Prognostic value of baseline neutrophil/lymphocyte ratio in HER2-positive metastatic breast cancer: exploratory analysis of data from the CLEOPATRA trial.

PURPOSE: This study aimed to evaluate the prognostic role of the baseline neutrophil/lymphocyte ratio (NLR) in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab/pertuzumab. EXPERIMENTAL DESIGN: Data from 780 patients from the CLEOPATRA trial and 248 local patients were collected. Patients were divided into the low and high NLR subgroups by the NLR cutoff value. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) methods were used to control bias. Associations between the NLR and progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: The baseline characteristics of the subgroups were well balanced after PSM and IPTW. A low baseline NLR was associated with better PFS and OS in the trastuzumab and docetaxel (TH) group in the unadjusted, PSM and IPTW models. After IPTW, a low NLR, versus a high NLR, was associated with improved PFS (HR 1.35, 95% CI 1.07-1.70, P = 0.012) and OS (HR 1.47, 95% CI 1.12-1.94, P = 0.006) in the TH group. In patients undergoing treatment with trastuzumab and pertuzumab and docetaxel (THP), a low baseline NLR was also correlated with better PFS but not OS across the three models. After IPTW, a low NLR was associated with better PFS (HR 1.52, 95% CI 1.20-1.93, P = 0.001) than a high NLR in the THP group. Multivariate analyses showed that a low baseline NLR was a predictor for PFS and OS in the TH group and for PFS in the THP group in all three models. In the real-world setting, a low baseline NLR was a predictor of better PFS among patients treated with docetaxel plus trastuzumab without or with pertuzumab in the multivariate model (P = 0.015 and 0.008, respectively). CONCLUSIONS: A low baseline NLR is associated with better survival outcomes among HER2-positive MBC patients receiving docetaxel plus trastuzumab/pertuzumab as first-line therapy.

An ultrasound-based nomogram for predicting axillary node pathologic complete response after neoadjuvant chemotherapy in breast cancer: Modeling and external validation.

INTRODUCTION: The staging and treatment of axillary nodes in breast cancer have become a focus of research. For breast cancer patients with fine-needle aspiration-or core needle biopsy-confirmed positive nodes, axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) is still a standard treatment. However, some patients achieve an axillary pathologic complete response (pCR) after NAC. In this study, the authors sought to construct a model to predict axillary pCR in patients with positive axillary lymph nodes (cN+) breast cancer. METHODS: Data from patients with pathologically proven cN+ breast cancer treated with NAC followed by ALND between January 2010 and April 2019 at the Peking University Cancer Hospital were reviewed. Axillary lymph node status was assessed using ultrasonography before and after NAC. The patient cohort was assigned to the construction and internal validation cohorts according to admission time. A nomogram was constructed based on the significant factors associated with axillary pCR. The predictive performance of the model was externally validated using data from Peking University First Hospital. RESULTS: This study included 953 and 267 patients from Peking University Cancer Hospital and Peking University First Hospital, respectively. In the construction cohort, 39.7% (238 of 600) of patients achieved axillary pCR after NAC. The result of multivariate logistic regression analysis showed that tumor grade, clinical nodal response, NAC regimen, tumor pCR, lymphovascular invasion, and tumor biologic subtype were significant independent predictors of ypN0 (p < 0.05). The areas under the receiver operating characteristic curves for the construction, validation, and independent testing cohorts were 0.87 (95% confidence interval [CI], 0.84-0.90), 0.83 (95% CI, 0.79-0.87), and 0.84 (0.79-0.89), respectively. CONCLUSIONS: A nomogram was constructed to predict the pCR of axillary lymph nodes after NAC for breast cancer. Validation of both the internal and external cohorts achieved good predictive performance, indicating that the model has preliminary clinical application prospects.

CT Radiomics for Predicting Pathological Complete Response of Axillary Lymph Nodes in Breast Cancer After Neoadjuvant Chemotherapy: A Prospective Study.

