乳腺癌新辅助化疗疗效与分子分型的关系

目的探讨乳腺癌分子分型与表柔比星联合多西他赛（TE）方案新辅助化疗疗效的关系。方法根据纳入和排除标准,共纳入我院2011年5月至2012年12月期间至少接受过3周期TE方案治疗的乳腺癌患者共239例,其各项临床指标均完整。根据免疫组织化学雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2（HER-2）及Ki-67表达水平将患者分为4种亚型,分别为luminal A型、luminalB型、HER-2阳性型和三阴型。分析不同亚型乳腺癌患者的各项相关指标,如病理完全缓解（pCR）率、年龄、月经状态等。结果239例患者中,luminalA型67例（28．03％）,luminalB型84例（35．15％）,HER．2阳性型21例（8．79％）,三阴型67例（28．03％）。4型乳腺癌患者的年龄、月经状态、肿瘤大小、淋巴结状态等临床病理指标差异均无统计学意义（P〉0．05）。三阴型对TE方案的新辅助化疗的pCR率（14．93％）最高,其次依次为luminalB型（7．14％）、HER-2阳性型（4．76％）及luminalA型（1．49％）,差异有统计学意义（P=0．027）。结论三阴型相对luminalA型、luminalB型和HER-2阳性型对TE方案的新辅助化疗治疗更敏感,pCR率最高,治疗时需根据患者不同的分子亚型来选用特定的治疗方案。     

淋巴细胞亚群对乳腺癌新辅助化疗疗效的预测价值

目的 本研究旨在探讨治疗前淋巴细胞亚群对乳腺癌新辅助化疗(NAC)疗效的预测价值.方法 本研究选取2016年4月至2020年6月在中山大学孙逸仙纪念医院接受NAC的乳腺癌患者109例.采用卡方检验及logistics回归分析不同淋巴细胞亚群比例与病理完全缓解(pCR)的相关性,并通过Kaplan-Meier曲线评估其与...     

局部晚期乳腺癌分子亚型与新辅助化疗疗效关系的研究

Objective To explore the relationship between the four different molecular subtypes of locally advanced breast cancer(LABC) and the clinical effect of neoadjuvant chemotherapy containing docetaxel and anthracyclines on breast cancer. Methods The record of 68 patients with LABC who were treated with the therapeutic scheme was reviewed. Breast cancer molecules were diagnosed by core needle biopsy through IHC and were divided into four subtypes. After 3 to 5 courses of treatment, the relationship of molecular subtype and clinical effects was analyzed. Results Univariate analysis showed that absence of estrogen receptor (ER) expression and size of tumor (≤5cm) were predictive factors for clinical complete response (cCR) (P<0.05).Over expression of HER-2 and molecular subtypes were predictive for pathologic complete response (pCR) (P<0.05). pCR rate of HER2+/ER- subtype in this therapeutic scheme was, higher than that of other subtypes and pCR rate of Luminal A subtype was the lowest. Multivariate analysis showed that molecular subtypes cant be the predictive factors for this therapeutic scheme (P>0.05) and only HER-2 (P<0.05) was the independent variable in predicting pCR for this therapeutic scheme. Conclusion Molecular subtypes can not independently predict pCR for neoadjuvant chemotherapy regimen containing docetaxel and anthracyclines.     

Argus软件评估乳腺癌新辅助化疗疗效

目的探讨采用心脏专用Argus软件评估乳腺癌新辅助化疗(NAC)疗效的可行性。方法收集经病理学确诊的乳腺浸润性导管癌患者23例(1例为双侧病变,共计24侧),分别于化疗前及4次化疗后接受3.0T动态增强磁共振扫描(DCE-MRI)。将DCE-MRI第2期图像经3D软件重建后载入心脏专用Argus浏览器,由2名放射科医师分别盲法绘制并计算肿瘤体积,最终结果取二者的平均值。采用配对t检验比较NAC前后肿块体积差异。结果化疗前24侧乳腺癌肿块体积为3.9~42.1cm~3,平均(13.71±9.47)cm~3,4次化疗后体积为0.3~29.4cm~3,平均(4.81±4.15)cm~3,二者差异有统计学意义(t=6.36,P0.01)。结论 Argus心脏专用软件包可方便、准确地测量乳腺癌肿块体积、用于评估乳腺癌NAC化疗疗效。     

