Chemotherapy In Node-positive Breast Cancer Research Articles

Survival Benefit of Adjuvant Chemotherapy in Node-Positive Breast Cancer With a 21-Gene Recurrence Score of 14 to 25: A Real-World Study Based on the Inverse Probability of Treatment Weighting Method

IntroductionThe role of recurrence score in predicting the benefits of adjuvant chemotherapy for lymph-node-positive breast cancer remains uncertain. We studied chemotherapy usage in patients with 1 to 3 positive lymph nodes and a recurrence score (RS) of 25 or lower to assess changes in clinical practice based on the RxPONDER trial. MethodsA retrospective study using the SEER database identified female patients diagnosed with ER-positive, HER2-negative breast cancer, 1 to 3 positive lymph nodes, and an RS of 25 or lower between 2010 and 2015. Patients were divided into nonchemotherapy and chemotherapy groups, with propensity score weighting to balance clinicopathologic factors. ResultsAmong 7965 patients, 5774 (72.5%) were in the nonchemotherapy group, while 2191 (27.5%) were in the chemotherapy group. Median follow-up was 39 months. Breast cancer accounted for 67 deaths, while 128 deaths were due to other causes. The weighted 5-year overall survival (OS) rates were 95.7% for the nonchemotherapy group and 97.2% for the chemotherapy group. For high-risk patients, the weighted 5-year OS rates were 95.2% and 97.0% for the nonchemotherapy and chemotherapy groups, respectively, with a significant absolute difference of 1.8% (P = .014). Multivariate analysis showed a significant difference in weighted hazard ratios for OS between the nonchemotherapy and chemotherapy groups in high-risk patients (hazard ratio: 0.64; 95% CI: 0.48-0.86). However, there were no significant differences in weighted hazard ratios for lower-risk patients, and similar results were observed for breast cancer-specific survival (BCSS). ConclusionPatients with ER-positive, HER2-negative breast cancer and 1 to 3 positive lymph nodes, assessed by a 21-gene RS of 0 to 25, exhibited heterogeneous prognosis. Adjuvant chemotherapy provided a significant survival benefit, especially for patients with RS of 14 to 25, particularly those with invasive ductal carcinoma (IDC) and 2 to 3 positive lymph nodes.

Repeated core needle biopsy and targeted fine-needle aspiration to optimize axillary surgery after neoadjuvant chemotherapy in node-positive breast cancer: prospective clinical study.

Journal Article Repeated core needle biopsy and targeted fine-needle aspiration to optimize axillary surgery after neoadjuvant chemotherapy in node-positive breast cancer: a prospective clinical study Get access Si-Yu Wu, Si-Yu Wu Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Centre, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, China https://orcid.org/0000-0001-7005-8257 Search for other works by this author on: Oxford Academic Google Scholar Jian-Wei Li, Jian-Wei Li Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Centre, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Search for other works by this author on: Oxford Academic Google Scholar Ying Zhang, Ying Zhang Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Centre, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, China https://orcid.org/0000-0003-0180-9592 Search for other works by this author on: Oxford Academic Google Scholar Huai-Liang Wu, Huai-Liang Wu Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Centre, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Search for other works by this author on: Oxford Academic Google Scholar Miao Mo, Miao Mo Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Cancer Prevention, Fudan University Shanghai Cancer Centre, Shanghai, China Search for other works by this author on: Oxford Academic Google Scholar Na Hu, Na Hu Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Ultrasound, Fudan University Shanghai Cancer Centre, Shanghai, China Search for other works by this author on: Oxford Academic Google Scholar Zhi-Ming Shao, Zhi-Ming Shao Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Centre, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Search for other works by this author on: Oxford Academic Google Scholar Guang-Yu Liu Guang-Yu Liu Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Centre, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, China Correspondence to: Guang-Yu Liu, Department of Breast Surgery, Fudan University Shanghai Cancer Centre, 270 DongAn Road, Shanghai 200032, China (e-mail: liugy688@163.com) https://orcid.org/0000-0001-5464-4395 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, znad106, https://doi.org/10.1093/bjs/znad106 Published: 30 May 2023 Article history Received: 13 November 2022 Revision received: 10 January 2023 Accepted: 02 April 2023 Published: 30 May 2023

SPECT/CT Lymphoscintigraphy Accurately Localizes Clipped and Sentinel Nodes After Neoadjuvant Chemotherapy in Node-Positive Breast cancer.

