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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 -
JAMA Oncology Nov 2023Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging of patients with early breast cancer (BC), but its necessity can be questioned since...
Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial.
IMPORTANCE
Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging of patients with early breast cancer (BC), but its necessity can be questioned since surgery for examination of axillary nodes is not performed with curative intent.
OBJECTIVE
To determine whether the omission of axillary surgery is noninferior to SLNB in patients with small BC and a negative result on preoperative axillary lymph node ultrasonography.
DESIGN, SETTING, AND PARTICIPANTS
The SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound) trial was a prospective noninferiority phase 3 randomized clinical trial conducted in Italy, Switzerland, Spain, and Chile. A total of 1463 women of any age with BC up to 2 cm and a negative preoperative axillary ultrasonography result were enrolled and randomized between February 6, 2012, and June 30, 2017. Of those, 1405 were included in the intention-to-treat analysis. Data were analyzed from October 10, 2022, to January 13, 2023.
INTERVENTION
Eligible patients were randomized on a 1:1 ratio to receive SLNB (SLNB group) or no axillary surgery (no axillary surgery group).
MAIN OUTCOMES AND MEASURES
The primary end point of the study was distant disease-free survival (DDFS) at 5 years, analyzed as intention to treat. Secondary end points were the cumulative incidence of distant recurrences, the cumulative incidence of axillary recurrences, DFS, overall survival (OS), and the adjuvant treatment recommendations.
RESULTS
Among 1405 women (median [IQR] age, 60 [52-68] years) included in the intention-to-treat analysis, 708 were randomized to the SLNB group, and 697 were randomized to the no axillary surgery group. Overall, the median (IQR) tumor size was 1.1 (0.8-1.5) cm, and 1234 patients (87.8%) had estrogen receptor-positive ERBB2 (formerly HER2 or HER2/neu), nonoverexpressing BC. In the SLNB group, 97 patients (13.7%) had positive axillary nodes. The median (IQR) follow-up for disease assessment was 5.7 (5.0-6.8) years in the SLNB group and 5.7 (5.0-6.6) years in the no axillary surgery group. Five-year distant DDFS was 97.7% in the SLNB group and 98.0% in the no axillary surgery group (log-rank P = .67; hazard ratio, 0.84; 90% CI, 0.45-1.54; noninferiority P = .02). A total of 12 (1.7%) locoregional relapses, 13 (1.8%) distant metastases, and 21 (3.0%) deaths were observed in the SLNB group, and 11 (1.6%) locoregional relapses, 14 (2.0%) distant metastases, and 18 (2.6%) deaths were observed in the no axillary surgery group.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, omission of axillary surgery was noninferior to SLNB in patients with small BC and a negative result on ultrasonography of the axillary lymph nodes. These results suggest that patients with these features can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02167490.
Topics: Humans; Female; Middle Aged; Sentinel Lymph Node Biopsy; Breast Neoplasms; Prospective Studies; Negative Results; Neoplasm Recurrence, Local; Lymph Nodes; Ultrasonography; Recurrence
PubMed: 37733364
DOI: 10.1001/jamaoncol.2023.3759 -
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 -
Ugeskrift For Laeger Mar 2024Surgical treatment of breast cancer has changed towards less invasive procedures as summarised in this review. Breast conserving surgery (BCS) and radiotherapy (RT) are... (Review)
Review
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.
Topics: Female; Humans; Axilla; Breast Neoplasms; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Mastectomy, Segmental; Sentinel Lymph Node Biopsy
PubMed: 38533870
DOI: 10.61409/V01230033 -
Breast (Edinburgh, Scotland) Apr 2024The results of several studies aiming to tailor early breast cancer treatment to individual risk were released in 2023. Axillary lymph node dissections and radiotherapy...
The results of several studies aiming to tailor early breast cancer treatment to individual risk were released in 2023. Axillary lymph node dissections and radiotherapy may be safely omitted in carefully selected patients. Sustained benefit from adjuvant CDK4/6 inhibitors was observed in high-risk hormone receptor-positive disease and the addition of immunotherapy to neoadjuvant chemotherapy improved pathological response. Continued benefit from perioperative pembrolizumab was reported in patients with triple negative breast cancer, while atezolizumab did not improve the risk of recurrence either pre- or postoperatively. The chance of pregnancy was higher in younger patients attempting to conceive after breast cancer.
Topics: Humans; Female; Breast Neoplasms; Lymph Node Excision; Triple Negative Breast Neoplasms; Neoadjuvant Therapy
PubMed: 38422625
DOI: 10.1016/j.breast.2024.103700 -
JMA Journal Jul 2023Somatostatin analogs are expected to reduce lymphatic leakage. However, whether they can be used after axillary lymphadenectomy is unclear. This study aimed to assess... (Review)
Review
BACKGROUND
Somatostatin analogs are expected to reduce lymphatic leakage. However, whether they can be used after axillary lymphadenectomy is unclear. This study aimed to assess the efficacy and safety of somatostatin analogs in axillary lymphadenectomy for breast cancer patients.
METHODS
We performed a random-effects meta-analysis by searching electronic databases for randomized trials and trial registries until June 2022. The primary outcomes were the volume of drained fluid, the duration of drainage, and seroma incidence. Bias was assessed using the Cochrane Collaboration's tool and the Grading of Recommendations, Assessment, Development, and Evaluations approach.
RESULTS
Six trials (738 participants) and one protocol without results were included. Somatostatin analogs may reduce the volume of drained fluid (mean difference = -22.07 mL, 95% confidence interval [CI] = -42.09 to -2.05; I = 56%) while resulting in a slight-to-no difference in the duration of drainage (mean difference = -0.48 days, 95% CI = -1.43 to 0.46; I = 87%) and seroma incidence (risk ratio = 0.91, 95% CI = 0.61-1.34; I = 55%). The certainty of the evidence was low.
CONCLUSIONS
There was limited evidence supporting somatostatin analogs for lymphorrhea after axillary lymphadenectomy. Multicenter randomized controlled trials are needed to confirm the efficacy and safety of somatostatin analogs after axillary lymphadenectomy.
PubMed: 37560373
DOI: 10.31662/jmaj.2022-0219 -
Critical Reviews in Oncology/hematology Jul 2023The present white paper, referring to the 4th Assisi Think Tank Meeting on breast cancer, reviews state-of-the-art data, on-going studies and research proposals. <70%... (Review)
Review
The present white paper, referring to the 4th Assisi Think Tank Meeting on breast cancer, reviews state-of-the-art data, on-going studies and research proposals. <70% agreement in an online questionnaire identified the following clinical challenges: 1: Nodal RT in patients who have a) 1-2 positive sentinel nodes without ALND (axillary lymph node dissection); b) cN1 disease transformed into ypN0 by primary systemic therapy and c) 1-3 positive nodes after mastectomy and ALND. 2. The optimal combination of RT and immunotherapy (IT), patient selection, IT-RT timing, and RT optimal dose, fractionation and target volume. Most experts agreed that RT- IT combination does not enhance toxicity. 3: Re-irradiation for local relapse converged on the use of partial breast irradiation after second breast conserving surgery. Hyperthermia aroused support but is not widely available. Further studies are required to finetune best practice, especially given the increasing use of re-irradiation.
Topics: Humans; Female; Breast Neoplasms; Mastectomy; Lymph Node Excision; Sentinel Lymph Node Biopsy; Mastectomy, Segmental; Axilla; Lymph Nodes
PubMed: 37244324
DOI: 10.1016/j.critrevonc.2023.104035