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...     

隐匿性乳腺癌的诊断与治疗

隐匿性乳腺癌多以同侧腋窝淋巴结肿大为首发症状,临床少见,诊断是其难点。诊断过程建议先行肿大淋巴结空芯针穿刺,并加做免疫组化,如支持乳腺癌转移,同时排除其他部位原发肿瘤后可确诊。治疗以全乳切除加腋窝淋巴结清扫术为标准,新辅助化疗是影响其预后的独立因素,术前推荐先行新辅助化疗,术后根据免疫组化结果,辅以化疗、放疗、内分泌治疗等。隐匿性乳腺癌的预后与同期其他类型的乳腺癌相似。     

Pathologic evaluation of response to neoadjuvant therapy drives treatment changes and improves long‐term outcomes for breast cancer patients

Systemic therapy for breast cancer may be given before (neoadjuvant) or after (adjuvant) surgery. When neoadjuvant systemic therapy is given, response to treatment can be evaluated. However, some prognostic information (for example, pathologic tumor size pretreatment) is then lost and pathologic evaluation of breast specimens after neoadjuvant therapy is more difficult. Pathologic complete response (pCR), defined as no invasive disease in the breast (ypT0/is or ypT0) and no disease in all sampled lymph nodes (ypN0), identifies patients with a lower risk of recurrence or death compared to those with residual disease. Multidisciplinary collaboration, marking of the tumor site and any lymph node involvement pretreatment, and access to specimen imaging to facilitate correlation of gross and microscopic findings are critical for accurate determination of pCR. For HER2‐positive and triple negative tumors requiring systemic therapy, giving the treatment before surgery identifies a high‐risk group of patients that can receive additional adjuvant therapy after surgery if a pCR is not achieved. Recent clinical trials have demonstrated that this approach reduced recurrence risk. More than ever, pathologic evaluation of response to neoadjuvant systemic therapy directs treatment received after surgery. Using a single standardized protocol for sampling of the post‐neoadjuvant surgical specimen allows pathologists to ensure accurate determination of pCR or residual disease and quantify residual disease. Residual cancer burden (RCB) and AJCC stage provide complementary quantitative information about residual disease and prognosis.     

Utility of neoadjuvant chemotherapy in the treatment of operable breast cancer

Neoadjuvant chemotherapy (NAC) is a legitimate alternative to first‐line surgical therapy for the treatment of breast cancer patients, as level one evidence shows the effect on overall survival is equivalent to that of adjuvant chemotherapy. In the treatment of women with operable breast cancer, NAC provides a number of potential advantages including: improving the chance of achieving breast‐conserving surgery, improving cosmesis after breast‐conserving surgery, downstaging the breast and axilla, allowing time to fully consider surgical options, time for genetic testing and facilitating breast reconstruction in otherwise high‐risk patients. However, in Australia, NAC is poorly utilized with less than 3% of women with operable breast cancer receiving NAC. This review discusses the potential harms and benefits of NAC, discusses areas of controversy in the use of NAC and describes how we have used NAC in our own practice. We conclude that if it is obviously necessary for the newly presenting breast cancer patient to have chemotherapy as part of the treatment, it is worth considering NAC. In many patients, the potential benefits of NAC outweigh the harms. However, maximizing these benefits is closely aligned with appropriate patient selection and timely multidisciplinary team communication.     

Development of malignant breast microcalcifications after neoadjuvant chemotherapy in advanced breast cancer

The increased interest in the use of neoadjuvant chemotherapy for patients with locally advanced or large tumors at initial presentation necessitates the recognition of sequelae of this therapy. This article describes the interval appearance of malignant, linear-branching, microcalcifications during neoadjuvant chemotherapy for locally advanced breast cancer. Mammographically the malignant microcalcifications appeared only in the region of the breast where the primary tumor was found. Pathologically only a subpopulation of malignant cells responded to the chemotherapy, demonstrating viability of the majority of the tumor, with cell death only in the subpopulation. With the increased use of neoadjuvant chemotherapy, it is important to recognize previously undescribed mammographic findings secondary to this therapeutic approach.     

