Avoid Sentinel Lymph Node Biopsy Research Articles

Future Directions in the Assessment of Axillary Lymph Nodes in Patients with Breast Cancer.

Background and Objectives: Breast cancer (BC) is a leading cause of morbidity and mortality worldwide, and accurate assessment of axillary lymph nodes (ALNs) is crucial for patient management and outcomes. We aim to summarize the current state of ALN assessment techniques in BC and provide insights into future directions. Materials and Methods: This review discusses various imaging techniques used for ALN evaluation, including ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography. It highlights advancements in these techniques and their potential to improve diagnostic accuracy. The review also examines landmark clinical trials that have influenced axillary management, such as the Z0011 trial and the IBCSG 23-01 trial. The role of artificial intelligence (AI), specifically deep learning algorithms, in improving ALN assessment is examined. Results: The review outlines the key findings of these trials, which demonstrated the feasibility of avoiding axillary lymph node dissection (ALND) in certain patient populations with low sentinel lymph node (SLN) burden. It also discusses ongoing trials, including the SOUND trial, which investigates the use of axillary ultrasound to identify patients who can safely avoid sentinel lymph node biopsy (SLNB). Furthermore, the potential of emerging techniques and the integration of AI in enhancing ALN assessment accuracy are presented. Conclusions: The review concludes that advancements in ALN assessment techniques have the potential to improve patient outcomes by reducing surgical complications while maintaining accurate disease staging. However, challenges such as standardization of imaging protocols and interpretation criteria need to be addressed. Future research should focus on large-scale clinical trials to validate emerging techniques and establish their efficacy and cost-effectiveness. Over-all, this review provides valuable insights into the current status and future directions of ALN assessment in BC, highlighting opportunities for improving patient care.

Is 18 F-fluorodeoxyglucose-positron emission tomography or computed tomography scan a triaging technique for axillary dissection in breast cancer?

Background: To determine if fluorodeoxyglucose-positron emission tomography/ computed tomography (FDG PET/CT) scan identifies axillary nodal disease in conjunction with ultrasound (US) guided fine needle aspiration cytology (FNAC) of suspicious axillary nodes in breast cancer. To determine if this will enable axillary node dissection upfront, avoiding sentinel lymph node biopsy (SLNB). Methods: Study was performed in Apollo main hospital, Off Greams-lane, Greams road, Chennai IRB approval was obtained from institutional ethical committee-bio medical research-Apollo hospitals, (IEC application number: AMH-C-S-029/04-23). Informed consent was obtained from all the patients who met the exclusion criteria. The 61 patients with cT1-T3, N0-N1, and M0 disease underwent 18F-FDG-PET/CT scans after mammographic evaluation and an US guided FNAC of nodes which were seen to be suspicious in the mammogram and correlated US of the Axilla. All patients underwent axillary lymph node dissection (ALND levels 1 and 2) without a SLNB. Results: Out of 61 patients, 40 (65.6%) had axillary node uptake on PET/CT scan. But, after ALND, only 32 patients were found to have metastatic nodes on the histopathological examination (HPE) of the operative specimen. Out of these 32 patients, results for axillary metastasis had been noted on PET/CT, US, and guided FNAC in 18 patients (56.3%). Discordant results were noted in 14 (43.8%) patients, 29 patients had no metastasis on HPE. Negative results for axillary metastasis were noted on PET/CT, US and guided FNAC in 26 patients (89.7%). The results were discordant in 3 (10.3%) patients. Conclusions: An expanded preoperative axillary assessment does not have sufficient reliability to serve as a reliable triaging technique in axillary management. Concordant positive results may permit directly proceeding to ALND without resorting to SLNB. Concordant negative results may similarly permit avoiding axillary surgery. But discordant results warrant SLNB for assessment of axilla.

Patient-reported outcomes for the Intergroup Sentinel Mamma study (INSEMA): A randomised trial with persistent impact of axillary surgery on arm and breast symptoms in patients with early breast cancer.

