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.

Self-assembling anticaries mucosal vaccine containing ferritin cage nanostructure and glucan-binding region of S. mutans glucosyltransferase effectively prevents caries formation in rodents.

Anticaries protein vaccines that induce a mucosal immune response are not effective. Therefore, development of effective and convenient anticaries vaccines is a priority of dental research. Here we generated self-assembling nanoparticles by linking the glucan-binding region of Streptococcus mutans glucosyltransferase (GLU) to the N-terminal domain of ferritin to determine whether these novel nanoparticles enhanced the immunogenicity of an anticaries protein vaccine against GLU in rodents. We constructed the expression plasmid pET28a-GLU-FTH and purified the proteins from bacteria using size-exclusion chromatography. BALB/c mice were used to evaluate the ability of GLU-ferritin (GLU-FTH) nanoparticles to induce GLU-specific mucosal and systemic responses. The protective efficiency of GLU-FTH nanoparticles was compared with that of GLU alone or a mixture of GLU and poly(I:C) after administering an intranasal infusion to Wistar rats. The phagocytosis and maturation of dendritic cells (DCs) exposed in vitro to the nanoparticles were assessed using flow cytometry. The GLU-FTH nanoparticle vaccine elicited significantly higher levels of GLU-specific antibodies compared with GLU or a mixture of GLU and poly(I:C). Immunization with GLU-FTH achieved lower caries scores compared with those of the other vaccines. Administration of GLU-FTH nanoparticles enhanced phagocytosis by DCs and their maturation. Thus, self-assembling GLU-FTH is a highly effective anticaries mucosal vaccine that enhanced antibody production and inhibited S. mutans infection in rodents.

Effects of different concentrations and exposure time of sodium hypochlorite on the structural, compositional and mechanical properties of human dentin.

This study evaluated the effects of sodium hypochlorite (NaOCl) with different concentrations and exposure time on the structural, compositional and mechanical properties of human dentin in vitro. Sixty dentin slabs were obtained from freshly extracted premolars, randomly distributed into four groups (n=15), and treated with 1%, 5%, 10% NaOCl and distilled water (control group), respectively, for a total of 60 min. Attenuated total reflection infrared (ATR-IR) spectroscopy, Raman spectroscopy and X-ray diffraction (XRD) were carried out before, 10 min and 60 min after the treatment. Scanning electron microscopy (SEM) and flexural strength test were conducted as well. The results showed that dentins experienced morphological alterations in the NaOCl groups, but not in the control group. Two-way repeated-measures analysis of variance revealed that the carbonate:mineral ratio (C:M), Raman relative intensity (RRI), a-axis, c-axis length and full width at half maximum (FWHM) with the increase of time and concentration in the NaOCl groups were not significantly different from those in the control group (P>0.05). Nevertheless, the mineral:matrix ratio (M:M) increased and the flexural strength declined with the increase of concentration and the extension of time in the NaOCl groups (P<0.05). Additionally, it was found that the M:M and the flexural strength remained unchanged after 1% NaOCl treatment (P>0.05), and the morphology changes were unnoticeable within 10 min in 1% NaOCl group. These results indicated that NaOCl has no significant effects on the inorganic mineral of human dentin; but it undermines and eliminates the organic content concentration- and time-dependently, which in turn influences the flexural strength and toughness of dentins. In addition, an irrigation of 1% NaOCl within 10 min can minimize the effects of NaOCl on the structural and mechanical properties of dentin during root canal treatment.

Effects of Different Concentrations and Exposure Time of Sodium Hypochlorite on the Structural, Compositional and Mechanical Properties of Human Dentin / 华中科技大学学报（医学）（英德文版）

