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BACKGROUND: In luminal breast cancer, adjuvant CDK4/6 inhibitors (eg, abemaciclib) improve invasive disease-free survival. In patients with T1-2, grade 1-2 tumours, and one or two sentinel lymph node metastases, completion axillary lymph node dissection (cALND) is the only prognostic tool available that can reveal four or more nodal metastases (pN2-3), which is the only indication for adjuvant abemaciclib in this setting. However, this technique can lead to substantial arm morbidity in patients. We aimed to pragmatically describe the potential benefit and harm of this strategy on the individual patient level in patients from the ongoing SENOMAC trial. METHODS: In the randomised, phase 3, SENOMAC trial, patients aged 18 years or older, of any performance status, with clinically node-negative T1-T3 breast cancer and one or two sentinel node macrometastases from 67 sites in five European countries (Denmark, Germany, Greece, Italy, and Sweden) were randomly assigned (1:1), via permutated block randomisation (random block size of 2 and 4) stratified by country, to either cALND or its omission (ie, they had a sentinel lymph node biopsy only). The primary outcome is overall survival, which is yet to be reported. In this post-hoc analysis, patients from the SENOMAC per-protocol population, with luminal oestrogen-receptor positive, HER2-negative, T1-2, histological grade 1-2 breast cancer, with tumour size of 5 cm or smaller were selected to match the characteristics of cohort 1 of the monarchE trial who would only have an indication for adjuvant abemaciclib if found to have 4 or more nodal metastases. The primary study objective was to determine the number of patients who developed patient-reported severe or very severe impairment of physical arm function after cALND (as measured by the Lymphedema Functioning, Disability, and Health [Lymph-ICF] Questionnaire) 1 year after surgery to avoid one invasive disease-free survival event at 5 years with 2 years of adjuvant abemaciclib, using invasive disease-free survival event data from cohort 1 of the monarchE trial. The SENOMAC trial is registered with ClincialTrials.gov, NCT02240472, and is closed to accrual and ongoing. FINDINGS: Between Jan 31, 2015, and Dec 31, 2021, 2766 patients were enrolled in SENOMAC and randomly assigned to cALND (n=1384) or sentinel node biopsy only (n=1382), of whom 2540 were included in the per-protocol population. 1705 (67%) of 2540 patients met this post-hoc study's eligibility criteria, of whom 802 (47%) had a cALND and 903 (53%) had a sentinel lymph node biopsy only. Median age at randomisation was 62 years (IQR 52-71), 1699 (>99%) of 1705 patients were female, and six (<1%) were male. Among 1342 patients who responded to questionnaires, after a median follow-up of 45·2 months (IQR 25·6-59·8; data cutoff Nov 17, 2023), patient-reported severe or very severe impairment of physical arm function was reported in 84 (13%) of 634 patients who had cALND versus 30 (4%) of 708 who had sentinel lymph node biopsy only (χ2 test p<0·0001). To avoid one invasive disease-free survival event at 5 years with adjuvant abemaciclib, cALND would need to be performed in 104 patients, and would result in nine patients having severe or very severe impairment of physical arm function 1 year after surgery. INTERPRETATION: As a method to potentially identify an indication for abemaciclib, and subsequently avoid invasive disease-free survival events at 5 years with 2 years of adjuvant abemaciclib, cALND carries a substantial risk of severe or very severe arm morbidity and so cALND should be discouraged for this purpose. FUNDING: Swedish Research Council, the Swedish Cancer Society, the Nordic Cancer Union, and the Swedish Breast Cancer Association.
