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Purpose: This study aimed to determine the long-term prognosis of breast cancer patients with 99mTc-rituximab for sentinel lymph node biopsy (SLNB).Methods: A total of 2947 patients with negative sentinel lymph nodes (SLNs) omitting axillary lymph node dissection (ALND), treated between June 2005 and December 2013, were retrospectively analyzed. SLNB was performed prior to adjuvant therapy.Results: After a median follow-up of 62 months, 22 cases of axillary recurrence (AR) were observed. The 5-year AR rate (ARR) was 0.7% [95% confidence interval (CI) 0.3-1.1%] and the 5-year relapse-free survival (RFS) was 95.2% (95% CI 94.4-96.0%). Multivariate analysis showed that abnormal axillary ultrasound with negative fine-needle aspiration (FNA) [hazard ratio (HR) 3.79, 95% CI 1.55-9.28; P = 0.004], not receiving radiotherapy (HR 4.38, 95% CI 1.47-13.05; P = 0.008), and age ≤ 40 years (HR 2.93, 95% CI 1.19-7.20; P = 0.020) were independent risk factors for AR.Conclusions: ARR of SLNB-negative patients with 99mTc-rituximab is low. Abnormal axillary ultrasound with negative FNA, not receiving radiotherapy, and age ≤ 40 years were prognostic factors for higher ARRs. [ABSTRACT FROM AUTHOR]

Many factors (pathological subtype differences, etiology, clinical practice, etc.) may cause ethnic sensitivities in drugs. For drugs approved in one region, their differences among ethnic groups and the potential impacts of such differences on their safety and efficacy must be explained before seeking approvals in another region. Despite potential ethnic sensitivities, if pharmaceutical companies are required to repeat the clinical research and development process in various countries, it will result in waste of resources and delays in drug approval. To address this issue, the International Conference on Harmonization (ICH) published a guideline entitled Ethnic Factors in the Acceptability of Foreign Clinical Data , known as ICH E5, in 1998. With an attempt to offer guidance on the monitoring and research & development (R&D) of innovation drugs, the concept of bridging studies was for the first proposed, which allows the adequate assessment of ethnic differences in safety, efficacy, dosage, or dose regimen of an innovation drug, and meanwhile minimizes the duplication of clinical data in two different regions to speed up the licensing of the drug in the new region. Here we take breast cancer as an example to describe the concept, types, strategies, statistical methods, and clinical practice of bridging studies, focusing on their development in China., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tbcr.amegroups.com/article/view/10.21037/tbcr-21-43/coif). The authors have no conflicts of interest to declare., (2022 Translational Breast Cancer Research. All rights reserved.)

Objective: Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer allows therapy to be individualized. The optimal assessment method has not been established. We investigated the accuracy of automated breast ultrasound (ABUS) to predict pathological outcomes after NAC., Methods: A total of 290 breast cancer patients were eligible for this study. Tumor response after 2 cycles of chemotherapy was assessed using the product change of two largest perpendicular diameters (PC) or the longest diameter change (LDC). PC and LDC were analyzed on the axial and the coronal planes respectively. Receiver operating characteristic (ROC) curves were used to evaluate overall performance of the prediction methods. Youden's indexes were calculated to select the optimal cut-off value for each method. Sensitivity, specificity, positive and negative predictive values (PPV and NPV) and the area under the ROC curve (AUC) were calculated accordingly., Results: ypT0/is was achieved in 42 patients (14.5%) while ypT0 was achieved in 30 patients (10.3%) after NAC. All four prediction methods (PC on axial planes, LDC on axial planes, PC on coronal planes and LDC on coronal planes) displayed high AUCs (all>0.82), with the highest of 0.89 [95% confidence interval (95% CI), 0.83-0.95] when mid-treatment ABUS was used to predict final pathological complete remission (pCR). High sensitivities (85.7%-88.1%) were observed across all four prediction methods while high specificities (81.5%-85.1%) were observed in two methods used PC. The optimal cut-off values defined by our data replicate the WHO and the RECIST criteria. Lower AUCs were observed when mid-treatment ABUS was used to predict poor pathological outcomes., Conclusions: ABUS is a useful tool in early evaluation of pCR after NAC while less reliable when predicting poor pathological outcomes.

