Search Results (7)

The ACOSOG Z0011 and IBCSG 23-01 trials demonstrated that axillary lymph node dissection (ALND) offers no prognostic benefit in breast cancer patients with clinically negative axillae and low disease burden (one to two positive nodes) on sentinel lymph node biopsy (SLNB). However, uncertainty remains regarding the management of patients with clinically negative axillae (cN0) who are found to have suspicious lymph nodes on imaging that are subsequently confirmed positive by biopsy. The current practice often directs these patients to upfront ALND, potentially exposing them to unnecessary surgical morbidity. This study aimed to assess the role of axillary ultrasound in predicting high axillary nodal burden and guiding surgical management. Using the Alberta Cancer Registry, we identified 107 cN0 breast cancer patients from 2010 to 2017 who underwent preoperative axillary ultrasound with positive biopsy followed by ALND. Our findings reveal that 42% of these patients had low axillary nodal burden on final pathology, meeting Z0011 criteria, and might potentially have avoided ALND. Furthermore, axillary ultrasound findings were not predictive of high axillary burden. These results highlight that many patients undergoing upfront ALND based on positive ultrasound-guided biopsy could benefit from SLNB alone. This supports the 2023 NCCN guidelines advocating for more selective use of ALND to minimize overtreatment and associated morbidity. Full article

Background: Neoadjuvant therapy (NAT) plays a crucial role in breast cancer (BC) management by enabling tumor and nodal downstaging. While axillary lymph node dissection (ALND) remains the standard for patients with residual nodal disease after NAT, its prognostic benefit is debated. Identifying predictors of high-burden residual axillary disease may guide treatment intensification and surgical de-escalation strategies. Methods: We retrospectively analyzed 262 BC patients treated with NAT followed by ALND between 2006 and 2023. Patients were stratified into low- (ypN0-mi-1) and high-burden (ypN2-3) residual axillary disease groups. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of high-burden residual disease. Results: High-burden residual axillary disease was observed in 35.9% of patients. Baseline cN+ status (OR = 7.697, p = 0.013), HR+/HER2− subtype (OR = 3.945, p = 0.003), and larger post-NAT tumor size (OR = 1.043, p < 0.001) were independent predictors. Conclusions: Identifying patients at risk of high-burden residual axillary disease is essential to optimize neoadjuvant strategies. Increasing axillary pathological complete response may reduce the need for ALND, minimizing surgical morbidity without compromising oncological outcomes. Full article

Despite advancements in breast cancer surgery, the decision-making process for axillary treatment remains complex, necessitating new predictors like the tumor size to Ki67 proliferation index ratio. Intraoperative examination of the sentinel lymph node is performed to reduce the risk of a secondary surgery. Several studies have demonstrated that even in the presence of moderate nodal involvement, local disease control can be achieved by omitting axillary lymph node dissection (ALND). The aim of our retrospective study is to compare patients subjected to sentinel lymph node biopsy (SNLB) with or without intraoperative evaluation. This study included patients with breast cancer who underwent breast-conserving surgery and SNLB. Of the 551 patients, 333 (60.4%) underwent an SNLB intraoperative evaluation (SLNB-IE), while 218 (39.6%) underwent sentinel lymph node dissection diagnostic evaluation (SLNB-DE). Our analysis revealed that the tumor size to Ki67 ratio is an independent predictive factor for axillary tumor burden, suggesting its utility in surgical decision-making. A secondary ALND was performed in 2 (0.6%) vs. 7 (2.8%), p = 0.032, and in 1 (0.4%) vs. 4 (2.1%), p = 0.171, excluding patients with T ≥ 2. Surgical time was significantly shorter (p > 0.001) in the SLNB-DE group. According to a multivariate analysis, lesion dimension (OR 1.678; 95%CI 1.019–2.145; WALD:7.588; p = 0.006) and the ratio of lesion dimension to the Ki67 proliferation index (OR 0.08; 95%CI 0.011–0.141; WALD:11.004 p = 0.001) were both predictive factors for a higher axillary tumor burden. A value of 0.425, which is the ratio of tumor dimension to the Ki67 proliferation index, was identified as a predictor of tumor burden in the axilla (sensitivity, 78%; specificity, 87.5%). Intraoperative evaluation of SNLB may be omitted but could be considered in potential candidates for cyclin inhibitor and cN0 therapy with a higher ratio of tumor dimension to the Ki67 proliferation index in order to avoid secondary surgery. Full article

