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Knowledge of axillary nodal status is highly important for correct staging and treatment planning in patients with breast cancer. Axillary US is a recognized highly specific and cost-effective tool for assessing nodal status and guiding appropriate treatment. Axillary US imaging with US-guided biopsy is routinely performed throughout the world. However, because of recent developments in the surgical management of the axilla in patients with newly diagnosed breast cancer (American College of Surgeons Oncology Group [ACOSOG] Z0011 trial) and in patients with breast cancer receiving neoadjuvant systemic therapy (ACOSOG Z1071, SENTinel NeoAdjuvant [SENTINA] and Sentinel Node biopsy aFter NeoAdjuvant Chemotherapy [SN FNAC] trials), some have questioned the utility of axillary US for nodal staging. Here, we review the evidence to date supporting the additional value of axillary US for patients with breast cancer. Nodal US in patients with newly diagnosed breast cancer is useful for staging; in a significant proportion of patients, nodal US identifies additional axillary level II or level III nodal disease, which allows for appropriate treatment of disease. Furthermore, ongoing clinical trials may show that axillary surgery can be omitted in patients with negative findings on axillary US. In patients with lymph node–positive disease undergoing neoadjuvant systemic therapy, nodal US can guide the approach to axillary surgery. A more personalized patient approach, taking into the account tumor biology, among other factors, may help to mitigate the controversy surrounding the role of axillary US in breast cancer patients.

Background Targeted axillary dissection (TAD) involves locating and removing both clipped nodes and sentinel nodes for assessment of the axillary response to neoadjuvant chemotherapy (NAC) by clinically node-positive breast cancer patients. Initial reports described radioactive seeds used for localization, which makes the technique difficult to implement in some settings. This trial was performed to determine whether magnetic seeds can be used to locate clipped axillary lymph nodes for removal. Methods This prospective registry trial enrolled patients who had biopsy-proven node-positive disease with a clip placed in the node and treatment with NAC. A magnetic seed was placed under ultrasound guidance in the clipped node after NAC. All the patients underwent TAD. Results Magnetic seeds were placed in 50 patients by 17 breast radiologists. All the patients had successful seed placement at the first attempt (mean time for localization was 6.1 min; range 1-30 min). The final position of the magnetic seed was within the node (n = 44, 88%), in the cortex (n = 3, 6%), less than 3 mm from the node (n = 2, 4%), or by the clip when the node could not be adequately visualized (n = 1, 2%). The magnetic seed was retrieved at surgery from all the patients. In 49 (98%) of the 50 cases, the clip and magnetic seed were retrieved from the same node. Surgeons rated the transcutaneous and intraoperative localization as easy for 43 (86%) of the 50 cases. No device-related adverse events occurred. Conclusions Localization and selective removal of clipped nodes can be accomplished safely and effectively using magnetic seeds.

Introduction The early COVID‐19 pandemic rapidly transformed healthcare and medical education. We sought to evaluate the professional and personal impact of the pandemic on 2019–2020 Breast Surgical Oncology (BSO) fellows in Society of Surgical Oncology approved programs to capture the experience and direct future changes. Methods From July 15, 2020 to August 4, 2020 a survey was administered to the American Society of Breast Surgeons' fellow members. The survey assessed the impact of the pandemic on clinical experience, education/research opportunities, personal health/well‐being, and future career. Responses were collected and aggregated to quantify the collective experience of respondents. Results Twenty‐eight of fifty‐seven (54%) eligible fellows responded. Twenty‐one (75%) indicated the clinical experience changed. Twenty‐seven (96%) reported less time spent caring for ambulatory breast patients and sixteen (57%) reported the same/more time spent in the operating room. Fourteen (50%) stated their future job was impacted and eight (29%) delayed general surgery board examinations. Stress was increased in 26 (93%). Personal health was unaffected in 20 (71%), and 3 (10%) quarantined for COVID‐19 exposure/infection. Conclusion The COVID‐19 pandemic altered the clinical experience of BSO fellows; however, the operative experience was generally unaffected. The creation of frameworks and support mechanisms to mitigate potential challenges for fellows and fellowship programs in the ongoing pandemic and other times of national crisis should be considered.

Neoadjuvant systemic therapy (NST) is standard for locally advanced breast cancer and is now frequently considered for those with early-stage and node-positive disease. We aimed to evaluate the treatment course and outcomes in patients with disease progression during NST. Patients diagnosed with unilateral stage I–III breast cancer between 2005 and 2015 with documented local-regional progression while receiving NST, by clinical examination and/or imaging after two or more cycles of chemotherapy, were identified from a prospective database, stratified by receipt of surgery and outcomes analyzed. Of 6362 patients treated with NST during the study period, 124 (1.9%) developed disease progression. At a median live follow-up of 71 months, 23.4% were alive without disease and 70.2% had died from breast cancer. Median overall survival (OS) time for patients with progression was 26 months and median distant disease-free survival (DFS) was 14 months. Triple-negative breast cancer was associated with a higher likelihood of death (p

Nearly one-third of patients with inflammatory breast cancer (IBC) present with de novo stage IV disease. There are limited data on frequency and clinical outcomes of contralateral axillary metastasis (CAM) in IBC with no consensus diagnostic and treatment guidelines. Frequency of synchronous CAM was calculated in unilateral IBC patients at a single center (10/2004–6/2019). Clinicopathologic variables, diagnostic evaluation, treatment received, and overall survival (OS) were assessed and compared. Of 588 unilateral IBC patients, 49 (8.3%) had synchronous CAM. Of these, 32 (65.3%) also presented with metastatic disease at another distant site. CAM was not associated with age, tumor laterality, breast cancer subtype, grade, or cN stage (p > 0.05). The sensitivity/specificity to detect CAM was as follows: mammography (18.2%/99.2%), ultrasound (92.3%/95.5%), PET (90.1/99.1%), and MRI (76.0%/98.6%). Following systemic therapy, 22 patients had contralateral axillary surgery, and 18 received adjuvant contralateral nodal radiation. On multivariable analysis including tumor receptor subtypes, patients with stage IV-isolated CAM has statistically similar survival to stage III patients (HR 1.37, 95% CI 0.70–2.69, p = 0.36). Patients with Stage IV non-CAM (HR 2.18, 95% CI 1.66–2.85, p < 0.001) and stage IV-CAM plus other distant metastasis (HR 2.57, 95% CI 1.59–4.16, p < 0.001) had higher risk of death (reference: stage III disease). CAM in IBC was diagnosed in 8.3% of patients at presentation and was best identified by ultrasound and PET. We recommend routine contralateral axillary ultrasound as part of staging for all IBC patients. Diagnosis of CAM is a key first step toward much-needed prospective clinical trials evaluating management and outcomes of CAM in IBC.

Introduction The potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice. Methods A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach. Results According to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence). Discussion This review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients’ values. Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs.

