Liling Zhu

Which nomogram is best for predicting non-sentinel lymph node metastasis in breast cancer patients? A meta-analysis

To present a systemic review and meta-analysis to evaluate the nomograms developed to predict non-sentinel lymph node (NSLN) metastasis in breast cancer patients. We focused on the six nomograms (Cambridge, MSKCC, Mayo, MDA, Tenon, and Stanford) that are the most widely validated. The AUCs were converted to odds ratios for the meta-analysis. In total, the Cambridge, Mayo, MDA, MSKCC, Stanford, and Tenon models were validated in 2,156, 2,431, 843, 8,143, 3,700, and 3,648 patients, respectively. The pooled AUCs for the Cambridge, MDA, MSKCC, Mayo, Tenon, and Stanford models were 0.721, 0.706, 0.715, 0.728, 0.720, and 0.688, respectively. Subgroup analysis revealed that in populations with a higher micrometastasis rate in the SLNs, the Tenon and Stanford models had a significantly higher predictive accuracy. A meta-regression analysis revealed that the SLN micrometastasis rate, but not the NSLN-positivity rate, was associated with improved predictive accuracy in the Tenon and Stanford models. The performance of the MSKCC and Cambridge models was not influenced by these two factors. All of these prediction models perform better than random chance. The Stanford model seems to be relatively inferior to the other models. The accuracy of the Tenon and Stanford models is influenced by the tumor burden in the SLNs.

Reduced Let-7a Is Associated with Chemoresistance in Primary Breast Cancer

Chemotherapy resistance remains an important problem in the breast cancer clinic. The ability to predict the patients who would respond to a distinct therapy would help to optimize tailored treatment options. miRNAs can mediate a number of genes in response to drug-induced acute cellular stress. Several studies suggest that let-7 miRNA may be involved in the chemosensitivity of cancer cell lines in vitro. However, it is not known whether this phenomenon occurs in clinical breast tumors. The present study showed that lower let-7a expression was associated with epirubicin resistance in primary breast tumors. Moreover, upregulation of let-7a expression sensitized resistant breast tumor cell lines to epirubicin by enhancing cellular apoptosis in vitro. Collectively, these findings indicate that lower expression of let-7a miRNA can induce chemoresistance in breast cancer by enhancing cellular apoptosis and suggest that let-7a may be used as a therapeutic target to modulate epirubicin-based chemotherapy resistance.

Comparative effectiveness study of breast-conserving surgery and mastectomy in the general population: A NCDB analysis

Purpose Recent studies have revealed that breast-conserving surgery (BCS) with radiotherapy (RT) led to better survival than mastectomy in some populations. We compared the efficacy of BCS+RT and mastectomy using the National Cancer Database (NCDB, USA). Methods Non-metastatic breast cancers in the NCDB from 2004–2011 were identified. The Kaplan-Meier method, Coxregression and propensity score analysis were used to compare the overall survival (OS) among patients with BCS+RT, mastectomy alone and mastectomy+RT. Results A total of 160,880 patients with a median follow-up of 43.4 months were included. The respective 8-year OS values were 86.5%, 72.3% and 70.4% in the BCS+RT, mastectomy alone and mastectomy+RT group, respectively (P < 0.001). After exclusion of patients with comorbidities, mastectomy (alone or with RT) remained associated with a lower OS in N0 and N1 patients. However, the OS of mastectomy+RT was equivalent to BCS+RT in N2–3 patients. Among patients aged 50 or younger, the OS benefit of BCS+RT over mastectomy alone was statistically significant (HR1.42, 95% CI 1.16–1.74), but not clinically significant (<5%) in N0 patients, whereas in N2–3 patients, the OS of BCS+RT was equivalent to mastectomy+RT (85.2% vs. 84.8%). The results of the propensity analysis were similar. Conclusions BCS+RT resulted in improved OS compared with mastectomy ± RT in N0 and N1 patients. In N2–3 patients, BCS+RT has an OS similar to mastectomy+RT when patients with comorbidities were excluded. Among patients aged 50 or younger, the OS of BCS+RT is equivalent to mastectomy ± RT.