BACKGROUND: The diagnostic effectiveness of traditional imaging techniques is insufficient to assess the response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC), especially for pathological complete response (pCR). A radiomics model based on computed tomography (CT) could be helpful. PATIENTS AND METHODS: Prospective consecutive breast cancer patients with positive axillary LNs initially were enrolled, who received NAC prior to surgery. Chest contrast-enhanced thin-slice CT scan was performed both before and after the NAC (recorded as the first and the second CT respectively), and on both of them, the target metastatic axillary LN was identified and demarcated layer by layer. Using pyradiomics-based software that was independently created, radiomics features were retrieved. A pairwise machine learning workflow based on Sklearn (https://scikit-learn.org/) and FeAture Explorer was created to increase diagnostic effectiveness. An effective pairwise auto encoder model was developed by the improvement of data normalization, dimensionality reduction, and features screening scheme as well as the comparison of the prediction effectiveness of the various classifiers. RESULTS: A total of 138 patients were enrolled, and 77 (58.7%) in the overall group achieved pCR of LN after NAC. Nine radiomics features were finally chosen for modeling. The AUCs of the training group, validation group, and test group were 0.944 (0.919-0.965), 0.962 (0.937-0.985), and 1.000 (1.000-1.000), respectively, and the corresponding accuracies were 0.891, 0.912, and 1.000. CONCLUSION: The pCR of axillary LNs in breast cancer following NAC can be precisely predicted using thin-sliced enhanced chest CT-based radiomics.

Neoadjuvant endocrine therapy for strongly hormone receptor-positive and HER2-negative early breast cancer: results of a prospective multi-center study.

PURPOSE: For estrogen receptor (ER)-positive breast cancer, neoadjuvant endocrine therapy (NET) has been shown to be as effective as neoadjuvant chemotherapy (NACT). We evaluated the prognostic significance of Preoperative Endocrine Prognostic Index (PEPI). METHODS: We conducted a prospective, multi-center, non-randomized, controlled trial that enrolled postmenopausal early-stage strongly ER-positive (≥ 50%) and HER2-negative breast cancer patients. All patients were given 4-month NET before surgery. The primary objective was to investigate the 5-year recurrence-free survival (RFS) in patients who had PEPI 0-1 or pathological complete response (pCR) without chemotherapy. Patients who had PEPI 0-1 or pCR were recommended to receive adjuvant endocrine therapy only and patients had PEPI ≥ 2 may receive adjuvant chemotherapy at the discretion of the treating physician. RESULTS: A total of 410 patients were included and 352 patients constituted the per-protocol population. Overall, 9 patients (2.5%) had pCR (ypT0/is ypN0), 128 patients (36.4%) had PEPI = 0, and 56 patients (15.9%) had PEPI = 1. After a median follow-up of 60 months (4-104 months), patients who had PEPI 0-1 or pCR showed an improved 5-year RFS [99.5% (95% CI 98.5-99.9%) for PEPI 0-1 or pCR group vs. 93.7% (95% CI 89.6-97.8%) for PEPI ≥ 2 group, P = 0.028]. No survival difference was detected between patients received adjuvant chemotherapy vs. no chemotherapy among PEPI ≥ 2 cases. CONCLUSION: PEPI 0-1 or pCR may be used to define a group of ER-positive and HER2-negative postmenopausal early breast cancer patients with low relapse risk for whom adjuvant chemotherapy can be safely withheld. Studies on the identification and alternative treatment options for endocrine-resistant tumors are warranted. CLINICAL TRIAL REGISTRATION: NCT01613560.

Effect of Local Versus General Anesthesia in Breast-Conserving Surgery on Cancer Recurrence and Cost.

BACKGROUND: The association between the type of anesthesia used and the recurrence of cancer remains controversial. This study aimed to compare the effects of local vs general anesthesia on recurrence-free survival and cost after breast-conserving surgery. MATERIALS AND METHODS: We reviewed the data of 2778 patients who underwent breast-conserving surgery followed by radiation at our center between 1999 and 2014. We analyzed the data of 994 patients with hormone receptor-positive and Her2-negative tumors who underwent breast-conserving surgery without axillary lymph node dissection under local or general anesthesia. Patients were grouped according to whether local or general anesthesia was used for the surgery. RESULTS: Of the 994 patients enrolled in this study, 367 received local anesthesia and 627 patients received general anesthesia. The median follow-up duration for all patients was 93 months. The Kaplan-Meier survival curves did not reveal significant differences between the recurrence-free survival of the two groups, with 5-year recurrence-free survival rates of 96.3% (95% CI, 94.3-98.3%) in the local anesthesia group and 97.3% (95% CI, 95.9-98.7%) in the general anesthesia group. The total cost of hospitalization in the local anesthesia group was significantly lower than that in the general anesthesia group (P <.001). The difference in the cost between the two groups remained significant, irrespective of the type of hospitalization, after excluding 165 patients receiving chemotherapy during their hospitalization. CONCLUSIONS: Our analysis indicated no association between the type of anesthesia used during breast-conserving surgery and the long-term prognosis of breast cancer. However, breast-conserving surgery under local anesthesia may be a less expensive option than that under general anesthesia.

