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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.

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.

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.

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.

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?

Importance Most lymphedema studies include a heterogeneous population and focus on patients treated with adjuvant chemotherapy. Objective To examine factors associated with lymphedema after neoadjuvant chemotherapy (NAC) and axillary lymph node dissection in women with node-positive breast cancer. Design, Setting, and Participants This cohort study included data from 701 women 18 years or older with cT0-T4N1-2M0 breast cancer with documented axillary nodal metastasis at diagnosis who were enrolled in the American College of Surgeons Oncology Group Z1071 (Alliance for Clinical Trials in Oncology) trial, which took place from January 1, 2009, to December 31, 2012. Data analysis was performed from January 11, 2018, to November 9, 2018. Interventions All participants received NAC, breast operation, and axillary lymph node dissection. Participants underwent prospective arm measurements and symptom assessment after NAC completion and at 6-month intervals to 36 months postoperatively. Main Outcomes and Measures Factors associated with lymphedema were defined as self-reported arm heaviness or swelling (lymphedema symptoms) or an arm volume increase of 10% or more (V10) or 20% or more (V20). Results A total of 486 patients (mean [SD] age, 50.1 [10.8] years) were included in this study. Median follow-up for the 3 measures was 2.2 to 3.0 years. Cumulative lymphedema incidence at 3 years was 37.8% (95% CI, 33.1%-43.2%) for lymphedema symptoms, 58.4% (95% CI, 53.2%-64.1%) for V10, and 36.9% (95% CI, 31.9%-42.6%) for V20. Increasing body mass index (hazard ratio [HR], 1.04; 95% CI, 1.01-1.06) and NAC for 144 days or longer (HR, 1.48; 95% CI, 1.01-2.17) were associated with lymphedema symptoms. The V20 incidence was higher among patients who received NAC for 144 days or longer (HR, 1.79; 95% CI, 1.19-2.68). The V10 incidence was highest in patients with 30 nodes or more removed (HR, 1.70; 95% CI, 1.15-2.52) and increased with number of positive nodes (HR, 1.03; 95% CI, 1.00-1.06). On multivariable analysis, obesity was significantly associated with lymphedema symptoms (HR, 1.03; 95% CI, 1.01-1.06), and NAC length was significantly associated with V20 (HR, 1.74; 95% CI, 1.15-2.62). Conclusions and Relevance In this study, longer NAC duration and obesity were associated with increased lymphedema incidence, suggesting that patients in these groups may benefit from enhanced prospective lymphedema surveillance.

BACKGROUND: Successful breast conserving surgery requires achieving negative margins. At our institution, the whole surgical specimen is imaged, then serially sectioned with repeat imaging. A multi-disciplinary discussion then determines need for excision of additional margins. The goal of this study was to determine the benefit of each component of this approach in reducing the number of positive margin. METHODS: This single-institution prospective study included 10 breast surgical oncologists who were surveyed to ascertain whether they would have taken additional margins based their review of whole specimen images (WSI), and review of serially-sectioned images (SSI). These results were compared to the multidisciplinary decisions (MDD) and pathology results. Margin status was defined using consensus guidelines. RESULTS: One hundred surveys were completed. Margins on the original specimen were positive or close in 21%. After WSI, surgeons reported they would have taken additional margins in 26 cases reducing the number of positive/close margins from 21% to 13% (p

OBJECTIVE: To determine the accuracy of fine-needle aspiration (FNA) and vacuum-assisted core biopsy (VACB) in assessing the presence of residual cancer in the breast after neoadjuvant systemic therapy (NST). SUMMARY BACKGROUND DATA: Pathologic complete response (pCR) rates after NST have improved dramatically, suggesting that surgery might be avoided in some patients. Safe avoidance of surgery would require accurate confirmation of no residual invasive/in situ carcinoma. METHODS: Forty patients with T1-3N0-3 triple-negative or HER2-positive cancer receiving NST were enrolled in this single-center prospective trial. Patients underwent ultrasound-guided or mammography-guided FNA and VACB of the initial breast tumor region before surgery. Findings were compared with findings on pathologic evaluation of surgical specimens to determine the performance of biopsy in predicting residual breast disease after NST. RESULTS: Median initial clinical tumor size was 3.3 cm (range, 1.2–7.0 cm); 16 patients (40%) had biopsy-proven nodal metastases. After NST, median clinical tumor size was 1.1 cm (range, 0–4.2 cm). Nineteen patients (47.5%) had a breast pCR and were concordant with pathologic nodal status in 97.5%. Combined FNA/VACB demonstrated an accuracy of 98% (95% CI, 87%–100%), false-negative rate of 5% (95% CI, 0%–24%), and negative predictive value of 95% (95% CI, 75%–100%) in predicting residual breast cancer. VACB alone was more accurate than FNA alone (P = 0.011). CONCLUSIONS: After NST, image-guided FNA/VACB can accurately identify patients with a breast pCR. Based on these results, a prospective clinical trial has commenced in which breast surgery is omitted in patients with a breast pCR after NST according to image-guided biopsy.