Objective: To explore the relationship between response of primary tumor and positive axillary lymph node to neoadjuvant chemotherapy and examine its correlation with breast cancer distant disease-free survival (DDFS)., Methods: The clinical data of 678 needle biopsy proved node positive breast cancer patients on neoadjuvant chemotherapy were analyzed retrospectively., Results: The median follow-up period was 45 (6-143) months. The 4-year DDFS in group A (ypT0/is ypN0),B (ypT0/is ypN+), C (ypT ≥ 1mi ypN0) and D (ypT ≥ 1mi ypN+) were 96.4%, 85.7%, 86.7% and 80.2% respectively. As compared with group A, the relative risk ratios of groups B, C and D were 2.32, 2.09 and 4.07 (P = 0.006).Significant difference existed in DDFS between groups A and B (96.4% vs 85.7%, P = 0.045) and groups A and C (96.4% vs 86.7%, P = 0.040)., Conclusion: Pathological response of both primary tumor and positive axillary node are prognostic and crucial for evaluating the efficacy of neoadjuvant chemotherapy.

Objective: To evaluate the risk factors for non-sentinel lymph node (NSLN) metastasis in patients after neoadjuvant chemotherapy (NCT) so as to develop a new predictive model., Methods: A total of 512 consecutive patients with metastasis in sentinel lymph node (SLN) on neoadjuvant chemotherapy between August 2005 and March 2013 were recruited to evaluate the factors affecting the involvement of NSLN. Logistic regression analysis was performed to construct a predictive model., Results: There were 115 (22.4%) patients with metastasis in NSLN after axillary lymph node dissection. Univariate analysis showed that tumor size, number of positive SLN, hormone receptor (HR), micrometastasis and clinical response of primary tumor after NCT were associated with the involvement of NSLN (P < 0.05). Multivariate analysis indicated that tumor size, number of positive SLN, HR, micrometastasis and clinical response of primary tumor after NCT were significant independent predictors for NSLN metastasis. Area under the curve was 0.779., Conclusion: Tumor size, number of positive SLN, HR, micrometastasis and clinical response of primary tumor after NCT were significant independent predictors for NSLN metastasis in patients after NCT. The new model is to be further validated.

Objective: To explore retrospectively the risk factors of non-sentinel lymph node (NSLN) metastasis in breast cancer patients with sentinel lymph node metastasis ≤ 2 and examine the likelihood of non-sentinel lymph node prediction., Methods: A sentinel lymph node biopsy database containing 455 breast cancer patients admitted between July 2005 and February 2012 at Beijing Cancer Hospital was analyzed retrospectively. The patients had ≤ 2 positive sentinel lymph node and complete axillary lymph node dissection., Results: The SLNS⁺/SLNS ratio (P = 0.001), histological grade (P = 0.075), size of mass (P = 0.023) and onset age (P = 0.074) were correlated with NSLN metastases. Only SLNS⁺/SLNS (OR 0.502 95% CI 0.322-0.7844) , histological grade ratio (histological grade ratio II, III and others vs grade I OR 2.696, 2.102, 3.662) were significant independent predictors for NSLN metastases . The ROC value was 0.62 (0.56, 0.68)., Conclusions: For ≤ 2 positive sentinel lymph nodes of breast cancer, ratio of SLNS⁺/SLNS and histological grading are independent factors affecting NSLN metastases. However, the results remain unsatisfactory for predicting the status of NSLN.

Objective: To determine the predictive ability of biomarkers for responses to neoadjuvant endocrine therapy (NET) in postmenopausal breast cancer., Methods: Consecutive 160 postmenopausal women with T1-3N0-1M0 hormone receptor (HR)-positive invasive breast cancer were treated with anastrozole for 16 weeks before surgery. New slides of tumor specimens taken before and after treatment were conducted centrally for biomarker analysis and classified using the Applied Imaging Ariol MB-8 system. The pathological response was evaluated using the Miller & Payne classification. The cell cycle response was classified according to the change in the Ki67 index after treatment. Multivariable logistic regression analysis was used to calculate the combined index of the biomarkers. Receiver operating characteristic (ROC) curves were used to determine whether parameters may predict response., Results: The correlation between the pathological and cell cycle responses was low (Spearman correlation coefficient =0.241, P<0.001; Kappa value =0.119, P=0.032). The cell cycle response was significantly associated with pre-treatment estrogen receptor (ER) status (P=0.001), progesterone receptor (PgR) status (P<0.001), human epidermal growth factor receptor 2 (Her-2) status (P=0.050) and the Ki67 index (P<0.001), but the pathological response was not correlated with these factors. Pre-treatment ER levels [area under the curve (AUC) =0.634, 95% confidence interval (95% CI), 0.534-0.735, P=0.008] and combined index of pre-treatment ER and PgR levels (AUC =0.684, 95% CI, 0.591-0.776, P<0.001) could not predict the cell cycle response, but combined index including per-treatment ER/PR/Her-2/Ki67 expression levels could (AUC =0.830, 95% CI, 0.759-0.902, P<0.001)., Conclusions: The combined use of pre-treatment ER/PgR/Her-2/Ki67 expression levels, instead of HR expression levels, may predict the cell cycle response to NET.