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Background: Breast-conserving surgery (BCS) is a mainstay for breast cancer management, and obtaining negative margins is critical. Some have advocated for the use of preoperative magnetic resonance imaging (MRI) in reducing positive margins after BCS. We sought to determine whether preoperative MRI was associated with reduced positive margins., Patients and Methods: The SHAVE/SHAVE2 trials were multicenter trials in ten US centers with patients with stage 0-3 breast cancer undergoing BCS. Use of preoperative MRI was at the discretion of the surgeon. We evaluated whether or not preoperative MRI was associated with margin status prior to randomization regarding resection of cavity with shave margins., Results: A total of 631 patients participated. Median age was 64 (range 29-94) years, with a median tumor size of 1.3 cm (range 0.1-9.3 cm). Patient factors included 26.1% of patients (165) had palpable tumors, and 6.5% (41) received neoadjuvant chemotherapy. Tumor factors were notable for invasive lobular histology in 7.0% (44) and extensive intraductal component (EIC) in 32.8% (207). A preoperative MRI was performed in 193 (30.6%) patients. Those who underwent preoperative MRI were less likely to have a positive margin (31.1% versus 38.8%), although this difference was not statistically significant (p = 0.073). On multivariate analysis, controlling for patient and tumor factors, utilization of preoperative MRI was not a significant factor in predicting margin status (p = 0.110). Rather, age (p = 0.032) and tumor size (p = 0.040) were the only factors associated with margin status., Conclusion: These data suggest that preoperative MRI is not associated margin status; rather, patient age and tumor size are the associated factors., (© 2023. Society of Surgical Oncology.)

Introduction: De-escalation of breast cancer treatment aims to reduce patient and financial toxicity without compromising outcomes. Level I evidence and National Comprehensive Cancer Network guidelines support omission of adjuvant radiation in patients aged >70 y with hormone-sensitive, pT1N0M0 invasive breast cancer treated with endocrine therapy. We evaluated radiation use in patients eligible for guideline concordant omission of radiation., Methods: Subgroup analysis of patients eligible for radiation omission from two pooled randomized controlled trials, which included stage 0-III breast cancer patients undergoing breast conserving surgery, was performed to evaluate factors associated with radiation use., Results: Of 631 patients, 47 (7.4%) met radiation omission criteria and were treated by 14 surgeons at eight institutions. The mean age was 75.3 (standard deviation + 4.4) y. Majority of patients identified as White (n = 46; 97.9%) and non-Hispanic (n = 44; 93.6%). The mean tumor size was 1.0 cm; 37 patients (88.1%) had ductal, 4 patients (9.5%) had lobular, and 17 patients (40.5%) had low-grade disease. Among patients eligible for radiation omission, 34 (72.3%) patients received adjuvant radiation. Those who received radiation were significantly younger than those who did not (74 y, interquartile range = 4 y, versus 78 y, interquartile range = 11 y, P = 0.03). There was no difference in radiation use based on size (P = 0.4), histology (P = 0.5), grade (P = 0.7), race (P = 1), ethnicity (P = 0.6), institution (P = 0.1), gender of the surgeon (P = 0.7), or surgeon (P = 0.1)., Conclusions: Fewer than 10% of patients undergoing breast conservation met criteria for radiation omission. Nearly three-quarters received radiation therapy with younger age being a driver of radiation use, suggesting ample opportunity for de-escalation, particularly among younger eligible patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Factors contributing to the use of preoperative MRI remain poorly understood., Methods: Data from a randomized controlled trial of stage 0-3 breast cancer patients undergoing breast conserving surgery between 2016 and 2018 were analyzed., Results: Of the 396 patients in this trial, 32.6% had a preoperative MRI. Patient age, race, ethnicity, tumor histology, and use of neoadjuvant therapy were significant predictors of MRI use. On multivariate analysis, younger patients with invasive lobular tumors were more likely to have a preoperative MRI. Rates also varied significantly by individual surgeon (p < 0.001); in particular, female surgeons (39.9% vs. 24.0% for male surgeons, p = 0.001) and those in community practice (58.9% vs. 14.2% for academic, p < 0.001) were more likely to order preoperative MRI. Rates declined over the two years of the study, particularly among female surgeons., Conclusions: Preoperative MRI varies with patient age and tumor histology; however, there remains variability by individual surgeon., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The optimal treatment strategy for small node-negative human epidermal growth factor receptor 2-positive (HER2+) breast cancer remains controversial. Neoadjuvant chemotherapy may risk overtreatment, whereas surgery first fails to identify patients with residual disease in need of escalated adjuvant systemic therapy. We investigated patient characteristics associated with receipt of neoadjuvant chemotherapy., Methods: Adult women with cT1-T2/N0, HER2+ breast cancer between 2013 and 2017 in the National Cancer Database who underwent surgery within 8 months of diagnosis were included. Patients were classified as receiving neoadjuvant chemotherapy versus a surgery-first approach. We assessed the sociodemographic and clinical predictors of neoadjuvant chemotherapy versus surgery first and associations between neoadjuvant chemotherapy and breast cancer treatments using multivariable regression models., Results: We identified 56,784 women, of whom 12,758 (22%) received neoadjuvant chemotherapy, 29,139 (53%) received adjuvant chemotherapy, 12,907 (24%) received no chemotherapy, and 1980 were missing chemotherapy information. After adjustment, cT2 stage was the strongest predictor of neoadjuvant chemotherapy compared with surgery first. Younger age and later diagnosis year were positively associated with receipt of neoadjuvant chemotherapy. In contrast, hormone receptor positivity, Black race, rural county, and government-funded or no health insurance were inversely associated with neoadjuvant chemotherapy. In multivariable analyses, patients who received neoadjuvant chemotherapy were more likely to have a mastectomy (vs. lumpectomy) and sentinel lymph node biopsy or no nodal surgery (vs. axillary lymph node dissection). Patients who received neoadjuvant chemotherapy were more likely to receive multi-agent (vs. single-agent) chemotherapy than those who received adjuvant chemotherapy., Conclusions: Substantial differences in the utilization of neoadjuvant chemotherapy exist in women with HER2+ breast cancer, which reflect both clinical parameters and disparities. Optimal treatment strategies should be implemented equitably across sociodemographic groups., (© 2021. Society of Surgical Oncology.)