This study evaluated the effects of sodium hypochlorite (NaOC1) with different concentrations and exposure time on the structural,compositional and mechanical properties of human dentin in vitro.Sixty dentin slabs were obtained from freshly extracted premolars,randomly distributed into four groups (n=15),and treated with 1％,5％,10％ NaOC1 and distilled water (control group),respectively,for a total of 60 min.Attenuated total reflection infrared (ATR-IR) spectroscopy,Raman spectroscopy and X-ray diffraction (XRD) were carried out before,10 min and 60 min after the treatment.Scanning electron microscopy (SEM) and flexural strength test were conducted as well.The results showed that dentins experienced morphological alterations in the NaOC1 groups,but not in the control group.Two-way repeated-measures analysis of variance revealed that the carbonate:mineral ratio (C:M),Raman relative intensity (RRI),a-axis,c-axis length and full width at half maximum (FWHM) with the increase of time and concentration in the NaOC1 groups were not significantly different from those in the control group (P＞0.05).Nevertheless,the mineral:matrix ratio (M:M) increased and the flexural strength declined with the increase of concentration and the extension of time in the NaOC1 groups (P＜0.05).Additionally,it was found that the M:M and the flexural strength remained unchanged after 1％ NaOCl treatment (P＞0.05),and the morphology changes were unnoticeable within 10 min in 1％ NaOC1 group.These results indicated that NaOC1 has no significant effects on the inorganic mineral of human dentin;but it undermines and eliminates the organic content concentration-and time-dependently,which in turn influences the flexural strength and toughness of dentins.In addition,an irrigation of 1％NaOCl within 10 min can minimize the effects of NaOC1 on the structural and mechanical properties of dentin during root canal treatment.

[Analysis of associations between molecular subtypes and responses to neoadjuvant chemotherapy in primary breast cancer patients].

OBJECTIVE: To explore the correlations between molecular subtypes and responses to neoadjuvant chemotherapy in primary breast cancer patients. METHODS: The core-needle biopsy specimens were collected from 563 patients undergoing 4-8 cycles of neoadjuvant chemotherapy between January 2001 to January 2009. And immunohistochemical assays were employed to detect the levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 proliferation index simultaneously. Molecular subtypes were divided on the basis of immunohistochemical results. And the associations between molecular subtypes and responses to neoadjuvant chemotherapy were analyzed in 563 patients. RESULTS: The pathological complete response (pCR) rates of patients with hormone receptor-negative/HER2-negative subtype (HR-/HER2-) , HER2-positive subtype (HER2+) and hormone receptor-positive/HER2-negative subtype (HR+/HER2-) were 38.9%, 17.9% and 8.3% respectively. In univariate analysis, there were significant differences in pCR rates among the groups (P < 0.001) . In multivariate analysis, the patients with HER2+ subtype had a significantly higher pCR rate than those with HR+/HER2- subtype (OR = 0.344, P = 0.002) . Whereas the patients with HER2+ subtype had a significantly lower pCR rate than those with HR-/HER2- subtype (OR = 2.453, P = 0.007) . Among HR+/HER2-subtypes, a higher pCR rate was observed in the group of high expression level of Ki-67 proliferation index (Ki-67 ≥ 20%) (P = 0.004) . But no significant differences existed in pCR rates between the group of high expression level of hormone receptor and the group of non-high expression level (P = 0.256) . CONCLUSION: There were correlations between molecular subtypes and responses to neoadjuvant chemotherapy in primary breast cancer patients. Patients of HER2+and HR-/HER2- subtype are more likely to respond to neoadjuvant chemotherapy. Among HR+/HER2-subtypes, those with a high level of Ki-67 proliferation index tend to benefit from neoadjuvant chemotherapy.

[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.

[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.

[Efficacy analysis of THP-containing regimens as neoadjuvant and adjuvant chemotherapy for primary breast cancer].

OBJECTIVE: To evaluate the effect of anthracycline pirarubicin-based regimen in association with different ways of fluorouracil (5-Fu) as neoadjuvant and adjuvant chemotherapy for primary breast cancer. METHODS: Two hundred and eighty-nine primary breast cancer patients who were to be operated, two to eight cycles of pirarubicin in association with cyclophosphamide and 5-Fu (CTF or CTFci regimen) were given before operation. The pathological response rate, effect and its relation with the infusion routes of 5-Fu were analyzed. RESULTS: The overall pathological complete remission (pCR) rate was 28.4%. The median follow-up period was 39 months. The 5-year DFS was 87.6% (95% CI:82.1% to 92.7%), 5-year DDFS was 89.9% (95% CI:84.0% to 95.8%), and overall survival was 99.6%. CTFci (5-Fu, continuous infusion) regimen was superior to CTF regimen in pCR rates (32.3% vs. 20.2%, P = 0.037), and 5-year DDFS were 92.9% and 80.1%, respectively (P = 0.015). The pCR group was superior to non-pCR group in 5-year DDFS (92.4% vs. 85.6%, P = 0. 033). The pCR rate of patients with ER/PR-positive tumor was significantly lower than those of ER/PR-negative (P = 0.004). The 5-year DDFS rates of HER-2 (+) and HER-2(-) groups were 75.0% and 91.9%, respectively (P = 0.043). In the ER/PR-positve group, the 5-year DDFS of CTFci regimen was superior to those of CTF regimen, 91.4% vs. 81.4% (P = 0.047). CONCLUSIONS: CTF/CTFci regimen as neoadjuvant and adjuvant chemotherapy is effective for primary breast cancer. CTFci regimen is superior to CTF regimen in pathological complete response rate and 5-year DDFS. CTFci regimen may do better to ER/PR (+) patients' benefits compared with CTF regimen.