Obesity (BMI≥30) may be an etiologic and prognostic factor in inflammatory breast cancer (IBC). We examined the relationship between BMI, pathologic complete response (pCR), and circulating-tumor-cell (CTC) levels in IBC.Cohort included IBC patients diagnosed 2005-2015 who had neoadjuvant chemotherapy during a prospective trial on CTCs and pathologic review describing pCR. Chi-square, logistic regression, and Cox proportional hazards models were used to identify clinicopathologic associations with event-free survival (EFS).Of 73 patients, 61 (84%) had CTC values, 22 (30%) achieved a pCR, and 39 (53%) were obese. There was no difference between obese and non-obese patients for pCR rates (31% vs. 29%, p = 0.90) or presence of CTCs (23% vs. 26%, p = 0.80). Among non-obese patients, CTCs were associated with worse EFS (HR 11.69, p 0.01), but among obese patients, there was no difference in EFS between those with and without CTCs.BMI mediates CTCs' prognostic significance in IBC.

Background The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) provide guidelines regarding axillary nodal evaluation in ductal carcinoma in situ (DCIS), but data regarding national compliance with these guidelines remains incomplete. Methods We conducted a retrospective review of the National Cancer Data Base (NCDB) analyzing all surgical approaches to axillary evaluation in patients with DCIS. Logistic regression analysis was used to assess the multivariate relationship between patient demographics, clinical characteristics, and probability of axillary evaluation. Results We identified 88,083 patients diagnosed with DCIS between 1998 and 2011; 31,912 (37%) underwent total mastectomy (TM) and 55,349 (63%) had breast conserving therapy (BCT). Axillary evaluation increased from 44.4% in 1998 to 63.3% in 2011. In TM patients, axillary evaluation increased from 74.3% in 1998 to 93.4% in 2011. This correlated with an increase in sentinel lymph node biopsy (SLNB) from 24.3 to 77.1%, while ALND decreased from 50.0 to 16.3% (p

The practice of breast imaging in a collaborative multidisciplinary environment adds significant value to outcomes in women's health care. In this article, we describe multidisciplinary considerations in breast cancer screening and early detection, the impact of imaging and histopathologic findings in the diagnostic evaluation and management of breast abnormalities, and the contribution of imaging to surgical and radiation therapy planning for the breast cancer patient.The multidisciplinary delivery of breast care for women that incorporates screening, diagnosis of borderline and high-risk lesions, and management of the breast cancer patient adds considerable value to outcomes in health care.

Our need to create a program for individuals at high risk for breast cancer development led us to research the available data on such programs. In this paper, we summarize our findings and our thinking process as we developed our own program. Breast cancer incidence is increasing worldwide. Even though there are known risk factors for breast cancer development, approximately 60% of patients with breast cancer have no known risk factor, although this situation will probably change with further research, especially in genetics. For patients with risk factors based on personal or family history, different models are available for assessing and quantifying risk. Assignment of risk levels permits tailored screening and risk reduction strategies. Potential benefits of specialized programs for women with high breast cancer risk include more cost -effective interventions as a result of patient stratification on the basis of risk; generation of valuable data to advance science; and differentiation of breast programs from other breast cancer units, which can result in increased revenue that can be directed to further improvements in patient care. Guidelines for care of patients at high risk for breast cancer are available from various groups. However, running a high-risk breast program involves much more than applying a guideline. Each high-risk program needs to be designed by its institution with consideration of local resources and country legislation, especially related to genetic issues. Development of a successful high-risk program includes identifying strengths, weaknesses, opportunities, and threats; developing a promotion plan; choosing a risk assessment tool; defining "high risk"; and planning screening and risk reduction strategies for the specific population served by the program. The information in this article may be useful for other institutions considering creation of programs for patients with high breast cancer risk.

Early-stage breast cancer patients with minimal axillary disease identified by sentinel lymph node dissection (SLND) have low regional recurrence rates when treated with breast-conserving surgery and radiation therapy (XRT) and many avoid a completion axillary lymph node dissection (CLND). As the incidence of total mastectomy (TM) has increased, it has become important to characterize which TM patients with a positive SLN may not benefit from further axillary treatment. An institutional database was utilized to identify patients treated with a TM for invasive breast cancer and who had a positive SLN from 1994 to 2010. Clinicopathologic factors were analyzed. Regional recurrence rate, recurrence-free survival (RFS), and overall survival (OS) were determined. A total of 525 patients with invasive breast cancer and a positive SLN were treated with TM, including 58 patients who did not have CLND or XRT and 12 patients who did not have CLND but did receive XRT. Median follow-up was 66 months. The incidence of regional recurrence was not significantly different for patients who received no further axillary treatment compared to those who underwent CLND without XRT or those treated with XRT without CLND (10 years rate: 3.8 vs. 1.6 and 0 % respectively). RFS and OS were not significantly different among patients who received no further axillary treatment compared to those who underwent CLND, XRT, or both. In select patients with early-stage breast cancer treated with mastectomy with a positive SLN, CLND may be avoided without adversely affecting recurrence or survival.

