Purpose: Neoadjuvant chemotherapy (NAC) has resulted in the eradication of axillary lymph node metastasis in approximately 40% of patients. Sentinel lymph node biopsy (SLNB) could be an alternative surgical procedure for these patients to avoid complications from axillary lymph node dissection (ALND). However, high false-negative rates of SLNB for clinically node-positive patients were reported in previous prospective trials. The aim of the present 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 enables to identify candidates for SLNB in patients with clinically node-positive disease. Patients and methods: We identified 177 patients with clinically node-positive breast cancer who received NAC from May 2009 to May 2021. All patients underwent MRI and US before and after NAC. Patients were judged to be node-positive when they have the cytologically-proven nodal disease by fine-needle aspiration (FNA) or suspicious lymph nodes by diagnostic imaging. Lymph nodes with the cortical thickness (>3.5mm), loss of fatty hilum, or round shape (short-axis/long-axis ratio > 0.5) were defined as suspicious lymph nodes. To develop a predictive model for ypN0, the association between ypN0 status and clinicopathological and imaging characteristics was assessed by multivariate logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was used to evaluate discrimination by the model. The model was further evaluated in the validation cohort with 20 patients who received NAC from March 2021 to December 2021. Results: The median age was 54.0 (range: 22-79) years and the mean tumor size was 3.97 ±2.29cm. Of 177 patients, 90 (50.8%) patients had luminal, 47 (26.6%) had HER2-positive, and 40 (22.6%) had triple-negative disease. Sequential anthracycline and taxane were administered for 157 (88.7%) patients, and 45 (95.7%) patients with HER2-positive-disease received concomitant anti-HER2 agents preoperatively. Overall, 77 (43.5%) patients achieved ypN0. Independent predictors of ypN0 status were clinical stage N1 (odds ratio [OR]: 9.17 vs. cN2-3, p=0.002), absence of lymphadenopathy after NAC (OR: 8.54, p< 0.001), breast complete response (CR) by MRI (OR: 5.96, p< 0.001), HER2 positivity (OR: 3.80, p=0.008), nuclear grade (NG) 3 (OR: 2.77 vs. NG1-2, P=0.020) and hormone receptor negativity (OR: 2.52, p=0.048). In a model using these predictors, the area under the ROC curve was 0.887 (95% confidence interval: 0.839-0.935, p< 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the model were 80.0%, 82.8%, 77.9% and 84.5%, respectively. In the validation cohort, the sensitivity, specificity, positive predictive value and negative predictive value were 66.7%, 90.9%, 85.7% and 76.9%, respectively. Among 84 patients who were predicted ypN0 by the model, SLNB was performed in 42 (50.0%) patients, and the identification rate of SLN was 95.2% (40/42). Overall, ALND was omitted in 38 (45.2%) patients and irradiation to regional lymph nodes was performed in 23 (60.5%) out of 38 patients. After a median follow-up of 53.9 months, 5-year recurrence-free survival was comparable between patients with or without ALND (78.0% vs. 94.4%, p=0.259). Conclusions: Our predictive model based on clinicopathological factors and imaging characteristics by MRI and US could help to identify good candidates for the omission of ALND after NAC in patients with clinically node-positive breast cancer. Citation Format: Akiko Matsumoto, Saki Naruse, Yuka Isono, Yuka Maeda, Ayana Sato, Miki Yamada, Tatsuhiko Ikeda, Hiromitsu Jinno. A Predictive Model for Axillary Pathologic Response after Neoadjuvant Chemotherapy for Clinically Node-Positive Breast Cancer [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 P5-01-05.

