs. 83.1%, p < 0.001). Reexcision costs represented 39% of total costs, the cost per patient for surgery was fourfold higher for reexcision patients. Reexcision operations comprised 14% of total operating room (OR) time (1848 of 13,030 hours). The reexcision rate for 54 surgeons varied from 7.2-39.0% with 46% (n = 25) having a reexcision rate >20%. A model simulating reducing reexcision rates to 20% or below for all surgeons reduced the reexcision rate to 16.2% overall. Using per procedure data, the model predicted a decrease in reexcision operations by 18% (327 operations), OR costs by 14% ($287,534), and OR time by 11% (204 hours). CONCLUSIONS: Reexcision after BCS represents 39% of direct OR costs and 14% of OR time in our healthcare system. Modest improvements in surgeon reexcision rates may lead to significant economic and OR time savings.

DCIS: Risk Assessment in the Molecular Era.

Ductal carcinoma in situ (DCIS) represents 20% of all breast cancers. The treatment paradigm for the majority of patients with DCIS consists of breast-conserving surgery (BCS) and radiotherapy (RT), with adjuvant endocrine therapy offered for hormone-receptor positive disease. RT after BCS reduces the risk of in-breast recurrence, decreasing subsequent in-situ and invasive cancers by ≥50%, with 10-year breast-cancer specific survival outcomes approaching 98%. As local control rates are high, treatment efforts have focused on selective de-escalation of care. Traditionally, clinicians have used clinical-pathologic features (ie, grade, age, size, margin width) to guide selection of low-risk DCIS patients in whom postoperative RT may be omitted. More recently, genomic molecular assays including the Oncotype DX Breast DCIS Score and DCISionRT have been developed to provide individualized assessment of predicting RT benefit after BCS. These molecular assays have the potential for personalized risk assessment, particularly when used in combination with existing clinical-pathologic features for risk assessment. This article reviews the current status and existing published literature on DCIS molecular-risk assessment tools and their potential for guiding postoperative RT recommendations in the BCT setting. In addition, current trials studying omission of definitive surgery for low-risk DCIS are discussed.

Clinical Impact of Intraoperative Margin Assessment in Breast-Conserving Surgery With a Novel Pegulicianine Fluorescence-Guided System: A Nonrandomized Controlled Trial.

Importance: Positive margins following breast-conserving surgery (BCS) are often identified on standard pathology evaluation. Intraoperative assessment of the lumpectomy cavity has the potential to reduce residual disease or reexcision rate following standard of care BCS in real time. Objective: To collect safety and initial efficacy data on the novel pegulicianine fluorescence-guided system (pFGS) when used to identify residual cancer in the tumor bed of female patients undergoing BCS. Design, Setting, and Participants: This prospective single-arm open-label study was conducted as a nonrandomized multicenter controlled trial at 16 academic or community breast centers across the US. Female patients 18 years and older with newly diagnosed primary invasive breast cancer or ductal carcinoma in situ DCIS undergoing BCS were included, excluding those with previous breast cancer surgery and a history of dye allergies. Of 283 consecutive eligible patients recruited, 234 received a pegulicianine injection and were included in the safety analysis; of these, 230 were included in the efficacy analysis. Patients were enrolled between February 6, 2018, and April 10, 2020, and monitored for a 30-day follow-up period. Data were analyzed from April 10, 2020, to August 5, 2021. Interventions: Participants received an injection of a novel imaging agent (pegulicianine) a mean (SD) of 3.2 (0.9) hours prior to surgery at a dose of 1 mg/kg. After completing standard of care (SOC) excision, pFGS was used to scan the lumpectomy cavity to guide the removal of additional shave margins. Main Outcomes and Measures: Adverse events and sensitivity, specificity, and reexcision rate. Results: Of 234 female patients enrolled (median [IQR] age, 62.0 [55.0-69.0] years), 230 completed the trial and 1 patient with a history of allergy to contrast agents had an anaphylactic reaction and recovered without sequelae. Correlation of pFGS with final margin status on a per-margin analysis showed a marked improvement in sensitivity over standard pathology assessment of the main lumpectomy specimen (69.4% vs 38.2%, respectively). On a per-patient level, the false-negative rate of pFGS was 23.7% (9 of 38), and sensitivity was 76.3% (29 of 38). Among 32 patients who underwent excision of pFGS-guided shaves, pFGS averted the need for reexcision in 6 (19%). Conclusions and Relevance: In this pilot feasibility study, the safety profile of pegulicianine was consistent with other imaging agents used in BCS, and was associated with a reduced need for second surgery in patients who underwent intraoperative additional excision of pFGS-guided shaves. These findings support further development and clinical performance assessment of pFGS in a prospective randomized trial. Trial Registration: ClinicalTrials.gov Identifier: NCT03321929.

