Effect of functional variant rs11466313 on breast cancer susceptibility and TGFB1 promoter activity.

PURPOSE: This study aimed to investigate whether genetic polymorphisms in TGFB1 contribute to breast cancer (BC) susceptibility, and explore the mechanism of action. METHODS: A total of 7 tagging SNPs (tSNPs) were genotyped in 1161 BC cases and 1337 age-matched controls among Chinese Han population. Bioinformatics analysis was used to predict functional SNP closely linked to tSNPs. Luciferase gene reporter assay was performed to determine the effect of genetic variants on promoter activity. DNA pull-down assay and mass spectrometry were used to identify the differentially binding proteins to genetic variants. RESULTS: Genotyping analysis showed that rs1800469 (C>T) in the 5' regulatory region of TGFB1 was associated with reduced BC risk. Bioinformatics analysis predicted that rs11466313 (-2389_-2391 Del/AGG) in the 5' regulatory region of TGFB1, was closely linked to tSNP rs1800469 and could be functional. The genotyping of rs11466313 by PCR-SSCP showed that rs11466313 also conferred decreased BC risk. Luciferase assays demonstrated that rs11466313 minor allele reduced over ninefold of promoter activity compared with its major allele (p < 0.001). DNA pull-down assay and mass spectrometry revealed that rs11466313 minor allele lost the binding ability with FAM98B and HSP90B. Knocking down FAM98B but not HSP90B, the enhanced promoter activity driven by TGFB1 rs11466313 major allele was attenuated. CONCLUSIONS: This study elucidates the impact of functional polymorphism rs11466313 in the regulatory region of TGFB1 on breast cancer susceptibility and gene expression, and could be helpful for future research to determine the value of this TGFB1 variant in the clinical setting.

[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.

[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.

Genetic polymorphisms in centrobin and Nek2 are associated with breast cancer susceptibility in a Chinese Han population.

Centrosome aberrations have been suggested to cause chromosomal instability and aneuploidy, and eventually promote cancer development. The Centrobin and Nek2 proteins interact with each other and both are involved in centrosome duplication and chromosome segregation. This study aimed to investigate whether genetic polymorphisms in these two genes may affect breast cancer susceptibility in Chinese Han population using a haplotype-based analysis. Five single nucleotide polymorphisms (SNPs) in centrobin and four SNPs in Nek2 were genotyped in 1,215 cases of infiltrating ductal breast cancer and 1,215 age-matched cancer-free controls from Chinese Han population. The results showed that CATCG haplotype of centrobin was strongly associated with decreased breast cancer risk (adjusted OR = 0.14, 95 % CI = 0.09-0.22), which was mainly driven by the C allele of SNP rs11650083 (A>C, located in exon 12, resulting in Pro578Gln). None of the individual SNPs in Nek2 was associated with breast cancer risk. However, haplotype GTAT of Nek2 was associated with increased risk of breast cancer (adjusted OR = 1.56, 95 % CI = 1.18-2.06) and its risk was significantly elevated among women with both family history of cancer and a longer menarche-first full-term pregnancy (FFTP) interval (>11 years) (adjusted OR = 5.31, 95 % CI = 1.97-14.32). Furthermore, women harboring both at-risk haplotype GTAT of Nek2 and protective haplotype CATCG of centrobin were linked with decreased breast cancer risk, suggesting that the association between genetic variants of Nek2 and increased breast cancer risk was modified by genetic variants of centrobin. Our results indicate that genetic polymorphisms of centrobin and Nek2 are related to breast cancer susceptibility in Chinese Han women.

Genetic polymorphisms in AURKA and BRCA1 are associated with breast cancer susceptibility in a Chinese Han population.

