Impact of adjuvant chemotherapy on the survival of patients with estrogen receptor ≥50 ％, human epidermal growth factor receptor-2 negative, lymph node negative breast cancer / 中华普通外科杂志

Objective To study the effect of adjuvant chemotherapy on the survival of patients with ER ≥ 50％,HER2 negative,lymph node negative breast cancer.Methods 428 patients from Jan 1,2004 to Dec 31,2010 were enrolled.All patients received operation plus chemoendocrine therapy (CET,n =239) or endocrine therapy (ET,n =189).Result The median follow-up time was 76.5 months,with 8.2％ loss to follow-up.The recurrence-free survival (RFS) was 93.7％ in CET group and 95.2％ in ET group,the distant disease-free survival (DDFS) was 94.6％ and 97.4％ in CET and ET group respectively.Multivariate regression indicated that the risk of tumor size ＞ 2 cm was higher than that of tumor size ≤2 cm in recurrence (HR=2.31,95％ CI 1.07-5.29,P =0.047) and metastasis (HR=4.71,95％ CI 1.47-11.85,P =0.01).Compared with CET group,however,no statistical significance was found on RFS (HR =1.08,95 ％ CI 0.46-2.57,P =0.86) and DDFS (HR =0.72,95 ％ CI 0.17-1.37,P =0.55) in ET group.Conclusions Adjuvant chemotherapy cannot improve the RFS and DDFS of ER≥50％,HER2 negative,lymph node negative breast cancer.Tumor size ＞ 2 cm was the risk factor of recurrence and distant metastasis.

Safety of breast-conserving treatment for triple-negative breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of risk factors on ipsilateral breast tumor recurrence (IBTR) and distant disease-free survival (DDFS) for patients with triple-negative breast cancer (TNBC) who underwent breast-conserving treatment (BCT).</p><p><b>METHODS</b>A series of 1 835 patients with primary breast cancer treated with BCT in a single institute between December 1999 and August 2010 were analyzed retrospectively. Totally 1 614 patients, whose characteristics were intact, were analyzed to compare their outcomes with respect to the incidence of IBTR, DDFS and disease-free survival (DFS). All of patients were female. Median age was 47 years (ranging 21 to 92 years, interquartile range 14 years). According to the immunohistochemical results of the patients, 1 614 cases were divided into TNBC group (n=308) and non-TNBC group (n=1 306). The risk factors of relapse after breast-conserving treatment (age at diagnosis, spread to axillary lymph nodes, hormone receptor status, neoadjuvant chemotherapy, and maximal tumor diameter, human epidermal growth factor receptor 2 (HER-2) status, preoperative MRI, the location and extent of the tumor bed defined by CT scans for electron boost planning as part of breast radiotherapy) were studied.χ(2) test was used to compare the distribution of baseline characteristics among subtypes. The probability of survival (or relapse occurrence), and DDFS were calculated using the Kaplan-Meier method. Cumulative incidence functions were used to describe the cumulative hazard from LR, IBTR and DDFS in the presence of competing risks.</p><p><b>RESULTS</b>A total of 1 614 women with primary breast cancer underwent a breast-conserving surgery followed by radiotherapy. The median follow-up period was 77 months (interquartile range 36 months). One hundred and forty patients (8.6%) were lost to follow-up. Overall 5-year IBTR rate was 3.1% (95% CI: 2.2% to 4.0%), 5-year DDFS rate was 95.8% (95% CI: 94.9% to 96.7%) and 5-year DFS rate was 93.8% (95% CI: 92.7% to 94.9%). Lymph nodal involvement (HR=3.03, 95% CI: 1.66 to 5.51, P=0.000) and use of CT information in boost field planning (HR=0.40, 95% CI: 0.20 to 0.80, P=0.010) were associated significantly with IBTR in Cox multivariable analysis. Multivariable analysis showed that TNBC doesn't have a significantly increased risk of IBTR compared with the non-TNBC subtype (HR=0.90, 95% CI: 0.50 to 1.76, P=0.78). TNBC was not an independent risk factor for DDFS or DFS. The multivariable model showed significant effect of nodal status and age at diagnosis on 5-year DDFS rate and 5-year DFS rate.</p><p><b>CONCLUSIONS</b>Breast-conserving treatment for TNBC is not associated with increased IBTR compared with non-TNBC subtype. Use of CT information in boost field planning can reduce the risk of ipsilateral breast tumor recurrence for patients undergoing BCT.</p>