Axillary web syndrome following secondary breast-conserving surgery: a case report

BackgroundAxillary web syndrome is a cause of significant morbidity in the early postoperative period after axillary surgery.Case presentationA patient developed axillary web syndrome after secondary breast surgery and recovered in 3 weeks through physical therapy and using Aescuven Forte.DiscussionThe pathogenesis of axillary web syndrome is not clear. It is reported that axillary surgery is the main cause. The presented case indicates that tissue injury might be an important cause of axillary web syndrome. Though axillary web syndrome is self-limiting, special physical therapy and Aescuven Forte can shorten the natural duration.ConclusionSecondary breast surgery could cause axillary web syndrome. Physical therapy and Aescuven Forte could shorten the duration of the self-limited morbidity.

Validation and comparison of models to predict non-sentinel lymph node metastasis in breast cancer patients.

Several models for predicting the risk of non‐sentinel lymph node (NSLN) metastasis in breast cancer patients with positive sentinel lymph nodes (SLNs) have been developed. The purpose of this study was to validate and compare these models in Chinese patients. A total of 159 breast cancer patients with positive SLNs treated at our institution were included. Among them, 81 (50.9%) patients had at least one NSLN involvement. The Cambridge, Mou, Mayo, Tenon, MDA, Memorial Sloan‐Kettering Cancer Center (MSKCC), Ljubljana, SNUH, Turkish, Louisville, Stanford, and Saidi models were evaluated and compared using receiver operating characteristic (ROC) curves, calibration plots, and false negative (FN) rates. The Cambridge and Mou models outperformed the others, both with area under the ROC curves (AUCs) of 0.73. The Mayo, Tenon, MDA, MSKCC, Turkish, Ljubljana, SNUH, and Louisville models had AUCs of 0.68, 0.66, 0.66, 0.64, 0.63, 0.62, 0.61, and 0.60, respectively. The Stanford and Saidi models did not present any discriminative capabilities, with AUCs of 0.54 and 0.50, respectively. The Cambridge, MSKCC, and Mayo models were well calibrated. With adjusted thresholds, the Mayo model outperformed the others by classifying the highest proportion of patients (20%) into the low‐risk group. Our study revealed that the Cambridge and Mou models performed well in Chinese patients. The ROC curves, calibration plots, and FN rates should be used together for the accurate evaluation of prediction models. Selection of these models should be based on the clinicopathological features of the targeted population. The models specifically designed for patients with micrometastases or macrometastases of SLNs are needed in the future. (Cancer Sci 2012; 103: 274–281)

HER-2 positive breast cancer is associated with an increased risk of positive cavity margins after initial lumpectomy

BackgroundThe effect of breast cancer subtype on margin status after lumpectomy remains unclear. This study aims to determine whether approximated breast cancer subtype is associated with positive margins after lumpectomy, which could be used to determine if there is an increased risk of developing local recurrence (LR) following breast-conserving surgery.MethodsWe studied 1,032 consecutive patients with invasive cancer who received lumpectomies and cavity margin (CM) assessments from January 2003 to November 2012. The following data were collected: patient age, cT stage, pT stage, grade, status of CM, lymph node status, menopausal status, ER, PR, HER-2, and Ki67, as well as the presence of extensive intraductal component (EIC) and lymphovascular invasion (LVI). A χ2 test was used to compare categorical baseline characteristics. Univariate and multivariate logistic regression analyses were performed to evaluate associations between pathologic features of CM status. Kaplan-Meier actuarial cumulative rates of LR (ipsilateral in-breast) were calculated.ResultsA total of 7,884 pieces of marginal tissue were collected from 1,032 patients, and 209 patients had positive CMs. Of the patients tested, 52.3% had luminal A subtype, 14.9% were luminal B, 12.8% were luminal-HER-2, 8.1% were HER-2 enriched, and 11.8% were triple negative. Univariate analysis showed that EIC (P <0.001), LVI (P = 0.026), pN stage (N1 vs. N0: P = 0.018; N3 vs. N0: P <0.001), and luminal B (P = 0.001) and HER-2 (P <0.001) subtypes were associated with positive CMs. Multivariable analysis indicated that only EIC (P <0.001), pN stage (P = 0.003), and HER-2 subtype (P <0.001) were significantly correlated with positive CMs. On multivariable analysis, HER-2 subtype was an independent prognostic factor in LR (P = 0.031).ConclusionsThe HER-2 subtype was the predictive factor most associated with positive CMs and an independent prognostic factor for LR. This result suggests that the increased risk of LR in HER-2 breast cancer is due to an increased microscopic invasive tumor burden, which is indicated by margin status after lumpectomy.