三阴性乳腺癌新辅助治疗现状

目的 三阴性乳腺癌高侵袭、高复发、高转移且预后差,对内分泌治疗、抗Her-2靶向治疗不敏感。本研究总结了近年来三阴性乳腺癌新辅助治疗进展。方法 应用PubMed、CNKI、万方等数据库,以“TNBC、新辅助治疗、病理完全缓解”等作为搜索关键词,检索近年的相关文献。结果 病理完全缓解被认为是新辅助治疗预后评判的重要标准之一。蒽环类联合紫杉类药物仍然是TNBC患者的首选新辅助化疗方案,铂类药物的应用使BRCA基因突变TNBC患者有了更优的新辅助化疗方案,但血液学、消化系统等相关不良反应不可忽视。免疫调定点抑制剂相关药物被证实在TNBC新辅助治疗上能提高pCR,改善长期生存预后,且因药物不良反应停药较铂类药物发生率更低。肿瘤微环境靶向药物、多聚ADP核糖聚合酶抑制剂、PI3K/AKT/mTOR通路抑制剂等相关药物在多药联合方面上的临床研究有积极治疗效果。结论 TNBC新辅助治疗中,化疗是基础,免疫治疗已有相关临床试验成果,肿瘤微环境靶向药物、多聚ADP核糖聚合酶抑制剂、PI3K/AKT/mTOR通路抑制剂具有很大研究前景。     

Diagnosis of complete response to neoadjuvant chemotherapy using diagnostic imaging in primary breast cancer patients

Advances in the therapeutic agents used for neoadjuvant chemotherapy (NAC) have recently achieved higher response rates and induced a greater number of pathologic complete responses (pCR) than ever before. The aim of this study is the diagnosis of pCR after NAC by diagnostic imaging of clinical complete response (cCR) patients. This study included 35 breast cancer patients who demonstrated cCR after receiving NAC with a combination of anthracycline and taxane from May 1998 to August 2003. Surgical treatment included breast-conserving therapy followed by radiotherapy or mastectomy. The identity of post-NAC lesions as either a complete response (CR) or partial response (PR) were made by mammography, ultrasonography, and contrast-enhanced computed tomography (CT). Among the 35 patients, 11 achieved pCR, including the disappearance of both invasive and intraductal components. Of the patients achieving pCR, eight were defined as CR and three were determined to be PR by CT. There was a significant relationship between the pCR and the determination of CR by CT. The determination of CR by ultrasonography was indicative of the disappearance of pathologic invasive components. While mammography appeared to reflect the observed histologic results, we did not observe any statistical differences. A subset of cases exhibited discrepancies between the imaging and pathologic results, likely due to the replacement of destroyed tumor cells by fibrosis and granulomatous tissue. The evaluation of CR by CT was significantly indicative of pCR. The positive predictive value, however, was not large enough to avoid surgical treatment. Further studies will be needed to establish a diagnosis of pCR.     

乳腺癌新辅助治疗个体化管理

近年来乳腺癌新辅助治疗作为标准治疗手段之一愈发受到关注,与辅助治疗相比是否有优势存在的争论也颇多。然而经新辅助化疗达到病理完全缓解（PCR）可以显著改善预后这个不争的事实展示了该治疗方式的美好前景,同时也促使外科医生思考哪类病人能够达到PCR,哪些方案能够使病人从新辅助化疗中最大获益。另外,在治疗过程中运用MRI、循环肿瘤细胞测定等手段对疾病进行监测和疗效预测,使乳腺癌新辅助治疗在安全、可控中进行,做到真正的个体化治疗。     

Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer

Background After neoadjuvant chemotherapy, women with locally advanced breast cancer (LABC) undergo a modified radical mastectomy or lumpectomy with axillary lymph node dissection (ALND) and radiotherapy. Sentinel lymphadenectomy (SL) is accepted for axillary evaluation in early breast cancer. We assessed the feasibility and predictive value of SL after neoadjuvant chemotherapy. Methods Eligible women received neoadjuvant therapy for LABC and were scheduled to undergo a definitive surgical procedure. Vital blue dye SL was attempted followed by level I and II axillary dissection. Results SL was successful in 29 of 34 patients (detection rate, 85%). Thirteen patients (45%) had positive nodes, and eight (28%) had negative nodes on both SL and ALND. In five patients (17%), the sentinel node was the only positive node identified. Overall, there was a 90% concordance between SL and ALND. The false-negative rate and negative predictive value were 14% and 73%, respectively. Among the subgroup without inflammatory cancer, the detection and concordance rates were 89% and 96%, respectively. The false-negative rate was 6%, and the negative predictive value was 88%. Conclusions SL after neoadjuvant chemotherapy may reliably predict axillary staging except in inflammatory breast cancer. Further studies are required to assess the utility of SL as the only mode of axillary evaluation in these women.     

