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Based on an estimating model, the aim of our study was to evaluate the axillary lymph node involvement of patients with primary invasive early human epidermal growth factor receptor 2 (HER2)-positive breast cancer before receiving neoadjuvant therapy (NAT). Patients with primary surgery (n = 63) were compared with patients who had received NAT (combined chemo/HER2-targeted antibody therapy) before surgery (n = 152). In patients receiving NAT, a positive N stage was estimated in 73.2 (49.8%) tumors resulting in a conversion (positive N stage-ypNpositive) of 35.5%. In 126 cases with ypN0 stage, a positive N stage was estimated in 41.4%. [ABSTRACT FROM AUTHOR]

Background: miR-491-5p has been reported to regulate the expression of FGFR4 and promote gastric cancer metastasis. Hsa_circ_0001361 was demonstrated to play an oncogenic role in bladder cancer invasion and metastasis by sponging the expression of miR-491-5p. This work aimed to study the molecular mechanism of the effect of hsa_circ_0001361 on axillary response in the treatment of breast cancer. Methods: Ultrasound examinations was performed to evaluate the response of breast cancer patients receiving NAC treatment. Quantitative real-time PCR, IHC assay, luciferase assay and Western blot were performed to analyze the molecular interaction between miR-491, circRNA_0001631 and FGFR4. Results: Patients with low circRNA_0001631 expression had a better outcome after NAC treatment. The expression of miR-491 was remarkably higher in the tissue sample and serum collected from patients with lower circRNA_0001631 expression. On the contrary, the FGFR4 expression was notably suppressed in the tissue sample and serum collected from patients with lower circRNA_0001631 expression when compared with patients with high circRNA_0001631 expression. The luciferase activities of circRNA_0001631 and FGFR4 were effectively suppressed by miR-491 in MCF-7 and MDA-MB-231 cells. Moreover, inhibition of circRNA_0001631 expression using circRNA_0001361 shRNA effectively suppressed the expression of FGFR4 protein in MCF-7 and MDA-MB-231 cells. Up-regulation of circRNA_0001631 expression remarkably enhanced the expression of FGFR4 protein in MCF-7 and MDA-MB-231 cells. Conclusion: Our study suggested that the up-regulation of hsa_circRNA-0001361 could up-regulate the expression of FGFR4 via sponging the expression of miR-491-5p, resulting in the alleviated axillary response after neoadjuvant chemotherapy (NAC) in breast cancer.

Background: One potential benefit of neoadjuvant therapy (NAT) in node-positive, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) patients is axillary downstaging to avoid axillary dissection. Objective: The aim of this study was to evaluate axillary response to NAT with chemotherapy (NCT) or endocrine therapy (NET) and identify potential predictors of response. Methods: A prospectively collected database was queried for node-positive, ER+, HER2− breast cancer patients treated with NAT and surgery from January 2011 to September 2020. Axillary response was categorized into pathologic complete response (pCR) versus no pCR, and was correlated to demographic and clinicopathologic parameters in a logistic regression model. Results: A cohort of 176 eligible patients was identified and 178 breast cancers were included in the study. The overall axillary pCR rate was 12.3% (22/178). NCT and NET achieved response rates of 13.9% (19/137) and 7.3% (3/41), respectively (p = 0.232). A significantly higher axillary pCR rate was identified in patients with clinical stage II at diagnosis (12/60, 20%) compared with stage III (10/118, 8.4%; p = 0.03). NET patients with ypN0 were younger and were treated for a longer period of time (>6 months). Completion axillary dissection was omitted in the majority (73.7%) of NCT patients achieving axillary pCR. Conclusions: For patients with node-positive, ER+, HER2− breast cancer, a lower burden of disease at the time of diagnosis (stage II) is associated with a significantly higher axillary pCR, enabling those patients to be spared axillary dissection. Further studies are necessary to define the role of genomic profiling in predicting axillary response. [ABSTRACT FROM AUTHOR]