The aim of this study was to evaluate the impact of SPECT/CT lymphoscintigraphy on targeted axillary dissection (TAD) in node-positive breast cancer (BC) patients who had undergone neoadjuvant chemotherapy (NAC). Sixty-two female BC patients with biopsy-confirmed axillary nodal metastases underwent NAC, followed by breast surgery with TAD. A metallic clip was placed in the sampled LN before NAC. On the day of surgery, a periareolar intradermal 99mTc-nanocolloid injection was administered, followed by SPECT/CT lymphoscintigraphy. The clipped nodes were localized on CT images, assessed for 99mTc uptake before surgery, and confirmed during the procedure. T1-4, N1-2 patients were enrolled in the study. All patients underwent sentinel lymph node (SLN) biopsy. The clipped node was the SLN in 54 (88.5%) patients. In 3 patients (4.9%), a clip was found in a nonsentinel lymph node. In 4 patients, the clips were not visible on SPECT/CT images, and lymph nodes were not found during the procedure. SPECT/CT correctly localized the clipped lymph node in all patients. The overall false-negative rate for TAD was 3.33%. The mean follow-up duration was 29 months, and there were no axillary recurrences. SPECT/CT lymphoscintigraphy can accurately localize clipped nodes and SLNs after NAC in patients with node-positive BC.

Abstract PD15-03: PD15-03 Incorporation of Repeated Core Needle Biopsy and Targeted Fine Needle Aspiration to Optimize Axillary Surgery After Neoadjuvant Chemotherapy in Node-positive Breast Cancer: A Prospective Feasibility Study

Abstract Background: It is of substantial importance to tailor axillary surgery after neoadjuvant chemotherapy (NAC) based on tumor biology and response to treatment. This study aimed to determine the accuracy of repeated core needle biopsy (RCNB) in breast to predict nodal response after NAC. Methods: Eligible patients with clip insertment into pathologically-proven positive node underwent RCNB during NAC. Targeted fine needle aspiration (TFNA) of clipped lymph node (CLN) was performed in a subset of patients after NAC. All patients ultimately underwent axillary surgery. RCNB and TFNA results were compared with surgical pathology. Results: Data from 189 eligible patients were analyzed. The overall axillary pCR was 57.1%. The false-negative rate (FNR) of RCNB across the whole cohort was 12.1% (95% CI, 5.3%–18.9%), and exploratory subgroup analysis revealed an excellent ability to predict the presence of residual nodal disease in estrogen receptor-positive breast cancer with a low FNR of 1.6% (95% CI, 0.0%–4.9%) (Table 1). Adopting a strategy where only patients with negative RCNB undergo targeted axillary dissection (TAD) would potentially reduce the FNR of TAD from 9.3% to 2.3%. Furthermore, combination of RCNB and TFNA demonstrated a FNR of 2.2% (95% CI, 0.0%–6.6%), and negative predictive value of 94.1% (95% CI, 81.6%–100.0%) (N = 87) (Table 2). The proposed algorithm based on RCNB and TFNA is helpful in optimizing axillary surgery by avoiding 25 unnecessary attempts as well as 2 false-negative cases in TAD and conferring 10 patients omission of axillary surgery. Conclusions: Combination of RCNB and TFNA allows for an accurate assessment of nodal response after NAC. These results may facilitate reliable identification of suitable candidates for de-escalation or elimination in axillary surgery. Table 1: Overall Cohort Diagnostic Accuracy of Repeated Core Needle Biopsy to Predict Nodal Response (N = 189) Abbreviations: ER, estrogen receptor; HER2, human epidermal factor receptor 2; NPV, negative predictive value; PPV, positive predictive value. Table 2. Diagnostic Accuracy of Repeated Core Needle Biopsy in Breast, Targeted Fine Needle Aspiration and the Combination in Cohort 2 (N = 87) Abbreviations: NPV, negative predictive value; PPV, positive predictive value; RCNB, repeated core needle biopsy; TFNA, targeted fine needle aspiration. Citation Format: Siyu Wu, Jianwei Li, Ying Zhang, Na Hu, Guangyu Liu. PD15-03 Incorporation of Repeated Core Needle Biopsy and Targeted Fine Needle Aspiration to Optimize Axillary Surgery After Neoadjuvant Chemotherapy in Node-positive Breast Cancer: A Prospective Feasibility Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-03.

