Shunrong Li

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.

Comparison of ER/PR and HER2 statuses in primary and paired liver metastatic sites of breast carcinoma in patients with or without treatment

PurposeThe aim of this study was to determine whether estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor type 2 (HER2) statuses between primary tumors and paired liver metastatic localizations of breast carcinoma were modified by treatment or during the natural metastatic process.MethodsER, PR, and HER2 expressions were analyzed on paired tissue specimens taken from the primary and the liver metastatic tumors in breast cancer patients. The first group included 46 women who presented with T1–T4, N0–N3, M0 breast carcinoma when first diagnosed and were treated by neoadjuvant therapy or directly underwent surgery, then received postoperative treatment and developed liver metastasis several months/years later. The second group included 12 patients with liver metastatic breast carcinoma when first diagnosed for breast cancer. HER2 status was determined by immunohistochemistry as well as fluorescence in situ hybridization.ResultsAmong the 46 patients in the first group, the ER/PR and HER2 statuses (when considered as a whole histological subtype) were changed between primary tumor and liver metastatic lesions in 12 patients (26.1%). While ER and PR status were modified in 14 (30.4%) and 25 (54.3%) patients, respectively, there were only 5 (10.9%) cases showed a discrepancy in the HER2 status. In the second group, the ER/PR and HER2 statuses (when considered as a whole subtype) were consistent between primary and liver metastatic tumor in 10 of 12 (83.3%) patients. ER, PR, and HER2 statuses were modified in 0 of 12 (0%), 4 of 12 (33.3%), and 1 of 12 (8.3%) cases, respectively.ConclusionsER/PR and HER2 statuses between primary and liver metastatic lesions of breast carcinoma can be modified after treatment but are stable in most cases during the natural metastatic process.

A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients: a retrospective cohort study.

BackgroundIn premenopausal women, endocrine adjuvant therapy for breast cancer primarily consists of tamoxifen alone or with ovarian suppressive strategies. Toremifene is a chlorinated derivative of tamoxifen, but with a superior risk-benefit profile. In this retrospective study, we sought to establish the role of toremifene as an endocrine therapy for premenopausal patients with estrogen and/or progesterone receptor positive breast cancer besides tamoxifen.MethodsPatients with early invasive breast cancer were selected from the breast tumor registries at the Sun Yat-Sen Memorial Hospital (China). Premenopausal patients with endocrine responsive breast cancer who underwent standard therapy and adjuvant therapy with toremifene or tamoxifen were considered eligible. Patients with breast sarcoma, carcinosarcoma, concurrent contralateral primary breast cancer, or with distant metastases at diagnosis, or those who had not undergone surgery and endocrine therapy were ineligible. Overall survival and recurrence-free survival were the primary outcomes measured. Toxicity data was also collected and compared between the two groups.ResultsOf the 810 patients reviewed, 452 patients were analyzed in the study: 240 received tamoxifen and 212 received toremifene. The median and mean follow up times were 50.8 and 57.3 months, respectively. Toremifene and tamoxifen yielded similar overall survival values, with 5-year overall survival rates of 100% and 98.4%, respectively (p = 0.087). However, recurrence-free survival was significantly better in the toremifene group than in the tamoxifen group (p = 0.022). Multivariate analysis showed that recurrence-free survival improved independently with toremifene (HR = 0.385, 95% CI = 0.154-0.961; p = 0.041). Toxicity was similar in the two treatment groups with no women experiencing severe complications, other than hot flashes, which was more frequent in the toremifene patients (p = 0.049). No patients developed endometrial cancer.ConclusionToremifene may be a valid and safe alternative to tamoxifen in premenopausal women with endocrine-responsive breast cancer.

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.

Cavity margins and lumpectomy margins for pathological assessment: Which is superior in breast-conserving surgery?

PURPOSE This prospective cohort study aimed to compare the efficacy of cavity margins (CMs) and lumpectomy margins (LMs) for pathological assessment in breast-conserving surgery. METHODS We assessed the CMs and LMs of 163 breast cancer patients during breast-conserving surgery. We compared and analyzed the positivity rates of CM and LM. RESULTS The positivity rate of CM at the case level and individual margin level was 30.7% and 8.0%, respectively. The positivity rate of LM was 12.3%, 33.1%, and 45.4% at the case level and 1.8%, 6.2%, and 9.1% at the individual margin level, when we used the National Surgical Adjuvant Breast and Bowel Project criteria (ink-free), 1 mm-free criteria and 2 mm-free criteria, respectively. The positivity rate of LM with 1 mm-free criteria was similar to that of CM. Delivery of neoadjuvant chemotherapy increased the positivity rate of CM (50.0% versus 25.2%; P < 0.01) but not LM (41.6% versus 30.7%; P > 0.05) at the case level, whereas the positivity rate of CM and LM both increased after neoadjuvant chemotherapy at the margin level (CMs: 15.5% versus 5.6%, P < 0.001; and LMs: 10.7% versus 4.9%, P < 0.001). In univariate and multivariate analysis, delivery of neoadjuvant chemotherapy, higher node-positive stage, and presence of ductal carcinoma in situ component were correlated with positive CM, whereas positive human epidermal growth factor receptor 2 status and higher node-positive stage were associated with positive LM. CONCLUSIONS Ink-free criteria may be insufficient for LM assessment in breast-conserving surgery, and at least 1 mm width LM is suggested. After the delivery of neoadjuvant chemotherapy, CM assessment should be routinely performed in addition to LM assessment.

Clinical outcomes of 1,578 Chinese patients with breast benign diseases after ultrasound-guided vacuum-assisted excision: recurrence and the risk factors

BACKGROUND The aim of this study was to evaluate the clinical outcomes of 1,578 patients with breast benign diseases after excisions and the risk factors. METHODS AND RESULTS With a median follow-up of 34 months, 69 patients were identified to have recurrence (local recurrence: 45; new lesion: 24). Univariate and multivariate analyses revealed that multiple lesions, a larger lesion size, and a hematoma were independent risk factors for recurrence. Patients with in situ recurrence tended to have fewer lesions and more samples taken per lesion. Patients with new lesions tended to have multiple lesions. After re-excisions, there was no second recurrence events observed in the patients with local recurrence (0/30), whereas 5 patients with new lesions (5/14) were noted to have second recurrence events. CONCLUSIONS Ultrasound-guided vacuum-assisted biopsy for the complete excision of breast benign diseases is safe and effective. Local recurrence and new lesions may have different clinicopathological features and underlying mechanisms. Different management might be given to patients with a different pattern of recurrence.

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.