Background: To develop a convenient modality to predict axillary response to neoadjuvant chemotherapy (NAC) in breast cancer patients., Materials and Methods: In this multi-center study, a total of 1019 breast cancer patients with biopsy-proven positive lymph node (LN) receiving NAC were randomly assigned to the training and validation groups at a ratio of 7:3. Clinicopathologic and ultrasound (US) characteristics of both primary tumors and LNs were used to develop corresponding prediction models, and a nomogram integrating clinicopathologic and US predictors was generated to predict the axillary response to NAC., Results: Axillary pathological complete response (pCR) was achieved in 47.79% of the patients. The expression of estrogen receptor, human epidermal growth factor receptor -2, Ki-67 score, and clinical nodal stage were independent predictors for nodal response to NAC. Location and radiological response of primary tumors, cortical thickness and shape of LNs on US were also significantly associated with nodal pCR. In the validation cohort, the discrimination of US model (area under the curve [AUC], 0.76) was superior to clinicopathologic model (AUC, 0.68); the combined model (AUC, 0.85) demonstrates strong discriminatory power in predicting nodal pCR. Calibration curves of the nomogram based on the combined model demonstrated that substantial agreement can be observed between the predictions and observations. This nomogram showed a false-negative rates of 16.67% in all patients and 10.53% in patients with triple negative breast cancer., Conclusion: Nomogram incorporating routine clinicopathologic and US characteristics can predict nodal pCR and represents a tool to aid in treatment decisions for the axilla after NAC in breast cancer patients., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Incorporating dual human epidermal growth factor receptor 2 (HER2) blockade into neoadjuvant systemic therapy (NST) led to higher response in patients with HER2‐positive breast cancer. However, axillary response to treatment regimens, including single or dual HER2 blockade, in patients with clinically node‐positive breast cancer remains uncertain. Our study aimed to examine the pathologic axillary response according to the type of NST, that is, single or dual HER2 blockade. In our study, 546 patients with clinically node‐positive, HER2‐positive breast cancer who received NST followed by axillary surgery were retrospectively selected and divided into three groups: chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab. The primary outcome was the axillary pathologic complete response (pCR). Among 471 patients undergoing axillary lymph node dissection, the axillary pCR rates were 43.5%, 74.5% and 68.8% in patients who received chemotherapy alone, chemotherapy + trastuzumab and chemotherapy + trastuzumab with pertuzumab, respectively. There was no difference in axillary pCR rates between patients who received single or dual HER2 blockade (P =.379). Among patients receiving chemotherapy + trastuzumab, patients without breast pCR had the greatest risk for residual axillary metastases (relative risk, 9.8; 95% confidence interval, 3.2‐14.9; P <.0001). In conclusion, adding trastuzumab to chemotherapy increased the axillary pCR rate in patients with clinically node‐positive, HER2‐positive breast cancer; furthermore, dual HER2‐blockade with trastuzumab and pertuzumab did not elevate the axillary response compared with trastuzumab alone. Breast pCR could be a strong predictor for axillary pCR in clinically node‐positive patients treated with HER2‐targeting therapy. What's new? Dual blockade of the human epidermal growth factor receptor 2 (HER2) with trastuzumab and pertuzumab is the preferred option for neoadjuvant systemic therapy (NST) against node‐positive, HER2‐positive breast cancer. Whether this approach effectively improves pathologic complete response (pCR), however, remains unclear. Here, comparison of pCR for single or dual HER2 blockade shows that trastuzumab effectively increases axillary pCR rate in clinically node‐positive, HER2‐positive breast cancer. The addition of pertuzumab to trastuzumab did not further elevate pCR rate. The findings are relevant to decisions regarding axillary surgery in breast cancer patients with pCR after NST with HER2 targeted agents. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to perform a systematic review and meta-analysis to determine the diagnostic performance of current noninvasive imaging modalities for assessment of axillary response after neoadjuvant systemic therapy (NST) in clinically node-positive breast cancer patients. Summary of Background Data: NST can lead to downstaging of axillary lymph node disease. Imaging can potentially provide information about the axillary response to NST and, consequently, tailor the surgical management. Methods: PubMed and Embase were searched for studies that compared noninvasive imaging after NST with axillary surgery outcome to identify axillary response in patients with initial pathologically proven axillary lymph node metastasis. Two reviewers independently screened the studies and extracted the data. A meta-analysis was performed by computing the pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Thirteen studies describing 2380 patients were included for final analysis. Of these patients, 1322 had undergone axillary ultrasound, 849 breast MRI, and 209 whole-body 18F-FDG PET-CT. The overall axillary pathologic complete response rate was 39.5% (941/2380). For axillary ultrasound, the pooled sensitivity, specificity, PPV, and NPV were 65%, 69%, 77%, 50%, respectively. For breast MRI, the pooled sensitivity, specificity, PPV, and NPV were 60%, 76%, 78%, 58%, respectively. For whole-body 18F-FDG PET-CT, the pooled sensitivity, specificity, PPV, and NPV were 38%, 86%, 78%, 49%, respectively. Conclusions: The diagnostic performance of current noninvasive imaging modalities is limited to accurately assess axillary response after NST in clinically node-positive breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: One of the current therapeutic challenges for women with breast cancer receiving neoadjuvant chemotherapy (NAC) is distinguishing women with complete axillary nodal response from those with axillary residual disease to promote a personalized therapeutic strategy including sparing axillary surgery. This study set out to develop a risk scoring system (RSS) for predicting probability of nodal pathological complete response (pCR) in women presenting with cN1 breast cancer who received NAC. Methods: Data of 116 women with cN1 breast cancer who received NAC between January 2009 and December 2013 were abstracted from our prospectively maintained database. A risk model based on factors impacting nodal axillary was developed. Results: The overall nodal conversion rate was 36.2% (42/116). Axillary nodal response was associated with three variables: menopausal status [Odds ratio (OR) = 0.23; 95% confidence interval (CI) 0.09-0.60], the radiological % of breast tumour shrinkage ≥50% (OR = 3.71; 95% CI 1.51-9.10), and negative hormone receptors (ER-, PR-) (OR = 2.41; 95% CI 0.99-5.87). These variables were included in the RSS and assigned scores ranging from 0 to 2. The discrimination of the RSS was 0.78 [95% confidence interval (CI) 0.69-0.86]. A total score of 3 points corresponded to the optimal threshold of the RSS. The diagnostic accuracy was 74.1%. Conclusions: This study shows that the probability of axillary nodal pCR after NAC can be accurately predicted so that women at high probability may be spared of axillary surgery. [ABSTRACT FROM AUTHOR]

