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The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer–focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor–positive, HER2-negative breast cancer.

PURPOSE We report on our early experience of our prospective multicenter phase 1 dose- escalation study of single-fraction stereotactic partial breast irradiation (S-PBI) for early stage breast cancer after partial mastectomy using a robotic stereotactic radiation system. METHODS AND MATERIALS Thirty women with in situ or invasive breast cancer stage 0, I, or II with tumor size

Our purpose was to evaluate cosmetic changes after 5-fraction adjuvant stereotactic partial breast irradiation (S-PBI).Seventy-five women with in situ or invasive breast cancer stage 0, I, or II, with tumor size ≤3 cm, were enrolled after lumpectomy in a phase 1 dose escalation trial of S-PBI into cohorts receiving 30, 32.5, 35, 37.5, or 40 Gy in 5 fractions. Before S-PBI, 3 to 4 gold fiducial markers were placed in the lumpectomy cavity for tracking with the Synchrony respiratory tracking system. S-PBI was delivered with a CyberKnife robotic radiosurgery system. Patients and physicians evaluated global cosmesis using the Harvard Breast Cosmesis Scale. Eight independent panelists evaluated digital photography for global cosmesis and 10 subdomains at baseline and follow-up. McNemar tests were used to evaluate change in cosmesis, graded as excellent/good or fair/poor, from baseline to year 3. Wilcoxon signed rank tests were used to evaluate change in subdomains. Cohen's kappa (κ) statistic was used to estimate interobserver agreement (IOA) between raters, and Fleiss' κ was used to estimate IOA between panelists.Median cosmetic follow-up was 5, 5, 5, 4, and 3 years for the 30, 32.5, 35, 37.5, and 40 Gy cohorts. Most patients reported excellent/good cosmesis at both baseline (86.3%) and year 3 (89.8%). No dose cohort had significantly worsened cosmesis by year 3 on McNemar analysis. No cosmetic subdomain had significant worsening by year 3. IOA was fair for patient-physician (κ = 0.300, P.001), patient-panel (κ = 0.295, P.001), physician-panel (κ = 0.256, P.001), and individual panelists (Fleiss κ = 0.327, P.001).Dose escalation of S-PBI from 30 to 40 Gy in 5 fractions for early stage breast cancer was not associated with a detectable change in cosmesis by year 3. S-PBI is a promising modality for treatment of early stage breast cancer.

This study reports predictive dosimetric and physiologic factors for fat necrosis after stereotactic-partial breast irradiation (S-PBI).Seventy-five patients with ductal carcinoma-in situ or invasive nonlobular epithelial histologies stage 0, I, or II, with tumor size3 cm were enrolled in a dose-escalation, phase I S-PBI trial between January 2011 and July 2015. Fat necrosis was evaluated clinically at each follow-up. Treatment data were extracted from the Multiplan Treatment Planning System (Cyberknife, Accuray). Univariate and stepwise logistic regression analyses were conducted to identify factors associated with palpable fat necrosis.With a median follow-up of 61 months (range: 4.3-99.5 months), 11 patients experienced palpable fat necrosis, 5 cases of which were painful. The median time to development of fat necrosis was 12.7 months (range, 3-42 months). On univariate analyses, higher V32.5-47.5 Gy (P.05) and larger breast volume (P.01) were predictive of any fat necrosis; higher V35-50 Gy (P.05), receiving 2 treatments on consecutive days (P = .02), and higher Dmax (P = .01) were predictive of painful fat necrosis. On multivariate analyses, breast volume larger than 1063 cmEarly-stage breast cancer patients treated with breast conserving surgery and S-PBI in our study had a fat necrosis rate comparable to other accelerated partial breast irradiation modalities, but S-PBI is less invasive. To reduce risk of painful fat necrosis, we recommend not delivering fractions on consecutive days; limiting V42.550 cm

Background Breast cancer metastases to an ipsilateral supraclavicular lymph node is assigned a N3 status in the TNM system and thus classified as stage III disease in the American Joint Commission on Cancer staging manual. Breast cancer metastatic to contralateral axillary lymph node (CAM) without metastases to any other distant organ is currently assigned M1 status (stage IV) instead of N3 (stage III). Patients and Methods We retrospectively reviewed the medical records of breast cancer patients diagnosed with CAM for their clinical presentation, pathologic diagnoses, treatment, and follow-up data. Patients who had distant metastases at the time of CAM diagnosis were excluded from the study. Results We report 12 breast cancer patients who developed CAM but no evidence of metastases in any other distant organ documented with extensive imaging workup. Imaging studies and thorough pathologic evaluation of the prophylactic total mastectomy specimen did not reveal a primary in the breast to account for the metastases in the axillary node. Conclusion Findings of our study as well as previous studies support that lymph node metastases in the contralateral axilla represents a locoregional spread of the tumor from the index breast via lymphatics rather than hematogenous spread. Therefore, isolated CAM in breast cancer patients should not be classified as stage IV disease.

PURPOSE/OBJECTIVE(S) We report on our early experience of a phase I dose escalation study of single fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer after partial mastectomy using a robotic stereotactic radiation system. MATERIALS/METHODS Patient eligibility included DCIS or invasive epithelial histologies, AJCC clinical stage 0, I, or II with tumor size < 3 cm, and negative margins. Prior to simulation, 3-4 gold fiducials were placed around the lumpectomy cavity to be used for real-time tracking during treatments. Dose limiting toxicity (DLT) was defined as grade ≥ 3 toxicity by CTCAE (version 4) deemed definitely related to treatment for: skin, ribs/bone (fracture), pulmonary (radiation pneumonitis), or neurological (intercostal or brachial plexus nerves) or any grade 4 or 5 toxicity definitely attributed to therapy. Both patients and physicians completed baseline and subsequent cosmesis outcome questionnaires using a 4-point scale ranging from excellent, good, fair, or poor. Cohort 1 was 22.5 Gy, cohort 2 26.5 Gy, and cohort 3 30 Gy all delivered in a single fraction. Dose escalation was permitted provided that one or fewer of the first seven, or two or fewer of nine patients experienced a DLT within 90 days of treatment within each dose group. If more patients had DLT in a given dose cohort, the maximum tolerable dose (MTD) would have been exceeded. RESULTS From 4/2016 to 1/2021, 11, 9, and 10 patients were treated on cohorts 1, 2 and 3 respectively. Of these, data from 18 evaluable patients from cohorts 1 and 2 and 6 patients from cohort 3, with at least 12 months of follow up are reported. Median f/u for cohort 1 was 36 m (r 24-48m), cohort 2 was 18 m (r 18-24m), and cohort 3 12 m (r 1-18m). Average age was 66.8 (r 47-84). Histology included 11 DCIS, and 19 invasive carcinomas. Of 11 DCIS, 9 were ER+, and 2 were ER-. All 19 invasive tumors were ER+. 23/29 patients received endocrine therapy, and no patient received chemotherapy. No patients experienced grade 3 or higher treatment related toxicity in the acute period (≤ 90 days), and MTD was not reached. There were two delayed grade 3 toxicities, (dose cohort 1 and 2, one patient had breast pain, and another had mastitis at 12 months and 9 months). No patients experienced grade 4 or 5 toxic events. Five patients developed fat necrosis in all three cohorts. Physicians scored cosmesis excellent or good at last follow-up in (10/11) 90%, (7/8) 87.5%, and (6/6)100%, in cohort 1,2, and 3 respectively, while patients scored excellent or good in (11/11) 100%, 8/8 (100%), and 5/6 (83%) patients. There has been no report of disease recurrences. CONCLUSION Dose was escalated to 30 Gy in single fraction, and the majority of patients maintained good or excellent cosmetic outcome, without grade 3 or 4 toxicity. Continued analysis of all cohorts are in progress.