In clinically node-negative breast cancer patients, the INSEMA trial (NCT02466737) assessed the non-inferiority of avoiding sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Here we present patient-reported outcomes (PROs) as a secondary endpoint. PROs were assessed for patients with no axillary surgery, SLNB alone, and ALND. Quality of life (QoL) questionnaire EORTC QLQ-C30 and its breast cancer module (BR23) were used at baseline (pre-surgery) and 1, 3, 6, 12, and 18 months after surgery. The QoL scores were compared using repeated measures mixed models based on the safety set. Between 2015 and 2019, 5502 patients were recruited for the first randomization, and 5154 were included inthe intent-to-treat set (4124 SLNB versus 1030 no SLNB). In the case of one to three macrometastases after SLNB, 485 patients underwent second randomization (242 SLNB alone versus 243 ALND). Questionnaire completion response remained high throughout the trial: over 70% at all time points for the first randomization. There were significant differences for the BRBS (breast symptoms) and BRAS (arm symptoms) scores favoring the no SLNB group in all post-baseline assessments. Patients in the SLNB group showed significantly and clinically relevant higher scores for BRAS (differences in mean values ≥5.0 points at all times), including pain, arm swelling, and impaired mobility in all postoperative visits, with the highest difference at one month after surgery. Scoring of theQLQ-C30 questionnaire revealed no relevant differences between the treatment groups, although some comparisons were statistically significant. This is one of the first randomized trials investigating the omission of SLNB in clinically node-negative patients and the first to report comprehensive QoL data. Patients with no SLNB benefitted regarding arm symptoms/functioning, while no relevant differences in other scales were seen. Supported by German Cancer Aid (Deutsche Krebshilfe, Bonn, Germany), Grant No. 110580 and Grant No. 70110580 to University Medicine Rostock.

The Integrated 31-Gene Expression Profile (i31-GEP) Test for Cutaneous Melanoma Outperforms a Clinicopathologic-only Nomogram at Identifying Patients who can Forego Sentinel Lymph Node Biopsy

Introduction: National guidelines for cutaneous melanoma suggest avoiding sentinel lymph node biopsy (SLNB) if the risk of SLN positivity is <5% (T1a with no high-risk features), considering SLNB if the risk is 5-10% (T1a with additional high-risk features (T1aHR) and T1b), and offering SLNB if the risk is >10% (T2-T4). Because most patients (88%) who undergo an SLNB have a negative result, novel tools to identify patients who can safely forgo SLNB are critical. The integrated 31-gene expression profile (i31-GEP for SLNB) test for cutaneous melanoma combines tumor molecular biology with clinicopathologic features to provide a precise risk of SLN positivity. The Melanoma Institute of Australia (MIA) developed a nomogram that uses only clinicopathologic features to predict SLN positivity.
 Methods: We compared the i31-GEP for SLNB to the MIA nomogram in patients with T1-T2 tumors with complete data (n=582). The precision of each tool to identify patients with <5% SLN positivity risk was analyzed using 95% confidence intervals. To be considered low risk, the predicted risk must be <5% and the upper 95% confidence interval must be ≤10%, and to be considered high-risk, the predicted risk must be >10% and the lower 95% CI ≥5%.
 Results: The i31-GEP for SLNB identified 28.5% (166/582) of patients as having a <5% risk of SLN positivity while also having an upper 95% CI ≤10% compared with 0.9% (5/582, p<0.001) using the MIA nomogram. In patients with a pre-test likelihood of SLN positivity of 5-10% (T1aHR-T1b), the i31-GEP reclassified risk in 60.2% (171/284) of patients as being <5% or >10% compared to 13.7% (39/284, p<0.001) using the MIA nomogram. In patients with a known SLN status (n=466), the i31-GEP for SLNB identified 22.1% (103/466) of patients as having <5% risk, with a 3.9% (4/103) SLN positivity rate compared to 0.6% (3/466, p<0.001) identified by the MIA as having a <5% risk with a 33.3% (1/3) SLN positivity rate.
 Conclusions: The i31-GEP test outperformed the MIA nomogram in identifying patients who could safely forego SLNB. Integrating the 31-GEP molecular risk stratification tool with clinicopathologic features provides precise SLN positivity risk to better guide patient management in patients with T1-T2 tumors, for whom SLNB guidance could be most impactful.