Neoadjuvant chemotherapy using epirubicin, cyclophosphamide and fluorouracil: neutropenia and elevation of transaminase, and their management / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To retrospectively investigate the incidence of severe neutropenia and elevation of transaminase during neoadjuvant chemotherapy using epirubicin, cyclophosphamide and fluorouracil in breast cancer patients.</p><p><b>METHODS</b>From January 2011 to December 2012, 303 consecutive breast cancer patients with complete treatment data treated in our department were included in this analysis. All patients received neoadjuvant chemotherapy with equal dose of EPI (100 mg/m(2)) administered every 3 weeks for 4 cycles before surgery.</p><p><b>RESULTS</b>200 patients (66.0%) experienced at least one episode of grade 3/4 neutropenia/leukopenia, among them 176 patients experienced their first episode after the first cycle. Febrile neutropenia (FN) occurred in 13 patients for 14 episodes. Elevation of transaminase occurred in a total of 46 patients (15.2%), among them, grade 2 or higher elevation occurred in 15 patients (5.0%). Three blood test plans were adopted to monitor the patients during chemotherapy: (1) Routine blood count repeated every week; (2) Routine blood count before and on day 10 of each chemotherapy episode; (3) Routine blood count before and on day 7, 10 and 14 of each chemotherapy episode. The number of patients whose chemotherapy was delayed due to 3/4 neutropenia/leucopenia in each blood test plan was 3 (5.0%), 7 (3.9%) and 2 (3.2%), respectively. The number of patients with febrile neutropenia (FN) in each blood test plan was 2 (3.3%), 8 (4.4%) and 3 (4.8%), respectively. No statistically significant difference in treatment delay or the incidence of FN was observed among different blood test plans. No statistically significant difference in the incidence of grade 3/4 neutropenia/leukopenia or grade 2 or higher transaminase elevation was observed among different 5-Fu regimens.</p><p><b>CONCLUSIONS</b>During neoadjuvant chemotherapy using FE100 C, Fci E100 C or E100 C for breast cancer patients without routine prophylactic G-CSF, the incidence of grade 3/4 neutropenia/leukopenia is 66.0%. With the patient management plan we adopted, 4.3% of patients developed febrile neutropenia. Prophylactic medication may not be necessary for patients without evident liver dysfunction.</p>

The study of associations between circulating tumor cells and clinicopathologic characteristics in axillary lymph node positive primary breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the correlations between circulating tumor cell (CTC) and clinicopathologic characteristics of tumors obtained by core needle biopsy in axillary lymph node positive primary breast cancer patients.</p><p><b>METHODS</b>The peripheral venous blood samples were collected from 126 patients with axillary lymph node positive primary breast cancer and were detected to found CTCs using the CellSearch automatic detection system. The associations between CTCs and clinicopathologic characteristics of tumors were analyzed in axillary lymph node positive primary breast cancer patients. All patients were female, age ranging from 27 to 65 years (median, 49 years).</p><p><b>RESULTS</b>One or more CTCs were detected from the peripheral blood in 25.4% (32/126) patients. The positive rate of CTCs was 36.2% (17/47) in the human epidermal growth factor receptor 2 (HER-2) (+) patients, 19.0% (15/79) in the HER-2 (-) patients. In univariate analysis, there were significant differences about the positive rate of CTCs between the two groups (χ² = 4.592, P < 0.05). In multivariate analysis, the risk of circulating tumor cells positive in HER-2 (+) patients was 2.712 times higher than in HER-2 (-) patients (OR = 2.712, 95% CI: 1.117-6.584, P = 0.027), whereas the positive rate of CTCs in axillary lymph node positive primary breast cancer patients showed no significant differences among the different subgroups with regards to age, menopausal status, the T staging of the tumor, histological type, histological grade, hormone receptor status and Ki-67 expression level (P > 0.05).</p><p><b>CONCLUSIONS</b>There are significant correlations between the presence of CTCs and the HER-2 status of the tumor in axillary lymph node positive primary breast cancer patients. No significant correlations are found between the presence of CTCs and the age, menopausal status, T staging of the tumor, histological type, histological grade, hormone receptor status and Ki-67 expression level.</p>