Purpose: Neoadjuvant systemic treatment elicits a pathologic complete response (pCR) in an average of 35% of women with breast cancer. In such cases, breast surgery may be considered overtreatment. However, imaging and vacuum-assisted biopsy (VAB) alone showed high rates of missed cancer compared to standard breast surgery. We therefore evaluated multivariate algorithms using patient, tumor, and VAB variables to accurately identify patients with breast pCR. Methods: We developed and tested three multivariate approaches: elastic net regression, Support Vector Machines (SVM), and a deep neural network. We analyzed 452 patients, randomly partitioned into training and test samples (2:1 ratio), who participated in three prospective studies assessing the feasibility of VAB to accurately detect residual disease after neoadjuvant systemic treatment (NST). The studies were conducted at 23 sites in the United States, Germany, and South Korea. The trials enrolled women who presented with clinical stage I-III breast cancer of any biological subtype and a partial or complete response to NST confirmed by ultrasonography, mammography, or magnetic resonance imaging; all patients underwent guideline-adherent surgery. We compared the performance of the multivariate algorithms to the histopathologic evaluation of disease response in the surgical specimen (reference standard) - false-negative rate (FNR, missed residual cancer) and specificity (identification of breast pCR) were the main outcome measures. The best performing algorithm on the test set with respect to sensitivity and specificity was validated using data of an independent fourth trial. We compared the performance of the multivariate approaches to the performance of imaging and/or VAB. Results: In the test set (n=152), elastic net regression, SVM and the neural network revealed an FNR of 1.2% (1 of 85 patients with missed residual disease). Specificity of the elastic net regression was 46.3% (31 of 67 women with surgically confirmed breast pCR identified), of the SVM 62.7% (42 of 67) and of the neural network 67.2% (45 of 67). All multivariate algorithms performed better than imaging or VAB: FNR 25.9% (22 of 85) and 16.5% (14 of 85), respectively. Subsequent external validation (n=50) of the neural network algorithm showed a false-negative rate of 0% (0 of 27) and a specificity of 65.2% (15 of 23). The area under the ROC curve for the deep neural network was 0.97 (95% CI, 0.94 to 1.00). Analyzing the coefficients of the elastic net regression (regularized beta; ß) showed that the lesion diameter on imaging after NST (ß = 0.31) and VAB results (ß = 0.49) were the most important variables in the prediction of residual tumor. Other variables were also important: age (ß = 0.18), in-situ in the initial diagnostic (not VAB) biopsy (ß = 0.11), difficulties during the pathologic evaluation of the VAB specimen (ß = 0.11); needle size 7G (ß = -0.06, as opposed to 8G, 9G, 10G), multicentricity on imaging after NST (ß = 0.06), hormone-receptor positivity (ß = 0.01), and a clip marker positioned within the (former) lesion (ß = -0.01, as opposed to a clip marker positioned 5mm from the lesion Conclusion: A multivariate algorithm can accurately select breast cancer patients without residual disease after neoadjuvant treatment. This finding may pave the way to study omission of breast surgery in these patients in the future. Performance of multivariate algorithms compared to imaging and vacuum-assisted biopsyFalse-negative rate - value (95% CI)Specificity - value (95% CI)Negative predictive value - value (95% CI)Positive predictive value - value (95% CI)Test set (n=152)Imaging25.9% (17.0-36.5%)61.2% (48.5-72.9%)65.1% (52.0-76.7%)70.8% (60.2-79.9%)VAB16.5% (9.3-26.1%)89.6% (79.7-95.7%)81.1% (70.3-89.3%)91.0% (82.4-96.3%)Imaging + VAB5.9% (1.9-13.2%)52.2% (39.7-64.6)87.5% (73.2-95.8%)71.4% (62.1-79.6%)Elastic net regression1.2% (0.0-6.4%)46.3% (34.0-58.9%)96.9% (83.8-99.9%)70.0% (61.0%-78.0%)Support Vector Machine1.2% (0.0-6.4%)62.7% (50.0 - 74.2%)97.7% (87.7-99.9%)77.1% (68.0-84.6%)Deep Neural Network1.2% (0.0-6.4%)67.2% (54.6-78.2%)97.8% (88.5-99.9%)79.3% (70.3-86.5%)Validation set (n=50)Deep Neural Network0.0% (0.0-12.8%)65.2% (42.7-83.6%)100% (78.2-100%)77.1% (59.9-89.6%) Citation Format: André Pfob, Chris Sidey-Gibbons, Han-Byoel Lee, Marios Konstantinos Tasoulis, Vivian Koelbel, Michael Golatta, Gaiane M. Rauch, Benjamin D. Smith, Vicente Valero, Fiona MacNeill, Wonshik Han, Walter Paul Weber, Geraldine Rauch, Henry Kuerer, Joerg Heil. Identify breast cancer patients with pathologic complete response in the breast after neoadjuvant systemic treatment - an international, multicenter analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-42.

Background: Over the last decade, patients with early-stage breast cancer have been undergoing total mastectomy (TM) with increasing frequency. Our center reported that local recurrence rates with breast conserving therapy (BCT) declined throughout the 27-year period: from 7.1% for patients treated during 1970–1984 to 1.3% for patients treated during 1994–1996. More recently, several groups have published slightly improved survival rates in patients undergoing BCT compared with TM. The aim of this study was to evaluate trends in TM rates and compare overall survival (OS), distant metastasis-free survival (DMFS), local-regional recurrence (LRR) and disease-specific survival (DSS) between BCT and TM in patients with early-stage breast cancer undergoing upfront surgery. Methods: We identified women with clinical stage T1–2, N0–1, M0 breast cancer who underwent surgery as first treatment modality from 1/1/2000 to 12/31/2014 at our center. TM rates and survival outcomes were evaluated. Because the decision for surgery for those patients was not random, differences in patient, tumor and treatment characteristics with respect to surgery types were adjusted using inverse probability weighting (IPW) based on propensity scores. Variables in the model included age at diagnosis, clinical tumor T category, clinical nodal category, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) status and year of surgery, and a multinomial logit model was used for surgery treatment assignment and a Gamma model was used for the time to censor. IPW models were used to adjust for impact of surgery types on survival outcomes. Similar analysis was used in 6 subsets: Stage I & hormone receptor (HR)+/HER2-, Stage I & HER2+, Stage I &triple negative breast cancer (TNBC), Stage II & HR+/HER2-, Stage II & HER2+, Stage II & TNBC. Patients undergoing TM with RT were excluded from subset analysis due to small sample size. Results: A total of 8,256 patients were included, of them, 4701 (56.9%) underwent BCT, 2862 (34.7%) underwent TM without RT and 693 (8.4%) underwent TM+RT. Patients who underwent TM were younger and were more likely to have larger tumors, positive lymph nodes, higher grade, and HER2-positive tumors. TM rates increased in patients Table 1. Results from multivariable Cox models for factors associated with survival outcomes and IPW adjusted models for factors associated with survival outcomesCox ModelIPW adjusting modelsFactorsHRP95%CIRRP95% CIOSSurgery typeTM without RTBCT0.80.020.70.991.01.00.9-1.1TM with RT1.00.960.81.31.10.60.9-1.3DSSSurgery typeTM without RTRefBCT1.10.40.81.51.20.031.02-1.4TM with RT1.70.0051.22.61.30.021.04-1.6DMFSSurgery typeTM without RTRefBCT1.10.40.91.41.00.50.9-1.2TM with RT1.70.0021.22.40.90.70.7-1.2 LRRSurgery typeTM without RTRefBCT1.30.11.01.71.00.70.7-1.2TM with RT0.40.020.20.90.80.10.6-1.1Subsets IPW adjusted models for factors associated with LRRBCT vs. TM without RTStage I & HR+/HER2-No. of patientsTM without RT/BCTRRP95% CIStage I & HER2+1469/29451.00.90.8-1.3Stage I & TNBC199/2850.70.30.3-1.5Stage II & HR+/HER2-128/3170.4 Citation Format: Min Yi, Mariana Chavez Mac Gregor, Benjamin Smith, Abigail S Caudle, Sarah M DeSnyder, Henry M Kuerer, Kelly K Hunt. Comparing survival differences between breast-conserving therapy and mastectomy in patients with early-stage breast cancer undergoing upfront surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-17.

The role of modified radical mastectomy (MRM) in patients with de novo stage IV inflammatory breast cancer (IBC) remains controversial. We evaluated the impact of MRM on outcomes in this population. Ninety-seven women presenting with stage IV IBC were identified in an institutional database (2007–2016) and were stratified by receipt of MRM or no surgery (non-MRM). Demographic, clinicopathologic, and treatment factors were compared. Local–regional recurrence patterns were described and survival analyses were conducted. All patients initially received chemotherapy. Fifty-two patients (53.6%) underwent MRM; 47 received post-mastectomy radiation. Differences between the non-MRM and MRM groups included tumor receptor subtypes (hormone receptor-positive [HR+]/human epidermal growth factor receptor 2-positive [HER2+]: 4.4% vs. 19.2%; HR+/HER2-negative [HER2−]: 31.1% vs. 44.2%; HR-negative [HR−]/HER2+: 24.4% vs. 15.4%; and HR−/HER2−: 40.0% vs. 21.2%; p = 0.03), number of metastatic sites (3 vs. 2; p = 0.01), and clinical partial/complete response to chemotherapy (13.3% vs. 75.0%; p

Background Neoadjuvant systemic treatment elicits a pathologic complete response (pCR) in about 35% of women with breast cancer. In such cases, breast surgery may be considered overtreatment. We evaluated multivariate algorithms using patient, tumor, and vacuum-assisted biopsy (VAB) variables to identify patients with breast pCR. Methods We developed and tested four multivariate algorithms: a logistic regression with elastic net penalty, an Extreme Gradient Boosting (XGBoost) tree, Support Vector Machines (SVM), and neural network. We used data from 457 women, randomly partitioned into training and test set (2:1), enrolled in three trials with stage 1–3 breast cancer, undergoing VAB before surgery. False-negative rate (FNR) and specificity were the main outcome measures. The best performing algorithm was validated in an independent fourth trial. Results In the test set (n = 152), the logistic regression with elastic net penalty, XGboost tree, SVM, and neural network revealed an FNR of 1.2% (1 of 85 patients with missed residual cancer). Specificity of the logistic regression with elastic net penalty was 52.2% (35 of 67 women with surgically confirmed breast pCR identified), of the XGBoost tree 55.2% (37 of 67), of SVM 62.7% (42 of 67), and of the neural network 67.2% (45 of 67). External validation (n = 50) of the neural network showed an FNR of 0% (0 of 27) and a specificity of 65.2% (15 of 23). Area under the ROC curve for the neural network was 0.97 (95% CI, 0.94–1.00). Conclusion A multivariate algorithm can accurately select breast cancer patients without residual cancer after neoadjuvant treatment.

