Residual Axillary Metastases in Node-Positive Breast Cancer Patients After Neoadjuvant Treatment: A Register-Based Study.

BACKGROUND: Lymph node (LN) metastasis after neoadjuvant chemotherapy (NACT) generally warrants axillary lymph node dissection, which opposes guidelines of upfront surgery in many cases. We investigated the risk of having additional metastases in the axilla when the LNs removed by targeted axillary dissection (TAD) harbored metastases after NACT. We aimed to identify subgroups suitable for de-escalated axillary treatment. METHODS: This register-based study used data from the Danish Breast Cancer Cooperative Group database. Data were analyzed with logistic regression models. The primary outcome was the metastatic burden in non-TAD LNs in patients with positive TAD LNs after NACT. RESULTS: Among 383 patients, < 66.6% positive TAD LNs (adjusted odds ratio [OR] 0.34, 95% confidence interval [CI] 0.17-0.62), only isolated tumor cells (ITCs) [OR 0.11, 95% CI < 0.01-0.82], and breast pathological complete response (pCR) [OR 0.07, 95% CI < 0.01-0.56] were associated with a low risk of having more than three positive non-TAD LNs. In 315 patients with fewer than three positive non-TAD LNs, the proportion of positive TAD LNs (OR 0.45, 95% CI 0.27-0.76 for 33.3-66.6% vs. > 66.6%), size of the TAD LN metastasis (OR 0.14, 95% CI 0.04-0.54 for ITC vs. macrometastasis), tumor size at diagnosis (OR 0.30, 95% CI 0.15-0.64 for 20-49 mm vs. ≥ 50 mm) and breast pCR (OR 0.38, 95% CI 0.15-0.96) were associated with residual LN metastases in the axilla. CONCLUSIONS: Breast pCR or ITC only in TAD LNs can, with reasonable certainty, preclude more than three positive non-TAD LNs. Additionally, patients with only ITCs in the TAD LN had a low risk of having any non-TAD LN metastases after NACT. De-escalated axillary treatment may be considered in both subgroups.

Axillary lymph node recurrence following wire-directed sentinel lymph node dissection for breast cancer patients with biopsy-proven axillary metastases prior to neoadjuvant chemotherapy at a safety net medical center.

BACKGROUND: Although sentinel lymph node dissection (SLND) after neoadjuvant chemotherapy (NAC) is feasible, axillary management for patients with pretreatment biopsy-proven axillary metastases and who are clinically node-negative after NAC (ycN0) remains unclear. This retrospective study was performed to determine the rate of axillary lymph node recurrence for such patients who had wire-directed (WD) SLND. METHODS: Patients treated with NAC from 2015 to 2020 had axillary nodes evaluated by pretreatment ultrasound. Core biopsies were done on abnormal nodes, and microclips were placed in nodes during biopsy. For patients with biopsy-proven node metastases who received NAC and were ycN0 by clinical exam, WD SLND was done. Patients with negative nodes on frozen section had WD SLND alone; those with positive nodes had WD SLND plus axillary lymph node dissection (ALND). RESULTS: Of 179 patients receiving NAC, 62 were biopsy-proven node-positive pre-NAC and ycN0 post-NAC. Thirty-five (56%) patients were node-negative on frozen section and had WD SLND alone. Twenty-seven (43%) patients had WD SLND + ALND. Forty-seven patients had postoperative regional node irradiation. With median follow-up of 40 months, there were recurrences in 4 (11%) of 35 patients having WD SLND and 5 (19%) of 27 having WD SLND + ALND, but there was only one axillary lymph node recurrence, identified by CT scan. CONCLUSIONS: Axillary node recurrence was very uncommon after WD SLND for patients who had pretreatment biopsy-proven node metastases and were ypN0 after NAC. These patients would be unlikely to derive clinical benefit from the addition of completion ALND to SLND.