Background: This is a prospective, single-institution study to evaluate feasibility and accuracy of radar-localized reflector (RLR)-targeted axillary dissection (TAD) in node-positive breast cancer patients after neoadjuvant systemic therapy (NST)., Methods: Patients with biopsy-proven T1-2, N1-3 disease were eligible. Before NST, a marker clip and/or RLR was placed into the positive node. After NST, RLR was inserted if not placed previously. All patients underwent RLR TAD followed by axillary lymph node dissection (ALND). Primary end points of the trial were feasibility of RLR TAD and false negative rate (FNR)., Results: Between 2017 and 2021, 101 patients with N1-3 disease underwent NST. Five patients withdrew from the study, 1 was ineligible, and there were 9 technical failures, thus our final study cohort comprised 86 patients. RLR TAD was performed with probe guidance and confirmed with intraoperative specimen radiograph. After RLR TAD, ALND was performed. Median number of RLR TAD nodes removed was 2 (range 1-10), and the RLR TAD nodes remained positive in 56 patients. Median number of ALND nodes removed was 18 (range 4-46). Accounting for 9 technical failures, feasibility was 90%. All technical failures occurred with attempted placement of RLR after NST. Feasibility rate was 100% when RLR placement occurred at diagnosis. Of the evaluable 86 patients, RLR TAD accurately predicted axillary status in 83 patients, with FNR of 5.1%., Conclusion: We demonstrate high accuracy of RLR TAD, especially when RLR is placed before NST. For patients who present with N1-3 disease, this is another step towards axillary surgery de-escalation strategies., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: The COVID-19 pandemic has required new treatment paradigms to limit exposures and optimize hospital resources, including the use of neoadjuvant endocrine therapy (NAET) as bridging therapy for HR+/HER2-invasive tumors and DCIS. While this approach has been used in locally advanced disease, it is unclear how it may affect outcomes in resectable HR+/HER2- tumors., Methods: Women ≥18 years diagnosed with in situ (Tis) or non-metastatic HR+/HER2- breast cancer from March-May 2019 and 2020 were included. Fisher's exact test and two-sample t test were used to compare baseline characteristics and surgical outcomes between strata. Sub-analysis was performed between patients who received primary surgery vs a bridging NAET approach., Results: Despite similar clinical characteristics, patients in 2019 were more likely to have a surgery-first approach (75% vs 42%, P -value = .0007), receive surgery sooner (22 vs 29 days, P -value < .001), and within 60 days from diagnosis date (100% vs 85%, P -value = .0301). Neoadjuvant endocrine therapy was a more prevalent approach in 2020 (48% vs 7%, P -value < .0001). Rates of clinical to pathologic up-staging remained consistent across primary surgery vs bridging NAET subgroups ( P -value = .9253)., Discussion: Pandemic-driven treatment protocols provide a unique opportunity to assess the utility of bridging endocrine therapy for resectable HR+/HER2- tumors. Differences in clinical and pathologic staging were similar across groups and did not appear to be affected by receipt of NAET. Our limited cohort demonstrates this strategic therapeutic avenue can optimize health care utilization and may be a reasonable approach when delaying surgery is preferred.

Background: De-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) requires careful patient selection. We seek to determine predictors of nodal pathologic complete response (ypN0) among patients treated on CALGB 40601 or 40603, which tested NAC regimens in HER2+ and triple-negative breast cancer (TNBC), respectively., Patients and Methods: A total of 760 patients with stage II-III HER2+ or TNBC were analyzed. Those who had axillary surgery before NAC (N = 122), or who had missing pretreatment clinical nodal status (cN) (N = 58) or ypN status (N = 41) were excluded. The proportion of patients with ypN0 disease was estimated for those with and without breast pathologic complete response (pCR) according to pretreatment nodal status., Results: In 539 patients, the overall ypN0 rate was 76.3% (411/539) to 93.2% (245/263) in patients with breast pCR and 60.1% (166/276) with residual breast disease (RD) (P < 0.0001). For patients who were cN0 pretreatment, the ypN0 rate was 88.8% (214/241), 96.3% (104/108) with breast pCR, and 82.7% (110/133) with RD. For patients who were cN1, 66.2% (157/237) converted to ypN0, 91.7% (111/121) with breast pCR and 39.7% (46/116) with RD. For patients who were cN2/3, 65.6% (40/61) converted to ypN0, 88.2% (30/34) with breast pCR and 37.0% (10/27) with RD. On multivariable analysis, only pretreatment clinical nodal status and breast pCR/RD were associated with ypN0 status (both P < 0.0001)., Conclusions: Breast pCR and pretreatment nodal status are predictive of ypN0 axillary nodal involvement, with < 5% residual nodal disease among cN0 patients who experience breast pCR. These findings support the incorporation of axillary surgery de-escalation strategies into NAC trials., (© 2021. Society of Surgical Oncology.)

Objective: Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings., Methods: In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0-III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM ("shave" group) or not ("no shave" group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates., Results: Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the "shave" group and 200 to the "no shave" group. Median patient age was 65 years (range; 29-94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the "shave" and "no shave" groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the "shave" group were significantly less likely than those in the "no shave" group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001)., Conclusion: Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Inflammatory breast cancer (IBC) has historically been characterized by high rates of recurrence and poor survival; however, there have been significant improvements in systemic therapy. We sought to investigate modern treatment of IBC and define the yield and prognostic significance of axillary lymph nodes after neoadjuvant chemotherapy (NAC)., Methods: Women with clinical stage T4d, N0-N3, M0 IBC from 2012 to 2016 in the National Cancer Database were included. Kaplan-Meier survival curves and Cox regression were used to assess mortality by receptor subtype and nodal status., Results: We identified 5265 patients; 37% hormone receptor (HR) +/HER2 - , 19% HR +/HER2 + , 18% HR -/HER2 + , and 26% triple-negative, and 5-year overall survival was 51.6%. Only 34% were treated according to guidelines with NAC, modified radical mastectomy, and adjuvant radiation. Pathologically positive lymph nodes (ypN +) after NAC varied by subtype and clinical nodal status (cN) ranging from 82% in cN + HR +/HER2 - patients to 19% in cN0 HR -/HER2 + patients. ypN + strongly correlated with survival in all subtypes with the most pronounced impact in HR +/HER2 + patients, with 90% 5-year overall survival in ypN0 versus 66% for ypN + (HR 4.29, 95% CI 1.58-11.70, p = 0.03)., Conclusions: Five-year survival in M0 IBC is 51.6%. Positive nodes after NAC varied by subtype and clinical N status but is sufficiently high and provided meaningful prognostication in all subtypes to support continued routine pathologic assessment. Future study is warranted to identify reliable, less morbid, methods of staging the axilla in IBC patients appropriate for deescalation of axillary surgery.

Background: We examined the impact of cavity shave margins (CSMs) on margin status in patients with pure ductal carcinoma in situ (DCIS) undergoing partial mastectomy (PM)., Methods: One hundred and nine patients from 2 multicenter, randomized controlled trials were identified with pure DCIS (no invasive cancer). Surgeons performed their best PM, with specimen radiography and resection of selective margins per surgeon discretion. Patients were then randomized to have CSM resected or not. A positive margin was defined as <2 mm from ink., Results: Median patient age was 63 years; median size of DCIS was 1.20 cm; 43.6% of patients had high-grade DCIS; and 58 (53.2%) patients were randomized to take CSM. The "shave" and "no-shave" groups were well-matched for age, race, ethnicity, palpability, grade, and size of DCIS. Although 33 (56.9%) of the patients in the shave group had a positive margin before randomization, only 12 (20.7%) had a positive margin after randomization to CSM (p < 0.001). In the no-shave group, 17 patients (33.3%) had a positive margin. Controlling for size and grade of DCIS, taking CSM resulted in a nearly 65% reduction in the positive-margin rate (odds ratio 0.366; 95% CI, 0.136 to 0.981; p = 0.046). Size of DCIS remained an independent predictor of positive margins in the model (odds ratio 1.646; 95% CI, 1.227 to 2.209; p = 0.001)., Conclusions: CSM reduces positive-margin rates in patients with pure DCIS, and can be a practical solution for DCIS patients who tend to have a high rate of margin positivity., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Intraoperative radiation therapy (IORT) is a specialized form of accelerated partial breast irradiation in which a single dose of radiation is delivered to the tumor bed at the time of breast conserving surgery. With completion of radiation to the tumor bed at the time of surgery, IORT promises improved patient convenience, compliance, and quality of life. In addition, with its potentially skin-sparing properties and ability to deliver a high biologically effective dose to the tumor bed while reducing dose to nontarget tissues, IORT results in different but overall less toxicities compared with other modalities of radiation for breast cancer. However, skepticism over the role of IORT in breast cancer exists, and the 2 randomized trials that have analyzed IORT as the definitive radiation component of breast conservation therapy have shown an increase in local recurrence rates with IORT compared with whole breast irradiation, but similar rates of overall survival. In this review, we discuss the practicalities of IORT, the prospective data supporting and negating the role of IORT in lieu of whole breast irradiation, and the toxicity after IORT in early-stage breast cancer. We also review the role of IORT as a radiation boost and specific strategies for successful implementation of IORT in breast cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: In the past two decades, three prospective randomized trials demonstrated that elderly women with early stage hormone positive breast cancer had equivalent disease-specific mortality regardless of axillary surgery. In 2016, the Choosing Wisely campaign encouraged patients and providers to reconsider the role of axillary surgery in this population. We sought to identify factors that contribute to adopting non-operative management of the axilla in these patients., Materials and Methods: We performed a retrospective analysis of women ≥ 70 years old with cT1/T2, hormone positive invasive ductal carcinoma who underwent partial or total mastectomy, with/without axillary surgery, and did not receive adjuvant chemotherapy from the National Cancer Database from 2004 to 2015. We used multivariable log-binomial regression to model the risk of undergoing axillary surgery across region, care setting, and Charlson-Deyo scores, and analyzed temporal trends using Poisson regression. From 2004 to 2015, 87,342 of 99,940 women who met inclusion criteria (83%) had axillary surgery. Over time, axillary surgery increased from 78% to 88% (p < 0.001). This rise was consistent across region (p = 0.81) and care setting (p = 0.09), but flattened as age increased (p < 0.001). Omitting axillary surgery was more likely in patients treated in New England (RR 0.88, 95% CI 0.86, 0.89) and patients ≥ 85 (RR 0.66, 95% CI 0.65, 0.67)., Conclusions: Axillary surgery continues to be the preferred option of axillary management in elderly women with early stage, clinically node negative, hormone-positive, invasive breast cancer despite no survival benefit. Identifying factors to improve patient selection and dissemination of current recommendations can improve adoption of current evidence on axillary surgery in the elderly.