[Morphology-based criteria for ultrasonic assessment of axillary lymph node status in primary breast cancer].

OBJECTIVE: To evaluate the morphology-based criteria for the ultrasonic assessment of axillary lymph node in primary breast cancer. METHODS: A total of 2256 T0-2N0 patients underwent axillary ultrasound preoperatively. Lymph nodes were classified as normal if no node was found or cortex thickness was even and < 3 mm; abnormal, (1) if cortex thickness was even but ≥ 3 mm or (2) focally thickened cortex ≥ 3 mm or (3) fatty hilum was absent. The patients in the abnormal group underwent ultrasound guided fine-needle aspiration (US-FNA). Except for positive lymph nodes, all the others underwent sentinel lymph node biopsy (SLNB). RESULTS: In this series, 692 (30.7%) were pathologically confirmed positive LNs. Among them, 214 (9.5%) were identified by US-FNA. And 361 were abnormal according to the above mentioned criteria. The proportions were 11.6%, 54.8% and 33.5% in Group 1-3 respectively. The sensitivity, specificity, positive and negative predictive values of these criteria alone were 35.8%, 92.8%, 68.7% and 76.6% respectively. CONCLUSION: The present morphology-based criteria for the ultrasonic assessment of lymph node status is both effective and practical in primary breast cancer.

[Morphological changes associated with low-tone hearing loss in guinea pig models of early endolymphatic hydrops].

The present study was to explore the functional and morphological changes in cochleas of guinea pig models of early endolymphatic hydrops. Thirty albino guinea pigs were randomly divided into three groups: control, 4-week model and 8-week model groups. For each group, n = 10. Model groups were operated on the right ears to result in endolymphatic hydrops with the method of slight destruction of endolymphatic sac and duct from extradural posterior cranial fossa approach, and the animals in control group were sham operated. Electrocochleogram recorded by trans-tympanic approach and auditory brainstem response (ABR) were tested in preoperative model groups, control group, 4-week model group and 8-week model group to assess the hearing changes. Histologic morphometry was used to quantify hydrops by testing scala media area (SMA) ratio. Scanning electron microscope was used to assess the changes of cochlea hair cells. The results showed that the summating potential/compound action potential (SP/AP) ratio of electrocochleogram in 4-week model group (0.33 ± 0.14) and 8-week model group (0.43 ± 0.14) increased significantly, compared with that in control group (0.07 ± 0.06). The maximum SMA ratio in 4-week model group (2.64 ± 0.10) and 8-week model group (3.54 ± 0.13) increased significantly, compared with that in control group (1.06 ± 0.08). The results of maximum SMA ratio correlated with SP/AP ratio of electrocochleogram (r = 0.86). The results of hearing threshold of ABR revealed that the operated ears of model groups were higher than the preoperative results at frequencies of 2 kHz and 4 kHz. And the damage of cochlea hair cells in operated ears occurred in apical and subapical turns. These results suggest the increased SP/AP ratio of electrocochleogram can indicate early endolymphatic hydrops. There is low-tone hearing loss in guinea pig models of early endolymphatic hydrops, and it may be associated with the abnormalities of the stereocilia among the outer hair cells in operated ears which occurs in apical and subapical turns.

[Diagnostic value and health economic evaluation of ultrasound-combined fine-needle aspiration cytology in primary breast cancer].