An MRI-based Scoring System for Preoperative Prediction of Axillary Response to Neoadjuvant Chemotherapy in Node-Positive Breast Cancer: A Multicenter Retrospective Study

To develop and validate a simplified scoring system by integrating MRI and clinicopathologic features for preoperative prediction of axillary pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in clinically node-positive breast cancer. A total of 389 patients from three hospitals were retrospectively analyzed. To identify independent predictors for axillary pCR, univariable and multivariable logistic regression analyses were performed on pre- and post-NAC MRI and clinicopathologic features. Then, a simplified scoring system was constructed based on regression coefficients of predictors in the multivariable model, and its predictive performance was assessed with the receiver operating characteristic curve and calibration curve. The added value of the scoring system for reducing false-negative rate (FNR) of the sentinel lymph node biopsy (SLNB) was also evaluated. The simplified scoring system including seven predictors: progesterone receptor-negative (Three points), HER2-positive (Two points), post-NAC clinical T0-1 stage (Two points), pre-NAC higher ADC value of breast tumor (One point), absence of perinodal infiltration at pre-NAC (One point) and post-NAC MRI (Two points), and absence of enhancement in the tumor bed at post-NAC MRI (Two points), showed good calibration and discrimination, with AUCs of 0.835, 0.828 and 0.798 in the training, internal and external validation cohorts, respectively. The axillary pCR rates were increased with the total points of the scoring system, and patients with a score of ≥11 points had a pCR rate of 86%-100%. In test cohorts for simulating clinical application, the diagnostic accuracy for axillary pCR was 80%-90% among four different radiologists. Compared to standalone SLNB, combining the scoring system with SLNB reduced the FNR from 14.5% to 4.8%. The clinicopathologic-image scoring system with good predictive performance for axillary pCR in clinically node-positive breast cancer, may guide axillary management after NAC and improve patient selection for de-escalating axillary surgery to reduce morbidity.

Diagnostic Accuracy of Radioactive Iodine Seed Placement in the Axilla With Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer

Several less-invasive staging procedures have been proposed to replace axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) in patients with initially clinically node-positive (cN+) breast cancer, but these procedures may fail to detect residual disease. Owing to the lack of high-level evidence, it is not yet clear which procedure is most optimal to replace ALND. To determine the diagnostic accuracy of radioactive iodine seed placement in the axilla with sentinel lymph node biopsy (RISAS), a targeted axillary dissection procedure. This was a prospective, multicenter, noninferiority, diagnostic accuracy trial conducted from March 1, 2017, to December 31, 2019. Patients were included within 14 institutions (general, teaching, and academic) throughout the Netherlands. Patients with breast cancer clinical tumor categories 1 through 4 (cT1-4; tumor diameter <2 cm and up to >5 cm or extension to the chest wall or skin) and pathologically proven positive axillary lymph nodes (ie, clinical node categories cN1, metastases to movable ipsilateral level I and/or level II axillary nodes; cN2, metastases to fixed or matted ipsilateral level I and/or level II axillary nodes; cN3b, metastases to ipsilateral level I and/or level II axillary nodes with metastases to internal mammary nodes) who were treated with NAC were eligible for inclusion. Data were analyzed from July 2020 to December 2021. Pre-NAC, the marking of a pathologically confirmed positive axillary lymph node with radioactive iodine seed (MARI) procedure, was performed and after NAC, sentinel lymph node biopsy (SLNB) combined with excision of the marked lymph node (ie, RISAS procedure) was performed, followed by ALND. The identification rate, false-negative rate (FNR), and negative predictive value (NPV) were calculated for all 3 procedures: RISAS, SLNB, and MARI. The noninferiority margin of the observed FNR was 6.25% for the RISAS procedure. A total of 212 patients (median [range] age, 52 [22-77] years) who had cN+ breast cancer underwent the RISAS procedure and ALND. The identification rate of the RISAS procedure was 98.2% (223 of 227). The identification rates of SLNB and MARI were 86.4% (197 of 228) and 94.1% (224 of 238), respectively. FNR of the RISAS procedure was 3.5% (5 of 144; 90% CI, 1.38-7.16), and NPV was 92.8% (64 of 69; 90% CI, 85.37-97.10), compared with an FNR of 17.9% (22 of 123; 90% CI, 12.4%-24.5%) and NPV of 72.8% (59 of 81; 90% CI, 63.5%-80.8%) for SLNB and an FNR of 7.0% (10 of 143; 90% CI, 3.8%-11.6%) and NPV of 86.3% (63 of 73; 90% CI, 77.9%-92.4%) for the MARI procedure. In a subgroup of 174 patients in whom SLNB and the MARI procedure were successful and ALND was performed, FNR of the RISAS procedure was 2.5% (3 of 118; 90% CI, 0.7%-6.4%), compared with 18.6% (22 of 118; 90% CI, 13.0%-25.5%) for SLNB (P < .001) and 6.8% (8 of 118; 90% CI, 3.4%-11.9%) for the MARI procedure (P = .03). Results of this diagnostic study suggest that the RISAS procedure was the most feasible and accurate less-invasive procedure for axillary staging after NAC in patients with cN+ breast cancer.