Efficacy analysis of THP-containing regimens as neoadjuvant and adjuvant chemotherapy for primary breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Comparison of other cancers in Chinese han women with familial and sporadic breast cancer / 国际外科学杂志

ObjectiveTo investigate the family history of other cancers in Chinese han women with familial or sporadic breast cancer.Methodswe analyzed the clinical date of 4 847 primary breast cancer patients cancer patients were treated at the Breast Cancer,Peking University Cancer Hospital between October 2003 and February 2011,among them,465 were familial and4 382 were sporadic breast cancer patients.The differences of family history of cancers other than breast or ovarian cancers were compared between the patients with familial breast cancer and sporadic breast cancer.Results The proportion of cancers other than breast or ovarian cancers in familial breast cancer patients was significantly higher than that in sporadic breast cancer patients(29.7％ vs 20.8％,odds ratio 1.61,P＜ 0.001).Furthermore,the proportion in pancreatic cancer,prostate cancer,and renal cancer in familial breast cancer patients was significantly higher than that of sporadic breast cancer patients ( pancreatic cancer:2.2％ vs 0.8％,P =0.002 ; prostate cancer:1.5％ vs 0.3％,P ＜ 0.001 ; renal cancer:1.1％ vs 0.4％,P =0.03,respectively).And the relative risks of pancreatic cancer,prostate cancer,and renal cancer in the familial breast cancer patients were 2.90-fold,6.07-fold,and 2.97-fold higher than that of sporadic breast cancerpatients,respectively.ConclusionsOur results suggest that the relative risk of cancer other than breast or ovarian in familial breast cancer patients is significantly higher than that in sporadic breast cancer patients,especially pancreatic cancer,prostate cancer,and renal cancer.

Association between MDM2 SNP309 Polymorphism and Breast Cancer Risk in Chinese Women / 中国肿瘤临床

Objective: To investigate the correlation of MDM2 SNP309 polymorphism with breast cancer risk in Chinese women. Methods: The polymorphism of MDM2 SNP309 was detected by PCR-restriction frag-ment length polymorphisms assay (PCR-RFLP) in 698 women with primary breast cancer and 525 healthy controls. Results: Compared with the T/T genotype, the G allele (T/G or G/G) was not associated with an in-creased risk of breast cancer in the entire population studied (T/G, adjusted OR=1.2, 95% CI: 0.8-1.6, P=0.30; G/G, adjusted OR=1.0, 95% CI: 0.7 ～ 1.5, P=0.88). Among postmenopausal women, the G allele (T/G or G/G) was significantly associated with an increased risk of breast cancer (T/G, adjusted OR=1.8, 95% CI:1.2～3.0, P=0.011; G/G, adjusted OR=1.9, 95% CI: 1.2～3.3, P=0.014). But this association was not ob-served among premenopausal women. Conclusion: MDM2 SNP309 heterozygous T/G genotype and homozy-gous mutant GIG genotype increase breast cancer risk in postmenopausal Chinese women.

The clinical research of local recurrence after breast-conserving therapy for breast cancer / 中华外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Different influence of Her-2 expression on the prognosis in node-positive and node-negative breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the prognostic significance of Her-2 expression in node-positive and node-negative breast cancer in Chinese women.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Prognostic role of apoptosis-related gene Fas-1377 and -670 polymorphisms in breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlations between Fas-1377 and -670 polymorphisms and survival in Chinese women with breast cancer.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Correlation of BRCA1 and APC aberrant methylation with the response to anthracycline-based neoadjuvant chemotherapy in primary breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the correlation of hypermethylation of BRCA1 and APC gene promoters with the response to anthracycline-based neoadjuvant chemotherapy in primary breast cancer.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Outcome of total mesorectal excision for lower rectal cancer: micrometastasis in the mesorectum / 中华外科杂志

