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Background: Axillary lymph node dissection is the current standard for management of the axilla in inflammatory breast cancer (IBC). The present study aims to determine whether the initially positive node identified by clip placement accurately represents the overall nodal status of axilla after neoadjuvant chemotherapy (NAC) in IBC., Patients and Methods: A retrospective study was conducted on patients with IBC who underwent operation (2014-2023). For patients with IBC who had clip placement in a positive axillary node at diagnosis, operative notes, specimen radiographs, and pathology reports were reviewed to confirm final pathologic status of clipped nodes., Results: In total, 92 patients with IBC (90 cN+) were identified (median age 54 years, 78% invasive ductal, 10% invasive lobular, and 12% mixed); 81 (90%) were biopsy-proven cN+, with a clip placed in the positive node for 62/81 (77%). All patients were treated with NAC and axillary surgery with median 19 (range 4-49) nodes removed. Among 28 (out of 56) patients with retrieved clipped nodes that were pathologically negative (ypN0), only 1 had an additional positive node with micrometastasis for a false negative rate of 4% (95% CI 1-19%). Conversely, 3/3 patients with isolated tumor cells (ITCs) only in the clipped node had additional axillary disease (ITCs in 1, macrometastasis in 2), and 20/23 (87%) of patients with pathologically positive clipped node (micrometastasis or greater) had additional positive nodes [19/20 (95%) with macrometastasis]., Conclusions: The clipped biopsy-positive axillary node in IBC accurately represented the post-NAC overall axillary nodal status. ITCs post-NAC should be considered positive as an indicator of additional nodes with metastasis., (© 2024. The Author(s).)

Mixed invasive ductolobular breast cancer (MIDLC) is a rare breast cancer with varying lobular and ductal components. Characteristics, management, and outcomes of MIDLC are not well understood due to the rarity of the cancer and the lack of uniform diagnostic criteria and reporting. There is a need for better understanding and individualized management of this heterogeneous spectrum of breast cancers., (© 2023. Society of Surgical Oncology.)

Background: Mixed invasive ductolobular breast cancer (MIDLC) is a rare histological subtype of breast cancer (BC), with components of both invasive ductal cancer (IDC) and invasive lobular cancer (ILC). Its clinicopathological features and outcomes have not been well characterized., Method: The National Cancer Database 2010-2017 was reviewed to identify women with stage I-III BCs. Univariate analysis was performed using Chi-square or Wilcoxon rank-sum tests and multivariable analysis with logistic regression to predict surgical decisions. Survival was assessed using multivariable Cox proportional hazards regression analysis., Results: We identified 955,828 women with stage I-III BCs (5.7% MIDLC, 10.3% ILC, and 84.0% IDC). MIDLC was more like ILC than IDC in terms of multicentricity (14.2% MIDLC, 13.0% ILC, 10.0% IDC), hormone receptor positivity (96.6% MIDLC, 98.2% ILC, 81.2% IDC), and use of neoadjuvant chemotherapy (NAC; 5.8% MIDLC, 5.2% ILC, 10.8% IDC). 744,607 women underwent upfront surgery. The mastectomy rates were 42.3% for MIDLC, 46.5% for ILC, and 33.3% for IDC (all p < 0.001). With 5.5 years of median follow-up, the adjusted overall survival in the upfront surgery hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) biological subgroup was better in MIDLC (hazard ratio 0.88, p < 0.001) and ILC (hazard ratio 0.91, p < 0.001) than in IDC. Like ILC, MIDLC also had a lower pathological complete response to NAC than IDC (12.3% MIDLC, 7.3% ILC, 28.6% IDC)., Conclusions: MIDLC displays a mixed pattern of characteristics favoring features of ILC compared with IDC, with favorable 5-year overall survival compared with IDC within the HR+/HER2- subtype who underwent upfront surgery., (© 2023. Society of Surgical Oncology.)

Background: Bilateral breast cancer (BC) has an incidence of 1 to 3 %. This study aimed to describe the clinicopathologic characteristics and management of bilateral BC, estimate disease-free survival (DFS), and compare DFS with unilateral BC., Methods: A retrospective analysis was performed for patients who had bilateral invasive BC or unilateral invasive BC and contralateral ductal carcinoma in situ (DCIS) treated at Mayo Clinic Rochester from 2008 to 2022. A 4:1 matched cohort of patients with unilateral invasive BC was used for comparison. The groups were compared using Wilcoxon rank-sum or chi-square tests. Disease-free survival was analyzed using the Kaplan-Meier method and log-rank test, with Cox proportional hazards regression used for multivariable analysis., Results: The study identified 278 cases of bilateral breast cancer (177 cases of bilateral invasive cancer and 101 cases of unilateral invasive cancer with contralateral DCIS), representing 4.1 % of invasive BCs. Biologic subtype was concordant between sides in 79.8 % of the patients. Initial surgery was bilateral mastectomy for 76.6 %, bilateral lumpectomy for 20.5 %, and unilateral mastectomy with unilateral lumpectomy for 2.9 % of the patients. Pathogenic variants in breast cancer predisposition genes were present in 21.7 % of those tested. The patients who had bilateral BC presented with a higher cT category than the patients who had unilateral BC (p = 0.02), and a higher proportion presented with ILC (17.3 % vs 10.9 %; p = 0.004), estrogen receptor-positive (ER+) disease (89.2 % vs 84.2 %; p = 0.04), multicentric/multifocal disease (37.1 % vs 24.3 %; p < 0.001), breast cancer pathogenic variant (21.7 % vs 12.4 %; p = 0.02), and palpable presentation (48.2 % vs 40.8 %; p = 0.03). The patients with bilateral BC showed DFS similar to that for the unilateral BC cohort (p = 0.71)., Conclusions: Bilateral BCs most commonly are biologically concordant between sides. Bilateral BC presented more commonly with larger tumors, lobular histology, ER+ status, multicentricity or multifocality, pathogenic variant, and palpable disease. Bilateral BC is not associated with worse DFS than unilateral BC., (© 2023. Society of Surgical Oncology.)

Purpose: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined., Methods: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy., Results: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p < 0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p = 0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p < 0.001)., Conclusion: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Ductal carcinoma in situ (DCIS) is noninvasive breast cancer and therefore nodal staging is not routinely recommended. We evaluated the use of and factors associated with axillary surgery in DCIS in the National Cancer Database (NCDB)., Methods: DCIS cases were identified from the NCDB 2012-2018. Use of axillary surgery was evaluated over time, and factors associated with axillary surgery were assessed for breast-conserving surgery (BCS) and mastectomy groups., Results: We identified 178,762 patients, median age of 60 years. Majority of DCIS (87%) was ER-positive, and 14% low, 43% intermediate, and 44% high grade. Median DCIS size was 1.1 cm. BCS was performed in 72%, whereas 28% had mastectomy. Overall axillary surgery was performed in 38% and was higher in patients undergoing mastectomy compared with patients undergoing BCS (88% vs. 19%, p < 0.001). At axillary surgery, the vast majority (92%) had 1-5 nodes examined, whereas 8% had >5 nodes examined. Over time, axillary surgery decreased in BCS patients (21% in 2012 to 17% in 2018, p < 0.001) but increased slightly in mastectomy patients (86% in 2012 to 90% in 2018, p < 0.001). On multivariable analysis, factors significantly associated with axillary surgery were younger patient age, larger tumor size, higher grade, and ER-negative status., Conclusions: Factors associated with axillary surgery reflect higher risk disease for upstage to invasive cancer, indicating surgeon judgment. However, despite axillary surgery being overtreatment of DCIS, it is common in mastectomy and is performed for one in five patients undergoing BCS. This provides opportunity for improvement in breast cancer care delivery., (© 2022. Society of Surgical Oncology.)

