A WNT4- and DKK3-driven canonical to noncanonical Wnt signaling switch controls multiciliogenesis.

Multiciliated cells contain hundreds of cilia whose directional movement powers the mucociliary clearance of the airways, a vital host defense mechanism. Multiciliated cell specification requires canonical Wnt signaling, which then must be turned off. Next, ciliogenesis and polarized ciliary orientation are regulated by noncanonical Wnt/planar cell polarity (Wnt/PCP) signaling. The mechanistic relationship between the Wnt pathways is unknown. We show that DKK3, a secreted canonical Wnt regulator and WNT4, a noncanonical Wnt ligand act together to facilitate a canonical to noncanonical Wnt signaling switch during multiciliated cell formation. In primary human airway epithelial cells, DKK3 and WNT4 CRISPR knockout blocks, whereas ectopic expression promotes, multiciliated cell formation by inhibiting canonical Wnt signaling. Wnt4 and Dkk3 single-knockout mice also display defective ciliated cells. DKK3 and WNT4 are co-secreted from basal stem cells and act directly on multiciliated cells via KREMEN1 and FZD6, respectively. We provide a novel mechanism that links specification to cilium biogenesis and polarization for proper multiciliated cell formation.

To Dissect or Not to Dissect: Can We Predict the Presence of Four or More Axillary Lymph Node Metastases in Postmenopausal Women with Clinically Node-Negative Breast Cancer?

BACKGROUND: Axillary lymph node (ALN) involvement is important for prognosis and guidance of multidisciplinary treatment of breast cancer patients. This study sought to identify preoperative clinicopathologic factors predictive of four or more pathologically positive ALNs in patients with cN0 disease and to develop a predictive nomogram to inform therapy recommendations. METHODS: Using an institutional prospective database, the study identified postmenopausal women with cN0 invasive breast cancer undergoing upfront sentinel lymph node biopsy (SLNB) with or without completion ALND (cALND) between 1993 and 2007. Logistic regression analyses identified factors predictive of four or more positive nodes in the cN0 population and patients with one, two, or more SLNs. RESULTS: The study identified 2532 postmenopausal women, 615 (24.3%) of whom underwent cALND. In the univariate analysis, tumor size, lymphovascular (LVI), histology, estrogen receptor (ER)-positive status, and multifocality/multicentricity were predictive of four or more positive nodes (n = 63; p < 0.05), and all except ER status were significant in the multivariate analysis. Of the 2532 patients, 1263 (49.2%) had hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative disease, and 30 (2.4%) were found to have four or more positive nodes. Of the 130 patients with exactly one positive SLN who underwent cALND (n = 130, 5.4%), 7 had four or more positive nodes, with grade as the only predictive factor (p = 0.01). Of the 33 patients with two or more positive SLNs who underwent cALND, 9 (27.3%) had four or more positive nodes after cALND, but no factors were predictive in this subset. CONCLUSION: Postmenopausal women with early-stage cN0 HR-positive, HER2-negative breast cancer with a single positive SLN had a very low risk (5%) of having four or more positive nodes on final pathology. With such a low risk of N2 disease, limited staging with SLNB may be sufficient to guide therapy decisions for this subset of patients.

Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and deregulated metabolism. The role of the stroma in PDAC biology is complex and it has been shown to play critical roles that differ depending on the biological context. The stromal reaction also impairs the vasculature, leading to a highly hypoxic, nutrient-poor environment. As such, these tumours must alter how they capture and use nutrients to support their metabolic needs. Here we show that stroma-associated pancreatic stellate cells (PSCs) are critical for PDAC metabolism through the secretion of non-essential amino acids (NEAA). Specifically, we uncover a previously undescribed role for alanine, which outcompetes glucose and glutamine-derived carbon in PDAC to fuel the tricarboxylic acid (TCA) cycle, and thus NEAA and lipid biosynthesis. This shift in fuel source decreases the tumour's dependence on glucose and serum-derived nutrients, which are limited in the pancreatic tumour microenvironment. Moreover, we demonstrate that alanine secretion by PSCs is dependent on PSC autophagy, a process that is stimulated by cancer cells. Thus, our results demonstrate a novel metabolic interaction between PSCs and cancer cells, in which PSC-derived alanine acts as an alternative carbon source. This finding highlights a previously unappreciated metabolic network within pancreatic tumours in which diverse fuel sources are used to promote growth in an austere tumour microenvironment.

Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk.

Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression. Genetic deletion of Gal1 in a Kras-driven mouse model of PDA (Ela-KrasG12Vp53-/- ) results in a significant increase in survival through mechanisms involving decreased stroma activation, attenuated vascularization, and enhanced T cell infiltration leading to diminished metastasis rates. In a human setting, human pancreatic stellate cells (HPSCs) promote cancer proliferation, migration, and invasion via Gal1-driven pathways. Moreover, in vivo orthotopic coinjection of pancreatic tumor cells with Gal1-depleted HPSCs leads to impaired tumor formation and metastasis in mice. Gene-expression analyses of pancreatic tumor cells exposed to Gal1 reveal modulation of multiple regulatory pathways involved in tumor progression. Thus, Gal1 hierarchically regulates different events implicated in PDA biology including tumor cell proliferation, invasion, angiogenesis, inflammation, and metastasis, highlighting the broad therapeutic potential of Gal1-specific inhibitors, either alone or in combination with other therapeutic modalities.

Correlation of circulating or disseminated tumor cells with the Oncotype DX Recurrence Score.

PURPOSE: New biomarkers are emerging to predict recurrence risk in women with early-stage breast cancer. High Oncotype DX Recurrence Score® (RS) is associated with worse disease-free and overall survival. Similarly, circulating tumor cells (CTCs, blood) and disseminated tumor cells (DTCs, bone marrow) have prognostic value in breast cancer. We investigated the association between high RS and CTCs or DTCs. METHODS: Using a prospective database, we evaluated patients with hormone receptor-positive/HER2-negative, node-negative invasive breast cancer from 1/2005 to 1/2017. RS was classified using TAILORx study cutoff points: low (< 11), intermediate (11-25), and high (> 25). CTCs were assessed using CellSearch® and DTCs using cytospin specimens of bone marrow aspirates. Positive result was defined as one or more CTCs or DTCs identified. Chi-square analyses were utilized to evaluate the relationship between RS and CTCs or DTCs. RESULTS: 233 patients were identified from a prospective database, of which 96 had RS results. Of these patients, 88 had CTC results and 58 had DTC results. CTCs were detected in 17/88 (19%) patients, while DTCs were detected in 20/58 (34%). Patients with high RS were not more likely to have CTCs (18%) compared to patients with low/intermediate RS (20%; p = 0.919). Similarly, high RS was not associated with DTC detection, with DTCs present in 40% of patients with high RS versus 33% with low/intermediate RS (p = 0.687). In the subgroup of patients ≤ 50 years, no associations were found between high RS and CTCs (p = 0.383) or DTCs (p = 0.234). CONCLUSIONS: High Oncotype DX RS did not correlate with CTCs in blood or DTCs in bone marrow in our study.

Ductal Carcinoma In Situ and Margins <2 mm: Contemporary Outcomes With Breast Conservation.

OBJECTIVE: To determine the relationship between negative margin width and locoregional recurrence (LRR) in a contemporary cohort of ductal carcinoma in situ (DCIS) patients. BACKGROUND: Recent national consensus guidelines recommend an optimal margin width of 2 mm or greater for the management of DCIS; however, controversy regarding re-excision remains when managing negative margins <2 mm. METHODS: One thousand four hundred ninety-one patients with DCIS who underwent breast-conserving surgery from 1996 to 2010 were identified from a prospectively managed cancer center database and analyzed using univariate and multivariate Cox proportional hazard models to determine the relationship between negative margin width and LRR with or without adjuvant radiation therapy (RT). RESULTS: A univariate analysis revealed that age <40 years (n = 89; P = 0.02), no RT (n = 298; P = 0.01), and negative margin width <2 mm (n = 120; P = 0.005) were associated with LRR. The association between margin width and LRR differed by adjuvant RT status (interaction P = 0.02). There was no statistical significant difference in LRR between patients with <2 mm and ≥2 mm negative margins who underwent RT (10-yr LRR rate, 4.8% vs 3.3%, respectively; hazard ratio, 0.8; 95% CI, 0.2-3.2; P = 0.72). For patients who did not undergo RT, those with margins <2 mm were significantly more likely to develop a LRR than were those with margins ≥2 mm (10-yr LRR rate, 30.9% vs 5.4%, respectively; hazard ratio, 5.5; 95% CI, 1.8-16.8, P = 0.003). CONCLUSIONS: Routine additional surgery may not be justified for patients with negative margins <2 mm who undergo RT but should be performed in patients who forego RT.

