The use of sentinel lymph node surgery after neoadjuvant chemotherapy for patients who present with cN1 breast cancer provides an opportunity to avoid axillary lymph node dissection for those patients who have eradication of their nodal disease with chemotherapy. Since the initial publication of prospective trials demonstrating the false-negative rate of sentinel lymph node (SLN) surgery in this setting, this practice has been increasing. [1][2][3][4] A recent survey of the American Society of Breast Surgeons (ASBrS) reported that 85% of respondents offered SLN surgery to some patients in this setting. 5

A B S T R A C T PurposeSentinel lymph node biopsy was adopted for the staging of the axilla with the assumption that it would reduce the risk of lymphedema in women with breast cancer. The aim of this study was to determine the long-term prevalence of lymphedema after SLN biopsy (SLNB) alone and after SLNB followed by axillary lymph node dissection (SLNB/ALND). Patients and MethodsAt median follow-up of 5 years, lymphedema was assessed in 936 women with clinically nodenegative breast cancer who underwent SLNB alone or SLNB/ALND. Standardized ipsilateral and contralateral measurements at baseline and follow-up were used to determine change in ipsilateral upper extremity circumference and to control for baseline asymmetry and weight change. Associations between lymphedema and potential risk factors were examined. ResultsOf the 936 women, 600 women (64%) underwent SLNB alone and 336 women (36%) underwent SLNB/ALND. Patients having SLNB alone were older than those having SLNB/ALND (56 v 52 years; P Ͻ .0001). Baseline body mass index (BMI) was similar in both groups. Arm circumference measurements documented lymphedema in 5% of SLNB alone patients, compared with 16% of SLNB/ALND patients (P Ͻ .0001). Risk factors associated with measured lymphedema were greater body weight (P Ͻ .0001), higher BMI (P Ͻ .0001), and infection (P Ͻ .0001) or injury (P ϭ .02) in the ipsilateral arm since surgery. ConclusionWhen compared with SLNB/ALND, SLNB alone results in a significantly lower rate of lymphedema 5 years postoperatively. However, even after SLNB alone, there remains a clinically relevant risk of lymphedema. Higher body weight, infection, and injury are significant risk factors for developing lymphedema.

A B S T R A C T PurposeSentinel lymph node (SLN) biopsy was adopted for the staging of the axilla with the assumption that it would reduce the risk of lymphedema in women with breast cancer. This study was undertaken to examine patient perceptions of lymphedema and use of precautionary behaviors several years after axillary surgery. Patients and MethodsNine hundred thirty-six women who underwent SLN biopsy (SLNB) alone or SLNB followed by axillary lymph node dissection (SLNB/ALND) between June 1, 1999, and May 30, 2003, were evaluated at a median of 5 years after surgery. Patient-perceived lymphedema and avoidant behaviors were assessed through interview and administered a validated instrument, and compared with arm measurements. ResultsCurrent arm swelling was reported in 3% of patients who received SLNB alone versus 27% of patients who received SLNB/ALND (P Ͻ .0001), as compared with 5% and 16%, respectively, with measured lymphedema. Only 41% of patients reporting arm swelling had measured lymphedema, and 5% of patients reporting no arm swelling had measured lymphedema. Risk factors associated with reported arm swelling were greater body weight (P Ͻ .0001), higher body mass index (P Ͻ .0001), infection (P Ͻ .0001), and injury (P ϭ .007) in the ipsilateral arm since surgery. Patients followed more precautions if they had measured or perceived lymphedema. ConclusionBody weight, infection, and injury are significant risk factors for perceiving lymphedema. There is significant discordance between the presence of measured and patient-perceived lymphedema. When compared to SLNB/ALND, SLNB-alone results in a significantly lower rate of patientperceived arm swelling 5 years postoperatively, and is perceived by fewer women than are measured to have it. J Clin

Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis that lacks targeted therapies, especially in patients with chemotherapy-resistant disease. Since DNA methylation-induced silencing of tumor suppressors is common in cancer, reversal of promoter DNA hypermethylation by 5-aza-2'-deoxycytidine (decitabine), an FDA-approved DNA methyltransferase (DNMT) inhibitor, has proven effective in treating hematological neoplasms. However, its antitumor effect varies in solid tumors, stressing the importance of identifying biomarkers predictive of therapeutic response. Here, we focused on the identification of biomarkers to select decitabine-sensitive TNBC through increasing our understanding of the mechanism of decitabine action. We showed that protein levels of DNMTs correlated with response to decitabine in patient-derived xenograft (PDX) organoids originating from chemotherapy-sensitive and -resistant TNBCs, suggesting DNMT levels as potential biomarkers of response. Furthermore, all 3 methytransferases, DNMT1, DNMT3A, and DNMT3B, were degraded following low-concentration, long-term decitabine treatment both in vitro and in vivo. The DNMT proteins could be ubiquitinated by the E3 ligase, TNF receptor-associated factor 6 (TRAF6), leading to lysosome-dependent protein degradation. Depletion of TRAF6 blocked decitabine-induced DNMT degradation, conferring resistance to decitabine. Our study suggests a potential mechanism of regulating DNMT protein degradation and DNMT levels as response biomarkers for DNMT inhibitors in TNBCs.

This study aims to validate radioactive seed localization (RSL) as an alternative to wire localization (WL) in the operative excision of nonpalpable breast lesions. Eligible patients were recruited sequentially. A sample of 99 patients treated with WL was compared to the next 383 patients treated with RSL. Margins were considered "negative" if > or =2 mm from in-situ and invasive disease. Pain and convenience scores were recorded on a 10-point scale. Patient characteristics and histology were similar. The lesion and localization device were retrieved in all patients. Margins of the first specimen were negative in 73% of RSL patients, versus 54% of WL patients (p < 0.001). A second operation was required in 8% of RSL patients to achieve negative margins, versus 25% of WL patients (p < 0.001). Pain scores were not statistically different. However, the RSL group had higher convenience scores (p = 0.015). RSL is safe, effective, and compared to WL, reduces the rates of intraoperative re-excision and reoperation for positive margins by 68%. Patient satisfaction is improved with RSL. We strongly favor RSL over WL.

Nipple-sparing mastectomies are highly preventive against breast cancer in a BRCA population. Although the follow-up remains relatively short, NSM should be offered as a breast cancer risk-reducing strategy to appropriate patients with BRCA mutations.

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Background: Breast cancer patients with residual disease after neoadjuvant chemotherapy (NAC) have increased recurrence risk. Molecular characterization, knowledge of NAC response, and simultaneous generation of patient-derived xenografts (PDXs) may accelerate drug development. However, the feasibility of this approach is unknown.Methods: We conducted a prospective study of 140 breast cancer patients treated with NAC and performed tumor and germline sequencing and generated patient-derived xenografts (PDXs) using core needle biopsies. Chemotherapy response was assessed at surgery.Results: Recurrent “targetable” alterations were not enriched in patients without pathologic complete response (pCR); however, upregulation of steroid receptor signaling and lower pCR rates (16.7%, 1/6) were observed in triple-negative breast cancer (TNBC) patients with luminal androgen receptor (LAR) vs basal subtypes (60.0%, 21/35). Within TNBC, TP53 mutation frequency (75.6%, 31/41) did not differ comparing basal (74.3%, 26/35) and LAR (83.3%, 5/6); however, TP53 stop-gain mutations were more common in basal (22.9%, 8/35) vs LAR (0.0%, 0/6), which was confirmed in The Cancer Genome Atlas and British Columbia data sets. In luminal B tumors, Ki-67 responses were observed in tumors that harbored mutations conferring endocrine resistance (p53, AKT, and IKBKE). PDX take rate (27.4%, 31/113) varied according to tumor subtype, and in a patient with progression on NAC, sequencing data informed drug selection (olaparib) with in vivo antitumor activity observed in the primary and resistant (postchemotherapy) PDXs.Conclusions: In this study, we demonstrate the feasibility of tumor sequencing and PDX generation in the NAC setting. “Targetable” alterations were not enriched in chemotherapy-resistant tumors; however, prioritization of drug testing based on sequence data may accelerate drug development.