Abstract GS4-03: Patient-reported outcomes (PROs) for the intergroup sentinel mamma study (INSEMA, GBG75, ABCSG43): Persistent impact of axillary surgery on arm and breast symptoms in early breast cancer

Abstract Background: Despite increasing evidence disfavoring axillary lymph node dissection (ALND) for locoregional control, it remains part of guidelines for breast cancer (BC) treatment. In an attempt to re-evaluate standard local therapy, the INSEMA trial was designed to assess non-inferiority of avoiding sentinel lymph node biopsy (SLNB) or completion ALND (cALND) in early-stage clinically node-negative BC patients. Here we present PROs from the INSEMA trial. Methods: INSEMA (NCT02466737) investigates non-inferiority of invasive disease-free survival (iDFS) after no axillary surgical staging versus SLNB (first randomization 1:4) in patients with clinically node-negative BC (tumor size ≤5 cm) and primary breast-conserving surgery (BCS). In case of pN1a(sn) in the SLNB arm, patients underwent a second randomization to either SLNB alone or cALND (1:1). PROs were assessed at baseline (pre-surgery) and at 1, 3, 6, 12, and 18 months after final axillary surgery using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) and its breast cancer (BR23) module. Higher scores of C30 and BR23 (range 0-100) indicate better functioning and global health status (GHS)/quality of life (QoL) or worse symptom severity, respectively. The QoL scores were compared using the Mann-Whitney U test based on the safety set. Results: Between September 2015 and April 2019, 5,502 patients were recruited for the 1st randomization and 5,173 of them were included in the intent-to-treat set (4,138 SLNB vs 1,035 no SLNB). Patient and tumor characteristics were well-balanced between treatment arms. Median age at diagnosis was 62.0 years (range 24.0 - 89.0). Overall, recruited patients presented with low-risk BC marked by 85.6% clinically stage T1, 98.5% hormone-receptor positivity, 2.4% HER2-positivity, and 3.7% G3 tumors. The majority (73.5%) had an invasive carcinoma of no special type (72.8% in SLNB vs 76.0% in no SLNB arm) and 87.0% had Ki-67 ≤ 20%. Questionnaire completion response remained high throughout the trial: n=3,915 (75.7%) returned questionnaires at 1 month after final axillary surgery, n=3,938 (76.1%) at 3 months, n=4,024 (77.8%) at 6 months, n=3,907 (75.5%) at 12 months, and n=3,637 (70.3%) at 18 months. All QoL baseline parameters regarding GHS, functional scales, and symptom scales/items were well-balanced between arms (total 4,117 SLNB vs 1,056 no SLNB as treated; 270 of 4,117 received cALND). There were significant differences for the BRBS (breast symptoms) and BRAS (arm symptoms) scores favoring the no SLNB group in all post-baseline assessments Patients in the SLNB group showed persistent higher scores for BRAS (differences in mean values ≥5.0 points at all times of assessment) including pain, arm swelling, and impaired mobility in all postoperative visits with the highest difference at 1 month after final surgery (mean scores, 23.6 vs. 12.8, p<0.001). Differences between treatment arms regarding BRBS including pain, breast swelling, hypersensitivity, and other skin problems showed a smaller range, but still a continuous trend for improved QoL in the no SLNB arm. Scoring of the QLQ-C30 questionnaire revealed no relevant differences between the treatment groups postoperatively. Conclusions: This is one of the first randomized trials investigating the omission of SLNB in clinically node-negative patients and the first to report QoL data. Patients with no SLNB benefitted regarding arm symptoms/functioning while no relevant differences in other QoL scales were seen. Data for the primary outcome of the study (iDFS) are expected for the end of 2024. Citation Format: Bernd Gerber, Angrit Stachs, Kristina Veselinovic, Silke Polata, Thomas Müller, Thorsten Kühn, Jörg Heil, Beyhan Ataseven, Roland Reitsamer, Guido Hildebrandt, Michael Knauer, Michael Golatta, Andrea Stefek, Dirk-Michael Zahm, Marc Thill, Valentina Nekljudova, David Krug, Fenja Seither, Sibylle Loibl, Toralf Reimer. Patient-reported outcomes (PROs) for the intergroup sentinel mamma study (INSEMA, GBG75, ABCSG43): Persistent impact of axillary surgery on arm and breast symptoms in early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-03.