With improvements in chemotherapy regimens, targeted therapies, and our fundamental understanding of the relationship of tumor subtype and pathologic complete response (pCR), there has been dramatic improvement in pCR rates in the past decade, especially among triple-negative and human epidermal growth factor receptor 2-positive breast cancers. Rates of pCR in these groups of patients can be in the 60 % range and thus question the paradigm for the necessity of breast and nodal surgery in all cases, particularly when the patient will be receiving adjuvant local therapy with radiotherapy. Current practice for patients who respond well to neoadjuvant chemotherapy (NCT) is often to proceed with the same breast and axillary procedures as would have been offered women who had not received NCT, regardless of the apparent clinical response. Given these high response rates in defined subgroups among exceptional responders it is appropriate to question whether surgery is now a redundant procedure in their overall management. Further, definitive radiation without surgical resection with or without systemic therapy has been proven effective for several other malignant disease sites including some stages of esophageal, anal, laryngeal, prostate, cervical, and lung carcinoma. The main impediments for potential elimination of surgery have been the fact that prior and current standard and functional breast imaging methods are incapable of accurate prediction of residual disease and that integrating percutaneous biopsy of the breast primary and nodes following NCT may circumvent this issue. This article highlights historical attempts at omission of surgery following NCT in an earlier era, the current status of breast and nodal imaging to predict residual carcinoma, and ongoing and planned trials designed to identify appropriate patients who might be selected for clinical trials designed to test the safety of selected elimination of breast cancer surgery in percutaneous image-guided biopsy-proven exceptional responders to NCT.

The impact of close margins in patients with ductal carcinoma-in situ (DCIS) treated with mastectomy is unclear; however, this finding may lead to a recommendation for postmastectomy radiotherapy (PMRT). We sought to determine the incidence and consequences of close margins in patients with DCIS treated with mastectomy.The records of 810 patients with DCIS treated with mastectomy from 1996 through 2009 were reviewed. Clinical and pathologic factors were analyzed with respect to final margin status. Median follow-up was 6.3 years.Overall, 94 patients (11.7 %) had close margins (positive, n = 5; negative but ≤1 mm, n = 54; 1.1-2.9 mm, n = 35). Independent risk factors for close margins included multicentricity, pathologic lesion size ≥1.5 cm, and necrosis, but not age, use of skin-sparing mastectomy, or immediate reconstruction (p0.05). Seven patients received PMRT, and none had a locoregional recurrence (LRR). Among the remaining 803 patients, the 10-year LRR rate was 1 % (5.0 % for margins ≤1 mm, 3.6 % for margins 1.1-2.9 mm, and 0.7 % for margins ≥3 mm [p0.001]). The 10-year rate of contralateral breast cancer was 6.4 %. On multivariate analysis, close margins was the only independent predictor of LRR (p = 0.005).Close margins occur in a minority of patients undergoing mastectomy for DCIS and is the only independent risk factor for LRR. As the LRR rate in patients with close margins is low and less than the rate of contralateral breast cancer, PMRT is not warranted except for patients with multiple close/positive margins that cannot be surgically excised.

The clinicopathologic, mammographic, and sonographic findings in patients with pure ductal carcinoma in situ (DCIS) were assessed by estrogen receptor (ER) expression. After institutional review board approval, patients with pure DCIS evaluated from January 1996 to July 2009 with known ER status and available imaging were identified. Images were reviewed as per the ACR BI-RADS® lexicon (4th edition). Clinical, pathologic, and imaging characteristics were analyzed by ER status using t test, Chi square test, and Fisher’s exact test. Of 1,219 patients with pure DCIS and known ER status identified, 1,187 with complete data were included. Mammography was performed in all 1,187 patients and sonography in 519 (44 %). There were 972 (82 %) patients with ER-positive and 215 (18 %) with ER-negative disease. ER-negative DCIS was more likely to be high grade (93 vs 44 %, p

Learning Objectives Discuss known data regarding outcomes in pregnancy-associated breast cancer. Evaluate outcomes in a single institution when compared to nonpregnant breast cancer patients. Background. The purpose of this analysis was to compare disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) between pregnant and nonpregnant patients with breast cancer. Methods. From 1989 to 2009, 75 women were treated with chemotherapy during pregnancy. Each pregnant case was matched on age and cancer stage to two nonpregnant patients with breast cancer (controls). Fisher's exact test, the Kaplan-Meier method, and Cox proportional hazards regression models were used. Results. Median follow-up time for patients who were alive at the end of follow-up (n = 159) was 4.20 years (range: 0.28–19.94 years). DFS at 5 years was 72% (95% confidence interval [CI]: 58.3%–82.1%) for pregnant patients and 57% (95% CI: 46.7%–65.8%) for controls (p = .0115). Five-year PFS was 70% (95% CI: 56.8%–80.3%) for pregnant patients and 59% (95% CI: 49.1%–67.5%) for controls (p = .0252). Five-year OS was 77% (95% CI: 63.9%–86.4%) for pregnant patients and 71% (95% CI: 61.1%–78.3%) for controls (p = .0461). Hazard ratio estimates favored improved survival for pregnant patients in univariate analyses and multivariate analyses, controlling for age, year of diagnosis, stage, and tumor grade. Conclusions. For patients who received chemotherapy during pregnancy, survival was comparable to—if not better than—that of nonpregnant women. Pregnant patients with breast cancer should receive appropriate local and systemic therapy for breast cancer.