Importance: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer strongly correlates with overall survival and has become the standard end point in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual ductal carcinoma in situ (DCIS)., Objective: To examine the association of residual DCIS in surgical specimens after neoadjuvant chemotherapy for breast cancer with survival end points to inform standards for the assessment of pathologic complete response., Design, Setting, and Participants: The study team analyzed the association of residual DCIS after NAC with 3-year event-free survival (EFS), distant recurrence-free survival (DRFS), and local-regional recurrence (LRR) in the I-SPY2 trial, an adaptive neoadjuvant platform trial for patients with breast cancer at high risk of recurrence. This is a retrospective analysis of clinical specimens and data from the ongoing I-SPY2 adaptive platform trial of novel therapeutics on a background of standard of care for early breast cancer. I-SPY2 participants are adult women diagnosed with stage II/III breast cancer at high risk of recurrence., Interventions: Participants were randomized to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery., Main Outcomes and Measures: The presence of DCIS and EFS, DRFS, and LRR., Results: The study team identified 933 I-SPY2 participants (aged 24 to 77 years) with complete pathology and follow-up data. Median follow-up time was 3.9 years; 337 participants (36%) had no residual invasive disease (residual cancer burden 0, or pCR). Of the 337 participants with pCR, 70 (21%) had residual DCIS, which varied significantly by tumor-receptor subtype; residual DCIS was present in 8.5% of triple negative tumors, 15.6% of hormone-receptor positive tumors, and 36.6% of ERBB2-positive tumors. Among those participants with pCR, there was no significant difference in EFS, DRFS, or LRR based on presence or absence of residual DCIS., Conclusions and Relevance: The analysis supports the definition of pCR as the absence of invasive disease after NAC regardless of the presence or absence of DCIS., Trial Registration: ClinicalTrials.gov Identifier NCT01042379.

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., (© 2022. Society of Surgical Oncology.)

Background: Given reports of low response rates to neoadjuvant chemotherapy (NAC) in invasive lobular carcinoma (ILC), we evaluated whether use of alternative strategies such as neoadjuvant endocrine therapy (NET) is increasing. Additionally, we investigated whether NET is associated with more breast conservation surgery (BCS) and less extensive axillary surgery in those with ILC., Patients and Methods: We queried the NCDB from 2010 to 2016 and identified all women with stage I-III hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) ILC who underwent surgery. We used Cochrane-Armitage tests to evaluate trends in utilization of the following treatment strategies: NAC, short-course NET, long-course NET, and primary surgery. We compared rates of BCS and extent of axillary surgery stratified by clinical stage and tumor receptor subtype for each treatment strategy., Results: Among 69,312 cases of HR+/HER2- ILC, NAC use decreased slightly (from 4.7 to 4.2%, p = 0.007), while there was a small but significant increase in long-course NET (from 1.6 to 2.7%, p < 0.001). Long-course NET was significantly associated with increased BCS in patients with cT2-cT4 disease and less extensive axillary surgery in clinically node positive patients with HR+/HER2- tumors., Conclusions: Primary surgery remains the most common treatment strategy in patients with ILC. However, NAC use decreased slightly over the study period, while the use of long-course NET had a small increase and was associated with more BCS and less extensive axillary surgery., (© 2021. Society of Surgical Oncology.)

Background: Reoperation rates following breast-conserving surgery (BCS) range from 10 to 40%, with marked surgeon and institutional variation., Objective: The aim of this study was to identify factors associated with intraoperative margin re-excision, evaluate for any differences in local recurrence based on margin re-excision and determine reoperation rates with use of intraoperative margin analysis., Patients and Methods: We analyzed consecutive patients with ductal carcinoma in situ (DCIS) or invasive breast cancer who underwent BCS at our institution between 1 January 2005 and 31 December 2016. Routine intraoperative frozen section margin analysis was performed and positive or close margins were re-excised intraoperatively. Univariate analysis was used to compare margin status and the Kaplan-Meier method was used to compare recurrence. Multivariable logistic regression was utilized to analyze factors associated with re-excision., Results: We identified 3201 patients who underwent BCS-688 for DCIS and 2513 for invasive carcinoma. Overall, 1513 (60.2%) patients with invasive cancer and 434 (63.1%) patients with DCIS had close or positive margins that underwent intraoperative re-excision. Margin re-excision was associated with larger tumor size in both groups. The permanent pathology positive margin rate among all patients was 1.2%, and the 30-day reoperation rate for positive margins was 1.1%. Five-year local recurrence rates were 0.6% and 1.2% for patients with DCIS and invasive cancer, respectively. There was no difference in recurrence between patients with and without intraoperative margin re-excision (p = 0.92)., Conclusion: Both DCIS and invasive carcinoma had similar rates of intraoperative margin re-excision. Although intraoperative margin re-excision was common, the reoperation rate was extremely low and there was no difference in recurrence between those with or without intraoperative re-excision.

OBJECTIVE. The purpose of this study is to prospectively compare the size of invasive breast cancer before and after neoadjuvant chemotherapy (NAC) at breast MRI and molecular breast imaging (MBI) and to assess the accuracy of post-NAC MBI and MRI relative to pathologic analysis. SUBJECTS AND METHODS. Women with invasive breast cancer greater than or equal to 1.5 cm were enrolled to compare the longest dimension before and after NAC at MRI and MBI. MBI was performed on a dual-detector cadmium zinc telluride system after administration of 6.5 mCi (240 MBq) 99m Tc-sestamibi. The accuracy of MRI and MBI in assessing residual disease (invasive disease or ductal carcinoma in situ) was determined relative to pathologic examination. RESULTS. The longest dimension at MRI was within 1.0 cm of that at MBI in 72.3% of cases before NAC and 70.1% of cases after NAC. The difference between the longest dimension at imaging after NAC and pathologic tumor size was within 1 cm for 58.7% of breast MRI cases and 59.6% of MBI cases. Ninety patients underwent both MRI and MBI after NAC. In the 56 patients with invasive residual disease, 10 (17.9%) cases were negative at MRI and 23 (41.1%) cases were negative at MBI. In the 34 patients with breast pathologic complete response, there was enhancement in 10 cases (29.4%) at MRI and uptake in six cases (17.6%) at MBI. Sensitivity, specificity, positive predictive value, and negative predictive value after NAC were 82.8%, 69.4%, 81.4%, and 71.4%, respectively, for MRI and 58.9%, 82.4%, 84.6%, and 54.9%, respectively, for MBI. CONCLUSION. Breast MRI and MBI showed similar disease extent before NAC. MBI may be an alternative to breast MRI in patients with a contraindication to breast MRI. Neither modality showed sufficient accuracy after NAC in predicting breast pathologic complete response to obviate tissue diagnosis to assess for residual invasive disease. Defining the extent of residual disease compared with pathologic evaluation was also limited after NAC for both breast MRI and MBI.