Is Axillary Assessment of Ductal Carcinoma In Situ of the Breast Necessary in All Cases?

BACKGROUND: Staging of the axilla in women with ductal carcinoma in situ (DCIS) is a point of controversy. We aimed to assess whether there is a group of patients in whom axillary assessment can be avoided and whether the likelihood of underdiagnosis of infiltrating carcinoma is sufficient to justify this evaluation. MATERIALS AND METHODS: This was a multicenter, prospective, observational study of patients who were operated on between 2008 and 2018 in three Spanish hospitals, with a diagnosis by radiological or excisional biopsy of DCIS and clinically and radiologically negative axilla. RESULTS: A total of 530 patients with a preoperative diagnosis of DCIS were studied. An axillary assessment was performed in 77% of the patients. In 397 patients, selective sentinel lymph node biopsy was performed. Axillary involvement was found in 7.2% of all patients, which dropped to 2.15% if we only included DCIS diagnosed after a definitive anatomical pathology analysis. Underdiagnosis was correlated with the type of biopsy performed: the risk was 1.34 times as high if the biopsy was performed with a core needle. The risk of lymph node metastasis was higher when there was lymphovascular invasion and when mastectomy was performed. CONCLUSIONS: We propose an axilla management algorithm in patients with a preoperative diagnosis of DCIS. The patients who would benefit from sentinel lymph node biopsy would be those who are not candidates for breast-conserving surgery, those with a BIRADS 5 lesion biopsied by core-needle biopsy, and those whose definitive diagnosis is lymphovascular invasion.

Magnetic resonance imaging system for intraoperative margin assessment for DCIS and invasive breast cancer using the ClearSight™ system in breast-conserving surgery-Results from a postmarketing study.

BACKGROUND AND OBJECTIVES: Breast-conserving surgery (BCS) is followed by reoperations in approximately 25%. Reoperations lead to an increased risk of infection and wound healing problems as well as a worse cosmetic outcome. Several technical approaches for an intraoperative margin assessment to decrease the reoperation rate are under evaluation, some of them are still experimental. METHODS: A prospective single-arm post-marketing study with 60 patients undergoing BCS for ductal carcinoma in situ (DCIS) and invasive breast cancer was conducted. The specimen was intraoperatively examined by the ClearSight™ system, a mobile magnetic resonance imaging system that is based on a diffusion-weighted imaging protocol. However, the results were blinded to the surgeon. RESULTS: The ClearSight™ system was performed for both ductal and lobular breast cancer and DCIS, with a sensitivity of 0.80 (95% confidence interval [CI]: 0.44-0.96) and a specificity of 0.84 (95% CI 0.72-0.92), with an overall diagnostic accuracy of 80%. CONCLUSION: Had the ClearSight™ been known to the surgeon intraoperatively, the reoperation rate would have been reduced by 83% for invasive carcinoma, from 10% to 2%, and 50% for DCIS, from 30% to 15% reoperations. A trial designed to examine the impact on reoperation rates is currently ongoing.

Positive margins after mastectomy in patients with invasive lobular carcinoma of the breast: Incidence and management strategies.

BACKGROUND: Surgical treatment of invasive lobular carcinoma (ILC) is challenging due to its diffuse growth pattern, and the positive margin rate after mastectomy is poorly described. METHODS: We retrospectively determined the positive margin rate in those with stage I-III ILC undergoing mastectomy. We evaluated the relationship between management strategy and recurrence free survival (RFS). RESULTS: In 357 patients, the positive margin rate was 10.6% overall and 18.7% in those with T3 tumors. Having a positive margin was associated with significantly shorter RFS on multivariate analysis (p = 0.01). Undergoing additional local treatment (radiation or re-excision) for a positive margin was significantly associated with improved RFS (p = 0.004). Older women with positive margins were significantly less likely to undergo additional local therapy. CONCLUSIONS: Even mastectomy fails to clear margins in a high proportion of patients with large ILC tumors, a finding which may warrant testing neoadjuvant strategies even prior to planned mastectomy.

Nuclear morphology in breast lesions: refining its assessment to improve diagnostic concordance.