Background: Although neoadjuvant endocrine therapy has been used to improve breast conservation rate, its prognostic relevance is unknown. The search for a valid prognostic factor equivalent to pCR in neoadjuvant chemotherapy is a current challenge in neoadjuvant endocrine therapy. In this study, we investigated the efficacy of short term neoadjuvant endocrine therapy utilizing the waiting period for surgery and the prognostic factor including Preoperative Endocrine Prognostic Index (PEPI) score. Patients and Methods: A total of 269 postmenopausal women with hormone receptor-positive, HER2-negative breast cancer was treated with endocrine therapy with non-steroidal aromatase inhibitor during the waiting period for surgery between October 2012 and November 2021. Of the entire 269 patients, 92 and 177 patients had anastrozole and letrozole, respectively. The primary endpoint was change in tumor size by ultrasound and Ki67 before and after short-term endocrine therapy. The secondary endpoint was prognosis of patients divided by PEPI score which was calculated using tumor size, lymph node metastasis, Ki67, and ER Allred score. This study was approved by the institutional review board of Teikyo University. Results: Median age was 68 years old (range, 41-89). ER and PgR was positive in 266 (98%) and 232 (86%) of the entire 269 patients, respectively. Median tumor size was 1.65 cm (range, 0.4-7.5). Seventeen (6.3%) pts were clinically node-positive. Patients with histological grade I tumor were 190 (70.6%). The median duration of endocrine therapy was 39 days (range, 2-88). Average pretreatment Ki67 expression was 10% (range, 0-90). Tumor diameter was significantly decreased to 1.43cm (range,0.45-5.83) after short-term endocrine therapy (p=0.01). The Ki67 expression was significantly decreased to 3.0% (range, 0-85) after endocrine therapy (p< 0.01) and only five patients (1.9%) showed marked increase in Ki-67 expression. PEPI score 0, 1-3 and ≥ 4 was found in 83 (30.9%),147 (54.7%) and 39 patients (14.5%), respectively. After the median observation period of 928 days, patients with PEPI score ≥ 4 showed worse disease-free survival (Figure) compared with patients with PEPI score 0 and 1-3 (p=0.06). In terms of mortality, patients with PEPI score ≥ 4 had worse overall survival than patients with PEPI score 0 and 1-3 (p=0.07). Conclusions: These results suggested that neoadjuvant endocrine therapy during the waiting period for surgery might be effective in reducing the size and Ki67 expression level and PEPI score might be useful in predicting the prognosis of postmenopausal hormone receptor positive breast cancer patients. Citation Format: Yuka Maeda, Saki Naruse, Yuka Isono, Ayana Sato, Miki Yamada, Akiko Matsumoto, Tatsuhiko Ikeda, Hiromitsu Jinno. The efficacy of neoadjuvant endocrine therapy during the waiting period for surgery in postmenopausal hormone receptor positive breast cancer [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 P2-03-19.

Background Tumor embolization due to venous infiltration of breast cancer pulmonary metastases is very rare. Case presentation A 72-year-old female was diagnosed with triple-negative breast cancer. Neoadjuvant chemotherapy was discontinued because of progressive disease, and a right mastectomy with sentinel lymph node biopsy was performed. The pathological analysis of surgical specimens revealed carcinoma with cartilaginous and/or osseous metaplasia. At 22 months after surgery, lung metastasis was observed, and 6 months after initiating treatment for lung metastases, she complained of sudden numbness in the left-lower limb with trouble walking. Ultrasonography showed an embolism in the left popliteal artery, and contrast computed tomography showed enlarged lung metastases and infiltration of the left-upper lobe disease into the left superior pulmonary vein and left atrium. Acute arterial occlusive disease in the left-lower limb caused by the tumor embolism was suspected, so an endovascular thrombectomy was performed. Tumor emboli were removed by embolectomy catheter. Conclusion This report of lung metastasis from breast cancer with cartilaginous and/or osseous metaplasia and acute lower-limb artery occlusion due to a tumor thrombus adds useful information to the literature on these extremely rare cases.

Background Nipple-areola complex (NAC) necrosis, which is caused by local ischemia, remains one of the complications associated with nipple-sparing mastectomy. Obesity, smoking, diabetes mellitus, and immediate breast reconstruction have been identified as risk factors of NAC necrosis. The current study examined the correlation between NAC necrosis and nipple volume. Materials and methods A total of 83 patients who underwent NSM for primary breast cancer from January 2016 to December 2019 were retrospectively analyzed. Nipple volume was determined using the formula: volume (mm 3 )= length 9 width 9 height (mm), with measurements determined using contrast-enhanced magnetic resonance imaging. Total and partial NAC necrosis was defined as full-thickness necrosis requiring surgical procedures and epidermal necrosis managing local wound care, respectively. Results NAC necrosis was observed in 30 patients (36%), with 3 and 27 patients having total and partial necrosis, respectively. Large nipple volume (56% vs. 24%, p = 0.006), as well as smoking and immediate breast reconstruction (57 vs. 28%, p = 0.017; 48% vs. 20%, p = 0.009, respectively), were significantly correlated with NAC necrosis. Multivariate analysis identified nipple volume as an independent risk factor for NAC necrosis (OR, 3.75; 95% CI,; p = 0.02). Smoking (OR, 4.68; 95% CI,; p = 0.014) and immediate breast reconstruction (OR, 3.43; 95% CI,; p = 0.042) were also independently associated with NAC necrosis. Conclusions This study suggested that a large nipple volume could be one of the risk factors for NAC necrosis following NSM.

In the original online version of this article all instances of volume (cc) were incorrect. The correct measurement is mm 3 . The original article was corrected.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.