Centrosome defects can result in aneuploidy and genomic instability, and have important implications for breast cancer development. The Aurora-A and BRCA1 proteins interact and both are strongly involved in centrosome regulation. Genetic variants in these two genes may have an effect on breast cancer development. Here, we report a comprehensive single nucleotide polymorphism (SNP) and haplotype-tagging association study on these two genes in 1334 breast cancer cases and 1568 unaffected controls among the Chinese Han population. Apart from a missense SNP, rs2273535 (Phe31Ile), and a probable risk SNP, rs2064863, six htSNPs were analysed in three high-LD blocks of AURKA spanning from 10 kb upstream to 2 kb downstream of AURKA. For BRCA1, six htSNPs were analysed in a large high-LD region covering 98 kb (10 kb was extended to each end of BRCA1). The results showed that four SNPs in AURKA (data in recessive model, rs2273535: OR = 2.19, 95% CI = 1.03-4.66, p = 0.0422; rs2298016: OR = 0.38, 95% CI = 0.18-0.82, p = 0.0141; rs6024836: OR = 1.54, 95% CI = 1.18-2.00, p = 0.0014; rs10485805: OR = 0.68, 95% CI = 0.47-0.98, p = 0.0380) and one SNP in BRCA1 (rs3737559, dominant model OR = 1.35, 95% CI = 1.11-1.64, p = 0.0030) were associated with breast cancer susceptibility. After correction for multiple comparisons (FDR = 0.05), only rs6024836 and rs3737559 remained significant. Two haplotypes (CC of block 2, OR = 20.74, 95% CI = 4.35-98.88, p = 0.0001; GG of block 3, OR = 1.32, 95% CI = 1.12-1.56, p = 0.0010) and one diplotype (AG-GG of block 3, OR = 1.63, 95% CI = 1.18-2.26, p = 0.0031) within AURKA showed strong associations with breast cancer risk. One haplotype of BRCA1 (CTGTTG, OR = 1.30, 95% CI = 1.06-1.59, p = 0.0118) was also associated with breast cancer risk. However, women harbouring both at-risk genotypes of Aurora-A and BRCA1 were at a slightly increased risk compared with those harbouring either at-risk variant alone. Common genetic variants in the AURKA and BRCA1 genes may contribute to breast cancer development.

[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.

[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.

[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.

[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.

Current status of diagnosis and treatment of primary breast cancer in beijing, 2008.

OBJECTIVE: To investigate the status of diagnosis and treatment of primary breast cancer in Beijing, 2008. METHODS: All the patients who were diagnosed as primary breast cancer in Beijing in 2008 were enrolled in this study. Information of these patients, including the features of tumors, clinical diagnosis and treatment was collected, and filled in the well-designed questionnaire forms by trained surveyors. The missing data was partly complemented through telephone interviews. RESULTS: A total of 3473 Beijing citizens were diagnosed as primary breast cancer (25 patients with synchronal bilateral breast cancer) in Beijing, 2008. Of them 82.09% were symptomatic. 19.02% and 34.11% were diagnosed using fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB), respectively. 15.92% received sentinel lymph node biopsy (SLNB) and 24.27% received breast conserving surgery (BCS). Among 476 cases with Her-2 positive, only 96 received anti-Her-2 therapy. We found that the standardization level varied in hospitals of different grades, with higher level in Grade-III hospitals. Of note, some breast cancer patients received non-standard primary tumor therapy: 65.63% of the patients with ductal carcinoma in situ (DCIS) received axillary lymph node dissection and 36.88% received chemotherapy; 25.89% of the patients underwent breast conserving surgery without margin status; 12.10% of the patients received chemotherapy less than 4 cycles. CONCLUSION: Although most breast cancer patients received basic medical care, the mode of diagnosis and treatment should be improved and should be standardized in the future in Beijing.

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.

Weekly paclitaxel improved pathologic response of primary chemotherapy compared with standard 3 weeks schedule in primary breast cancer.