Metástasis axilares contralaterales en cáncer de mama: ¿Enfermedad sistémica, carcinoma oculto o progresión locorregional? Unidad de Mastología Hospital J.A. Fernández / Contralateral axillary metastases in breast cancer: systemic disease, occult carcinoma, or locoregional progression? Mastology Unit Hospital J.A. Fernandez

Introducción: Las metástasis de los ganglios axilares contralaterales (MAC) en cáncer de mama (CM), son consideradas metástasis a distancia, aunque estudios retrospectivos muestran mejor pronóstico comparado con la enfermedad sistémica. Objetivo: Reportar la estrategia terapéutica de una paciente con CM y MAC metacrónicas. Caso clínico: Paciente de 73 años diagnosticada en 2019 con CM izquierda locorregionalmente avanzado, luminal B like. Realizó neoadyuvancia, con enfermedad clínica estable. Se efectuó cirugía radical, obteniendo respuesta patológica parcial (ypT4bypN2). Cumple radioterapia e inicia hormonoterapia adyuvante. En 2021, presenta una metástasis axilar contralateral aislada. Realizó cirugía axilar, radioterapia y hormonoterapia adyuvante. Discusión: La biología de las MAC es controvertida, pudiendo originarse por drenaje linfático aberrante o por diseminación sistémica. Según AJCC, se consideran metástasis a distancia aunque por su comportamiento clínico podrían abordarse terapéuticamente como enfermedad locorregional. Conclusiones: El pronóstico de las MAC parece ser más favorable que el de la enfermedad sistémica, por lo que el tratamiento con intención curativa estaría ampliamente justificado(AU)

Introduction: Contralateral axillary lymph node metastases (MAC) in breast cáncer (BC) are considered distant metastases, although retrospective studies show a better prognosis compared to systemic disease. Objetivo: To report the therapeutic strategy of a patient with BC and metachronous MAC. Clinical case: 73-year-old patient diagnosed in 2019 with locoregionally advanced left BC, luminal B like. She underwent neoadjuvant therapy, with stable clinical disease. A radical surgery was performed, obtaining a partial pathological response (ypT4bypN2). She completed radiotherapy and started adjuvant hormone therapy. In 2021, She presented an isolated contralateral axillary metastasis and performed axillary surgery, radiotherapy and adjuvant hormonal therapy. Discussion : The biology of MAC is controversial, and may be caused by aberrant lymphatic drainage or systemic dissemination. According to the AJCC, it is considered distant metastasis, although due to its clinical behavior it could be treated therapeutically as locoregional disease. Conclusions: The prognosis of MAC seems to be more favorable than a systemic disease, so treatment with curative intent would be highly justified(AU)

Analyzing non-sentinel axillary metastases in patients with T3-T4 cN0 early breast cancer and tumor-involved sentinel lymph nodes undergoing breast-conserving therapy or mastectomy.

PURPOSE: In the ACOSOG Z0011 trial, completing axillary lymph node dissection (cALND) did not benefit patients with T1-T2 cN0 early breast cancer and 1-2 positive sentinel lymph nodes (SLN) undergoing breast-conserving surgery (BCT). This paper reports cALND rates in the clinical routine for patients who had higher (T3-T4) tumor stages and/or underwent mastectomy but otherwise met the ACOSOG Z0011 eligibility criteria. Aim of this study is to determine cALND time trends and non-sentinel axillary metastases (NSAM) rates to estimate occult axillary tumor burden. METHODS: Data were included from patients treated in 179 German breast cancer centers between 2008 and 2015. Time-trend rates were analyzed for cALND of patients with T3-T4 tumors separated for BCT and mastectomy and regarding presence of axillary macrometastases or micrometastases. RESULTS: Data were available for 188,909 patients, of whom 19,009 were identified with 1-2 positive SLN. Those 19,009 patients were separated into 4 cohorts: (1) Patients with T1-T2 tumors receiving BCT (ACOSOG Z0011 eligible; n = 13,741), (2) T1-T2 with mastectomy (n = 4093), (3) T3-T4 with BCT (n = 269), (4) T3-T4 with mastectomy (n = 906). Among patients with T3-T4 tumors, cALND rates declined from 2008 to 2015: from 88.2 to 62.6% for patients receiving mastectomy and from 96.6 to 58.1% in patients receiving BCT. Overall rates for any NSAM after cALND for cohorts 1-4 were 33.4%, 42.3%, 46.9%, 58.8%, respectively. CONCLUSIONS: The cALND rates have decreased substantially in routine care in patients with 'extended' ACOSOG Z0011 eligibility criteria. Axillary tumor burden is higher in these patients than in the ACOSOG Z0011 trial.