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PURPOSE: Phyllodes tumors of the breast are rare fibroepithelial lesions that are classified as benign, borderline or malignant. There is little consensus on best practice for the work-up, management, and follow-up of patients with phyllodes tumors of the breast, and evidence-based guidelines are lacking. METHODS: We conducted a cross-sectional survey of surgeons and oncologists with the aim to describe current clinical practice in the management of phyllodes tumors. The survey was constructed in REDCap and distributed between July 2021 and February 2022 through international collaborators in sixteen countries across four continents. RESULTS: A total of 419 responses were collected and analyzed. The majority of respondents were experienced and worked in a university hospital. Most agreed to recommend a tumor-free excision margin for benign tumors, increasing margins for borderline and malignant tumors. The multidisciplinary team meeting plays a major role in the treatment plan and follow-up. The vast majority did not consider axillary surgery. There were mixed opinions on adjuvant treatment, with a trend towards more liberal regiments in patients with locally advanced tumors. Most respondents preferred a five-year follow-up period for all phyllodes tumor types. CONCLUSIONS: This study shows considerable variation in clinical practice managing phyllodes tumors. This suggests the potential for overtreatment of many patients and the need for education and further research targeting appropriate surgical margins, follow-up time and a multidisciplinary approach. There is a need to develop guidelines that recognize the heterogeneity of phyllodes tumors.
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Neoplasias da Mama , Oncologistas , Tumor Filoide , Cirurgiões , Humanos , Feminino , Tumor Filoide/cirurgia , Tumor Filoide/patologia , Estudos Transversais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Some subgroups of breast cancer patients receiving neoadjuvant chemotherapy (NACT) show high rates of pathologic complete response (pCR) in the breast, proposing the possibility of omitting surgery. Prediction of pCR is dependent on accurate imaging methods. This study investigated whether magnetic resonance imaging (MRI) is better than ultrasound (US) in predicting pCR in breast cancer patients receiving NACT. METHODS: This institutional, retrospective study enrolled breast cancer patients receiving NACT who were examined by either MRI or combined US and mammography before surgery from 2016 to 2019. Imaging findings were compared with pathologic response evaluation of the tumor. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for prediction of pCR were calculated and compared between MRI and US. RESULTS: Among 307 patients, 151 were examined by MRI and 156 by US. In the MRI group, 37 patients (24.5 %) had a pCR compared with 51 patients (32.7 %) in the US group. Radiologic complete response (rCR) was found in 35 patients (23.2 %) in the MRI group and 26 patients (16.7 %) in the US group. In the MRI and US groups, estimates were calculated respectively for sensitivity (87.7 % vs 91.4 %), specificity (56.8 % vs 33.3 %), PPV (86.2 % vs 73.8 %), NPV (60.0 % vs 65.4 %), and accuracy (80.1 % vs 72.4 %). CONCLUSIONS: In predicting pCR, MRI was more specific than US, but not sufficiently specific enough to be a valid predictor of pCR for omission of surgery. As an imaging method, MRI should be preferred when future studies investigating prediction of pCR in NACT patients are planned.
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Neoplasias da Mama , Terapia Neoadjuvante , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Resultado do Tratamento , UltrassonografiaRESUMO
PURPOSE: To determine the incidence and risk factors of sentinel lymph node (SN) and non-SN metastases in patients with microinvasive breast cancer (MIBC, T1mic). This to identify MIBC patients in whom axillary staging can be safely omitted. METHODS: The Danish Breast Cancer Group database was used to identify a total of 409 women with breast cancer ≤ 1 mm who underwent sentinel lymph node biopsy (SLNB) between 2002 and 2015. After validation, 233 patients were eligible for the analysis. The incidence rates of SN and non-SN metastases were determined. The associations between clinicopathological variables and a positive SN [pN1, pN1mi, or pN0(i+)] were analyzed using univariate and multivariate designs. RESULTS: Of 233 patients with MIBC, only 9 (3.9%) had SN macrometastases. An additional 18 (7.7%) and 23 (9.9%) had SN micrometastases and isolated tumor cells (ITCs), respectively. Of patients with SN macrometastases, two (22.2%) had non-SN macrometastases. In the adjusted analysis, a positive SN was associated with younger age (P = 0.0001) and a positive human epidermal growth factor 2 receptor (HER2) status (P = 0.03). CONCLUSIONS: The low incidence of SN macrometastases < 4% suggests omission of axillary staging in MIBC patients without staging at primary surgery, especially in older (≥ 50 years) HER2- patients. Still, the relatively high proportion of patients with non-SN macrometastases indicates that axillary treatment might be considered in SN positive patients, especially in younger HER2+ MIBC patients.
