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Breast Cancer Research and Treatment Jul 2023Breast cancer-related lymphedema (BCRL) represents a lifelong risk for breast cancer survivors and once acquired becomes a lifelong burden. This review summarizes... (Review)
Review
PURPOSE
Breast cancer-related lymphedema (BCRL) represents a lifelong risk for breast cancer survivors and once acquired becomes a lifelong burden. This review summarizes current BCRL prevention and treatment strategies.
FINDINGS
Risk factors for BCRL have been extensively studied and their identification has affected breast cancer treatment practice, with sentinel lymph node removal now standard of care for patients with early stage breast cancer without sentinel lymph node metastases. Early surveillance and timely management aim to reduce BCRL incidence and progression, and are further facilitated by patient education, which many breast cancer survivors report not having adequately received. Surgical approaches to BCRL prevention include axillary reverse mapping, lymphatic microsurgical preventative healing (LYMPHA) and Simplified LYMPHA (SLYMPHA). Complete decongestive therapy (CDT) remains the standard of care for patients with BCRL. Among CDT components, facilitating manual lymphatic drainage (MLD) using indocyanine green fluorescence lymphography has been proposed. Intermittent pneumatic compression, nonpneumatic active compression devices, and low-level laser therapy appear promising in lymphedema management. Reconstructive microsurgical techniques such as lymphovenous anastomosis and vascular lymph node transfer are growing surgical considerations for patients as well as liposuction-based procedures for addressing fatty fibrosis formation from chronic lymphedema. Long-term self-management adherence remains problematic, and lack of diagnosis and measurement consensus precludes a comparison of outcomes. Currently, no pharmacological approaches have proven successful.
CONCLUSION
Progress in prevention and treatment of BCRL continues, requiring advances in early diagnosis, patient education, expert consensus and novel treatments designed for lymphatic rehabilitation following insults.
Topics: Humans; Female; Breast Neoplasms; Breast Cancer Lymphedema; Lymphedema; Manual Lymphatic Drainage; Risk Factors; Lymph Node Excision
PubMed: 37103598
DOI: 10.1007/s10549-023-06947-7 -
Seminars in Oncology Dec 2020This historical surgical retrospection focuses on the temporal de-escalation axillary surgery, focusing on the unceasing efforts of researchers toward new challenges, as... (Review)
Review
This historical surgical retrospection focuses on the temporal de-escalation axillary surgery, focusing on the unceasing efforts of researchers toward new challenges, as documented by extensive studies and trials. Axillary surgery has evolved, aiming to offer the best oncologic treatment and improve the quality of life of women. Axillary lymph-node dissection (ALND) has been replaced by sentinel lymph-node biopsy (SLNB) in women with early clinically node-negative breast cancer, providing adequate axillary nodal staging information with minimal morbidity, and becoming the standard of care in the management of breast cancer. However, this is only the beginning. Strategies in defining systemic and radiotherapeutic treatments have gradually been optimized, offering increasingly refined and targeted breast cancer treatment tools. In recent years, the paradigm of completion ALND after a positive SLNB has been questioned, and several studies have led to revolutionary changes in clinical practice. Moreover, the increasingly pivotal role played by neoadjuvant chemotherapy (NAC) has had a profound effect on the extent of axillary surgery, paving the way to a more finite "targeted" procedure in women with node-positive breast cancer who convert to negative nodes clinically after NAC. The utility of SLNB itself and its subsequent omission in women with negative nodes clinically and breast conservative surgery is also under scientific evaluation. The changes over time in the surgical approach to breast cancer have been numerous and significant. The novel emerging perspective characterized by recent advances in biology and genetics, in dedicated axillary ultrasound imaging and chemotherapy regimens, is the present reality that points to the future of axillary node treatment in breast cancer.
Topics: Axilla; Breast Neoplasms; Chemotherapy, Adjuvant; History, 15th Century; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; History, Medieval; Humans; Lymph Node Excision; Sentinel Lymph Node Biopsy
PubMed: 33131896
DOI: 10.1053/j.seminoncol.2020.09.001 -
Seminars in Nuclear Medicine Sep 2022Breast cancer is the most frequent cancer diagnosed in women worldwide. Accurate lymph node staging is essential for both prognosis (of early-stage disease) and... (Review)
Review
Breast cancer is the most frequent cancer diagnosed in women worldwide. Accurate lymph node staging is essential for both prognosis (of early-stage disease) and treatment (for regional control of disease) in patients with breast cancer. The sentinel lymph nodes are the regional nodes that directly drain lymph from the primary tumor. No imaging modality is accurate enough to detect lymph node metastases when a primary breast cancer is at an early stage (I or II), but sentinel lymph node biopsy is a highly reliable method for screening axillary nodes and for identifying metastatic (including micro-metastatic) disease in regional lymph nodes. Despite the widespread use of sentinel lymph node biopsy for early-stage breast cancer, relevant variations have been described regarding practical aspects of the procedure, and some variability has initially been reported regarding the rates of intraoperative sentinel lymph node identification and of false-negative findings, most likely because of differences in the size of the populations being investigated and in lymphatic mapping techniques. Nevertheless, using adequate learning curves and once a multidisciplinary team is experienced with the procedure, improved levels of accuracy are achieved.