Background: Ki67 values >10% 2-4 weeks (wks) after starting neoadjuvant ET (NET) indicates persistent cell proliferation, resistance to ET, and is associated with increased risk of recurrence. The ACOSOG Z1031 trial suggested that these tumors are also relatively chemotherapy (chemo) resistant with a low pathologic complete response (pCR) rate to NCT. The ALTERNATE trial (NCT01953588) is a randomized study of neoadjuvant anastrozole (ANA), fulvestrant (FUL), or ANA + FUL in postmenopausal patients (pt) with newly diagnosed clinical stage II or III ER+ (Allred score 6-8)/HER2- BC. Ki67 >10% at wk 4 or 12 after starting NET triggered triage to NCT of physician choice or weekly paclitaxel. Pts who refused protocol-directed therapy, were not candidates for NCT, or decided to undergo immediate surgery are being followed per protocol. Here we report the rates of pCR and residual cancer burden (RCB) following NCT for pts triaged to NCT due to Ki67 >10% at wk 4 or 12. Results: Of the 1,299 eligible pts randomized to receive ANA, FUL, or ANA + FUL, 286 (22%) had Ki67 >10% at wk 4 or 12. 168 of these 286 pts (58.7%) chose to switch to NCT, 32 went to surgery (11.2%), and 86 discontinued further protocol-directed therapy (30.1%). Among the 168 pts who underwent NCT, the presenting clinical T stages were cT2 (n=113; 67.26%), cT3 (n=47; 27.98%) and cT4 (n=8; 4.76%) and N stages were cN0 (n=82; 48.8%), cN1 (n=75; 44.6%), cN2/3 (n=9; 5.4%) and cNx (n=2; 1.2%). Central ER testing was performed on pre-treatment biopsies and confirmed ER Allred score 6-8 in 155 of 168 (92.2%) pts, with the rest being ER Allred score 4-5 (n=5; 3%), ER- (Allred score 0) (n=2; 1.2%), or not tested (n=6; 3.6%). Most (n=139; 82.7%) were ER+/PR+, while 17.3% (n=29) were ER+/PR-, and tumor grades were G1 (n=10; 6%), G2 (n=99; 58.9%), G3 (n=54; 32.1%), not reported (n=5; 3%). Baseline Ki67 levels prior to NET were >10% in 94% (n=158), ≤10% in 3% (n=5), and not done in 3% (n=5). NCT regimens administered included doxorubicin/cyclophosphamide (AC) followed by paclitaxel (T) (n=60; 35.71%); weekly paclitaxel (n=56; 33.33%), docetaxel/cyclophosphamide (TC) (n=33; 19.65%), other doxorubicin and/or taxane containing regimen (n=17; 10.12%), and cyclophosphamide/methotrexate/fluorouracil (CMF) (n=2; 1.19%). 35 (20.8%) pts did not complete planned course of NCT due to toxicity (n=27) or refusal (n=8). 154 NCT pts underwent surgery (mastectomy in 40.3%, and breast conserving surgery in 59.7%). The path ypT stages were Tis/0 (n=10; 6.5%), T1 (n=62; 40.3%), T2 (n=61; 39.6%), and T3/4 (n=21; 13.6%), and the ypN stages were N0 (n=66; 42.9%), N1 (n=57; 37%), N2/3 (n=30; 19.5%), and Nx (n=1; 0.6%). Among the 168 pts who started on NCT (intent to treat population), there were 8 pCRs (no invasive disease in the breast or lymph nodes) (4.8%; 95% CI: 2.1% to 9.2%). Residual Cancer Burden (RCB) categories include RCB 0 (n=8; 4.8%), RCB 1 (n=15; 8.9%), RCB 2 (n=82; 48.8%), RCB 3 (n=42; 25.0%), and not determined (n=21; 12.5%). Correlations of baseline pt and tumor characteristics with pathology response to NCT will also be presented. Conclusion: In pts with NET-resistant ER+/HER2- BC, salvage NCT is not likely to induce a complete or near complete response. More effective treatments are needed for this high-risk ER+/HER2- pt population. Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG); NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org. Clinical Trials.gov Identifier: NCT01953588 Citation Format: Cynthia X Ma, Vera Suman, A. Marilyn Leitch, Souzan Sanati, Kiran Vij, Gary W Unzeitig, Jeremy Hoog, Mark Watson, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erika Crouch, Horacio Maluf, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Travis Dockter, Jo Anne Zujewski, Anna Weiss, Kelly Hunt, Clifford Hudis, Eric P Winer, Matthew J Ellis, Lisa A Carey, Ann H Partridge. Neoadjuvant chemotherapy (NCT) response in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) resistant to endocrine therapy (ET) in the ALTERNATE trial (Alliance A011106) [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 GS4-05.

Intraoperative specimen radiographs performed during breast conservation surgery for cancer reduces the need for re-excision for positive margins. We studied 2D versus 3D image-guided cavity margin excision and compared it to final pathology and need for additional surgery. We conducted a retrospective review of 657 breast-conserving operations performed for cancer from 2013 to 2018. Procedures were performed by four surgeons at a single tertiary institution with access intraoperatively to 2D and 3D radiographs. Data collected included demographics, intraoperative margin assessment, final pathology, and re-excision rates. A total of 466 patients had 2D and 191 had 3D specimen imaging. The 2D group had a lower mean age and a higher body mass index and proportion of minority patients than the 3D group (P < 0.01). In the 3D group, there was a higher percentage of patients with mammographically denser breasts (P < 0.06); 58% of patients in the 3D group had additional imaging-directed cavity margins excised versus 32% of patients in the 2D group (P < 0.01). In the 2D group, 44 patients (9%) had positive final margins versus 8 patients (4%) in the 3D group (P = 0.02). No difference was found on total volume of excision (P = 0.56). The re-excision rate for the 2D group was 11% versus 5% for the 3D group (P = 0.02; adjusted odds ratio = 0.41, 95% confidence interval 0.19–0.86). Re-excision rates using both modalities are low. A lower re-excision rate is independently associated with 3D tomosynthesis. This allows surgeons to excise additional margins at the index operation, decreasing reoperations and anxiety/costs for patients.

We conducted a randomized, double-blind, vehicle-controlled clinical trial to investigate the use of a new proprietary hyaluronan (HA) formulation for the prevention of acute skin toxicity in breast cancer patients undergoing radiotherapy (RT). Thirty women with breast cancer undergoing whole breast RT were enrolled. Each patient was randomly assigned to HA formulation (study cream, S) on the medial or lateral half of the irradiated breast and the control cream (placebo, P) on the other half. The primary endpoint was physician’s evaluation of skin symptoms at week 5 during RT and week 2 post-RT. We also collected patients’ independent assessment of skin after RT, patient’s product preference, and an independent physician panel assessment of skin reactions based on photographs. Twenty-eight patients were evaluable. On physician’s evaluation, there was no significant difference in radiation dermatitis between S and P and no overall preference to either cream at week 5 during or week 2 post-RT. More patients preferred S in evaluating skin appearance and skin reactions, but this did not reach statistical significance. Univariate analysis showed that physicians had an overall preference to the S cream at week 2 post-RT in patients with larger breasts. On the independent panel assessment, 3 reviewers saw no significant difference in radiation toxicity, whereas one reviewer reported better skin outcome with S cream at week 5. We found a nonstatistically significant patient preference but overall no significant radioprotective effects for this HA formulation compared with placebo except in patients with larger breasts. The study was registered at www.clinicaltrials.gov (NCT02165605).

