| Objective: In recent years the incidence of breast cancer increased.According to statistics, in the developed countries and large and medium-sizedcities in China, breast cancer has been the first malignant tumors in female.Though neoadjuvant chemotherapy is used for locally advanced breast cancerwith more and more attention paid to the primary treatment, a variety ofcytotoxic drugs combination therapy is still can’t stop the progress of thedisease sometimes. Studies indicates that breast cancer occurrence anddevelopment is closely related to the generation of tumor blood vessels,Endostar as our independent research and development of human recombinantendostatin injection, which can inhibit angiogenesis and nutrition supply oftumor cells and accelerate the apoptosis of cancer cells. The vitro experimentshave established that EN and chemotherapy drugs have synergy. Since2006,EN has been applicated in clinician lonely or combination chemotherapy inlung cancer, colon cancer, rectal cancer and other solid tumors which hasmade obvious effect.To investigate the recent efficacy and safety of EN plus TEC program asneoadjuvant chemotherapy to locally advanced breast cancer by clinical andpathological effects and indirectly explored the correlation between molecularsubtypes of breast cancer and the efficacy of neoadjuvant chemotherapy. It canguide the further selection of drugs for neoadjuvant chemotherapy andindividualized treatment.Methods: This study recruited40patients of stage Ⅱ-Ⅲ with primarybreast cancer from May2011to January2013at the department of BreastCenter in The4th Affiliated Hospital of Hebei Medical University in China.Follow the principle of randomized divided into TEC+EN group (20cases)and TEC+EN group (20cases) and all of them received four cycles of preoperative chemotherapy until surgery. HE staining to observe MPclassification and histologic grades in the postoperative residual carcinomatissue and immunohistochemical MaxVisionTMone-step measures theexpression of VEGF, MVD, ER, PR, HER-2in breast cancer tissue before andafter neoadjuvant chemotherapy. Use SPSS16.0statistical software packagefor data processing, evaluating the efficacy of EN plus TEC program, andaccording to RECIST solid tumor curative effect evaluation standard, pCR,MP classification. And indirect explored the correlation between molecularsubtypes of breast cancer and the efficacy of neoadjuvant chemotherapy.Results:1The near short curative effect and toxicity between TEC program andTEC+EN program1.1The evaluation of clinical response (combined with ultrasound, MRI andclinical palpation)The OR%of TEC group was90%(18/20), while the TEC+EN group was95%(19/20), P>0.05, there was no significant difference.The cCR%of TEC group was15%(3/20), while the TEC+EN group was40%(8/20), P>0.05, there was no significant difference.1.2The evaluation of pathologyComparison of pCR: TEC group was0%(0/20), while TEC+EN groupwas15%(3/20), P>0.05, there was no significant difference.Comparison of response in MP grading system: the rate of MHR in TECgroup was40%(5/20), while in TEC+EN group was60%(12/20), P<0.05,there was significant difference.Comparison of the expression of VEGF, MVD in before and after thetreatment. TEC group (20cases): VEGF positive expression rate in before andafter the treatment respectively was70%,45%, not significant difference（P=0.110>0.05）; MVD value respectively was（76.82±22.96）,（63.43±14.68）, significant difference.（P<0.05）TEC+EN group (20cases): VEGFpositive expression rate in before and after the treatment respectively was85%,35%with significant difference（P<0.05）; MVD value respectively was （84.36±23.74）,（62.73±17.95）with significant difference.