Purpose: Primary endocrine therapy for ductal carcinoma in situ (DCIS) as a potential alternative to surgery has been understudied. This trial explored the feasibility of a short-term course of letrozole and sought to determine whether treatment results in measurable radiographic and biologic changes in estrogen receptor (ER)-positive DCIS., Patients and Methods: A phase II single-arm multicenter cooperative-group trial was conducted in postmenopausal patients diagnosed with ER-positive DCIS without invasion. Patients were treated with letrozole 2.5 mg per day for 6 months before surgery. Breast magnetic resonance imaging (MRI) was obtained at baseline, 3 months, and 6 months. The primary end point was change in 6-month MRI enhancement volume compared with baseline., Results: Overall, 79 patients were enrolled and 70 completed 6 months of letrozole. Of these, 67 patients had MRI data available for each timepoint. Baseline MRI volumes ranged from 0.004 to 26.3 cm 3 . Median reductions from baseline MRI volume (1.4 cm 3 ) were 0.6 cm 3 (61.0%) at 3 months ( P < .001) and 0.8 cm 3 (71.7%) at 6 months ( P < .001). Consistent reductions were seen in median baseline ER H-score (228; median reduction, 15.0; P = .005), progesterone receptor H-score (15; median reduction, 85.0; P < .001), and Ki67 score (12%; median reduction, 6.3%; P = .007). Of the 59 patients who underwent surgery per study protocol, persistent DCIS remained in 50 patients (85%), invasive cancer was detected in six patients (10%), and no residual DCIS or invasive cancer was seen in nine patients (15%)., Conclusions: In a cohort of postmenopausal women with ER-positive DCIS, preoperative letrozole resulted in significant imaging and biomarker changes. These findings support future trials of extended endocrine therapy as primary nonoperative treatment of some DCIS.

Background: Despite data demonstrating the safety of omitting axillary surgery in older women with early-stage breast cancer, the incidence of axillary surgery remains high. It was hypothesized that the prevalence of nodal positivity would decrease with advancing age., Methods: The National Cancer Data Base was used to construct a cohort of adult women with early-stage, clinically node-negative, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative breast cancer treated between 2013 and 2015. Multivariable logistic regression was used to assess the relationship between age and nodal positivity, and this was stratified by the axillary surgery category. Modified Poisson regression was used to estimate the proportion of women receiving adjuvant therapy according to age and nodal status., Results: The incidence of axillary surgery among women aged 70 and older (n = 51,917) remained high nationwide (86%). There was a significant decrease in nodal positivity with advancing age in women with early-stage, ER+, clinically node-negative breast cancer from the youngest cohort up to patients aged 70 to 89 years, and this was independent of histologic subtype (ductal vs lobular), race, comorbidities, and socioeconomic factors. Overall, less than 10% of women aged 70 or older who underwent surgery had node-positive disease, regardless of axillary surgery type, and almost 95% of node-positive patients aged 70 or older were at pathological stage N1mi or N1., Conclusions: Axillary surgery may be safely omitted for many older women with ER+, clinically node-negative, early-stage breast cancer. Nodal positivity declines with advancing age, and this suggests varied biology in older patients versus younger patients., (© 2019 American Cancer Society.)

Historically, through the conduct of prospective clinical trials, breast cancer surgeons have performed less radical breast and axillary surgeries with no survival decrement to our patients. Currently, other opportunities exist for the treating breast surgeon to do less. Possibilities include active surveillance for ductal carcinoma in situ, ablative therapy for small primary breast cancers, selective omission of a sentinel node biopsy, and selective elimination of breast surgery after neoadjuvant systemic therapy. Breast surgeons must be leaders in the development and testing of effective therapy with the least intervention possible.

Benign cystic epithelial inclusions with squamous, glandular, or Müllerian phenotypes are known to occur in the axillary lymph nodes of patients with benign and malignant breast disease. Careful evaluation of hematoxylin and eosin-stained slides and correlation with the histologic findings in the ipsilateral breast are paramount in evaluation of suspected benign inclusions. In this case of ductal carcinoma in situ (DCIS) of the breast in a 73-year-old woman, DCIS also involved epithelial inclusions in an ipsilateral axillary lymph node. The recognition of these benign epithelial elements, and awareness that they can be involved by DCIS, is crucial to avoid the overdiagnosis of metastatic carcinoma.

Importance: The results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial were first reported in 2005 with a median follow-up of 6.3 years. Longer follow-up was necessary because the majority of the patients had estrogen receptor-positive tumors that may recur later in the disease course (the ACOSOG is now part of the Alliance for Clinical Trials in Oncology)., Objective: To determine whether the 10-year overall survival of patients with sentinel lymph node metastases treated with breast-conserving therapy and sentinel lymph node dissection (SLND) alone without axillary lymph node dissection (ALND) is noninferior to that of women treated with axillary dissection., Design, Setting, and Participants: The ACOSOG Z0011 phase 3 randomized clinical trial enrolled patients from May 1999 to December 2004 at 115 sites (both academic and community medical centers). The last date of follow-up was September 29, 2015, in the ACOSOG Z0011 (Alliance) trial. Eligible patients were women with clinical T1 or T2 invasive breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases., Interventions: All patients had planned lumpectomy, planned tangential whole-breast irradiation, and adjuvant systemic therapy. Third-field radiation was prohibited., Main Outcomes and Measures: The primary outcome was overall survival with a noninferiority hazard ratio (HR) margin of 1.3. The secondary outcome was disease-free survival., Results: Among 891 women who were randomized (median age, 55 years), 856 (96%) completed the trial (446 in the SLND alone group and 445 in the ALND group). At a median follow-up of 9.3 years (interquartile range, 6.93-10.34 years), the 10-year overall survival was 86.3% in the SLND alone group and 83.6% in the ALND group (HR, 0.85 [1-sided 95% CI, 0-1.16]; noninferiority P = .02). The 10-year disease-free survival was 80.2% in the SLND alone group and 78.2% in the ALND group (HR, 0.85 [95% CI, 0.62-1.17]; P = .32). Between year 5 and year 10, 1 regional recurrence was seen in the SLND alone group vs none in the ALND group. Ten-year regional recurrence did not differ significantly between the 2 groups., Conclusions and Relevance: Among women with T1 or T2 invasive primary breast cancer, no palpable axillary adenopathy, and 1 or 2 sentinel lymph nodes containing metastases, 10-year overall survival for patients treated with sentinel lymph node dissection alone was noninferior to overall survival for those treated with axillary lymph node dissection. These findings do not support routine use of axillary lymph node dissection in this patient population based on 10-year outcomes., Trial Registration: clinicaltrials.gov Identifier: NCT00003855.