The purpose of this study is to compare the efficacy of weekly paclitaxel to every-3-week schedule in terms of pathologic response and toxicity which caused treatment delay in primary chemotherapy of breast cancer. After pretreatment of two cycles of cyclophosphamide/ pirarubicin/ fluorouracil (cyclophosphamide 500 mg/m(2) days 1, 8; pirarubicin 35 mg/m(2) days 1, 8; 5-Fu 200 mg/m(2) day ci day 1-28, every 4 weeks), 219 women with histologically confirmed T(1-3) N(0-2) M(0) invasive breast cancer, whose vertical diameters production of breast tumor reduced not more than 75%, were randomized to receive four cycles of Pq3wC (arm A: paclitaxel 175 mg/m(2) day 1, carboplatin AUC 6 d1, every 3 weeks) or Pq1wC (arm B: paclitaxel 60 mg/m(2) days 1, 8, 15, carboplatin AUC 6 day 1 for every 3 weeks) before surgery, stratified by partial or no response (stable disease and progression of disease) evaluated by ultrasonography. Pathologic response of the primary tumor was assessed by using Miller and Payne grading system. We defined grade 4/5 as excellent response, grade 3/4/5 as response and treatment delay as paclitaxel administration being delayed at least 1 week because of toxicity in this study. 213 patients (2 cases with concurrent bilateral breast cancer) were eligible for analysis, 109 patients with 110 lesions in arm A and 104 patients with 105 lesions in arm B. Patients in arm B had a higher excellent pathologic response rate and a higher pathologic response rate compared with patients in arm A (59.0 vs. 45.5%, P = 0.046 and 86.7 vs. 71.8%, P = 0.007). Pathologic complete response (pCR) rate in breast alone was similar between two arms (P = 0.733), but there was a higher pCR rate in patients with partial response to two cycles of cyclophosphamide/pirarubicin/fluorouracil than those with no response (32.4 vs. 13.9%, P = 0.001). There was no treatment-related death, however more patients in arm B than in arm A experienced treatment delay caused by toxicity (60.6 vs. 11.9%, P < 0.001). Under the condition of same cumulative doses, weekly paclitaxel was more effective than 3 weeks schedule in terms of pathologic response to primary chemotherapy in breast cancer, and caused more treatment delay related to toxicity though well tolerant.

[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.

[Feasibility of predicting pathological evaluation by ultrasonic evaluation in initial stage of neoadjuvant chemotherapy for primary breast cancer].

OBJECTIVE: To investigate the correlation between change of tumor size after 2 cycles of neoadjuvant chemotherapy and pathological evaluation after 4 cycles of neoadjuvant chemotherapy. And to evaluate the feasibility of predicting pathological evaluation by ultrasonic evaluation in the initial stage of neoadjuvant chemotherapy for primary breast cancer. METHODS: Retrospective analysis was performed in women with primary breast cancer, including 138 patients receiving 4 cycles of anthracycline-based neoadjuvant chemotherapy (CTX500 mg/m(2), D1, D8 Q28D; THP35 mg/m(2), D1, D8 Q28D; 5-Fu200 mg/m(2)/day.ci D1-D28), and 84 patients receiving 4 cycles of taxane-based neoadjuvant chemotherapy (PTX60-80 mg/m(2), D1, D8, D15 Q21D). The ROC (receiver operating characteristic) curve was employed to evaluate whether the product change of 2 largest perpendicular diameters of tumor as observed by ultrasonography after 2 cycles of neoadjuvant chemotherapy could exactly predict the pathologic evaluation by the Miller & Payne grading system criteria after 4 cycles of neoadjuvant chemotherapy. RESULTS: When no response, excellent response or pathologic complete remission to neoadjuvant chemotherapy were predicted by ultrasonic evaluation. And the areas under the curve ROC were 0.689, 0.655 and 0.647 respectively (all P values < 0.05). It was predicted as no response by using the traditional standard of ultrasonic evaluation of < 50% or excellent response at > or = 50% (kappa < 0.40). CONCLUSION: Pathological evaluation after 4 cycles of anthracycline- or taxane-based primary chemotherapy in breast cancer can't be predicted reliably only by the product change of 2 largest perpendicular diameters of tumor as observed by ultrasound after 2 cycles of neoadjuvant chemotherapy.

[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.

[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.

[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.

[Role of ultrasound-guided needle biopsy of ultrasonographic abnormal axillary lymph nodes in patients with breast cancer].

OBJECTIVE: To evaluate the utility of ultrasound (US)-guided needle biopsy of ultrasonographic abnormal axillary lymph nodes in the patients with breast cancer. METHODS: The pathological results of US-guided needle biopsy and clinical data of 395 primary breast cancer patients with ultrasonographic abnormal axillary nodes, all female, aged 24 - 83, were analyzed retrospectively. RESULTS: Node metastasis were detected in 277 (70.1%) cases by mean of ultrasound-guided needle biopsy. Among 136 patients with clinical N(0) breast cancer, 65 (47.8%) were proved node positive. Sixty-two patients were diagnosed as pathologically negative by needle biopsy and underwent sentinel lymph node biopsy or axillary lymph node clearance, and pathological examination showed negative axillary lymph node negative. The complete pathological complete remission rate of the metastatic lymph nodes after new adjuvant chemotherapy was 32.3% (62/192). CONCLUSION: Ultrasonographic examination of axilla combined with ultrasound-guided needle biopsy of suspicious axillary node is valuable in primary breast cancer treatment.