Objectives: In this paper, we investigate the association of glycoprotein 96 (GP96) and androgen receptor (AR) expression with clinicopathological factors, additional axillary lymph node burden, and their potential role in predicting 5-year overall survival (OS) and disease-free survival (DFS) in breast cancer (BC) patients with sentinel lymph node (SLN) involvement. We also explore the prognostic value of the presence of extranodal extension (ENE) in SLN. Methods: We retrospectively enrolled 107 female patients with cT1-T2 invasive BC and positive SLN biopsy. GP96 and AR expression were immunohistochemically evaluated on tissue microarrays constructed from two 2 mm diameter cores of formalin-fixed paraffin-embedded tumor tissues from each patient. ENE in SLN was measured in the highest (HD-ENE) and widest diameter (WD-ENE). Relative GP96 gene expression was determined using real-time quantitative PCR. Results: The analysis revealed ENE in SLN as the strongest predictive factor for non-SLN metastases. Patients with WD-ENE > HD-ENE had a higher risk of non-SLN metastases and worse DFS compared to those with WD-ENE ≤ HD-ENE. High GP96 expression was associated with a greater relative risk for locoregional recurrence but showed no significant impact on OS or DFS. Histological grade 3, extensive intraductal component (EIC), higher lymph node ratio (LNR), and negative AR were associated with worse DFS, while age, histological grade 3, EIC, and higher LNR were independent predictors of OS. GP96 mRNA levels were elevated in BC tissue compared to normal breast tissue. Conclusions: ENE in SLN is the strongest predictor of non-SLN involvement and could also have prognostic significance. While GP96 expression does not influence survival outcomes, AR expression could be used as a valuable biomarker in the follow-up of BC patients. Full article

Background: We aimed to construct an expert knowledge-based Bayesian network (BN) model for assessing the overall disease burden (ODB) in (y)pN1 breast cancer patients and compare ODB across arms of ongoing trials. Methods: Utilizing institutional data and expert surveys, we developed a BN model for (y)pN1 breast cancer. Expert-derived probabilities and disability weights for radiotherapy-related benefit (e.g., 7-year disease-free survival [DFS]) and toxicities were integrated into the model. ODB was defined as the sum of disability weights multiplied by probabilities. In silico predictions were conducted for Alliance A011202, PORT-N1, RAPCHEM, and RT-CHARM trials, comparing ODB, 7-year DFS, and side effects. Results: In the Alliance A011202 trial, 7-year DFS was 80.1% in both arms. Axillary lymph node dissection led to higher clinical lymphedema and ODB compared to sentinel lymph node biopsy with full regional nodal irradiation (RNI). In the PORT-N1 trial, the control arm (whole-breast irradiation [WBI] with RNI or post-mastectomy radiotherapy [PMRT]) had an ODB of 0.254, while the experimental arm (WBI alone or no PMRT) had an ODB of 0.255. In the RAPCHEM trial, the radiotherapy field did not impact the 7-year DFS in ypN1 patients. However, there was a mild ODB increase with a larger irradiation field. In the RT-CHARM trial, we identified factors associated with the major complication rate, which ranged from 18.3% to 22.1%. Conclusions: The expert knowledge-based BN model predicted ongoing trial outcomes, validating reported results and assumptions. In addition, the model demonstrated the ODB in different arms, with an emphasis on quality of life. Full article

Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is a strong prognostic factor in breast cancer (BC). The aim of this study was to investigate whether semiquantitative parameters derived from baseline [¹⁸F]Fluorodeoxyglucose ([¹⁸F]FDG) positron emission computed tomography/computed tomography (PET/CT) could predict pCR after NAC and survival outcomes in patients affected by different molecular subtypes of BC. We retrospectively retrieved patients from the databases of two Italian hospitals (Centre A: University Hospital of Ferrara; Centre B: University of Padua) meeting the following inclusion criteria: (1) diagnosis of BC; (2) history of NAC; (3) baseline [¹⁸F]FDG PET/CT performed before the first cycle of NAC; (4) available follow-up data (response after NAC and survival information). For each [¹⁸F]FDG PET/CT scan, semiquantitative parameters (SUVmax, SUVmean, MTV and TLG) related to the primary tumor (B), to the reference lesion for both axillary (N) and distant lymph node (DN), and to the whole-body burden of disease (WB) were evaluated. Patients enrolled were 133: 34 from centre A and 99 from centre B. Patients’ molecular subtypes were: 9 luminal A, 49 luminal B, 33 luminal B + HER-2, 10 HER-2 enriched, and 32 triple negative (TNBC). Luminal A and HER-2 enriched BC patients were excluded from the analysis due to the small sample size. pCR after NAC was achieved in 47 patients (41.2%). [¹⁸F]FDG PET/CT detected the primary tumor in 98.3% of patients and lymph node metastases were more frequently detected in Luminal B subgroup. Among Luminal B patients, median SUVmean_B values were significantly higher (p = 0.027) in responders (7.06 ± 5.9) vs. non-responders (4.4 ± 2.1) to NAC. Luminal B + HER-2 non-responders showed a statistically significantly higher median MTV_B (7.3 ± 4.2 cm³ vs. 3.5 ± 2.5 cm³; p = 0.003) and TLG_B (36.5 ± 24.9 vs. 18.9 ± 17.7; p = 0.025) than responders at baseline [¹⁸F]FDG PET/CT. None of the semiquantitative parameters predicted pCR after NAC in TNBC patients. However, among TNBC patients who achieved pCR after NAC, 4 volumetric parameters (MTV_B, TLG_B, MTV_WB and TLG_WB) were significantly higher in patients dead at follow-up. If confirmed in further studies, these results could open up a widespread use of [¹⁸F]FDG PET/CT as a baseline predictor of response to NAC in luminal B and luminal B + HER-2 patients and as a prognostic tool in TNBC. Full article

Background and objectives: With improved diagnostic means of early breast cancer, the percentage of cases with metastasis in axillary lymph nodes has decreased from 50–75% to 15–30%. Lymphadenectomy and sentinel lymph node biopsy are not treatment procedures, as they aim at axillary nodal staging in breast cancer. Being surgical interventions, they can lead to various complications. Therefore, recently much attention has been paid to the identification of non-invasive methods for axillary nodal staging. In many countries, ultrasound is a first-line method to evaluate axillary lymph node status. The aim of this study was to evaluate the prognostic value of ultrasound in detecting intact axillary lymph nodes and to assess the accuracy of ultrasound in detecting a heavy nodal disease burden. The additional objective was to evaluate patients’ and tumor characteristics leading to false-negative results. Materials and Methods: A total of 227 women with newly diagnosed pT1 breast cancer were included to this prospective study conducted at the Breast Surgery Unit, Clinic of Surgery, Hospital of Lithuanian University of Health Sciences Kauno Klinikos, between May 1, 2016, and May 31, 2018. All patients underwent preoperative axillary ultrasound examination. Ultrasound data were compared with the results of histological examination. The accuracy and true-negative rate of ultrasound were calculated. The reasons of false-negative results were analyzed. Results: Of the 189 patients who had normally appearing axillary lymph nodes on preoperative ultrasound (PAUS-negative), 173 (91.5%) patients were also confirmed to have intact axillary lymph nodes (node-negative) by histological examination after surgery. The accuracy and the negative predictive value of ultrasound examination were 84.1% and 91.5%, respectively. In ≥3 node-positive cases, the accuracy and the negative predictive value increased to 88.7% and 98.3%, respectively. In total, false-negative results were found in 8.5% of the cases (n = 16); in the PAUS-negative group, false-negative results were recorded only in 1.6% of the cases (n = 3). The results of PAUS and pathological examination differed significantly between patients without and with lymphovascular invasion (LV0 vs. LV1, p < 0.001) as well as those showing no human epidermal growth factor receptor 2 (HER2) expression and patients with weakly or strongly expressed HER2 (HER2(0) vs. HER2(1), p = 0.024). Paired comparisons revealed that the true-negative rate was significantly different between the LV0 and LV1 groups (91% vs. 66.7%, p < 0.05), and the false-negative rate was statistically significant different between the HER2(0) and HER2(1) groups (10.5% vs. 1.2%, p < 0.05). Evaluation of other characteristics showed both the groups to be homogenous. Conclusions: Negative axillary ultrasound excluded axillary metastatic disease in 91.5% of the patients. PAUS had an accuracy of 88.7% in detecting a heavy nodal disease burden. With the absence of lymphovascular invasion (LV0), we can rely on PAUS examination that axillary lymph nodes are intact (PAUS-negative), and this patients’ group could avoid sentinel lymph node biopsy. Patients without HER2 expression are at a greater likelihood of false-negative results; therefore, the findings of ultrasound that axillary lymph nodes are intact (PAUS-negative results) should be interpreted with caution. Full article