BCSG1基因在乳腺癌新辅助化疗疗效评估中的价值

目的:探讨乳腺癌特异基因（BCSG1）在乳腺癌新辅助化疗疗效评估中的价值。方法:采用免疫组化S P法和荧光定量PCR方法检测36例乳腺癌患者新辅助化疗(CEF方案)前后乳腺癌组织BCSG1的表达，比较化疗前后肿瘤体积的变化情况，分析新辅助化疗前后BCSG1蛋白表达与肿瘤形态学变化的关系。结果:36例乳腺癌患者新辅助化疗后肿瘤体积均有明显缩小（P<0.01），病灶缓解率(CR+PR)为85.6%；新辅助化疗后BCSG1 mRNA表达水平亦明显低于化疗前（P<0.05），BCSG1蛋白高表达率低于新辅助化疗前（P<0.01）。结论:乳腺癌新辅助化疗后BCSG1在分子和蛋白水平表达均明显降低，与新辅助化疗后疗效呈负相关（r=-0.539,P<0.01），提示BCSG1可作为乳腺癌新辅助化疗疗效的预测因子。     

乳腺癌个体化新辅助治疗

乳腺癌新辅助治疗是局部进展期乳腺癌的标准治疗方式。在早期乳腺癌中,大型临床试验显示新辅助治疗与辅助治疗具有相似的疗效,并能提高保乳手术的比例,使其在临床上被广泛接受,成为     

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。     

新辅助化疗及保乳手术在Ⅱ|Ⅲ期乳腺癌中的治疗作用

目的探讨新辅助化疗及保乳手术在Ⅱ,Ⅲ期乳腺癌治疗中的作用。方法对观察组46例Ⅱ,Ⅲ期乳腺癌经新辅助化疗后接受保乳手术治疗的患者进行随访观察,并与59例患者对照研究。新辅助化疗方案为表阿霉素60 mg/m2第1天静脉注射,紫杉醇150 mg/m2。第2天持续3 h静脉滴注,21 d为1个疗程。保乳手术方式为象限切除或肿块局部广泛切除联合腋窝淋巴结清除。对照组常规行根治性切除术。术后对乳房外形及局部复发、远处转移进行随访观察。结果新辅助化疗后,观察组术前肿瘤病灶临床完全缓解(CR)9例,部分缓解(PR)37例。术后病理学检查发现,观察组癌细胞均有不同程度的变性、坏死,细胞间质水肿,纤维增生,炎性细胞浸润;其中病理完全缓解(PCR)4例。对保乳综合治疗(放疗+化疗)结束后1年的31例患者进行外形评估,其中优19.4%(6/31),良58.1%(18/31),差22.6%(7/31)。观察组局部复发率为8.7%(4/46),对照组为6.8%(4/59),两组比较无统计学意义(P0.05);观察组远处转移率为6.5%(3/46),与对照组(15.3%,9/59)比较无统计学意义(P0.05)。结论新辅助化疗后行保乳手术治疗Ⅱ,Ⅲ期乳腺癌基本是安全的,可达到根治性手术的效果。新辅助化疗,规范化切除,术后放疗、化疗是保乳治疗成功的关键。     

Current and future role of neoadjuvant therapy for breast cancer

Neoadjuvant systemic chemotherapy is a possible therapeutic approach for the treatment of locally advanced operable, primarily non-operable or inflammatory breast cancer. Neoadjuvant systemic chemotherapy is an option for breast cancer patients who would require adjuvant chemotherapy otherwise based on clinical and histological examination and imaging. The use of neoadjuvant systemic therapy in operable breast cancer is currently increasing because of its advantages that include higher rates of breast conserving surgery and the possibility of measuring early in-vivo response to systemic treatment. The timing of axillary sentinel lymph node diagnosis (i.e. before or after neoadjuvant chemotherapy) is critical in that it may influence the likelihood of axillary preservation. It is not yet clear if neoadjuvant therapy might improve outcomes in certain subgroups of breast cancer patients. Neoadjuvant treatment modalities require a close collaboration between oncology professionals, including surgeons, gynecologists, medical oncologists, radiation oncologists, radiologists and pathologists. The most important parameter for treatment success and improved overall survival is the achievement of a pathologic complete response (pCR), although the role of pCR in patients with luminal A like tumours might be less informative. Identification of patient subgroups with high pCR rates may allow less invasive surgical or radiological interventions. Patients not achieving a pCR may be candidates for postoperative clinical trials exploring novel systemic treatments.     