Is ultrasound-guided fine needle aspiration biopsy of axillary lymph nodes a viable alternative to sentinel lymph node biopsy?

Axillary lymph node (ALN) ultrasound-guided fine needle aspiration biopsy (US-FNAB), a minimally invasive procedure, may be used for the preoperative evaluation of ALN status of breast cancer patients. Despite the relative ease of use and low cost, paucity of comparative studies and variation in the reported sensitivity of FNAB preclude its clinical utility in evaluation of ALNs. This study aims to determine the accuracy of US-FNAB in detecting metastasis in ALN pre-operatively and to assess US-FNAB as a viable alternative to sentinel lymph node (SLN) excision. The 228 consecutive ALN US-FNABs with subsequent histologic follow up performed from 2005 to 2020 in patients with breast carcinoma were retrospectively evaluated. FNAB results were correlated with histologic diagnosis. Sensitivity, specificity, accuracy, and risk of malignancy of FNAB were calculated. 157/228 (69%) FNABs were concordant with histology, 37/228 (16%) discordant. Positive FNAB findings correlated with primary tumor size, grade, number of metastatic lymph nodes and size of metastases. FNAB with negative diagnosis carried a 22% risk of malignancy, atypical 43%, suspicious 80%, and positive a 100% risk of malignancy (100% positive predictive value [PPV]). The sensitivity and specificity were 78% and 95% respectively; accuracy was 77%. SLN biopsy was avoided in all 82 (36%) cases with positive FNAB results. Negative FNAB result does not exclude metastatic carcinoma. With 100% PPV, full ALN dissection and/or neoadjuvant chemotherapy can be safely planned after a positive FNAB result, avoiding SLN biopsy, reducing management costs and shortening time interval to definitive therapy.

Abstract PS9-56: High compliance with choosing wisely breast procedures at a safety net hospital

Abstract The Choosing Wisely campaign has emerged recently in setting guidelines for surgical procedures of low utility and cost-ineffectiveness. Hospitals caring for underserved medical populations represent a unique opportunity to assess for quality of care and adherence to these guidelines. The Choosing Wisely campaign for breast surgery has highlighted: avoiding surgical re-excision for invasive cancer close to margins of excised breast tissue, avoiding double mastectomy in patients who have a single breast with cancer, avoidance of axillary lymph node dissection in women undergoing lumpectomy with limited nodal disease, and avoiding sentinel lymph node biopsy in patients ≥ 70 years of age with early stage breast cancer. Recent studies have shown variable adherence to these recommendations. In order to evaluate cost-effective surgery at our hospital serving a poorer patient population, we retrospectively analyzed patients who underwent surgery for breast cancer from 2015-2020. A total of 231 patients were identified. There were no patients who underwent re-excision for close margins of invasive cancer. Only 0.9% of patients (2/231) received contralateral mastectomy and only 1.6% of eligible patients (3/191) received axillary lymph node dissection instead of sentinel lymph node biopsy. Although 77.7% of patients ≥ 70 years of age with stage 1 hormone positive breast cancer (14/18) received sentinel lymph node biopsy, there was a downward trend during 2015 to 2020 from 100% to 50% of eligible patients receiving sentinel lymph node biopsy. De-implementation of traditional surgical practices, deemed as low-value care, towards newer cost-effective guidelines are achievable even at community hospitals serving a low socioeconomic community while preserving patient outcome and avoiding overtreatment. By avoiding overtreatment, cost savings can be achieved which allow for social distributive justice amongst breast cancer patients by ensuring careful utilization of scarce health economic resources. Citation Format: Annie Tang, Colin Mooney, Shannon Ugarte, Kevin Knopf, Amal Khoury. High compliance with choosing wisely breast procedures at a safety net hospital [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 PS9-56.

Preoperative Axillary Ultrasound versus Sentinel Lymph Node Biopsy in Patients with Early Breast Cancer.