The objective is to define the therapeutic role of antiplatelet agents in a triple-negative breast cancer (TNBC) population. We performed retrospective analysis using the UTSW TNBC registry containing data from 222 Stage II–III TNBC patients treated between 1998 and 2016. Univariate analysis and multivariable logistic regression models were constructed to identify factors associated with disease-free survival (DFS), distant metastases rate (DMR), and overall survival outcomes. Antiplatelet drug use was determined by review of electronic medical records. A total of 65 patients used antiplatelet (AP) agents, and 157 patients did not use AP agents. Median follow-up for AP and non-AP groups was 41.3 and 40.9 months, respectively. There was an improvement in the AP group compared with the control group in 5-year DFS (80.4% at 5 years compared with 62.3% in the control group, p = 0.04) and 5-year DMR (8.8 vs. 31.9%, p = 0.007). In multivariate analysis, AP use was found to be significantly associated with improvements in DFS and DMR. We illustrate that antiplatelet agent use improves DMR and DFS among a stage II and III TNBC population despite our short follow-up evaluation. Longer follow-up evaluation will be required to determine additional outcome advantage for antiplatelet agent use. Our findings support consideration of investigation of antiplatelet therapy as an adjunctive therapy for TNBC at high risk for disease recurrence.

BACKGROUND Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2)/neu receptors, and is aggressive and therapeutically challenging. Genetic ancestry testing is an emerging medical field. Mitochondrial DNA (mtDNA), which is distinct from nuclear DNA, is maternally inherited and allows for origin determination. Patients with TNBC tend to be younger and are more likely to be African American, making this an ideal disease for mtDNA exploration. To the authors' knowledge, the current study is the first to perform mtDNA for self-described African American, White, and Hispanic patients with TNBC to identify mtDNA patterns. METHODS Patients with TNBC who were at any stage of therapy/survivorship were included. Self-reported ethnicity was confirmed at the time of the prospective buccal swab. Haplogroup prediction was performed on sequencing of hypervariable region 1. Using sequence similarity scores and lineage databases, sequence patterns were determined. Data regarding presentation and treatment, tumor features, and outcomes was collected. RESULTS A total of 92 patients were included: 31 self-described African American, 31 White, and 30 Hispanic individuals. Hispanic patients were found to have the largest tumor size (4.5 cm; P = .01) and youngest age (41 years; P

504 Background: For PM patients (pts) with locally advanced ER+ HER2- BC, NET improves breast conservation surgery (BCS) rates, and modified preoperative endocrine prognostic index (mPEPI) 0, defined as pT1-2 pN0 Ki67< 2.7%, or pathologic complete response (pCR: no invasive disease in breast or lymph node) is associated with low risk of recurrence without adjuvant chemotherapy (CT). The ALTERNATE trial was initiated to assess if the endocrine-sensitive disease rate (ESDR: number of mPEPI 0 pts/number of eligible pts initiating NET) with fulvestrant (F) or F+anastrozole (A) is improved relative to A alone (reported here) and if the 5-year (yr) recurrence-free survival (RFS) rate for pts with mPEPI 0 on A alone without CT is ≥ 95% (awaits further follow-up). Methods: PM pts with clinical stage II/III ER+ HER2- BC were randomized 1:1:1 to 1 mg A po daily, 500 mg F IM every 4 week (wk)s after loading dose, or A+F for 6 months. Ki67 was tested centrally on biopsies acquired prior to NET, wk 4, wk 12 and at surgery. Pts with Ki67 >10% at wk 4 or 12 were recommended to go off protocol-directed ET and switch to CT. Pts with mPEPI 0 at surgery were recommended to continue assigned ET for 1.5 yrs followed by A for a total of 5 yrs ET (and not to receive CT). The primary endpoint of the neoadjuvant phase was ESDR. ESDR of each F arm was compared to that of the A alone arm. With 425 pts per arm, a one-tailed alpha = 0.025 chi-square test of two independent proportions has 84% power to detect an increase of ≥10% in ESDR for F or F+A compared to the A arm, assuming ESDR ≤30% in A. Results: 1362 pts (A 452; F 454; A+F 456) were enrolled Feb 2014 to Nov 2018. 63 pts were excluded (did not start NET). Of the remaining 1299 pts (A 434; F 431, A+F 434), 42% were cN1-3 and 73% were considered candidates for BCS. ESDR was 18.6% (95%CI: 15.1-22.7%) with A, 22.7% (95%CI: 18.9-27.0%) with F, and 20.5% (95%CI: 16.8-24.6%) with A+F. No significant difference in ESDR was found between A and F (p=0.15) or A and A+F (p=0.55). Among the 825 pts with wk 4 Ki67 < 10% who completed NET and surgery, ESDR and the BCS rate were 27.7% and 70.3% with A; 29.6% and 68.1% with F, and 26.8% and 69.9% with A+F, respectively. Conclusion: Neither F nor F+A significantly improved ESDR compared to A alone in PM pts with locally advanced ER+ HER2- BC. RFS data are awaited. Support: U10CA180821, U10CA180882, U24CA196171, https://acknowledgments.alliancefound.org ; NCI BIQSFP, BCRF, Genentech, AstraZeneca. Clinical trial information: NCT01953588 .

Background: The Preoperative Endocrine Prognostic Index (PEPI) is a method to predict outcome after neoadjuvant endocrine therapy that integrates Ki67, estrogen receptor (ER) analysis and pathological stage from the surgical specimen (Ellis, JNCI 100:1380, 2008). We sought to further develop the PEPI for use in clinical trials by: a) establishing an efficient SOP for Ki67 analysis, b) determining the effect of simplifying the score by removing the ER component (modified "mPEPI") and c) independent validation of mPEPI in the ACOSOG (Alliance) Z1031 neoadjuvant aromatase inhibitor trial (Ellis, M, JCO 29:234, 2011). Methods: Ki-67 assay development focused on reproducing a 2.7% Ki-67 cut point (CP) required for PEPI. Ventana Image analysis (IA) to replace labor-intensive visual point counting (VPC) was assessed to increase scoring efficiency. Discordant scores led to a triage approach where cases with complex histological features that could not be resolved by IA were flagged for VPC. The Ki-67 scoring approach was preliminarily validated on T1/2 N0 cases from the P024 and POL trials (SABCS 2013, abstract P3-05-190). Models with and without ER suggested ER was dispensable. A locked SOP for mPEPI was subsequently applied to the Z1031A trial. The primary endpoint was time from the date of surgery to local, regional, or distant recurrence in the mPEPI-0 group (T1/2 N0, Ki67 0 group. Results. mPEPI by IA was evaluated on 202 of 377 (53%) patients enrolled into Z1031A (6% of IA results were triaged to VPC). All patients have been followed a minimum of 2 years (median: 5 years; max: 7 years). Only 10 patients in the mPEPI-0 group (22.7%) received adjuvant chemotherapy, versus 78 in the mPEPI>0 group (49.4%). Time to breast cancer recurrence was decreased among those with mPEPI>0 status relative to those with mPEPI-0 status (log rank p=0.012). Only one disease event among 44 (2%) cases with mPEPI-0 was observed versus 26 of 158 cases with mPEPI>0 (16.5%) Conclusions. mPEPI-0 status can identify patients at low risk of relapse after neoadjuvant endocrine therapy: therefore mPEPI-0 status has operational characteristics similar to pCR after chemotherapy for ER-negative disease. mPEPI is undergoing prospective validation in the Alliance ALTERNATE trial that will assess whether Fulvestrant increases the mPEPI-0 rate and also will prospectively determine whether patients with mPEPI-0 status can safely be managed without adjuvant chemotherapy treatment. Citation Format: Souzan Sanati, Vera J Suman, Rodrigo Goncalves, Katherine DeSchryver, Cynthia X Ma, Jeremy Hoog, Erika Crouch, Michael Barnes, Gary Unzeitig, A Marilyn Leitch, Kelly K Hunt, Matthew J Ellis. Validation of the preoperative endocrine prognostic index in the ACOSOG (Alliance) Z1031 neoadjuvant aromatase inhibitor trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-13.