Ultrasound-based prediction of pathologic response to neoadjuvant chemotherapy in breast cancer patients

BackgroundAccuracy in predicting pathologic response to neoadjuvant chemotherapy (NACT) in breast cancer is essential for the determination of therapeutic efficacy and surgical planning. This study aimed to assess the precision of ultrasound (US) for predicting pathologic complete response (pCR = ypT0) after NACT.MethodsThis retrospective mono-center study included 124 invasive breast cancer patients treated with NACT. Patients received US before and after NACT with documentation of clinical partial response (cPR) and clinical complete response (cCR). Post-operatively, the pathologic response was defined as absence of tumor cells (ypT0), presence of non-invasive tumor cells (ypTis) or invasive tumor cells (ypTinv). Sensitivity and specificity of US as well as false negative rate (FNR), negative predictive value (NPV) and positive predictive value (PPV) were analysed for receptor subtypes. A multivariable logistic regression model assessed the influence of patient- and tumor-associated covariates as predictors for pCR.Results50 patients (40.3%) achieved pCR, 39 (78.0%) had a corresponding cCR. Overall sensitivity was 60.8% and specificity 78.0% for US-predicted remission. NPV and FNR differed substantially between subtypes. NPV was highest (75.0%) in triple negative (TN) subtype, while FNR was low (37.5%). Therefore, pathological response was most accurately predicted for TN cancers. NPV for human-epidermal-growth-factor-receptor-2-positive/hormone-receptor-positive (HER2+/HR+) was 55.6%, for HER2+/HR- 64.3% and for HER2-/HR+ 16.7%, FNRs were 40.0%, 71.4% and 32.3%, respectively. Receptor subtypes impacted pCR significantly (p-value: 0.0033), cCR correlated positively with pCR (p-value: 0.0026).ConclusionUS imaging is insufficient to predict pCR with adequate accuracy. Receptor subtypes, however, affect diagnostic precision of US and pathologic outcome.     

The effect of molecular subtype and body mass index on neo-adjuvant chemotherapy in breast cancer patients

The aim of the present study was to analyze the effect of subtype and body mass index (BMI) on neo-adjuvant chemotherapy (NAC) and postoperative prognosis. Two-hundred and forty nine patients who underwent surgery after NAC were included. A multivariate analysis and survival analysis were used to clarify the relationship between BMI, subtype, and NAC. In the logistic regression model, the pCR rate had a significant relationship with the subtype and tumor stage. In the non-pCR group, more overweight patients had significantly a worse disease-free survival (DFS) compared to normal range patients (Log lank test, p < 0.05). In the Cox proportional hazards model, subtype and tumor stage were significantly associated with decreased DFS. In conclusion, patients with the ER (+), HER (−) type and a high BMI had a high risk for recurrence when they achieved non-pCR after NAC.     

新辅助化疗对乳腺癌患者血脂影响及因素分析

目的研究新辅助化疗（NAC）对乳腺癌患者血脂水平的影响及相关因素,为降低乳腺癌患者心血管疾病相关死亡率和改善乳腺癌预后提供诊疗依据。 方法收集整理青岛大学附属医院乳腺诊疗中心299例完成4~6周期化疗的乳腺癌患者临床病理资料及血脂水平结果,分析患者接受NAC前后的血脂水平变化及相关影响因素。 结果接受NAC后乳腺癌患者血清三酯甘油（TG）、总胆固醇（TC）及低密度脂蛋白胆固醇（LDL-C）水平均显著高于术前,而高密度脂蛋白胆固醇（HDL-C）水平低于术前,差异均有统计学意义[（2.26±1.77）mmol/L vs（1.47±1.13）mmol/L、（5.81±1.20）mmol/L vs （5.17±1.07）mmol/L、（3.42±0.89）mmol/L vs （2.87±0.77）mmol/L、（1.28±0.33）mmol/L vs （1.45±0.32）mmol/L,t=-10.02、-9.80、-9.36、9.28,均P<0.01]。单因素分析提示患者肿瘤病理类型（χ²=7.676,P=0.022）及化疗方案（χ²=10.747,P=0.005）是接受NAC后血清TG水平升高的相关因素;患者年龄（χ²=4.065,P=0.044）及是否绝经（χ²=5.134,P=0.023）与NAC后血清LDL-C水平升高相关;血清HDL-C的降低与患者年龄（χ²=7.284,P=0.007）、分子分型（χ²=8.626,P=0.003）及是否绝经（χ²=9.608,P=0.002）有关,而体质量指数（BMI）和化疗疗效与各血脂水平变化无关。多因素分析显示病理类型为浸润性非特殊癌（OR=3.624,P=0.008）及蒽环类联合紫衫类化疗方案（OR=3.508,P=0.001）是影响TG水平升高的独立危险因素;未绝经（OR=2.237,P=0.017）、分子分型为三阴性（OR=3.184,P=0.001）是影响HDL-C水平降低的独立危险因素。 结论NAC后乳腺癌患者各血脂水平的变化对心血管系统及肿瘤复发、转移等预后不利,临床医师应重视患者血脂代谢变化及相关危险因素,定期检测并及时给予指导干预,降低癌症患者心血管疾病的死亡率并改善预后。     

High TFAP2C/low CD44 expression is associated with an increased rate of pathologic complete response following neoadjuvant chemotherapy in breast cancer

Background

In luminal breast cancer cell lines, TFAP2C regulates expression of key genes in the estrogen receptor–associated cluster and represses basal-associated genes including CD44. We examined the effect of TFAP2C overexpression in a basal cell line and characterized the expression of TFAP2C and CD44 in breast cancer specimens to determine if expression was associated with clinical response.