Evolution in practice patterns of axillary management following mastectomy in patients with 1-2 positive sentinel nodes.

PURPOSE: The optimal management of breast cancer patients with a positive sentinel lymph node (SLN) who undergo mastectomy remains controversial. This study aimed to describe treatment patterns of patients with positive SLNs who undergo mastectomy using a large population-based database. METHODS: The NCDB was queried for cT1-2N0 breast cancer patients treated with mastectomy between 2006 and 2014 who had 1-2 positive SLNs. Patients receiving neoadjuvant chemotherapy were excluded. Axillary management included SLN dissection (SLND) alone, axillary lymph node dissection (ALND), post-mastectomy radiation (PMRT) alone, and ALND + PMRT. Trends of axillary management and patient characteristics were examined. RESULTS: Among 12,190 patients who met study criteria, the use of ALND dropped with a corresponding increase in other approaches. In 2006, 34% of patients had SLND alone, 47% ALND, 8% PMRT and 11% ALND + PMRT. By 2014, 37% had SLND, 23% ALND, 27% PMRT and 13% ALND + PMRT. Patients who underwent SLND alone were older (mean 60.6 years) with more comorbidities (Charlson-Deyo score > 2), smaller primary tumors (mean 2.1 cm), well-differentiated histology, hormone receptor-positive, HER2-negative tumors, without lymphovascular invasion (all P values < 0.01). Treatment with SLND alone was more likely if patients had only one positive SLN (P < 0.001) or micrometastatic disease (P < 0.001), and were treated at community centers compared with academic centers (P < 0.001). CONCLUSIONS: The management of breast cancer patients undergoing mastectomy with positive SLNs has evolved over time with decreased use of ALND and increased use of radiation. Some patient subsets are underrepresented in recent clinical trials, and therefore, future trials should focus on these patients.

Patient Selection for Clinical Trials Eliminating Surgery for HER2-Positive Breast Cancer Treated with Neoadjuvant Systemic Therapy.

BACKGROUND: Patients with epidermal growth factor receptor 2-positive (HER2+) breast cancer and pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) may be candidates for nonoperative clinical trials if residual invasive and in situ disease are eradicated. METHODS: This study analyzed 280 patients with clinical T1-2N0-1 HER2+ breast cancer who underwent NST followed by surgical resection to determine key characteristics of patients with pCR in the breast and lymph nodes compared with those with residual disease. RESULTS: Of the 280 patients, 102 (36.4%) had pCR in the breast and lymph nodes after NST, and 50 patients (17.9%) had residual ductal carcinoma in situ (DCIS) in the breast only. For 129 patients (46.1%), DCIS was present on the pretreatment biopsy, and NST failed to eradicate the DCIS component in 64.3%. Patients with residual disease were more likely to have hormone receptor-positive (HR+) tumors than those with negative tumors (73.4% vs. 50.8%; p < 0.0001). Radiologic response (odds ratio [OR], 5.62; p = 0.002) and HR+ status (OR, 2.56; p < 0.0001) were predictive of residual disease. Combined imaging methods after NST had a sensitivity of 97.1% and a negative predictive value of 70.6% for detection of residual disease. Patients with invasive disease and DCIS shown on the pretreatment core biopsy were less likely than those without DCIS to achieve pCR in the breast (31% vs. 43%; p = 0.038). CONCLUSION: The study results delineate and identify unique characteristics associated with HER2+ breast cancers that are important in selecting patients for inclusion in clinical trials assessing nonoperative management after NST, and the low negative predictive value of imaging mandates image-guided biopsy for selection.