Background: Management of the axilla in stage II/III breast cancer undergoing neoadjuvant systemic therapy (NST) is controversial. To understand current patterns of care, we collected axillary data from 2 NST trials: HER2-positive (Cancer and Leukemia Group B [CALGB] 40601) and triple-negative (CALGB 40603)., Study Design: Axillary evaluation pre- and post-NST was per the treating surgeon and could include sentinel node biopsy. Post-NST, node-positive patients were recommended to undergo axillary lymph node dissection (ALND). We report pre-NST histopathologic nodal evaluation and post-NST axillary surgical procedures with correlation to clinical and pathologic nodal status., Results: Seven hundred and forty-two patients were treated, 704 had complete nodal data pre-NST and post-NST. Pre-NST, 422 (60%) of 704 patients underwent at least 1 procedure for axillary node evaluation (total of 468 procedures): fine needle aspiration (n = 234; 74% positive), core needle biopsy (n = 138; 72% positive), and sentinel node biopsy (n = 96; 33% positive). Pre-NST, 304 patients were considered node-positive. Post-NST, 304 of 704 patients (43%) underwent sentinel node biopsy; 44 were positive and 259 were negative (29 and 36 patients, respectively, had subsequent ALND). Three hundred and ninety-one (56%) patients went directly to post-NST ALND and 9 (1%) pre-NST node-positive patients had no post-NST axillary procedure. Post-NST, 170 (24%) of the 704 patients had residual axillary disease. Agreement between post-NST clinical and radiologic staging and post-NST histologic staging was strongest for node-negative (81%) and weaker for node-positive (N1 31%, N2 29%), with more than half of the clinically node-positive patients found to be pathologic negative (p < 0.001)., Conclusions: Our results suggest there is no widely accepted standard for axillary nodal evaluation pre-NST. Post-NST staging was highly concordant in patients with N0 disease, but poorly so in node-positive disease. Accurate methods are needed to identify post-NST patients without residual axillary disease to potentially spare ALND., (Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Fat transfer is an increasingly popular method for refining postmastectomy breast reconstructions. However, concern persists that fat transfer may promote disease recurrence. Adipocytes are derived from adipose-derived stem cells and express adipocytokines that can facilitate active breast cancer cells in laboratory models. The authors sought to evaluate the association between fat transfer to the reconstructed breast and cancer recurrence in patients diagnosed with local or regional invasive breast cancers., Methods: A multicenter, case-cohort study was performed. Eligible patients from four centers (Memorial Sloan Kettering, M. D. Anderson Cancer Center, Alvin J. Siteman Cancer Center, and the University of Chicago) were identified by each site's institutional tumor registry or cancer data warehouse. Eligibility criteria were as follows: mastectomy with immediate breast reconstruction between 2006 and 2011, age older than 21 years, female sex, and incident diagnosis of invasive ductal carcinoma (stage I, II, or III). Cases consisted of all recurrences during the study period, and controls consisted of a 30 percent random sample of the study population. Cox proportional hazards regression was used to evaluate for association between fat transfer and time to recurrence in bivariate and multivariate models., Results: The time to disease recurrence unadjusted hazard ratio for fat transfer was 0.99 (95 percent CI, 0.56 to 1.7). After adjustment for age, body mass index, stage, HER2/Neu receptor status, and estrogen receptor status, the hazard ratio was 0.97 (95 percent CI, 0.54 to 1.8)., Conclusion: In this population of breast cancer patients who had mastectomy with immediate reconstruction, fat transfer was not associated with a higher risk of cancer recurrence., Clinical Question/level of Evidence: Therapeutic, III.

Objective: To assess how informed patients are about breast reconstruction, and how involved they are in decision making., Summary Background Data: Breast reconstruction is an important treatment option for patients undergoing mastectomy. Wide variations in who gets reconstruction, however, have led to concerns about decision making., Methods: We conducted a prospective cross-sectional study of patients planning mastectomy at a single site, over 20 months. Before surgery, patients completed a survey with validated scales to assess knowledge about breast reconstruction and involvement in decision making. Factors associated with knowledge were examined in a multivariable linear regression model., Results: A total of 145 patients enrolled (77% enrollment rate), and 126 remained eligible. The overall knowledge score was 58.5% (out of 100%). Knowledge about risk of complications was especially low at 14.3%. Knowledge did not differ by treatment (reconstruction or not). On multivariable analysis, non-white race was independently associated with lower knowledge. Most patients (92.1%) reported some discussion with a provider about reconstruction, and most (90.4%) reported being asked their preference. More patients reported discussing the advantages of reconstruction (57.9%) than the disadvantages (27.8%)., Conclusions: Women undergoing mastectomy in this sample were highly involved in decision making, but had major deficits in knowledge about the procedure. Knowledge about the risk of complications was particularly low. Providers seemed to have discussed the advantages of reconstruction more than its disadvantages.

Objective: It had been previously shown that patients who receive neoadjuvant systemic therapy (NST) are more likely to undergo breast-conserving therapy (BCT) than those who have primary surgery. However, the frequency with which patients who are not BCT-eligible prior to NST convert to BCT-eligible with treatment is unknown. To document this conversion rate in a subset of patients expected to have a high clinical response rate to NST, we studied surgical assessment and management of patients enrolled on a randomized neoadjuvant trial for stage II-III HER2-positive breast cancer (HER2 + BC)(CALGB 40601)., Methods: The treating surgeon assessed BCT candidacy based on clinico-radiographic criteria both before and after NST. Definitive breast surgical management was at surgeon and patient discretion. We sought to determine (1) the conversion rate from BCT-ineligible to BCT-eligible (2) the percentage of BCT-eligible patients who chose breast conservation, and (3) the rate of successful BCT. We also evaluated surgeon-determined factors for BCT-ineligibility and the correlation between BCT eligibility and pathologic complete response (pCR)., Results: Of 292 patients with pre- and post-NST surgical assessments, 59 % were non-BCT candidates at baseline. Of the 43 % of these patients who converted with NST, 67 % opted for BCT, with an 80 % success rate. NST increased the BCT-eligible rate from 41 to 64 %. Common factors cited for BCT-ineligibility prior to NST including tumor size (56 %) and probable poor cosmetic outcome (26 %) were reduced by 67 and 75 %, respectively, with treatment, while multicentricity, the second most common factor (33 %), fell by only 16 %. Since 23 % of the BCT-eligible patients chose mastectomy, BCT was the final surgical procedure in just 40 % of the patients. Patients considered BCT-eligible both at baseline and after NST had a pCR rate of 55 %, while patients who were BCT-ineligible prior to NST had the same pCR rate (44 %) whether they converted to BCT-eligible or not., Conclusions: Many patients with HER2 + BC deemed ineligible for BCT at baseline can be converted to BCT-eligible with NST; excluding patients with multicentric disease substantially increases that percentage. In converted patients who opt for BCT, the success rate is similar to that of patients considered BCT-eligible at baseline. Whether a BCT-ineligible patient converts to BCT eligibility or not does not appear to affect the likelihood of achieving a pCR. Despite the efficacy of NST in this patient cohort, only 40 % of patients had successful BCT; further research into why BCT-eligible patients often opt for mastectomy is needed., Competing Interests: All the authors declare no conflict of interest.

