Influence Of Neoadjuvant Chemotherapy On HER-2Status In Invasive Breast Cancer

【Background】Reliably estimating HER-2expression in breast cancer is important forpredicting patient prognosis and optimizing adjuvant therapeutic strategies.Neoadjuvant chemotherapy (NAC) has become a standardized treatment strategyfor both locally advanced invasive breast cancer and operable breast cancer. Theinfluences of NAC on ER, PgR, Ki-67expresion in invasive breast cancer havebeen illustrated in the literatures. However, there was no consensus on HER-2status which was an important marker for treatment guidance and prognosisassessment. The relationships between the alteration of HER-2status and thesubtypes of tumor, NAC pathological response, chemotherapy regimen, timeinterval from the last chemotherapy to surgery remain unclear.【Objective】1. To analyze the effects of anthracycline-and taxane-based NAC on HER-2statusin invasive breast cancer. 2. To evaluate the relationships between HER-2status alterations and pathologicalresponses to NAC, chemotherapy regimen, time interval from the lastchemotherapy to surgery and the subtypes of tumor.3. To investigate the correlation between HER-2status and pathological responseto anthracycline-and taxane-based NAC.【Methods】One hundred thirty-one primary invasive breast cancer patients were treatedwith neoadjuvant anthracycline-and taxane-based chemotherapy. The evaluationsof pathological response to NAC was performed according to HistopathologicalCriteria for Assessment of Therapeutic Response of the Japanese Breast CancerSociety (JBCS criteria) and Miller and Payne grading system (MP criteria). HER-2status was evaluated by immunohistochemistry (IHC) on sequential core needlebiopsies of primary tumors before receiving pre-operative NAC and surgicalresection specimens of post-NAC residual breast cancers or tumor-positive axillarylymph nodes. Thirty-two pairs of specimens with discordant HER-2IHC scoreswere analyzed by HER-2fluorescence in situ hybridization (FISH) before and afterNAC. Thirty-seven invasive breast cancer without receiving NAC were studied asthe control group.【Results】The average age of breast cancer patients receiving NAC was49.6ages, andinvasive ductal carcinoma was the most common histological type (84.7%). TheNAC regimens mainly included TEC, TE and TE+RHEI (Recombinant HumanEndostatin Injection), and most patients received3-4cycles of NAC. Based oncriteria of the Japanese Breast Cancer Society and the Miller and Payne system,pathological complete responses to NAC were observed in11.5%(15/129) ofprimary tumors. A significant difference in HER-2status by IHC between core needle biopsies and surgical resection specimens in patients receiving NAC wasobserved. HER-2IHC scores changed in35.48%(44/124) of patients receivingNAC compared to16.22%(6/37) of control patients without NAC (P=0.026).Furthermore,65.91%(29/44) of tumors showed down-regulated HER-2expressionby IHC in NAC group. Alterations of HER-2IHC scores did not significantlycorrelate with tumor subtype, pathological response to NAC, adjuvant regimen ortime interval from the last chemotherapy to surgery. HER-2protein overexpressionlevels both in core biopsies and in resected specimens were associated withfavorable pathological response to anthracycline-and taxane-based chemotherapy.However, tumors with altered HER-2IHC scores after NAC revealed stable HER-2gene amplification/non-amplification by FISH analysis.【Conclusions】1. Neoadjuvant anthracycline-and taxane-based chemotherapy for breastcarcinoma resulted in the decrease of HER-2protein expression by IHC.2. HER-2protein overexpression in core biopsies or surgical resection specimensindicated greater sensitivity to neoadjuvant anthracycline-and taxane-basedchemotherapy and may be a predictive marker for pathological completeresponse.3. No correlation was detected between the alteration of HER-2/neu IHC statusand tumor subtype, pathological response to NAC, adjuvant regimen or timeinterval from the last chemotherapy to surgery. The pathological response didnot significantly correlate with the course of chemotherapy neither.4. Retesting HER-2IHC status in residual tumors after NAC should be suggested,and FISH may be a more accurate method than IHC for determining HER-2status in post-NAC resection specimens.