<p><b>OBJECTIVE</b>To assess the correlation between micrometastasis in mesorectum and pathological factors after total mesorectal excision(TME) in lower rectal cancer.</p><p><b>METHODS</b>All lymph nodes were obtained by fat clearance from 31 lower rectal cancer patients with TME. The lymph nodes which had previously been considered negative of metastasis by conventional examination were submitted to immunohistochemical examination to identify the micrometastases using anti-cytokeratin antibody. The correlation between micrometastasis and pathological factors were analyzed.</p><p><b>RESULTS</b>One thousand and seven LNs were collected from 31 patients. One hundred and five LNs were found positive by conventional examination, and the mean diameter was (5.5 +/- 3.1) mm. The mean diameter of conventional negative LNS was (2.8 +/- 1.5) mm. The diameter differed significantly between conventional positive and negative LNS (P < 0.05). In 902 conventional negative LNs, 26 contained micrometastasis (209%) and the mean diameter was (3.3 +/- 1.2) mm. The diameter of LNs with micrometastasis was significantly smaller than that of conventional positive LNs (P < 0.05). The diameter of most of the micrometastatic LNs(88.5%) was less than 5 mm. Fourteen patients (38.7%) contained micrometastasis. The pathological stage, serum carcinoembryonic antigen level and tumor differentiation were related to micrometastasis (P < 0.05).</p><p><b>CONCLUSIONS</b>With the detection of micrometastasis after fat clearance, we can estimate the LN metastasis status more accurately. It can be useful in clinical staging and individual treatment of rectal cancer.</p>

Ultrasound-guided core needle biopsy in the diagnosis of breast lesions / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the accuracy and utility of ultrasound-guided core needle biopsy (CNB) in the diagnoses of breast lesions.</p><p><b>METHODS</b>The clinical data of 2152 consecutive breast lesions examined by CNB were reviewed. The histological agreement between core pathology and subsequent excision pathology was studied. The benign diseases without repeat biopsy were followed up.</p><p><b>RESULTS</b>There were 1461 cancers in final diagnosis among 2152 breast lesions, 1339 cancers were diagnosed by CNB. The false-negative rate of CNB was 3.5% (51/1461), and the underestimation rate was 4.9% (71/1461). In the repeat biopsy, carcinoma was found in 17 (50.0%) of 34 atypical ductal hyperplasia lesions and 25 (46.3%) of 54 papillary lesions. In 1461 cancers, the false-negative rate of ultrasound-guided CNB (2.1%, 22/1068) was significantly lower than that of free-hand-guided CNB (7.4%, 29/393) (P < 0.05). The false-negative rate of two special doctors for CNB (1.2%, 8/681) was significantly lower than that of other doctors (5.5%, 43/780) (P < 0.05). In 738 of benign lesions, 417 cases were excised and 50 malignant lesions were found, 205 cases were followed up by 2 - 29 months (median, 10.2 months), and one malignant lesion was found.</p><p><b>CONCLUSIONS</b>Ultrasound-guided core needle biopsy with histopathological assessment is an accurate method in diagnosis of breast lesions. Excisional biopsy is required to the high-risk lesions in CNB.</p>

Association between hormone receptors and response to neoadjuvant anthracycline-based chemotherapy in breast cancer patients / 北京大学学报(医学版)

Objective:To investigate the associations between the hormone receptors,Ki67 expression and response to neoadjuvant anthracycline-based chemotherapy in breast cancer patients.Methods:One hundred sixty-eight primary breast cancer patients received anthracycline-based neoadjuvant chemotherapy.The expression of estrogen receptor(ER),progesterone receptor(PR),and Ki67 were determined by immunohistochemistry assay in core-needle biopsy specimens prior to the chemotherapy,and pathologic response was assessed by Miller & Payne grade(G1 to G5).Results:40%(67/168)of the patients had a good pathologic response,defined as complete pathologic response(pCR or G5)and minimal residual disease(G4).Among the patients,20%(33/168)had a complete pathologic response(G5).ER or PR status was significantly associated with pathological response.Patients with PR-negative tumors had a higher pathological response rate or pCR than those with PR-positive tumors(17/67 vs 45/90,P=0.002;6/67 vs 25/90,P=0.003,respectively),whereas patients with ER-negative tumors had a higher pathological response rate than those with ER-positive tumors.Moreover,Patients with both ER-and PR-negative tumors exhibited a remarkable pathological response as compared with those with any single factor(36/17 vs 26/86,P=0.009).No association between Ki67 expression and pathological was found in this cohort of patients.There was a linear correlation between the expression of Ki-67,ER or PR status and pathologic response.Conclusion:There is a significant association between the hormone receptors and pathological response to neoadjvant anthracycline-based chemotherapy in breast cancer patients,and patients with PR-negative tumors are more likely to respond to chemotherapy.