IHC与FISH检测浸润性乳腺癌患者HER2蛋白表达和基因扩增的差异性分析

目的:探讨并比较免疫组织化学法（IHC）与荧光原位杂交法（FISH）检测浸润性乳腺癌人表皮生长因子受体-2（HER2）蛋白表达和基因扩增的差异性。方法:采用IHC法和FISH法分别检测桂西地区120例乳腺癌患者石蜡标本中HER2蛋白表达与基因扩增情况,比较IHC与FISH检测结果一致性并进行结果相关性分析。对检测不一致的病例重新检测及判读,分析差异原因。结果:120例乳腺癌患者中IHC 33例阳性（3+）中FISH检测阳性33例,阳性符合率100%;IHC 61例不确定（2+）中FISH检测阳性24例,阳性符合率39.34%;IHC 26例阴性（0/1+）中FISH检测阴性21例,阴性符合率80.77%。结果显示,除IHC（2+）外,IHC检测HER2蛋白表达与FISH检测HER2基因扩增有较好的一致性（P＜0.05）。造成两种检测方法差异的原因可能有标本固定不及时,抗体浓度偏低等。结论:IHC法检测HER2与FISH法一致性较好。临床实践中可根据实际情况,结合使用,以便指导临床治疗。     

HER2阳性乳腺癌治疗的研究进展

[摘要] 人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）阳性乳腺癌侵袭性高,预后差。随着抗HER2药物的不断出现及广泛应用,HER2 阳性乳腺癌患者的预后出现了非常显著的改善。10 年随访结果证实1 年曲妥珠单抗辅助治疗可以显著降低疾病复发风险;对于术后的高危人群,曲妥珠单抗联合帕妥珠单抗或者曲妥珠单抗序贯来那替尼可以进一步减少复发。5 年随访结果表明帕妥珠单抗+曲妥珠单抗为基础的新辅助治疗可使病理完全缓解（pathological complete response,pCR）转化为长期生存获益;白蛋白紫杉醇代替普通紫杉醇与抗HER2 药物联用可以进一步提高pCR率;而抗HER2 药物联合内分泌治疗尚不能达到与联合化疗在新辅助治疗中疗效,即使联合CDK4/6 抑制剂,对于pCR的提高依然有限。曲妥珠单抗+帕妥珠单抗联合紫杉类药物是晚期HER2 阳性乳腺癌的标准一线方案;对于老年、体弱的患者,节拍环磷酰胺可以作为紫杉类药物的替代品;拉帕替尼+曲妥珠单抗联合内分泌治疗可以作为HER2 阳性伴激素受体阳性的选择,疗效优于曲妥珠单抗联合内分泌治疗;T-DM1 无论是作为二线治疗还是三线及以后的治疗均提高了患者生存获益,是治疗晚期、耐药HER2阳性乳腺癌的首选。     

HER2低表达乳腺癌的靶向治疗研究进展

乳腺癌是全球女性的第一大恶性肿瘤，发病率在逐年增加。人表皮生长因子受体2(human epidermal growth factor receptor2,HER2)在乳腺癌的生物学行为及发病机制中起着重要作用。乳腺癌HER2低表达是指HER2免疫组织化学染色1+或2+且原位杂交（in situ hybridization,ISH）阴性，占全部类型的45%～55%。尽管在目前的临床实践中，HER2低表达大多数仍被报告为HER2阴性或三阴性乳腺癌，但HER2低表达与HER2未检出乳腺癌不仅在HER2蛋白表达水平上不同，在雌激素受体（estrogen receptor,ER）状态、原发肿瘤体积、淋巴结受累情况、新辅助治疗后的病理学完全缓解率（pathologic complete response,pCR）以及无病生存期（disease-free survival,DFS）等方面也存在差异。在针对早期HER2低表达乳腺癌靶向治疗的临床试验中，NSABP B-31及N9831试验表现出乳腺癌患者受益于曲妥珠单抗辅助治疗的可能性，然而，在Ⅲ期前瞻性随机对照研究NSABP B-47中，曲妥珠单抗并...     