Internal mammary node irradiation in node-positive breast cancer treated with mastectomy and taxane-based chemotherapy

BackgroundIt is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy. MethodsWe analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups. ResultsAfter a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220–0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018). ConclusionsIMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.

Abstract PS1-29: Predicting axillary pathologic response to neoadjuvant chemotherapy for node-positive breast cancer: Clinical predictive model by using MRI and ultrasound

Abstract Purpose: Neoadjuvant chemotherapy (NAC) has been shown to eradicate axillary lymph node metastasis in approximately 40% of patients. Sentinel lymph node biopsy (SLNB) could be an alternative surgical approach for these patients to avoid morbidity from axillary lymph node dissection (ALND). However, high false-negative rates of SLNB for initially node-positive patients were reported in previous trials. The aim of this study was to evaluate clinicopathological factors and imaging characteristics by MRI and ultrasound (US) as predictors of axillary pathologic complete response (ypN0) after NAC, which enable to identify candidates for SLNB in patients with clinically node-positive disease. Patients and methods: We identified 153 patients with clinically node-positive breast cancer who received NAC from May 2009 to December 2019. Clinicopathological data including age, clinical T/N status, nuclear grade, hormone receptor (HR) and HER2 status were collected. All patients underwent MRI and US before and after NAC. Patients were judged to be node-positive when they have cytologically-proven nodal disease by fine-needle aspiration (FNA) or suspicious lymph nodes by diagnostic imaging. Lymph nodes with cortical thickness (&amp;gt;3.5mm), loss of fatty hilum or round shape (short-axis/long-axis ratio &amp;gt; 0.5) were defined as suspicious lymph nodes. All imaging data were evaluated at baseline and after NAC. To develop a predictive model for ypN0, the association between ypN0 status and clinicopathological and imaging characteristics were assessed by multivariate logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was used to evaluate discrimination by the model. Results: The median age was 55.0 (range: 22-79) years and the mean tumor size was 3.86 ± 2.04 cm. Pretherapeutic lymph node status was assessed by FNA in 88 (57.5%) patients. Of 153 patients, 80 (52.3%) patients had luminal, 39 (25.5%) had HER2-positive, and 34 (22.2%) had triple negative disease. Sequential anthracycline and taxane were administered for 138 (90.2%) patients, and 37 (94.9%) patients with HER2-positive-disease received concomitant anti-HER2 agents preoperatively. Overall, 62 (40.5%) patients achieved ypN0. Independent predictors of ypN0 status were breast complete response by MRI (odds ratio [OR]: 9.01, p&amp;lt;0.001), clinical stage N1 (OR: 6.64 vs. cN2-3, p=0.009), absence of lymphadenopathy after NAC (OR: 6.09, p&amp;lt;0.001), HR negativity (OR: 3.10, p=0.02) and HER2 positivity (OR: 2.87, p=0.04). In a model using these predictors, the area under the ROC curve was 0.870 (95% confidence interval: 0.814-0.925, p&amp;lt;0.001). Sensitivity, specificity, positive predictive value and negative predictive value of the model were 72.6%, 86.8%, 78.9% and 82.3%, respectively. After a median follow-up of 49.7 months, 5-year disease-free survival (DFS) was significantly higher in patients who achieved ypN0 than patients with residual axillary disease (88.7% vs. 76.9%, p=0.046). Among 62 patients who achieved ypN0 after NAC, ALND was omitted in 24 (38.7%) patients and irradiation to regional lymph nodes was performed in 8 (33.3%) out of 24 patients. Five-year DFS was comparable between patients with or without ALND (86.8% vs. 91.7%, p=0.815). Conclusions: Our predictive model based on imaging characteristics by MRI and US could help to identify good candidates for omission of ALND after NAC in patients with initially node-positive breast cancer. Citation Format: Akiko Matsumoto, Miki Yamada, Daisuke Tsukahara, Yasuko Umemoto, Hiromitsu Jinno. Predicting axillary pathologic response to neoadjuvant chemotherapy for node-positive breast cancer: Clinical predictive model by using MRI and ultrasound [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 PS1-29.