Background and objectives: With improved diagnostic means of early breast cancer, the percentage of cases with metastasis in axillary lymph nodes has decreased from 50–75% to 15–30%. Lymphadenectomy and sentinel lymph node biopsy are not treatment procedures, as they aim at axillary nodal staging in breast cancer. Being surgical interventions, they can lead to various complications. Therefore, recently much attention has been paid to the identification of non-invasive methods for axillary nodal staging. In many countries, ultrasound is a first-line method to evaluate axillary lymph node status. The aim of this study was to evaluate the prognostic value of ultrasound in detecting intact axillary lymph nodes and to assess the accuracy of ultrasound in detecting a heavy nodal disease burden. The additional objective was to evaluate patients’ and tumor characteristics leading to false-negative results. Materials and Methods: A total of 227 women with newly diagnosed pT1 breast cancer were included to this prospective study conducted at the Breast Surgery Unit, Clinic of Surgery, Hospital of Lithuanian University of Health Sciences Kauno Klinikos, between May 1, 2016, and May 31, 2018. All patients underwent preoperative axillary ultrasound examination. Ultrasound data were compared with the results of histological examination. The accuracy and true-negative rate of ultrasound were calculated. The reasons of false-negative results were analyzed. Results: Of the 189 patients who had normally appearing axillary lymph nodes on preoperative ultrasound (PAUS-negative), 173 (91.5%) patients were also confirmed to have intact axillary lymph nodes (node-negative) by histological examination after surgery. The accuracy and the negative predictive value of ultrasound examination were 84.1% and 91.5%, respectively. In ≥3 node-positive cases, the accuracy and the negative predictive value increased to 88.7% and 98.3%, respectively. In total, false-negative results were found in 8.5% of the cases (n = 16); in the PAUS-negative group, false-negative results were recorded only in 1.6% of the cases (n = 3). The results of PAUS and pathological examination differed significantly between patients without and with lymphovascular invasion (LV0 vs. LV1, p < 0.001) as well as those showing no human epidermal growth factor receptor 2 (HER2) expression and patients with weakly or strongly expressed HER2 (HER2(0) vs. HER2(1), p = 0.024). Paired comparisons revealed that the true-negative rate was significantly different between the LV0 and LV1 groups (91% vs. 66.7%, p < 0.05), and the false-negative rate was statistically significant different between the HER2(0) and HER2(1) groups (10.5% vs. 1.2%, p < 0.05). Evaluation of other characteristics showed both the groups to be homogenous. Conclusions: Negative axillary ultrasound excluded axillary metastatic disease in 91.5% of the patients. PAUS had an accuracy of 88.7% in detecting a heavy nodal disease burden. With the absence of lymphovascular invasion (LV0), we can rely on PAUS examination that axillary lymph nodes are intact (PAUS-negative), and this patients’ group could avoid sentinel lymph node biopsy. Patients without HER2 expression are at a greater likelihood of false-negative results; therefore, the findings of ultrasound that axillary lymph nodes are intact (PAUS-negative results) should be interpreted with caution.

Impact of older age on local treatment decisionss

Managing elderly breast cancer patients brings challenges both to physicians and patients themselves. There are certain controversial issues regarding local treatment of early breast cancer in this population. Since elderly patients are more likely to have comorbidities and functional limitations, they are more prone to undertreatment.Although surgical treatment in elderly patients were reported to be safe, severity and number of comorbidities are shown to be related with increased complications, hence may lead to higher mortality and lower life quality. Therefore, frailty is one of the concerns which prevents elderly patients to receive standard-of-care local treatment. Nevertheless, breast cancers developing in elderly are more likely to be low grade and luminal type. Until now, primary endocrine treatment without surgical resection, omitting whole breast irradiation after partial mastectomy and avoiding sentinel lymph node biopsy, which are otherwise accepted as standard-of-care, were questionned in healthy, low-risk, elderly fit patients. Two main issues were suggested to be considered when assessing the impact of local treatment options in this patient group; the clinical significance of treatments’ effects, and the patients’ expectations. Due to their vulnerability, baseline geriatric assessment should be the initial step for management in elderly breast cancer patients. Even in those who are healthy and fit with long life-expectancy, de-escalation in management might be an option in low-risk patients after considering patients’ individual expectations and limited clinical benefits of standard local treatment options.

Determining Whether High Nodal Burden in Early Breast Cancer Patients Can Be Predicted Preoperatively to Avoid Sentinel Lymph Node Biopsy.