Comparisons of breast conserving therapy versus mastectomy in young and old women with early-stage breast cancer: long-term results using propensity score adjustment method.

PURPOSE: This study aimed to compare the effect of BCT versus mastectomy on the recurrence and survival of different-aged patients, and to investigate whether effects of BCT versus mastectomy on survival of young patients were consistent with those of old patients. METHODS: Data on women with primary invasive breast cancer between 2007 and 2011 were extracted from the institutional database of Breast Center. Disparities in hormone receptor, tumor size, lymph node status, and Her-2 status between BCT and mastectomy groups were adjusted using the propensity score (PS) adjustment method. Patients were divided by age into two groups (≤ 40 years and > 40 years). We assessed proportions of local recurrence (LR), distant disease-free survival (DDFS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) in different-aged groups; this assessment was further stratified by surgical treatment. RESULTS: A total of 2964 patients were included; 565 (19%) were aged ≤ 40 years. In the entire cohort, hazard ratios (HR) of BCT versus mastectomy for DDFS and DFS were 0.56 (P = 0.029) and 0.55 (P = 0.008), respectively. After PS adjustment, there was no significant difference between BCT and mastectomy in LR, DDFS, DFS and BCSS in the young age group. In the old age group, women who underwent BCT exhibited improved DDFS (HR 0.57, 95% CI 0.39-0.84, P = 0.004). CONCLUSIONS: BCT did not significantly affect survival outcomes of young patients with breast cancer. Superior survival of BCT compared to mastectomy was observed only in old patients.

Risk of ipsilateral breast tumor recurrence in primary invasive breast cancer following breast-conserving surgery with BRCA1 and BRCA2 mutation in China.

PURPOSE: BRCA1/2 germline mutations are associated with a high risk of breast cancer, which may preclude mutation carriers from breast-conserving surgery (BCS). This study retrospectively examined whether mutation status influenced the rate of ipsilateral breast tumor recurrence (IBTR) after BCS  in Chinese women. METHODS: Patients who underwent BCS were enrolled in carriers group and non-carriers group according to their BRCA1/2 mutation status in the study. The correlations were analyzed between IBTR incidence and BRCA1/2 mutation. The IBTR cases were further separated into new primary tumor (NP) and true local recurrences (TR). The risk factors of NP were studied in multivariate analysis. RESULTS: 1947 consecutive Chinese women with primary invasive breast cancer were selected. 103 patients were identified as BRCA1/2 mutation carriers and 1844 were non-carriers. BRCA1/2 mutation carriers were younger (P < 0.001) with more often negative HER-2 expression (P = 0.01) and tumor size over 2 cm (P = 0.04) than non-carriers. The median follow-up for all patients was 80 months. The rate of IBTR was 3.9% in mutated carriers and 2.0% in non-carriers, respectively (P = 0.16). In IBTR cases, NP incidence was 3.9% in carrier group and 0.6% in non-carrier group, respectively (P < 0.01). After adjustment of all clinical-pathological factors, BRCA1/2 mutation was the only statistical risk factor of NP incidence (HR = 6.29, P = 0.002), while positive lymph node was nearly statistically significant (HR = 2.70, P = 0.06). CONCLUSIONS: BCS may be a rational option for Chinese BRCA1/2 mutation carriers. High NP incidence in mutation carriers should be paid close attention in the future.

Efficacy of pegfilgrastim to support neoadjuvant dose-dense epirubicin and cyclophosphamide chemotherapy in breast cancer.