This study was performed to evaluate long-term local-regional control rates after breast-conserving therapy (BCT) for patients undergoing surgery before or after neoadjuvant chemotherapy.There were 2983 patients who underwent segmental mastectomy with whole-breast irradiation from 1987 to 2005. Clinicopathological and outcome data were reviewed, and comparisons were made between those undergoing surgery before and those undergoing surgery after neoadjuvant chemotherapy.There were 2331 patients (78%) who underwent surgery first and 652 (22%) received neoadjuvant chemotherapy. Patients receiving neoadjuvant chemotherapy had more advanced disease at baseline and more adverse clinicopathological features. The 5- and 10-year local-regional recurrence (LRR)-free survival rates were 97% [95% confidence interval (CI), 96-98) and 94% (95% CI, 93-95) for surgery first and 93% (95% CI, 91-95) and 90% (95% CI, 87-93) after neoadjuvant chemotherapy (P0.001). However, there were no differences in LRR-free survival rates when comparing the presenting clinical stage (P = NS). Of 607 patients presenting with clinical stage II/III disease, chemotherapy downstaged 313 patients (52%) to pathological stage 0/I disease; 294 (48%) had residual stage II/III disease. In multivariate analysis, an age less than 50 years, clinical stage III, grade 3, estrogen receptor (ER)-negative disease, estrogen receptor-positive disease without receipt of endocrine therapy, lymphovascular invasion, multifocal disease on pathology, and close/positive margins were associated with LRR. Use of neoadjuvant chemotherapy was not significant when added to the model. Adjusting for adverse factors, there were no differences in LRR between patients who underwent surgery before and those who underwent neoadjuvant chemotherapy after surgery.LRR after BCT is driven by tumor biology and disease stage. Appropriately selected patients can achieve high rates of local-regional control with BCT with either upfront surgery or surgery after neoadjuvant chemotherapy.

Our purpose was to examine the incidence and impact on survival of other primary malignancies (OPM) outside of the breast in breast cancer patients and to identify risk factors associated with OPM.Patients with stage 0-III breast cancer treated with breast conserving therapy at our center from 1979 to 2007 were included. Risk factors were compared between patients with/without OPM. Logistic regression was used to identify factors that were associated with OPM. Standardized incidence ratios (SIRs) were calculated.Among 4,198 patients in this study, 276 (6.6 %) developed an OPM after breast cancer treatment. Patients with OPM were older and had a higher proportion of stage 0/I disease and contralateral breast cancer compared with those without OPM. In a multivariate analysis, older patients, those with contralateral breast cancer, and those who did not receive chemotherapy or hormone therapy were more likely to develop OPM after breast cancer. Patients without OPM had better overall survival. The SIR for all OPM sites combined after a first primary breast cancer was 2.91 (95 % confidence interval: 2.57-3.24). Significantly elevated risks were seen for numerous cancer sites, with SIRs ranging from 1.84 for lung cancer to 5.69 for ovarian cancer.Our study shows that breast cancer patients have an increased risk of developing OPM over the general population. The use of systemic therapy was not associated with increased risk of OPM. In addition to screening for a contralateral breast cancer and recurrences, breast cancer survivors should undergo screening for other malignancies.

We previously developed a prognostic index for assessing local-regional recurrence (LRR) risk in patients undergoing breast conservation therapy (BCT) after neoadjuvant chemotherapy. The prognostic index assigns a point for each of the following variables: clinical N2/N3 disease, lymphovascular invasion, residual pathologic tumor size >2 cm, and multifocal residual disease on pathology. The current study was undertaken to evaluate this prognostic index in an independent cohort. We identified 551 patients treated from 2001 to 2005 with neoadjuvant chemotherapy, mastectomy or BCT, and radiation. These patients were not used in the original development of the prognostic index. Outcomes were stratified by prognostic index. The 5-year LRR-free survival was calculated using the Kaplan–Meier method, and differences were compared using the log-rank test. For patients undergoing BCT, the 5-year LRR-free survival rates were 92, 92, 84, and 69% when the prognostic index was 0 (n = 91), 1 (n = 82), 2 (n = 38), or 3–4 (n = 13) (P = 0.01). The 5-year LRR-free survival rates were similar between patients undergoing mastectomy or BCT when the prognostic index score was 0, 1, or 2. When the prognostic index score was 3–4, the 5-year LRR-free survival was significantly lower for patients treated with BCT compared with mastectomy (69 vs. 93%, P = 0.007). The previously developed prognostic index was successful in stratifying patients with respect to LRR in an independent cohort undergoing BCT after neoadjuvant chemotherapy. The prognostic index can be used to identify patients at high risk for LRR who may be considered for more extensive surgery or enrollment into clinical trials evaluating novel strategies for local-regional control.