Background: Variables such as tumor size, histology, and grade, tumor biology, presence of lymphovascular invasion, and patient age have been shown to impact likelihood of nodal positivity. The aim of this study is to determine whether primary location of invasive disease within the breast is associated with nodal positivity., Patients and Methods: Patients with invasive breast cancer undergoing axillary staging from 2010 to 2014 were identified from the National Cancer Data Base. Rates of axillary nodal positivity by primary tumor locations were compared, and multivariable analysis performed using logistic regression to control for factors known to impact nodal positivity., Results: A total of 599,722 patients met inclusion criteria. Likelihood of nodal positivity was greatest with primary tumors located in the nipple (43.8%), followed by multicentric disease (40.8%), central breast lesions (39.4%), and axillary tail lesions (38.4%). Tumor location remained independently associated with nodal positivity on multivariable analysis adjusting for variables known to affect nodal positivity with odds ratio 2.8 for tumors in the nipple [95% confidence interval (CI) 2.5-3.1], 2.2 for central breast (95% CI: 2.2-2.3), and 2.7 for axillary tail (95% CI: 2.4-2.9). When restricted to patients with clinically negative nodes (n = 430,949), a similar association was seen., Conclusion: Patients with invasive breast cancer located in the nipple, central breast, and axillary tail have the highest risk of positive axillary lymph nodes independent of patient age, tumor grade, biologic subtype, histology, and size. This should be considered along with other factors in preoperative counseling and decision-making regarding plans for axillary lymph node staging.

Background: The standard of care for breast cancer patients treated with neoadjuvant chemotherapy (NAC) who have a positive sentinel lymph node (+SLN) after NAC is completion axillary lymph node dissection (ALND). This study aimed to develop a nomogram to predict additional nodal disease in patients with +SLN after NAC., Methods: The study reviewed patients 18 years of age or older who had invasive breast cancer treated with NAC followed by SLN surgery with +SLN and ALND between 2006 and 2017 at the authors' institution. Factors predictive of positive non-SLNs were analyzed using uni- and multivariable logistic regression., Results: The study identified 120 patients with +SLN after NAC and ALND. Of these patients, 30.8% were clinically node-negative (cN-), and 69.2% were clinically node-positive (cN+) before NAC. Tumor biology was human epidermal growth factor receptor 2-positive (HER2+) for 20%, hormone receptor-positive (HR+)/HER2- for 66.7%, and triple-negative breast cancer (TNBC) for 13.3% of the patients. Additional nodal disease was found on ALND for 63.3% of the patients. In the univariate analysis, the factors predictive of positive non-SLNs were biologic subtype (TNBC and HR+/HER2- vs HER2+; p < 0.001), higher grade (p = 0.047), higher pT category (p = 0.02), SLN extranodal extension (p = 0.03), larger SLN metastasis size (p < 0.001), and higher number of +SLNs (p = 0.02). The factors significant in the multivariable analysis included number of +SLNs, grade 3 vs grade 1 or 2, HER2+ versus HER2-, cN+ versus cN-, and larger SLN metastasis size. The resulting model showed excellent discrimination (area under the curve, 0.82; 95% confidence interval, 0.74-0.90) and good calibration (p = 0.54, Hosmer-Lemeshow)., Conclusion: A clinical prediction model incorporating biologic subtype, grade, clinical node status, size of the largest SLN metastasis, and number of +SLNs can help physicians and patients estimate the likelihood of additional nodal disease and may be useful for guiding decision making regarding axillary management.

Background: While breast cancer has historically been treated with surgery followed by adjuvant chemotherapy (AC) and radiation when indicated, neoadjuvant chemotherapy (NAC) use is thought to be increasing; however, the trends of its use in various biological subtypes have not been evaluated. We sought to evaluate the trend of NAC use over time by biological subtype., Methods: We identified all patients with invasive breast cancer who underwent curative intent surgery and were treated with chemotherapy from 2010 to 2015 from the National Cancer Database. An unadjusted analysis of trends in proportions over time was performed using Cochran-Armitage trend tests stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status., Results: Of 315,264 patients who received chemotherapy, 251,726 (79.8%) received AC and 63,538 (20.2%) received NAC. From 2010 to 2015, significant increases in NAC use were seen in all biologic subtypes (all p < 0.001). The highest proportions and greatest increases in proportions of NAC were seen among triple-negative breast cancers (TNBC; 19.5-33.7%) and HER2+ (HR-/HER2+, 21.5-39.8%; HR+/HER2+, 17.0-33.7%) tumors. HR+/HER2- tumors also had a statistically significant increase in use but this increase was less dramatic (13.0-16.8%) and NAC use in recent years was significantly lower than in other subtypes (p < 0.001)., Conclusion: Within patients receiving chemotherapy for breast cancer, its receipt in the neoadjuvant setting has been increasing among all biologic subtypes. The highest use of NAC is in TNBC and HER2+ disease, with use in these subgroups being twice as frequent as in HR+/HER2- disease.

For patients with ductal carcinoma In Situ (DCIS), sentinel lymph node (SLN) surgery is generally reserved for patients at high risk of being upstaged to invasive disease. The use of frozen section (FS) pathologic analysis of the primary tumor may allow for selective surgical nodal staging within one procedure. We sought to define the reliability of FS for detection of upstaging. Eight hundred and twenty-seven patients were identified with DCIS on core needle biopsy that underwent 834 operations at our institution between January 2004 and October 2014. We calculated the rate of upstage from DCIS to invasive cancer on both intraoperative FS and final pathology to determine the performance of FS. Upstage rate on final pathology was 118/834 (14.1%) 95 per cent confidence interval 11.8 to 16.7 per cent. FS identified 88/118 (74.6%) of the upstages. Specificity was 99.3 per cent (711/716). Overall accuracy was 95.8 per cent (799/834) and the positive predictive value was 96.0 per cent (711/741 patients). Mean size of invasive cancers identified on FS was 5.6 mm, versus 3.5 mm for those identified only on permanent section, P = 0.11. Intraoperative FS analysis of DCIS is useful for identification of upstage to invasive disease. This may facilitate a selective approach to SLN surgery that both decreases unnecessary SLN surgery and the need for a second operation.