PurposeThe Z0011 trial showed that axillary lymph node dissection (ALND) can be safely avoided in breast cancer patients with low nodal burden (LNB). ALND can be performed in patients with high nodal burden (HNB). We aimed to determine whether HNB in early breast cancer patients can be predicted preoperatively to avoid sentinel lymph node biopsy (SLNB).MethodsEarly invasive breast cancer patients (cT1-2cN0) were retrospectively reviewed. We excluded patients with neoadjuvant chemotherapy and incomplete data. The patients were divided into the following groups based on surgical histology: no positive (N0), LNB, and HNB, defined as 0, 1–2, and ≥ 3 metastatic lymph nodes (LNs), respectively. Of the patients with metastatic nodal disease, only those with ALND were included in the analysis. Clinical, radiological, and histological parameters were evaluated using logistic regression analysis as predictors of HNB versus LNB and N0 combined.ResultsOf the 1,298 included patients, 832 (64.1%), 286 (22.0%), and 180 (13.9%) had N0, LNB, and HNB, respectively. Univariate logistic regression analysis revealed that sonographic features of breast tumor size (p < 0.0001), number of abnormal LNs (p < 0.0001), cortical thickness (p = 0.0002), effacement of the fatty hilum (p < 0.0001), and needle biopsy being performed (p < 0.0001) were indicators of HNB. Breast tumor grade (p = 0.0001) and human epidermal growth factor receptor 2 status (p = 0.0262) were also statistically significant. Among these significant features, multivariable stepwise logistic regression showed that the number of abnormal LNs is the sole independent predictor of HNB (p < 0.0001, area under the curve = 0.774). The positive predictive value of HNB in patients with ≥ 4 abnormal LNs was 92.9%.ConclusionThe detection of ≥ 4 abnormal LNs on ultrasound can help to identify HNB patients who require upfront ALND and thus avoid SLNB.

Management of axilla in breast cancer: the past, present and the future

The role of surgery in treatment of breast cancer has evolved substantially during the last century where radical surgery has gradually been replaced by more conservative approaches. Similarly, surgical treatment of the axilla has changed rapidly especially over last three decades. This is mostly as a result of improvements in understanding of disease behaviour and advances in systemic therapy. Axillary surgery has the dual uses of removing the disease from the axilla and providing information for prognostication which help guide adjuvant therapy. However, surgery to the axilla is associated with substantial morbidly including lymphedema and shoulder stiffness. Hence, less radical approaches for the treatment of the axilla have been of interest. The traditional gold standard of axillary lymph node dissection was challenged by many clinical trials. As result sentinel lymph node biopsy was introduced as an alternative for patients with clinically negative axillae which later became the standard of care for such patients. Subsequent studies proved the safety of omitting completion axillary dissection or replacing with radiotherapy for selected patients with minimal sentinel lymph node involvement. The application of sentinel lymph node biopsy for axillary staging after neoadjuvant chemotherapy has become an area of clinical interest. However, sentinel lymph node biopsy in node-positive patients who become node negative after neoadjuvant chemotherapy is controversial at present due to the relatively high false-negative rate. This however, is improved by careful patient selection combined with some minor changes to the surgical technique of sentinel lymph node biopsy. Novel techniques for lymphatic mapping have shown promising results which further simplify the procedure while improving the accuracy. Axillary reverse mapping, a technique to preserve lymph nodes draining the arm during axillary surgery for breast cancer has been described recently which has further reduced surgical morbidity. The omission of axillary surgery in selected patients with an acceptably low risk of nodal metastasis has gained increasing research interest in the recent past. Furthermore, advances in treatment and newer prognostication techniques have reduced the dependence on axillary nodal status on adjuvant therapy decision-making. This has led to several ongoing clinical trials which will assess the feasibility of avoiding sentinel lymph node biopsy altogether in selected groups of patients without compromising outcomes.

18F-fluorodeoxyglucose uptake as predictor for invasion in preoperatively diagnosed breast ductal carcinoma in situ: Significance in cases without mass formation.