To classify ipsilateral breast tumor recurrences (IBTR) as either new primary tumors (NP) or true local recurrence (TR). We utilized 2 different methods and compared sensitivities and specificities between them. Our goal was to determine whether distinguishing NP from TR had prognostic value.After breast-conservation therapy, IBTR may be classified into 2 distinct types (NP and TR). Studies have attempted to classify IBTR by using tumor location, histologic subtype, DNA flow cytometry data, or gene-expression profiling data.A total of 447 (7.9%) of 5660 patients undergoing breast-conservation therapy from 1970 to 2005 experienced IBTR. Clinical data from 397 patients were available for review. We classified IBTRs as NP or TR on the basis of either tumor location and histologic subtype (method 1) or tumor location, histologic subtype, estrogen receptor status and human epidermal growth factor receptor 2 status (method 2). Kaplan-Meier curves and log-rank tests were used to evaluate overall and disease-specific survival differences between the 2 groups. Classification methods were validated by calculating sensitivity and specificity values using a Bayesian method.Of 397 patients, 196 (49.4%) were classified as NP by method 1 and 212 (53.4%) were classified as NP by method 2. The sensitivity and specificity values were 0.812 and 0.867 for method 1 and 0.870 and 0.800 for method 2, respectively. Regardless of method used, patients classified as NP developed contralateral breast carcinoma more often but had better 10-year overall and disease-specific survival rates than those classified as TR. Patients with TR were more likely to develop metastatic disease after IBTR.Ipsilateral breast tumor recurrences classified as TR and NP had clinically different features, suggesting that classifying IBTR may provide clinically significant data for the management of IBTR.

Background Complete axillary lymph node dissection (ALND) after a positive sentinel lymph node biopsy (SLNB) remains the standard practice. As nodal surgery has long been considered a staging procedure without a clear survival benefit, the need for ALND in all patients is debatable. The purpose of this study was to examine differences in survival for patients undergoing SLNB alone versus SLNB with complete ALND.

We sought to evaluate the utilization of blue dye in addition to radioisotope and its relative contribution to sentinel lymph node (SLN) mapping at a high-volume institution.Using a prospectively maintained database, 3,402 breast cancer patients undergoing SLN mapping between 2002 and 2006 were identified. Trends in utilization of blue dye and results of SLN mapping were assessed through retrospective review. Statistical analysis was performed with Student t test and chi-square analysis.2,049 (60.2%) patients underwent mapping with dual technique, and 1,353 (39.8%) with radioisotope only. Blue dye use decreased gradually over time (69.8% in 2002 to 48.3% in 2006, p 0.0001). Blue dye was used significantly more frequently in patients with lower axillary counts, higher body mass index (BMI), African-American race, and higher T stage, and in patients not undergoing skin-sparing mastectomy. There was no difference in SLN identification rates between patients who had dual technique versus radiocolloid alone (both 98.4%). Four (0.8%) of 496 patients who had dual mapping and a positive SLN had a blue but not hot node as the only involved SLN. None of these four had significant counts detected in the axilla intraoperatively. Nine (0.4%) of 2,049 patients who had dual mapping had allergic reactions attributed to blue dye.Blue dye use has decreased with increasing institutional experience with SLN mapping. In patients with adequate radioactive counts in the axilla, blue dye is unlikely to improve the success of sentinel node mapping.

Neoadjuvant (preoperative) chemotherapy is considered standard therapy for patients with locally advanced breast cancer and patients with initially large tumors who desire breast-conserving therapy. Although neoadjuvant chemotherapy has not been shown to improve survival compared with conventional postoperative chemotherapy for patients with operable breast cancer,1 neoadjuvant chemotherapy does allow for in vivo evaluation of the response of the primary tumor and metastatic lymph nodes to chemotherapy, and this response carries prognostic significance. Neoadjuvant chemotherapy can produce a pathologic complete response (pCR) in both the breast and axilla, and such a response has been shown to correlate with improved disease-free and overall survival.1-3 In addition, as our group first reported,4 in patients with cytologically confirmed axillary metastases at diagnosis, pCR in the axilla alone after neoadjuvant chemotherapy, regardless of the primary tumor response, also correlates with improved disease-free and overall survival. In that study using the best available systemic breast cancer agents, we reported that neoadjuvant chemotherapy resulted in conversion to pathologically negative axillary lymph node status in 23% of patients.4 Systemic agents for breast cancer are now targeted toward specific subtypes and patients whose tumors over-express human epidermal growth factor receptor 2 (HER2) now routinely receive neoadjuvant chemotherapy regimens containing trastuzumab. Studies have shown that patients with pCR in both the breast and the axilla after treatment with trastuzumab-containing neoadjuvant chemotherapy have improved disease-free survival.5-7 However, to the best of our knowledge, the incidence and the prognostic significance of eradication of cytologically confirmed axillary lymph node metastases by trastuzumab-containing neoadjuvant chemotherapy have not been reported to date. The evaluation of the regional lymph node basins with ultrasonography and fine-needle aspiration biopsy of suspicious-appearing lymph nodes provides improved axillary staging over clinical examination alone. With this approach, nonpalpable axillary lymph nodes can be more appropriately characterized before the initiation of chemotherapy.8 Pathologic evaluation of the lymph nodes after chemotherapy can provide an even better assessment of the effectiveness of trastuzumab-containing neoadjuvant chemotherapy regimens when the pretreatment lymph node status has been clearly defined. Ultimately, knowledge of the expected pCR rates in the regional lymph nodes can help to guide the extent and need for surgical management of the axillary lymph nodes. In this study, we examined the incidence and prognostic significance of the complete eradication of axillary lymph node metastases and the clinicopathologic factors associated with this finding in 109 consecutive patients. Each patient had HER2-positive breast cancer and axillary lymph node metastases confirmed by ultrasound-guided fine-needle aspiration biopsy and received trastuzumab-containing neoadjuvant chemotherapy at The University of Texas M. D. Anderson Cancer Center.