A Clinical Feasibility Trial for Identification of Exceptional Responders in Whom Breast Cancer Surgery Can Be Eliminated Following Neoadjuvant Systemic Therapy.

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.

Factors impacting the accuracy of intra-operative evaluation of sentinel lymph nodes in breast cancer.

Sentinel lymph node dissection (SLND) is a standard axillary staging technique in breast cancer and intraoperative sentinel lymph node (SLN) assessment is important for decision-making regarding additional treatment and reconstruction. This study was undertaken to investigate clinicopathologic factors impacting the accuracy of intraoperative SLN evaluation. Records of patients with clinically node-negative, invasive breast cancer who underwent SLND with frozen section intraoperative pathologic evaluation from 2004 to 2007 were reviewed. Intraoperative SLN assessment results were compared to final pathology. Patients with positive SLNs that were initially reported as negative during intraoperative assessment were considered false negative (FN) events. Primary tumor histology, grade, receptor status, size, lymphovascular invasion (LVI), multifocality, neoadjuvant chemotherapy or hormonal therapy, number of SLNs retrieved, and SLN metastasis size were evaluated. The study included 681 patients, of whom 262 (38%) received neoadjuvant therapy. There were 183 (27%) patients who had a positive SLN on final pathology, of whom 60 (33%) had FN events. On univariate analysis, lobular histology, favorable histology, absence of LVI and micrometastasis were associated with a higher FN rate. On multivariate analysis, favorable and lobular histology and micrometastasis were independent predictors of FN events whereas LVI and receipt of neoadjuvant therapy were not statistically significant predictors. The accuracy of intraoperative SLN evaluation for breast cancer is affected by primary tumor histology and size of the SLN metastasis. There was no significant association between neoadjuvant therapy and the FN rate by intraoperative assessment. This information may be helpful in counseling patients about their risk for a FN intraoperative SLN assessment and for planning for immediate breast reconstruction in patients undergoing mastectomy.

Cancer cell chemokines direct chemotaxis of activated stellate cells in pancreatic ductal adenocarcinoma.

The mechanisms by which the extreme desmoplasia observed in pancreatic tumors develops remain unknown and its role in pancreatic cancer progression is unsettled. Chemokines have a key role in the recruitment of a wide variety of cell types in health and disease. Transcript and protein profile analyses of human and murine cell lines and human tissue specimens revealed a consistent elevation in the receptors CCR10 and CXCR6, as well as their respective ligands CCL28 and CXCL16. Elevated ligand expression was restricted to tumor cells, whereas receptors were in both epithelial and stromal cells. Consistent with its regulation by inflammatory cytokines, CCL28 and CCR10, but not CXCL16 or CXCR6, were upregulated in human pancreatitis tissues. Cytokine stimulation of pancreatic cancer cells increased CCL28 secretion in epithelial tumor cells but not an immortalized activated human pancreatic stellate cell line (HPSC). Stellate cells exhibited dose- and receptor-dependent chemotaxis in response to CCL28. This functional response was not linked to changes in activation status as CCL28 had little impact on alpha smooth muscle actin levels or extracellular matrix deposition or alignment. Co-culture assays revealed CCL28-dependent chemotaxis of HPSC toward cancer but not normal pancreatic epithelial cells, consistent with stromal cells being a functional target for the epithelial-derived chemokine. These data together implicate the chemokine CCL28 in the inflammation-mediated recruitment of cancer-associated stellate cells into the pancreatic cancer parenchyma.

Operative and Oncologic Outcomes in 9861 Patients with Operable Breast Cancer: Single-Institution Analysis of Breast Conservation with Oncoplastic Reconstruction.