A diagnosis of ductal carcinoma in situ (DCIS) at needle biopsy often changes to that of invasive ductal carcinoma as the definitive pathological diagnosis following the surgical procedure. The present study sought to identify the factors associated with invasive disease in cases diagnosed as DCIS on needle biopsy by analyzing 18F-fluorodeoxyglucose-proton emission tomography (FDG-PET) findings. The present study retrospectively investigated the cases of 24 consecutive patients with primary breast cancer who were preoperatively diagnosed with DCIS by needle biopsy. The cases were divided into two groups based on the presence of invasion in the primary tumor. Among the 24 patients, 13 (54.7%) patients had invasive carcinoma and 11 (45.8%) had DCIS. The analysis revealed that the presence of FDG uptake in the tumor was the only independent predictor of presence of the invasive disease. No cases without FDG uptake exhibited invasion and all of these were ultimately diagnosed as DCIS. In the present study, all cases, including DCIS, with a nodular growth pattern demonstrated FDG uptake in the tumors, and all cases without FDG uptake were interpreted as having a diffuse growth pattern. The present findings suggested that the presence of FDG uptake in the tumor can be considered a predictor for invasion in cases with DCIS by needle biopsy, particularly in cases with a diffuse growth pattern. Patients preoperatively diagnosed as DCIS without mass formation and without FDG uptake in the tumor may avoid sentinel lymph node biopsy.

Axillary Ultrasound: For All, for None, to Diagnose Positive Nodes, or to Support Avoiding Sentinel Lymph Node Biopsy Altogether.

Axillary ultrasound is increasingly utilized for nodal staging preoperatively in patients presenting with invasive breast cancer to provide guidance for preoperative chemotherapy or proceeding directly to surgery. Improvements in ultrasound technology make it possible to assess the nodal burden in order to identify those patients not eligible for ACOSOG Z0011 management. However, its ability to detect metastasis is variable and dependent on operator's skills, size of metastatic deposit, and primary tumor histology subtype. Therefore, sentinel lymph node biopsy is still performed with a normal axillary ultrasound. Current debate questions whether there is a benefit to diagnosing metastasis with ultrasound-guided needle biopsy as this may lead to more axillary node dissections in an era of its decreasing role. In node-positive patients, axillary ultrasound has been preliminarily shown to be helpful in assessing nodal response after preoperative chemotherapy and improve the accuracy of sentinel node dissection which may spare future patients' axillary node dissection. Improvements in axillary ultrasound and other imaging modalities along with predictive models based on tumor biology may make axillary surgery a procedure of the past for many breast cancer patients.

Validation of Statistical Predictive Models Meant to Select Melanoma Patients for Sentinel Lymph Node Biopsy

To identify melanoma patients at sufficiently low risk of nodal metastases who could avoid sentinel lymph node biopsy (SLNB), several statistical models have been proposed based upon patient/tumor characteristics, including logistic regression, classification trees, random forests, and support vector machines. We sought to validate recently published models meant to predict sentinel node status. We queried our comprehensive, prospectively collected melanoma database for consecutive melanoma patients undergoing SLNB. Prediction values were estimated based upon four published models, calculating the same reported metrics: negative predictive value (NPV), rate of negative predictions (RNP), and false-negative rate (FNR). Logistic regression performed comparably with our data when considering NPV (89.4 versus 93.6%); however, the model's specificity was not high enough to significantly reduce the rate of biopsies (SLN reduction rate of 2.9%). When applied to our data, the classification tree produced NPV and reduction in biopsy rates that were lower (87.7 versus 94.1 and 29.8 versus 14.3, respectively). Two published models could not be applied to our data due to model complexity and the use of proprietary software. Published models meant to reduce the SLNB rate among patients with melanoma either underperformed when applied to our larger dataset, or could not be validated. Differences in selection criteria and histopathologic interpretation likely resulted in underperformance. Statistical predictive models must be developed in a clinically applicable manner to allow for both validation and ultimately clinical utility.