OBJECTIVE: To explore the diagnostic value and health economic evaluation of ultrasound-combined fine-needle aspiration cytology for axillary lymph node status in breast cancer. METHODS: We reviewed retrospectively collected the data from 2503 cases of biopsy-proved breast cancer (T0-2) at our breast center between May 2005 and June 2010. The diagnostic fees of ultrasound-combined fine-needle aspiration cytology and clinical examination were calculated and assessed with cost-minimization analysis. RESULTS: Ultrasound-combined fine-needle aspiration cytology prevented 10.9 percent of the patients with positive clinical findings from unnecessary sentinel lymph node biopsy and achieved a saving of 155.55 RMB per patient. However, only 29.4 percent of the cases were diagnosed with ultrasonographic abnormal axillary nodes. CONCLUSIONS: Ultrasound-combined fine-needle aspiration cytology has great application values. The ultrasonic diagnostic criteria of abnormal axillary nodes should be loosened.

[Clinicopathologic characteristics and prognosis in young Chinese women with breast cancer].

OBJECTIVE: To analyze the clinicopathologic characteristics and evaluate the prognosis in young Chinese women with breast cancer. METHODS: A total of 1538 female patients with operable primary breast cancer (stage I-III) treated at our hospital from December 1994 to December 2003 were analyzed retrospectively. Among them, 1075 patients (≤ 60 yrs) with the complete follow-up data were divided into two groups according to age: young breast cancer group (≤ 40 yrs, n = 208) and control group (41 - 60 yrs, n = 867) to analyze the differences in their clinicopathologic characteristics and evaluate the prognosis of both groups. RESULTS: The patients with young breast cancer were more likely to have positive lymph nodes (P = 0.016), a negative expression of ER (estrogen receptor) (P = 0.016) and a positive expression of HER2 (P = 0.001). The 5-year disease-free survival (DFS) rates of young breast cancer group and control group were 73.3% and 84.1% (P < 0.001) and the 5-year overall survival (OS) rates 83.5% and 89.1% (P = 0.004) respectively. Moreover, the patients with young breast cancer had a worse DFS than control group in patients with stage I-II disease but not in those with stage III disease. And ≤ 40 years was an independent unfavorable prognostic factor of DFS (HR = 1.78, 95%CI: 1.19 - 2.66, P = 0.005) and OS (HR = 1.71, 95%CI: 1.01 - 2.90, P = 0.046) in the patients with stage I-II disease. CONCLUSION: Chinese women with young breast cancer have a worse prognosis, particularly in those with stage I-II disease.

[Impact of response of positive axillary nodes to neoadjuvant chemotherapy on breast cancer survival].

OBJECTIVE: To compare the distant disease-free survival between breast cancer patients with nodal pathological complete response (pCR) and those with nodal residual disease (RD) after neoadjuvant chemotherapy. METHODS: The clinical and pathological data of 376 needle biopsy proved node positive breast cancer patients undergoing neoadjuvant chemotherapy were retrospectively analyzed. RESULTS: The median follow-up time was 24 months (range: 5 - 100). The pCR rate of axillary lymph node was 30.9%. And the three-year distant disease-free survival (DDFS) rates were 91.7% and 78.8% in the patients with axillary lymph node pCR and RD respectively. According to the Log-rank test, there were significant differences in survival curves (P = 0.016). Multivariate analysis showed that the relative risk of DDFS for patients with RD was 2.14 folds of than that of the pCR group (P = 0.047). No significant difference existed between the disease-free survival (DFS) curve in two groups. DDFS had significant differences between the patients with the number of lymph node metastasis ≤ 3 and ≥ 4 in the RD group (P = 0.001). CONCLUSION: The distant disease-free survival of node positive breast cancer is associated with the status of axillary lymph node after neoadjuvant chemotherapy.

[Ototoxicity of kanamycin sulfate in adult rats and its underlying mechanisms].

The aim of the present study was to assess the ototoxicity of kanamycin sulfate (KM) in adult rats and its underlying mechanism. Forty male Sprague-Dawley rats (6-7 weeks old) were randomly divided into the experimental group and the control group. The animals in the experimental group were injected subcutaneously with KM (500 mg/kg per day) for two weeks, and the control group received equal volume of normal saline. To assess the ototoxicity of KM, the auditory brainstem response (ABR) was recorded to monitor the changes in hearing thresholds, and the density of spiral ganglion cells (SGCs) and morphology of cochlea were observed using surface preparations and frozen sections of cochlea. The results showed that the hearing threshold of rats in the experimental group was elevated by more than 60 dB across all the frequencies two weeks after the first administration of KM. And in the experimental group, the density of SGCs became lower, and organ of Corti suffered loss of hair cells. The loss of outer hair cells (OHCs) was more severe than that of inner hair cells (IHCs), correlated with the density decrease of SGCs. We conclude that the ototoxicity of KM in the adult rats was apparent and the underlying mechanism is associated with the loss of SGCs and hair cells.