Background: miR-491-5p has been reported to regulate the expression of FGFR4 and promote gastric cancer metastasis. Hsa&#95;circ&#95;0001361 was demonstrated to play an oncogenic role in bladder cancer invasion and metastasis by sponging the expression of miR-491-5p. This work aimed to study the molecular mechanism of the effect of hsa&#95;circ&#95;0001361 on axillary response in the treatment of breast cancer., Methods: Ultrasound examinations was performed to evaluate the response of breast cancer patients receiving NAC treatment. Quantitative real-time PCR, IHC assay, luciferase assay and Western blot were performed to analyze the molecular interaction between miR-491, circRNA&#95;0001631 and FGFR4., Results: Patients with low circRNA&#95;0001631 expression had a better outcome after NAC treatment. The expression of miR-491 was remarkably higher in the tissue sample and serum collected from patients with lower circRNA&#95;0001631 expression. On the contrary, the FGFR4 expression was notably suppressed in the tissue sample and serum collected from patients with lower circRNA&#95;0001631 expression when compared with patients with high circRNA&#95;0001631 expression. The luciferase activities of circRNA&#95;0001631 and FGFR4 were effectively suppressed by miR-491 in MCF-7 and MDA-MB-231 cells. Moreover, inhibition of circRNA&#95;0001631 expression using circRNA&#95;0001361 shRNA effectively suppressed the expression of FGFR4 protein in MCF-7 and MDA-MB-231 cells. Up-regulation of circRNA&#95;0001631 expression remarkably enhanced the expression of FGFR4 protein in MCF-7 and MDA-MB-231 cells., Conclusion: Our study suggested that the up-regulation of hsa&#95;circRNA-0001361 could up-regulate the expression of FGFR4 via sponging the expression of miR-491-5p, resulting in the alleviated axillary response after neoadjuvant chemotherapy (NAC) in breast cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V.)

Background: Recently there are efforts to use sentinel lymph node biopsy (SLNB) techniques after neoadjuvant chemotherapy (NAC) to minimize axillary surgery. However, studies have shown higher false negative rates in this scenario, which might result in inaccurate assessment of treatment response and patient prognosis as well as leaving residual disease behind. In this study, we describe the use of reflector-guided excision of the percutaneously biopsied node (PBN) as an aid to conventional SLNB and its predictor of the axillary status after NAC., Patients and Methods: This was a single-institution analysis of patients who underwent axillary fiducial-reflector placement and subsequent SLNB compared with conventional SLNB., Results: Nineteen patients in the reflector group were matched with 19 patients who underwent conventional SLNB (conventional group). The PBN was identified in the SLNB in 19 patients (100%) in the reflector group and in 9 patients (47.3%) in the conventional group (P = .002). In the remaining 10 patients in the conventional group, the PBN was identified in the axillary lymph node dissection specimen in 4 patients (21%) and not identified in 6 patients (31.7%). Among the 38 patients, traditional mapping failed to identify the PBN in 13 patients (34.2%). The PBN was negative in 10 patients (36%) and positive in 18 patients (64%); no additional positive nodes were identified among patients with a negative PBN, correctly reflecting the status of the axilla in 100% of cases., Conclusion: Mapping failure after NAC might compromise SLNB. Reflector-guided excision of the PBN is not only facile and feasible, but more accurately reflects the status of the axilla after NAC., (Copyright © 2018 Elsevier Inc. All rights reserved.)