Researchers are using the intraductal approach to advance breast cancer risk assessment, prevention, diagnosis, and treatment. Procedures and technologies that can access and interrogate the ductal-alveolar systems include nipple aspiration, ductal lavage and ductoscopy. Ductoscopic papillectomy, ductoscopic margin evaluation, and intraductal therapy are considered promising investigational and innovative treatments. These techniques are used to explore the biology of the normal breast; collect and analyze breast fluid and cells to identify biomarkers that can be used in breast cancer detection and risk assessment; and to identify new ways to find and administer therapeutic and/or preventive agents to the breast tissue. This report summarizes the latest research findings in these areas, presented at The 6th International Symposium on the Intraductal Approach to Breast Cancer in 2009.

Background The goal of the current study was to evaluate the effect of regional anesthesia using paravertebral block (PVB) on postoperative pain after breast surgery. Methods Patients undergoing unilateral breast surgery without reconstruction were randomized to general anesthesia (GA) only or PVB with GA and pain scores assessed. Results Eighty patients were randomized (41 to GA and 39 to PVB with GA). Operative times were not significantly different between groups. Pain scores were lower after PVB compared to GA at 1 hour (1 vs 3, P = .006) and 3 hours (0 vs 2, P = .001) but not at later time points. The overall worst pain experienced was lower with PVB (3 vs 5, P = .02). More patients were pain-free in the PVB group at 1 hour (44% vs 17%, P = .014) and 3 hours (54% vs 17%, P = .005) postoperatively. Conclusions PVB significantly decreases postoperative pain up to 3 hours after breast cancer surgery.

We aimed to evaluate the feasibility of sentinel lymph node biopsy (SLNB) in multicentric ⁄ multifocal breast cancer. In this prospective study, 23 women with multicentric ⁄ multifocal breast cancer underwent SLNB at our institution from April 2002 to February 2006. Presence of preoperative axillary metastases was confirmed by FNA. Patients underwent sub-areolar radiopharmaceutical injection ± isosulfan blue to perform SLNB, then completion ALND. The false-negative (FN) rate of SLNB was determined based upon final pathology. Twenty women with multicentric and three with multifocal invasive carcinoma were enrolled. The SLN identification rate was 100%. The overall FN rate of SLNB was 15% (95% CI 0.0466, 0.4281). Both cases with FN SLNB had multicentric disease, pathologic stage III breast cancer and a larger tumor burden compared with the study population. SLNB using sub-areolar injection is feasible for patients with multicentric ⁄ multifocal breast cancer yet may be associated with a higher FN rate in patients with large additive tumor burden.

Background: The aim of this study was to compare the extent of pathologic response in patients with HER2-positive (HER2+) breast cancer treated with standard neoadjuvant chemotherapy, with or without trastuzumab (H), according to hormone receptor (HR) status. Patients and methods: We included 199 patients with HER2+ breast cancer from three successive cohorts of neo-adjuvant chemotherapy on the basis of paclitaxel (Taxol) (P) administered weekly (w) or three weekly (3-w), followed by 5-fluorouracil (F), doxorubicin (A) or epirubicin (E), and cyclophosphamide (C). Residual cancer burden (RCB) was determined from pathologic review of the primary tumor and lymph nodes and was classified as pathologic complete response (pCR) or minimal (RCB-I), moderate (RCB-II), or extensive (RCB-III) residual disease. Results: In HR-positive (HR+) cancers, a higher rate of pathologic response (pCR/RCB-I) was observed with concurrent H + 3-wP/FEC (73%) than with 3-wP/FEC (34%, P = 0.002) or wP/FAC (47%; P = 0.02) chemotherapy alone. In HR-negative (HR−) cancers, there were no significant differences in the rate of pathologic response (pCR/RCB-I) from 3-wP/FAC (50%), wP/FAC (68%), or concurrent H + 3-wP/FEC (72%). Conclusions: Patients with HR+/HER2+ breast cancer obtained significant benefit from addition of trastuzumab to P/FEC chemotherapy; pathologic response rate was similar to that seen in HR−/HER2+ breast cancers.