Breast cancer subtypes and survival in chinese women with operable primary breast cancer.

OBJECTIVE: To investigate the associations between the different breast cancer subtypes and survival in Chinese women with operable primary breast cancer. METHODS: A total of 1538 Chinese women with operable primary breast cancer were analyzed in this study, the median follow-up was 77 months. Estrogen receptor (ER), progesterone receptor (PR), and HER2 status were available for these patients. RESULTS: Luminal A (ER+ and/or PR+, HER2-) had a favorable disease-free survival (DFS) and overall survival (OS) compared with other subtypes in the entire cohort. Using the luminal A as a reference, among the patients with lymph node positive disease, HER2+ (ER-, PR-, HER2+) had the worst DFS (hazard ratio, HR=1.80, 95% CI 1.11 to 2.91, P=0.017) and luminal B (ER+ and/or PR+, HER2+) had the worst OS (HR=2.27, 95% CI 1.50 to 3.45, P<0.001); among the patients with lymph node negative disease, triple-negative (ER-, PR-, HER2-) had the worst DFS (HR=2.21, 95% CI 1.43 to 3.41, P<0.001), whereas no significant difference in DFS between HER2+ and luminal B or luminal A was observed. CONCLUSION: As compared with luminal A, luminal B and HER2+ have the worst survival in patients with lymph node positive disease, but this is not the case in patients with lymph node negative disease; triple-negative subtype has a worse survival in both lymph node positive and lymph node negative patients.

[Different influence of Her-2 expression on the prognosis in node-positive and node-negative breast cancer].

OBJECTIVE: To investigate the prognostic significance of Her-2 expression in node-positive and node-negative breast cancer in Chinese women. METHODS: The Her-2 expression in breast cancers from 981 patients was detected by immunohistochemistry with anti-Her-2 (CB11) monoclonal antibody. The survival curves were analyzed by Kaplan-Meier method, and Cox regression model was applied to determine whether this factor is an independent predictor of survival in multivariate analysis. RESULTS: Nineteen point seven percent of the patients showed positive Her-2 expression in their tumors. Patients with Her-2-positive tumors tended to be younger. The high level Her-2 expression was significantly associated with negative estrogen receptor and progesterone receptor status in their tumors (P < 0.05). Among 387 patients with node-positive disease, the 5-year disease-free survival (DFS) rate and 5-year overall survival (OS) rate were significantly lower in patients with Her-2-positive tumors than in patients with Her-2-negative tumors (DFS: 48.8% vs. 66.9%, P = 0.009; OS: 55.2% vs. 76.4%, P = 0.001), and Her-2 expression was an independent unfavorable prognostic factor for OS, but not for DFS in patients with node-positive disease. Among 591 patients with node-negative disease, Her-2 expression was not significantly associated with DFS and OS (P > 0.05). CONCLUSION: Her-2 expression is an important prognostic factor in patients with node-positive disease, but not for patients with node-negative disease in Chinese women.

[The clinical research of local recurrence after breast-conserving therapy for breast cancer].

OBJECTIVE: To compare and analyze the data of breast cancer recurrence after breast-conserving therapy (BCT), and to find high risk factors that can affect local recurrence. METHODS: A total of 1034 patients in the data base between January 2000 and June 2008 were analyzed retrospectively. The patients aged 23 to 94 years when diagnosed (median age, 48 years). The data was investigated to compare of two different groups in local recurrence rate and survival rate. The high risk factors of recurrence after BCT [estrogen receptor (ER)/progesterone receptor (PR), human epidermal growth factor receptor (HER-2), age, lymph node involvement, tumor diameter, neoadjuvant chemotherapy, pathological status] were studied. RESULTS: The patients were followed-up to June 2010, and the median period was 42 months (range, 3-126 months). During the period, 35 patients developed ipsilateral breast tumor recurrence (3.3%), 47 patients had metastasis to distant organs (4.5%). The 5-year disease-free survival was 87.7%, 5-year distant disease-free survival was 94.0%. The lymph node status, HER-2 status and age were significant risk factors for ipsilateral breast tumor recurrence on univariate analysis. One peak recurrence period was from the 2nd to 3rd year, and the other was from the 5th to 6th year after the operation. The HER-2 status was independent factors of ipsilateral breast tumor recurrence on multivariate analysis. CONCLUSIONS: The recurrence happens primarily in the 2nd to 3rd and the 5th to 6th year after the breast-conserving therapy. HER-2 status is an independent factor of ipsilateral breast tumor recurrence. The patients with high risk factors of recurrence should be treated more aggressively.