（P<0.05）1.3Comparison of toxicitiesThis research mainly toxicities were bone marrow suppression, hair loss,gastrointestinal reaction, liver function damage, and so on. TEC group andTEC+EN group Ⅲ, Ⅳ degree of bone marrow inhibition rate was75%(15/20),80%(16/20), respectively. After actively symptomatic,appropriate to reduce chemotherapy drug dose, prolong the time interval doesnot affect patients continue treatment. Other side effects for severe hair loss(TEC100%, TEC+EN100%), Severe gastrointestinal reaction (TEC20%andTEC+EN30%), liver function damage (TEC15%, TEC+EN15%), no moreserious nerve system, cardiovascular system and other aspects of side effects.There were no significant diferences in the incidence of bone marrowsuppression, hair loss, gastrointestinal reaction and liver function damage.(P<0.05)220cases of TEC+EN group can be divided into: VEGF (+)17cases, VEGF(-)3cases, according to the expression of VEGF before chemotherapy2.1The evaluation of clinical responseThe OR%of VEGF（+）group was100%（17/17）, while the OR%ofVEGF（-）group was66.67%(2/3), P>0.05, there was no significant difference.The cCR%of VEGF（+）group was47.06%（8/17）, while the cCR%ofVEGF（-）group was (cCR)0%（0/3）, P>0.05, there was no significantdifference.2.2The evaluation of pathologyComparison of pCR: VEGF（+） group was17.65%（3/17）, while VEGF（-）group was0, P>0.05, there was no significant difference.Comparison of response in MP grading system: the rate of MHR inVEGF（+）group was70.59%(12/17), while the rate of MHR in VEGF（-）group was0(0/3), P<0.05, there was significant difference.3Comparison of the efficacy of neoadjuvant chemotherapy in differentmolecular subtype of breast cancer.According to tne molecular subtype of breast cancer, all cases were divided into3subgroups:（ER+and/or PR+, HER-2-）18cases,（any ER andPR, HER-2+）12cases,（ER-, PR-, HER-2-）10cases.3.1The evaluation of Clinical responseComparison of OR: OR of （ER+and/or PR+, HER-2-）was94.44%(17/18),（any ER and PR, HER-2+）was91.67%(11/12), while （ER-, PR-,HER-2-）was90%(9/10), between the three groups, P>0.05, there was nosignificant difference.Comparison of cCR: the rate of cCR of （ER+and/or PR+, HER-2-）subtype was11.11%(2/18),（any ER and PR, HER-2+）subtype was25%(3/12), while （ER-, PR-, HER-2-）subtype was60%(6/10), between the threegroups, P<0.05, there was significant difference.3.2The evaluation of pathologyComparison of pCR: the rate of pCR of （ER+and/or PR+, HER-2-）subtype was0%(0/18),（any ER and PR, HER-2+）subtype was16.7%(2/12),while （ER-, PR-, HER-2-）subtype was10%(1/10), between the three groups,P<0.05, there was significant difference.Comparison of response in MP grading system: the rate of MHR in（ER+and/or PR+, HER-2-）subtype was22.22%(4/18), the rate of MHR in（any ER and PR, HER-2+）subtype was HER2+50%(6/12), while the rateof MHR in（ER-, PR-, HER-2-）subtype was70%(7/10), between the threegroups, P<0.05, there was significant difference.Conclusions:1EN plus TEC program has the trend of enhancing OR, cCR rate,pCR rate. The advantage of EN+TEC program embodied in Inhibiting theexpression of VEGF, reducing tumor microvascular density, enhancing tumorresponse to chemotherapy, there was significant difference compared withpure TEC program. EN and TEC have synergy.2EN will not increase the incidence of the side effects ofchemotherapy drugs when applied alone，and severity.3VEGF is a certain degree of expression in locally advanced primarybreast cancer tissue. CD34markers of microvascular(MV) in breast cancer tissues were visible. The expression of VEGF and MVD in breast cancertissue were positively correlated. VEGF can promote the formation of tumormicrovascular, so inhibit VEGF expression can prevent the formation oftumor microvascular. The expression of VEGF in breast cancer tissue may beused to predict efficacy of Clinical application of EN.4There is no significant difference between molecular subtypes of breastcancer in the clinical effective rate of neoadjuvant chemotherapy.（ER-, PR-,HER-2-）and（any ER and PR, HER-2+）subtype are higher sensitivity tochemotherapy than（ER+and/or PR+, HER-2-）subtype... |
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