Topics: Axilla; Breast Neoplasms; Female; Humans; Neoplasm Staging; Sentinel Lymph Node; Sentinel Lymph Node Biopsy
PubMed: 35241267
DOI: 10.1053/j.semnuclmed.2022.01.006 -
Nature Communications Mar 2020Accurate identification of axillary lymph node (ALN) involvement in patients with early-stage breast cancer is important for determining appropriate axillary treatment...
Accurate identification of axillary lymph node (ALN) involvement in patients with early-stage breast cancer is important for determining appropriate axillary treatment options and therefore avoiding unnecessary axillary surgery and complications. Here, we report deep learning radiomics (DLR) of conventional ultrasound and shear wave elastography of breast cancer for predicting ALN status preoperatively in patients with early-stage breast cancer. Clinical parameter combined DLR yields the best diagnostic performance in predicting ALN status between disease-free axilla and any axillary metastasis with areas under the receiver operating characteristic curve (AUC) of 0.902 (95% confidence interval [CI]: 0.843, 0.961) in the test cohort. This clinical parameter combined DLR can also discriminate between low and heavy metastatic burden of axillary disease with AUC of 0.905 (95% CI: 0.814, 0.996) in the test cohort. Our study offers a noninvasive imaging biomarker to predict the metastatic extent of ALN for patients with early-stage breast cancer.
Topics: Adult; Aged; Aged, 80 and over; Axilla; Breast; Breast Neoplasms; Deep Learning; Elasticity Imaging Techniques; Female; Humans; Image Processing, Computer-Assisted; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Mastectomy; Middle Aged; Neoplasm Staging; Preoperative Period; Prognosis; Prospective Studies; ROC Curve; Reference Standards; Ultrasonography
PubMed: 32144248
DOI: 10.1038/s41467-020-15027-z -
Cancer Treatment Reviews Jun 2023The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and... (Meta-Analysis)
Meta-Analysis Review
The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register.
Topics: Humans; Female; Breast Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Sentinel Lymph Node Biopsy
PubMed: 37126938
DOI: 10.1016/j.ctrv.2023.102556 -
The Oncologist Feb 2020The detection of lymph node metastasis affects the management of patients with primary breast cancer significantly in terms of staging, treatment, and prognosis. The... (Review)
Review
The detection of lymph node metastasis affects the management of patients with primary breast cancer significantly in terms of staging, treatment, and prognosis. The main goal for the radiologist is to determine and detect the presence of metastatic disease in nonpalpable axillary lymph nodes with a positive predictive value that is high enough to initially select patients for upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with different imaging modalities, but ultrasound is the method of choice for evaluating axillary lymph nodes and for performing image-guided lymph node interventions. This review aims to provide a comprehensive overview of the available imaging modalities for lymph node assessment in patients diagnosed with primary breast cancer. IMPLICATIONS FOR PRACTICE: The detection of lymph node metastasis affects the management of patients with primary breast cancer. The main goal for the radiologist is to detect lymph node metastasis in patients to allow for the selection of patients who should undergo upfront axillary lymph node dissection. Features that are suggestive of axillary adenopathy may be seen with mammography, computed tomography, and magnetic resonance imaging, but ultrasonography is the imaging modality of choice for evaluating axillary lymph nodes. A normal axillary lymph node is characterized by a reniform shape, a maximal cortical thickness of 3 mm without focal bulging, smooth margins, and, depending on size, a discernable central fatty hilum.
Topics: Axilla; Breast Neoplasms; Female; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Sensitivity and Specificity; Sentinel Lymph Node Biopsy
PubMed: 32043792
DOI: 10.1634/theoncologist.2019-0427 -
JAMA Surgery Aug 2023The increasing use of neoadjuvant systemic therapy (NST) has led to substantial pathological complete response rates in patients with initially node-positive, early...
IMPORTANCE
The increasing use of neoadjuvant systemic therapy (NST) has led to substantial pathological complete response rates in patients with initially node-positive, early breast cancer, thereby questioning the need for axillary lymph node dissection (ALND). Targeted axillary dissection (TAD) is feasible for axillary staging; however, data on oncological safety are scarce.
