表柔比星联合紫杉醇新辅助化疗治疗乳腺癌保乳术患者的疗效及安全性

目的：探讨表柔比星联合紫杉醇（E+T）新辅助化疗对乳腺癌保乳术患者的效果及安全性。 方法：选取2014年1月—2018年1月收治的107例IIa~IIIa期女性原发性乳腺癌患者,患者均于保乳术前行3周E+T方案新辅助化疗,且患者化疗前均检测空芯针穿刺标本雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）、Ki-67、p53及Bcl-2表达情况。评价临床及病理疗效并评估毒副反应情况。 结果：所有患者均完成了4个或6个疗程的术前3周E+T新辅助化疗,5例IIIa期患者化疗后降期为IIb;患者均于化疗后12~16 d行乳腺癌保乳术治疗。临床有效率为89.72%,病理性完全缓解（pCR）率为17.76%,腋窝淋巴结转阴率为54.76%。不同ER、PR、Ki-67、p53表达状态患者间pCR率有统计学差异（均P<0.05）,而不同HER-2、Bcl-2表达状态患者间pCR率无统计学差异（均P>0.05）。除出现IV度白细胞减少5例、IV度中性粒细胞减少5例外,其余毒性反应均可耐受。86例术后随访12~60个月,复发转移19例,死亡6例,2例出现对侧乳腺癌,其余患者均恢复良好。 结论：E+T新辅助化疗方案治疗乳腺癌保乳术患者可获得较高的pCR率,毒副反应可耐受。ER、PR、Ki-67、p53可作为E+T新辅助化疗方案疗效的预测因子。     

Pathologic complete response after neoadjuvant chemotherapy in HER2-overexpressing breast cancer according to hormonal receptor status

ObjectiveFor patients with HER2-positive breast cancer, the prognostic impact of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is unclear when stratified by hormonal receptor (HR) status; however, the impact of pCR on survival when stratified by hormonal receptor (HR) status is uncertain.Patients and methodsThis multicenter retrospective study investigated the predictors of pCR and its prognostic value in Japanese patients 366 HER2-positive breast cancer who received NAC. pCR was defined as no invasive residual tumor in the breast or axilla.ResultsMedian follow-up was 55 months. Multivariate analysis revealed that HR status (OR, 0.37; p < 0.001) was one of the independent predictors of pCR. Five-year recurrence-free survival was higher in HR-negative patients with pCR (93%) than in those without pCR (68%), and pCR was independently prognostic (hazard ratio, 0.32; p = 0.005). However, 5-year recurrence-free survival was not different between HR-positive patients with pCR (94%) and those without pCR (84%), and pCR was not significantly prognostic (hazard ratio, 0.53; p = 0.39). In addition, 5-year overall survivals were high and similar (97% in pCR, 94% in non-pCR). Among 204 patients treated with neoadjuvant trastuzumab, pCR was not significantly prognostic in the HR-positive group (hazard ratio, 0.63; p = 0.56).ConclusionOur study suggested that the HER2-positive HR-positive patients had a good prognosis despite the lower achievement rate of pCR, whose prognostic impact was smaller than that in the HER2-positive HR-negative patients. The treatment strategy for HER2-positive breast cancer can be stratified by HR status.     

Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy: A meta-analysis

BackgroundThis meta-analysis assessed the predictive and prognostic value of tumor infiltrating lymphocytes (TILs) in neoadjuvant chemotherapy (NACT) treated breast cancer and an optimal threshold for predicting pathologic complete response (pCR).MethodsA systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible studies published before April 2022. Either a fixed or random effects model was applied to estimate the pooled hazard ratio (HR) and odds ratio (OR) for prognosis and predictive values of TILs in breast cancer patients treated with NACT. The study is registered with PROSPERO (CRD42020221521).ResultsA total of 29 published studies were eligible. Increased levels of TILs predicted response to NACT in HER2 positive breast cancer (OR = 2.54 95%CI, 1.50–4.29) and triple negative breast cancer (TNBC) (OR = 3.67, 95%CI, 1.93–6.97), but not for hormone receptor (HR) positive breast cancer (OR = 1.68, 95 %CI, 0.67–4.25). A threshold of 20% of H & E-stained TILs was associated with prediction of pCR in both HER2 positive breast cancer (P = 0.035) and TNBC (P = 0.001). Moreover, increased levels of TILs (either iTILs or sTILs) were associated with survival benefit in HER2-positive breast cancer and TNBC. However, an increased level of TILs was not a prognostic factor for survival in HR positive breast cancer (pooled HR = 0.64, 95%CI: 0.03–14.1, P = 0.78).ConclusionsIncreased levels of TILs were associated with increased rates of response to NACT and improved prognosis for the molecular subtypes of TNBC and HER2-positive breast cancer, but not for patients with HR positive breast cancer. A threshold of 20% TILs was the most powerful outcome prognosticator of pCR.     

多西他赛+卡铂联合曲妥珠单抗方案对早期人表皮生长因子受体2阳性乳腺癌的新辅助治疗效果

目的探讨多西他赛+卡铂联合曲妥珠单抗(TCH)方案对早期人表皮生长因子受体2(HER2)阳性乳腺癌的新辅助治疗效果。方法回顾性分析2013年1月至2018年12月北京大学第一医院乳腺疾病中心经治的522例早期HER2阳性乳腺癌患者的临床资料,占同期收治早期浸润性乳腺癌患者的21.80%(522/2 394)。其中113例接受TCH方案进行新辅助治疗,年龄[M(QR)]52(13)岁(范围:23~69岁)。记录TCH方案新辅助治疗后病理完全缓解(pCR,ypT0N0M0期)的例数,采用Miller-Payne标准进行病理学评价。采用Kaplan-Meier法计算无病生存率和总体生存率,采用Log-rank检验比较组间生存差异。结果接受曲妥珠单抗规范治疗患者(294例)的无病生存率优于未规范治疗患者(177例)(84.4%比72.4%,χ²=4.095,P=0.046)。发生3~4级不良反应的患者占全部患者的15.9%(18/113),包括3~4级中性粒细胞减少12例,腹泻6例。31例患者获得pCR(ypT0N0M0),pCR率为27.4%(31/113)。pCR患者与非pCR患者的无病生存率和总体生存率无差异(91.8%比85.0%,92.5%比90.5%,P值均>0.05)。病理学评价为G4~5的患者无病生存率优于G1~3患者(89.6%比81.5%,χ²=5.340,P=0.021),而总体生存率的差异无统计学意义(91.4%比89.1%,χ²=1.008,P=0.315)。结论早期HER2阳性乳腺癌采用TCH方案行新辅助治疗的效果较好,新辅助治疗后病理学评价为G4~5的患者的无病生存率更高。     

表阿霉素联合多西紫杉醇新辅助化疗治疗三阴乳腺癌的疗效及预后评价

目的探讨三阴乳腺癌(TNBC)与非三阴乳腺癌(non-TNBC)接受表阿霉素联合多西紫杉醇方案(ET方案)的化疗敏感性及预后方面的差别。方法对接受ET新辅助化疗方案治疗的249例乳腺癌患者进行回顾性分析。依据免疫组化雌激素受体(ER)、孕激素受体(PR)、表皮生长因子受体2(HER2)表达水平将乳腺癌分为三阴乳腺癌及非三阴乳腺癌两类,分析三阴与非三阴乳腺患者接受ET新辅助化疗方案后,二者病理疗效及远期生存的差别。结果 249例患者中,54(21.7%)例为三阴乳腺癌,195(78.3%)例为非三阴乳腺癌。三阴乳腺癌的病理完全缓解(pCR)率为25.9%,明显高于非三阴乳腺癌的12.3%(P=0.019)。三阴乳腺癌患者,特别是新辅助化疗后仍有癌残留的患者,其5年无病生存率(DFS)及5年的总生存率(OS)均明显低于非三阴乳腺癌(P值均<0.05)。获得pCR的乳腺癌患者5年的DFS和OS均明显高于化疗后仍有癌残留的患者(P值均<0.05)。获得pCR的三阴乳腺癌与非三阴乳腺癌患者的DFS(P=0.837)及OS(P=0.398)均无统计学差异。结论本研究结果表明,相比于非三阴乳腺癌患者,三阴乳腺癌患者具有更高的病理完全缓解率,但预后却较差。     