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Neoplasias da Mama/patologia , Metástase Linfática/patologia , Micrometástase de Neoplasia/patologia , Biópsia de Linfonodo Sentinela/métodos , Fatores Etários , Idade de Início , Idoso , Neoplasias da Mama/metabolismo , Dinamarca , Feminino , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Sistema de Registros , Estudos RetrospectivosRESUMO
INTRODUCTION: Neoadjuvant endocrine treatment (NET) is a low-toxicity approach to achieve operability in locally advanced breast cancer, and to facilitate breast conservation in early breast cancer, particular in patients with highly estrogen receptor (ER) positive and HER2-negative disease. Here, we report the results obtained by neoadjuvant letrozole in patients with early breast cancer in a phase-II design. MATERIAL AND METHODS: A total of 119 postmenopausal women with ER-positive, HER2-negative operable breast cancer were assigned to four months of neoadjuvant letrozole before definitive surgery. Sentinel node or diagnostic fine needle aspiration cytology procedure was performed prior to treatment and the women were assessed prior, at two months, and before surgery with clinical examination, mammography and ultrasonography. Surgical specimens were examined for pathological response. Primary outcome was pathological and clinical response. RESULTS: The per protocol population consisted of 112 patients. Clinical response was evaluated in 109 patients and pathological response in 108. Overall a mean decrease in tumor size was 15% (p ≤ .0001). One patient had complete pathological response and 55% of patients had partial pathological response. ER at 100%, ductal subtype, tumor size below 2 cm and lymph node-negative status was significantly associated with a better response to NET and malignancy grade 3 with a poorer response to NET. One patient progressed during treatment and received neoadjuvant chemotherapy. Eight patients received adjuvant chemotherapy due to lack of response. CONCLUSION: Neoadjuvant aromatase inhibitor therapy is an acceptable strategy in selected postmenopausal patients with ER-rich and HER2-negative early breast cancer with ductal histology and should be considered when chemotherapy either isn't indicated or feasible.
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Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Terapia Neoadjuvante , Nitrilas/uso terapêutico , Triazóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Dinamarca , Feminino , Humanos , Letrozol , Excisão de Linfonodo , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Pós-Menopausa , Receptores de Estrogênio/metabolismoRESUMO
BACKGROUND: Only a few studies of limited size have examined whether oncoplastic breast surgery delays the onset of adjuvant chemotherapy as compared to conventional breast surgery. We investigated whether oncoplastic breast surgery causes a delay in the onset of adjuvant chemotherapy in comparison to lumpectomy and mastectomy. MATERIAL AND METHODS: The study is a population-based cohort study. Within the nationwide registry of the Danish Breast Cancer Group (DBCG), we identified 1798 patients who received adjuvant chemotherapy following mastectomy, lumpectomy or oncoplastic breast surgery for early and unilateral invasive breast cancer. Women treated with neoadjuvant chemotherapy were excluded. RESULTS: We found no significant difference between the three groups (mastectomy, lumpectomy, oncoplastic breast surgery) in the time from biopsy to surgery (mean time 17.9, 17.0 and 18.3 days, respectively), the time from surgery to onset of adjuvant chemotherapy, nor total time from biopsy to the onset of adjuvant chemotherapy (mean time 52.7, 51.9 and 53.2 days, respectively). CONCLUSIONS: Our study shows that oncoplastic breast surgery does not delay the onset of adjuvant chemotherapy in comparison with mastectomy and lumpectomy. Accordingly, patients should not be excluded from treatment with oncoplastic breast surgery due to concerns of delay in adjuvant chemotherapy.