Sentinel lymph node mapping following neoadjuvant chemotherapy for breast cancer

The purpose of this study was to evaluate the feasibility of sentinel lymph node mapping in patients undergoing neoadjuvant chemotherapy for breast carcinoma prior to lumpectomy or mastectomy and sentinel lymph node mapping followed by complete axillary dissection. A retrospective analysis of 14 patients from February 1998 to July 2000 with stage I to stage IIIB breast cancer diagnosed by core biopsy underwent neoadjuvant chemotherapy (doxorubicin/cyclophosphamide) prior to definitive surgery, including lumpectomy or mastectomy and sentinel lymph node mapping, followed by full axillary dissection. Thirteen of 14 patients had successful sentinel lymph node identification (93%), and all 14 underwent full axillary dissection. An average of 2.2 sentinel nodes and a median of 16 axillary lymph nodes (including sentinel nodes) were found per patient. Of the 13 patients in whom a sentinel lymph node was identified, 10 were positive for metastases (77%). Only 4 of the 10 had further axillary metastases (40%). Three patients had negative sentinel lymph nodes shown by hematoxylin and eosin and cytokeratin stainings and had no axillary metastases (0% false negative). The single patient in whom a sentinel lymph node could not be identified had stage IIIA disease with extensive lymphatic tumor emboli. Sentinel lymph node mapping is feasible in neoadjuvant chemotherapy breast cancer patients and can spare a significant number of patients the morbidity of full axillary dissection. Further study to evaluate sentinel lymph node mapping in this patient population is warranted.     

多西他赛、环磷酰胺与多西他赛、吡柔比星新辅助化疗方案治疗局部晚期乳腺癌疗效分析

目的观察多西他赛、环磷酰胺（DC方案）与多西他赛、吡柔比星（DT方案）新辅助化疗方案治疗局部晚期乳腺癌的临床疗效和不良反应。方法经麦默通穿刺确诊局部晚期乳腺癌可手术患者73例,随机分为DC组（35例）,DT组（38例）,分别给予DC方案,DT方案化疗3个周期,DC组35例,DT组38例化疗结束2周后行乳腺癌改良根治术。比较DC组,DT组疗效和不良反应,治疗前、后TNM分变化、术后并发症及化疗前后ER、PR、HER2变化比较。结果临床疗效比较DT组优于DC组,其差异有统计学意义（P〈0．05）;TNM分期均较新辅助化疗前降低（P〈0．05）,不良反应比较差异无统计学意义（P〉0．05）;术后并发症比较差异无统计学意义（P〉0．05）,ER、PR均为阴性患者对化疗敏感,DT方案对于HER2高表达患者疗更敏感。结论DT及DC新辅助化疗方案疗对局部晚期乳腺癌均有效,DT方案优于DC方案。     

Twenty‐five years of change in the management of the axilla in breast cancer

Sentinel lymph node (SLN) biopsy is now used worldwide. It has led to many changes in how we manage the axilla in patients with breast cancer. This review covers four areas of management of the axilla in breast cancer: assessing the clinically node‐negative axilla, managing the clinically negative axilla found to be involved at SLN biopsy, management of the clinically positive axilla in the context of neo‐adjuvant chemotherapy, and treatment of the diseased axilla when radical therapy is required. We suggest that the evidence supports an optimum number of 3 nodes to be removed for accurate SLN biopsy. Breast cancer departments that have not adopted Z0011 patient management cannot continue to avoid change. The evidence is clear: Not all patients with limited axillary nodal disease on sentinel node biopsy need axillary lymph node dissection. For patients who do need axillary treatment, axillary radiotherapy continues to be under‐used. Patients undergoing neo‐adjuvant chemotherapy can be safely assessed by post‐therapy SLN biopsy, with retrieval of any previously biopsied involved nodes by targeted axillary dissection. There is much to support the trend to doing less in the axilla. We are obliged to act based on the available robust clinical trial data in a way that limits morbidity while at the same time does not increase the risk of disease recurrence.     