Modified radical mastectomy (MRM), which includes axillary dissection, is the standard of care for inflammatory breast cancer (IBC). While more limited axillary staging after neoadjuvant chemotherapy (NAC) in clinically node-positive non-IBC has been increasingly adopted, the impact of these techniques in IBC is not clear. To inform patient selection for further study of limited axillary surgery, we aimed to describe the frequency and factors associated with pathological node-negativity (ypN0) in IBC. Patients with IBC who received NAC and MRM were identified from a prospective institutional database (2004–2019). Binary logistic regression analyses were conducted to identify factors associated with ypN0. Of 453 patients, 189 (41.7%) had a post-NAC clinical nodal stage (ycN stage) of N0 (ycN1: 150, 33.1%; ycN2: 4, 0.9%; ycN3: 47, 10.4%; unknown: 63, 13.9%); 156 (34%) were ypN0. On multivariable analysis, higher tumor grade was not associated with ypN0 (odds ratio [OR] 1.59, 95% confidence interval [CI] 0.90–2.81, p =0.11). Compared with hormone receptor (HR)-negative/human epidermal growth factor receptor 2 (HER2)-negative tumors (n =113, 24.9%), HR-positive/HER2-negative tumors (n =169, 37.3%) had a trend toward less ypN0 (OR 0.55, 95% CI 0.29–1.02, p =0.06); HR-positive/HER2-positive tumors (n =79, 17.4%) were similar to HR-negative/HER2-negative tumors (OR 0.72, 95% CI 0.35–1.48, p =0.37); and HR-negative/HER2-positive tumors (n =92, 20.3%) were associated with increased ypN0 (OR 4.82, 95% CI 2.41–9.63, p

PURPOSE To our knowledge, NRG/RTOG 9804 is the only randomized trial to assess the impact of whole breast irradiation (radiation therapy [RT]) versus observation (OBS) in women with good-risk ductal carcinoma in situ (DCIS), following lumpectomy. Long-term results focusing on ipsilateral breast recurrence (IBR), the primary outcome, are presented here. PATIENTS AND METHODS Eligible patients underwent lumpectomy for DCIS that was mammogram detected, size ≤ 2.5 cm, final margins ≥ 3 mm, and low or intermediate nuclear grade. Consented patients were randomly assigned to RT or OBS. Tamoxifen use was optional. Cumulative incidence was used to estimate IBR, log-rank test and Gray's test to compare treatments, and Fine-Gray regression for hazard ratios (HRs). RESULTS A total of six hundred thirty-six women were randomly assigned from 1999 to 2006. Median age was 58 years and mean pathologic DCIS size was 0.60 cm. Intention to use tamoxifen was balanced between arms (69%); however, actual receipt of tamoxifen varied, 58% RT versus 66% OBS ( P = .05). At 13.9 years' median follow-up, the 15-year cumulative incidence of IBR was 7.1% (95% CI, 4.0 to 11.5) with RT versus 15.1% (95% CI, 10.8 to 20.2) OBS ( P = .0007; HR = 0.36; 95% CI, 0.20 to 0.66); and for invasive LR was 5.4% (95% CI, 2.7 to 9.5) RT versus 9.5% (95% CI, 6.0 to 13.9) OBS ( P = .027; HR = 0.44; 95% CI, 0.21 to 0.91). On multivariable analysis, only RT (HR = 0.34; 95% CI, 0.19 to 0.64; P = .0007) and tamoxifen use (HR = 0.45; 95% CI, 0.25 to 0.78; P = .0047) were associated with reduced IBR. CONCLUSION RT significantly reduced all and invasive IBR for good-risk DCIS with durable results at 15 years. These results are not an absolute indication for RT but rather should inform shared patient-physician treatment decisions about ipsilateral breast risk reduction in the long term following lumpectomy.

Tailoring of breast cancer treatment to the individual has especially occurred in breast cancer surgery: paradigms have changed from Halsted's radical mastectomy in 1882, to simple mastectomy, to lumpectomy. Within the next decade, we might face another paradigm change of omitting breast cancer surgery at all in case of a complete response after neoadjuvant systemic treatment. In this article, we provide an overview of the reasoning for this new paradigm change, the criticism it has evoked, and under which conditions it might be incorporated into clinical practice. We also take a look at previous paradigm changes in breast cancer surgery and the insights they provide us in the current situation on a statistical but also on a psychological level.

Background: Multigene panel testing (MPG) for hereditary breast cancer has recently increased significantly. While clinical and pathological characteristics for invasive breast cancer in patients with non BRCA germline mutations is emerging, there is very limited data in patients with ductal carcinoma in situ (DCIS). This study evaluates the clinical and pathological characteristics of patients with DCIS who underwent MPG testing for hereditary breast cancer. Methods: Patients with DCIS who underwent MPG testing between 2014-2019 were identified from our prospectively maintained and IRB-approved research registry study and included in this analysis. Clinical and tumor characteristics were analyzed using descriptive statistics. Variables included in the analysis included: Age at diagnosis, family history of breast and ovarian cancer, tumor characteristics including ER/PR and nuclear grade and genetic testing results. Results: In this prospective cohort, 324 patients with DCIS underwent multigene panel testing. Age of diagnosis was 50.5 years (range: 18-86), a family history of breast and/or ovarian cancer was positive in 283 (87.3%) patients. Genetic testing results were as follows: Pathogenic or likely pathogenic mutations were found in 28 (8.6%) patients: BRCA1 2 (7.1%), BRCA2 6 (21.4%), PALB2 6 (21.4%), CHEK2 5 (17.9%), ATM 3 (10.7%), APC 2 (7.1%), BARD1 1 (3.6%), BRIP1 1 (3.6%), MSH2 1 (3.6%), MUTYH 1 (3.6%). The variant of uncertain significance rate was 16% (52): 7 (13.5%) in BRCA1 or 2 and 45 (86.5%) in other genes. 244 (75.3%) of patients had negative results. Conclusion: Our data demonstrates that, in addition to BRCA 1 and 2 genes, patients with DCIS have other hereditary genes involved. In fact, 71.4% of the germline mutations were in non-BRCA genes. Regardless of gene status, most patients had ER positive disease, this can have implications for chemopreventive therapy. Furthermore, patients with germline mutations have a higher percentage of nuclear grade III DCIS than gene negative patients. Larger studies are needed to evaluate the clinical implications of these findings. Genetic testing with a larger panel, other than BRCA1 and BRCA2 genes only, should be considered for patients with DCIS. NegativeBRCA1+BRCA2+PALB2+CHEK2+ATM+Variablesn%n%n%n%n%n%ERpositive17471.32100.0583.3350.0480.03100.0negative187.400.000.0116.7120.000.0unknown5120.900.0116.7233.300.000.0PRpositive15262.3150.0583.3350.0480.03100.0negative3815.6150.000.0116.7120.000.0unknown5422.100.0116.7233.300.000.0NGI187.4150.000.000.0240.000.0II10041.000.0116.7350.0240.0133.3III8534.8150.0466.7233.300.0266.7unknown4116.800.0116.7116.7120.000.0Totals244100.02100.06100.06100.05100.03100.0 Citation Format: Loredana Militello, Angelica M Gutierrez Barrera, Henry Kuerer, Constance Albarracin, Banu K Arun. Characteristics of ductal carcinoma in situ (DCIS) in patients who underwent multigene panel testing for hereditary breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-06.