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Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Mamoplastia , Mastectomia Segmentar , Mastectomia , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de TempoRESUMO
PURPOSE: To determine the recurrence rate of benign and borderline phyllodes tumors (PTs) of the breast, the association between the size of resection margin and risk of recurrence and the risk of progression of histological grading at recurrence. METHODS: Nationwide retrospective study on Danish women aged 18 years or older, operated from 1999 to 2014, with resected benign or borderline PTs. Information on age, size of primary tumor and recurrence, histological grade, surgical treatment, margin size, and local recurrence were collected from the national Danish Pathology Register. RESULTS: A total of 479 cases were identified; 354 benign (74 %), 89 borderline (19 %), 6 uncertain histological grading (1.2 %), and 30 possibly PT (6 %). The mean age at presentation was 45.6 years (range 18-85), the mean tumor size was 3.5 cm (range 0.5-21), and the mean follow-up time was 98 months (range 1.1-192). We identified 30 local recurrences, i.e., a recurrence rate of 6.3 %. Twenty-three recurrences had similar or lower histological grading than the primary tumor, one primary benign PT recurred as a tumor with unclear diagnosis, and one primary borderline PT recurred as malignant. The number of recurrences was too low, and the information on the size of the closest resection margin was too sparse to estimate an adequate margin size for excision of nonmalignant PTs. CONCLUSIONS: The recurrence rate of PTs was considerably lower than previously stated in literature. No apparent pattern of progression in histological grading was found. The results do not justify wide excision margins of nonmalignant phyllodes tumors of the breast.
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Neoplasias da Mama/cirurgia , Mastectomia/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Tumor Filoide/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Gradação de Tumores , Tumor Filoide/patologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Background We examined time trends in axilla management among patients with early breast cancer in European clinical settings. Material and methods EUROCANPlatform partners, including population-based and cancer center-specific registries, provided routinely available clinical cancer registry data for a comparative study of axillary management trends among patients with first non-metastatic breast cancer who were not selected for neoadjuvant therapy during the last decade. We used an additional short questionnaire to compare clinical care patterns in 2014. Results Patients treated in cancer centers were younger than population-based registry populations. Tumor size and lymph node status distributions varied little between settings or over time. In 2003, sentinel lymph node biopsy (SLNB) use varied between 26% and 81% for pT1 tumors, and between 2% and 68% for pT2 tumors. By 2010, SLNB use increased to 79-96% and 49-92% for pT1 and pT2 tumors, respectively. Axillary lymph node dissection (ALND) use for pT1 tumors decreased from between 75% and 27% in 2003 to 47% and 12% in 2010, and from between 90% and 55% to 79% and 19% for pT2 tumors, respectively. In 2014, important differences in axillary management existed for patients with micrometastases only, and for patients fulfilling the ACOSOG Z0011 criteria for omitting ALND. Conclusion This study demonstrates persisting differences in important aspects of axillary management throughout the recent decade. The results highlight the need for international comparative patterns of care studies in oncology, which may help to identify areas where further studies and consensus building may be necessary.
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Neoplasias da Mama/patologia , Excisão de Linfonodo/estatística & dados numéricos , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Idoso , Axila/patologia , Europa (Continente) , Feminino , Humanos , Excisão de Linfonodo/tendências , Linfonodos/patologia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Sistema de Registros , Biópsia de Linfonodo Sentinela/tendências , Fatores de TempoRESUMO
We examined the association between the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status of women with primary breast cancer and the risk of axillary lymph node (ALN) involvement at the time of diagnosis. Information on 20,009 women diagnosed with primary breast cancer between 2008 and 2012 was retrieved from the Danish Breast Cancer Cooperative Group database. The associations between clinical and pathological variables and ALN involvement at the time of diagnosis were evaluated in univariate and multivariate regression analyses, as well as the significance of tumor subtypes in ALN involvement. The risk of ALN metastases at the time of diagnosis was significantly reduced in HR-negative patients compared to HR-positive patients [adjusted odds ratio (OR) 0.69; 95 % CI 0.63-0.76; P = 0.0009]. A HER2-positive status was associated with an increased risk of ALN involvement at diagnosis compared to a HER2-negative status (OR 1.37; 95 % CI 1.24-1.50; P < 0.0001). An interaction between HER2 and HR was observed, with a HER2-positive status significantly associated with ALN involvement at the time of diagnosis only in HR-negative patients (P < 0.0001). The triple-negative breast cancer (TNBC) patients showed a significantly reduced risk of ALN involvement at the time of diagnosis compared to patients with HR-positive/HER2-negative tumors (OR 0.55; 95 % CI 0.49-0.62; P < 0.0001). The HR and HER2 statuses are significantly associated with ALN involvement at the time of diagnosis. Despite the poor prognosis, TNBC patients have a reduced risk of ALN involvement at the time of diagnosis compared to patients with other subtypes, when adjusting for other risk factors. This may indicate that TNBC tends to spread hematogenously rather than lymphogenously.
