Unfavorable pathological complete response rate of neoadjuvant chemotherapy epirubicin plus taxanes for locally advanced triple-negative breast cancer / 华中科技大学学报（医学）（英德文版）

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer (TNBC). Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2) or docetaxel 75 mg/m(2) every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response (pCR), which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Thirty-nine (90.7%) patients were at clinical stages IIB-IIIC. Thirty-seven (86%) completed 4-6 cycles of preoperative chemotherapy, and objective response rate (ORR) was 81.4% (35/43). Forty-two patients underwent radical surgery subsequently. The pCR rate was 14.3% (6/42). The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting (88.4%, 38/43) and neutropenia (88.4%). After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally advanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.

Unfavorable pathological complete response rate of neoadjuvant chemotherapy epirubicin plus taxanes for locally advanced triple-negative breast cancer / 华中科技大学学报（医学）（英德文版）

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer (TNBC). Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m(2) plus paclitaxel 175 mg/m(2) or docetaxel 75 mg/m(2) every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response (pCR), which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival (RFS) and overall survival (OS) were secondary endpoints. Thirty-nine (90.7%) patients were at clinical stages IIB-IIIC. Thirty-seven (86%) completed 4-6 cycles of preoperative chemotherapy, and objective response rate (ORR) was 81.4% (35/43). Forty-two patients underwent radical surgery subsequently. The pCR rate was 14.3% (6/42). The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting (88.4%, 38/43) and neutropenia (88.4%). After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally advanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.

Phase II clinical trial of neoadjuvant therapy with carboplatin plus paclitaxel for locally advanced triple-negative breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy, safety and survival of combination of carboplatin plus paclitaxel as neoadjuvant chemotherapy (NACT) for patients with locally advanced triple-negative breast cancer (TNBC), and explore an optimal regimen for TNBC.</p><p><b>METHODS</b>Patients with core needle biopsy confirmed pathological diagnosis of IIA ∼ IIIC invasive breast cancer, negative for estrogen and progesterone receptors and HER2 by immunohistochemistry, and with indication for NACT were eligible in this study. The biopsy tumor tissues were tested for CK5/6, CK14, EGFR and Ki67. The patients received paclitaxel 175 mg/m(2) on day 1, carboplatin at an area under the curve 5 mg×min/ml on day 2 of every 21 days. The clinical response was evaluated every 2 cycles according to Standard RECIST 1.0 criteria and surgery was done after four to six cycles. Pathological complete remission (pCR) was defined if absence of invasive tumor in the breast and axillary lymph nodes samples or residual carcinoma in situ only.</p><p><b>RESULTS</b>Overall, thirty-one patients were enrolled from January 2008 to November 2010. The median age was 51 years and 83.9% of the patients were diagnosed as stage IIB to IIIC diseases. 30 Patients completed chemotherapy as planed while one patient changed regimen due to paclitaxel allergy. Twenty-eight patients could be evaluated for clinical efficacy, of which CR, PR, SD, PD were achieved in 4, 20, 3 and 1 women, respectively. The objective response rate was 85.7%. The expression rate of CK5/6, CK14 and EGFR were 88.9% (24/27), 59.3% (16/27) and 63% (17/27), respectively. Among 27 patients who received modified radical mastectomy or breast-conserving surgery, 11 patients obtained pCR, with a pCR rate of 40.7% (95%CI 22.2% - 59.3%). Five of six CK5/6- and CK14-positive patients achieved pCR. All the 31 patients could be evaluated for toxicity according to the NCI-CTC v3.0 criteria. The major toxicities were neutropenia (93.5%), vomiting (45.2%) and ALT/AST increase (32.3%), and grade 3-4 toxicities accounted for 74.2%, 3.2%, 0, respectively. Until December 2011, at a median follow-up of 28.9 months (range 5 - 47.9), eight patients developed recurrence including 5 patients died. Among 11 patients with pCR, one suffered from lung metastasis at 45 months after diagnosis and survived with tumor until now. The other ten were alive and disease free. The 3-year DFS and OS were 62% and 74.7%, respectively.</p><p><b>CONCLUSIONS</b>As a neoadjuvant treatment for triple-negative breast cancer, carboplatin plus paclitaxel regimen achieves notable higher objective response rate and pCR rate compared with the anthracycline plus paclitaxel regimen reported in the literature, and is well tolerable. It is an optimized regimen for TNBC.</p>