Postmastectomy radiotherapy (PMRT) is often a component of treatment algorithms for locally advanced or node-positive breast cancer. Breast reconstruction may be delayed or not performed due to negative effects of PMRT on the reconstruction. Administering radiotherapy in the preoperative setting allows for immediate breast reconstruction (IBR) to be performed in patients who have indications for PMRT and desire IBR. This review summarizes the current literature on this new concept. Most prospective treatment protocols included neoadjuvant systemic therapy followed by radiotherapy (RT) dose of 50–50.4 Gy conventionally fractionated and mastectomy with immediate autologous reconstruction after 6–8 weeks. There were no cases of IBR being aborted due to technical complications and overall postoperative complications ranged from 3 to 36%. These were typically non-operatively managed, and cosmetic results when evaluated were favorable. Initial oncologic outcomes indicate low locoregional recurrence rates (≤ 10%) and high 5-year overall survival rates of 87–98%. Although published studies are heterogeneous in nature, they suggest that preoperative RT followed by mastectomy with IBR is technically feasible and safe. Larger prospective studies with longer follow-up times may establish this as a new standard in the multidisciplinary treatment of high-risk breast cancer.

Patients with epidermal growth factor receptor 2-positive (HER2+) breast cancer and pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) may be candidates for nonoperative clinical trials if residual invasive and in situ disease are eradicated. This study analyzed 280 patients with clinical T1-2N0-1 HER2+ breast cancer who underwent NST followed by surgical resection to determine key characteristics of patients with pCR in the breast and lymph nodes compared with those with residual disease. Of the 280 patients, 102 (36.4%) had pCR in the breast and lymph nodes after NST, and 50 patients (17.9%) had residual ductal carcinoma in situ (DCIS) in the breast only. For 129 patients (46.1%), DCIS was present on the pretreatment biopsy, and NST failed to eradicate the DCIS component in 64.3%. Patients with residual disease were more likely to have hormone receptor-positive (HR+) tumors than those with negative tumors (73.4% vs. 50.8%; p

Postmastectomy radiotherapy currently is used for locally advanced breast cancers that carry a high risk of locoregional failure. However, radiotherapy can have deleterious effects on immediate breast reconstruction (IBR). Neoadjuvant radiotherapy (NART) to facilitate postmastectomy IBR is an emerging new therapeutic sequence. A systematic review was undertaken to evaluate the current evidence on the feasibility and safety of this sequence. A comprehensive search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov from inception to 2018 was conducted, resulting in 592 records. The review included 18 retrospective and prospective studies of NART and IBR. The majority of the studies used whole-breast radiotherapy with 50 Gy, conventionally fractionated, and waited 6–8 weeks before surgery. The IBR methods were varied, with both implant and autologous reconstructions. No intraoperative complications occurred, and the postoperative complication rates ranged from 3 to 36%. The partial and total flap loss rates were very low. Studies reporting cosmetic outcomes rated the majority of cases as good or excellent. The pathologic complete response rates ranged from 17 to 55%, and the locoregional recurrence rates were low (≤ 10%), with a short follow-up period. The current MD Anderson Cancer Center prospective clinical trial is described. The initial results of NART and IBR demonstrate the safety of this treatment both technically and oncologically. Longer follow-up evaluation of these studies and larger prospective controlled clinical trials are needed to establish this new therapeutic sequence as a standard of care.

Background The purpose of this consensus guideline is to outline recommendations for genetic testing that medical professionals can use to assess hereditary risk for breast cancer. Methods Literature review included large datasets, basic and clinical science publications, and recent updated national guidelines. Genetic testing to assess hereditary risk of cancer is a complex, broad, and dynamic area of medical research. The dominant focus of this guideline is limited in scope to breast cancer. Results There is a lack of consensus among experts regarding which genes among many should be tested in different clinical scenarios. There is also variation in the degree of consensus regarding the understanding of risk and appropriate clinical management of mutations in many genes. Conclusions Genetic testing should be made available to all patients with a personal history of breast cancer. Recent data are reviewed that support genetic testing being offered to each patient with breast cancer (newly diagnosed or with a personal history). If genetic testing is performed, such testing should include BRCA1/BRCA2 and PALB2, with other genes as appropriate for the clinical scenario and family history. For patients with newly diagnosed breast cancer, identification of a mutation may impact local treatment recommendations. Patients who had genetic testing previously may benefit from updated testing. Genetic testing should be made available to patients without a history of breast cancer who meet National Comprehensive Cancer Network guidelines. Finally, variants of uncertain significance are not clinically actionable and these patients should be managed based on their individual risk factors.

Purpose Optimal treatment of patients diagnosed with de novo metastatic breast cancer limited to the mediastinum or sternum has never been delineated. Herein, we sought to determine the efficacy of multimodality treatment, including metastasis-directed radiation therapy, in curing patients with this presentation. Methods and Materials This is a single-institution retrospective cohort study of patients with de novo metastatic breast cancer treated from 2005 to 2014, with a 50-month median follow-up for the primary cohort. The primary patient cohort had metastasis limited to the mediastinum/sternum treated with curative intent (n = 35). We also included a cohort of patients with stage IIIC disease treated with curative intent (n = 244). Additional groups included a mediastinal/sternal palliative cohort (treatment did not include metastasis-directed radiation therapy; n = 14) and all other patients with de novo stage IV disease (palliative cohort; n = 1185). The primary study outcomes included locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), which were calculated using the Kaplan-Meier method. Cox multivariable models compared survival outcomes across treatment cohorts adjusted for molecular subtype, age, and race. Results For the mediastinal/sternal curative-intent cohort, 5-year LRRFS was 85%, RFS was 52%, and OS was 63%. After adjustment, there was no statistically significant difference in LRRFS (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.13-1.13; P = .08), RFS (HR, 0.87; 95% CI 0.50-1.49; P = .61), or OS (HR, 0.79; 95% CI 0.44-1.43; P = .44) between the stage IIIC cohort and the mediastinal/sternal curative-intent cohort (referent). In contrast, RFS was worse for the mediastinal/sternal palliative cohort (HR, 2.29; 95% CI 1.05-5.00; P = .04). OS was worst for the de novo stage IV palliative cohort (HR, 2.61; 95% CI 1.50-4.53; P Conclusions For select patients presenting with breast cancer metastatic to the sternum and/or mediastinum, curative-intent treatment with chemotherapy, surgery, and radiation yields outcomes similar to those of stage IIIC disease and superior to de novo stage IV breast cancer treated with palliative intent.

BACKGROUND Few guidelines exist for an opioid prescription after breast surgical oncology (BSO) procedures. We sought to characterize opioid prescribing and use patterns by surgery type. METHODS Patients (n = 332) undergoing BSO procedure were surveyed one week postoperatively for opioid use. The surgeons were surveyed about pain management preferences surgery type. CPT codes were collected for 2017 to calculate the amount of opioids used by surgery type relative to surgeon preference. RESULTS Mean oral morphine equivalent (OME) preferred prescription for surgeons who did not tailor prescriptions by surgery type (n = 7, group A) was 177, whereas for those who did tailor (n = 10, group B) varied from 137 to 257 OME. There was a significant difference in opioid use by surgery type: 32 OME for segmental mastectomy (SM) ± sentinel lymph node dissection (SLND), 63 for SM + axillary lymph node dissection (ALND), 76 for total mastectomy (TM) ± SLND, 115 for TM + ALND (P

OBJECTIVE: To determine the relationship between negative margin width and locoregional recurrence (LRR) in a contemporary cohort of ductal carcinoma in situ (DCIS) patients. BACKGROUND: Recent national consensus guidelines recommend an optimal margin width of 2 mm or greater for the management of DCIS; however, controversy regarding re-excision remains when managing negative margins < 2 mm. METHODS: One thousand four hundred ninety-one patients with DCIS who underwent breast-conserving surgery from 1996 to 2010 were identified from a prospectively managed cancer center database and analyzed using univariate and multivariate Cox proportional hazard models to determine the relationship between negative margin width and LRR with or without adjuvant radiation therapy (RT). RESULTS: A univariate analysis revealed that age