Purpose: American College of Surgeons Oncology Group Z1071 was a prospective trial evaluating the false negative rate of sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) in breast cancer patients with initial node-positive disease. Radiation therapy (RT) decisions were made at the discretion of treating physicians, providing an opportunity to evaluate variability in practice patterns following NAC., Methods and Materials: Of 756 patients enrolled from July 2009 to June 2011, 685 met all eligibility requirements. Surgical approach, RT, and radiation field design were analyzed based on presenting clinical and pathologic factors., Results: Of 401 node-positive patients, mastectomy was performed in 148 (36.9%), mastectomy with immediate reconstruction in 107 (26.7%), and breast-conserving surgery (BCS) in 146 patients (36.4%). Of the 284 pathologically node-negative patients, mastectomy was performed in 84 (29.6%), mastectomy with immediate reconstruction in 69 (24.3%), and BCS in 131 patients (46.1%). Bilateral mastectomy rates were higher in women undergoing reconstruction than in those without (66.5% vs 32.2%, respectively, P<.0001). Use of internal mammary RT was low (7.8%-11.2%) and did not differ between surgical approaches. Supraclavicular RT rate ranged from 46.6% to 52.2% and did not differ between surgical approaches but was omitted in 193 or 408 node-positive patients (47.3%). Rate of axillary RT was more frequent in patients who remained node-positive (P=.002). However, 22% of patients who converted to node-negative still received axillary RT. Post-mastectomy RT was more frequently omitted after reconstruction than mastectomy (23.9% vs 12.1%, respectively, P=.002) and was omitted in 19 of 107 patients (17.8%) with residual node-positive disease in the reconstruction group., Conclusions: Most clinically node-positive patients treated with NAC undergoing mastectomy receive RT. RT is less common in patients undergoing reconstruction. There is wide variability in RT fields. These practice patterns conflict with expert recommendations and ongoing trial guidelines. There is a significant need for greater uniformity and guidelines regarding RT following NAC., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Dual human epidermal growth factor receptor 2 (HER2) targeting can increase pathologic complete response rates (pCRs) to neoadjuvant therapy and improve progression-free survival in metastatic disease. CALGB 40601 examined the impact of dual HER2 blockade consisting of trastuzumab and lapatinib added to paclitaxel, considering tumor and microenvironment molecular features., Patients and Methods: Patients with stage II to III HER2-positive breast cancer underwent tumor biopsy followed by random assignment to paclitaxel plus trastuzumab alone (TH) or with the addition of lapatinib (THL) for 16 weeks before surgery. An investigational arm of paclitaxel plus lapatinib (TL) was closed early. The primary end point was pCR in the breast; correlative end points focused on molecular features identified by gene expression-based assays., Results: Among 305 randomly assigned patients (THL, n = 118; TH, n = 120; TL, n = 67), the pCR rate was 56% (95% CI, 47% to 65%) with THL and 46% (95% CI, 37% to 55%) with TH (P = .13), with no effect of dual therapy in the hormone receptor-positive subset but a significant increase in pCR with dual therapy in those with hormone receptor-negative disease (P = .01). The tumors were molecularly heterogeneous by gene expression analysis using mRNA sequencing (mRNAseq). pCR rates significantly differed by intrinsic subtype (HER2 enriched, 70%; luminal A, 34%; luminal B, 36%; P < .001). In multivariable analysis treatment arm, intrinsic subtype, HER2 amplicon gene expression, p53 mutation signature, and immune cell signatures were independently associated with pCR. Post-treatment residual disease was largely luminal A (69%)., Conclusion: pCR to dual HER2-targeted therapy was not significantly higher than single HER2 targeting. Tissue analysis demonstrated a high degree of intertumoral heterogeneity with respect to both tumor genomics and tumor microenvironment that significantly affected pCR rates. These factors should be considered when interpreting and designing trials in HER2-positive disease., Competing Interests: Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2015 by American Society of Clinical Oncology.)

Background: Increasingly, women with stage 2 and 3 breast cancers receive neoadjuvant therapy, after which many are eligible for breast-conserving surgery (BCS). The question often arises as to whether BCS, if achievable, provides adequate local control. We report the results of local recurrence (LR) from the I-SPY 1 Trial in the setting of maximal multidisciplinary treatment where approximately 50 % of patients were treated with BCS., Methods: We analyzed data from the I-SPY 1 Trial. Women with tumors ≥3 cm from nine clinical breast centers received neoadjuvant doxorubicin, cyclophosphamide and paclitaxel followed by definitive surgical therapy, and radiation at physician discretion. LR following mastectomy and BCS were analyzed in relation to clinical characteristics and response to therapy as measured by residual cancer burden., Results: Of the 237 patients enrolled in the I-SPY 1 Trial, 206 were available for analysis. Median tumor size was 6.0 cm, and median follow-up was 3.9 years. Fourteen patients (7 %) had LR and 45 (22 %) had distant recurrence (DR). Of the 14 patients with LR, nine had synchronous DR; one had DR > 2 years later. Only four (2 % of evaluable patients) had LR alone. The rate of LR was low after mastectomy and after BCS, even in the setting of significant residual disease., Conclusions: Overall, these patients at high risk for early recurrence, treated with maximal multidisciplinary treatment, had low LR. Recurrence was associated with aggressive biological features such as more advanced stage at presentation, where LR occurs most frequently in the setting of DR.

Importance: Sentinel lymph node (SLN) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection (ALND) for patients with clinically node-negative (cN0) breast cancer. The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies., Objective: To determine the false-negative rate (FNR) for SLN surgery following chemotherapy in women initially presenting with biopsy-proven cN1 breast cancer., Design, Setting, and Patients: The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had clinical T0 through T4, N1 through N2, M0 breast cancer and received neoadjuvant chemotherapy. Following chemotherapy, patients underwent both SLN surgery and ALND. Sentinel lymph node surgery using both blue dye (isosulfan blue or methylene blue) and a radiolabeled colloid mapping agent was encouraged., Main Outcomes and Measures: The primary end point was the FNR of SLN surgery after chemotherapy in women who presented with cN1 disease. We evaluated the likelihood that the FNR in patients with 2 or more SLNs examined was greater than 10%, the rate expected for women undergoing SLN surgery who present with cN0 disease., Results: Seven hundred fifty-six women were enrolled in the study. Of 663 evaluable patients with cN1 disease, 649 underwent chemotherapy followed by both SLN surgery and ALND. An SLN could not be identified in 46 patients (7.1%). Only 1 SLN was excised in 78 patients (12.0%). Of the remaining 525 patients with 2 or more SLNs removed, no cancer was identified in the axillary lymph nodes of 215 patients, yielding a pathological complete nodal response of 41.0% (95% CI, 36.7%-45.3%). In 39 patients, cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND, resulting in an FNR of 12.6% (90% Bayesian credible interval, 9.85%-16.05%)., Conclusions and Relevance: Among women with cN1 breast cancer receiving neoadjuvant chemotherapy who had 2 or more SLNs examined, the FNR was not found to be 10% or less. Given this FNR threshold, changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND., Trial Registration: clinicaltrials.gov Identifier: NCT00881361.