SNP rs16917496 within SET8 3'UTR is associated with the age of onset of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>We have identified a SNP within the seed-binding region for miR-502 in the 3'-UTR of the SET8 gene that codes for a methyltransferase for histone H4. SET8 methylates TP53 and thus regulates cell proliferation and genome stability. This study is to investigate the role for this SNP and its interaction with the TP53 codon 72 SNP in the age of onset of breast cancer.</p><p><b>METHODS</b>We conducted a case-only study of 1, 110 breast cancer cases. PCR-RFLP was used for SNP genotyping. Ages of onset of breast cancer among different genotypes were analyzed using SAS software.</p><p><b>RESULTS</b>Our analysis revealed that the SET8 CC and TP53 GG genotypes were independently associated with earlier age of onset of breast cancer in an allele-dose dependent manner. Moreover, individuals with both SET8 CC and p53 GG genotypes developed cancer at age of 47.74 years, compared with 54.55 years for individuals with both SET8 TT and TP53 CC genotypes.</p><p><b>CONCLUSIONS</b>miR-502-binding SNP in SET8 may modulate SET8 expression and contribute to early development of breast cancer either independently or together with the TP53 codon 72 SNP.</p>

Polymorphisms of GSTP1 is associated with differences of chemotherapy response and toxicity in breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although chemotherapy is one of the most important treatments of breast cancer, it is limited by significant inter-individual variations in response and toxicity. The metabolism of epirubicin (EPI) and cyclophosphamide (CTX) is mainly mediated by cytochrome P450s (CYPs) and glutathione S-transferases (GSTs). It has been well-known that the activities of these enzymes are polymorphic in population due to their genetic polymorphisms. The aim of this research was to examine the effects of genetic polymorphisms in CYP3A, GSTP1 and MDR1 genes on treatment response and side-effects of breast cancer patients receiving EPI/CTX chemotherapy.</p><p><b>METHODS</b>One hundred and twenty patients with stage II or III invasive breast cancer were recruited and treated with three to four cycles of EPI 80 mg/m(2) and CTX 600 mg/m(2) every two weeks. The AJCC TNM staging system (sixth edition) was used to evaluate the pathological response of primary tumor and axillary lymph nodes. The genotypes of gene polymorphisms were determined by using PCR-restriction fragment length polymorphism methods.</p><p><b>RESULTS</b>Patients carrying GSTP1 (105)Ile/Val or (105)Ile/Ile genotype were more likely to have good response (OR, 0.40; 95%CI, 0.16 - 0.96; P = 0.024) and light toxicity (OR, 0.35; 95%CI, 0.13 - 0.78; P = 0.006) than those carrying (105)Val/Val genotypes. The response to the treatment was not correlated with estrogen receptor, progesterone receptor and Her2/neu status of tumors. No correlation was found between toxicity effect and patient's age, tumor staging, menopause status, and dose intensity of the drugs.</p><p><b>CONCLUSION</b>GSTP1 polymorphism was associated with the chemotherapy response or adverse effects of EPI and CTX regimens.</p>

Comparison of touch imprint cytology of core needle biopsy and section histopathology in breast cancer diagnosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the sensitivity, specificity of touch imprint cytology (TIC), and to compare its conformity rate with histopathology, to observe the consistence of immunocytochemistry (ICC) with immunohistochemistry (IHC), and to assess the diagnostic value of TIC prior to neoadjuvant chemotherapy for breast cancer.</p><p><b>METHODS</b>289 cases of TIC and 287 cases with core needle biopsy (CNB) histopathology accumulated from October 2005 to October 2008 in our hospital were included in this study. One hundred ninety cases TIC results were compared with that of final histopathology. 64 cases were tested for ER, PR, HER-2 by immunocytochemistry.</p><p><b>RESULTS</b>Twenty-four benign cases and 263 malignant cases were diagnosed. 4 specimens were unsatisfactory. False negative rate and unsatisfactory rate were 1.4%, both, and false positive rate was 0.35%. The accuracy rate of TIC and CNB was 95.8% and 95.3%, respectively (P = 0.804). The sensitivity of TIC and CNB was 96.2% and 95.0% (P = 0.601), specificity 87.5% and 100% (P = 0.471) were found, when compared with the results of routine histopathology. 52 cases had a control with IHC of CNB in 64 ICC, and 43 cases had a final histopathology IHC. The ICC conformity rate of ER, PR, HER-2 with IHC of CNB was 86.5%, 75.0%, 78.8%, and that with IHC of final histopathology was 88.4%, 74.4%, 75.6%, respectively. The conformity rate of IHC between CNB and final histopathology was 83.7%, 74.4%, 76.5%, respectively. There was no significant statistical difference between them.</p><p><b>CONCLUSION</b>Compared with routine CNB histopathology, TIC has a high accuracy and sensitivity, and can provide a rapid and reliable cytological diagnosis to complement CNB for breast lesions. The conformity rates are high in ER, PR, HER-2 expression between ICC and IHC. ICC of TIC can be used to determine the estrogen and progesterone receptor levels in breast cancer before neoadjuvant chemotherapy.</p>