PURPOSE: The role of long-acting hematopoietic growth factor in supporting dose-dense chemotherapy and minimizing hematologic toxicity has not been established. We investigated the efficacy and safety of once-per-cycle pegfilgrastim in breast cancer patients receiving neoadjuvant dose-dense epirubicin and cyclophosphamide (ddEC). METHODS: Newly diagnosed stage I to III breast cancer patients received four cycles of ddEC (E, 100 mg/m2 and C, 600 mg/m2 every 2 weeks) and 6 mg of subcutaneous pegfilgrastim on day 2 of each cycle. The primary endpoint was to evaluate the incidence of chemotherapy delay. Secondary endpoints include the incidences of febrile neutropenia (FN) and grade 3/4 neutropenia during the four ddEC cycles. RESULTS: A total of 240 patients were enrolled and 913 ddEC cycles were administered in the study. Chemotherapy delay occurred in 15 patients (6.3% of patients, 95% CI 3.2-9.4%) for 17 cycles (1.9% of cycles, 95% CI 1.0-2.8%). The most frequent cause of chemotherapy delay was transaminase elevation (10 patients, 12 cycles). A total of 12 patients (5.0%, 95% CI 2.2-7.8%) developed 13 episodes of FN. Of the 221 patients that completed four ddEC cycles with pegfilgrastim support, 209 patients (94.6%, 95% CI 91.6-97.6%) had a 100% relative dose intensity (RDI). A RDI ≥ 85% was achieved in 217 of 221 patients (98.2%, 95% CI 96.5-99.9%). Bone pain of any grade was recorded in 85 of 220 evaluable patients (38.6%, 95% CI 32.2-45.0%). CONCLUSIONS: Pegfilgrastim is effective and safe in facilitating four cycles of neoadjuvant ddEC, with low incidences of chemotherapy delay and febrile neutropenia.

99mTc-rituximab as a tracer for sentinel lymph node biopsy in breast cancer patients: a single-center analysis.

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.

A new model to predict risk of nonsentinel lymph node status in Chinese sentinel lymph node-positive patients after neoadjuvant chemotherapy.

There is no previous predictive model to assess risk of nonsentinel lymph node metastases (NSLN) in sentinel lymph node (SLN)-positive breast cancer patients after neoadjuvant chemotherapy (NAT). Our goal was to develop a new predictive model for SLN-positive patients after NAT, and validate this new model. A series of 513 patients with metastases in SLN who received NAT were used to evaluate factors affecting NSLN status. Logistic regression analysis was performed to develop a predictive model, which was validated by a subsequent prospective 138 patients. There were 115 (22.4%) patients with metastases in NSLN followed by axillary lymph node dissection (ALND). Multivariate analysis indicated that tumor (T) stage, number of positive SLN,micrometastases, extracapsular extension (ECE), and clinical response of primary tumor after NAT were significant independent predictors for the NSLN metastases. Area under the curve (AUC) of the model was 0.795 (95% CI, 0.734-0.861). When applied to the prospective series, the model accurately predicted the risk of NSLN disease, AUC was 0.772 (95% CI, 0.653-0.845). We present a new predictive model to assess the risk of NSLN status in Chinese SLN-positive breast cancer patients after NAT. The predictive model performed well in prospective validation but needs to be further studied in external center patients before application to clinical use.

A single-center, randomized, parallel controlled study comparing the efficacy and safety aspects of three anthracycline-based regimens as neoadjuvant chemotherapy in primary breast cancer.