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Linfonodos/patologia , Prognóstico , Neoplasias de Mama Triplo Negativas/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Axila/patologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Medição de Risco , Neoplasias de Mama Triplo Negativas/genéticaRESUMO
We estimated the impact of axillary lymph node dissection (ALND) on the risk of axillary recurrence (AR) and overall survival (OS) in breast cancer patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes. We used the Danish Breast Cancer Cooperative Group (DBCG) database to identify patients with micrometastases or ITC in sentinel nodes following surgery for primary breast cancer between 2002 and 2008. A Cox proportional hazard regression model was developed to assess the hazard ratios (HR) for AR and OS between patients with and without ALND. We identified 2074 patients, of which 240 did not undergo further axillary surgery. The 5-year cumulated incidence for AR was 1.58 %. No significant difference in AR was seen between patients with and without ALND. The age adjusted HR for AR if ALND was omitted was 1.79 (95 % CI 0.41-7.80, P = 0.44) in patients with micrometastases and 2.21 (95 % CI 0.54-8.95, P = 0.27), in patients with ITC after a median follow-up of 6 years and 3 months. There was no significant difference in overall survival between patients with and without ALND, when adjusting for age, co-morbidity, tumor size, histology type, malignancy grade, lymphovascular invasion, hormone receptor status, adjuvant systemic treatment and radiotherapy, with a HR for death if ALND was omitted of 1.21 (95 % CI 0.86-1.69, P = 0.27) in patients with micrometastases and 0.96 (95 % CI 0.57-1.62, P = 0.89) in patients with ITC after a medium follow-up on 8 and 5 years. In this nationwide study, we found a low risk of AR on 1.58 % and we did not find a significantly increased risk of AR if ALND was omitted in patients with micrometastases or ITC in sentinel nodes. Furthermore, no significant difference in overall survival was seen between patients with and without ALND when adjusting for adjuvant treatment.
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Axila , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Linfonodos/patologia , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Terapia Combinada , Comorbidade , Dinamarca/epidemiologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Micrometástase de Neoplasia , Prognóstico , Modelos de Riscos Proporcionais , Sistema de RegistrosRESUMO
BACKGROUND: The aim of this study was to investigate the use of sentinel lymph node dissection (SLND) in the treatment of patients with locally recurrent breast cancer. METHODS: A total of 147 patients with locally recurrent breast cancer were included from five different breast surgery departments in Denmark. Data on previous breast and axillary surgery, adjuvant treatment, second operation in the breast and axilla, and lymphoscintigraphy were collected retrospectively from the original patient files. RESULTS: SLND after recurrence (SLNDAR) was successful in 72 of 144 patients (50 %). The detection rate was significantly higher after previous SLND (66 %) compared with previous ALND (34 %) [p = 0.0001]. Thirty-seven patients (51 %) who had previous SLND had a negative sentinel node. These patients could be spared an ALND. Six patients (8 %) who had a previous ALND had a metastatic sentinel node at recurrence; 17 % of patients had a sentinel node located outside the ipsilateral axilla; and eight patients with negative sentinel node at SLNDAR underwent completion ALND. None of these patients had metastases at completion ALND, corresponding to a false negative rate of 0 %. CONCLUSIONS: SLNDAR seems to be a feasible procedure in locally recurrent breast cancer and can spare a clinically significant number of patients an unnecessary ALND and the following risk of sequelae. In patients who had previous ALND, SLNDAR identified metastases that would have been overlooked following the current guidelines. A large proportion of patients had aberrant drainage, suggesting a need for lymphoscintigraphy.