BACKGROUND: Oncoplastic reconstruction is an approach that enables patients with locally advanced or adversely located tumors to undergo breast conserving surgery (BCS). The objectives were to identify the use of BCS with oncoplastic reconstruction (BCS + R) and determine the operative and oncologic outcomes compared with other breast surgical procedures for breast cancer. METHODS: This retrospective cohort study interrogated a single institution's prospectively maintained databases to identify patients who underwent surgery for breast cancer between 2007 and 2014. Surgeries were categorized as BCS, BCS + R, total mastectomy (TM), or TM with immediate reconstruction (TM + R). Demographic and clinicopathologic characteristics and postoperative complications were analyzed. RESULTS: There were 10,607 operations performed for 9861 patients. Median follow-up was 3.4 years (range, 0-9.1 years). The use of BCS + R had a nearly fourfold increase in the percentage of all breast cancer surgeries during the study period; 75 % of patients who underwent BCS + R had a T1 or T2 tumor. There was no difference in the use of BCS + R compared with BCS for any quadrant of the breast except the lower outer quadrant (11.1 vs. 6.8 %; p < .0001). BCS + R had a lower rate of seroma formation (13.4 vs. 18 %; p = .002) and positive or close margins compared with BCS (5.8 vs. 8.3 %; p = .04). There was no difference in overall survival or recurrence-free survival when comparing BCS and BCS + R. CONCLUSIONS: Patients undergoing BCS + R are not disadvantaged in terms of complications and short-term (3-year) outcomes compared with BCS patients or patients who underwent TM.

Value-Based Breast Cancer Care: A Multidisciplinary Approach for Defining Patient-Centered Outcomes.

PURPOSE: Value in healthcare-i.e., patient-centered outcomes achieved per healthcare dollar spent-can define quality and unify performance improvement goals with health outcomes of importance to patients across the entire cycle of care. We describe the process through which value-based measures for breast cancer patients and dynamic capture of these metrics via our new electronic health record (EHR) were developed at our institution. METHODS: Contemporary breast cancer literature on treatment options, expected outcomes, and potential complications was extensively reviewed. Patient perspective was obtained via focus groups. Multidisciplinary physician teams met to inform a 3-phase process of (1) concept development, (2) measure specification, and (3) implementation via EHR integration. RESULTS: Outcomes were divided into 3 tiers that reflect the entire cycle of care: (1) health status achieved, (2) process of recovery, and (3) sustainability of health. Within these tiers, 22 patient-centered outcomes were defined with inclusion/exclusion criteria and specifications for reporting. Patient data sources will include the Epic Systems EHR and validated patient-reported outcome questionnaires administered via our institution's patient portal. CONCLUSIONS: As healthcare costs continue to rise in the United States and around the world, a value-based approach with explicit, transparently reported patient outcomes will not only create opportunities for performance improvement but will also enable benchmarking across providers, healthcare systems, and even countries. Similar value-based breast cancer care frameworks are also being pursued internationally.

A Phase II Trial Exploring the Success of Cryoablation Therapy in the Treatment of Invasive Breast Carcinoma: Results from ACOSOG (Alliance) Z1072.

BACKGROUND: Cryoablation is a well-established technique to treat fibroadenomas. Pilot studies suggest this could be an effective non-surgical treatment for breast cancer. American College of Surgeons Oncology Group Z1072 is a phase II trial exploring the effectiveness of cryoablation in the treatment of breast cancers. METHODS: The primary endpoint of Z1072 was the rate of complete tumor ablation, defined as no remaining invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) on pathologic examination of the targeted lesion. A secondary objective was to evaluate the negative predictive value of magnetic resonance imaging (MRI) to determine residual IBC or DCIS. Eligible patients included those with unifocal invasive ductal breast cancer ≤2 cm, with <25 % intraductal component and tumor enhancement on MRI. A total of 19 centers contributed 99 patients, of which 86 patients (87 breast cancers) were evaluable for data analysis. RESULTS: Final pathology results, regardless of whether residual IBC/DCIS was in the targeted ablation zone or elsewhere in the breast, showed successful ablation in 66/87 (75.9 %) cancers. The 90 % confidence interval for the estimate of successful cryoablation was 67.1-83.2, with the one-sided lower-sided 90 % CI of 69.0. The negative predictive value of MRI was 81.2 % (90 % CI 71.4-88.8). When multifocal disease outside of the targeted cryoablation zone was not defined as an ablation failure, 80/87 (92 %) of the treated cancers had a successful cryoablation. CONCLUSION: Further studies with modifications on the Z1072 protocol could be considered to evaluate the role for cryoablation as a non-surgical treatment of early-stage breast cancer.