Targeted Axillary Dissection for Patients Who Convert to Clinically Node Negative After Neoadjuvant Chemotherapy for Node-Positive Breast Cancer

The use of neoadjuvant chemotherapy (NAC) for breast cancer (BC) can eradicate axillary disease in > 40% of patients. The standard of care for node-positive BC has been axillary lymph node dissection. In this review, we examine the data for de-escalating axillary surgery after NAC. Studies have shown that sentinel lymph node biopsy (SLNB) is accurate after NAC. False negative rates (FNR) of SLNB after NAC in node-positive patients have been reduced with a combination of dual tracers and localization of the clipped positive node. Clipped nodes may be localized with a variety of methods. Targeted axillary dissection (removal of clipped node in conjunction with SLNB) results in an acceptable FNR and can be considered in certain patients with axillary clinical response to neoadjuvant chemotherapy. Patient selection is important, as those with persistently positive nodes on clinical exam should proceed directly to axillary dissection.

Combining Wire Localization of Clipped Nodes with Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Node-Positive Breast Cancer: Preliminary Results from a Prospective Study.

The ideal technique for lymph node staging for patients with pathologically confirmed node-positive breast cancer at diagnosis and neoadjuvant chemotherapy (NAC) is unclear. The aim of this study was to analyze the feasibility of wire/clip localization and sentinel lymph node biopsy (SLNB) for the axillary staging of these patients. We conducted a prospective study in which lymph node staging was performed using wire localization of positive lymph nodes and an SLNB with dual tracer. All patients who presented no metastatic involvement of the sentinel lymph node (SLN) or clip/wire-marked lymph node were spared an axillary lymph node dissection (ALND). The multidisciplinary committee agreed on axillary treatment for patients with lymph node involvement. Forty-two patients met the inclusion criteria. We identified and extirpated the clip/wire-marked node in all patients (100%), with SLNB performed successfully in 95.3% of patients. The SLN and wire-marked node matched in 80% of patients; 73.8% of patients did not undergo ALND. Several studies have evaluated the efficacy of various procedures for lymph node marking for women with prechemotherapy lymph node involvement. Most of the studies reported high identification rates (> 94.8%), with false negative rates of < 7%. Similarly, our study allows us to conclude that combined axillary marking (clip and SLNB) in patients with metastatic lymph node at diagnosis and NAC offers a high identification rate (100%) and a high correlation between the wire-marked lymph node and the SLN (80%). This procedure has enabled the suppression of ALND for a significant number of patients (73%).

Sequential Anthracycline-Taxane Chemotherapy in Node-positive Breast Cancer Amongst Asian Patients - Real-world Outcomes

Abstract Background The use of taxanes in the adjuvant setting has been contradictory in randomized trials. Two meta-analyses supported the use of adjuvant taxanes which have since been incorporated into standard guidelines. However, their benefit needs to be validated in the real-world population. Methods We retrospectively analyzed the outcomes of patients with node positive breast cancer treated with sequential 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and docetaxel (FEC-D) compared to FEC alone in a university hospital in Kuala Lumpur, Malaysia. The primary outcome was overall survival (OS) and the secondary outcomes were disease free survival (DFS) and toxicity. Results Between 2007 and 2011, 318 patients with node-positive breast cancer were recruited with 131 received FEC and 187 received FEC-D. Mean duration of follow up was 59.7 months for both groups. The 5-year OS was significantly higher with FEC-D (78.8% vs 64.2%; p value = 0.014). Greater benefit was seen in postmenopausal patients, patients with 1-3 positive nodes and T2- 4 tumours. The 5-year DFS was no different between the two groups with 55.4% in the FEC arm vs. 69.4% in the FEC-D arm (p value =0.063). However the median DFS was not reached for FEC-D. The use of FEC-D with the hazard ratio 0.6 (95% CI 0.4 - 0.9; p value = 0.014), tumours 2cm or less, 1-3 positive nodes and hormone receptor positivity were prognostic for survival. Patients with FEC-D experienced higher toxicity with hospitalization rates of 25.1% of patients needing at least one hospitalization (p value = 0.005). Grade 3 and 4 febrile neutropenia was higher with FEC-D (22.5% vs. 8.4%, p value = 0.001) as was the use of granulocyte colony stimulating factors (GCSF). The rates of chemotherapy interruptions and dose reductions were similar in both treatment arms. Conclusions Our study confirmed the benefit of sequential anthracycline-taxane chemotherapy in node positive breast cancer in the real-world albeit with higher toxicity.