578 Background: Advances in radiotherapy allow the ability to deliver ablative treatments without compromising outcomes, but there has been limited application of these treatments to early-stage breast cancers. The purpose of this study was to explore patients’ interest in pursuing nonsurgical treatment approaches for their early-stage breast cancer. Methods: Investigators conducted a qualitative descriptive study involving semi-structured interviews with 21 early-stage breast cancer patients eligible for participation in a phase 2 trial offering omission of surgery. Interviews were transcribed, and three independent reviewers performed an inductive, thematic analysis to generate themes and subthemes. Results: Data analysis revealed the following factors that impacted patients’ willingness and desire to explore nonsurgical treatment options: Perceptions and feelings about their cancer; Current quality of life and the level of support available in their daily life; External conversations focusing on family members’ and friends’ experiences with cancer and/or cancer treatments; Personal healthcare experiences, including with their current breast cancer diagnosis; Perceptions and feelings about their physicians; Conversations with their physicians about their treatment options; and Self-identified desire to direct care decisions. Specifically, patients described fearing surgery and surgical recovery and wanting to avoid negative surgery-related events previously experienced by friends, family, and themselves. Participants also expressed a desire to preserve their breast(s), receive treatment per the latest research, match the level of treatment with the severity of their cancer, and avoid other comorbidities as reasons for omitting surgery. Patient reasons for pursuing surgery included the desire to remove their cancer immediately, prior positive experiences of friends, family, and themselves with surgery, lack of concern about preserving their breast(s), and prior negative experiences of friends, family, and themselves with radiation. Conclusions: The results of this study highlight that there is patient interest in nonsurgical options for biologically favorable early stage breast cancers. A key factor hindering patient education and awareness of nonsurgical options is how the physician frames the discussion and presents treatment options. In addition, patients’ self-identity and the prior experiences of friends, family, and self with cancer treatment and surgery in general appear to be key factors in their decision-making. The findings from this study demonstrate an unmet need to explore nonsurgical options for early-stage breast cancer. Study results can help shape conversations around shared decision making and clinical trial design and result in more personalized treatment options for women with early-stage breast cancer.

PURPOSE: To evaluate the acceptability and impact of 3D printed breast models (3D-BM) on treatment-related decisional conflict (DC) of breast cancer patients. METHODS: Patients with breast cancer were accrued in a prospective IRB-approved trial. All patients underwent contrast-enhanced breast MRI (MRI). A personalized 3D-BM was derived from MRI. DC was evaluated pre and post 3D-BM review. 3D-BM acceptability was assessed post 3D-BM review. RESULTS: DC surveys before and after 3D-BM review and 3D-BM acceptability surveys were completed by 25 patients. 3D-BM were generated in 2 patients with bilateral breast cancer. The mean patient age was 48.8 years (28–72). Tumor stage was Tis (7), 1 (8), 2 (8) and 3 (4). Nodal staging was 0 (19), 1 (7), 3 (1). Tumors were unifocal (15), multifocal (8) or multicentric (4). Patients underwent mastectomy (13) and segmental mastectomy (14) with (20) or without (7) oncoplastic intervention. Neoadjuvant therapy was given to 7 patients. Patients rated the acceptability of the 3D-BM as good/excellent in understanding their condition (24/24), understanding disease size (25/25), 3D-BM detail (22/25), understanding their surgical options (24/25), encouraging to ask questions (23/25), 3D-BM size (24/25) and impartial to surgical options (17/24). There was significant reduction in overall DC post 3D-BM review, indicating patients became more assured of their treatment choice (p=0.002). Reduction post 3D-BM review was also observed in the uncertainty (p=0.012), feeling informed about options (p=.005), clarity about values (p=0.032) and effective (p=0.002) DCS subscales. CONCLUSIONS: 3D-BMs are an acceptable tool to decrease decisional conflict in breast cancer patients. CLINICAL RELEVANCE: Breast cancer patients may experience decisional conflict when considering their surgical options. 3D-BM are an acceptable, impartial tool that reduces decisional conflict in patients with breast cancer.

International audience; Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.

Background This study characterizes the physiological drainage of the normal upper extremity using single-photon emission computed tomography/computed tomography (SPECT/CT) lymphoscintigraphy axillary reverse lymphatic mapping (ARM). Methods A consecutive series of patients assessed with SPECT/CT lymphoscintigraphy ARM of the upper extremity were included. Anatomical localization of the axillary sentinel lymph nodes (SLN) was completed in normal axillae in relation to consistent anatomic landmarks. Retrospective case note analysis was performed to collect patient demographic data. Results A total of 169 patients underwent SPECT/CT lymphoscintigraphy, and imaging of 182 normal axillae was obtained. All patients (100%) had an axillary SLN identified: 19% had a single contrast-enhanced SLN in the axilla and the remainder had multiple. The SLN(s) of the upper extremity was located in the upper outer quadrant (UOQ) of the axilla in 97% of cases (177 axillae). When the SLN(s) was found in the UOQ of the axilla, second-tier lymph nodes were found predominantly in the upper inner quadrant (50% of cases). Conclusions The upper extremity SLN(s) is located in a constant region of the axilla. This study provides the most complete investigation to date and results can be directly applied clinically to ARM techniques and adjuvant radiation planning.

Importance Image-guided breast biopsy of a residual imaging abnormality or tumor bed after neoadjuvant chemotherapy (NACT) is increasingly used to assess residual cancer, facilitate risk-adaptive surgery, and potentially identify exceptional responders in whom local therapy may be de-escalated. Objective To further assess the accuracy of post-NACT image-guided biopsy to predict residual cancer in the breast. Design, setting, and participants This diagnostic study analyzed multicenter patient-level data of patients with breast cancer who were treated with NACT and underwent image-guided biopsy before surgery at Royal Marsden Hospital in London, UK; Seoul National University Hospital in Seoul, South Korea; and MD Anderson Cancer Center in Houston, Texas. Data were analyzed from June to July 2019. Main outcomes and measures Diagnostic accuracy of post-NACT image-guided biopsy. Final surgical pathology was used as reference standard. Results Data from 166 women were analyzed. The median (range) age was 49 (25-76) years. The median (range) tumor size on pretreatment and posttreatment imaging was 33.5 (12-100) mm and 10 (0-100) mm, respectively. The overall pathologic complete response rate was 51.2% (n = 85) (16.1% [5 of 31] for hormone receptor-positive/ERBB2 (formerly HER2)-negative; 44.7% [21 of 47] for hormone receptor-positive/ERBB2-positive; 69% [20 of 29] for hormone receptor-negative/ERBB2-positive; and 66.1% [39 of 59] for triple negative). The majority (143 [86.1%]) underwent image-guided vacuum-assisted biopsy (VAB), and 23 had core-cut biopsy. The median (range) needle gauge was 10 (7-14), and the median (range) number of samples was 6 (2-18). When image-guided biopsy (VAB and core-cut biopsy) was representative (159 [95.8%]), the false-negative rate across the whole cohort was 18.7% (95% CI, 10.6%-29.3%). Subgroup analysis of patients with a complete/partial clinical response and residual imaging abnormality of 2 cm or smaller with at least 6 VABs taken (76 [45.8%]) demonstrated a false-negative rate of 3.2% (95% CI, 0.1%-16.7%), a negative predictive value of 97.4% (95% CI, 86.5%-99.9%), and an overall accuracy of 89.5% (95% CI, 80.3%-95.3%). Conclusions and relevance This large multicenter pooled data analysis suggests that a standardized protocol using image-guided VAB of a tumor bed measuring 2 cm or smaller with 6 or more representative samples allows reliable prediction of residual disease. These results could inform the design of de-escalation trials in NACT exceptional responders testing the safety of eliminating surgery.