Pathological response and survival after neoadjuvant therapy for breast cancer: A 30-year study

Purpose of the researchHER2-positive and triple-negative breast cancer (TNBC) still have a poor prognosis. Pathological complete response (pCR) is usually considered a surrogate marker for outcome. The aim of this study was to reconsider these parameters on a large population after a long follow-up. 348 patients with unilateral breast cancer who received neoadjuvant treatment at our institution over 30 years were included.ResultsPatients were classified according to hormonal receptors (HR) and HER2. Median follow-up was 7 years. pCR was significantly lower in HR+/HER2? tumors (P < 0.0001). The 7-year OS rates were 76.1% (HR+/HER2?), 60.1% (TNBC), 72.4% (HR+/HER2+), and 49.9% (HR?/HER2+). Disease-free survival (DFS) and OS differed significantly according to pCR. Among HER2+ patients, pCR rate, DFS and OS were greater with trastuzumab.ConclusionsTNBC and HR?/HER2+ tumors have the worst outcome. pCR remains a significant prognostic factor. Trastuzumab strongly improves pCR and survival in HER2+ tumors.     

Trastuzumab in Primary Inflammatory Breast Cancer (IBC): High Pathological Response Rates and Improved Outcome

Abstract: Inflammatory breast cancer (IBC) represents a rare but aggressive and lethal form of locally advanced breast cancer (LABC) and frequently with HER‐2 neu overexpressed or amplified. We retrospectively identified 16 newly diagnosed HER‐2/neu‐positive IBC patients who were treated with preoperative trastuzumab. We determined the pathological complete response rate (pCR) when trastuzumab was added to preoperative chemotherapy in patients with HER2/neu‐positive IBC. Furthermore, we assessed the expression of CXCR4 in metastatic recurrence sites. Ten patients (62.5%) achieved a pCR. Six patients (37.5%) achieved a partial response. Median follow‐up of all patients was 24.2 months. Four (25%) patients have experienced a progression, of which three were in the brain. Two‐year progression‐free survival was 59.4% (95% CI 35–100). High expression of CXCR4 was detected in the brain metastases. We conclude that in spite of high pCR rates among women with HER‐2/neu‐positive IBC treated with neoadjuvant trastuzumab‐based regimens the outcome remains dismal and brain recurrences are frequent. CXCR4 may represent a novel therapeutic target.     

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??Analysis of the predicted factors of pathological complete response (pCR) after neoadjuvant systemic therapy in primary breast cancer and the prognostic value of pCR GAO Guo-xuan*??ZHANG Yan??ZHANG Hong??et al. *Breast Disease Center??Peking University First Hospital??Beijing 100034??China
Corresponding author??ZHANG Hong??E-mail??zhanghong1030@gmail.com
Abstract Objective To explore the predicted factors and the prognostic value of pathological complete response (pCR). Methods The clinical data of patients with primary breast cancer received neoadjuvant systemic therapy ??NST????subsequent surgery between January 2008 and December 2014 in Breast Disease Center??Peking University First Hospital were analyzed retrospectively. Data of the pathological characteristics and events in follow-up were analyzed to explore the predicted factors and the prognostic value of pCR. Results The pCR rate was 21.9%??and the patients achieved a pCR had better survival than the patients who didn’t (DFS??P=0.003??OS??P=0.009). Different subtypes differed in pCR rate (P??0.001)??Luminal B-like(HER2 negative)??HER2 positive (non-luminal) and triple-negative breast cancer (TNBC) were easier to achieve a pCR (30.6%, 37.5% and 32.4% respectively). The predicted factors of pCR in the multivariate model are the PR status before NST(OR=0.297??95%CI??0.167-0.530??P??0.001????the HER2 status before NST(OR=2.351??95%CI=1.340-4.125??P??0.003????the Ki67 status before NST??OR=6.870??95%CI??0.885-53.303??P=0.065??. Conclusion The predicted factors of pCR are the PR??HER2 and Ki67 expression before NST. PCR could be a predictor of DFS and OS??but its values differ in subtypes??and the correlationships have statistical significance in HER2 positive (non-luminal) and TNBC.     