Background Obesity and high radiologic breast density independently increase breast cancer risk. We evaluated the effect of surgical weight loss on mammographic density (MD). Methods Patients undergoing bariatric surgery and screening mammography (MG) were identified, data regarding demographics, comorbidities, calculated and genetic breast cancer risk was collected. Patients had a MG before and after surgery. Fellowship-trained breast radiologists assigned Breast Imaging Reporting and Data System density categories. Results Patients underwent sleeve gastrectomy (n = 56) or gastric bypass (n = 7), 78% had hypertension, 48% had diabetes. Four had deleterious BRCA mutations, four were calculated high risk. Mean weight loss = 28.7 kg. Mean initial BMI = 44.3 kg/m2 (range:33–77), final BMI = 33.6 kg/m2 (range:20–62;p

Purpose To determine the pathologic complete response (pCR) rate in estrogen receptor (ER) –positive primary breast cancer triaged to chemotherapy when the protein encoded by the MKI67 gene (Ki67) level was > 10% after 2 to 4 weeks of neoadjuvant aromatase inhibitor (AI) therapy. A second objective was to examine risk of relapse using the Ki67-based Preoperative Endocrine Prognostic Index (PEPI). Methods The American College of Surgeons Oncology Group (ACOSOG) Z1031A trial enrolled postmenopausal women with stage II or III ER-positive (Allred score, 6 to 8) breast cancer whose treatment was randomly assigned to neoadjuvant AI therapy with anastrozole, exemestane, or letrozole. For the trial ACOSOG Z1031B, the protocol was amended to include a tumor Ki67 determination after 2 to 4 weeks of AI. If the Ki67 was > 10%, patients were switched to neoadjuvant chemotherapy. A pCR rate of > 20% was the predefined efficacy threshold. In patients who completed neoadjuvant AI, stratified Cox modeling was used to assess whether time to recurrence differed by PEPI = 0 score (T1 or T2, N0, Ki67 < 2.7%, ER Allred > 2) versus PEPI > 0 disease. Results Only two of the 35 patients in ACOSOG Z1031B who were switched to neoadjuvant chemotherapy experienced a pCR (5.7%; 95% CI, 0.7% to 19.1%). After 5.5 years of median follow-up, four (3.7%) of the 109 patients with a PEPI = 0 score relapsed versus 49 (14.4%) of 341 of patients with PEPI > 0 (recurrence hazard ratio [PEPI = 0 v PEPI > 0], 0.27; P = .014; 95% CI, 0.092 to 0.764). Conclusion Chemotherapy efficacy was lower than expected in ER-positive tumors exhibiting AI-resistant proliferation. The optimal therapy for these patients should be further investigated. For patients with PEPI = 0 disease, the relapse risk over 5 years was only 3.6% without chemotherapy, supporting the study of adjuvant endocrine monotherapy in this group. These Ki67 and PEPI triage approaches are being definitively studied in the ALTERNATE trial (Alternate Approaches for Clinical Stage II or III Estrogen Receptor Positive Breast Cancer Neoadjuvant Treatment in Postmenopausal Women: A Phase III Study; clinical trial information: NCT01953588).

Multiple localizers placed in a bracketed fashion facilitates excision of radiographically extensive breast lesions. In this study, bracketed radioactive seed localization (bRSL) was compared to bracketed wire localization (bWL). We hypothesized that bRSL would achieve adequate margins and decrease re-operation rates with similar or less specimen volumes (SV) than bWL. Retrospective review identified patients who underwent bracketed breast procedures at an academic medical center. Data collected included patient demographics, tumor features, treatment variables, and surgical outcomes. Wilcoxon rank-sum test and chi-square test were used to compare continuous and categorical data, respectively. A multivariable logistic regression model was used to evaluate the association between re-excision and localization technique after adjusting for clinically relevant variables. Patients who underwent bWL were 3.9 times more likely to undergo re-excision compared to patients in bRSL group (OR=3.9, 95% CI: 2.0-7.4). Initial and total SV did not significantly differ between the two groups (P=.4). Patients were significantly more likely to undergo a mastectomy in the bWL group than in the bRSL group (24% vs 7%; P

The early results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated no difference in locoregional recurrence for patients with positive sentinel lymph nodes (SLNs) randomized either to axillary lymph node dissection (ALND) or sentinel lymph node dissection (SLND) alone. We now report long-term locoregional recurrence results.ACOSOG Z0011 prospectively examined overall survival of patients with SLN metastases undergoing breast-conserving therapy randomized to undergo ALND after SLND or no further axillary specific treatment. Locoregional recurrence was prospectively evaluated and compared between the groups.Four hundred forty-six patients were randomized to SLND alone and 445 to SLND and ALND. Both groups were similar with respect to age, Bloom-Richardson score, Estrogen Receptor status, adjuvant systemic therapy, histology, and tumor size. Patients randomized to ALND had a median of 17 axillary nodes removed compared with a median of only 2 SLNs removed with SLND alone (P0.001). ALND, as expected, also removed more positive lymph nodes (P0.001). At a median follow-up of 9.25 years, there was no statistically significant difference in local recurrence-free survival (P = 0.13). The cumulative incidence of nodal recurrences at 10 years was 0.5% in the ALND arm and 1.5% in the SLND alone arm (P = 0.28). Ten-year cumulative locoregional recurrence was 6.2% with ALND and 5.3% with SLND alone (P = 0.36).Despite the potential for residual axillary disease after SLND, SLND without ALND offers excellent regional control for selected patients with early metastatic breast cancer treated with breast-conserving therapy and adjuvant systemic therapy.

Background: Accurate assessment of HER2 status is critical for selecting patients who will benefit from trastuzumab therapy. There is still no consensus regarding the optimal method to assess HER2 status. Computerized image analysis has been shown to provide a more accurate and objective way for quantification of HER2 expression by IHC than manual evaluation. It has been suggested that the use of image analysis may help to resolve some of the discrepancies between IHC and FISH assay. We compared the results of HER2 expression by IHC using automated image analysis with fluorescent in situ hybridization (FISH) assay. Design: Testing for HER2 expression by IHC and FISH was performed on 2853 specimens at UT Southwestern Medical Center between the years 2002 to 2011. Quantification of IHC HER2 expression was done by image analysis and scored as positive (>2.0), borderline (1.5 to 2.0) and negative. (2.0, 1.8 to 2.0 and Results: IHC compared to FISH Conclusion: Despite improvements in IHC testing, the FISH assay may be a better method for determining HER2 status. Factors such as tissue fixation, scoring methods and choice of antibodies may contribute to the lower specificity of IHC. In the amplified group, the gene amplification ratio correlated with protein expression, being highest in the IHC positive cases and lowest in those that were negative. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-04.