Background We determined the incidence of positive sentinel lymph nodes (SLNs) in patients with ductal carcinoma in situ (DCIS) or microinvasive breast cancer (MIC) and the predictive factors of SLN metastasis in these patients. Methods Of 4,503 patients who underwent SLN dissection between March 1994 and March 2006 at our institution, we identified those with a preoperative diagnosis or final diagnosis of DCIS or MIC. Clinicopathologic factors were examined by logistic regression analysis. Results Of the 624 patients with a preoperative diagnosis of DCIS or MIC, 40 had positive SLNs (6.4%). Of the 475 patients with a final diagnosis of DCIS or MIC, 9 had positive SLNs (1.9%). Clinical DCIS size >5 cm was the only independent predictor of positive SLN for patients with a preoperative diagnosis and patients with a final diagnosis of DCIS or MIC. Core biopsy as the method of preoperative diagnosis and DCIS size >5 cm were independent predictors for a final diagnosis of invasive carcinoma in the 149 patients who had a preoperative diagnosis of DCIS or MIC. Conclusions SLN dissection for patients with a diagnosis of DCIS should be limited to patients who are planned for mastectomy or who have DCIS size >5 cm. Patients who have a core-needle biopsy diagnosis of DCIS have a higher risk of invasive breast cancer on final pathologic assessment of the primary tumor. This information can be used in preoperative counseling of patients with DCIS regarding the timing of SLN biopsy.

To minimize treatment variations, we have implemented clinical pathways for all breast cancer patients undergoing surgery. We sought to determine the incidence of postoperative venous thromboembolism (VTE) in patients treated on these pathways.Cancer patients have an increased risk of VTE because of a hypercoagulable state. The risk of VTE following breast cancer surgery is not well established.We retrospectively reviewed prospectively collected data for all patients who underwent breast cancer surgery and were treated on the clinical pathways with mechanical antiembolism devices and early ambulation in the postoperative period between January 2000 and September 2003.During the study period, 3898 patients underwent 4416 surgical procedures. Seven patients with postoperative VTE within 60 days were identified, for a rate of 0.16% per procedure. Six patients presented with only a deep venous thrombosis or a pulmonary embolism; 1 patient had both. The median time from surgery to diagnosis of VTE was 14 days (range, 2-60 days; mean, 22 days). No relationship was identified between stage of breast cancer or type of breast surgery and development of VTE. Two (29%) of the 7 patients with VTE had received neoadjuvant chemotherapy. VTE treatment consisted of subcutaneous low-molecular-weight heparin (n = 5) or intravenous heparin (n = 2) followed by warfarin. There were no deaths.VTE following breast cancer surgery is rare in patients who are treated on clinical pathways with mechanical antiembolism devices and early ambulation in the postoperative period. We conclude that systemic VTE prophylaxis is not indicated in this group of patients.

Objective: To determine the identification of sentinel lymph node biopsy (SLNB) in breast cancer patients after intraoperative injection of unfiltered technetium-99m sulfur colloid (Tc-99) and blue dye. Background: SLNB guided by a combination of radioisotope and blue dye injection yields the best identification rates in breast cancer patients. Radioisotope is given preoperatively, without local anesthesia, whereas blue dye is given intraoperatively. We hypothesized that, because of the rapid drainage noted with the subareolar injection technique of radioisotope, intraoperative injection would be feasible and less painful for SLN localization in breast cancer patients. Methods: Intraoperative injection of Tc-99 and confirmation blue dye was performed using the subareolar technique for SLNB in patients with operable breast cancer. The time lapse between injection and axillary incision, the background count, the preincision and ex vivo counts of the hot nodes, and the axillary bed counts were documented. The identification rate was recorded. Results: Ninety-six SLNB procedures were done in 88 patients with breast cancer employing intraoperative subareolar injection technique for both radioisotope (all 96 procedures) and blue dye (93 procedures) injections. Ninety-three (97%) procedures had successful identification; all SLNs were hot; 91 (of 93 procedures with blue dye) were blue and hot. The mean time from radioisotope injection to incision was 19.9 minutes (SD 8.5 minutes). The mean highest 10 second count was 88,544 (SD 55,954). Three of 96 (3%) patients with failure of localization had previous excisional biopsies: circumareolar and 2 upper outer quadrant incisions that may have disrupted the lymphatic flow. Conclusion: Intraoperative subareolar injection of radioisotope rapidly drains to the SLNs and allows immediate staging of the axilla, avoiding the need to coordinate diagnostic services and a painful preoperative procedure.

The authors previously compared the local tissue rearrangement, breast reduction, and latissimus dorsi flap reconstruction techniques for repairing partial mastectomy defects and showed the benefits of breast reduction.

Breast cancer is a significant health problem worldwide and is one of the leading causes of cancer-related mortality in women. Preoperative chemotherapy has become the standard of care for patients with locally advanced disease and is being used more frequently in patients with early-stage breast cancer. Sentinel lymph node biopsy has shown great promise in the surgical management of breast cancer patients, but its use following preoperative chemotherapy is yet to be determined. Eleven studies have been published with respect to the accuracy of sentinel lymph node biopsy following neoadjuvant chemotherapy. Ten studies showed favourable results, with the ability to identify a sentinel lymph node in 84% to 98% of cases, and reported false negative rates ranging from 0% to 20%. The accuracy of sentinel lymph node biopsy following preoperative chemotherapy for breast cancer ranges from 88% to 100%, with higher rates when specific techniques and inclusion criteria are applied. The published literature supports the use of sentinel lymph node biopsy for assessment of the axilla in patients with clinically node-negative disease following preoperative chemotherapy.