Background: Intraoperative radiation therapy (IORT) allows delivery of high-dose radiation at the time of lumpectomy, potentially sparing adjuvant daily radiation. A phase 2 study of pre-excision IORT was performed for early-stage breast cancer., Methods: Patients ≥ 48 years of age with invasive ductal carcinoma, ≤ 3 cm, and clinically node-negative were eligible for this study, which was approved by institutional review board. Ultrasound was used to select electron energy and cone size to cover the tumor plus 1.5- to 2.0-cm lateral margins and 1-cm-deep margins (90% isodose). Fifteen Gy was delivered with a Mobetron irradiator, and immediate needle-localized partial mastectomy followed. Local event results were updated using the Kaplan-Meier method., Results: A total of 53 patients received IORT alone. Median age was 63 years, and median tumor size was 1.2 cm. Of these, 81% were positive for estrogen receptor or progesterone receptor, 11% were positive for human epidermal growth factor receptor 2, and 15% were triple-negative. Also, 42%, 49%, and 9% would have fallen into the Suitable, Cautionary, and Unsuitable groups, respectively, of the American Society of Therapeutic Radiation Oncology consensus statement for accelerated partial breast irradiation. Median follow-up was 69 months. Ipsilateral events occurred in 8 of 53 patients. The 6-year actuarial rate of ipsilateral events was 15% (95% confidence interval = 7%-29%). The crude event rate for Suitable and Cautionary groups was 1 of 22 (5%) and 7 of 26 (27%), respectively. Overall survival was 94.4%, and breast cancer-specific survival was 100%., Conclusions: The rate of local events in this study is a matter of concern, especially in the Cautionary group. On the basis of these findings, pre-excision IORT, as delivered in this study, may not provide adequate local control for less favorable early-stage breast cancers., (Copyright © 2013 American Cancer Society.)

Purpose: This phase I study assessed the toxicity and safety of combining daily lapatinib with radiation therapy. Sequential tumor biopsies were obtained to evaluate changes in biomarkers, such as epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2) signaling pathways., Methods: Eligibility for this dose-escalation study included unresectable and locally recurrent or chemotherapy-refractory and locally advanced breast cancer, and adequate organ function. Patients underwent three serial biopsies: at baseline, after 1 week of lapatinib alone, and after 1 week of lapatinib and radiation. Endpoints included determination of toxicity, maximum tolerated dose, and analysis of the effect of lapatinib with or without radiation on EGFR and HER2 signaling pathways by immunohistochemistry., Results: Doses of lapatinib up to 1,500 mg/day were well tolerated. Toxicity of grade 3 or more was limited to radiation dermatitis and pain. Out of 19 patients treated, in field responses per response evaluation criteria in solid tumors criteria were complete in four patients and partial in six patients. Serial biopsies were obtained in 16 patients with no complications. Total Her2 was relatively unchanged while phospho-Her2, phospho-Akt, and phospho-ERK showed variable responses to both lapatinib alone and dual therapy with lapatinib and radiation., Conclusions: The combination of lapatinib and radiation was well tolerated in this patient cohort. Overall local response rates were comparable to those reported in other studies in this patient population. Biopsies were safely performed at all time points. Inhibition of HER2 and downstream signaling pathways was identified, although no strong correlation with response was seen.

Background: Practice variation in breast cancer surgery has raised concerns about the quality of treatment decisions. We sought to evaluate the quality of decisions about surgery for early-stage breast cancer by measuring patient knowledge, concordance between goals and treatments, and involvement in decisions., Study Design: A mailed survey of stage I/II breast cancer survivors was conducted at 4 sites. The Decision Quality Instrument measured knowledge, goals, and involvement in decisions. A multivariable logistic regression model of treatment was developed. The model-predicted probability of mastectomy was compared with treatment received for each patient. Concordance was defined as having mastectomy and predicted probability >0.5 or partial mastectomy and predicted probability <0.5. Frequency of discussion about partial mastectomy was compared with discussion about mastectomy using chi-square tests., Results: Four hundred and forty patients participated (59% response rate). Mean overall knowledge was 52.7%; 45.9% knew that local recurrence risk is higher after breast conservation and 55.7% knew that survival is equivalent for the 2 options. Most participants (89.0%) had treatment concordant with their goals. Participants preferring mastectomy had lower concordance (80.5%) than those preferring partial mastectomy (92.6%; p = 0.001). Participants reported more frequent discussion of partial mastectomy and its advantages than of mastectomy, and 48.6% reported being asked their preference., Conclusions: Breast cancer survivors had major knowledge deficits, and those preferring mastectomy were less likely to have treatment concordant with goals. Patients perceived that discussions focused on partial mastectomy, and many were not asked their preference. Improvements in the quality of decisions about breast cancer surgery are needed., (Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Gene expression studies have identified distinct breast cancer subtypes, including luminal A, luminal B, Her2-enriched, and Basal-like, which differ in survival. The impact of subtypes on locoregional recurrence (LRR) after neoadjuvant chemotherapy for locally advanced breast cancer is unknown., Methods: A total of 149 patients with stage II and III breast cancer with known ER, PR, and HER2 who underwent neoadjuvant chemotherapy from 1991 to 2005 were analyzed. We used clinical assays to distinguish luminal A (ER or PR+/HER2-, n = 55), luminal B (ER or PR+/HER2+, n = 25), HER2 (ER and PR-/HER2+, n = 20), and Basal-like (ER, PR, and HER2-, n = 49) subtypes. Covariates associated with LRR were evaluated by logistic regression and differences between subtypes tested using Wald χ(2)., Results: Median follow-up was 55 months. Forty-nine (33%) patients had breast conservation (BCT) with radiation, 82 (55%) had a mastectomy with radiation, and 18 (12%) had a mastectomy alone. Eighty-eight (59%) were clinically node positive. A pathologic complete response was seen in 39 (26%) patients. LRR was identified in 11 (7%) patients: 2 after BCT (4%) and 9 after mastectomy (9%). LRR rates by subtype are as follows: luminal A 2 of 55 (4%), luminal B 1 of 25 (4%), Her2 1 of 20 (5%), and basal-like 7 of 49 (14%). Compared with all other subtypes, basal-like patients were more likely to have a LRR (7/49 (14%) vs. 4/100 (4%), p = 0.03)., Conclusions: Molecular subtype predicts LRR with basal-like patients more likely to develop LRR. These patients may be candidates for investigation with novel chemotherapy regimens and radiation sensitizing agents, which may offer improvement in local control.

Background: Multiple partial breast radiotherapy techniques are available. We have previously presented the technical details of our procedure of delivering partial breast irradiation with a single fraction of intraoperative radiotherapy (IORT) targeting the tumor in situ prior to partial mastectomy. This study details our completed, single-institution trial., Materials and Methods: An IRB-approved, DSMB-monitored phase II trial was performed with the following inclusion criteria: women age ≥48, ultrasound-visible invasive ductal cancers <3 cm, clinically negative axillary nodes. IORT was delivered using mobile electron irradiator, at least a 1.5-cm radial and 1-cm deep margin; patients received 15 Gy and immediately underwent partial mastectomy. Ipsilateral breast recurrence was classified as true/marginal, elsewhere in the breast or nodal basin. Kaplan-Meier methods were used to estimate survival functions and exact 95% confidence intervals are reported., Results: Between 2003 and 2007, 71 women underwent IORT (median follow-up: 3.5 years). For patients with tumor-involved or close margins, additional therapy was required: 7 patients, total mastectomy; 11, whole breast radiation. Four women experienced invasive ipsilateral breast failures (1 new primary, 3 margin recurrences) for a 3-year local control rate of 49 of 53 (94.8%; 95% confidence interval 92.4% [95% CI] 84.2–98.3%), actuarial three-year in breast recurrence was 8% (95% CI 2–18%), and breast cancer-specific survival was 100%., Conclusions: Intraoperative radiotherapy delivered to an in situ tumor is feasible, but our local control rate at 3.5 years is concerning. Possible changes to this technique to improve local control rates include better preoperative imaging (MRI), routine intraoperative ultrasound, and improved IORT delivery (larger cone, increased dose).