Morphologic assessment of response to neoadjuvant chemotherapy in breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the histological criteria of breast cancer response to neoadjuvant therapy.</p><p><b>METHODS</b>One hundred and fifty-four cases of breast cancer receiving neoadjuvant therapy were collected from June, 2005 to June, 2007 and the clinical data were analyzed. All patients were operated on within 4 weeks after neoadjuvant therapy. All specimens were assessed by the standard method of Miller and Payne (MP) grading system. The response to neoadjuvant therapy were assessed by two pathologists independently, using MP grading system and common grading system separately.</p><p><b>RESULTS</b>The response rate using the MP grading system were grade 1 in 12 cases (7.8%), grade 2 in 33 cases (21.4%), grade 3 in 64 cases (41.6%), grade 4 in 31 cases (20.1%) and grade 5 in 14 cases (9.1%). Using the common grading system, the response were mild in 51 cases (33.1%), moderate in 71 cases (46.1%) and severe in 32 cases (20.8%). MP grading system may be related to common grading system (chi2 = 186.660, P < 0.01). Follow up information were available in 147 cases, with 14 cases showing recurrence, metastasis or death from the disease. The MP grading system may be related to the outcome (chi2 = 11.612, P = 0.020), but not the common grading system (chi2 = 0.881, P = 0.644).</p><p><b>CONCLUSION</b>MP grading system may be one of the prognostic factors in the neoadjuvant therapy of breast cancer.</p>

Diagnostic value of core needle biopsy before neoadjuvant chemotherapy for breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To assess the diagnostic value of core needle biopsy (CNB) before neoadjuvant chemotherapy for breast cancer.</p><p><b>METHODS</b>One hundred and nineteen breast cancer cases underwent neoadjuvant chemotherapy in our hospital during the period from June, 2005 to January, 2007 were analyzed. CNB was carried out before starting chemotherapy. The hematoxylin and eosin-stained slides of CNB taken before and after neoadjuvant chemotherapy were reviewed independently by two pathologists, and the rate of consistency was verified.</p><p><b>RESULTS</b>Amongst the 119 cases studied, 110 cases were confirmed to be carcinoma, including 105 cases of invasive carcinoma and 5 cases of ductal carcinoma-in-situ. The rate of consistency was 97.22% (105/108).</p><p><b>CONCLUSION</b>CNB has important value in distinguishing benign from malignant lesions, as well as in confirming the diagnosis of invasive carcinoma before starting neoadjuvant chemotherapy.</p>

The effects of the tangfukang capsules on cytokines of early diabetic nephropathy / 中国中药杂志

<p><b>OBJECTIVE</b>To find out the mechanism of Tangfukang on the diabetic nephropathy(DN).</p><p><b>METHOD</b>A Model of streptorotocin diabetic rats was used. The expressions of the AGEs, ICAM-1, IV-C and FN were observed in renal cortex of diabetic rats with immunohistochemical method. The level of the IL-1 beta in blood serum was measured by radioimmunoassay method and the level of TNF was determined in blood serum by ELISA method. Aminoguanidine was selected as the control medicine which could inhibit the expression of monenzymatic glycosylation end products of protein. All the results were compared to analyze the effect of Tangfukang on monenzymatic glycosylation of protein and cytokine expression in early diabetic nephropathy rats.</p><p><b>RESULTS</b>Both Tangfukang and aminoguanidine significantly decreased the expression of AGEs, but Tangfukang was greatly superior to aminoguanidine in suppressing the expression of cytokine like ICAM-1, IL-1 beta, TNF-alpha and the ingredients of extracellular matrix like IV-C, FN.</p><p><b>CONCLUSION</b>It may be the partical mechanism of Tangfukang to suppress the monenzymatic glycosylation of protein and to reduce the expression of cytokine in diabetes. The effect of Tangfukang is superior to that of aminoguanidine.</p>