261P - The application of indocyanine green fluorescence navigation method to a sentinel lymph node biopsy after neoadjuvant chemotherapy in node-positive breast cancer

261P - The application of indocyanine green fluorescence navigation method to a sentinel lymph node biopsy after neoadjuvant chemotherapy in node-positive breast cancer

535 (PB-168) - Less invasive axillary staging after neoadjuvant chemotherapy in nodepositive breast cancer: A systematic review

535 (PB-168) - Less invasive axillary staging after neoadjuvant chemotherapy in nodepositive breast cancer: A systematic review

Abstract PD6-07: Clinical significance of CD73 expression in triple-negative breast cancer from the BIG 02-98 adjuvant phase III clinical trial

Abstract Background: CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials. Objective: To investigate the prognosis significance of CD73 in human triple-negative breast cancer. Design and setting: This is a prospective-retrospective biomarker analysis. Using multiplex immunofluorescence and image analysis, we assessed CD73 protein expression on tumor cells, tumor-infiltrating leukocytes and stromal cells on full-face sections from formalin-fixed paraffin-embedded primary breast tumors. Participants: 122 samples of triple-negative breast cancer from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis. This trial compared the addition of taxanes to anthracyclines-based chemotherapy in node-positive breast cancer. Results: Our results demonstrated that high levels of CD73 expression on epithelial tumor cells were significantly associated with reduced disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer. Using the median as a threshold between low and high levels of CD73 on epithelial cells, hazard ratios (HR) adjusted for grade, number of positive lymph nodes and tumor size, were of 2.21 (95% confidence interval (CI): 1.15-4.25); p=0.02 for DFS and of 2.47 (95%CI: 1.21-5.07); p=0.01 for OS. CD73 expression negatively correlated with tumor immune infiltration (Spearman's R= -0.50, p&amp;lt;0.0001). Patients with high levels of CD73 and low levels of tumor-infiltrating leukocytes had the worse clinical outcome (HR: 4.24 (1.90-9.45), p&amp;lt;0.001 for DFS, HR: 3.91 (1.65-9.31), p=0.002 for OS) compared to patients with low CD73 and high tumor-immune infiltration. Flow cytometric analysis of tumor-infiltrating leukocytes revealed a high frequency of CD73-expressing B cells and higher CD73 expression on tumor-infiltrating myeloid cells and natural killer cells compared to peripheral blood. Conclusion and relevance: Taken together, our study provides further support that CD73 expression is associated with a poor prognosis and reduced anti-tumor immunity in human triple-negative breast cancer and that targeting CD73 could be a promising strategy to reprogram the tumor microenvironment in this breast cancer subtype. Citation Format: Buisseret L, Pommey S, Allard B, Garaud S, Bergeron MA, Cousineau I, Ameye L, Paesmans M, Crown JPA, Di Leo A, Piccart-Gebhart M, Willard-Gallo K, Sotiriou C, Stagg J. Clinical significance of CD73 expression in triple-negative breast cancer from the BIG 02-98 adjuvant phase III clinical trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD6-07.