New SOMAmer-based assay to discover biomarkers relevant to malignant melanoma

Abstract Malignant melanoma is a serious form of skin cancer with approximately 138,000 new cases predicted worldwide in 2010 and an estimated 48,000 deaths. The number is expected to double in less than a decade. There is an unmet need for new molecular technologies that provide for cost-effective, reliable and accurate detection of malignant melanoma at tumor burden levels below those currently observable with standard imaging or histopathological techniques. It would be desirable if a new test could predict a) sentinel lymph node (SLN) positivity in order to avoid SLN biopsy, an invasive and expensive procedure, b) recurrence to help monitor disease and make treatment decisions and c) survival time in metastatic melanoma. Secreted proteins and those released during apoptosis from tumor cells and surrounding tissues undoubtedly contain important biologic information that would theoretically enable early diagnosis and prognostic and therapeutic decisions in oncology. However, there is great difficulty in finding and quantifying such signals for large numbers of low abundance proteins. SomaLogic therefore created a highly multiplexed proteomic assay which is continuously expanding in breadth. It currently measures 825 proteins simultaneously from ~15ul blood, with throughput of 300 samples /day. The average dynamic range of each protein in the assay is &amp;gt;3 logs — with nearly seven logs of dynamic range achieved through multiple dilutions — and the median lower limit of quantification is below 1 pM. The median coefficient of variation for each protein is &amp;lt;5%. This assay performance arises from the selection of high affinity aptamers (SOMAmers) that bind selectively to their target proteins with slow off-rates. Retrospective analysis of serum, collected from patients before or after wide local excision / sentinel lymph node removal was done using this aptamer proteomics platform. In patients with metastatic stage IV disease at the time of diagnosis follow-up data was collected for several years to monitor time to survival. A naïve Bayesian statistical program was used for analysis of each comparison, negative to positive SLN cases, recurrence and non recurred cases and in case of metastatic melanoma alive vs. dead of disease within a year of blood draw. Of the 39 patients who had SLN biopsy, 25 were negative (stage II) and 14 were positive (stage III) by pathological analysis. 13 proteins were significantly differentially expressed (p&amp;lt;0.01). A three protein marker panel generated a Receiver Operating Characteristic (ROC) curve area under the curve (AUC) of 0.9 and could identify SLN positive patients with a specificity and sensitivity of 0.92 and 0.93 respectively. Comparison of patients alive with stage IV disease (N=22) verses those dead of disease in 1 year after blood draw (N=15) to yielded 37 proteins significantly different (p=&amp;lt;0.01). A signature of 2 proteins had an area under the ROC curve of 0.89 with a sensitivity and specificity of 0.87 and 0.91 respectively. Thus in a preliminary study we have discovered new proteins associated with a regional verses local disease at the time of diagnosis in patients with melanoma lesions &amp;gt;1mm. In metastatic melanoma, we were able to build classifier to predict survival time within a year. These results will be further validated on a larger sample set.

Ultrasonographically-guided fine-needle aspiration of axillary lymph nodes: role in breast cancer management.

The knowledge of the status of axillary lymph nodes (LN) of patients with breast cancer is a fundamental prerequisite in the therapeutic decision. In the present work, we evaluated the impact of fine-needle aspiration cytology (FNAC) of ultrasonographically (US) selected axillary LN in the diagnosis of LN metastases and subsequently in the treatment of patients with breast cancer. Axillary US was performed in 298 patients with diagnosed breast cancer (267 invasive carcinomas and 31 ductal carcinoma in situ DCIS), and in 95 patients it was followed by FNAC of US suspicious LN. Smears were examined by routine cytological staining. Cases of uncertain diagnosis were stained in immunocytochemistry (ICC) with a combination of anticytokeratin and anti-HMFG2 antibodies. Eighty-five FNAC were informative (49 LN were positive for metastases, 36 were negative). In 49 of 267 patients with invasive breast carcinoma (18%), a preoperative diagnosis of metastatic LN in the axilla could be confirmed. These patients could proceed directly to axillary dissection. In addition, US-guided FNAC presurgically scored 49 out of 88 (55%) metastatic LN. Of all others, with nonsuspicious LN on US (203 cases including 31 DCIS), in which no FNAC examination was performed, 28 invasive carcinomas (16%) turned out to be LN positive on histological examination. Based on these data, US examination should be performed in all patients with breast cancer adding ICC-supported FNAC only on US-suspect LN. This presurgical protocol is reliable for screening patients with LN metastases that should proceed directly to axillary dissection or adjuvant chemotherapy, thus avoiding sentinel lymph node biopsy.