乳腺癌内乳区前哨淋巴结活检术研究进展

内乳区淋巴结的转移状况是乳腺癌的独立预后指标,也：是乳腺癌淋巴分期的重要依据之一。内乳区淋巴结转移的患者预后较差。随着前哨淋巴结活检技术的不断发展和新型注射技术的出现,内乳区前哨淋巴结活检的显像率显著提高,经肋间行内乳区前哨淋巴结活检术可以最小的风险评估内乳区淋巴结状况,并进一步完善乳腺癌的淋巴结分期．有助于为患者制定更为准确的个体化治疗方案。     

Internal mammary sentinel node biopsy for breast cancer

Background

The purpose of this study was to determine the value of lymphoscintigraphy (LS) for internal mammary sentinel node (IMSN) identification, the metastatic rate, and the change in staging and treatment.

Methods

Between 2001 and 2007 a prospective database was obtained of all patients undergoing IMSN biopsies using an open or thoracoscopic approach. Radiotracer injection was peritumoral.

Results

Thirty-four patients were included. There was one man. Three had ductal carcinoma in situ. LS showed IMSN in 47.1%. The IMSN biopsy success rate was 91.2%. Seven of the 28 successfully biopsied invasive cancer patients had metastatic IMSNs (25%). Positive IMSNs were associated with positive axillary nodes in 71.4% (P = .036). All patients with positive IMSNs were upstaged and received radiation to the internal mammary chain. In 4 of 28 patients (14%) the chemotherapy plans were probably altered. In univariate and multivariate analyses tumor size, location, nuclear grade, estrogen receptors, progesterone receptors, Her-2, and histology were not significant predictors of positivity.

Conclusions

IMSNs were positive in 25% of the invasive cancer patients. All had treatment changes. LS identified less than 50% of IMSNs. There are no good tumor-related predictors of IMSN positivity.     

Internal mammary sentinel node metastases in an otherwise lymph-node negative breast cancer patient

A 35 year old woman with biopsy proved breast cancer was submitted for sentinel node (SN) biopsy. Preoperative lymphoscintigraphy displayed both axillary and internal mammary (IM) uptake foci consistent with SNs. Full axillary dissection was completed because of a greater-than 2 cm primary lesion. Two axillary SNs were excised. An IM SN was also excised through the second intercostal space, with the aid of the gamma probe. Fourteen axillary nodes, including SNs, were negative, whereas the IM SN harbored several metastatic implants. Implications for staging, prognosis and further therapy of such IM-only positive sentinel nodes are discussed.     

Internal mammary lymph node metastasis in breast cancer: predictive models to assist with prognostic influence

Background

Metastatic breast cancer in the internal mammary nodes (IMN) indicates a poor prognosis. Several recent epidemiological surveys have determined a reduction in survival for patients with medial compared to lateral sector tumors attributing this to a higher rate of unrecognized IMN metastasis and hence these patients are undertreated with adjuvant therapy. ^{[1], [2], [3], [4], [5] and [6]}

Aim

Through mathematical modeling based on large datasets we aim to quantify the impact on survival of IMN metastases at different tumor and axillary stages.

Methods

Mathematical models were created to estimate the survival of patients with and without IMN metastasis. It was assumed that the different rate of survival between medial and lateral sector breast cancers was a result of the differential rate of unrecognized IMN metastases with resultant under-staging and under treatment. We applied these models on a retrospective database analysis from the Surveillance, Epidemiology and End-Results (SEER) registries from 1994 to 2003.

Results

The 10-year odds of death (OOD) from breast cancer for patients with medial compared with lateral sector tumors ranged from 1.2 to 1.5 depending on stage. The predicted odds of breast cancer death for patients with unrecognized IMN metastases ranged from 2.4 to 20, with the highest OOD in the groups with small tumors and no axillary node metastasis.

Conclusions

Through modeling we have been able to predict and quantify the significantly worse survival outcomes for patients with undiagnosed IMN metastasis.     

Internal mammary node involvement in patients with axilla-negative early breast cancer: a narrative review

Early breast cancer staging involves radiological and pathological evaluation of the tumour and regional lymph nodes. The internal mammary nodes (IMN) are an important site of possible metastasis and influence disease stage and prognosis. However, the recommendation for routine IMN assessment remains unclear. Internal mammary sentinel lymph node biopsy (SLNB) is associated with increased morbidity and an unknown survival benefit. Furthermore, the IMN are traditionally thought to be involved only synchronous with, or following, axillary node (AXN) metastasis. The aim of this review is to determine the prevalence of IMN metastasis in patients with axilla-negative early breast cancer. A narrative review of studies assessing IMN metastasis was performed. The literature search was completed using the database Medline (Ovid). Twenty-two retrospective studies were identified. The studies included data from SLNB, US, MRI, PET/CT and opportunistic biopsy during free-flap reconstruction (FFR). The prevalence of isolated IMN metastasis ranged from 1.2% to 17.9%.     