Objective The aim of this study was to determine the impact of the results of the 12-gene DCIS Score assay on (i) radiotherapy recommendations for patients with pure ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), and (ii) patient decisional conflict and state anxiety. Methods Thirteen sites across the US enrolled patients (March 2014–August 2015) with pure DCIS undergoing BCS. Prospectively collected data included clinicopathologic factors, physician estimates of local recurrence risk, DCIS Score results, and pre-/post-assay radiotherapy recommendations for each patient made by a surgeon and a radiation oncologist. Patients completed pre-/post-assay decisional conflict scale and state-trait anxiety inventory instruments. Results The analysis cohort included 127 patients: median age 60 years, 80 % postmenopausal, median size 8 mm (39 % ≤5 mm), 70 % grade 1/2, 88 % estrogen receptor-positive, 75 % progesterone receptor-positive, 54 % with comedo necrosis, and 18 % multifocal. Sixty-six percent of patients had low DCIS Score results, 20 % had intermediate DCIS Score results, and 14 % had high DCIS Score results; the median result was 21 (range 0–84). Pre-assay, surgeons and radiation oncologists recommended radiotherapy for 70.9 and 72.4 % of patients, respectively. Post-assay, 26.4 % of overall recommendations changed, including 30.7 and 22.0 % of recommendations by surgeons and radiation oncologists, respectively. Among patients with confirmed completed questionnaires (n = 32), decision conflict (p = 0.004) and state anxiety (p = 0.042) decreased significantly from pre- to post-assay. Conclusions Individualized risk estimates from the DCIS Score assay provide valuable information to physicians and patients. Post-assay, in response to DCIS Score results, surgeons changed treatment recommendations more often than radiation oncologists. Further investigation is needed to better understand how such treatment changes may affect clinical outcomes. Electronic supplementary material The online version of this article (doi:10.1245/s10434-016-5583-7) contains supplementary material, which is available to authorized users.

Circulating tumor cells (CTCs) can be identified in approximately 25 % of stage I-III breast cancer patients; CTCs presence is a predictor of poor outcome in metastatic breast cancer, but little is known regarding the prognostic significance of CTCs in non-metastatic triple-negative breast cancer (TNBC) patients. The aim of this study was to determine whether CTCs predict worse outcome in non-metastatic TNBC patients. We evaluated CTCs in 113 patients with stages I-III TNBC at the time of definitive surgery. CTCs were assessed using the CellSearch System®. Progression-free and overall survival were defined as time elapsed between date of diagnosis and either date of clinical disease progression, death, or last follow-up. Log-rank test and Cox regression analysis were used to determine associations of CTCs with progression-free and overall survival. The median follow-up was 40 months. CTCs were identified in 23/113 (20 %) of patients. No primary tumor characteristic or lymph node status predicted the presence of CTCs. The identification of ≥2 CTCs predicted shorter progression-free (log rank P ≤ 0.001; hazard ratio 8.30, 95 % CI 2.61–26.37) and overall survival (log rank P = 0.0004; hazard ratio 7.19, 95 % CI 1.98–26.06) versus survival for patients with

Background Isotope-coded affinity tag (ICAT) tandem mass spectrometry (MS) allows for qualitative and quantitative analysis of paired protein samples. We sought to determine whether ICAT technology could quantify and identify differential expression of tumor-specific proteins in nipple aspirate fluid (NAF) from the tumor-bearing and contralateral disease-free breasts of patients with unilateral early-stage breast cancer. Methods Paired NAF samples from 18 women with stage I or II unilateral invasive breast carcinoma and 4 healthy volunteers were analyzed using ICAT labeling, sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE), liquid chromatography, and MS. Proteins were identified by sequence database analysis. Western blot analysis of NAF from an independent sample set from 12 women (8 with early-stage breast cancer and 4 healthy volunteers) was also performed. Results 353 peptides were identified from tandem mass spectra and matched to peptide sequences in the National Center for Biotechnology Information database. Equal numbers of peptides were up- versus down-regulated. Alpha2HS-glycoprotein [Heavy:Light (H:L) ratio 0.63] was underexpressed in NAF from tumor-bearing breasts, while lipophilin B (H:L ratio 1.42), beta-globin (H:L ratio 1.98), hemopexin (H:L ratio 1.73), and vitamin D-binding protein precursor (H:L ratio 1.82) were overexpressed. Western blot analysis of pooled samples of NAF from healthy volunteers versus NAF from women with breast cancer confirmed the overexpression of vitamin D-binding protein in tumor-bearing breasts. Conclusion ICAT tandem MS was able to identify and quantify differences in specific protein expression between NAF samples from tumor-bearing and disease-free breasts. Proteomic screening techniques using ICAT and NAF may be used to find markers for diagnosis of breast cancer.