循环肿瘤细胞在乳腺癌新辅助化疗中的应用进展

·综 述·     

背阔肌肌皮瓣修复新辅助化疗后局部晚期乳腺癌组织缺损的疗效观察

目的:探讨我科12例局部晚期伴有皮肤侵犯导致溃疡形成的乳腺癌患者,术前行新辅助化疗后行改良根治术,即刻应用背阔肌肌皮瓣即时修复组织缺损的疗效观察。方法:12例患者均于术前行4~6周期新辅助化疗TEC方案,后达到临床部分缓解(PR)、创面缩小后,行乳腺癌改良根治术、即刻背阔肌肌皮瓣转移修复胸壁组织缺损。结果:12例患者手术均成功,接受新辅助化疗和术后放疗。随访l0~24个月,术后远处转移l例,无局部复发和死亡病例。结论:局部晚期乳腺癌新辅助化疗后,应用背阔肌肌皮瓣转移至胸壁修复组织缺损切实可行。     

HER-2/neu-positive breast cancer neoadjuvant chemotherapy response after implementation of 2018 ASCO/CAP focused update

Human Epidermal Growth Factor Receptor 2 (HER2), a routinely tested breast cancer marker, is associated with worse prognosis yet increased sensitivity to targeted neoadjuvant therapy (NAT) in breast cancer patients. The presence of HER2 in breast carcinoma can be detected with either immunohistochemistry (IHC) or in situ hybridization (ISH). In this study, we examine the relationship between clinicopathological features, HER2 detection method (IHC vs ISH), and prognostic outcomes in NAT-treated HER2-positive breast cancer patients. We included 99 HER2-positive patients from three academic institutions following 2018 HER2 testing updates and conducted a retrospective correlational study. Seventy-one (72%) were HER2-positive by IHC and 28 (28%) were positive following reflexive ISH. Multivariate analysis showed biomarker status to be significantly associated with pathologic complete response (pCR) (p = 0.003), Residual Cancer Burden (RCB) (p = 0.007), and tumor size downstaging (p = 0.002) and HER2 detection method of IHC to be significantly associated with pCR (p = 0.05), RCB (p = 0.004), and nodal downstaging (p= 0.03). In conclusion, HER2 detection method and biomarker subtype allow for further prognostic stratification of HER2-positive patients when 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline updates are applied.     

Breast cancer subtypes affect the nodal response after neoadjuvant chemotherapy in locally advanced breast cancer: Are we ready to endorse axillary conservation?

We evaluated the impact of breast cancer subtypes on pathologic complete response (pCR) in 181 patients with positive nodes undergoing neoadjuvant chemotherapy (NAC). After NAC, patients underwent surgery, with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND). In 28.2% of cases a pCR was achieved, with the highest rate in Her2+ and triple negative tumors. Overall, nodal pCR was more frequent than breast pCR (P = 0.003) with higher percentages in Her2+ and LLB‐Her2+ (P < 0.05). In the Her2+ group, nodal pCR was observed only with breast pCR. Thus, in Her2+ tumors, breast pCR predicts node pCR, supporting the use of SLNB in this subgroup to stage the axilla avoiding ALND.     

