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.

Targeted Axillary Dissection with 125I Seed Placement Before Neoadjuvant Chemotherapy in a Danish Multicenter Cohort.

BACKGROUND: Targeted axillary dissection (TAD), with marking of the metastatic lymph node before neoadjuvant chemotherapy (NACT), is increasingly used for breast cancer axillary staging. In the case of axillary pathological complete response (ax-pCR), axillary lymph node clearance can be omitted. Several marking methods exist, most using re-marking before surgery. Feasibility, learning curve, and identification rate (IR) vary. Marking with 125I seed before NACT makes re-marking at surgery redundant, possibly increasing feasibility and IR. Here, TAD with 125I seed placed before NACT is evaluated in a Danish multicenter cohort. METHODS: Patients staged with 125I TAD in Denmark between 1 January 2016 and 31 August 2021 were included. Patients were identified in radioactivity-emitting implant registries at the radiology departments and from the Danish Breast Cancer Group database. Data were extracted from patients' medical records. Information on patient/tumor characteristics, 125I seed activity, marking period, TAD success, number of sentinel nodes (SNs), the histopathological status of excised nodes, and whether the marked lymph node (MLN) was an SN were registered. RESULTS: 142 patients were included. The IR of the MLN was 99.3%, and the IR of the SLNB was 91.5%. TAD success was 91.5%. Minor challenges in marking or removal of the MLN were noted in three patients. In 72.3% of the patients, the MLN was a sentinel node. Overall, 40.8% had axillary pCR. CONCLUSION: TAD with 125I seed marking before NACT is feasible without re-marking at surgery and with only minor surgical challenges. The IR is high. Staging with TAD spares 41% of breast cancer patients an axillary dissection.

Comparing Methods for Targeted Axillary Dissection in Breast Cancer Patients: A Nationwide, Retrospective Study.

BACKGROUND: Several techniques exist for performing targeted axillary dissection (TAD) after neoadjuvant chemotherapy with the removal of the sentinel node and a marked metastatic lymph node (LN). Two-step methods include coil-marking of the metastatic LN at diagnosis and re-marking with an intraoperatively identifiable marker before surgery. Because nondetection of the marked lymph node (MLN) warrants axillary clearance and many patients achieve axillary pathological complete response (ax-pCR), the success of TAD is crucial. We compare various two-step TAD methods in a Danish national cohort. METHODS: We included patients who received two-step TAD between January 1, 2016 and August 31, 2021. Patients were identified from the Danish Breast Cancer Group database and cross-checked with locally accessible lists. Data were extracted from the patient's medical files. RESULTS: We included 543 patients. In 79.4%, preoperative, ultrasound-guided re-marking was possible. Nonidentification of the coil-marked LN was more likely in patients with ax-pCR. The second markers used were hook-wire, iodine seeds, or ink marking on the axillary skin. Of patients with successful secondary marking, the MLN identification rate (IR) was 91%, and the sentinel node (SN) IR was 95%. Marking with iodine seeds was significantly more successful than ink marking with an odds ratio of 5.34 (95% confidence interval 1.62-17.60). The success rate of the complete TAD with the removal of MLN and SN was 82.3%. CONCLUSIONS: With two-step TAD, nonidentification of the coiled LN before surgery is frequent, especially in patients with ax-pCR. Despite successful remarking, the IR of the MLN at surgery is inferior to one-step TAD.

Early postnatal BMI adaptation is regulated during a fixed time period and mainly depends on maternal BMI.

In the present study, we investigated whether there are critical time periods which influence the course of BMI during the first 6 years of life. From 5,433 children who participated in preschool examinations those 212 children were selected who crossed the BMI percentiles as a result of an extreme postnatal BMI rise (from <10th to 90th percentile) or fall (from >90th to <10th percentile) or who have persistently low or high BMI both at birth and at the age of 6 years. Forty children with a BMI close to the 50th percentile both at birth and age 6 years were selected to serve as controls. The courses of weight and height during the first 6 years of age were assessed and BMI was calculated. To identify influences connected with BMI development, we investigated genetic, social, nutritional, and other factors proceeding from the mother during pregnancy. Finally completed data sets of 57 children were available. Our study shows that during two critical time periods a significant move toward low or high BMI takes place among the groups: in early infancy from ~0.5 to 1.5 years and again from 5 to 6 years. At the age of 1.5 years the final state of BMI is already fixed in all study groups. Mothers of overweight 6-year-old children are overweight, whereas mothers of underweight 6-year-old children have a below-normal BMI. All other investigated factors only had a minor influence on postnatal BMI development. We conclude that postnatal BMI development follows a fixed genetic program and is mainly programmed by maternal metabolism.