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Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Excisão de Linfonodo , Linfonodos/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Dissecação , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Cintilografia , Reoperação , Estudos RetrospectivosRESUMO
Surgical treatment of breast cancer has changed towards less invasive procedures as summarised in this review. Breast conserving surgery (BCS) and radiotherapy (RT) are now recommended as standard of care. Several flexible marking methods for removal of non-palpable tumours have gradually replaced wire-guided localisation. Neoadjuvant systemic treatment increases tumour shrinkage and BCS and may lead to omission of axillary clearance (AC). The prognostic significance of AC in patients with metastases to 1-2 sentinel nodes at primary surgery is questioned. Results from the SENOMAC trial are expected to change guidelines from AC to axillary RT.
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Neoplasias da Mama , Feminino , Humanos , Axila/patologia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Mastectomia Segmentar , Biópsia de Linfonodo SentinelaAssuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Cuidados Pré-Operatórios , Sistema de Registros/estatística & dados numéricos , Axila , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Dinamarca , Feminino , Seguimentos , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Estudos RetrospectivosAssuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Fatores Etários , Idoso , Axila , Biópsia por Agulha Fina , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Reações Falso-Negativas , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Período Pré-Operatório , Linfonodo Sentinela/diagnóstico por imagem , Biópsia de Linfonodo Sentinela , Carga Tumoral , UltrassonografiaRESUMO
Background and Objective: With the improved survival for breast cancer there is now an increased focus on quality of life after treatment. Axillary surgery is known to be associated with significant risk of arm morbidity feared by the patients, and several studies have shown de-escalation is possible in different settings. In this review, an overview will be given on new techniques and procedures for de-escalation of axillary surgery in breast cancer patients and the subsequent implications for adjuvant systemic treatment. Methods: This study is a narrative review. PubMed was searched for relevant publications in English published between January 2018-June 2023. Only publications with major impact on clinical practice have been included with main emphasis on meta-analysis. In addition, Clinicaltrial.gov has been searched for on-going studies. Key Content and Findings: New tracer techniques are described as well as the on-going reduction in axillary lymph node dissection (ALND) at primary surgery even in node positive patients, and the axillary staging possibilities after down-staging of the axilla by neoadjuvant treatment. Finally axillary staging at local recurrence and in case of ductal carcinoma in situ is described. Conclusions: ALND is no longer routinely recommended in many node positive patients and further de-escalation is investigated. The lack of knowledge on precise axillary status will require cooperating studies between oncologists and breast surgeons in order to avoid escalation of systemic treatment due to the lack of applicability of trial eligibility criteria. Furthermore, investigations on the use of axillary imaging for staging are needed.
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Axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel nodes is under debate. We aimed to establish two models to predict non-sentinel node (NSN) metastases in patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes, to guide the decision for ALND. A total of 1,577 breast cancer patients with micrometastases and 304 with ITC in sentinel nodes, treated by sentinel lymph node dissection and ALND in 2002-2008 were identified in the Danish Breast Cancer Cooperative Group database. Risk of NSN metastases was calculated according to clinicopathological variables in a logistic regression analysis. We identified tumor size, proportion of positive sentinel nodes, lymphovascular invasion, hormone receptor status and location of tumor in upper lateral quadrant of the breast as risk factors for NSN metastases in patients with micrometastases. A model based on these risk factors identified 5% of patients with a risk of NSN metastases on nearly 40%. The model was however unable to identify a subgroup of patients with a very low risk of NSN metastases. Among patients with ITC, we identified tumor size, age and proportion of positive sentinel nodes as risk factors. A model based on these risk factors identified 32% of patients with risk of NSN metastases on only 2%. Omission of ALND would be acceptable in this group of patients. In contrast, ALND may still be beneficial in the subgroup of patients with micrometastases and a high risk of NSN metastases.