Background Oncoplastic breast-conserving surgery (OBCS) is most commonly performed using established or modified mastopexy/breast reduction techniques. Although the comparative complication profiles of Wise-pattern mastopexy/breast reduction techniques compared with vertical scar techniques are well understood, outcomes in the setting of OBCS are unknown. Methods A retrospective study was conducted of all patients that underwent OBCS using mastopexy/breast reduction techniques at a single center over a 6-year period. Patients who underwent Wise-pattern techniques were compared with those who underwent vertical scar techniques. Demographic, treatment, and outcomes data were collected. Descriptive statistics were used, and multivariate analysis was performed to evaluate the relationship between these multiple variables and complications. Results Of 413 eligible patients, 278 patients (67.3%) received a Wise-pattern technique and 135 (32.7%) underwent a vertical scar technique. The overall complication rate was significantly higher in the Wise-pattern than in the vertical scar group (30.6% vs 18.5%, respectively; P = 0.012), as was the major complication rate (11.9% vs 4.4%; P = 0.011) including need for additional surgery for complications (6.8% vs 1.5%; P = 0.029). Complications resulted in a delay to any adjuvant therapy in 20 patients (4.8%); however, the difference between the groups was not significant (6.1% for Wise pattern vs 2.2% for vertical scar; P = 0.098). In a multivariable logistic model, use of a Wise-pattern technique (odds ratio, 0.37 [95% confidence interval, 0.14-0.99]; P = 0.049) was a significant predictor of major complications. Conclusions The Wise-pattern mastopexy/breast reduction OBCS technique was associated with a significantly higher complication and major complication rate than vertical scar techniques. The findings should be considered during choice of surgical technique in oncoplastic breast conservation.

In patients with operable early breast cancer, neoadjuvant systemic treatment (NST) is a standard approach. Indications have expanded from downstaging of locally advanced breast cancer to facilitate breast conservation, to in vivo drug-sensitivity testing. The pattern of response to NST is used to tailor systemic and locoregional treatment, that is, to escalate treatment in nonresponders and de-escalate treatment in responders. Here we discuss four questions that guide our current thinking about 'response-adjusted' surgery of the breast after NST. (i) What critical diagnostic outcome measures should be used when analyzing diagnostic tools to identify patients with pathologic complete response (pCR) after NST? (ii) How can we assess response with the least morbidity and best accuracy possible? (iii) What oncological consequences may ensue if we rely on a nonsurgical-generated diagnosis of, for example, minimally invasive biopsy proven pCR, knowing that we may miss minimal residual disease in some cases? (iv) How should we design clinical trials on de-escalation of surgical treatment after NST?

Background After publication of American College of Surgeons Oncology Group (ACOSOG) Z0011, surgeons at our institution limited axillary surgery to sentinel lymph node dissection (SLND) in 76% of patients meeting trial eligibility criteria. Our study objective was to assess incorporation of the trial data into practice 5 years later. Patients and Methods Patients with clinical T1-2, N0 invasive breast cancer undergoing breast conserving surgery were included. Comparisons were made between patients who underwent axillary lymph node dissection (ALND) and those that had no further surgery. Results A total of 396 patients were included. Twelve percent (48/396) had positive SLNs; ALND was performed in 8% (4/48). Patients who underwent ALND were more likely to have 2 positive SLNs (50%, 2/4 vs. 2%, 1/44; P = .02) and microscopic extranodal extension (75%, 3/4 vs. 18%, 8/44; P = .03) than those that did not undergo ALND. Patients who underwent ALND also had a higher nomogram-predicted probability of having additional positive non-SLNs (53%) than those who had SLND alone (22%) ( P = .0002). No patients had intraoperative assessment of SLNs performed. Conclusions The practice of omitting ALND in ACOSOG Z0011-eligible patients has expanded over 5 years. Clinicopathologic features continue to impact this decision. Intraoperative SLN assessment is no longer performed.

The SSO-ASTRO-ASCO consensus guideline on margins for breast-conserving surgery with whole breast irradiation in ductal carcinoma in situ (DCIS) recommended a 2-mm margin. We sought to determine the impact of guideline publication on clinician practice. A total of 3081 members of the American Society of Breast Surgeons (ASBrS) received a survey. Respondents’ clinical practice type and duration, guideline familiarity, and margin width preferences before and after publication were assessed. Clinical practice pattern differences before and after publication were investigated using McNemar’s test. A total of 767 (24.9%) of those surveyed responded. Most (92.4%) indicated guideline familiarity. Of those familiar, re-excision preference for DCIS and a positive margin remained the same before (94.4%) and after (94.3%) publication (McNemar’s test p = 1.0). Following publication, surgeons were more likely to avoid re-excision to achieve margins wider than 2-mm (82.3% pre versus 87.5% post, p = 0.002). More surgeons performed re-excision for a close margin with pure DCIS (25.9% pre versus 36.5% post, p

Breast cancer metastasizes through the lymphovascular system to the regional lymph nodes in the axilla and to both visceral and non-visceral sites. Renewed interest in the route by which tumor cells gain access to blood and lymphatic capillaries are the subject of research at mechanical, anatomic, pathologic, genetic, epidemiologic and molecular levels. Two papers presented at the 7th International Symposium on Cancer Metastasis in San Francisco showed tumor cells entering the systemic circulation through the sentinel lymph node. This information challenges the current paradigm where clinicians believe that access is gained through intra- and peri-tumoral blood vessels and that metastasis to axillary lymph nodes is an interesting epi-phenomenon. The sentinel lymph node era has changed the modern surgical approach to the axilla and the basis of this change is summarized in this paper. A new approach to the management of axillary metastases after systemic therapy relies on determining whether there is a complete pathologic response; if no tumor is found in the previously biopsied node, a complete axillary lymph node dissection may be avoided. African American women seem to inherit a trait from West African ancestors and tend to develop more lethal types of breast cancer. These tumors may have a molecular machinery that enhances their ability to metastasize to visceral sites and future research may unearth the mechanisms for this phenomenon.

Although multigene panel testing is increasingly common in patients with cancer, the relationship between its use among breast cancer patients with non‐BRCA mutations or variants of uncertain significance (VUS) and disease management decisions has not been well described. This study evaluated the rate and predictive factors of CPM patients who underwent multigene panel testing. Three hundred and fourteen patients with breast cancer who underwent multigene panel testing between 2014 and 2017 were included in the analysis. Of the 314 patients, 70 elected CPM. Election of CPM by gene status was as follows: BRCA carriers (42.3%), non‐BRCA carriers (30.1%), and VUS (10.6%). CPM election rates did not differ between non‐BRCA carriers and BRCA carriers (P = 0.6205). Among non‐BRCA carriers, negative hormone receptor status was associated with CPM (P = 0.0115). For those with a VUS, hormone receptor status was not associated with CPM (P = 0.1879). Although the rate of CPM between BRCA carriers and non‐BRCA carriers was not significantly different, the predictors of CPM were different in each group. Our analyses shed the light on the increasing use of CPM among patients who are non‐BRCA carriers as well those with a VUS. Our study elucidates the differing predictive factors of CPM election among BRCA carriers, non‐BRCA carries, and those with a VUS. Our findings reveal the need for providers to be cognizant that non‐BRCA genes and VUS drive women to elect CPM despite the lack of data for contralateral breast cancer risk associated with these genes.

This study was designed to present the secondary imaging endpoints of the trial for evaluating mammogram (MMG), ultrasound (US) and image guided biopsy (IGBx) assessment of pathologic complete response (pCR) in breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC). Patients with T1–3, N0–3, M0 triple-negative or HER2-positive BC who received NAC were enrolled in an Institutional Review Board-approved prospective, clinical trial. Patients underwent US and MMG at baseline and after NAC. Images were evaluated for residual abnormality and to determine modality for IGBx [US-guided (USG) or stereotactic guided (SG)]. Fine-needle aspiration and 9-G, vacuum-assisted core biopsy (VACBx) of tumor bed was performed after NAC and was compared with histopathology at surgery. Forty patients were enrolled. Median age was 50.5 (range 26–76) years; median baseline tumor size was 2.4 cm (range 0.8–6.3) and 1 cm (range 0–5.5) after NAC. Nineteen patients had pCR: 6 (32%) had residual Ca2+ presurgery, 5 (26%) residual mass, 1 (5%) mass with calcifications, and 7 (37%) no residual imaging abnormality. Sensitivity, specificity, and accuracy of US, MMG, and IGBx for pCR were 47/95/73%, 53/90/73%, and 100/95/98%, respectively. Twenty-five (63%) patients had SGBx and 15 (37%) had US-guided biopsy (USGBx). Median number of cores was higher with SGBx (12, range 6–14) than with USGBx (8, range 4–12), p

