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Background The optimal surgical staging procedure of the axilla in patients who convert from a clinically positive (cN+) to a clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Widely diverse techniques such as full Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Targeted Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy alone (SLNB) are given preference in different international guidelines. So far, no comparative data on the oncological outcome or the morbidity of the different procedures are available. Further research is needed to safely de-escalate the extent of axillary surgery in this patient group. Trial design The AXSANA study is an international prospective cohort study including cN+ patients converting to ycN0 status and treated with different axillary staging techniques according to the standard at their treating institution. The study is initiated by the EUBREAST network. The trial includes patients with cT1-4c tumors, who present initially with axillary lymph node metastasis and are scheduled for neoadjuvant chemotherapy. According to an amendment in 2020 the inclusion of patients with highly suspicious nodes without minimally invasive biopsy is allowed. All patients converting to ycN0 status undergo follow-up for 5 years irrespectively of the ypN status. Primary endpoints: Invasive disease-free survival, axillary recurrence rate and health-related quality of life (HRQoL). HRQoL are evaluated using four standardized questionnaires (EORTC QLQ-C 30, EORTC QLQ BR 23, Lymph ICF and SOC-13) at baseline and after 1, 3 and 5 years after surgery. Secondary endpoints are the feasibility and performance of different axillary staging techniques (detection rate, number of removed lymph nodes and association with complications, arm morbidity and quality of life, operating time and use of clinical and economic resources); impact of learning curve, and the detailed mapping of surgical and oncological treatment standards in different countries. The impact on different regional treatment strategies (radiotherapy, ALND) in patients with ypN0(i+), ypN1(mi) and ypN1 is assessed. Current status of the study: On June 30th 157 study sites from 15 countries are open for recruitment (Austria 2, Czech Republic 1, Finland 1, Germany 112, Greece 3, Italy 1, Norway 1, Poland 3, Portugal 5, Romania 2, Russia 1, Sweden 4, Switzerland 4, Spain 6, Turkey 11). 620 patients have been included in the study. Among patients who converted to ycN0 status, 144 have been scheduled for ALND, 157 for TAD and 49 for SLNB. The study is still open for further international study sites. Funding: AGO-B, Claudia-von Schilling Foundation, Ehmann Foundation, AWOgyn, Merit Medical, Endomagnetics, Mammotome Target accrual: 3000 patients worldwide Citation Format: Thorsten Kühn, Steffi Hartmann, Elmar Stickeler, Jana de Boniface, Oreste Gentilini, Sarah Fröhlich, Franziska Ruf, Marc Thill, Michael Hauptmann, Guldeniz Karadeniz Cakmak, Isabel Rubio, Maria Luisa Gasparri, Michaelis Kontos, Eduard-Alexandru Bonci, Laura Niinikoski, Rosa Di Micco, Dawid Murawa, David Pinto, Florentia Peintinger, Christine Solbach, Matilda Appelgren, Jens-Uwe Blohmer, Michael Weigel, Gabriele Kaltenecker, Michael Schrauder, Janine Simons, Marjolein Smidt, Ellen Schlichting, Lukas Dostalek, Alexander Sergeevich Emelyanov, Elisabeth Thiemann, Semra Gunay, Sybille Loibl, Maggie Banys-Paluchowski. AXSANA - EUBREAST 3 (axillary surgery after neoadjuvant treatment): An international prospective multicenter cohort study of the EUBREAST study group to evaluate different surgical methods of axillary staging (sentinel lymph node biopsy, targeted axillary dissection, axillary dissection) in clinically node-positive breast cancer patients treated with neoadjuvant chemotherapy (NCT04373655) [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 OT1-04-04.