[Axillary lymph node metastases with an occult breast: About 16 cases from a cohort of 7770 patients]. / Envahissement ganglionnaire axillaire sans tumeur primitive mammaire retrouvée : à propos de 16cas issus d'une cohorte de 7770patientes.

OBJECTIVES: Isolated axillary lymph node metastases is an unusual clinical presentation of breast carcinoma. We studied its different issues. METHODS: This study is a follow-up study of 16patients, treated between 1996 and 2012, presenting with axillary metastases with an occult breast carcinoma, which could not be identified by physical examination nor by a conventional imaging or a breast MRI. Clinical characteristics, histological analysis, treatment, monitoring and five-year survival rate were studied. RESULTS: The incidence of this kind of breast cancer was 0.20%. A breast MRI was performed in 75% of the patients. The histology of these tumors showed a rate of hormono-sensibility of 50% and an HER2 overexpression of 44%. Sixty-nine percent of the patients had no breast surgery or radiotherapy; global five-year survival rate for these women was 77.4%±11.5. CONCLUSION: The survival rates of this study should lead the practitioner to choose a less aggressive breast therapy. Moreover, the histological characteristics explain the high metastatic potential of these tumors, and relate them to the HER2+ subclass of gene expression patterns of breast carcinomas.

Breast cancer lymphoscintigraphy: Factors associated with sentinel lymph node non visualization.

OBJECTIVE: To evaluate factors associated with non identification of the sentinel lymph node (SLN) in lymphoscintigraphy of breast cancer patients and analyze the relationship with SLN metastases. MATERIAL AND METHODS: A single-center, cross-sectional and retrospective study was performed. Forty patients with lymphoscintigraphy without sentinel lymph node identification (negative lymphoscintigraphy - NL) were enrolled. The control group included 184 patients with SLN identification (positive lymphoscintigraphy - PL). Evaluated factors were age, body mass index (BMI), tumor size, histology, localization, preoperative breast lesion hookwire (harpoon) marking and SLN metastases. The statistical analysis was performed with uni- and multivariate logistic regression models and matched-pairs analysis. RESULTS: Age (p=0.036) or having BMI (p=0.047) were the only factors significantly associated with NL. Being ≥60 years with a BMI ≥30 increased the odds of having a NL 2 and 3.8 times, respectively. Marking with hookwire seems to increase the likelihood of NL, but demonstrated statistical significance is lacking (p=0.087). The other tested variables did not affect the examination result. When controlling for age, BMI and marking with the harpoon, a significant association between lymph node metastization and NL was not found (p=0.565). CONCLUSIONS: The most important factors related with non identification of SLN in the patients were age, BMI and marking with hook wire. However, only the first two had statistical importance. When these variables were controlled, no association was found between NL and axillary metastases.

A logistic regression model for predicting axillary lymph node metastases in early breast carcinoma patients.

Nodal staging in breast cancer is a key predictor of prognosis. This paper presents the results of potential clinicopathological predictors of axillary lymph node involvement and develops an efficient prediction model to assist in predicting axillary lymph node metastases. Seventy patients with primary early breast cancer who underwent axillary dissection were evaluated. Univariate and multivariate logistic regression were performed to evaluate the association between clinicopathological factors and lymph node metastatic status. A logistic regression predictive model was built from 50 randomly selected patients; the model was also applied to the remaining 20 patients to assess its validity. Univariate analysis showed a significant relationship between lymph node involvement and absence of nm-23 (p = 0.010) and Kiss-1 (p = 0.001) expression. Absence of Kiss-1 remained significantly associated with positive axillary node status in the multivariate analysis (p = 0.018). Seven clinicopathological factors were involved in the multivariate logistic regression model: menopausal status, tumor size, ER, PR, HER2, nm-23 and Kiss-1. The model was accurate and discriminating, with an area under the receiver operating characteristic curve of 0.702 when applied to the validation group. Moreover, there is a need discover more specific candidate proteins and molecular biology tools to select more variables which should improve predictive accuracy.

Metastatic syringoid eccrine carcinoma of the nipple.

Syringoid eccrine carcinoma is a very rare skin tumor. Herein we describe a 72-year-old male patient presenting with a syringoid eccrine carcinoma of the nipple with associated axillary lymph node metastases. Surgery associated with adjuvant radiotherapy was performed. To the best of our knowledge, this is the first case of syringoid eccrine carcinoma of the nipple ever reported.