Predictive Factors of Residual Metastatic Axillary Lymph Nodes after Neoadjuvant Chemotherapy in Node-Positive Breast Cancer

Purpose Sentinel lymph node biopsy (SLNB) has been a reliable technique in breast cancer staging. However, some authors reported that SLNB after neoadjuvant chemotherapy (NAC) could lead to low identification rates and high false-negative rates. Hence, whether only SLNB can be applied after NAC is controversial. The aim of this study was to identify predictive factors of residual metastatic axillary lymph nodes after NAC. Methods In this study, 71 breast cancer patients with clinically positive lymph nodes (cN1), who received axillary lymph node dissection (ALND) after NAC between July 2012 and September 2014, were enrolled. The patients were divided into N1 and N0 groups according to the presence of residual axillary metastatic lymph nodes after ALND. We compared the clinical, radiological, and immunohistological factors between two groups. Results In the 71 patients with cN1who received NAC, N1 and N0 status were confirmed after surgery in 43 and 28 patients, respectively. The clinical stage at diagnosis was IIA in one patient, IIB in 15 patients, IIIA in 35 patients, IIIB in two patients, IIIC in 10 patients, and IV in eight patients. Most of the patients (n=57) received eight cycles (four cycles of anthracycline and four of taxane) of chemotherapy. Our study showed that the primary tumor was downstaged in 58 of the 71 patients (81.7%). Sixteen patients (22.5%) had pathological complete response (pCR) and 42 (59.2%) had pathological partial response. In a multivariate analysis, tumor response and human epidermal growth factor receptor 2 (HER2) were identified as significant factors. However, no significant differences were observed in the results of postchemotherapy ultrasonography, and pre- or post-positron emission tomography computed tomography (maximum standardized uptake value reduction). Conclusion In the NAC setting, SLNB before ALND is feasible for tumors predicted to have a pCR or if target therapy had been administered for HER2-positive breast cancer. Keywords: Breast neoplasms; Neoadjuvant chemotherapy; Sentinel lymph node biopsy

Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741 (Alliance).

Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors. CALGB 9741 was a randomized trial of dose density and sequence of chemotherapy for node-positive breast cancer. All patients received doxorubicin, cyclophosphamide, and paclitaxel, dosed by actual body weight. Height and weight at diagnosis were abstracted from patient records, and the PAM50 assay was performed from archived specimens using the NanoString platform. Relationships between body mass index (BMI), PAM50, and recurrence-free and overall survival (RFS and OS) were evaluated using proportional hazards regression, adjusting for number of involved nodes, estrogen receptor (ER) status, tumor size, menopausal status, drug sequence, and dose density. All statistical tests were two-sided. Baseline height and weight were available for 1909 of 2005 enrolled patients; 1272 additionally had subtype determination by PAM50. Median baseline BMI was 27.4kg/m(2). After 11 years of median follow-up, there were 619 RFS events and 543 deaths. Baseline BMI was a statistically significant predictor of RFS (adjusted hazard ratio [HR] for each five-unit increase in BMI = 1.08, 95% confidence interval [CI] = 1.02 to 1.14, P = .01) and OS (adjusted HR = 1.08, 95% CI = 1.01 to 1.14, P = .02) BMI and molecular phenotypes were independent prognostic factors for RFS, with no statistically significant interactions detected. BMI at diagnosis was a statistically significant prognostic factor in a group of patients receiving optimally dosed chemotherapy. Additional research is needed to determine the impact of weight loss on breast cancer outcomes and to evaluate whether this impact is maintained across tumor subtypes.

Axillary Ultrasound After Preoperative Chemotherapy in Node-Positive Breast Cancer

Axillary ultrasound (AUS) imaging is routinely used to evaluate axillary lymph-node morphology in patients with newly diagnosed invasive breast cancer. To determine whether it can help identify residual nodal disease after preoperative neoadjuvant chemotherapy in patients who present with node-positive disease, investigators reviewed postchemotherapy AUS images for 611 eligible patients with initial biopsy-proved, axillary-nodal metastases. The study radiologist was blinded to imaging, pathology, and surgical reports. AUS images were classified as normal or abnormal based on cortical thickness …

Dose-Dense Epirubicin and Cyclophosphamide Followed by Docetaxel as Adjuvant Chemotherapy in Node-Positive Breast Cancer