Purpose: We examined whether the response predicted by a 30-gene pharmacogenomic test correlated with the residual cancer burden (RCB) after preoperative chemotherapy with paclitaxel, 5-fluorouracil, doxorubicin, and cyclophosphamide (T/FAC). Experimental Design: Gene expression profiling was done at diagnosis in 74 patients with stages I to III breast cancer and was used to calculate a pharmacogenomic score and predict response to chemotherapy [pathologic complete response (pCR) or residual disease (RD)]. All patients received 6 months of preoperative T/FAC. Following pathologic review, a RCB score was calculated based on residual tumor and lymph node features. Four RCB classes were assigned; RCB-0 (pCR), RCB-I (near-PCR), RCB-II (moderate RD), and RCB-III (extensive RD). The correlations between the pharmacogenomic score, predicted pathologic response, RCB score, and RCB class were examined. Results: Thirty-three patients were predicted to have pCR, and 40 were predicted to have RD. Observed responses were RCB-0: n = 20 (27%); RCB-I: n = 5 (7%); RCB-II: n = 36 (49%); and RCB-III: n = 13 (16%) patients. Pharmacogenomic and RCB scores were correlated (Pearson's R = −0.501, P < 0.0001). There was no difference between the mean genomic predictor scores for RCB-0/I groups (P = 0.94), but these were different from the mean scores of the RCB-II/III groups (P < 0.001). Among the 25 patients with RCB-0/I response, 19 (76%) were predicted to achieve pCR. The pharmacogenomic test correctly predicted RD in 92% of the patients with RCB-III, which corresponds to chemotherapy-resistant disease. Conclusions: The 30-gene pharmacogenomic test showed good correlation with the extent of residual invasive cancer burden measured as both continuous and categorical variables.

Background: Micrometastatic disease in the sentinel lymph node is still an indication for complete axillary lymph node dissection. To further reduce morbidity in breast cancer patients the omission of complete axillary lymph node dissection in patients with micrometastasis in the sentinel lymph node would be desirable.Methods: We retrieved our data-base and looked for the non-sentinel lymph node status in patients with micrometastasis in the sentinel lymph node.Patients with primary T1/T2 breast cancer and sentinel lymph node biopsy were examined for their sentinel lymph node status. Patients with a micrometastasis in the sentinel lymph node, who received a complete axillary lymph node dissection were eligible for evaluation. Patients with a micrometastisis in the sentinel lymph node, who did not receive complete axillary lymph node dissection and patients after primary systemic therapy were excluded.Results: 103 patients were eligible for evaluation. All patients had micrometastases (0,2 to 2,0mm) in the sentinel lymph nodes. In total 15/103 patients (14.6%) had a further metastasis in one or two non-sentinel lymph nodes. 8/103 patients (7.8%) had one macrometastasis in a non-sentinel lymph node with sizes from 2.1mm to 5.0mm. 3/103 patients (2.9%) had a micrometastasis in two non-sentinel lymph nodes and 4/103 patients (3.9%) had one micrometastasis in one non-sentinel lymph node.Mean age of the patients was 57 years, 34 (33%) being premenopausal and 69 (67%) being postmenopausal. 22 patients (21.4%) received immediate axillary dissection after sentinel lymph node biopsy, but 81 patients (78.6%) had a secondary axillary lymph node dissection after the final pathological report. In 19 patients (18.4%) the micrometastasis in the sentinel lymph node could be detected by frozen sections, in 77 patients (74.8%) by serial sections at 250µm in the paraffin embedded sentinel lymph node and in 22 patients (21.4%) by immunohistochemistry only.Discussion: As long as we are lacking reliable methods for predicting the non-sentinel lymph node status for patients with micrometastases in the sentinel lymph node, and as long as the impact of micrometastases in the axilla are subject of debate, axillary lymph node dissection should be performed after sentinel lymph node biopsy with micrometastases in the sentinel lymph node. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1034.

Abstract #701 Background: Controversy surrounds the prognosis of breast cancer patients with T1a,bN0M0 tumors following locoregional therapy and the need for adjuvant systemic therapy, especially for HER2+ disease. The purposes of the study were to determine the recurrence-free survival (RFS), and distant recurrence-free survival (DRFS) in small HER2+ tumors compared with hormone receptor ( HR)+ and triple receptor- (TN) tumors. Methods: Stage T1a,bN0M0 breast cancers diagnosed between 1973-2003 were reviewed by dedicated breast pathologists. HER2+ tumors were defined as 3+ by IHC or gene amplification. Patients were categorized into 3 groups:TN (ER-, PR-and HER2-), HER2+ (regardless of HR status) and HR+ (HER2-). RFS and DRFS were estimated by the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards models were fit to determine the association of each group with the risk of recurrence after adjustment for other characteristics. Results: Of the 1796 patients, 427 were excluded from the analysis due to being male (2), lack of receptor information (249), and adjuvant chemotherapy (176) leaving 1369 pts for analysis. Median age was 57 years,(range, 26-88). There were 381(28%) T1a and 988(72%) T1b tumors; HR+ 68%, TN 23%, HER2+ 9%. Patients who had HER2+ breast cancer tended to be younger,(p=0.001); have more T1a tumors, (p=0.001); and have higher nuclear grade,(p Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 701.