Purpose: Determine cosmetic outcome and toxicity profile of intraoperative radiation delivered before tumor excision for patients with early-stage breast cancer., Methods and Materials: Patients age 48 or older with ultrasound-visible invasive ductal cancers <3 cm and clinically negative lymph nodes were eligible for treatment on this institutional review board-approved Phase II clinical trial. Treatment planning ultrasound was used to select an electron energy and cone size sufficient to cover the tumor plus a 1.5- to 2.0-cm circumferential margin laterally and a 1-cm-deep margin with the 90% isodose line. The dose was prescribed to a nominal 15 Gy and delivered using a Mobetron electron irradiator before tumor excision by segmental mastectomy. Physician- and patient-assessed cosmetic outcome and patient satisfaction were determined by questionnaire., Results: From March 2003 to July 2007, 71 patients were treated with intraoperative radiation therapy. Of those, 56 patients were evaluable, with a median follow-up of 3.1 years (minimum 1 year). Physician and patient assessment of cosmesis was "good or excellent" (Radiation Therapy Oncology Group cosmesis scale) in 45/56 (80%) and 32/42 (76%) of all patients, respectively. Eleven patients who received additional whole breast radiation had similar rates of good or excellent cosmesis: 40/48 (83%) and 29/36 (81%), respectively). Grade 1 or 2 acute toxicities were seen in 4/71 (6%) patients. No Grade 3 or 4 toxicities or serious adverse events have been seen., Conclusion: Intraoperative radiotherapy delivered to an in situ tumor is feasible with acceptable acute tolerance. Patient and physician assessment of the cosmetic outcome is good to excellent., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The purpose of this survey was to ascertain the most common surgical practices for attaining negative (tumor-free) surgical margins in patients desiring breast-conservation treatment for breast cancer to see if a consensus exists for optimal treatment of patients., Study Design: We sent a survey to 1,000 surgeons interested in the treatment of breast cancer. Three hundred eighty-one surgeons responded to this survey and 351 were used for the analysis (response rate of 38%)., Results: Answers showed a large variety in clinical practices among breast surgeons across the country. There was little intraoperative margin analysis; only 48% of surgeons examine the margins grossly with a pathologist and even fewer used frozen sections or imprint cytology. Decisions to reexcise specific margins varied greatly. For example, 57% of surgeons would never reexcise for a positive deep margin, but 53% would always reexcise for a positive anterior margin. Most importantly, there was a large range in answers about acceptable margins with ductal carcinoma in situ and invasive carcinoma. Fifteen percent of surgeons would accept any negative margin, 28% would accept a 1-mm negative margin, 50% would accept a 2-mm negative margin, 12% would accept a 5-mm negative margin, and 3% would accept a 10-mm negative margin., Conclusions: Results of this survey highlight the wide variety of practice patterns in the US for handling surgical margins in breast-conservation treatment. This issue remains controversial, with no prevailing standard of care. Consequently, additional study is needed in the modern era of multimodality treatment to examine the minimal amount of surgical treatment necessary, in conjunction with chemotherapy and radiation, to attain adequate local control rates in breast-conservation treatment.

Purpose: Gene expression analysis identifies several breast cancer subtypes. We examined the relationship of neoadjuvant chemotherapy response to outcome among these breast cancer subtypes., Experimental Design: We used immunohistochemical profiles [human epidermal growth factor receptor 2-positive (HER2+)/hormone receptor-negative for HER2+/estrogen receptor-negative (ER-), hormone receptor and HER2- for basal-like, hormone receptor-positive for luminal] to subtype a prospectively maintained data set of patients with breast cancer treated with neoadjuvant anthracycline-based (doxorubicin plus cyclophosphamide, AC) chemotherapy. We analyzed each subtype for clinical and pathologic response to neoadjuvant chemotherapy and examined the relationship of response to distant disease-free survival and overall survival., Results: Of the 107 patients tested, 34 (32%) were basal-like, 11 (10%) were HER2+/ER-, and 62 (58%) were luminal. After neoadjuvant AC, 75% received subsequent chemotherapy and all received endocrine therapy if hormone receptor-positive. The chemotherapy regimen and pretreatment stage did not differ by subtype. Clinical response to AC was higher among the HER2+/ER- (70%) and basal-like (85%) than the luminal subtypes (47%; P < 0.0001). Pathologic complete response occurred in 36% of HER2+/ER-, 27% of basal-like, and 7% of luminal subtypes (P = 0.01). Despite initial chemosensitivity, patients with the basal-like and HER2+/ER- subtypes had worse distant disease-free survival (P = 0.04) and overall survival (P = 0.02) than those with the luminal subtypes. Regardless of subtype, only 2 of 17 patients with pathologic complete response relapsed. The worse outcome among basal-like and HER+/ER- subtypes was due to higher relapse among those with residual disease (P = 0.003)., Conclusions: Basal-like and HER2+/ER- subtypes are more sensitive to anthracycline-based neoadjuvant chemotherapy than luminal breast cancers. Patients that had pathologic complete response to chemotherapy had a good prognosis regardless of subtype. The poorer prognosis of basal-like and HER2+/ER- breast cancers could be explained by a higher likelihood of relapse in those patients in whom pathologic complete response was not achieved.

Introduction: Intraoperative radiotherapy (IORT) has the potential to eliminate the access problems associated with standard 6-week post-operative external beam radiotherapy for patients with breast cancer. However, accurate delivery of the IORT dose for breast cancer has been problematic due to difficulty estimating the tumor bed after tumor removal and tissue re-approximation. We are investigating the feasibility of partial breast irradiation using a single fraction of IORT delivered to the tumor in vivo prior to surgical resection., Methods: In a trial, approved by the University of North Carolina School of Medicine Institutional Review Board, patients > or =55 years old with infiltrating ductal carcinoma without an extensive intraductal component with an overall tumor size < or =3.0 cm receive a single dose of IORT in place of standard post-operative radiotherapy., Results: All patients undergo preoperative ultrasonography to define the target volume. In a standard operating room, the tumor is exposed through a standard partial mastectomy incision. IORT is then delivered using a mobile, self-shielded, magnetron-driven X-band linear accelerator (Intraop Corp, Santa Clara, CA, USA). 15 Gy is delivered to the 90% isodose line covering the tumor with a 1 cm margin anterior-posterior and 2 cm margins laterally. After IORT, partial mastectomy is performed in the usual manner., Conclusions: IORT for breast cancer, delivered to the exposed tumor in vivo, is feasible and allows accurate estimation of the tumor bed. Further follow-up is ongoing to determine the efficacy of this approach.

Background: Accelerated partial breast irradiation (APBI) has gained widespread interest as a means of improving the convenience and availability of breast conserving radiotherapy. Intraoperative radiation therapy (IORT) is an APBI technique that delivers breast radiotherapy as a single dose at the time of partial mastectomy. We adapted the technique of Veronesi to deliver IORT prior to tumor excision to improve delivery to the region at risk and reduce the volume of normal tissue irradiated., Methods: Patients age >or=55 with ultrasonographically defined tumors

The diagnosis of breast cancer or melanoma in a pregnant patient presents some unique and difficult challenges for both patients and providers. Lymphatic mapping and sentinel lymph node (SLN) biopsy has become an attractive alternative to elective lymphadenectomy procedures for patients with breast cancer and melanoma. However, there is no data on the safety or utility of sentinel node mapping in pregnant patients. Therefore, we reviewed our experience with mapping in gravid patients. Academic institutions throughout North Carolina were asked to contribute cases of mapping performed during pregnancy. A total of nine women underwent sentinel node mapping during pregnancy. All nine were Caucasian with an average age of 32. SLN were found in all cases and mapping procedures were for breast cancer (three), and melanoma (six). There were no adverse reactions to the SLN procedures and one patient developed a seroma at a biopsy site. All went on to have term deliveries without known adverse effects. This limited experience shows that SLN mapping procedures are feasible in pregnant patients. However, this is not a general endorsement of such procedures in pregnant patients. We suggest that potential risks of vital dye or radioactive tracers be clearly explained to the parents when the mother is a candidate for a mapping procedure, and be balanced against the risk of delaying therapy or omitting nodal staging.