172例乳腺浸润性癌 HER -2免疫组化与 FISH 技术检验对比研究

目的：比较免疫组化（IHC）和荧光原位杂交（FISH）技术在检测乳腺浸润性癌患者中 HER -2蛋白表达和基因扩增的一致性。方法：分别用 IHC 和 FISH 技术对172例乳腺浸润性癌 HER -2进行蛋白表达和基因扩增检测,比较两者检测的结果和相关性。结果：172例浸润性乳腺癌标本行 IHC 检测结果30例为（1＋）,88例为（2＋）,42例为（3＋）,12例为（-）。172例乳腺癌标本进行 FISH 检测结果71例为阳性,101例为阴性。其中 FISH 结果阳性标本中 IHC 检测有2例（1＋）,30例（2＋）,39例（3＋）。IHC 检测 HER -2为（3＋）的病例 FISH 检测中阳性符合率92.9%（39/42）,且检测 HER -2（-）的病例 FISH 检测均为阴性, IHC 检测 HER -2（2＋）的88例患者中有58例经 FISH 检测证实 HER -2呈阴性,30例呈阳性。FISH 检测共发现47例17号染色体多体,其发生率为27.3%。用 IHC 检测 HER -2发现有25例标本存在肿瘤之间的不同表达,而在这25例标本的 FISH 检测结果中有11例存在 HER -2基因瘤内遗传异质性。结论：HER -2蛋白表达和基因扩增 IHC 和 FISH 检测在免疫组化强阳性的标本中具有较好的一致性,且免疫组化染色强度与HER -2基因扩增呈正相关。理解和判断 HER -2基因遗传异质性对肿瘤药物应用及 HER -2基因检测方法具有指导意义。     

乳腺癌HER2基因扩增的临床病理意义

目的 检测乳腺癌组织中HER2基因扩增状态,评价其临床病理意义。方法 应用FISH、IHC方法分析55例乳腺癌HER2基因扩增/蛋白表达状态与临床病理特征的关系,比对IHC法与FISH检测的一致性程度。结果 55例乳腺癌FISH检测有32例（58.2%）HER2基因扩增。IHC法HER2（+++）22例中21例（95.5%）HER2基因扩增;HER2（++）12例中10例（83.3%）HER2基因扩增;HER2（+/－）21例中1例（4.7%）HER2基因扩增。39例浸润性导管癌中30例（76.9%）有HER2基因扩增,12例浸润性小叶癌中仅1例（8.3%）HER2基因扩增。HER2基因扩增在浸润性导管癌的组织学分级间差异有统计学意义（P<0.001）,组织学Ⅲ级的浸润性导管癌较Ⅰ、Ⅱ级有较高的HER2基因扩增率。HER2基因扩增与ER、PR阴性状态及腋淋巴结转移有显著相关性（P<0.01）,与患者是否绝经无相关性（P>0.05）。结论 浸润性小叶癌,ER、PR阳性以及组织学Ⅰ级的浸润性导管癌常少有HER2基因扩增;对于组织学Ⅲ的浸润性导管癌,同时ER、PR阴性者尽管IHC检测结果为阴性,仍需做FISH检测以明确是否有HER2基因扩增。     

HER2阳性乳腺癌治疗模式的进展和优化

随着抗人表皮生长因子受体2（human epidermalgrowth factor receptor 2 ,HER2）抗肿瘤药物的不断出现及广泛应用,HER2 阳性乳腺癌患者的治疗以及预后得到了显著的改善。PEONY 研究结果的发布再次奠定了帕妥珠单抗+曲妥珠单抗的双靶治疗模式在新辅助治疗领域中的地位;结合TRYPHAENA 和TRAIN-2 两项研究,紫杉类+铂类应该是抗HER2 双靶治疗的首选化疗方案,疗程宜6 个周期。结合中国乳腺癌新辅助治疗专家共识和辅助APT 研究的最新随访结果,新辅助治疗适用人群为肿瘤直径超过3 cm 和/或淋巴结阳性的患者,新辅助治疗后如果没有获得pCR,T-DM1 应该是辅助治疗的首选模式,帕妥珠单抗+曲妥珠单抗的双靶辅助模式期待PEONY 研究的后续生存随访;对于没有淋巴结转移的小肿瘤（≤3 cm）低危患者可以考虑免除新辅助治疗,采取直接手术+术后给予曲妥珠单抗联合单药紫杉醇的辅助治疗模式。曲妥珠单抗+帕妥珠单抗联合紫杉类药物依然是晚期HER2 阳性患者的标准一线治疗;对于中国患者而言,吡咯替尼联合卡培他滨可以作为二线的优选;T-DM1 可以作为三线及后线选择;曲妥珠单抗、帕妥珠单抗、T-DM1 治疗失败的情况下,DS-8201 成为新的选择模式;伴有脑转移的HER2 阳性晚期乳腺癌患者则可以考虑图卡替尼与曲妥珠单抗和卡培他滨的联合治疗模式。     

IHC与FISH对HER2阳性乳腺癌新辅助靶向治疗疗效的预测价值

目的 探讨免疫组织化学染色(IHC)及荧光原位杂交(FISH)结果对人表皮生长因子受体2(HER2)阳性乳腺癌患者新辅助靶向疗效的预测意义.方法 回顾性分析2019-01-01-2020-09-30安徽医科大学第二附属医院(21例)及空军军医大学附属西京医院(91例)合计112例HER2阳性非特殊类型浸润性乳腺癌术前新...     