Background. Adding taxanes to anthracycline-based adjuvant chemotherapy has shown significant improvement particularly in node-positive patients, but optimal dose and schedule remain undetermined. Objectives. This study aimed to assess the feasibility of dose-dense epirubicin and cyclophosphamide followed by docetaxel in node-positive breast cancer. Methods. All Patients first received 4 cycles of epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) at 2-week interval then followed by docetaxel (100 mg/m2) at 2-week interval for 4 cycles, with daily Pegfilgrastim (G-CSF) that was administered in all patients on days 3–10 after each cycle of epirubicin and cyclophosphamide infusion. Results. Fifty-eight patients with axillary lymph node-positive breast cancer were enrolled in the study, of whom 42 (72.4%) completed the regimen. There were two toxicity-related deaths, one patient due to grade 4 febrile neutropenia and the other due to congestive heart failure. Grade 3/4 neutropenia and febrile neutropenia were 13.8% and 5.1%. The most common grade 3/4 nonhematological complications were as follows: skin-nail disorders (48.3%), hand-foot syndrome (34.4%), paresthesia (38%), arthralgia (27.5%), and paresis (24.1%). Conclusions. Dose-dense epirubicin and cyclophosphamide followed by docetaxel with G-CSF support are not feasible, and it is not recommended for further investigation.

A multicenter phase III prospective randomized trial of high-dose epirubicin in combination with cyclophosphamide (EC) versus docetaxel followed by EC in node-positive breast cancer. GOIM (Gruppo Oncologico Italia Meridionale) 9902 study

The Gruppo Oncologico Italia Meridionale 9902 trial compared four cycles of high-dose epirubicin plus cyclophosphamide (EC) with four cycles of docetaxel (Taxotere, D) followed by four cycles of EC as adjuvant treatment of node-positive breast cancer. Patients were randomly assigned to EC (E 120 mg/m(2), C 600 mg/m(2), arm A) for four cycles or four cycles of D (100 mg/m(2)) followed by four cycles of EC (arm B), both regimens every 21 days. Hormone receptor-positive patients were given hormonal therapy for 5 years. Primary end point was 5-year disease-free survival (DFS). Secondary objectives were overall survival (OS) and safety. There were 750 patients enrolled. With a median follow-up of 64 months, 5-year DFS was 73.4% in both arms, and 5-year OS was 89.5% versus 90.7% in arm A and B [hazard ratio was 0.99 (95% confidence interval for DFS 0.75-1.31; P = 0.95)], respectively. Grade 3-4 toxicity was more common in arm B. This study did not show advantages from the addition of docetaxel to high-dose EC as adjuvant chemotherapy in node-positive breast cancer. The small sample size and low number of DFS events may have limited the ability to observe statistically significant difference between the two arms.

Myelodysplastic Syndromes: It Is All in the Genes

REFERENCES 1. Hershman DL, Wilde ET, Wright JD, et al: Uptake and economic impact of first-cycle colony-stimulating factor use during adjuvant treatment of breast cancer. J Clin Oncol 30:806-812, 2012 2. Mukherjee S: The Emperor of All Maladies. New York, NY, Scribner, 2010, pp 423-429 3. Henderson IC, Berry DA, Demetri GD, et al: Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 21:976-983, 2003 4. Giordano SH, Duan Z, Kuo Y-F, et al: Impact of a scientific presentation on community treatment patterns for primary breast cancer. J Natl Cancer Inst 98:382-388, 2006 5. Citron ML, Berry DA, Cirrincione C, et al: Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21:1431-1439, 2003 6. Muss HB, Berry DA, Cirrincione C, et al: Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: The Cancer and Leukemia Group B Experience. J Clin Oncol 25:3699-3704, 2007 7. Piccart-Gebhart MJ: Mathematics and oncology: A match for life? J Clin Oncol 21:1425-1428, 2003 8. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG): Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 365:1687-1717, 2005 9. Venturini M, Del Mastro L, Aitini E, et al: Dose-dense adjuvant chemotherapy in early breast cancer patients: Results from a randomized trial. J Natl Cancer Inst 97:1724-1733, 2005 10. Berry DA, Cirrincione C, Henderson IC, et al: Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295:1658-1667, 2006 11. Bonilla L, Ben-Aharon I, Vidal L, et al: Dose-dense chemotherapy in nonmetastatic breast cancer: A systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst 102:1845-1854, 2010 12. Citron ML: Dose-dense chemotherapy: Principles, clinical results and future perspectives. Breast Care (Basel) 3:251-255, 2008 13. Hershman D, Neugut AI, Jacobson JS, et al: Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy. J Natl Cancer Inst 99:196-205, 2007 14. Smith TJ, Hillner BE: Bending the cost curve in cancer care. N Engl J Med 364:2060-2065, 2011 15. Goldhirsch A, Wood WC, Coates AS, et al: Strategies for subtypes: Dealing with the diversity of breast cancer—Highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22:1736-1747, 2011