Background: Retrieval of fewer than 10 lymph nodes at axillary dissection (ALND) for breast cancer can represent anatomic variation or inadequate dissection. We postulated that despite aggressive ALND, a lower lymph node count is more frequent after neoadjuvant chemotherapy., Methods: Patients who received neoadjuvant chemotherapy followed by ALND were compared with patients who received surgery first. All patients received a level I and II ALND at a single institution by one of the breast surgeons. The number of nodes retrieved at ALND was dichotomized into categories (< 10 and > or = 10), and compared using Fisher exact test., Results: A total of 143 neoadjuvant and 170 surgery-first patients were studied. Patients treated with neoadjuvant chemotherapy were significantly more likely to have fewer than 10 lymph nodes retrieved at ALND than were the surgery-first patients (19/143 or 13% vs. 6/170 or 4%, P = .003)., Conclusions: A low lymph node count is more common in patients after treatment with neoadjuvant chemotherapy and should not be assumed to represent an incomplete ALND.

Background: The prognostic significance of micrometastasis after neoadjuvant chemotherapy for locally advanced breast cancer is unknown. We examined the residual lymph node metastasis size in patients after treatment with neoadjuvant chemotherapy to determine the relevance of metastasis size on outcome., Methods: Stage II/III breast cancer patients treated with neoadjuvant chemotherapy at our institution from 1991 to 2002 were included. We examined the relationship of postneoadjuvant chemotherapy lymph node metastasis size and number with distant disease-free survival (DDFS) and overall survival (OS)., Results: In 122 patients with a median follow-up of 5.4 years, we found not only that patients with an increasing number of residual positive nodes had progressively worse DDFS and OS (P < .0001 for both) compared with patients with negative nodes, but also that the size of the largest lymph node metastasis was associated with worse DDFS and OS (P < .0001 for both) in both univariate and multivariate analysis. Compared with negative nodes, even lymph node micrometastasis (<2 mm) was associated with worsened DDFS and OS (adjusted P = .02 and P = .005, respectively)., Conclusions: Residual micrometastatic disease in the axillary lymph nodes after neoadjuvant chemotherapy is predictive of worse prognosis than negative nodes. In this study, the lymph node metastasis size and the number of involved lymph nodes were independent powerful predictors of DDFS and OS.

Background: In patients with breast cancer who choose mastectomy with immediate reconstruction, the sentinel lymph node (SLN) status on permanent histology may complicate treatment if a metastasis is found. The purpose of this study was to determine how performing an SLN biopsy (SLNB) before the definitive operation would influence subsequent surgical procedures., Methods: Our SLN database was searched for patients who underwent staged SLNB with subsequent mastectomy between 2001 and 2004., Results: Twenty-five patients with 27 breast cancers underwent SLNB before mastectomy. Of them, 9 of 27 (33%) were node positive. All 9 patients underwent modified radical mastectomy. Three node-positive patients did not undergo immediate reconstruction. Of the remaining 6 node-positive patients, 5 underwent reconstruction with autologous tissue rather than a tissue expander. In contrast, 6 of 16 (37%) node-negative patients underwent reconstruction with a tissue expander., Conclusions: Staged SLNB assists in selecting the appropriate operation in patients who are considering immediate reconstruction.

Background: Lymphatic mapping and sentinel lymphadenectomy (LM/SL) accurately evaluates the axilla in patients with small breast cancers. LM/SL in patients with large breast cancers is controversial. We examined the accuracy of LM/SL prior to neoadjuvant chemotherapy in patients with large (>3.5 cm) breast cancers., Methods: Patients with large breast cancers underwent LM/SL prior to neoadjuvant chemotherapy using 99m-technetium radiocolloid and isosulfan-blue dye technique., Results: Twenty-one patients with large (median 5.0 cm) breast cancers underwent LM/SL prior to neoadjuvant chemotherapy. Twelve patients had a tumor-free sentinel node (SN) and received doxorubicin-based chemotherapy; 9 patients had disease in the SN and received doxorubicin followed by a taxane. No patient progressed while receiving neoadjuvant chemotherapy, nor has there been an axillary recurrence (median 36 months)., Conclusions: LM/SL performed prior to neoadjuvant chemotherapy in patients with large breast cancers is an accurate method of axillary staging. Axillary staging prior to neoadjuvant chemotherapy may have prognostic and therapeutic implications.

Background: Response to neoadjuvant chemotherapy is used as an intermediate endpoint for breast cancer relapse and survival. Most breast cancer response classification systems use pathologic complete response, either alone or in conjunction with clinical assessments, to categorize response. We examined the ability of the revised 2003 American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system, which considers both the number of involved axillary lymph nodes and the extent of tumor in the breast to predict patient survival after neoadjuvant chemotherapy for breast cancer., Methods: We assessed the pathologic stage of residual tumor in 132 patients with nonmetastatic breast cancer after they had undergone neoadjuvant chemotherapy and examined the association between AJCC TNM stage and subsequent distant disease-free survival and overall survival. All statistical tests were two-sided., Results: At a median follow-up of 5 years, pathologic stage in the surgical specimens after neoadjuvant chemotherapy using the revised AJCC system was strongly associated with both distant disease-free survival and overall survival. A higher pathologic stage of residual tumor after neoadjuvant chemotherapy was associated with a statistically significant lower rate of distant disease-free survival (stage 0: 95%, stage I: 84%, stage II: 72%, and stage III: 47%; Ptrend < .001). The 5-year distant disease-free survival for patients with residual stage IIIC tumors was only 18% (95% CI = 0% to 36%)., Conclusion: Classification of residual tumor in the breast and axillary surgical specimens after neoadjuvant chemotherapy using the revised AJCC TNM system is useful for predicting distant relapse and survival.

Young women who carry a BRCA mutation face difficult decisions regarding radiologic screening modalities and prophylactic surgery. Decisions regarding these choices may have short and/or long-term consequences and significant impacts on breast cancer risk. A comprehensive review of currently available data supports the following recommendations for young women with BRCA mutations: perform monthly self breast exam, obtain clinical breast exam 2-4 times per year, discuss annual imaging options with a breast specialist, complete child-bearing by 35 with subsequent prophylactic oopherectomy, avoid hormone replacement therapy, and consider prophylactic mastectomy.

Background: The purpose of this study was to evaluate the efficacy of high-resolution axillary ultrasound in detecting axillary lymph node metastases after neoadjuvant chemotherapy in patients with locally advanced breast cancer., Methods: Fifty-three patients with stage II or III breast cancer undergoing neoadjuvant chemotherapy who had a physical examination, high-resolution axillary ultrasound, and axillary lymph node dissection from January 1999 to September 2003 were included in this study., Results: The positive predictive value of the postchemotherapy ultrasound for predicting pathologic nodal involvement was 83%, but the negative predictive value was only 52%. Postchemotherapy physical examination was also poor at predicting pathologic nodal involvement with a positive predictive value of 93% and a negative predictive value of only 58%., Conclusions: A negative post-neoadjuvant chemotherapy high-resolution axillary ultrasound or physical examination does not predict pathologic node status, and this test has limited value in this setting.