经肋间隙探查定位于内乳区的前哨淋巴结对乳腺癌淋巴分期的影响

目的 探讨乳腺癌前哨淋巴结在内乳区时对其探查与否对淋巴结分期的影响。方法 2006-01—2016-01间,对501例c T1-4N0-1M0期乳腺癌患者进行前哨淋巴结探查术,发现有蓝染淋巴管通向内乳区的患者,经肋间隙入路行内乳区前哨淋巴结活检术(IM-SLNB)+腋窝前哨淋巴结探查+改良根治术100例为A组;行腋窝前哨淋巴结探查+改良根治术401例为B组。观察A组经肋间隙入路IM-SLNB的病理结果与假设该组病例不探查相对比,了解探查对其淋巴分期的影响。观察经肋间隙入路的IMSLNB对手术时间、出血、并发症及恢复等的影响。结果 A组探查发现内乳区淋巴结癌转移19例相对于假设不探查为0例,其淋巴结分期修正率19.0%,(P0.05)有统计学意义;经肋间隙入路IM-SLNB阶段所用时间(23.93±5.89)min;仅1例术中胸廓内动脉出血,切断肋软骨显露血管后结扎止血,出血量约10~20 m L,其余99例均5 m L;胸膜破损0例、气胸0例;术后并发症和愈合时间与B组无统计学差异(P0.05)。结论 选择乳腺癌前哨淋巴结在内乳区时对其进行探查其阳性率高,有助于淋巴结准确分期;经肋间隙入路的内乳区淋巴结探查,创伤小、风险小、不增加并发症。     

经肋间隙入路行内乳淋巴结活检的探讨

目的研究胸前壁内乳区的局部解剖,探讨经肋间隙入路行内乳淋巴结活检的可行性和安全性。方法113例乳腺癌患者均接受不同术式的根治术及经肋间隙内乳淋巴结活检术。术中测量胸骨外缘距胸廓内动脉的距离和肋间隙的宽度,记录内乳淋巴结的部位和最大直径。结果胸廓内动脉距胸骨外缘的距离在第1、2、3和4肋间隙分别为(10．9±4．5)mm、(11．6±3．O)mm、(9．6±3．6)mm和(4．5±3．5)mmo第1、2、3、4肋间隙宽度分别为(14．2±4．1)mm、(16．2±4．2) mm、(13．9±4．3)mm和(9．9±3．6)mm c 113例乳腺癌共切除内乳淋巴结279枚。内乳淋巴结位于胸廓内动脉周围的脂肪组织中,在血管内侧占41．2％,外侧占51．6％,前方为7．2％。113例乳腺癌患者中内乳淋巴结转移者26例,其中仅有内乳淋巴结转移者5例。结论切开胸骨外缘肋间肌2-3．5 cm所提供的术野能完成内乳淋巴结活检,此方法具有操作简便、创伤小、安全性高的特点。     

Internal mammary sentinel lymph node biopsy should still be performed,especially in the patient with clinically positive axillary lymph nodes

Current studies suggest that the internal mammary sentinel lymph node biopsy (IM-SLNB) should not be performed routinely, for it did not alter clinical management of breast cancer patients in terms of adjuvant treatment. However, consideration should be given to the fact, the study population in all current research relate to IM-SLNB is the patients with clinically negative axillary lymph nodes. As internal mammary lymph nodes metastases are mostly found concomitantly with axillary metastases, clinical trials currently fail to evaluate the status of internal mammary lymph nodes who really in need. In consideration of the impact to staging and accurate indication of radiation to the internal mammary area, we recommend that research on IM-SLNB should still be encouraged, especially in patients with clinically positive axillary lymph nodes.     

Results of tailored treatment for breast cancer patients with internal mammary lymph node metastases

Although the internal mammary (IM) lymph node status is a major prognostic factor in breast cancer, IM nodal staging is not common practice. In order to improve nodal staging, we have routinely performed IM sentinel node (SN) biopsy and have adjusted adjuvant treatment accordingly. We reviewed the outcome of these patients. Data from 764 patients were available for follow-up. A total of 406 patients had no lymph node metastases (group 1), 330 patients had axillary metastases (group 2), 7 patients had IM metastases only (group 3) and 21 patients had both axillary and IM metastases (group 4). Mean follow-up was 46 months. Prognosis did not appear to be worse for patients with IM metastases compared to those with axillary metastases only, which might indicate that they benefit from improved staging and tailored adjuvant treatment algorithms. However, long-term follow-up data, preferably in larger series, are needed to support our findings.     