Objective: To identify factors predicting positive margins at lumpectomy prompting intraoperative reexcision in patients with breast cancer treated at a large referral center., Patients and Methods: We reviewed all breast cancer lumpectomy cases managed at our institution from January 1, 2012, through December 31, 2013. Associations between rates of positive margin and patient and tumor factors were assessed using χ 2 tests and univariate and adjusted multivariate logistic regression, stratified by ductal carcinoma in situ (DCIS) or invasive cancer., Results: We identified 382 patients who underwent lumpectomy for definitive surgical resection of breast cancer, 102 for DCIS and 280 for invasive cancer. Overall, 234 patients (61.3%) required intraoperative reexcision for positive margins. The reexcision rate was higher in patients with DCIS than in those with invasive disease (78.4% [80 of 102] vs 56.4% [158 of 280]; univariate odds ratio, 2.80; 95% CI, 1.66-4.76; P<.001). Positive margin rates did not vary by patient age, surgeon, estrogen receptor, progesterone receptor, or ERBB2 status of the tumor. Among the 280 cases of invasive breast cancer, the only factor independently associated with lower odds of margin positivity was seed localization vs no localization (P=.03)., Conclusion: Ductal carcinoma in situ was associated with a higher rate of positive margins at lumpectomy than invasive breast cancer on univariate analysis. Within invasive disease, seed localization was associated with lower rates of margin positivity., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Purpose: One of the Society of Surgical Oncology Choosing Wisely guidelines recommends avoiding routine sentinel lymph node (SLN) surgery in clinically node-negative women ≥70 years of age with hormone receptor-positive (HR+) breast cancer. We sought to assess the impact of tumor stage and grade on nodal positivity, and to develop a model to identify patients at low-risk of nodal positivity to aid adoption of the guideline., Methods: We identified women ≥70 years of age with HR+ cN0 invasive breast cancer in the National Cancer Database (NCDB; 2010-2013) and examined the impact of tumor stage and grade on nodal positivity to identify low-risk combinations. A multivariable logistic regression model was developed to incorporate additional factors. The area under the curve (AUC) and relative risks (RR) were used to assess performance., Results: Among 71,834 cases, the pathologic nodal positivity (pN+) rate was 15.3%. We identified low-risk criteria as grade 1, cT1mi-T1c (≤2.0 cm), or grade 2, cT1mi-T1b (≤1.0 cm), with pN+ rates of 7.8% compared with 22.3% in patients not meeting these criteria (RR 2.86, p < 0.001). On multivariable analysis, factors associated with pN+ status included clinical T stage, grade, and histology (each p < 0.001). The resulting model had AUC 0.70 and identified women with low predicted probability (<10%) of positive nodes, of whom 6.3% were pN+, versus 21.2% in those with predicted probability ≥10% (RR 3.34, p < 0.001)., Conclusion: The simple clinical rule (grade 1, cT1mi-T1c, or grade 2, cT1mi-T1b), as well as the predictive model, both identify women at low risk of nodal positivity where SLN surgery can be omitted.

Background: Adjuvant hormonal therapy (HT) reduces breast cancer recurrence risk in estrogen receptor-positive (ER+) ductal carcinoma in situ (DCIS). We assessed national practice patterns and influence of surgery and pathology on HT use in DCIS., Methods: Data on DCIS patients diagnosed from 2004 to 2014 were extracted from the National Cancer Database, and patients were classified according to ER status and whether HT was received. Factors associated with HT use were assessed using Chi square tests for univariate analysis and logistic regression for multivariate analysis., Results: Overall, 207,738 patients were evaluable as follows: ER+ (69.3%), ER- (13.7%), and ER unknown (17.0%). Among ER+ DCIS patients, 46.5% received HT, and HT use increased over time (42.3% in 2004 to 50.6% in 2014; p < 0.001). In contrast, 7.8% of ER- DCIS patients received HT, decreasing from 10.7% in 2004 to 5.9% in 2014 (p < 0.001). HT use varied by surgery type (BCS, 53.9%; unilateral mastectomy, 31.5%; and bilateral mastectomy, 8.1%; p < 0.001) and use was higher in BCS patients receiving adjuvant radiation than those not receiving radiation (62.7 vs. 29.1%; p < 0.001). Males treated with BCS were less likely to receive HT than females (43.2 vs. 54.0%; p < 0.001). In the BCS subset, higher use of HT was associated with more recent calendar year, age between 40 and 80 years, female sex, positive progesterone receptor status, and radiation use., Conclusion: Adjuvant HT use in ER+ DCIS has increased over time, with the highest rates in patients treated with BCS and radiation. While inappropriate HT use was observed in ER- and bilateral mastectomy patients, the frequency of use in these categories decreased over time.

Background: Approximately 8-56% of patients with a core needle biopsy (CNB) diagnosis of ductal carcinoma in situ (DCIS) will be upstaged to invasive disease at the time of excision. Patients with invasive disease are recommended to undergo axillary nodal staging, most often requiring a second operation. We developed and validated a nomogram to preoperatively predict percentage of risk for upstaging to invasive cancer., Methods: We reviewed 834 cases of DCIS on CNB between January 2004 and October 2014. Multivariable analysis was used to evaluate CNB and imaging factors to develop a nomogram to predict the risk of upstaging from DCIS to invasive cancer. This nomogram was validated with an external dataset of 579 similar patients between November 1998 and September 2016. An area under the receiver operating characteristic curve was constructed to evaluate nomogram discrimination., Results: The rate of upstaging to invasive disease was 118/834 (14.1%). On multivariable analysis, grade on CNB and imaging factors, including mass lesion, multicentric disease, and largest linear dimension, were associated with upstage to invasive disease, and was used to develop a nomogram (c-statistic 0.71). In the external validation dataset, 62/579 (10.7%) patients were upstaged to invasive disease. Our nomogram was validated in this dataset with a c-statistic of 0.71., Conclusion: For patients with a CNB diagnosis of DCIS, our validated nomogram using DCIS grade on biopsy, and imaging factors of mass lesion, multicentric disease, and largest linear dimension, may be used for preoperative assessment of risk of upstaging to invasive disease, allowing patient counseling regarding axillary staging at the time of definitive surgery.