This study aimed to compare the efficacy and safety aspects of three anthracycline-based regimens as neoadjuvant chemotherapy in primary breast cancer. Five-hundred and one patients with clinical stage I-III invasive breast cancer were randomly assigned to receive four cycles of neoadjuvant chemotherapy with either CEFci arm (5-Fu 200 mg/m(2) daily by 24-h continuous infusion and epirubicin 100 mg/m(2) and cyclophosphamide 600 mg/m(2) intravenous bolus on day 1), CEF arm (cyclophosphamide 600 mg/m(2), epirubicin 100 mg/m(2), and 5-Fu 600 mg/m(2) i.v. on day 1), or EC arm (epirubicin 100 mg/m(2) and cyclophosphamide 600 mg/m(2) i.v. on day 1). The pathologic responses to chemotherapy were assessed according to the Miller and Payne grading system (MP). A total of 485 patients were included in the intent-to-treat population. Breast pathologic complete response (pCR) rate was 18.9 % (31/164) in CEFci arm, 15.0 % (24/160) in CEF arm, and 12.4 % (20/161) in EC arm (P = 0.266). MP grading system 4/5 response rate was significantly higher in CEFci arm than that in CEF arm and EC arm (44.5, 31.3 and 27.3 %, respectively, P = 0.003). There was no significant difference on grade III/IV neutropenia among three arms (P = 0.538), but thrombocytopenia, decreased hemoglobin, and elevated aminotransferase appeared to be observed more in CEFci arm (P = 0.040, 0.059, and 0.073, respectively). CEFci did not reach a higher pCR rate compared with CEF or EC in patients with primary breast cancer. The potential advantage of CEFci in improving pathologic response still requires further research. The accompanied hematologic and biochemical toxicities, and the catheter-related complications should also be noted.

Breast cancer risk in Chinese women with BRCA1 or BRCA2 mutations.

BRCA1/2 mutations represent approximately 5 % of unselected Chinese women with breast cancer. However, the breast cancer risk of Chinese women with BRCA1/2 mutations is unknown. Therefore, the aim of this study was to estimate the age-specific cumulative risk of breast cancer in Chinese women who carry a BRCA1 or BRCA2 mutation. Our study included 1816 unselected Chinese women with breast cancer and 5549 female first-degree relatives of these probands. All probands were screened for BRCA1/2 mutation. The age-specific cumulative risks of BRCA1/2 carriers were estimated using the kin-cohort study by comparing the history of breast cancer in first-degree female relatives of BRCA1/2 carriers and non-carriers. Among the 1816 probands, 125 BRCA1/2 pathogenic mutations were identified (70 in the BRCA1 gene and 55 in the BRCA2 gene). The incidence of breast cancer in the first-degree female relatives of BRCA1/2 mutation carriers was significantly higher (3.7-fold and 4.4-fold for BRCA1 and BRCA2 mutation carriers, respectively) than in non-carriers. The estimated cumulative risks of breast cancer by age 70 years were 37.9 % [95 % confidence interval (CI) 24.1-54.4 %] for BRCA1 mutation carriers and 36.5 % (95 % CI 26.7-51.8 %) for BRCA2 mutation carriers, respectively. Our study suggests that the breast cancer risk of Chinese women with BRCA1/2 mutations appears to be relatively high by the age of 70. Therefore, genetic counseling, enhanced surveillance, and individual preventive strategies should be provided for Chinese women who carry a BRCA1/2 mutation.

Early prediction of pathological outcomes to neoadjuvant chemotherapy in breast cancer patients using automated breast ultrasound.

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.

Efficacy of physical examination, ultrasound, and ultrasound combined with fine-needle aspiration for axilla staging of primary breast cancer.

The aim of this study was to compare the efficacy of physical examination (PE), ultrasound (US), and US combined with fine-needle cytology (US-FNAC) in evaluation of node status before sentinel lymph node biopsy (SLNB) for breast cancer patients. We performed a retrospective study of 3,781 breast cancer patients and calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for PE, US, and US-FNAC, respectively. A total of 3,175 cases were documented as cN0 and 606 as cN1. Abnormal axillary nodes under US were detected in 1,152 cases, among which 821 were proven to have positive nodes by FNAC. The positive FNAC results enabled 11.7% of cN0 patients (373/3,175) to avoid unnecessary SLNB. All 331 cases with abnormal US but negative FNAC results, and the 2,629 cases with normal US underwent SLNB procedure for nodal staging, and metastatic nodes were identified in 745 patients. The sensitivity of PE was 32.2%, with a specificity of 95.5%, a PPV of 83.5%, a NPV of 65%, and an accuracy of 69.3%. The sensitivity, specificity, PPV, NPV, and accuracy of axillary US alone were 58.6, 89.4, 79.6, 75.3, and 76.7%, respectively. Combining axillary US with FNAC resulted in sensitivity, specificity, PPV, NPV, and accuracy of 52.4, 100, 100, 74.8, and 80.3%, respectively. Our study demonstrated that US-FNAC is a feasible and effective triage during axillary staging for newly diagnosed breast cancer patients.