Aims and objectives. This ABC to recovery study evaluated the combined and separate components of preoperative education and the effectiveness of wearing the Papilla Gown. Background. Surgical removal of the breast may lead to activity limitation, self-image issues, discomfort and later complication of lymphoedema. Design. This study used experimental and longitudinal design. Methods. One hundred and forty-five women undergoing mastectomies for stages two and three breast cancer were randomised into four groups: education and Papilla Gown, education only, gown only and control. The outcomes of activity (A), body image (B), comfort (C), knowledge and lymphoedema were assessed at baseline and/or 1 week and 6 months using three measures. All 145 participants completed the study questionnaires at first two measures, and forty-six of these participants completed the questionnaires at 6 months postoperatively. The setting for the study included two clinics and hospitals. To examine statistical significance at each time point after surgery, 2-way anovas were performed on ABC, knowledge and tape measurement to see whether there were any statistically significant differences between the four groups. All reported p-values are two sided. All statistical analyses were performed using sas 9.2 for Windows. Results. The mean age of the sample was 55 years. The study revealed that women who received the combined intervention demonstrated greater activity. Women who wore the gown only had a greater comfort level and decreased lymphoedema. Women that received preoperative education experienced increased knowledge. Conclusions. Outcomes suggest that the combined intervention (ABCs to recovery) can improve recovery following mastectomy. Relevance to clinical practice. The results will be used to further modify the intervention and to increase awareness of nurse practitioners and other healthcare professionals of the specific needs of postmastectomy patients.

Patient satisfaction in breast surgery is dependent on achieving a balance among all aesthetic subunits. The purpose of this study is to identify which subunit of the breast women consider important and correlate this clinically to improve patient satisfaction following breast surgery. A total of 313 subjects (ages, 20-80) were surveyed using a 25-point survey instrument collected via a telemedicine form. The data was analyzed to determine clinical significance. Of the subjects, 63% selected the upper inner quadrant as the most important subunit. Furthermore, 66% of the subjects indicated defects located in this region would lead them to seek operative intervention and this was consistent for all subgroups. Based on these results, defects in the upper inner quadrant of the breast are more likely to cause patient dissatisfaction. Patient outcomes following surgery can be enhanced by restoring volume and minimizing scars in this upper medial subunit of the breast.

Background and Objectives:HydroMARK® is a newly available biopsy marker for image-guided needle biopsies of non-palpable breast lesions. Objective was to determine if the marker could be utilized independently for lesion localization using intra-operative ultrasound alone.Methods:A single institutio

Background: Oncotype Dx (ODx) is a 21-gene RT-PCR based assay that provides prognostic and predictive information in patients with hormone receptor (HR) positive breast cancer. The test predicts the likelihood of disease recurrence in the form of a recurrence score (RS), which is categorized into low, intermediate and high-risk types. We examined the relationship between ODx RS and histologic parameters, DNA ploidy, tumor markers (ER, PR, Her2, Ki67, p53) expression by immunohistochemistry (IHC). Design: We identified 106 patients with HR-positive invasive breast cancer who were tested for ODx from the department files. Pathologic variables such as, tumor size, grade, histologic type, lymphovascular invasion (LVI) were reviewed. Tumor markers ER, PR, Her2, p53 expression, Ki67 index (KI) and ploidy were performed as part of the patient's diagnostic work-up using standard procedures. Scoring was done by automated image analysis. Results of biomarker expression were compared to the ODx RS. All Her2neu 3+ and 2+ results by IHC were confirmed by FISH. Ploidy was performed by the Autocyte system (Tripath) on Feulgen stained sections. Oncotype RS was reported as low (30). Results: Mean tumor size was 1.96 cm. Of the 106 cases, 87 (82%), 14 (13.2%) and 2(1.8%) were ductal, lobular and mixed types respectively. Grade 1, 2 and 3 comprised 35 (33.0%), 62 (58.4%) and 9 (8.5%) respectively. Twenty-one (19.8%) had LVI. Oncotype RS was low in 56 (52.8%), intermediate in 45 (42.4%) and high in 5 (4.7%). Mean tumor size in low RS group was 2.2 cm versus 1.6 cm in the intermediate/high RS group (p 14%) showed significant correlation with RS (p=0.0055). Her2neu IHC was negative in 43/49 (87.7%) and borderline in 6/49 (12.2%) and all were negative by FISH. Her2 FISH showed 100% (44/44) concordance with Her2 results by ODx. There was no association between DNA ploidy and RS (p=0.7143). P53 expression showed no significant correlation with RS (p=0.2602). Patients in the intermediate/high RS group were more likely to be treated with a combination of chemo plus anti-hormonal therapy (P Conclusions: This study shows a complete concordance between ER IHC and Her2 FISH with RT-PCR by ODx. Low PR scores and high KI predict high RS by ODx. There is a significant association between KI and ODx RS. Ki67 index identifies low and high RS groups, which correspond to the luminal A, and B subtypes of breast cancer respectively. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-10.

Background: Molecular subtypes of breast cancer have been characterized by gene expression analysis. Luminal subtypes are hormone receptor (HR) positive and Her2/neu negative. Immunohistochemistry (IHC) has been used as a surrogate test for gene expression. Ki67 is a proliferation marker that identifies high-risk subtype of luminal breast cancer. Recently, the proposed Ki67 index (KI) of 14% was suggested as a cut-off to distinguish between luminal A and luminal B tumors (JNCI. 2009;101:736-750). The oncotype dx (ODx) is a 21- gene test that provides prognostic and predictive information in early stage HR-positive breast cancer patients. The test is reported as low (30) risk recurrence scores (RS) Design: We investigated the relationship between ODx RS and luminal subtypes of breast cancers using the KI of 14% as the cut-off for distinguishing luminal A and B tumors. Biomarker analysis (ER, PR, Her2/neu, Ki67 and p53) was performed as part of the diagnostic work-up using standard IHC procedures. Scoring was done by automated image analysis. Her2/neu FISH was performed on all IHC 2+ and 3 + results. Pathologic parameters such as, tumor size, grade, and presence of LVI were evaluated. Ploidy was performed by the Autocyte system (Tripath) on Feulgen stained paraffin sections. Results: We identified 106 patients with HR positive breast cancer who were tested for ODx from February 2006 to May 2010. 85/106 had Ki67 data available for analysis. 46/85 (54%) were luminal A and 39/85 (46%) luminal B tumors. The mean KI in luminal A was 6.93% versus 31.1% in luminal B (P Conclusion: Ki67 is a useful marker that showed significant correlation with RS by ODx. Luminal A tumors are more likely to be low grade, diploid with low RS compared to luminal B tumors. Ki67 in conjunction with other pathologic parameters may serve as a surrogate marker for the ODx RS. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-08-07.