Factors predicting the axillary lymph node metastasis in breast cancer: is axillary node clearance indicated in every breast cancer patient?: factors predicting the axillary lymphnode metastases in breast cancer.

The study was carried out to find out predictors of axillary lymph node metastasis in breast cancer and to evaluate its significance in selecting the group of patients in whom axillary dissection could be avoided. Ninety-five breast cancer patients who underwent mastectomy and axillary dissection were included in the study. Factors like patient's age, tumor size, histopathological type, histological grade and estrogen and progesterone receptor status were correlated with the axillary metastases. Out of 95 cases axillary metastasis was found in 47 (49.47%) cases. There was no correlation between patient's age and tumor size with axillary metastasis (p > 0.05). Based on histopathological typing tumors like ductal carcinoma in situ, tubular carcinoma and mucinous carcinoma showed less tendency for axillary metastasis (p < 0.046). Association was found between histological grade and estrogen receptor and progesterone receptor positivity with presence of axillary metastasis (p < 0.001 and 0.002 respectively). The findings in this study indicate that breast cancer patients having favorable histological type, grade I tumors and estrogen and progesterone receptor negative tumor are good candidates to avoid axillary dissection.

Marcadores moleculares em câncer de mama preditivos de metástases axilares / Molecular features of breast cancer predictive of lymph node metastases

OBJETIVO: Avaliar e relacionar fatores morfológicos e moleculares de câncer de mama preditivos de metástases em linfonodos axilares. MÉTODOS: Selecionamos 123 casos de carcinomas mamários invasores subdivididos em três grupos de acordo com o status axilar (pacientes com macrometástases, com micrometástases e linfonodo-negativas). Avaliamos e correlacionamos a presença de metástases axilares com fatores morfológicos (tamanho do tumor, tipo e grau histológicos, invasão linfática e sangüínea em lâminas coradas pela hematoxilina e eosina) e moleculares do tumor primário (receptores de estrógeno e progesterona, Ki67, p53, E-caderina, Her2, e invasão linfática e sangüínea em lâminas coradas pela imunoistoquímica, para D2-40 e CD31). RESULTADOS: A ocorrência de metástases axilares esteve positivamente relacionada à embolização neoplásica em vasos linfáticos em lâminas coradas pela hematoxilina e eosina (HE), quando analisamos os casos com metástases e sem metástases (p=0,04), e, quando eles eram analisados em três subgrupos (p=0,002). Também identificamos relação positiva e estatisticamente significativa entre a presença de metástases axilares e invasão de vasos sangüíneos em lâminas coradas pelo CD31 (p=0,02). As demais variáveis moleculares e morfológicas não mostraram relação estatisticamente significativa com a presença de metástases. CONCLUSÃO: A invasão neoplásica em vasos linfáticos e sangüíneos identificadas em cortes histológicos corados pela HE e por marcadores imunoistoquímicos relaciona-se positivamente com a ocorrência de metástases, e é preditivo de metástases em linfonodos axilares em câncer de mama.

OBJECTIVE: The aim of our study was to analyze morphologic and molecular markers of breast cancer relating them to the presence of metastases in axillary lymph nodes. METHODS: We selected 123 cases of invasive mammary carcinomas stratified into three subgroups: with macrometastases, with micrometastases, and lymph node negative. Presence of metastases was evaluated relating them with morphologic factors (size of primary tumor, type and grade, presence of lymphatic and blood vessel invasion in hematoxylin and eosin-stained slides) and molecular factors of primary tumor (estrogen and progesterone receptors, E-cadherin, Ki67, p53, Her2 expression, and the presence of lymphatic and blood vessel invasion in immunostained sections for D2-40 and CD31). RESULTS: Axillary lymph node metastases were positively related to the presence of lymphatic vessel invasion in hematoxylin and eosin (H&E)-stained slides, when analyzed with or without metastases (p=0.04) and when analyzed in the three subgroups (p=0.002). Lymph node metastases were also positively related to presence of blood vessel invasion identified by immunohistochemistry (IHC) for CD31 (p=0.02). However other morphologic and molecular factors were not related to the presence of axillary node metastases. CONCLUSION: Lymphatic and blood vessel invasion identified in H&E and IHC-stained slides are positively related to the rmetastatic status of axillary lymph nodes and are predictive of axillary lymph node metastases in breast cancer.