AIMS: Although evaluation of nuclear morphology is important for the diagnosis and categorisation of breast lesions, the criteria used to assess nuclear atypia rely upon the subjective evaluation of several features that may result in inter- and intraobserver variation. This study aims to refine the definitions of cytonuclear features in various breast lesions. METHODS AND RESULTS: ImageJ was used to assess the nuclear morphological features including nuclear diameter, axis length, perimeter, area, circularity and roundness in 160 breast lesions comprising ductal carcinoma in situ (DCIS), invasive breast carcinoma of no special type (IBC-NST), tubular carcinoma, usual ductal hyperplasia (UDH), columnar cell change (CCC) and flat epithelial atypia (FEA). Reference cells included normal epithelial cells, red blood cells (RBCs) and lymphocytes. Reference cells showed size differences not only between normal epithelial cells and RBCs but also between RBCs in varied-sized blood vessels. Nottingham grade nuclear pleomorphism scores 1 and 3 cut-offs in IBC-NST, compared to normal epithelial cells, were < ×1.2 and > ×1.4 that of mean maximum Feret's diameter and < ×1.6 and > ×2.4 that of mean nuclear area, respectively. Nuclear morphometrics were significantly different in low-grade IBC-NST versus tubular carcinoma, low-grade DCIS versus UDH and CCC versus FEA. No differences in the nuclear features between grade-matched DCIS and IBC-NST were identified. CONCLUSION: This study provides a guide for the assessment of nuclear atypia in breast lesions, refines the comparison with reference cells and highlights the potential diagnostic value of image analysis tools in the era of digital pathology.

Breast-Conserving Surgeries With and Without Cavity Shave Margins Have Different Re-excision Rates and Associated Overall Cost: Institutional and Patient-Driven Decisions for Its Utilization.

BACKGROUND: Reducing the rate of margin positivity and reoperations remains a paramount goal in breast-conserving surgery (BCS). This study assesses the effectiveness of standard partial mastectomy with cavity shave margins (CSM) compared with partial mastectomy with selective margin resection (SPM), with regard to outcomes of the initial surgeries, re-excisions, and overall costs. PATIENTS AND METHODS: This is a retrospective review of 122 eligible breast cancer patients who underwent BCS at one institution. The CSM and SPM groups each included 61 patients, matched for presurgical diagnoses and clinical stage. Data including margin status, rates and reason for re-excision, associated operation times, and costs were analyzed. RESULTS: Patients undergoing CSM had less than half the rate of positive margins (PMs) (10% vs. 23%; P = .03) and re-excisions (8% vs. 23%; P = .02) compared with SPM. In the former group, the margin involvement was focal, and re-excisions were performed almost exclusively for PMs. For SPM, the majority (92%) of PMs were on the main lumpectomy specimen rather than the selective margins, and re-excisions included, in addition to PMs, extensive or multifocal negative but close margins. Reduced breast tissue volumes were removed with CSM, particularly for patients undergoing a single surgery (47 vs. 165 cm3; P < .001). The initial surgery with CSM is on average 27% more costly than that for SPM (P < .001), due to the increased pathology costs which are partially offset by the increased re-excision rates in SPM. CONCLUSION: Circumferential cavity shaving, associated with consistent lower PMs, tissue volumes excised, and re-excision rates, is appropriate for routine implementation as a method offering superior surgical outcomes.

Multi-magnification-based machine learning as an ancillary tool for the pathologic assessment of shaved margins for breast carcinoma lumpectomy specimens.

The surgical margin status of breast lumpectomy specimens for invasive carcinoma and ductal carcinoma in situ (DCIS) guides clinical decisions, as positive margins are associated with higher rates of local recurrence. The "cavity shave" method of margin assessment has the benefits of allowing the surgeon to orient shaved margins intraoperatively and the pathologist to assess one inked margin per specimen. We studied whether a deep convolutional neural network, a deep multi-magnification network (DMMN), could accurately segment carcinoma from benign tissue in whole slide images (WSIs) of shave margin slides, and therefore serve as a potential screening tool to improve the efficiency of microscopic evaluation of these specimens. Applying the pretrained DMMN model, or the initial model, to a validation set of 408 WSIs (348 benign, 60 with carcinoma) achieved an area under the curve (AUC) of 0.941. After additional manual annotations and fine-tuning of the model, the updated model achieved an AUC of 0.968 with sensitivity set at 100% and corresponding specificity of 78%. We applied the initial model and updated model to a testing set of 427 WSIs (374 benign, 53 with carcinoma) which showed AUC values of 0.900 and 0.927, respectively. Using the pixel classification threshold selected from the validation set, the model achieved a sensitivity of 92% and specificity of 78%. The four false-negative classifications resulted from two small foci of DCIS (1 mm, 0.5 mm) and two foci of well-differentiated invasive carcinoma (3 mm, 1.5 mm). This proof-of-principle study demonstrates that a DMMN machine learning model can segment invasive carcinoma and DCIS in surgical margin specimens with high accuracy and has the potential to be used as a screening tool for pathologic assessment of these specimens.