Benign Phyllodes Tumor of the Breast Diagnosed After Ultrasound-Guided Vacuum-Assisted Biopsy: Surgical Excision or Wait-and-Watch?

BackgroundThe role of tumor-free resection in the treatment of benign phyllodes tumors (PTs) is still unknown. Ultrasound-guided vacuum-assisted biopsy (UGVAB) has been used for complete removal of benign breast lesions. This retrospective study aimed to compare the risk of relapse between patients with benign PT who undergo UGVAB and those who receive surgical excision (SE).MethodsBenign PT patients with a pathology diagnosis who had received treatment between 2005 and 2013 at the authors’ hospital were identified. The patients who received UGVAB did not receive any SE. In the SE group, wide local excision or mastectomy was performed when appropriate. The Kaplan–Meier curve and Cox proportional hazards regression were used to analyze and compare the relapse-free survival (RFS) between the patients in the two groups.ResultsThe study enrolled 225 female patients with benign PT. The patients in the UGVAB group (n = 108) had significantly smaller tumors, more fibroadenoma, a higher body mass index (BMI), and a lower Breast Imaging-Reporting and Data System classification than the patients in the SE group (n = 117). The 5-year cumulative RFS was 81.6 and 88.7 % (p = 0.11) respectively for the patients receiving UGVAB and SE during a median follow-up period of 35.5 months. After adjustment for age, tumor size, BMI, or presence of fibroadenoma, treatment (UGVAB vs. SE) was not associated with increased risk for relapse events (hazard ratio 0.34; 95 % confidence interval 0.08–1.43; p = 0.14). No distant metastasis or death events occurred.ConclusionsThe patients with benign PT who received UGVAB alone did not have a significantly more compromised RFS than those who underwent SE. A prospective, randomized study is needed to confirm this observation.

Breast-conserving Surgery Rates in Breast Cancer Patients With Different Molecular Subtypes: An Observational Study Based on Surveillance, Epidemiology, and End Results (SEER) Database.

AbstractThis study used the Surveillance, Epidemiology, and End Results database to compare breast-conserving surgery (BCS) rates across patients with different molecular subtypes.We identified female breast cancer patients who were diagnosed between 2010 and 2012 using the Surveillance, Epidemiology, and End Results database. Patients without available critical clinicopathological information were excluded. The chi-square test and logistic regression analysis were used to investigate factors associated with BCS.This study identified 85,415 T1–2N0–3M0 breast cancer patients. Among the patients with HR+/HER2−, HR+/HER2+, HR−/HER2+, and HR−/HER2− diseases, 63.5% (38,823/61,142), 51.2% (4850/9473), 43.2% (1740/4030), and 55.7% (6000/10,770), respectively, received BCS (P < 0.01). Patients with HR−/HER2+ (odds ratio 0.58; 95% confidence interval, 0.54–0.62) disease were significantly less likely to receive BCS than patients with HR+/HER2− disease after adjustment for T-stage, N-stage, age, tumor grade, county type, and race. Differences in BCS rates between the HR+/HER2− and HR−/HER2+ subgroups were 29.1%, 14.0%, 10.1%, 8.5%, and 0.2% in patients with tumor sizes <10 mm, 10 to 20 mm, 20 to 30 mm, 30 to 40 mm, and 40 to 50 mm, respectively. Differences in BCS rates between the HR+/HER2− and HR−/HER2+ subgroups were 20.3% and 5.7% in node-negative and node-positive patients, respectively. BCS rates in patients with grades I, II, and III tumors in the HR+/HER2− and HR−/HER2+ subgroups were 72.2% and 34.6%, 62.7% and 42.3%, and 54.7% and 43.4%, respectively.Our study demonstrated that BCS rates varied significantly across molecular subtypes, especially in patients with lower tumor burden. HR+/HER2− and HR−/HER2+ patients exhibited the highest and lowest BCS rates, respectively.