乳腺癌新辅助化疗疗效及ER/PR,HER2,Ki67,CyclinA2的化疗预测作用

目的探讨乳腺癌新辅助化疗疗效及ER/PR,HER2,Ki67,CyclinA2的疗效预测价值。方法 2004年10月～2009年12月50例Ⅰ～Ⅲ期原发性乳腺癌,采用含紫杉类（TP/TC或TE/PE/TEC方案）或蒽环类（EC/FEC方案）联合方案,术前化疗2～6周期,45例接受手术,术后完成规定化疗,应用B超结合触诊判断临床疗效。结果化疗前后肿瘤中位最大径分别为3.6 cm和2.2 cm,有统计学差异（Z=-5.723,P=0.000）。临床疗效：CR 3例（6%）,PR 35例（70%）,SD 11例（22%）,PD 1例（2%）,临床RR 76.0%（38/50）。45例接受手术,术后3例pCR（3/45,6.7%）,3例tpCR（3/45,6.7%）。4年无病生存期（DFS）为86.2%,4年总生存率为93.1%,中位DFS 62.4月[SE：2.535,95%CI（57.450～67.388）]。不同情况下肿瘤缩小比例并无统计学差异,包括月经状态（绝经前vs.绝经后,46.4%vs.40.6%,P=0.536）、激素受体状况（阳性vs.阴性,43.0%vs.42.2%,P=0.929）、HER2（阳性vs.阴性,41.3%vs.43.9%,P=0.774）、Ki67（阳性vs.阴性,47.2%vs.43.1%,P=0.363）、CyclinA2（阳性vs.阴性,34.3%vs.50.0%,P=0.375）、分化程度（高分化vs.中分化vs.低分化,44.1%vs.42.9%vs.41.3%,P=0.983）以及不同化疗方案（TP/TC vs.TE/PE/TEC vs.EC/FEC,52.7%vs.39.8%vs.38.9%,P=0.440）。结论紫杉类及蒽环类药物联合方案用于浸润性乳腺癌的术前化疗,可有效控制肿瘤。ER/PR,HER2,Ki67,CyclinA2的状态与肿瘤缩小比例之间并无统计学意义的关联性。     

乳腺癌新辅助治疗病理完全缓解影响因素及预后分析

目的 分析乳腺癌新辅助治疗病理完全缓解（pCR）的影响因素,并探讨pCR对预后的意义。方法 回顾性分析2008年1月至2014年12月北京大学第一医院乳腺疾病中心接受新辅助治疗的324例女性乳腺癌病例资料,分析临床病理信息及预后随访数据,探讨pCR的预测因素及其对预后的意义。结果 新辅助治疗pCR率为21.9%;不同分子分型pCR率差异具有统计学意义（P<0.001）,其中Luminal B［人类表皮生长因子受体（HER2）阳性］型、HER2过表达型、三阴型更易获得pCR,pCR率分别为30.6%、37.5%、32.4%;pCR对于不同分子分型预后的意义存在差异,HER2过表达型［无病存活率（DFS）：P=0.048;总存活率（OS）：P=0.050］及三阴型乳腺癌（DFS：P=0.040;OS：P=0.045）pCR预后优于非pCR。治疗前肿瘤孕激素受体（OR=0.297,95%CI=0.167～0.530,P＜0.001）、HER2（OR=2.351,95%CI=1.340～4.125,P=0.003）、Ki67表达（OR=6.870,95%CI=0.885～53.303,P=0.065）是pCR的独立影响因素。结论 治疗前肿瘤孕激素受体和HER2表达状态、Ki67表达水平是pCR的独立影响因素;pCR可作为HER2过表达型和三阴型乳腺癌远期预后的预测指标之一。     

Predictors of complete pathological response after neoadjuvant systemic therapy for breast cancer

Background

The aim of the current study was to identify predictors of pathologic complete response (pCR) following neoadjuvant therapy.