PURPOSE: As triple-negative breast cancers are associated with earlier recurrences and poorer survival, optimal treatment of early-stage breast cancer is essential. Several retrospective studies in triple-negative breast cancer have reported conflicting results in overall survival in patients receiving neoadjuvant or adjuvant systemic therapy. This study aims to analyze outcomes of adjuvant versus neoadjuvant in patients with early-stage triple-negative breast cancer with and without BRCA germline mutations. METHODS: Patients with stage I or II triple-negative breast cancer who had BRCA testing were identified from a prospective cohort study of 4027 patients. Clinical, demographic, genetic test results, chemotherapy, recurrence, and survival data were analyzed. Overall survival and disease-free survival were estimated using the Kaplan–Meier method. RESULTS: 319 patients with stage I and II triple-negative breast cancer who met eligibility criteria were included in the analysis. 187 received adjuvant chemotherapy (58.6%) and 132 received neoadjuvant chemotherapy (41.4%). 135 were BRCA positive (42.3%) and 184 were BRCA negative (57.7%). There was no significant association between overall survival or disease-free survival and treatment with neoadjuvant versus adjuvant in the overall cohort. Furthermore, there were no significant differences between patient subgroups (neoadjuvant BRCA positive, neoadjuvant BRCA negative, adjuvant BRCA positive, and adjuvant BRCA negative) with respect to either overall survival or disease-free survival. CONCLUSIONS: Neoadjuvant versus adjuvant with standard anthracycline- and taxane-containing regimens results in similar disease-free survival and overall survival among patients with stage I and II triple-negative breast cancer regardless of BRCA status. Further studies are needed to evaluate whether similar results are observed with newer agents.

Background Most inflammatory breast cancer (IBC) patients have axillary disease at presentation. Current standard is axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NACT). Advances in NACT have improved pathologic complete response (pCR) rates increasing interest in performing sentinel lymph node (SLN) biopsy (SLNB). Previous studies on SLNB for IBC patients did not assess nodal response with imaging or use dual tracer mapping. We sought to prospectively determine false negative rates of SLNB in IBC patients using dual tracer mapping, and to correlate pathology with preoperative axillary imaging. Patients and Methods Patients with IBC were prospectively enrolled. Patients underwent axillary staging with physical examination and axillary ultrasound before and after NACT. All patients underwent SLNB using blue dye and radioisotope, followed by ALND. Results Sixteen patients were prospectively enrolled. Clinical N stage was N0 in 1 patient, N1 in 8, and N3 in 7. SLN mapping was successful in only 4 patients (25%) with 12 (75%) not draining either tracer to a SLN. Three of the 4 (75%) who mapped had an axillary pCR. The patient who mapped but did not have an axillary pCR had a positive SLNB with additional axillary nodal disease identified on ALND. All patients who successfully mapped had presumed residual nodal disease on preoperative axillary ultrasound. Conclusion SLNB was unsuccessful in most IBC patients. A small subset who have pCR might undergo successful SLNB, but preoperative axillary imaging failed to identify these patients. ALND should remain standard practice for IBC patients.

PURPOSE/OBJECTIVE(S) To report outcomes for women with pT1-2N1M0 breast cancer undergoing mastectomy and sentinel lymph node biopsy (SLNB) without completion axillary dissection, and to investigate the effect of post-mastectomy radiation therapy (PMRT). MATERIALS/METHODS Data from 5 North American institutions were pooled to include women with pT1-2N1M0 breast cancer from 1997-2015 who underwent mastectomy with a positive SLNB and ≤ 5 lymph nodes (LNs) resected. All patients were clinically N0 and none received neoadjuvant chemotherapy. Competing-risks regression was performed to identify factors associated with overall recurrence (OR), inclusive of locoregional (LR) and distant recurrence (DM). RESULTS Among 871 patients included, median age at diagnosis was 57 years, 92% were ER/PR-positive, 85% HER2-negative, and 60% received adjuvant chemotherapy. The 500 (57%) patients who received PMRT were significantly younger, had larger tumors, more positive LN, lymphovascular invasion (LVI), extracapsular extension (ECE), HER2-positive disease, and more frequently received adjuvant chemotherapy (all P < 0.05) compared to those not receiving PMRT. Median number of lymph nodes sampled in each group was 3 (range: 1-5). At a median follow up of 5.2 years, the 5-year cumulative incidence rates of LR, DM, OR, and breast cancer mortality (BCM) were 2%, 4%, 5%, and 3%, respectively. The 5-year rates of disease-free survival (DFS) and overall survival (OS) were 87% and 91%. LR was the only endpoint with a statistically significant difference between those receiving PMRT (0.4%) as compared to those without PMRT (3.9%), P < 0.001. On univariable competing risks regression, tumor size, nodal ratio, grade, LVI, and ER/PR status were significantly associated with OR and were included in multivariable analysis. On multivariable competing risks regression, larger tumor size (HR 1.47, 95% CI 1.19-1.81, P < 0.001), grade III (HR 1.81, 95% CI 1.07-3.05, P = 0.03), higher nodal ratio (HR 2.86, 95% CI 1.01-7.69, P = 0.049), and LVI (HR 2.04, 95% CI 1.27-3.28, P = 0.003) were significantly associated with increased risk of OR. PMRT was associated with decreased risk of OR (HR 0.60, 95% CI 0.26-1.00, P = 0.05), though this effect did not reach statistical significance. CONCLUSION In selected patients undergoing mastectomy and SLNB without completion axillary dissection for pT1-2N1 breast cancer, larger tumor size, higher grade, increased nodal ratio and the presence of LVI are associated with increased risk of overall recurrence. Further studies are needed to identify which subset of patients may benefit most from PMRT.

With current advances in neoadjuvant systemic therapy (NST) and improved breast imaging, the potential of nonoperative therapy for invasive breast cancer has emerged as a viable option when utilizing meticulous image-guided percutaneous biopsy to document pathologic complete response. Feasibility clinical trials utilizing this approach are being performed by teams of investigators from single and multicenter/cooperative groups around the world. Imaging alone after NST lacks sufficient sensitivity and specificity in predicting pCR and therefore cannot be utilized for clinical selection of patients for omission of surgery. Imaging with adequate sampling after NST of the residual lesions (or around the remaining clip if a complete radiologic response occurs) appears to be essential in selecting patients with pCR to lower the false-negative rates based on initial reported feasibility studies to identify pCR without surgery that range from 5 to 49%. In this manuscript, recently completed, ongoing, and planned clinical feasibility trials and a new omission of surgery trial are described. Drastic rethinking of all diagnostic and therapeutic management strategies that are ordinarily utilized for patients who receive standard breast cancer surgery is required. A roadmap of essential questions and issues that will have to be resolved as the field of nonoperative breast cancer management advances is described in detail.

Purpose To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation. Methods and Materials Eligibility criteria included in-breast recurrence occurring >1 year after whole-breast irradiation, Results Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 >1 to ≤2 cm, and 1 >2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 ( Conclusion Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare.

BACKGROUND Guidelines for the treatment of nonmetastatic inflammatory breast cancer (IBC) using trimodality therapy (TT) (chemotherapy, surgery, and radiotherapy) have remained largely unchanged since 2000. However, many patients with nonmetastatic IBC do not receive TT. It is unknown how patient-level (PL) and facility-level (FL) factors contribute to TT use. METHODS Using the National Cancer Data Base, patients with nonmetastatic IBC who underwent locoregional treatment from 2003 through 2011 were identified. The authors correlated PL factors, including demographic and tumor characteristics, with TT use. An observed-to-expected ratio for the number of patients treated with TT was calculated for each hospital by adjusting for significant PL factors. Hierarchical mixed effects models were used to assess the percentage of variation in TT use attributable to PL and FL factors, respectively. RESULTS Of the 542 hospitals examined, 55 (10.1%) and 24 (4.4%), respectively, were identified as significantly low and high outliers for TT use (P