Introduction: For patients who have an ipsilateral breast cancer recurrence following prior breast-conserving surgery and radiation, total mastectomy generally is recommended. However, little is known about the suitability and outcomes of nipple-sparing mastectomy (NSM) with immediate breast reconstruction for the treatment of recurrent breast cancer, prompting this investigation., Patients and Methods: From 1008 patients scheduled for NSM for breast cancer treatment at our institution between January 2009 and June 2016, we identified all patients who underwent surgery for ipsilateral recurrent breast cancer. We analyzed patient, tumor, and treatment variables, nipple preservation rates, and cancer outcomes., Results: Twenty-one patients with ipsilateral recurrent disease were scheduled for NSM with immediate breast reconstruction, of whom 19 had received prior whole breast radiation. Two patients (10%) underwent intraoperative conversion to skin-sparing mastectomy for atypia or ductal carcinoma in situ in the central nipple ducts. Postoperative complications requiring intervention occurred in 2 patients: focal flap necrosis requiring debridement in 1 patient and seroma aspiration in another. Three patients received planned (pre- and/or postoperative) hyperbaric oxygen therapy. After 14.6 months median follow-up (range, 3-48.5 months), all 19 patients retained their native nipple-areolar complex and are disease-free., Conclusions: NSM may be performed in carefully selected patients with recurrent breast cancer, despite prior ipsilateral surgery and radiation, with successful preservation of the nipple-areolar complex and an acceptably low complication rate. Our data suggest no short-term adverse effect of NSM on oncologic outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Breast mucocele-like lesions (MLLs) are rare breast lesions. There is a paucity of literature on the rate of pathologic upstaging of MLL to in situ or invasive breast cancer. We sought to review our experience with MLL at a tertiary care center and review published literature., Methods: A retrospective review was undertaken of all patients with breast MLL at the Mayo Clinic, Rochester, from 1998 to 2016. Descriptive statistics were performed., Results: Overall, 30 patients were diagnosed with MLL, with a mean age of 54.6 years (range 51-58). Calcifications on screening mammogram were the most common method of MLL detection (n = 26, 86.7 %), with core needle biopsy (CNB) being performed in 29/30 patients. MLL with atypia was identified in 14 patients (48 %), and surgical excision was performed in 26 patients. Disease was upstaged to invasive disease in one patient (3.8 %) who presented with a palpable mass. With a median duration of follow up of 3.5 years [interquartile range 1-7.1], two patients developed contralateral invasive breast cancer (both patients had a remote history of invasive breast cancer on that side), and one patient developed contralateral in situ disease. Review of the literature demonstrates a 2.9 % upgrade rate of MLL without atypia on excisional biopsy., Conclusions: The upstage rate of MLL identified on CNB to invasive disease at surgical excision in this series was 3.8 %. In cases with MLL presenting as calcifications, no cases were upstaged in this series. Across the literature, upstage rates of MLL without atypia on CNB are low, indicating excisional biopsy may be avoided in these cases.

Background: Data support the use of accelerated partial-breast irradiation (APBI) for early-stage breast cancer. We initiated a prospective protocol for intraoperative APBI catheter placement using a multi-lumen strut-based device. We hypothesized that with intraoperative pathology assessment of margins and sentinel nodes, all locoregional treatment (surgery and APBI) could be completed within 10 days with acceptable complication rates and cosmesis., Methods: Eligible patients included women age 50 years or older with clinical T1 estrogen receptor positive (ER+) sentinel lymph node (SLN)-negative invasive ductal cancer or pure ductal carcinoma in situ. Patients were prospectively registered. Cosmesis was assessed using photographs graded independently by three investigators for patients with photos taken 6 months or longer after treatment., Results: From October 2012 to August 2015, we enrolled 123 patients; 110 (90 %) underwent intraoperative catheter placement, whereas 13 did not due to intraoperative pathology findings. 109 APBI patients (99 %) completed their prescribed radiotherapy within 5 days, and all their locoregional therapy within 9 days, whereas one patient with a delayed positive SLN received only boost radiotherapy via catheter followed by conventional whole breast radiation. The 30-day complication rate was 6 %. In 81 patients with at least one-year followup, complications occurred in 14 (17 %) (including infection in five patients and symptomatic seroma in five patients) and correlated with device size (p = 0.05) but not with tumor size or location. The local recurrence rate was 1.8 % (two patients). Scored cosmesis was excellent or good in 88 % and fair in 12 % of patients., Conclusions: A protocol for intraoperative strut-based APBI catheter placement using careful patient selection and intraoperative pathology assessment can deliver efficient, effective treatment for early breast cancer.

Background: The American College of Surgeons Oncology Group Z1071 trial reported a false-negative rate (FNR) of 12.6% with sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy in women presenting with node-positive breast cancer. One proposed method to decrease the FNR is clip placement in the positive node at initial diagnosis with confirmation of clipped node resection at surgery., Methods: Z1071 was a multi-institutional trial wherein women with clinical T0-T4,N1-N2,M0 breast cancer underwent SLN surgery and axillary dissection (ALND) after neoadjuvant chemotherapy. In cases with a clip placed in the node, the clip location at surgery (SLN or ALND) was evaluated., Results: A clip was placed at initial node biopsy in 203 patients. In the 170 (83.7%) patients with cN1 disease and at least 2 SLNs resected, clip location was confirmed in 141 cases. In 107 (75.9%) patients where the clipped node was within the SLN specimen, the FNR was 6.8% (confidence interval [CI]: 1.9%-16.5%). In 34 (24.1%) cases where the clipped node was in the ALND specimen, the FNR was 19.0% (CI: 5.4%-41.9%). In cases without a clip placed (n = 355) and in those where clipped node location was not confirmed at surgery (n = 29), the FNR was 13.4% and 14.3%, respectively., Conclusions: Clip placement at diagnosis of node-positive disease with removal of the clipped node during SLN surgery reduces the FNR of SLN surgery after neoadjuvant chemotherapy. Clip placement in the biopsy-proven node at diagnosis and evaluation of resected specimens for the clipped node should be considered when conducting SLN surgery in this setting.

Background: Rates of contralateral prophylactic mastectomy (CPM) have been increasing nationally. The goal of this study was to evaluate recent trends in rates of CPM and immediate breast reconstruction (IBR)., Methods: After institutional review board approval, we evaluated all surgical procedures for women with newly diagnosed unilateral stages 0-III breast cancer from January 2009 to December 2014. Patients opting for therapeutic mastectomy were classified as either unilateral mastectomy or bilateral mastectomy, if CPM was performed, and according to whether or not they underwent IBR. Analysis was performed using trend tests for univariate associations and both binary and multinomial logistic regression for multivariate analysis., Results: There were 3,195 women who underwent surgery for breast cancer--51% lumpectomy, 49% therapeutic mastectomy. Of the 1,571 patients undergoing therapeutic mastectomy, 829 (53%) underwent bilateral mastectomy. The rates of therapeutic mastectomy did not change over the study period (P = .92), but the use of IBR among patients undergoing therapeutic mastectomy increased from 37% in 2009 to 68% in 2014 (P < .0001). The use of bilateral mastectomy with IBR increased from 26% in 2009 to 46% in 2014 (P < .0001), whereas conversely the use of bilateral mastectomy without IBR decreased from 22% to 12% (P < .0001). IBR was associated with bilateral mastectomy; 69% of patients opting for IBR also underwent bilateral mastectomy compared with 38% choosing bilateral mastectomy in the group without IBR (adjusted odds ratio, 2.7; 95% CI, 2.1-3.5; P < .0001)., Conclusion: Over recent years, rates of bilateral mastectomy have remained high. The use of IBR increased substantially for women undergoing therapeutic mastectomy and women undergoing IBR were significantly more likely to opt for bilateral mastectomy. The availability of IBR may influence patients' decisions to pursue bilateral mastectomy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Despite decreasing rates of subsequent contralateral breast cancer after diagnosis of unilateral primary breast cancer, the proportion of patients electing contralateral prophylactic mastectomy (CPM) is increasing. Our aim was to identify risk factors associated with the identification of occult malignancy (OM) or high-risk lesion (HRL) in CPM to facilitate patient counseling and operative planning., Methods: We identified patients undergoing CPM in addition to mastectomy for index breast cancer between October 2008 and June 2013. Patient and tumor factors were analyzed to identify associations with OM or HRL in CPM., Results: Among 740 CPM patients, an OM was identified in 4.1 % and an HRL was identified in 10.5 %. On multivariable analysis, factors associated with either occult finding included older age [odds ratio (OR) 1.37, per 10-year increase], invasive lobular index tumor histology (OR 2.60), progesterone receptor (PR)-positive index tumor (OR 1.79), and neoadjuvant therapy (OR 0.55). Overall, 244 patients (33 %) underwent BRCA testing, and 38 (16 %) had a deleterious mutation; 494 patients (67 %) had a preoperative breast MRI. Neither absence of a deleterious BRCA mutation nor a negative preoperative MRI decreased the likelihood of an occult finding in CPM., Conclusions: Although invasive cancer was identified infrequently in CPM specimens, the rate of HRL or OM in our study was 14.6 %. Older age and infiltrating lobular and PR-positive index breast cancers were associated with a higher risk of OM in CPM, while neoadjuvant therapy diminished the risk. BRCA testing and preoperative MRI were not associated with HRL or OM. This information is valuable for patient counseling and surgical planning.