Methods

From 2000 to 2007, 518 breast cancer patients received neoadjuvant therapy. Data were compared using χ² and Fisher's exact tests and multivariate analysis of variance, as appropriate.

Results

Of 518 breast cancer patients receiving neoadjuvant therapy, 81 (16%) had pCR (77 of 456 [17%] with chemotherapy, 4 of 62 [6%] with endocrine therapy; P < .05). Four factors were associated with pCR: higher tumor grade (P = .015), lack of estrogen receptor (ER) and progesterone receptor (PR) expression (P < .0001), HER2/neu amplification (P = .025), and negative lymph node status (P < .0001). On multivariate analysis, ER and PR negativity, HER2/neu amplification, and negative lymph node status were found to significantly correlate with pCR.

Conclusions

Patients with ER-negative and PR-negative and HER2/neu-amplified breast cancer phenotypes are more likely to experience pCR to neoadjuvant therapy. Although pCR is more frequently observed following neoadjuvant chemotherapy, it is rare following neoadjuvant endocrine therapy.     

The use of breast ultrasound for prediction of pathologic complete response in different subtypes of early breast cancer within the WSG-ADAPT subtrials

ObjectiveWe assessed the value of breast ultrasound (US) performed at week 3 and 6 and at the end (EOT) of neoadjuvant therapy (NAT) for prediction of pathologic complete response (pCR, ypT0/is ypN0) in patients with HR+/HER2+, HR-/HER2-or HR-/HER2+ early breast cancer enrolled in the WSG-ADAPT subtrials.MethodsUS was performed at week 3 and 6 of NAT and at EOT in 401, 517, and 553 patients, respectively. Tumors with complete or partial response by US (RECIST 1.1) were classified as responders and those with stable or progressive disease as non-responders.ResultspCR rate was higher in US responders than in non-responders. US tended to yield the highest positive predictive value in HR-/HER2+ (69%) and HR-/HER2-tumors (65%) at week 3, and the highest negative predictive value in HR+/HER2+ tumors at week 6 and at EOT (88.9% and 86.9%, respectively) and in HR-/HER2-tumors at EOT (87.9%). Multivariable analysis of patients with US at week 3 and 6 identified tumor subtype (HR-/HER2+ vs HR+/HER2+; odds ratio (OR) 2.77, 95%CI 1.45–5.29, and OR 4.17, 95%CI 2.26–7.68, respectively) and each 10% change in lesion dimension on US from baseline (OR 1.15, 95%CI 1.08–1.24, and OR 1.25, 95%CI 1.16–1.35, respectively) as parameters associated with pCR.ConclusionsOur data support the use of week 3 and EOT US for prediction of pCR in response-guided NAT and in planning of breast-conserving surgery. Change in tumor diameter on US as a continuous variable could be a valuable alternative to categorical RECIST 1.1 criteria.     

HER2阳性乳腺癌患者新辅助化疗后免疫分型变化的研究

目的探讨HER2阳性乳腺癌新辅助化疗后雌激素受体(ER)、孕激素受体(PR)、细胞增殖核抗原Ki－67(Ki－67)、HER2变化。 方法回顾性分析2012年1月至2017年12月进行乳腺癌新辅助化疗且HER2为阳性的患者66例资料。所有患者化疗前行经超声引导下穿刺取病理活检,并于术后行病理检查。采用SPSS19.0统计学软件处理,观察患者在辅助化疗前后ER、PR、Ki67、HER2水平变化,采用(例,%)表示,行卡方检验,以P<0.05为差异有统计学意义。 结果66例HER2阳性乳腺癌新辅助化疗患者化疗后,PR出现上调表达最高,为19.32%,同时也是下调表达最高,为25.57%;ER保持不变比例最高(74.43%);Ki67下调率为23.86%,明显高于上调率的12.50%,保持不变比例63.64%;66例患者中7例患者经过新辅助化疗后HER2转为阴性,转阴率为10.61%。 结论HER2阳性乳腺癌新辅助化疗后部分患者的ER、PR、会出现上调或者下调的变化,Ki－67出现一定比例的下降、HER2部分转阴,这种变化对乳腺癌的分型以及术后治疗药物的选择均会产生影响。     