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Neoplasias da Mama/patologia , Linfonodos/patologia , Micrometástase de Neoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Dinamarca , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Risco , Biópsia de Linfonodo Sentinela , Adulto JovemRESUMO
OBJECTIVES: Unexplained axillary metastases have been detected in some patients with ductal carcinoma in situ (DCIS), possibly because of occult invasion or iatrogenic tumor cell displacement. The significance of these metastases is unknown and brings into questions the need for upstaging and axillary surgery. What are the risk factors for sentinel lymph node (SN) and non-SN metastases, including the risk of iatrogenic displacement of tumor cells in relation to an excisional biopsy, in patients diagnosed with DCIS? METHODS: Nationwide data on 1787 women diagnosed with DCIS between 2001 and 2015 were retrieved from the Danish Breast Cancer Group database. The association of clinicopathological variables with a positive SN (isolated tumor cells (ITCs), micro- or macrometastases) was evaluated using univariate and multivariate analyses. RESULTS: Of the 1787 patients, 71 (4.0%) had a positive SN: 15 (0.8%) had macrometastases, 42 (2.4%) had micrometastases, and 14 (0.8%) had ITCs. Five patients with a positive SN also had a positive non-SN. In adjusted analysis, a positive SN was associated with younger age (Pâ¯=â¯0.036), increased size (Pâ¯=â¯0.002), palpability (Pâ¯=â¯0.0004) and surgical excisional biopsy (Pâ¯<â¯0.001). CONCLUSIONS: The overall risk of a positive SN in patients with DCIS on final pathology is low and less than 9% of these patients had positive non-SNs. This argues against using axillary lymph node dissection in this group. The odds of positive SN after surgical excisional biopsies showed more than a four-fold increase, indicating iatrogenic tumor cell displacement. It is questioned whether these patients should be upstaged and classified as having invasive carcinoma.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Linfonodo Sentinela/patologia , Adulto , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Protocolos Clínicos/normas , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fatores de Risco , Linfonodo Sentinela/cirurgiaRESUMO
This thesis is based on 10 original articles, of which 3 were previously included in the PhD thesis "Staging of women with breast cancer after introduction of sentinel node guided axillary dissection". In the PhD thesis is was shown that the introduction of sentinel lymph node dissection (SLND) in the treatment of breast cancer in Denmark has resulted in an increased identification of patients with micrometastases or isolated tumor cells (ITC) in the lymph nodes. Not all these small metastases are likely to disseminate to non-sentinel nodes. This thesis provides evidence that a previous surgical excision of a breast tumor is likely to lead to iatrogenic displacement of tumor cells resulting in a nearly four-fold increased risk of ITC in the sentinel node. These tumor cells are not associated with non-sentinel node metastases. Especially ITC, but also micrometastases and some macrometastases, are not identified on perioperative frozen sections, but found postoperatively at the conventional histopathological examination. These patients are offered an axillary lymph node dissection (ALND) as a second procedure. It has been suggested that this two-stage procedure reduces the number of lymph nodes removed, because of fibroses from previous surgery. In this thesis it was shown that a two-stage procedure does not result in a clinically relevant impairment of the number of lymph nodes removed by ALND. Based on patient, tumor, and sentinel node characteristics from the Danish Breast Cancer Group database, two predictive models for non-sentinel node metastases, when only micrometastases or ITC are found in the sentinel node, were developed, as a part of the PhD thesis. These two models have now been internally validated, and a cross-validation in a Finnish patient material has been performed in cooperation with researchers from Helsinki. The model for patients with micrometastases proved to be robust under internal as well as external validation and could be used to identify patients with micrometastases that might still benefit from an ALND. Efforts should continue to improve the model. As a part of the PhD thesis, new molecular markers were tested for prediction of non-sentinel node metastases. In addition, method