HER2阳性乳腺癌治疗中蒽环类药物应用的研究进展

摘 要：蒽环类药物是乳腺癌治疗的基石之一，鉴于蒽环类药物令人担忧的心脏毒性限制以及抗人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）治疗药物的发展，导致蒽环类药物在HER2阳性乳腺癌新辅助和辅助治疗中的地位受到挑战。全文从HER2阳性乳腺癌新辅助和辅助治疗的临床研究中探讨蒽环类药物的“去留”作一综述。     

“精准医疗”时代从乳腺癌分子分型探讨抗体-药物偶联物的临床价值及最新研究进展

乳腺癌的发病率目前已位居女性恶性肿瘤之首。乳腺癌具有高度异质性，可分为luminal A、luminal B、人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)过表达及三阴性型4种分子分型。然而既往的分子分型方法导致处于HER2低表达状态患者的治疗选择十分有限。近年来，随着抗体-药物偶联物（antibody-drug conjugate,ADC）的飞速发展，使HER2低表达乳腺癌患者获得了新的治疗选择，并促进了当前国内外指南中对HER2表达状态判定标准的更新——基于免疫组化（immunohistochemistry,IHC）和原位杂交（in situ hybridization,ISH）检测技术，将HER2的表达分为HER2阳性（IHC 3+或IHC 2+/ISH+）、HER2低表达（IHC 1+或IHC 2+/ISH-）以及HER2阴性（IHC 0）3种情况。ADC是一种由连接子将单克隆抗体与细胞毒性物质偶联而成的免疫偶联物。在乳腺癌领域，多项大型临床试验已经证明了以HER2为靶点的ADC恩美曲妥珠单抗（T-DM1）、...     

人表皮生长因子受体2阳性乳腺癌应用新辅助治疗的疗效及影响因素分析

目的 分析人表皮生长因子受体2(HER2)阳性乳腺癌应用新辅助治疗的疗效及影响因素。方法 选取47例HER2阳性乳腺癌患者,均接受曲妥珠单抗和帕妥珠单抗联合紫杉类+卡铂新辅助治疗。比较不同激素受体（HR）表达情况乳腺癌患者的临床特征,HER2阳性乳腺癌患者新辅助治疗总病理学完全缓解（tpCR）的影响因素采用Logistic回归分析。结果 47例HER2阳性乳腺癌患者中,HR阴性19例,HR阳性28例,HR阳性患者年龄≤50岁、月经状态为绝经前比例均明显高于HR阴性患者,乳腺病理学完全缓解（bpCR）率、tpCR率和客观缓解率（ORR）均明显低于HR阴性患者,差异均有统计学意义（P﹤0.01）。47例接受曲妥珠单抗和帕妥珠单抗联合紫杉类+卡铂新辅助治疗患者的tpCR率为70.21%(33/47),单因素分析结果显示,HER2阳性乳腺癌患者新辅助治疗的tpCR可能与雌激素受体（ER）和孕激素受体（PR）表达状态有关（P﹤0.01）;多因素Logistic回归分析结果显示,ER表达情况、PR表达情况均不是HER2阳性乳腺癌患者新辅助治疗tpCR的影响因素（P﹥0.05）。结论曲妥珠单抗和帕妥...     