乳腺癌分子亚型在预测新辅助化疗疗效及患者预后中的作用

目的 本研究旨在探讨乳腺癌的分子亚型与乳腺癌的病理完全缓解及患者预后的关系.方法 收集2007年1月-2010年1月在芜湖市第二人民医院接受新辅助治疗的101例乳腺癌患者的病例资料,按照ER、PR及Her-2的免疫组化的结果将其分为4型,单因素与多因素分析临床病理因素与病理完全缓解的关系.结果 19例(18.8％)患者取得病理完全缓解,三阴性乳腺癌是病理完全缓解的独立预测因素(OR=3.35,95％CI:1.25 ～ 9.79,P=0.012),而Her-2丰富型乳腺癌相比较于luminal A型乳腺癌则取得更高的病理完全缓解率(OR =3.11,95％CI:1.09 ～ 10.89,P=0.021).而病理缓解率与无病生存率密切相关(P =0.002).但三阴性乳腺癌的总生存期和无病生存期更短(P =0.008,P=0.0006).结论 三阴性乳腺癌和Her-2丰富型乳腺癌较luminal A型乳腺癌更容易获得新辅助化疗后的病理完全缓解,但三阴性乳腺癌的预后仍然较差,可能与其在治疗后仍有肿瘤残留有关.     

新辅助化疗联合曲妥珠单抗对HER-2过表达乳腺癌的疗效观察

目的:观察新辅助化疗联合曲妥珠单抗对HER-2过表达乳腺癌的临床疗效。方法:39例HER-2过表达的乳腺癌患者,均采用多西他赛及卡铂新辅助化疗联合曲妥珠单抗治疗,6个周期后观察疗效并对乳腺癌组织中雌激素受体(ER)表达状态与病理完全缓解(pCR)率之间行单因素分析。结果:39例患者总有效率(OR)为94.9%(37/39);其中临床完全缓解(cCR)26例(66.7%),部分缓解(PR)11例(28.2%),疾病稳定(SD)2例(5.1%),无疾病进展(PD)病例。病理完全缓解(pCR)27例(69.2%)。单因素分析显示,ER阴性组的pCR率为82.4%,ER阳性组为59.1%。结论:在HER-2过表达乳腺癌的新辅助化疗中,多西他赛及卡铂联合曲妥珠单抗疗效良好,且ER受体阴性患者可获较高的缓解率。     