Background: Pathologic nipple discharge is managed customarily with diagnostic subareolar duct excision. We evaluated for features predictive of malignancy to identify cases where operation might be avoided., Methods: We studied 311 consecutive subareolar duct excisions for pathologic nipple discharge from January 2008 to July 2014. χ(2) tests were used to test for associations with final pathology., Results: In 27 cases, cancer was diagnosed preoperatively. Among the remaining 284, 26 (9%) were diagnosed with cancer and 8 (3%) with atypia at operation. At greatest risk of upstage to cancer were patients with prior ipsilateral breast cancer (3/8; 38%), BRCA mutation (2/3; 67%) or atypia on core needle biopsy (CNB; 3/8 [38%]). Excluding these patients lowered cancer and atypia upstages (7% [18/265] and 3% [7/265]), with bloody (versus serous) discharge (P = .001), and focal imaging abnormality (P = .02), the strongest risk factors. Serous discharge and either normal imaging or a benign CNB had a 1.3% cancer upstage rate., Conclusion: Despite contemporary imaging, pathologic nipple discharge upstage rates to malignancy and atypia remain high, especially with prior ipsilateral breast cancer, BRCA mutation, or atypia on CNB. Absent these risk factors, patients with serous discharge and a benign CNB or normal imaging (cancer risk <2%) may be considered for nonoperative management., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Use of targeted therapy for human epidermal growth factor receptor-2 (HER2)-positive breast cancer has led to improvements in survival. Furthermore, neoadjuvant chemotherapy (NAC) with dual HER2 agents demonstrated improved pathological complete response (pCR) rates. With these data, and with US FDA approval in September 2013 of pertuzumab in the neoadjuvant setting, we hypothesized that the use of NAC for early-stage HER2-positive patients is increasing., Methods: With Institutional Review Board approval, we reviewed 267 patients with 268 clinical T1 and T2 HER2-positive tumors treated from October 2008 to September 2014. We compared treatment in the early (October 2008-September 2013) to recent (October 2013-September 2014) periods. Statistical analysis was performed using Chi square tests., Results: Mean patient age was 59 years. Clinical T stage included 6 (2%) T1mic, 11 (4%) T1a, 41 (15%) T1b, 95 (35%) T1c, and 115 (43%) T2. Targeted therapy included combinations of trastuzumab, lapatinib, pertuzumab, and neratinib. NAC use increased from 53/219 (24.2%) in the early group to 19/49 (38.8%) in the recent group (p = 0.04). Forty-two percent (8/19) of patients in the recent group received neoadjuvant pertuzumab versus 0/53 in the early group (p < 0.0001). More clinically node-negative (cN0) patients received NAC in the recent (12/41, 29.3%) versus early (20/167, 12.0%) period (p = 0.01). For T1 tumors, the use of NAC more than doubled between the two time periods (5.6-17.2%; p = 0.06), while NAC use increased from 48 to 70% for T2 tumors (p = 0.08). The overall pCR rate after NAC was 48.6% (35/72)., Conclusions: NAC for HER2-positive breast cancer patients is increasing. Most striking was a substantial increase in NAC for patients with T1 tumors and cN0 disease.

Objectives: We investigated the impact of neoadjuvant chemotherapy (NAC) on axillary disease burden in clinically node-negative (cN0) HER-2 positive breast cancer patients., Methods: We studied 215 cN0 patients with HER-2 positive tumors. Multivariable logistic regression was used to compare NAC versus primary surgery (PS) with respect to outcome of pathologic nodal disease., Results: Of 215 patients, 42 (20%) received NAC. NAC use correlated with higher clinical T stage (P < 0.0001) and younger age (P = 0.03) with no difference in ER/PR status or tumor grade. Despite higher clinical T stage in the NAC group, rate of pathologic positive axillary nodes was non-significantly lower (NAC 5/42 = 11.9%, PS 27/173 = 15.6%, P = 0.54). In multivariable analysis, after adjustment for confounders including clinical T stage, age, and multifocal/multicentric disease, NAC showed significant reduction in odds of pathologic nodal disease (OR 0.26, 95%CI:0.06-0.90, P = 0.03). Further, among those with pathologic nodal disease, the number of positive nodes was lower after NAC (adjusted P = 0.03). Extranodal extension was present in 8/27 (30%) PS patients vs. 1/5 (20%) of the NAC patients (adjusted P = 0.36)., Conclusion: NAC in cN0 HER-2 positive breast cancers reduces the rate of pathologic node-positive disease at operation and nodal disease burden and may decrease the need for axillary node dissection., (© 2015 Wiley Periodicals, Inc.)

Objective: The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles., Materials and Methods: Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests., Results: In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients., Conclusion: Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular breast imaging is less likely to show all foci of ILC compared with IDC.

Introduction: Obesity affects 36 % of American women and is a well-documented breast cancer risk factor. Preoperative axillary ultrasound (AUS) is used routinely for axillary staging in newly diagnosed breast cancer patients; However, the impact of obesity on the usefulness of AUS is unknown. Our aim was to evaluate the effect of body mass index (BMI) on the performance of AUS., Methods: From our prospective breast surgery database, we identified 1,510 consecutive invasive breast cancers in patients undergoing primary surgery, including axillary operation, from January 2010 to July 2013. Preoperative AUS was performed in 1,375 cases (91 %). We analyzed patient, pathology and imaging data., Results: Median BMI was 27.4 and 479 patients (36 %) were classified as obese (BMI ≥ 30). Most tumors were T1 (71 %) and estrogen receptor-positive (87 %). AUS was suspicious in 401 (29 %) patients, of whom 374 had ultrasound-guided lymph node fine-needle aspiration (FNA). Overall, 124 patients (33.2 %) were FNA positive. FNA identified disease preoperatively in 35.8 % of node-positive obese patients. For all BMI categories (normal, overweight, obese), AUS was predictive of pathologic nodal status (p < 0.0001). AUS sensitivity did not differ across BMI categories, while specificity and accuracy were better for overweight (p = 0.001 and 0.008, respectively) and obese (p = 0.007 and 0.02, respectively) patients, than for normal-BMI patients., Conclusions: Despite theoretical concern regarding both potential technical challenges and obesity-related lymph node alterations, the sensitivity of preoperative AUS for detecting nodal metastasis was similar in obese and non-obese patients, while specificity was better in obese patients. Preoperative AUS is valuable for preoperative nodal staging of obese breast cancer patients.