of detection of the breast cancer could be a possible predictor of non-sentinel node metastases. It has been hypothesized that breast cancers detected by screening represent a clinical indolent group of cancers with lower risk of non-sentinel node metastases compared to symptomatic cancers. This hypothesis was tested in this thesis in a large Danish dataset. No significant difference in the risk of non-sentinel node metastases was found between patients with screen-detected and symptomatic breast cancers, and a less aggressive treatment of the axilla in patients with screen-detected breast cancers cannot be supported. Likewise, the method of detection is not expected to be able to improve the predictive models. Until 2012, the standard treatment of Danish patients with micrometastases or ITC in the sentinel node was ALND. Still, in selected patients ALND was not performed. This thesis includes a comparison of the risk of axillary recurrence and survival between patients with and without ALND. The overall axillary recurrence rate was only 1.6% after 6 years of follow-up, despite between 9 - 18 % of these patients are expected to have non-sentinel node metastases. No significant difference was seen in axillary recurrence and overall survival between patients with and without ALND. These results support the safety of omitting ALND in patients with only micrometastases or ITC in the sentinel node and since 2012 Danish breast cancer patients with ITC or up to two micrometastatic sentinel nodes are no longer offered an ALND. In Denmark the standard surgical treatment of the axilla in locally recurrent breast cancer is no further treatment of the axilla in case of previous ALND, and ALND in case of previous SLND. To investigate whether SLND can be extended to this patient group, a Danish multicenter study was performed. Despite a reduced detection rate, especially after previous ALND, SLND seemed to be a feasible procedure in locally recurrent breast cancer. The procedure can spare a clinically significant number of patients an unnecessary ALND and improve staging and local control after previous ALND. The increased number of patients with aberrant drainage underlines the importance of preoperative lymphoscintigraphy at local recurrence.
Assuntos
Neoplasias da Mama/cirurgia , Linfonodos/cirurgia , Biópsia de Linfonodo Sentinela/efeitos adversos , Linfonodo Sentinela/cirurgia , Adulto , Axila , Neoplasias da Mama/patologia , Dinamarca , Feminino , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Micrometástase de Neoplasia/patologia , Recidiva Local de Neoplasia/etiologia , Complicações Pós-Operatórias/etiologia , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Resultado do TratamentoRESUMO
OBJECTIVES: The risk of axillary metastases in breast cancer patients with only ductal carcinoma in situ (DCIS) is low. Thus, axillary staging with sentinel lymph node biopsy (SLNB) should only be used according to the current guidelines to avoid over-treatment and unnecessary morbidity. In the present study, the use of SLNB in patients with DCIS was evaluated nationally and compared across Danish departments. MATERIAL AND METHODS: A register-based study was conducted using the Danish Breast Cancer Group database. The use of SLNB in DCIS patients according to year of diagnosis, age at diagnosis, size of lesion, Van Nuys classification, palpability, location and department of surgery was evaluated. The chi-squared test was used to test differences between the groups. RESULTS: Data from 2618 Danish female patients diagnosed with DCIS between 2004 and 2015 were included; 54.3% of patients underwent SLNB. The use of SLNB increased from 26.6% in 2004 to 65.1% in 2015. A total of 1877 (71.7%) patients underwent breast-conserving surgery (BCS), and 577 (22.0%) underwent mastectomy, of which 43.9% and 86.0% respectively had a concomitant SLNB. The SLNB was performed in 23.8% of 454 patients not included by the guidelines. The use of SLNB in combination with BCS differed significantly between departments ranging from 19.7% to 63.8%. A significant difference in the use of SLNB with BCS and mastectomy according to department capacity (high-volume departments versus low-volume departments) was observed. CONCLUSION: The use of SLNB in patients with DCIS and adherence to the Danish national guidelines varies among Danish breast surgery departments. To optimise the axillary treatment of patients with DCIS, an improved compliance to the national DCIS guidelines is necessary.