Breast-conserving therapy (BCT) is an accepted method of treating early breast cancer. We hypothesized that routine excision of additional cavity shave margins (CSM) at time of initial partial mastectomy reduces the need for additional surgery.A single-institution retrospective review was performed of women, 18 years or older, with a new diagnosis of breast cancer who underwent partial mastectomy between 1 January 2004 and 1 October 2009. Five hundred thirty-three charts were reviewed. Of those, 69 patients underwent CSM at time of initial operation. These 69 patients were matched with patients who had undergone partial mastectomy without CSM by tumor size, presence of extensive intraductal component, and primary histology.The two groups were well matched for age, nuclear grade, associated lymphovascular invasion (LVI), receptor status, and multifocality. We found that 31.9% (44/138) required return to the operating room (OR) for re-excision of margins. Rate of return to the OR was 21.7% (15/69) in the CSM group and 42.0% (29/69) in the matched group (p = 0.011). Multivariate analysis found factors significantly associated with need for additional operation included lack of CSM (odds ratio 9.2, 95% CI 2.8-30.5, p = 0.0003), larger extent of intraductal component (odds ratio 7.0, 95% CI 1.8-27.0, p = 0.005), and lack of directed re-excision (odds ratio 6.4, 95% CI 1.7-25.1, p = 0.007).CSM at time of initial partial mastectomy decreases rate of re-excision by as much as ninefold. CSM should be considered at time of initial operation to reduce the need for subsequent reoperation.

Time interval from diagnosis of breast cancer to treatment has been promulgated as one factor that can be used to evaluate cancer care quality. It remains controversial, however, whether a delay to treatment impacts survival. The purpose of this study was to evaluate whether delays from diagnosis to initial treatment in breast cancer impacts survival. A retrospective review of patients undergoing breast cancer treatment between August 2005 and December 2008 in a comprehensive, multidisciplinary breast oncology program was undertaken. Two hospital systems were included: a county hospital (CH) treating a primarily minority, indigent population and a university hospital (UH) treating a primarily Caucasian, insured population. Interval to treatment, calculated from date of diagnosis to surgery, chemotherapy, or radiation treatment, and overall survival was compared between the two groups. A total of 1337 patients were included; 634 patients were treated in the CH and 703 in the UH. Interval to treatment was longer in the CH compared with the UH (53.4 ± 2.0 vs 33.2 ± 1.2 days; mean ± standard error of the mean [SEM], P

e18678Background: The use of neoadjuvant chemotherapy (NAC) has allowed pathologic complete response (pCR) to become a predictive measure for breast cancer recurrence-free survival and overall surv...

Purpose Patients with breast cancer metastasis to the sentinel lymph nodes (SLNs) generally undergo completion axillary lymph node dissection (cALND), either concurrently with SLN biopsy or at a second procedure. The impact of the timing of cALND on pathologic results and complications in these patients has not been examined. Patients and Methods We examined outcomes from SLN-positive patients in American College of Surgeons Oncology Group (ACOSOG) trials Z0010 and Z0011. Pathologic data examined included primary tumor characteristics, total number of SLNs recovered, positive SLN(s) and non-SLN(s) identified. Complications assessed included axillary seroma, paresthesia, arm morbidity and range of motion, and lymphedema. Results A total of 1,003 assessable patients with SLN metastasis had immediate (n = 425) or delayed (n = 578) cALND. The median number of SLNs and axillary LNs removed were the same between groups. Patients who had immediate cALND more often had larger tumors, SLN metastasis identified intraoperatively, two or more positive SLNs, and higher pathologic N stage. Axillary paresthesia, seroma, and impaired extremity range of motion were more common in the immediate group during the early postoperative period, but not at later time points. There was no difference in lymphedema at any time point. Conclusion In ACOSOG trials Z0010 and Z0011, LN recovery and long-term complications were similar after either delayed or immediate cALND for patients with metastasis to SLNs. Patients who undergo immediate cALND experience more short-term morbidity. With respect to staging and complications, there is no clear detriment for patients with a positive SLN who undergo a second procedure for cALND.

We report 3 cases of sentinel lymph nodes (SLNs) containing benign glandular inclusions (BGIs) in patients with breast carcinoma that were initially misdiagnosed as metastatic carcinoma. The first case had an SLN with glandular elements adjacent to a squamous inclusion cyst, the second had an SLN with a single complex gland showing apocrine features, and the third had 2 SLNs, each containing rare glands lined by bland columnar cells and surrounded by thin, fibrous bands. All glandular elements were distinctly different from the corresponding invasive carcinoma. Immunostains for myoepithelial markers revealed smooth muscle myosin reactivity and scattered p63+ nuclei, indicating the presence of myoepithelial cells. Based on morphologic and immunohistochemical findings, a diagnosis of BGIs was established. Our case series report indicates that comparison with the morphologic features of primary breast carcinoma and using immunohistochemical analysis for myoepithelial markers are important ancillary tools in distinguishing BGIs from metastatic carcinoma.

Background: Many established breast cancer risk factors are related to the timing and duration of exposure to reproductive hormones, which are known to drive breast epithelial cell proliferation. The epigenetic molecular clock hypothesis suggests that CpG island methylation records the cell division history of benign epithelium. In proliferative epithelium, such as breast, this may provide an individualized cell-based measure of cancer risk.Methods: Methylation of cyclin D2, APC, HIN1, RASSF1A, and RAR-β2 was measured by quantitative multiplex methylation-specific PCR in 290 benign and malignant breast epithelial cell samples obtained by palpation-directed fine-needle aspiration biopsy from 164 women. Univariate, multivariate, and unsupervised cluster analysis was used to establish the relationship between TSG methylation and a personal history of breast cancer, predicted breast cancer risk, and specific breast cancer risk factors.Results: RASSF1A methylation was highly correlated with breast cancer risk [odds ratio (OR), 5.28; 95% confidence interval (95% CI), 1.95-14.32; P = 0.001], atypical cytology (OR, 4.11; 95% CI, 1.30-12.98; P = 0.016), and benign breast disease requiring biopsy (OR, 6.12; 95% CI, 1.41-26.51; P = 0.016). RASSF1A methylation increased linearly between ages 32 and 55. Increasing parity was associated with decreased APC methylation.Conclusions: TSG methylation increases in benign breast epithelium with increasing age. Because it is independently related to a personal history of benign or malignant breast disease and to predicted breast cancer risk, it may have value for breast cancer risk stratification and as a surrogate endpoint marker in prevention trials. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1051–9)

Background: Tumor suppressor gene (TSG) methylation is identified more frequently in random periareolar fine needle aspiration samples from women at high risk for breast cancer than women at lower risk. It is not known whether TSG methylation or atypia in nipple duct lavage (NDL) samples is related to predicted breast cancer risk.Methods: 514 NDL samples obtained from 150 women selected to represent a wide range of breast cancer risk were evaluated cytologically and by quantitative multiplex methylation-specific PCR for methylation of cyclin D2, APC, HIN1, RASSF1A, and RAR-β2.Results: Based on methylation patterns and cytology, NDL retrieved cancer cells from only 9% of breasts ipsilateral to a breast cancer. Methylation of ≥2 genes correlated with marked atypia by univariate analysis, but not multivariate analysis, that adjusted for sample cellularity and risk group classification. Both marked atypia and TSG methylation independently predicted abundant cellularity in multivariate analyses. Discrimination between Gail lower-risk ducts and Gail high-risk ducts was similar for marked atypia [odds ratio (OR), 3.48; P = 0.06] and measures of TSG methylation (OR, 3.51; P = 0.03). However, marked atypia provided better discrimination between Gail lower-risk ducts and ducts contralateral to a breast cancer (OR, 6.91; P = 0.003, compared with methylation OR, 4.21; P = 0.02).Conclusions: TSG methylation in NDL samples does not predict marked atypia after correcting for sample cellularity and risk group classification. Rather, both methylation and marked atypia are independently associated with highly cellular samples, Gail model risk classifications, and a personal history of breast cancer. This suggests the existence of related, but independent, pathogenic pathways in breast epithelium. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1812–21)