Background: Reoperation for positive margins after lumpectomy for breast cancer is common. Intraoperative analysis of frozen-section (FS) margins permits immediate re-excision, avoiding reoperation. The aim of this study was to compare reoperation rates between an institution using routine FS analysis of all margins and the National Surgical Quality Improvement Program (NSQIP) data., Methods: We designed a retrospective cohort analysis comparing the NSQIP data from a FS single institution with the national NSQIP data from 2006 to 2010. Women undergoing lumpectomy for cancer were identified (N = 24,217), and reoperation rates were compared by the use of χ(2) analyses and multivariable logistic regression. During this time period, NSQIP did not differentiate between reoperations for complications or oncologic reasons. Reoperation rates for mastectomy patients (N = 21,734) and lumpectomy patients without cancer (N = 2,777) over the same time period were analyzed as controls, because reoperations after these procedures likely would be for reasons other than positive margins., Results: The 30-day reoperation rate after lumpectomy for cancer was greater nationally than at the FS institution (13.2% vs 3.6%, P < .001). Multivariable analysis showed that patients in the national NSQIP data set were over four times as likely to undergo reoperation as those at the FS institution's (odds ratio 4.19). The reoperation rates were similar between the two, both for patients undergoing mastectomy (4.7% vs 4.5%, P = .84) and those undergoing lumpectomy for benign diagnosis (2.9% vs 5.9%, P = .39)., Conclusion: Intraoperative FS margin analysis decreases the number of reoperations for patients undergoing breast conservation for breast cancer. This technique has important implications for patient satisfaction and cost of care., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Memorial Sloan Kettering Cancer Center (MSKCC) and MD Anderson Cancer Center (MDACC) have established nomograms to predict sentinel node positivity. We propose the addition of two novel variables-distance of tumor from the nipple and from the skin-can improve their performance., Methods: Ultrasounds of clinical T1/T2 tumors were reviewed. Distances of the tumor from the skin and from the nipple were measured. MSKCC and MDACC nomogram predictions and the AUC-ROC for each model were calculated. The added utility of the two variables was then examined using multiple logistic regression., Results: Of 401 cancers studied, 79 (19.7 %) were node positive. The mean distance of tumors from the nipple in node-positive patients was 4.9 cm compared with 6.0 cm in node-negative patients (p = 0.0007). The mean distance of tumors from the skin was closer in node-positive cases (0.8 cm) versus node-negative cases (1.0 cm, p = 0.0007). The MSKCC and MDACC nomograms AUC-ROC values were 0.71 (95 % CI 0.64-0.77) and 0.74 (95 % CI 0.68-0.81). When adjusted for the MSKCC predicted probability, addition of both distance from nipple (p = 0.008) and distance from skin (p = 0.02) contributed significantly to prediction of nodal positivity and improved the AUC-ROC to 0.75 (95 % CI 0.70-0.81). Similarly, distance from nipple (p = 0.002), but not distance from skin (p = 0.09), added modestly to the MDACC nomogram performance (AUC 0.77; 95 % CI 0.71-0.83)., Conclusions: Distance of tumor from the nipple and from the skin are important variables associated with nodal positivity. Adding these to established nomograms improves prediction of nodal positivity.

Background: The American College of Surgeons Oncology Group Z0011 trial results provided convincing evidence that completion axillary lymph node dissection (CALND) was unnecessary in selected patients with 1 to 2 positive sentinel lymph nodes (SLNs). We hypothesized that preoperative axillary ultrasound (AUS) with fine-needle aspiration is sufficiently sensitive to detect worrisome macrometastasis to preclude the need for frozen-section pathology of SLNs., Study Design: We conducted a retrospective single-institution study at a tertiary academic referral center. A total of 1,140 T1 to 2 breast cancer patients who underwent SLN biopsy with or without CALND from January 1, 2007 to December 31, 2010 were reviewed. All patients had negative preoperative AUS with or without fine-needle aspiration., Results: One hundred forty-four (13%) patients were node positive at surgery. Mean age, tumor size, histology, and estrogen receptor and progesterone receptor status were similar comparing 996 SLN-negative with 144 (13%) SLN-positive patients. Of the SLN-positive patients, 25% were premenopausal, 9% were estrogen receptor-negative, and 19% had additional lymph nodes at CALND. Only 19 (2%) patients had SLN metastasis ≥6 mm, 10 (1%) had metastasis >7 mm, and only 1 patient had ≥3 positive SLNs., Conclusions: The addition of preoperative AUS with or without fine-needle aspiration to management of patients who meet American College of Surgeons Oncology Group Z0011 trial eligibility criteria reduced the risk of macrometastasis measuring ≥6 mm to only 2%; very few of these patients would be premenopausal, have estrogen receptor-negative tumors, or ≥3 positive SLNs. With the addition of AUS with or without fine-needle aspiration, we endorse the conclusions of the American College of Surgeons Oncology Group Z0011 trial to avoid CALND, and see marginal gain in frozen-section analysis of SLNs., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To determine factors important in local-regional recurrence (LRR) in patients with negative sentinel lymph nodes (SLNs) by hematoxylin and eosin (H&E) staining., Background: Z0010 was a prospective multicenter trial initiated in 1999 by the American College of Surgeons Oncology Group to evaluate occult disease in SLNs and bone marrow of early-stage breast cancer patients. Participants included women with biopsy-proven T1-2 breast cancer with clinically negative nodes, planned for lumpectomy and whole breast irradiation., Methods: Women with clinical T1-2,N0,M0 disease underwent lumpectomy and SLN dissection. There was no axillary-specific treatment for H&E-negative SLNs, and clinicians were blinded to immunohistochemistry results. Systemic therapy was based on primary tumor factors. Univariable and multivariable analyses were performed to determine clinicopathologic factors associated with LRR., Results: Of 5119 patients, 3904 (76.3%) had H&E-negative SLNs. Median age was 57 years (range 23-95). At median follow-up of 8.4 years, there were 127 local, 20 regional, and 134 distant recurrences. Factors associated with local-regional recurrence were hormone receptor-negative disease (P = 0.0004) and younger age (P = 0.047). In competing risk-regression models, hormone receptor-positive disease and use of chemotherapy were associated with reduction in local-regional recurrence. When local recurrence was included in the model as a time-dependent variable, older age, T2 disease, high tumor grade, and local recurrence were associated with reduced overall survival., Conclusions: Local-regional recurrences are rare in early-stage breast cancer patients with H&E-negative SLNs. Younger age and hormone receptor-negative disease are associated with higher event rates, and local recurrence is associated with reduced overall survival.