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目的分析胃癌新辅助化疗后原发病灶病理学完全缓解(pathological complete response,pCR)病人的临床特征。方法筛选北京大学肿瘤医院2001—2010年间胃癌新辅助化疗原发病灶pCR的11例病人的临床资料,分析其临床特征。结果 11例病人治疗前均为局部进展期胃癌,10例应用FOLFOX类方案、1例应用SOX化疗方案。1例病人术后病理提示有淋巴结转移;FOLFOX类方案的pCR率不足5%,现临床评效手段CT及超声胃镜(EUS)对于pCR病人的评估准确率低(2/11);所有病人至今均无病生存,提示预后好。结论从pCR角度判断,目前应用的胃癌新辅助化疗方案及临床评效手段有待改良。     

Diffusion-weighted imaging in evaluating the response to neoadjuvant breast cancer treatment

The aim of this study was to investigate the role of diffusion imaging in the evaluation of response to neoadjuvant breast cancer treatment by correlating apparent diffusion coefficient (ADC) value changes with pathological response. From June 2007 to June 2009, all consecutive patients with histopathologically confirmed breast cancer undergoing neoadjuvant chemotherapy were enrolled. All patients underwent magnetic resonance imaging (MRI) (including diffusion sequence) before and after neoadjuvant treatment. The ADC values obtained using two different methods of region of interest (ROI) placement before and after treatment were compared with MRI response (assessed using RECIST 1.1 criteria) and pathological response (assessed using Mandard's classification). Fifty-one women (mean age 48.41 years) were included in this study. Morphological MRI (RECIST classification) well evaluated the responder status after chemotherapy (TRG class; area-under-the-curve 0.865). Mean pretreatment ADC values obtained with the two different methods of ROI placement were 1.11 and 1.02 × 10(-3) mm(2) /seconds. Mean post-treatment ADC values were 1.40 and 1.35 × 10(-3) mm(2) /seconds, respectively. A significant inverse correlation between mean ADC increase and Mandard's classifications was observed for both the methods of ADC measurements. Diagnostic performance analysis revealed that the single ROI method has a superior diagnostic accuracy compared with the multiple ROIs method (accuracy: 82% versus 74%). The coupling of the diffusion imaging with the established morphological MRI provides superior evaluation of response to neoadjuvant chemotherapy treatment in breast cancer patients compared with morphological MRI alone. There is a potential in the future to optimize patient therapy on the basis of ADC value changes. Additional works are needed to determine whether these preliminary observed changes in tumor diffusion are a universal response to tumor cell death, and to more fully delineate the ability of ADC value changes in early recognizing responder from nonresponder patients.     

Treatment of the axilla in early breast cancer: past, present and future

Background: The optimal treatment of the axilla in early breast cancer is controversial. The present study reviews the pattern and predictors of regional recurrence (RR) and prognosis after RR in patients with early breast cancer treated by conservative surgery and radiotherapy (CS + RT). Implications of the results on current practice and future directions are explored. Methods: Between 1979 and 1994, 1158 patients with stage I or II breast cancer were treated with CS + RT at Westmead Hospital. Two groups of patients were compared: 782 patients who underwent axillary dissection (axillary surgery group) and 229 patients who received radiotherapy (axillary RT group) as the only axillary treatment. At least 10 lymph nodes were dissected in 82% of the axillary surgery group. Of the women in the RT group, 90% received RT to the axilla and supraclavicular fossa (SCF) only and 10% also received RT to the internal mammary chain (IMC). Results: With a median follow‐up period of 79 months for the axillary surgery group and 111 months for the axillary RT group, 27 patients developed a RR (2.8% and 2.2%, respectively). Seven patients (0.9%) in the axillary surgery group and three patients (1.3%) in the axillary RT group developed a RR in the axilla (P, not significant). Of the patients with SCF recurrences, 14 (1.8%) were in the axillary surgery group and one (0.4%) in the axillary RT group (P, not significant). One patient in the axillary surgery group developed concurrent axillary and SCF recurrences, while a patient in the axillary RT group developed an IMC recurrence. Twenty (74%) of the 27 patients with a RR developed a concurrent or subsequent distant relapse (30% and 44%, respectively). In the pathologically node‐positive patients, the axillary recurrence rate was higher in those who had less than five nodes removed (17%) than those who had 10 or more nodes removed (0%; P = 0.01). The SCF recurrence rate was higher in patients with four or more positive axillary nodes (9.5%) than in those with 0–3 positive nodes (1.5%; P = 0.003). Conclusion: Adequate treatment of the axilla by surgery or RT alone is associated with a low rate of RR. The incidence of distant relapse was substantial in patients who developed a RR, which gives emphasis to the importance of optimizing local–regional control.