Nipple sparing mastectomy in breast cancer patients and long-term survival outcomes: An analysis of the SEER database

Purpose To determine the prevalence of nipple-sparing mastectomy (NSM) and its long-term survival outcomes in breast cancer patients. Method We used the Surveillance, Epidemiology, and End Results database and identified 2,440 breast cancer patients who received NSM during 1998–2013. We used chi-square and binary logistic regression to identify factors associated with the use of radiotherapy after NSM. We used Kaplan-Meier analysis to estimate cancer-specific survival (CSS) and overall survival (OS). We used the log-rank test and Cox regression to identify factors associated with CSS and OS. Results The median age of the population was 50 years. There were 725 (29.7%), 1064 (43.6%) and 651 (26.7%) patients who had Tis, T1 and T2-3 disease and 1943 (79.6%), 401 (16.4%) and 96 (3.9%) patients who had N0, N1 and N2-3 disease, respectively. The rates of RT use were 61.4%, 39.6% and 10.9% in patients with N2-3 disease, N1 or T3/N0 disease and Tis/T1-2N0 disease, respectively. Elderly age, African American race, and higher T-stage and N-stage were associated with receiving radiotherapy. For patients diagnosed between 1998–2010 (N = 763), the median follow-up was 69 months. The 5- and 10-yr CSS were 96.9% and 94.9%, respectively. The 5- and 10-yr OS were 94.1% and 88.0%, respectively. Ethnicity, T-stage and N-stage were factors independently associated with CSS, and age and T-stage were factors independently associated with OS. Conclusions The use of NSM has increased, and it is oncologically safe for breast cancer patients.

The Extent of Axillary Surgery Is Associated With Breast Cancer-specific Survival in T1-2 Breast Cancer Patients With 1 or 2 Positive Lymph Nodes: A SEER-Population Study.

AbstractThis study aimed to compare the breast cancer-specific survival (BCSS) of a nonclinical trial population of T1–2 breast cancer patients with 1 to 2 positive lymph nodes who received breast-conserving surgery and either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND).We used the Surveillance, Epidemiology and End Results (SEER) database to identify 17,028 patients with a median follow-up of 7.1 years. We assigned the patients into a SLNB-cohort (⩽5 nodes) and an ALND-cohort (>5 nodes) based on the number of removed lymph nodes. We used Kaplan-Meier analysis to estimate the cumulative BCSS and used Cox-regression analysis to study the risk factors. We also performed subgroup analysis by the patients’ age and hormonal receptor (HR) status.The cumulative BCSS and Overall Survival (OS) of the entire population were 94.4% and 91.4% at 5 years and 88.2% and 79.9% at 10 years, respectively. Axillary surgery (ALND vs SLNB) had no association with BCSS when adjusted for stage, HR status, tumor grade, or other factors. In subgroup analysis by age and HR status, ALND was associated with a significantly improved BCSS relative to SNLB (HR = 0.70, HR = 0.026, 95% confidence interval 0.51–0.96) only in patients younger than 50 years with HR– disease (N = 1281), but not in other subgroup of patients.In early-stage breast cancer patients with limited lymph node metastasis, ALND had better BCSS than SLNB only in patients younger than 50 years and with HR– disease. More studies are needed to confirm our findings.