Cyclopamine-loaded core-cross-linked polymeric micelles enhance radiation response in pancreatic cancer and pancreatic stellate cells.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. Cyclopamine (CPA), a potent inhibitor for sonic hedgehog pathway (SHH), shows great promises in PDAC treatment, including the disruption of tumor-associated stroma, and enhancement of radiation therapy. However, CPA is insoluble in water and therefore requires a nanometric delivery platform to achieve satisfactory performance. We herein encapsulated CPA in a core-cross-linked polymeric micelle system (M-CPA). M-CPA was combined with Cs-137 radiation and evaluated in vitro in PDAC cell lines and a human pancreatic stellate cell line. The results showed that M-CPA had higher cytotoxicity than CPA, abolished Gli-1 expression (a key component of SHH), and enhanced the radiation therapy of Cs-137. M-CPA radiosensitization correlated with its ability to disrupt the repair of radiation-induced DNA damage. These findings indicate that the combination therapy of M-CPA and radiation is an effective strategy to simultaneously treat pancreatic tumors and tumor-associated stroma.

Impact of identification of internal mammary sentinel lymph node metastasis in breast cancer patients.

BACKGROUND: Accurate assessment of the internal mammary (IM) nodal basin can impact prognosis and treatment in breast cancer. The goal of this study was to identify characteristics associated with positive IM sentinel lymph nodes (SLNs) and the impact on adjuvant treatment. METHODS: Clinically node-negative breast cancer patients who underwent SLN dissection including removal of IM SLNs were identified and medical records were reviewed. Statistical analysis was performed using Fisher's exact test and rank-sum tests with a significance level of 0.05. RESULTS: IM SLNs were removed in 71 patients, 60 (85 %) had negative IM SLNs, whereas 11 (15 %) had positive IM SLNs. Clinicopathologic characteristics were similar between the groups. The majority of patients in both groups had axillary SLNs removed (95 % in the node-negative group vs. 91 % in the node-positive group). Four patients (36 %) with positive IM SLNs had axillary metastasis; thus, IM nodal metastases were the only nodal metastases in 64 % of patients with positive IM SLNs. The identification of IM metastases altered adjuvant therapy in 5 (45 %) patients with positive IM SLNs. CONCLUSIONS: Patients with positive IM SLNs have clinicopathologic features similar to those of patients with negative IM SLNs limiting the ability to predict IM nodal metastasis preoperatively. The identification of IM nodal metastases significantly impacts treatment decisions, especially when IM nodes are the only site of nodal metastasis. Removal of IM SLNs should be considered when lymphoscintigraphy reveals IM drainage.

Timing of infectious complications following breast-conserving therapy with catheter-based accelerated partial breast irradiation.

BACKGROUND: Accelerated partial breast irradiation (APBI) has been used as an alternative to whole-breast irradiation as part of breast-conserving therapy. Indications and outcomes are topics of ongoing investigation. Previous publications have focused on early postoperative infections and reported low rates of delayed infection. We investigated the pattern of infection after catheter-based APBI at our institution. METHODS: Patients who underwent single-entry catheter-based APBI were identified from an institutional prospective registry including data regarding comorbidities and outcomes. Time of infection was calculated from the date of definitive catheter insertion and classified as early (≤30 days) or delayed. RESULTS: A total of 91 breast cancer patients were treated with APBI and enrolled in the registry from 2009 to 2011. The median follow-up was 484 days. Breast infection occurred in 13 (14.3 %), with 3 (3.3 %) occurring within 30 days of catheter placement and 10 (11.0 %) in a delayed fashion. Four patients required hospital admission, five underwent percutaneous aspiration, and one underwent incision and drainage. Eight were treated as outpatients with oral antibiotics alone. CONCLUSIONS: Consistent with other reports, we found an overall infection rate of 14.3 % with single-entry catheter-based APBI. There were substantially fewer infections in the early postoperative period than reported elsewhere, but there were more delayed infections. The intensive follow-up in our study likely identified late infections that may not have otherwise been recognized. Vigilance for infectious complications must continue beyond the immediate treatment period in patients undergoing catheter-based APBI. These infections can range in severity but typically can be managed in an outpatient setting.