[Correlation of BRCA1 and APC aberrant methylation with the response to anthracycline-based neoadjuvant chemotherapy in primary breast cancer].

OBJECTIVE: To investigate the correlation of hypermethylation of BRCA1 and APC gene promoters with the response to anthracycline-based neoadjuvant chemotherapy in primary breast cancer. METHODS: One hundred and forty patients with primary breast cancer received anthracycline-based neoadjuvant chemotherapy, and pretreatment hypermethylation status of BRCA1 and APC genes promoters was detected by methylation-specific PCR. RESULTS: Of the 140 patients, 30 (21.4%) achieved pathological complete response (pCR), and methylation rates of BRCA1 and APC gene promoters were 21.4% (30/140) and 18.3% (24/131), respectively. Among the 110 patients with unmethylated BRCA1 gene, 28 (25.5%) achieved pCR, while in the 30 patients with methylated BRCA1 gene, only 2 (6.7%) had a pCR, with a significant difference between the two groups (chi(2) = 4.94, P = 0.026). However, no statistically significant correlation was found between the methylation of APC gene and pCR to neoadjuvant chemotherapy in this cohort of patients (P > 0.05). CONCLUSION: Primary breast cancer with an unmethylated BRCA1 gene is prone to achieve a pathological complete response to anthracycline-based neoadjuvant chemotherapy than those with a methylated BRCA1 gene. BRCA1 methylation status may be a useful predictor for anthracycline-based neoadjuvant chemotherapy in primary breast cancer patients.

[Prognostic role of apoptosis-related gene Fas-1377 and -670 polymorphisms in breast cancer].

OBJECTIVE: To investigate the correlations between Fas-1377 and -670 polymorphisms and survival in Chinese women with breast cancer. METHODS: Polymerase chain reaction-restriction fragment length polymorphism assay (PCR-RFLP) was used to detect the polymorphism of Fas gene in 310 breast cancer patients with a long-term follow-up (median 10.5 years, range 0.2 - 16.1 years). Survival curves were analyzed by Kaplan-Meier method. RESULTS: The polymorphism of neither Fas-1377 nor Fas-670 was significantly correlated with the overall survival in this series of 310 cases (P > 0.05). However, among 146 patients without lymph node metastasis, the 5-year overall survival (OS) rate was significantly lower in the patients with Fas-1377 AA genotype than that in the patients with Fas-1377 GA or GG genotype (OS: 66.7% vs. 95.4%, P = 0.03). Among 117 patients with lymph node metastasis, both the Fas-1377 and Fas-670 polymorphisms were not significantly correlated with OS (P = 0.42). CONCLUSION: Among breast cancer patients without lymph node metastasis, patients with Fas-1377 AA genotype may have a worse survival, while patients with Fas-1377 GA or GG genotype may not be so.

[Management of non-malignant results in core needle biopsy of breast lesions].

OBJECTIVE: To study the strategy of management of non-malignant results in core needle biopsy (CNB) of breast lesions. METHODS: Consecutive 2654 breast lesions underwent CNB with 14-gauge automated needles. 1130 lesions with diagnosis of non-malignant breast lesions examined by CNB were followed up. The histological diagnosis of CNB, subsequent excision or repeat CNB, and the follow-up for cases without repeat biopsy were studied. RESULTS: Among the 1130 non-malignant breast lesions examined by CNB, 530 underwent re-biopsy and 73 cases of carcinoma were found. 491 lesions were followed up for 1 - 38 months (median, 13.3 months) and another 4 cases of carcinoma were found during the follow-up. 109 cases were lost to follow-up. 57.9% (22/38) of the atypical ductal hyperplasia, 22.2% (4/18) of the atypical ductal cells, 27.9% (24/86) of the papillary lesions, and 90.0% (9/10) of the suspicious carcinoma diagnosed by CNB were re-diagnosed as breast cancer finally. CONCLUSIONS: Repeat biopsy is required for the high-risk lesions diagnosed by breast CNB. Excision can be avoided on the benign lesions whose CNB diagnosis is consistent with those by physical examination and imaging.