BACKGROUND. Nipple duct lavage (NDL) may be useful for breast cancer risk stratification. Published guidelines recommend that women with a 5-year Gail risk ≥1.7% should consider undergoing lavage for any fluid-yielding ducts, but it is not known whether increased breast cancer risk or nipple fluid production predict lavage atypia. METHODS. One hundred fifty women unselected for breast cancer risk underwent NDL with cannulation of all nipple aspirate fluid (NAF)-producing ducts and at least 1 dry duct. This resulted in 516 lavage samples. The rate of cytologic atypia was compared for NAF-positive ducts and NAF-negative ducts and for women with 5-year Gail risks ≥1.7% and

ContextThe American Society of Clinical Oncology/College of American Pathologists proposed several recommendations for human epidermal growth factor receptor 2 (HER2) test standardization. One suggestion was that image analysis (IA) could be useful for scoring of HER2/neu immunohistochemistry. The utilization of IA in a real-world practice in a large cohort of cases has not been previously reported.ObjectivesTo compare HER2/neu quantification by IA with gene amplification by fluorescence in situ hybridization (FISH); to determine sensitivity, specificity, and concordance rates with the FISH assay; and to determine association between HER2 status with estrogen receptor (ER), progesterone receptor (PR), and Ki-67 expression.DesignWe evaluated HER2 results performed by immunohistochemistry and FISH in conjunction with ER, PR, and Ki-67 in 3093 invasive breast cancer cases from 2002 to 2011.ResultsThe overall concordance between immunohistochemistry and FISH was 87.3% (1768 of 2026). When analyzed by year, there was an improvement in the positive concordance rate from 49.4% (44 of 89) to 95.0% (57 of 60) (P < .001). The negative concordance rate was at least 95% with a median false-negative rate of 1.5%. In the FISH+ group, amplification ratio showed significant correlation with IA scores (P < .001). Positive versus negative HER2 status was associated with lower ER and PR levels (P < .001) and higher Ki-67 expression (P < .001).ConclusionScoring of HER2/neu by IA was associated with high false-positive rates before 2008. Improvement in concordance rate after 2008 may be due to proper tissue handling, improved HER2/neu scoring by IA, and assay standardization.

To evaluate factors affecting sentinel lymph node (SLN) identification after neoadjuvant chemotherapy (NAC) in patients with initial node-positive breast cancer.SLN surgery is increasingly used for nodal staging after NAC and optimal technique for SLN identification is important.The American College of Surgeons Oncology Group Z1071 prospective trial enrolled clinical T0-4, N1-2, M0 breast cancer patients. After NAC, SLN surgery and axillary lymph node dissection (ALND) were planned. Multivariate logistic regression modeling assessing factors influencing SLN identification was performed.Of 756 patients enrolled, 34 women withdrew, 21 were ineligible, 12 underwent ALND only, and 689 had SLN surgery attempted. At least 1 SLN was identified in 639 patients (92.7%: 95% CI: 90.5%-94.6%). Among factors evaluated, mapping technique was the only factor found to impact SLN identification; with use of blue dye alone increasing the likelihood of failure to identify the SLN relative to using radiolabeled colloid +/- blue dye (P = 0.006; OR = 3.82; 95% CI: 1.47-9.92). The SLN identification rate was 78.6% with blue dye alone; 91.4% with radiolabeled colloid and 93.8% with dual mapping agents. Patient factors (age, body mass index), tumor factors (clinical T or N stage), pathologic nodal response to chemotherapy, site of tracer injection, and length of chemotherapy treatment did not significantly affect the SLN identification rate.The SLN identification rate after NAC was higher when mapping was performed using radiolabeled colloid alone or with blue dye compared with blue dye alone. Optimal tracer use is important to ensure successful identification of SLN(s) after NAC.

Background: American College of Surgeons Oncology Group Z0010 is a prospective multicenter trial designed to evaluate the prognostic significance of micrometastases in the sentinel lymph nodes and bone marrow aspirates of women with early-stage breast cancer. Surgical complications associated with the sentinel lymph node biopsy surgical procedure are reported. Methods: Eligible patients included women with clinical T1/2N0M0 breast cancer. Surgical outcomes were available at 30 days and 6 months after surgery for 5327 patients. Patients who had a failed sentinel node mapping (n = 71, 1.4%) or a completion lymph node dissection (n = 814, 15%) were excluded. Univariate and multivariate analyses were performed to identify predictors for the measured surgical complications. Results: In patients who received isosulfan blue dye alone (n = 783) or a combination of blue dye and radiocolloid (n = 4192), anaphylaxis was reported in .1% of subjects (5 of 4975). Other complications included axillary wound infection in 1.0%, axillary seroma in 7.1%, and axillary hematoma in 1.4% of subjects. Only increasing age and an increasing number of sentinel lymph nodes removed were significantly associated with an increasing incidence of axillary seroma. At 6 months, 8.6% of patients reported axillary paresthesias, 3.8% had a decreased upper extremity range of motion, and 6.9% demonstrated proximal upper extremity lymphedema (change from baseline arm circumference of >2 cm). Significant predictors for surgical complications at 6 months were a decreasing age for axillary paresthesias and increasing body mass index and increasing age for upper extremity lymphedema. Conclusions: This study provides a prospective assessment of the sentinel lymph node biopsy procedure, as performed by a wide range of surgeons, demonstrating a low complication rate.

Amplification and overexpression of the HER-2 oncogene in breast cancer is felt to be stable over the course of disease and concordant between primary tumor and metastases. Therefore, patients with HER-2 -negative primary tumors rarely will receive anti-Her-2 antibody (trastuzumab, Herceptin) therapy. A very sensitive blood test was used to capture circulating tumor cells (CTCs) and evaluate their HER-2 gene status by fluorescence in situ hybridization. The HER-2 status of the primary tumor and corresponding CTCs in 31 patients showed 97% agreement, with no false positives. In 10 patients with HER-2 -positive tumors, the HER-2 /chromosome enumerator probe 17 ratio in each tumor was about twice that of the corresponding CTCs (mean 6.64 ± 2.72 vs. 2.8 ± 0.6). Hence, the ratio of the CTCs is a reliable surrogate marker for the expected high ratio in the primary tumor. Her-2 protein expression of 10 CTCs was sufficient to make a definitive diagnosis of the HER-2 gene status of the whole population of CTCs in 19 patients with recurrent breast cancer. Nine of 24 breast cancer patients whose primary tumor was HER-2 -negative each acquired HER-2 gene amplification in their CTCs during cancer progression, i.e., 37.5% (95% confidence interval of 18.8–59.4%). Four of the 9 patients were treated with Herceptin-containing therapy. One had a complete response and 2 had a partial response.