[Impact of response of primary tumor and positive axillary lymph node to neoadjuvant chemotherapy on breast cancer survival].

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.

[Risk factors of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph node ≤ 2].

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.

[Risk factors for non-sentinel lymph node metastasis in patients after 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.

[Safety of omitting axillary lymph node dissection in primary breast cancer patients with negative sentinel lymph nodes].

OBJECTIVE: To explore the safety of omitting axillary lymph node dissection (ALND) in primary invasive breast cancer patients with negative sentinel lymph nodes (SLN). METHODS: Between June 2005 and June 2011, all SLN negative patients omitting ALND were analyzed retrospectively. They were all primary invasive breast cancer patients without clinic cytological evidence of axillary node involvement. SLN biopsy was performed prior to systemic treatment. And the tracer was (99)Tc(m) labeled Rituximab. RESULTS: A total of 1807 eligible patients were enrolled. Their median age was 50 years (21-87). And the median number of SLN was 2. The patients of T1, T2 and T3 were 1069 (59.2%), 712 (39.4%) and 26 (1.4%) respectively. After a median follow-up of 36 months, 14 (0.77%) cases of ipsilateral axillary recurrence were observed. Among them, 10 (0.55%) had single axillary recurrence. Second primary cancer occurred in 22 patients (1.2%). And distant metastases were found in 26 patients (1.4%). The 3-year axillary recurrence rate was 0.7%, disease-free survival 96.4% (95%CI 95.4%-97.4%) and recurrence-free survival 97.1% (95%CI 96.1%-98.1%). CONCLUSION: The omitting of ALND is safe in breast cancer patients with negative SLN.

[Reliability of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression in breast cancer evaluated by immunohistochemistry].

OBJECTIVE: To evaluate the reliability of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression in breast cancer by immunohistochemistry and discuss their influencing factors. METHODS: The pretreatment biopsy specimens were collected from 148 patients (from Beijing Cancer Hospital between 2004 to 2010) with invasive breast cancer. After reslicing and staining (ER:SP1, PR: 1E2, HER-2: 4B5), the status of ER, PR and HER-2 was analyzed by a pathological expert with automated imaging system Ariol MB-8. And their results were compared with the original reports. RESULTS: The concordance rates between original reports and automated image system were ER:76.35%, PR:49.32%, HER-2:63.51% while Kappa values 0.12 (P = 0.020) , 0.18 (P = 0.002) and 0.08 (P = 0.200) respectively. And the concordance rates between expert reports and automated image system were ER:93.92%, PR:81.08% and HER-2:76.35% while Kappa values 0.77 (P < 0.001) , 0.67 (P < 0.001) and 0.32 (P < 0.001) respectively. CONCLUSION: For the expressions of ER, PR and HER-2, the disaccording results of original reports and automated image system may be mainly due to the differences of antibodies, staining methods and interpretations.

[Survival analysis for different molecular subtypes of breast cancers after treatment].

OBJECTIVE: To explore the survival status after treatment for patients with different molecular subtypes of breast cancers. METHODS: A total of 4491 patients with invasive breast cancer from January 2000 to July 2011 were retrospectively recruited to receive pathological verification and treatment at our clinic. According to the immunohistochemical results of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2), they were assigned into 3 groups of HR+/HER2-, HER2+ and HR-/ HER2-. Survival analyses were conducted to examine the effects of molecular subtypes and lymph node status on survival. RESULTS: The 3-year recurrence free survival for HR+/HER2-, HER2+ and HR-/HER2- were 94.9%, 89.5% ane 92.3% respectively. Different molecular subtypes presented different survival patterns (P = 0.0001). The 3-year recurrence-free survival (RFS) for LN+ and LN- was 87.1% and 97.8% respectively. And statistical difference existed (P < 0.01). No difference was detected among three molecular subtypes of LN- (P = 0.102); However, for LN+ patients, HR+/HER2- showed a higher RFS than HER2+ and HR-/HER2 (P = 0.001). CONCLUSION: Different molecular subtypes of breast cancers have varying survival. And lymph node status is probably an important prognostic factor.