OBJECTIVE
To assess 3-year clinical outcomes in patients with node-positive breast cancer who underwent TAD alone or TAD with ALND.
DESIGN, SETTING, AND PARTICIPANTS
The SenTa study is a prospective registry study and was conducted between January 2017 and October 2018. The registry includes 50 study centers in Germany. Patients with clinically node-positive breast cancer underwent clipping of the most suspicious lymph node (LN) before NST. After NST, the marked LNs and sentinel LNs were excised (TAD) followed by ALND according to the clinician's choice. Patients who did not undergo TAD were excluded. Data analysis was performed in April 2022 after 43 months of follow-up.
EXPOSURE
TAD alone vs TAD with ALND.
MAIN OUTCOMES AND MEASURES
Three-year clinical outcomes were evaluated.
RESULTS
Of 199 female patients, the median (IQR) age was 52 (45-60) years. A total of 182 patients (91.5%) had 1 to 3 suspicious LNs; 119 received TAD alone and 80 received TAD with ALND. Unadjusted invasive disease-free survival was 82.4% (95% CI, 71.5-89.4) in the TAD with ALND group and 91.2% (95% CI, 84.2-95.1) in the TAD alone group (P = .04); axillary recurrence rates were 1.4% (95% CI, 0-54.8) and 1.8% (95% CI, 0-36.4), respectively (P = .56). Adjusted multivariate Cox regression indicated that TAD alone was not associated with an increased risk of recurrence (hazard ratio [HR], 0.83; 95% CI, 0.34-2.05; P = .69) or death (HR, 1.07; 95% CI, 0.31-3.70; P = .91). Similar results were obtained for 152 patients with clinically node-negative breast cancer after NST (invasive disease-free survival: HR, 1.26; 95% CI, 0.27-5.87; P = .77; overall survival: HR, 0.81; 95% CI, 0.15-3.83; P = .74).
CONCLUSIONS AND RELEVANCE
These results suggest that TAD alone in patients with mostly good clinical response to NST and at least 3 TAD LNs may confer survival outcomes and recurrence rates similar to TAD with ALND.
Topics: Humans; Female; Middle Aged; Breast Neoplasms; Neoadjuvant Therapy; Sentinel Lymph Node Biopsy; Lymphatic Metastasis; Lymph Node Excision; Lymph Nodes; Axilla
PubMed: 37285140
DOI: 10.1001/jamasurg.2023.1772 -
JAMA Oncology Dec 2021Prospective trials have demonstrated sentinel lymph node (SLN) false-negative rates of less than 10% when 3 or more SLNs are retrieved in patients with clinically...
IMPORTANCE
Prospective trials have demonstrated sentinel lymph node (SLN) false-negative rates of less than 10% when 3 or more SLNs are retrieved in patients with clinically node-positive breast cancer rendered clinically node-negative with neoadjuvant chemotherapy (NAC). However, rates of nodal recurrence in such patients treated with SLN biopsy (SLNB) alone are unknown because axillary lymph node dissection (ALND) was performed in all patients, limiting adoption of this approach.
OBJECTIVE
To evaluate nodal recurrence rates in a consecutive cohort of patients with clinically node-positive (cN1) breast cancer receiving NAC, followed by a negative SLNB using a standardized technique, and no further axillary surgery.
DESIGN, SETTING, AND PARTICIPANTS
From November 2013 to February 2019, a cohort of consecutively identified patients with cT1 to cT3 biopsy-proven N1 breast cancer rendered cN0 by NAC underwent SLNB with dual tracer mapping and omission of ALND if 3 or more SLNs were identified and all were pathologically negative. Metastatic nodes were not routinely clipped, and localization of clipped nodes was not performed. The study was performed in a single tertiary cancer center.
INTERVENTION
Omission of ALND in patients with cN1 breast cancer after NAC if 3 or more SLNs were pathologically negative.
MAIN OUTCOME AND MEASURES
The primary outcome was the rate of nodal recurrence among patients with cN1 breast cancer treated with SLNB alone after NAC.
RESULTS
Of 610 patients with cN1 breast cancer treated with NAC, 555 (91%) converted to cN0 and underwent SLNB; 234 (42%) had 3 or more negative SLNs and had SLNB alone. The median (IQR) age of these 234 patients was 49 (40-58) years; median tumor size was 3 cm; 144 (62%) were ERBB2 (formerly HER2)-positive, and 43 (18%) were triple negative. Most (212 [91%]) received doxorubicin-based NAC; 205 (88%) received adjuvant radiotherapy (RT), and 164 (70%) also received nodal RT. At a median follow-up of 40 months, there was 1 axillary nodal recurrence synchronous with local recurrence in a patient who refused RT. Among patients who received RT (n = 205), there were no nodal recurrences.