不同HER-2表达水平乳腺癌患者新辅助化疗疗效与生存分析

背景与目的 新辅助化疗是早期高危或局部晚期乳腺癌降期保乳和提高整体治愈率重要的治疗策略,新辅助化疗人群的选择和方案的制订依赖于分子分型。然而目前尚缺乏不同人表皮生长因子受体2（HER-2）表达水平的乳腺癌新辅助化疗疗效及生存预后差异的研究。本研究通过比较不同HER-2表达水平的乳腺癌患者新辅助化疗疗效及生存预后的差异,旨在明确其新辅助化疗疗效及生存预后的影响因素,为临床新辅助化疗人群选择和方案制订提供参考。方法 回顾性分析2018年1月—2022年5月于中南大学湘雅医院乳腺外科接受新辅助化疗且行根治性手术的乳腺癌患者资料。比较不同HER-2表达水平（0表达、低表达、过表达）患者临床病理特征的差异,用Logistic回归分析筛选病理完全缓解（pCR）的独立影响因素,用Kaplan-Meier方法估计患者的生存曲线,用Log-rank检验比较生存率的差异,通过Cox回归分析筛选预后的独立影响因素。结果 共纳入601例患者,其中HER-2 0表达231例（38.4%）、HER-2低表达137例（22.8%）、HER-2过表达233例（38.8%）。与HER-2 0表达患者和HER-2过表达患者比较,HER-2低表达患者具有更高的BMI,合并肿瘤家族史更少见,组织学分级更低,激素受体（HR）阳性比例更高;HER-2过表达患者的肿瘤纤维化程度明显低于HER-2 0表达和HER-2低表达患者（均P<0.05）。HER-2低表达患者中,HR阴性亚组患者较HR阳性亚组患者肿块更大,组织学分级更高,Ki-67水平更高（均P<0.05）。全组患者中,HER-2表达水平、pCR、临床淋巴结分期（cN）是患者无病生存（DFS）的独立影响因素（均P<0.05）。HER-2过表达患者的新辅助化疗pCR率及DFS率明显高于HER-2低表达和HER-2 0表达患者（均P<0.05）,但HER-2低表达和HER-2 0表达患者的新辅助化疗pCR率及DFS率无明显差异（均P>0.05）。肿瘤纤维化程度和雌激素受体（ER）状态是HER-2 0表达乳腺癌pCR的独立影响因素,间质肿瘤浸润淋巴细胞（sTILs）水平是HER-2低表达乳腺癌pCR的独立影响因素,肿瘤纤维化程度和ER状态是HER-2过表达乳腺癌pCR的独立影响因素（均P<0.05）。结论 新辅助化疗对HER-2过表达乳腺癌患者的疗效优于HER-2 0表达和HER-2低表达乳腺癌患者。ER状态和纤维化程度、sTILs水平分别是HER-2 0表达与低表达患者pCR的独立影响因素,而ER状态与纤维化程度是HER-2过表达患者pCR的独立影响因素。     

Neoadjuvant chemotherapy with sequential anthracycline–docetaxel with gemcitabine for large operable or locally advanced breast cancer: ANZ 0502 (NeoGem)

BackgroundNeoadjuvant chemotherapy has a sound rationale for use in women with large operable breast cancer, and achievement of pathological complete response (pCR) is prognostic. Epirubicin and cyclophosphamide followed by docetaxel is a standard chemotherapy regimen for early breast cancer. In metastatic breast cancer the combination of gemcitabine and a taxane has shown promising results. This phase II study investigated the efficacy and safety of incorporating gemcitabine into neoadjuvant therapy.MethodsFemale patients with operable breast cancer that was clinically T2 (≥3 cm) or T3-4, N0-1, M0 were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin and cyclophosphamide followed by docetaxel and gemcitabine, plus trastuzumab if HER2-positive. The primary endpoint was the pathological complete response (pCR) rate in the breast in separate HER2-negative and HER2-positive cohorts. Secondary endpoints included pCR in both the breast and axillary lymph nodes, clinical and radiological response rates, disease free survival and safety.Results81 patients were enrolled: 63 HER2-negative and 18 HER2-positive. 67 (84%) completed all cycles of chemotherapy, and 78 (96%) proceeded to surgery. pCR was achieved by 12 (20%) patients with HER2-negative, and 9 (53%) with HER2-positive disease. At the first interim analysis, addition of prophylactic G-CSF was recommended due to excess neutropenia. The HER2-negative cohort was closed to accrual because it did not meet the pre-specified target for pCR, and the HER2-positive cohort was closed due to slow accrual. At a median follow-up of 24 months, 12 of 81 (15%) patients had experienced a relapse of their breast cancer.ConclusionNeoadjuvant gemcitabine, when added to docetaxel, after epirubicin and cyclophosphamide, did not reach the pre-specified expectations for pCR rate in HER2-negative tumours. Excess neutropenia was observed, requiring growth factor support. Addition of gemcitabine to docetaxel in this schedule cannot be recommended.Australia and New Zealand Clinical Trials Registry (www.anzctr.org.au) registration number ACTRN12606000191594.