Background:The mammary sentinel lymph node procedure can increase the detection of axillary metastases by 45% compared with standard axillary dissection. Some investigators have reported that reverse transcriptase-polymerase chain reaction (RT-PCR) increases metastasis detection even more, but it is uncertain whether a positive RT-PCR test in the face of a negative histological evaluation is clinically meaningful. Methods:RT-PCR for epithelial glycoprotein 2 and cytokeratin 19 was performed on sentinel and pooled nonsentinel axillary lymph nodes from 108 women with clinical stage I or II breast cancer who were followed up for a median of 40 months. Results:Axillary metastases were detected on standard tissue sections in 26% and by RT-PCR in 30%. Results for the two tests were concordant for 80% of the cases. RT-PCR upstaged 16%. Tumors from women whose lymph nodes were positive only by RT-PCR were phenotypically similar to those from women with no metastases detected by any method. Moreover, 4-year actuarial distant disease-free survival was 100% for women with metastases detected by RT-PCR only, as compared with 74% for those with metastases detected by routine histology (P = .03) and 93% for those with no metastases detected by either method (P = .04). Conclusions:Analysis of sentinel lymph nodes by RT-PCR for epithelial glycoprotein 2 and cytokeratin 19 is unlikely to provide clinically useful information.

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials.

The Gail model is a risk assessment tool that is accurate for general breast cancer risk screening. Because of the limited way that this model incorporates family history information, however, there are concerns that it may underestimate risk for many women attending specialized breast cancer risk assessment clinics. We collected comprehensive breast cancer risk factor information for 213 women attending a specialized breast cancer risk assessment clinic using a modified version of the CancerGene software. Breast cancer risk was calculated using the models of Gail and Claus as well as BRCAPRO and the tables of Bodian (for women with lobular neoplasia). Eighty-six percent of the women had a family history of breast cancer. Although 74% of women had risk factor histories that are thought to confound the Gail model (family history of breast cancer in second-degree relatives, family history of breast cancer before the age of 50, family history of bilateral breast cancer, family history of ovarian cancer, or personal history of lobular neoplasia), the inclusion of other models increased the risk level assignment in only 13% of the cases. We conclude that the Gail model is an appropriate risk assessment tool for most women attending specialized clinics, although the inclusion of models better able to account for family history information and personal history of lobular neoplasia is required to accommodate all women.

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

Purpose To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. Methods and Materials Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size Results In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. Conclusion Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for early-stage breast cancer in the adjuvant setting.

To determine the impact of tumor biology on rates of breast-conserving surgery and pathologic complete response (pCR) after neoadjuvant chemotherapy.The impact of tumor biology on the rate of breast-conserving surgery after neoadjuvant chemotherapy has not been well studied.We used data from ACOSOG Z1071, a prospective, multicenter study assessing sentinel lymph node surgery after neoadjuvant chemotherapy in patients presenting with node-positive breast cancer from 2009 through 2011, to determine rates of breast-conserving surgery and pCR after chemotherapy by approximated biologic subtype.Of the 756 patients enrolled on Z1071, 694 had findings available from pathologic review of breast and axillary specimens from surgery after chemotherapy. Approximated subtype was triple-negative in 170 (24.5%), human epidermal growth factor receptor 2 (HER2)-positive in 207 (29.8%), and hormone-receptor-positive, HER2-negative in 317 (45.7%) patients. Patient age, clinical tumor and nodal stage at presentation did not differ across subtypes. Rates of breast-conserving surgery were significantly higher in patients with triple-negative (46.8%) and HER2-positive tumors (43.0%) than in those with hormone-receptor-positive, HER2-negative tumors (34.5%) (P = 0.019). Rates of pCR in both the breast and axilla were 38.2% in triple-negative, 45.4% in HER2-positive, and 11.4% in hormone-receptor-positive, HER2-negative disease (P0.0001). Rates of pCR in the breast only and the axilla only exhibited similar differences across tumor subtypes.Patients with triple-negative and HER2-positive breast cancers have the highest rates of breast-conserving surgery and pCR after neoadjuvant chemotherapy. Patients with these subtypes are most likely to be candidates for less invasive surgical approaches after chemotherapy.

Triple-negative breast cancer (TNBC) is an uncommon but aggressive subtype of breast cancer. Obesity has been associated with an increased risk of breast cancer and worse prognosis. Some studies suggest that obese patients are less likely to achieve pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) and experience worse overall survival. Ki-67 is a proliferation marker that correlates with tumor aggressiveness. The goal of this study was to examine the impact of weight change during NCT for TNBC on pathologic response and Ki-67 reduction. Retrospective review identified 173 TNBC patients treated between 2004 and 2011. Data were collected on patient demographics, pre- and post-NCT body mass index (BMI), Ki-67, and pCR. Data analysis was performed using the two-tailed Student's t-test, analysis of variance (ANOVA), and Fisher's exact test. Sixty-six patients met final study criteria. Forty-three patients lost weight during chemotherapy and 23 gained weight. Patients in the weight gain group were significantly younger (P = 0.0013). There was no significant difference between the two groups in terms of Ki-67 reduction (P = 0.98) or pCR (P = 0.58). When patients were separated into normal weight (BMI25 kg/m(2) ), overweight (BMI ≥ 25 and30 kg/m(2) ), and obese (BMI ≥ 30 kg/m(2) ), there was no significant difference in Ki-67 among those groups either before or after NCT. The degree of obesity did not have a significant impact on Ki-67 reduction. Weight change during NCT does not appear to correlate with Ki-67 change or achieving pCR in TNBC. This may reflect the nature of this subtype of breast cancer that is less responsive to the hormonal effects that adipose tissue exerts on cancer cell proliferation.

BackgroundCancer is one of the most common diseases that patients research on the Internet. The Commission on Cancer (CoC) recommended that Parkland Memorial Hospital (PMH) improve the oncology services website. PMH is Dallas County’s public health care facility, serving a largely uninsured, minority population. Most research regarding patient Internet use has been conducted in insured, Caucasian populations, raising concerns that the needs of PMH patients may not be extrapolated from available data. The PMH Cancer Committee, therefore, adopted a quality improvement initiative to understand patients’ Internet usage. ObjectiveThe objective of the study was to obtain and analyze data regarding patients’ Internet usage in order to make targeted improvements to the oncology services section of the institutional website. MethodsA task force developed an 11-question survey to ascertain what proportion of our patients have Internet access and use the Internet to obtain medical information as well as determine the specific information sought. Between April 2011 and August 2011, 300 surveys were administered to newly diagnosed cancer patients. Multivariate analyses were performed. ResultsOf 300 surveys, 291 were included. Minorities, primarily African-American and Hispanic, represented 78.0% (227/291) of patients. Only 37.1% (108/291) of patients had Internet access, most (256/291, 87.9%) having access at home. Younger patients more commonly had Internet access, with a mean age of 47 versus 58 years for those without (P

Twenty consecutive patients with breast cancer were evaluated following chemotherapy using MRI to assess the size of cancer residua and compare these data with subsequent histologic measurements of the viable tumor. This retrospective study also involved assessment of the preoperative size of the malignancy as determined by physical exam and x-ray mammogram. These values were later compared with the histology. The tumor size correlation coefficient between MRI and pathologic analysis was the highest, at 0.93. Physical exam and x-ray mammography (available for 17 patients) produced correlation coefficients of 0.72 and 0.63, respectively, compared to histologic measurement. The accuracy of MRI did not vary with the size of cancer residua. MRI is an accurate method for preoperative assessment of breast cancer residua following chemotherapy. J. Magn. Reson. Imaging 2001;13:868-875.