CONCLUSIONS AND RELEVANCE
This cohort study found that in patients with cN1 disease rendered cN0 with NAC, with 3 or more negative SLNs with SLNB alone, nodal recurrence rates were low, without routine nodal clipping. These findings potentially support omitting ALND in such patients.
Topics: Axilla; Breast Neoplasms; Cohort Studies; Female; Humans; Lymph Node Excision; Middle Aged; Neoadjuvant Therapy; Prospective Studies; Sentinel Lymph Node Biopsy
PubMed: 34617979
DOI: 10.1001/jamaoncol.2021.4394 -
JAMA Surgery Oct 2023The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive... (Randomized Controlled Trial)
Randomized Controlled Trial Observational Study
IMPORTANCE
The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown.
OBJECTIVE
To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT).
DESIGN, SETTING, AND PARTICIPANTS
This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required.
EXPOSURES
All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators.
RESULTS
A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]).
CONCLUSION
Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.
Topics: Humans; Female; Middle Aged; Breast Neoplasms; Sentinel Lymph Node Biopsy; Lymphatic Metastasis; Cohort Studies; Prospective Studies; Lymph Node Excision; Lymph Nodes; Neoadjuvant Therapy; Axilla
PubMed: 37466971
DOI: 10.1001/jamasurg.2023.2840 -
The British Journal of Surgery Aug 2023The initial results of the SINODAR-ONE randomized clinical trial reported that patients with T1-2 breast cancer and one to two macrometastatic sentinel lymph nodes... (Randomized Controlled Trial)
Randomized Controlled Trial
Sentinel lymph node biopsy versus axillary lymph node dissection in breast cancer patients undergoing mastectomy with one to two metastatic sentinel lymph nodes: sub-analysis of the SINODAR-ONE multicentre randomized clinical trial and reopening of enrolment.
BACKGROUND
The initial results of the SINODAR-ONE randomized clinical trial reported that patients with T1-2 breast cancer and one to two macrometastatic sentinel lymph nodes treated with breast-conserving surgery, sentinel lymph node biopsy only, and adjuvant therapy did not present worse 3-year survival, regional recurrence, or distant recurrence rates compared with those treated with axillary lymph node dissection. To extend the recommendation of axillary lymph node dissection omission even in patients treated with mastectomy, a sub-analysis of the SINODAR-ONE trial is presented here.
METHODS
Patients with T1-2 breast cancer and no more than two metastatic sentinel lymph nodes undergoing mastectomy were analysed. After sentinel lymph node biopsy, patients were randomly assigned to receive either axillary lymph node dissection followed by adjuvant treatment (standard arm) or adjuvant treatment alone (experimental arm). The primary endpoint was overall survival. The secondary endpoint was recurrence-free survival.
RESULTS
A total of 218 patients were treated with mastectomy; 111 were randomly assigned to the axillary lymph node dissection group and 107 to the sentinel lymph node biopsy-only group. At a median follow-up of 33.0 months, there were three deaths (two deaths in the axillary lymph node dissection group and one death in the sentinel lymph node biopsy-only group). There were five recurrences in each treatment arm. No axillary lymph node recurrence was observed. The 5-year overall survival rates were 97.8 and 98.7 per cent in the axillary lymph node dissection treatment arm and the sentinel lymph node biopsy-only treatment arm, respectively (P = 0.597). The 5-year recurrence-free survival rates were 95.7 and 94.1 per cent in the axillary lymph node dissection treatment arm and the sentinel lymph node biopsy treatment arm, respectively (P = 0.821).
CONCLUSION
In patients with T1-2 breast cancer and one to two macrometastatic sentinel lymph nodes treated with mastectomy, the overall survival and recurrence-free survival rates of patients treated with sentinel lymph node biopsy only were not inferior to those treated with axillary lymph node dissection. To strengthen the conclusion of the trial, the enrolment of patients treated with mastectomy was reopened as a single-arm experimental study.
REGISTRATION NUMBER
NCT05160324 (http://www.clinicaltrials.gov).
Topics: Humans; Female; Sentinel Lymph Node Biopsy; Sentinel Lymph Node; Breast Neoplasms; Mastectomy; Lymphatic Metastasis; Disease-Free Survival; Lymph Node Excision; Lymph Nodes; Axilla
PubMed: 37471574
DOI: 10.1093/bjs/znad215