Methods

MDA-MB-231 breast cancer cells were treated with a TFAP2C-containing plasmid and evaluated for effects on CD44 expression. Pretreatment biopsy cores from patients receiving neoadjuvant chemotherapy for breast cancer were evaluated for TFAP2A, p53, TFAP2C, and CD44 expression by immunohistochemistry.

Results

Overexpression of TFAP2C in MDA-MB-231 cells resulted in decreased expression of CD44 mRNA and protein, P < 0.05. A pathologic complete response (pCR) following neoadjuvant chemotherapy was achieved in 17% of patients (4/23). Average expression for TFAP2C by immunohistochemistry in patients with a pCR was 93%, compared with 46% in patients with residual disease, P = 0.016; and in tumors that stained at ≥80% for TFAP2C, 4 of 9 (44%) achieved pCR, compared with 0 of 14 below 80%, P = 0.01. Additionally, in tumors that stained ≤80% for CD44, 4 of 10 (40%) achieved pCR, compared with 0 of 13 >80%, P = 0.02. In tumors that stained high for TFAP2C (≥80%) and low for CD44 (≤80%), 4 of 7 (57%) achieved pCR, compared with 0 of 16 in all other groups (P = 0.004).

Conclusions

TFAP2C repressed CD44 expression in basal-derived breast cancer. In primary breast cancer specimens, high TFAP2C and low CD44 expression were associated with pCR after neoadjuvant chemotherapy and could be predictive of tumors that have improved response to neoadjuvant chemotherapy.     

胃癌新辅助化疗后原发灶病理完全缓解患者的病理学观察

目的观察胃癌新辅助化疗后原发灶病理学完全缓解（pCR）患者的病理学特征。方法收集北京肿瘤医院2002-2008年间完成新辅助化疗的胃癌患者病例资料．筛选出原发灶pCR者共5例。复习病理切片,并分别就胃壁的组织结构、肿瘤细胞形态、间质细胞的数量和形态进行分析评价。结果5例患者胃壁结构均可区分,有2例可见肌层弯折、断裂。1例可见胃壁各层包括浆膜层呈现渗出性炎性表现。3例溃疡型病变,上皮层脱落,溃疡存在,边缘可见不典型增生的细胞改变,间质血管内皮细胞肿胀。仅1例残留变性坏死的癌细胞,其余4例未见癌残留迹象。4例显示成纤维细胞显著增生,3例见大量淋巴细胞浸润。1例同时伴有浆细胞浸润,1例肌层可见多核巨细胞反应,1例黏液腺癌可见泡沫细胞聚集。5例原发灶pCR病例中有2例淋巴结可见癌转移。结论胃癌新辅助化疗后,原发灶pCR病例肿瘤区域间质细胞反应呈现不均一性,原发灶反应与淋巴结不相一致。     

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.     

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.     

Pathological complete response in invasive breast cancer treated by skin sparing mastectomy and immediate reconstruction following neoadjuvant chemotherapy and radiation therapy: Comparison between immunohistochemical subtypes

ContextEven if neoadjuvant chemotherapy (NACT) and oncoplastic techniques have increased the breast conserving surgery rate, mastectomy is still a standard for multifocal or extensive breast cancers (BC). In the prospect of increasing breast reconstruction, an alternative therapeutic protocol was developed combining NACT with neoadjuvant radiation therapy (NART), followed by mastectomy with immediate breast reconstruction (IBR). The oncological safety of this therapeutic plan still needs further exploration. We assessed pathological complete response (pCR) as a surrogate endpoint for disease free survival.MethodsBetween 2010 and 2016, 103 patients undergoing mastectomy after NACT and NART were recruited. After CT and RT were administrated, a completion mastectomy with IBR by latissimus dorsi flap was achieved 6 to 8 weeks later. pCR was defined by the absence of residual invasive disease in both nodes and breast. Histologic response was analyzed for each immunohistochemical subset.ResultspCR was obtained for 53.4% of the patients. This pCR rate was higher in hormonal receptor negative (HER2 and triple negative) patients when compared to luminal tumours (69.7% vs 45.7%, p=0.023).DiscussionThe pCR rate found in this study is higher than those published in studies analyzing NACT (12.5%-27.1%). This can be explained by the combination of anthracycline and taxane, the use of trastuzumab when HER2 was overexpressed but also by RT associated to NACT.ConclusionInverting the sequence protocol for BC, requiring both CT and RT, allows more IBR without diminishing pCR and should therefore be considered as an acceptable therapeutic option.