Different criteria for HER2 positivity by IHC can be applied in post-chemotherapy specimens in determining HER2 as a prognosticator in locally advanced breast cancer

Purpose We evaluated the clinical significance of HER2 in post-chemotherapy specimens after surgery in locally advanced breast cancer (LABC). Methods Thirty-four patients with LABC were treated with neoadjuvant chemotherapy, surgery, adjuvant chemotherapy, and radiotherapy. The HER2 status was determined using both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in the paraffin-embedded surgical specimens after neoadjuvant chemotherapy. Results The positive rate of HER2 was 41.2% and 32.4% by IHC and FISH, respectively. As the gene copy number of HER2 detected by FISH increased, the staining intensity by IHC increased with positive correlation (adjusted r ² = 0.743; P < 0.001). According to the cutoff values of IHC score 2+ and 3+ as the positivity criteria, the concordance rates of IHC and FISH were 91.2% (31/34) and 88.2% (30/34), respectively. With the positivity criteria of IHC score ≥2+, the locoregional recurrence-free survival was better in the HER2-negative patients (P = 0.04). Trends were also found for the prolonged distant recurrence-free, disease-free, and overall survivals in the HER2-negative patients by IHC (2+). Trends for poor clinical response (P = 0.06) and more axillary nodes involvement (P = 0.08) were noted in the HER2-positive group by IHC (2+). In post-chemotherapy specimens, the positive HER2 status by IHC staining score ≥ 2+ predicted higher recurrence in LABC. Conclusion This suggests that different criteria for the HER2 positivity by IHC can be applied in post-chemotherapy specimens compared with that from pre-chemotherapy biopsies.     

Association between HER2 status and response to neoadjuvant anthracycline followed by paclitaxel plus carboplatin chemotherapy without trastuzumab in breast cancer

Background

We recently showed HER2-positive breast cancers are less likely to respond to neoadjuvant anthracycline chemotherapy. Here, we investigated whether HER2-positive breast cancers responded to sequential neoadjuvant anthracycline followed by paclitaxel plus carboplatin regimen in the absence of trastuzumab.

Methods

Women (n=372) with operable primary breast cancer initially received two cycles of neoadjuvant anthracyclines, the clinical tumor response was assessed, then patients were received four cycles of paclitaxel plus carboplatin regimen. All the patients did not received trastuzumab treatment in the neoadjuvant setting. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core-biopsy breast cancer tissue obtained before the neoadjuvant chemotherapy.

Results

Eighteen percent (67/372) of patients achieved a pathologic complete response (pCR) in their breast. HER2-positive tumors had a significant higher pCR rate than HER2-negative tumors (33.0% versus 13.5%, P<0.001) in this cohort of 372 patients, and positive HER2 status remained an independent favorable predictor of pCR in a multivariate analysis [odds ratio (OR), 2.26; 95% confidence interval (CI), 1.18 to 4.36, P=0.015]. Furthermore, patients who responded to initial anthracycline regimens were more likely to respond to paclitaxel plus carboplatin than patients who did not (pCR, 27.2% versus 14.6%, P=0.005). Patients with HER2-positive tumors exhibited a significant higher pCR rate than did patients with HER2-negative tumors in both anthracycline response group (40.5% versus 20.0%, P=0.025) and anthracycline non-response group (28.3% versus 11.3%, P=0.002).

Conclusions

Under the circumstance of no trastuzumab treatment, women with HER2-positive cancers derive a large benefit from paclitaxel-carboplatin-based neoadjuvant chemotherapy.     

HER2 and response to anthracycline-based neoadjuvant chemotherapy in breast cancer

BackgroundThe predictive role of human epidermal growth factor receptor 2 (HER2) to adjuvant anthracycline-based chemotherapy remains controversial. Here, we investigated the association between HER2 status and pathological response in breast cancer patients who received neoadjuvant anthracycline-based regimens.Patients and methodsWomen (n = 538) with operable primary breast cancer received neoadjuvant anthracycline-based chemotherapy. Pathological complete response (pCR) was defined as no invasive breast tumor cells in breast after completion of neoadjuvant chemotherapy. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core biopsy breast cancer tissue obtained before initiation of neoadjuvant chemotherapy.ResultsIn this cohort of 538 patients, 23.9% of patients achieved a pCR in their breast. HER2-positive tumors had a lower rate of pCR than did HER2-negative tumors (14.7% versus 25.7%, P = 0.013); negative HER2 status remained as an independent favorable predictor of pCR after adjusted for age, estrogen receptor, progesterone receptor, tumor size, chemotherapy cycles, and tumor grade in a multivariate analysis (odds ratio = 3.14; 95% confidence interval = 1.60–6.16, P = 0.001). Furthermore, patients with a pCR had a higher 3-year disease-free survival (DFS) rate than did patients without a pCR (P = 0.007).ConclusionWomen with HER2-negative breast cancers rather than HER2-positive tumors benefit from anthracycline-based neoadjuvant chemotherapy.     