Background: Contemporary improved neoadjuvant systemic therapy (NST) for breast cancer may result in a pathologic complete response (pCR) in up to 60% of patients (pts) yet imaging alone has a poor negative predictive value to determine which pts might be spared surgery. This study was designed to evaluate the hypothesis that percutaneous image guided biopsy after NST can accurately identify patients who may forgo surgery. Methods: Prospective single-center IRB approved study of 34 pts with clinical T1-3 N0-3 triple-negative (TN, n=23) or HER2-positive (n=11) invasive ductal cancer who received standard NST and consented for ultrasound/mammography guided vacuum-assisted core biopsy (VACB) and fine-needle aspiration (FNA) biopsy prior to standard surgery. Main outcome measures included accuracy, false-negative rate (FNR), and negative predictive value of image guided biopsy in predicting residual disease after NST. Breast pCR was defined as no residual DCIS or invasive disease. Final biopsy showing atypia and/or suspicion of residual disease was recorded as positive. Results: Median initial maximum tumor size based on imaging and physical exam was 3 cm (1.2-7 cm) and 47.1% had FNA/core biopsy proved nodal metastases. Final median maximum residual tumor size after NST was 0.9 cm (0-4.2 cm) with 94.1% having no palpable abnormality. Median number of VACB (9G) removed following NST was 10 (4-14) and was performed by stereotactic (67.6%) or ultrasound (32.4%) guidance. Overall, a breast pCR occurred in 18 (52.9%) of pts and breast pathologic response was concordant with nodal pathologic response in 33 (97%) of pts (1 pt with a breast pCR had 1/15 nodes with metastases). Overall, VACB combined with FNA following NST had a 100% (95% CI 89.7-100) accuracy, 0% FNR (95% CI 0-20.6), and 100% (95% CI 81.5-100) negative predictive value for determination of residual breast disease. Grade 1 adverse events which resolved from biopsy (bleeding, hematoma, bruising) occurred in 6 pts (17.6%). Conclusions: High rates of pCR among pts with TN/HER2-positive breast cancer receiving NST occur in a significant proportion of pts. The use of image guided VACB/FNA can identify pts after NST where significant residual disease is unlikely. Based on these results, an IRB approved clinical trial will shortly commence for pts with T1-2 TN/HER2-positive breast cancer with documented image guided biopsy proved pCR after NST to be followed by standard definitive whole-breast radiotherapy without surgery.Background: Contemporary improved neoadjuvant systemic therapy (NST) for breast cancer may result in a pathologic complete response (pCR) in up to 60% of patients (pts) yet imaging alone has a poor negative predictive value to determine which pts might be spared surgery. This study was designed to evaluate the hypothesis that percutaneous image guided biopsy after NST can accurately identify patients who may forgo surgery. Methods: Prospective single-center IRB approved study of 34 pts with clinical T1-3 N0-3 triple-negative (TN, n=23) or HER2-positive (n=11) invasive ductal cancer who received standard NST and consented for ultrasound/mammography guided vacuum-assisted core biopsy (VACB) and fine-needle aspiration (FNA) biopsy prior to standard surgery. Main outcome measures included accuracy, false-negative rate (FNR), and negative predictive value of image guided biopsy in predicting residual disease after NST. Breast pCR was defined as no residual DCIS or invasive disease. Final biopsy showing atypia and/or suspicion of residual disease was recorded as positive. Results: Median initial maximum tumor size based on imaging and physical exam was 3 cm (1.2-7 cm) and 47.1% had FNA/core biopsy proved nodal metastases. Final median maximum residual tumor size after NST was 0.9 cm (0-4.2 cm) with 94.1% having no palpable abnormality. Median number of VACB (9G) removed following NST was 10 (4-14) and was performed by stereotactic (67.6%) or ultrasound (32.4%) guidance. Overall, a breast pCR occurred in 18 (52.9%) of pts and breast pathologic response was concordant with nodal pathologic response in 33 (97%) of pts (1 pt with a breast pCR had 1/15 nodes with metastases). Overall, VACB combined with FNA following NST had a 100% (95% CI 89.7-100) accuracy, 0% FNR (95% CI 0-20.6), and 100% (95% CI 81.5-100) negative predictive value for determination of residual breast disease. Grade 1 adverse events which resolved from biopsy (bleeding, hematoma, bruising) occurred in 6 pts (17.6%). Conclusions: High rates of pCR among pts with TN/HER2-positive breast cancer receiving NST occur in a significant proportion of pts. The use of image guided VACB/FNA can identify pts after NST where significant residual disease is unlikely. Based on these results, an IRB approved clinical trial will shortly commence for pts with T1-2 TN/HER2-positive breast cancer with documented image guided biopsy proved pCR after NST to be followed by standard definitive whole-breast radiotherapy without surgery. Citation Format: Kuerer HM, Rauch GM, Krishnamurthy S, Adrada BE, Caudle AS, DeSnyder SM, Santiago L, Lucci A, Hobbs BP, Gilcrease M, Hwang R, Candelaria RP, Chavez Mac-Gregor M, Arribas E, Moseley T, Teshome M, Miggins MV, Smith BD, Valero V, Hunt KK, Yang WT. Feasibility trial for identification of patients for eliminating breast cancer surgery following neoadjuvant systemic therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-30.

Background: Availability of multiplex gene (MPG) testing for hereditary cancer has led to increase use of panel testing versus single gene testing for hereditary cancer. These panels include high, but also moderate penetrance genes. For some of these genes, associated cancer risk and risk management guidelines do not exist. Furthermore there is a high rate of variant of unknown significant (VUS) findings in non-BRCA genes. Currently, in the absence or minimal available data, health care providers and patients are faced with important risk management decisions, especially regarding preventive surgeries, such as prophylactic mastectomy. Currently, there is no data regarding prophylactic mastectomy rate among patients with breast cancer who underwent (MPG) testing. Therefore, our aim was to evaluate the rate of contralateral prophylactic mastectomy (CPM) in a cohort of individuals who underwent multiplex gene testing. Methods: Eight hundred thirty five patients with breast cancer who underwent MPG testing between the years 2013 and 2016 were identified using Institutional Clinical Cancer Genetics Database. Patients with pathogenic, likely pathogenic variants or who had a VUS were included in the analysis. Results: Of 835 patients with a diagnosis of breast cancer; 105 (13%) had a pathogenic or likely pathogenic mutation: 29 (28%) BRCA1, 26 (25%) BRCA2, 11 (11%) ATM, 2 (2%) BARD1, 3 (3%) BRIP, 9 (9%) CHEK2, 1 (1%) MSH2, 1 (1%) NBN, 5 (5%) PALB2, 4 (4%) PTEN, 1 (1%) RAD51C, 5 (5%) TP53, 4 (4%) CDH1, 2 (2%) MUTYH, 1 (1%) PMS2, 1 (1%) APC (1). A total of 102 (12%) VUS were found. Average age of diagnosis was 44 (Range 21-81). CPM rate was 32% (n=66) for the total cohort. Twenty nine % (n=19) of patients with non-BRCA mutations, 24.2% (n=16) with VUS and 46% (n=31) with BRCA mutations opted for CPM. Conclusion: Overall 32% of breast cancer patients with germline mutations or VUS opt for CPM at our institution. The rate for CPM in non- BRCA mutations carriers is high despite no available data regarding contralateral breast cancer risk and benefit of CPM. This finding should be validated in larger cohorts, including identification of reasons behind decision for CPM in these cohorts. Citation Format: Elsayegh N, Gutierrez Barrera AM, Kuerer HM, Hernandez ND, Litton JK, Arun BK. CPM rate among individuals with breast cancer who underwent multiplex gene testing for hereditary cancer: Single institution experience [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-09.

Rationale and Objectives This study aims to determine if locoregional restaging with diagnostic mammography and ultrasound (US) of the whole breast and regional nodes performed for quality assurance in women with newly diagnosed breast cancer who were referred to a tertiary care center yields incremental cancer detection. Materials and Methods An institutional review board-approved retrospective, single-institution database review was performed on the first 1000 women referred to our center in 2010 with a provisional breast cancer diagnosis. Locoregional restaging consisted of diagnostic full-field digital mammography combined with US of the whole breast and regional nodal basins. Bilateral whole-breast US was performed in women with contralateral mammographic abnormality or had heterogeneously or extremely dense parenchyma. Demographic, clinical, and pathologic factors were analyzed. Results Final analyses included 401 women. Of the 401 women, 138 (34%) did not have their outside images available for review upon referral. The median age was 54 years (range 21–92); the median tumor size was 2.9 cm (range 0.6–18.0) for women whose disease was upstaged and 2.2 cm (range 0.4–15.0) for women whose disease was not upstaged. Incremental cancer detection rates were 15.5% (62 of 401) in the ipsilateral breast and 3.9% (6 of 154) in the contralateral breast (P