Background: Local recurrence (LR) after breast conservation surgery (BCS) varies with risk factors. This study was designed to evaluate the impact of young age on LR., Methods: All patients (excluding those who received neoadjuvant chemotherapy) who underwent BCS from 1988-2001 at our institution were identified and evaluated for risk factors of LR., Results: A total of 3,064 patients underwent 3,131 BCS. Mean age at surgery was 61 (range, 21-98) years: 175 (5.6%) patients were aged<40 years; 492 (15.7%) were 40-49 years; 761 (24.3%) were 50-59 years; 801 (25.6%) were 60-69 years; and 902 (28.8%) were age 70+years. A total of 212 patients (6.8%) developed LR at a mean of 4.5 (range, 0.1-14.4) years after BCS. Mean follow-up was 8.9 (range, 0-20.2) years. The 5-year LR-free survival rate was 94.9%. The frequencies of LR by age group were: <40 years--11.4%; 40-49 years--5.7%; 50-59 years--6.2%; 60-69 years--7.6%; 70 years and older--6.2%. The 5-year LR-free survival rates for these age groups were 90.5%, 95.4%, 95.5%, 95.4%, and 94.7%, respectively (P=0.09, log-rank test). On univariable analysis, patients aged<40 years were nearly twice as likely to experience LR (hazards ratio (HR), 1.81; P=0.012). Multivariable analysis of patients with complete data (n=2,122) demonstrated that age<40 years and node positivity were associated with increased risk of LR, whereas ER positivity and radiation therapy were associated with decreased risk., Conclusions: Risk factors for LR after BCS include age<40 years, node positivity, ER negativity, and absence of adjuvant radiation therapy. Patients younger than age 40 years are at increased risk of LR after BCS.

Background and Objective: Sentinel lymph node (SLN) metastasis size is an important predictor of non-SLN involvement. The goal of this study was to construct a nomogram incorporating SLN metastasis size to accurately predict non-SLN involvement in patients with SLN-positive disease., Methods: We identified 509 patients with invasive breast cancer with a positive SLN who underwent completion axillary lymph node dissection (ALND). Clinicopathologic data including age, tumor size, histology, grade, presence of multifocal disease, estrogen and progesterone receptor status, HER2/neu status, presence of lymphovascular invasion (LVI), number of SLN(s) identified, number of positive SLN(s), maximum SLN metastasis size and the presence of extranodal extension were recorded. Univariate and multivariate logistic regression analyses identified factors predictive of positive non-SLNs. Using these variables, a nomogram was constructed and subsequently validated using an external cohort of 464 patients., Results: On univariate analysis, the following factors were predictive of positive non-SLNs: number of SLN identified (P < 0.001), number of positive SLN (P < 0.001), SLN metastasis size (P < 0.001), extranodal extension (P < 0.001), tumor size (P = 0.001), LVI (P = 0.019), and histology (P = 0.034). On multivariate analysis, all factors remained significant except LVI. A nomogram was created using these variables (AUC = 0.80; 95% CI, 0.75-0.84). When applied to an external cohort, the nomogram was accurate and discriminating with an AUC = 0.74 (95% CI, 0.68-0.77)., Conclusion: SLN metastasis size is an important predictor for identifying non-SLN disease. In this study, we incorporated SLN metastasis size into a nomogram that accurately predicts the likelihood of having additional axillary metastasis and can assist in personalizing surgical management of breast cancer.

Breast cancer most often presents as a palpable mass or with an abnormal mammogram. Much less commonly, breast cancer may present as a paraneoplastic syndrome. Dermatomyositis (DM) is a rare disease most often considered a complement-mediated idiopathic inflammatory myopathy manifested by classic skin findings and proximal muscle weakness. However, DM may also be due to a paraneoplastic syndrome associated with an underlying malignancy. The authors present a case report of a woman with presumed contact dermatitis who was diagnosed with breast cancer in the setting of progressive fatigue and muscle weakness. DM was subsequently diagnosed. Treatment of DM simultaneous with treatment of the breast cancer led to regression of DM. The diagnosis of DM in an adult should raise suspicion of an underlying malignancy. Breast cancer is a common disease that may rarely present with uncommon features that may divert attention from the underlying malignancy.

Background: Patients with metastases in four or more axillary lymph nodes (≥4+ALN) represent a subset of patients with breast cancer who are at increased risk of local recurrence and who benefit from postmastectomy radiation. Risk prediction models designed to identify such patients have been published by Rivers et al., Chagpar et al., and Katz et al. We sought to evaluate and compare the performance of these models in an independent patient population., Methods: We reviewed 454 patients with breast cancer with one to three positive sentinel lymph nodes who underwent completion axillary lymph node dissection at our institution. Each of the three published models was applied to our sample as described in the respective publications. The models' performances were analyzed with the Hosmer-Lemeshow goodness-of-fit test and with the area under the curve (AUC). Sensitivity, specificity, and false-negative percentages were calculated for clinically meaningful cutoff points of each score., Results: Of 454 eligible patients, 87 (19.2%) had four or more positive axillary nodes. The Rivers, Chagpar, and Katz models demonstrated good calibration in our population based on the Hosmer-Lemeshow test (p = 0.82, p = 0.73, p = 0.71, respectively). Assessment of discriminatory ability for the models resulted in AUCs of 0.81, 0.73, and 0.81, respectively., Conclusions: The Rivers and Katz models performed well in our patient population and may be clinically useful to predict patients with ≥4+ALN. However, their clinical utility is limited by the current controversy surrounding the use of postmastectomy radiation for all node-positive patients.

Purpose: Preoperative axillary lymph node ultrasound (US) and fine-needle aspiration (FNA) biopsy can identify a proportion of node-positive patients and avoid sentinel lymph node (SLN) surgery and direct surgical treatment. We compared the costs with preoperative US/FNA to without US/FNA (standard of care) for invasive breast cancer., Methods: Using decision-analytic software we constructed a model to assess the costs associated with the two preoperative strategies. Diagnostic test sensitivities and specificities were obtained from literature review. Costs were derived from Medicare payment rates and actual resource utilization. Base-case results were fully probabilistic to capture parameter uncertainty in economic results., Results: Base-case results estimate total mean costs per patient of $10,947 ("$" indicates US dollars throughout) with the US/FNA strategy and $10,983 with standard of care, an incremental cost savings of $36, on average, per patient [95% confidence interval (CI) of cost difference: -$248 to $179]. Most (63%) of the simulations resulted in cost saving with axillary US/FNA. One-way sensitivity analyses suggest that results are sensitive to assumed diagnostic and surgical costs and selected diagnostic test parameters. US/FNA approach was similar in costs or cost saving relative to the standard of care for all tumor stages., Conclusions: The additional cost of performing axillary US with possible FNA in every patient is balanced, on average, by the savings from avoiding SLN in cases where metastasis can be documented preoperatively. Routine use of preoperative axillary US with FNA to guide surgical planning can decrease the overall cost of patient care for invasive breast cancer.

Recurrent breast carcinoma is usually detected by imaging studies and biopsy. We present a case with unusual clinical presentation and discuss the diagnosis and treatment. While core needle biopsy and fine-needle aspiration are important in the diagnosis of early-stage breast cancer, physical examination and close follow-up are important in the absence of a diagnosis.