A gene expression signature of Retinoblastoma loss-of-function predicts resistance to neoadjuvant chemotherapy in ER-positive/HER2-positive breast cancer patients

Purpose

HER2-positive (HER2+) breast cancers show heterogeneous response to chemotherapy, with the ER-positive (ER+) subgroup deriving less benefit. Loss of retinoblastoma tumor suppressor gene (RB1) function has been suggested as a cardinal feature of breast cancers that are more sensitive to chemotherapy and conversely resistant to CDK4/6 inhibitors. We performed a retrospective analysis exploring RBsig, a gene signature of RB loss, as a potential predictive marker of response to neoadjuvant chemotherapy in ER+/HER2+ breast cancer patients.

Methods

We selected clinical trials of neoadjuvant chemotherapy?±?anti-HER2 therapy in HER2+ breast cancer patients with available information on gene expression data, hormone receptor status, and pathological complete response (pCR) rates. RBsig expression was computed in silico and correlated with pCR.

Results

Ten studies fulfilled the inclusion criteria and were included in the analysis (514 patients). Overall, of 211 ER+/HER2+ breast cancer patients, 49 achieved pCR (23%). The pCR rate following chemotherapy?±?anti-HER2 drugs in patients with RBsig low expression was significantly lower compared to patients with RBsig high expression (16% vs. 30%, respectively; Fisher’s exact test p?=?0.015). The area under the ROC curve (AUC) was 0.62 (p?=?0.005). In the 303 ER-negative (ER?)/HER2+ patients treated with chemotherapy?±?anti-HER2 drugs, the pCR rate was 43%. No correlation was found between RBsig expression and pCR rate in this group.

Conclusions

Low expression of RBsig identifies a subset of ER+/HER2+ patients with low pCR rates following neoadjuvant chemotherapy?±?anti-HER2 therapy. These patients may potentially be spared chemotherapy in favor of anti-HER2, endocrine therapy, and CDK 4/6 inhibitor combinations.

     

18F-fluorodeoxyglucose (FDG) PET/CT after two cycles of neoadjuvant therapy may predict response in HER2-negative,but not in HER2-positive breast cancer

The aim of this prospective study was to assess the ability of 18F-fluorodeoxyglucose (¹⁸FDG) positron emission tomography/computed tomography (PET/CT) scanning to predict pathological complete response (pCR) in breast cancer, and to investigate whether timing of the scan and trastuzumab treatment influence the accuracy of pCR prediction in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients. We treated 81 locally advanced breast cancer patients with four cycles of neoadjuvant chemotherapy (NAC). HER2-negative breast cancer patients received NAC alone, while HER2-positive breast cancer patients received NAC plus trastuzumab. ¹⁸FDG PET/CT scans were scheduled at baseline and after the second cycle of NAC. Axillary lymph node (ALN) dissection was performed after the last cycle of neoadjuvant therapy. Relative changes in standardized uptake values (SUV) between the two PET/CT scans (ΔSUV) in primary tumors and ALN metastases were calculated. There were 75 patients with 150 PET/CT scans in the final analysis, including 41 HER2-negative and 34 HER2-positive cases. In the HER2-negative group, the ΔSUV predicted overall and ALN pCR; the receiver operating characteristics-areas under curve (ROC-AUC) were 0.87 and 0.80 (P = 0.0014 and 0.031, respectively) and the negative predictive values were 94% and 89% respectively. However, in the HER2-positive group, ΔSUV could predict neither overall nor ALN pCR; the ROC-AUCs were only 0.56 and 0.53, with P = 0.53 and 0.84, respectively. Hence, the ΔSUV after two cycles of neoadjuvant therapy could predict pCR in HER2-negative patients treated with NAC alone, but not in HER2-positive patients treated with NAC plus trastuzumab.     

Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab

Background: The aim of this study was to compare the extent of pathologic response in patients with HER2-positive (HER2+) breast cancer treated with standard neoadjuvant chemotherapy, with or without trastuzumab (H), according to hormone receptor (HR) status.Patients and methods: We included 199 patients with HER2+ breast cancer from three successive cohorts of neo-adjuvant chemotherapy on the basis of paclitaxel (Taxol) (P) administered weekly (w) or three weekly (3-w), followed by 5-fluorouracil (F), doxorubicin (A) or epirubicin (E), and cyclophosphamide (C). Residual cancer burden (RCB) was determined from pathologic review of the primary tumor and lymph nodes and was classified as pathologic complete response (pCR) or minimal (RCB-I), moderate (RCB-II), or extensive (RCB-III) residual disease.Results: In HR-positive (HR+) cancers, a higher rate of pathologic response (pCR/RCB-I) was observed with concurrent H + 3-wP/FEC (73%) than with 3-wP/FEC (34%, P = 0.002) or wP/FAC (47%; P = 0.02) chemotherapy alone. In HR-negative (HR-) cancers, there were no significant differences in the rate of pathologic response (pCR/RCB-I) from 3-wP/FAC (50%), wP/FAC (68%), or concurrent H + 3-wP/FEC (72%).Conclusions: Patients with HR+/HER2+ breast cancer obtained significant benefit from addition of trastuzumab to P/FEC chemotherapy; pathologic response rate was similar to that seen in HR-/HER2+ breast cancers.     

Molecular subtyping of early-stage breast cancer identifies a group of patients who do not benefit from neoadjuvant chemotherapy

The aim of this study was to analyze the correlation between the pathologic complete response (pCR) rate after neoadjuvant chemotherapy and long-term outcome (distant metastases-free survival [DMFS]) in patients with early-stage breast cancer using BluePrint and MammaPrint molecular subtyping versus clinical subtyping using immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) for the determination of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (HER2). Data were analyzed from 437 patients in four neoadjuvant chemotherapy trials. BluePrint and MammaPrint outcomes were determined from 44K Agilent arrays, the I-SPY 1 data portal, or Affymetrix U133A arrays. The pCR rate differed substantially among BluePrint molecular subgroups: 6 % in Luminal A-type, 10 % in Luminal B-type, 47 % in HER2-type, and 37 % in Basal-type patients. In the Luminal A-type group (n = 90; including seven HER2-positive patients and eight triple-negative patients by IHC/FISH), the 5-year DMFS rate was 93 %. The pCR rate provided no prognostic information, suggesting these patients may not benefit from chemotherapy. Forty-three of 107 (40 %) HER2-positive patients were classified as Luminal-type by BluePrint and may have lower response rates to targeted therapy. Molecular subtyping identified 90 of 435 (21 %) patients as Luminal A-type (BluePrint Luminal-type/MammaPrint Low Risk) with excellent survival. The pCR rate provided no prognostic information. Molecular subtyping can improve the stratification of patients in the neoadjuvant setting: Luminal A-type (MammaPrint Low Risk) patients have a good prognosis with excellent survival and do not seem to benefit from chemotherapy. We observed marked benefit in response and DMFS to neoadjuvant treatment in patients subtyped as HER2-type and Basal-type. BluePrint with MammaPrint molecular subtyping helps to improve prognostic estimation and the choice of therapy versus IHC/FISH.     

Loss of HER2 positivity and prognosis after neoadjuvant therapy in HER2-positive breast cancer patients

BackgroundEmerging literature data are showing that a change in human epidermal growth factor receptor (HER2) status adversely affects breast cancer patient's prognosis. The aim of this study was to evaluate the prognostic impact of HER2 loss in patients with HER2-positive disease treated with neoadjuvant therapy with or without anti-HER2 agents.MethodsOne hundred and seven consecutive HER2-positive patients were identified from a prospectively maintained database. The first cohort includes 40 patients treated with chemotherapy (CT) alone. The second cohort includes 67 patients treated with neoadjuvant CT plus anti-HER2 agents (trastuzumab and/or lapatinib). HER2 expression was evaluated by immunihistochemistry or fluorescence in situ hybridization on pretreatment core biopsy and on surgical specimen after therapy.ResultsThe rates of pathologic complete response (pCR) and breast-conserving surgery were higher in the CT + anti-HER2 cohort. A loss of HER2 expression was observed in 40% of the patients with residual disease after CT alone versus 14.7% of the patients after CT + anti-HER2 agents (P = 0.019). Patients not achieving a pCR have a significant increase in the risk of relapse when compared with those achieving a pCR (hazard ratio [HR] 9.55, P = 0.028). Patients with HER2 loss tended to have a higher risk of relapse as comparing to patients with maintained HER2 positivity (HR 2.41, P = 0.063).ConclusionThe pCR is confirmed as a powerful predictor of long-term outcome. The rate of HER2 loss is higher in patients receiving neoadjuvant CT without anti-HER2 agents. HER2 status on residual disease after preoperative therapy can be helpful in selecting patients at different risk of relapse, to be included in prospective trial exploring further adjuvant therapy.