Stage migration and therapy modification after thoracoscopic internal mammary lymph node dissection in breast cancer patients

Although internal mammary lymph node (IMN) status is a major prognostic factor in breast cancer, it is not routinely assessed. To evaluate the impact of IMN status on staging and treatment of breast cancer, we enrolled 50 consecutive patients with inner or central tumors who received IMN dissection by video-assisted thoracoscopic surgery (VATS) after breast surgery. Of the 50 patients, 20 (40%) had IMN metastases. Of the 20 patients, 6 (12%) were upstaged from N0 to N2b and 5 (10%), 3 (6%) and 6 patients (12%) were upstaged from N1a, N2a, and N3a, respectively, to N3b. Because of the upstaging, 6 patients (12%) with only IMN metastases received more aggressive adjuvant chemotherapy. Because the whole IMN chain was removed in all patients, radiotherapy on IMN field was not required in our cohort independent of IMN status. In conclusion, VATS IMN dissection might lead to stage migration and therapy modification.     

胸腔镜内乳前哨淋巴结活检和内乳淋巴链切除的实验研究

目的探讨胸腔镜下内乳前哨淋巴结活检和内乳淋巴链切除的可行性。方法实验用小型母猪6头，双腔管气管插管全身麻醉。胸前第1对乳房皮下注射亚甲蓝4ml，经胸腔镜观察内乳前哨淋巴结蓝染时问，超声刀切除内乳前哨淋巴结和内乳淋巴链，记录手术时间。结果6头小型母猪共12侧内乳前哨淋巴结和内乳淋巴链，采用胸腔镜联合淋巴结蓝染定位法成功切除，内乳前哨淋巴结蓝染时间5～15min，平均8．9min；活检时间15—50min，平均30．4min；内乳淋巴链切除时间分别为左侧30—56min，右侧22～48min，平均38．2min。无出血、肺损伤等手术并发症发生。结论胸腔镜内乳前哨淋巴结活检和内乳淋巴链切除是可行的，手术操作简便、创伤较小。     

Therapeutic attitude towards internal mammary chain drainage in patients with breast cancer

Internal mammary chain (IMC) is one of the main local lymph drainages in breast cancer. However, internal mammary chain sentinel lymph node biopsy (IMC-SLNB) is not always performed.The purpose of this research is to evaluate the outcomes of IMC-SLNB in our institution from 2008 to 2014. We analyzed 1346 women with breast cancer. Six-hundred twenty-two sentinel node biopsies were carried out, one out of ten in IMC territory. Adjuvant radiotherapy in this area was added when positive.IMC-SLNB is feasible, it may change tumour stage, modify adjuvant therapy and change prognosis in selected patients.     

Reappraisal of internal mammary lymph node dissection in selected patients with invasive breast cancer

We performed a new type of en bloc extended radical mastectomy (EXT) as a clinical trial in 118 patients from 1980 through 1985. A variety of conventional radical mastectomies (RDL) were also undertaken in 105 patients from 1973 through 1985. In this retrospective study, univariate and multivariate analyses were performed to compare the results of EXT and RDL. The univariate analysis showed that the 10-year survival rates for the EXT and the RDL groups were 86% ± 3.3% and 77% ± 4.2%, respectively (P = 0.073 with the Cox-Mantel test). For the subgroups stratified according to the status of axillary lymph node involvement, the EXT was significantly better in patients with one to three metastatic axillary lymph nodes (P = 0.016). The adjusted Cox regression analysis revealed that the favorable results of EXT were most encouraging in the patients with one to three metastatic axillary lymph nodes (P = 0.058). Therefore, it is suggested that an EXT may be more advantageous than RDL in selected patients with resectable invasive breast cancer.     

Outcome of radiotherapy for clinically overt metastasis to the internal mammary lymph node in patients receiving neoadjuvant chemotherapy and breast cancer surgery

PurposeThis study was aimed to assess the outcome of radiotherapy and determine prognostic factors for survival in breast cancer patients with clinically overt metastasis to the internal mammary lymph node (IMN+).MethodsWe retrospectively reviewed the medical records of 193 patients with IMN + breast cancer who received neoadjuvant chemotherapy (NAC), breast surgery without internal mammary lymph node (IMN) dissection, and postoperative radiotherapy at 9 hospitals between 2009 and 2013. Breast-conserving surgery or mastectomy was performed after taxane-based NAC. Radiotherapy was administered to the whole breast/chest wall and regional nodes. IMN-covering radiotherapy was performed in 92.2% of patients with median dose of 58.4 Gy (range, 44.9–69.1 Gy). The overall survival (OS), disease-free survival (DFS), and IMN failure-free survival (IMNFFS) were analyzed.ResultsAfter median follow-up of 71 months, 9 patients (4.7%) developed IMN failure and simultaneous distant metastasis. The 5-year DFS, OS, and IMNFFS was 68.6%, 81.8%, and 95.3%, respectively. Non-triple-negative breast cancer, Ki-67 ≤ 10%, pathological complete response (CR) in tumor and axillary node, and radiologic CR of IMN after NAC were significant factors for predicting higher DFS; however, IMN radiation dose was not significant determinants for DFS. The 5-year DFS of patients with IMN-dose ≤ 50.0 Gy and those with >50.0 Gy was 86.7% and 76.7%, respectively (p = 0.41).ConclusionsA multimodality strategy including NAC, breast surgery, and IMN-covering radiotherapy was effective for patients with overt IMN + breast cancer. Even without an IMN dissection, most patients were IMN failure-free with an IMN-focusing radiotherapy.     

Radical mastectomy with parasternal node dissection or radiation to the parasternal region for breast cancer of medial or central location

In order to establish a therapeutic approach for primary breast cancer of medial and central origin, we reviewed 183 patients who had been treated by one of the following three modalities at the Second Department of Surgery, Osaka University Medical School between January, 1965 and December, 1980. Group A (n=70): standard radical mastectomy alone; Group B (n=34): standard radical mastectomy followed by postoperative irradiation to the parasternal and supraclavicular regions, and; Group C (n=62): extended radical mastectomy that included removal of the parasternal lymph nodes. The background factors of the three groups were not significantly different. The overall survival five and ten years following surgery in the three groups were 91 per cent and 79 per cent in group A, 82 per cent and 67 per cent in group B, and 82 per cent and 70 per cent in group C, respectively, showing no significant difference in overall survival among the three groups. When the patients were classified according to the extent of axillary lymph node involvement, there was no difference in survival among the three treatments in patients who had less than three lymph node metastases in the axilla. However, treatment of the parasternal lymph nodes improved survival in the patients who had more than four lymph node metastases in the axilla. Parasternal lymph node involvement definitely worsened the prognosis, showing it to be a good prognostic factor. Thus, extended radical mastectomy should be considered for patients with breast cancer of medial or central location, when extended axillary lymph node involvement is found.     

淋巴结比率在淋巴结阳性阴茎癌预后中的价值

目的探讨淋巴结比率在淋巴结阳性阴茎癌中的预后价值。方法分析1990年至2008年间复旦大学附属肿瘤医院诊治的60例淋巴结转移性阴茎鳞状细胞癌患者的临床资料。所有患者均接受了区域淋巴结清扫手术。阳性淋巴结数和淋巴结比率都转化为分类变量加以分析。无复发生存曲线通过Kaplan-Meier方法绘制并通过Log-rank检验加以分析。结果本组患者的阳性淋巴结数中位数为2个（1～27）,淋巴结比率的中位数为0.0896（0.031～0.406）。随着淋巴结清扫总数的增多,阳性淋巴结数目也逐渐增多。Log-rank成对比较的结果显示淋巴结比率比阳性淋巴结数能更好地区分各组间的生存差异。结论淋巴结比率是比阳性淋巴结数目更好的预后指标,更进一步的大宗病例研究有助于确定淋巴结比率的界值来具体界定低危和高危患者。     

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.     

乳腺癌新辅助化疗后前哨淋巴结活检术的研究

目的 探讨乳腺癌病人新辅助化疗后前哨淋巴结活检的可行性。方法对2003年11月至2004年10月住院治疗中的57例Ⅱ、Ⅲ期乳腺癌病人行新辅助化疗后，临床检查腋窝淋巴结阴性行前哨淋巴结活检术（SLNB）。结果57例中检出前哨淋巴结（SLN）53例，检出率93．0％。SLN对腋窝淋巴结状况预测的敏感性为89．7％，特异性为100．0％，准确性为94．3％，阳性预测值为100．0％，阴性预测值为88．9％，假阴性率为5．7％。肿瘤对化疗反应为CR（完全缓解）、PR（部分缓解）和SD（稳定）的SLN检出率分别为100．0％、96．7％和70．0％（P〈0．01）。SLN假阴性3例均为腋窝淋巴结转移数〉4个者。结论Ⅱ、Ⅲ期乳腺癌实施新辅助化疗后。行SLNB可获得与早期乳腺癌SLNB相似的效果。