The Critical Role of Axillary Ultrasound and Aspiration Biopsy in the Management of Breast Cancer Patients with Clinically Negative Axilla

Background Sonographic evaluation of the axilla can predict node status in a significant proportion of clinically node-negative patients. This review focuses on the value of ultrasound followed by ultrasound-guided cytology in assessing the need for sentinel node mapping and conservative versus complete axillary dissections. Design Breast primaries from 168 sentinel node candidates were prospectively assessed for clinicopathologic variables associated with increased incidence of axillary metastases. Patients were classified accordingly, and those at a higher risk underwent ultrasound of their axillae, followed by aspiration biopsy if needed. Sentinel node mapping was performed in all low-risk patients, and in high-risk patients with normal axillary ultrasounds or negative cytology. Final axillary status was compared in terms of nodal stage, number of positive nodes, and size of metastasis. Results 112 patients were at high risk for nodal disease (67%), with a statistically significant lower probability for remaining node-negative and a statistical significantly higher risk for having more than one positive node. All patients with more than three positive nodes were detected by ultrasound-guided cytology. High-risk patients with final positive axillae missed by ultrasound or ultrasound guided cytology had tumor deposits measuring ≤5 mm. Conclusion Extent of axillary dissections can be decided based on the risk for axillary metastases: sentinel node mapping for low-risk patients; less-aggressive axillary dissections for high-risk patients with negative ultrasound and/or negative cytology; and a standard dissection for high-risk patients with positive cytology.     

Detection and Significance of Occult Axillary Metastatic Disease in Breast Cancer Patients

▪ Abstract: After clinical staging, the single most important prognostic factor for patients with newly diagnosed primary breast cancer is the presence or absence of detectable metastases to axillary lymph nodes when examined by conventional light microscopy. More sensitive methods of determination of lymph node status, such as evaluation of serial sections, immunohistochemical staining, and use of molecular biological assays increase the rate of detection of micrometastases. Although the feasibility of enhanced detection of occult axillary metastatic disease is well established, the prognostic significance of such detection is only recently starting to emerge. Furthermore, the enormous recent interest in the application of sentinel lymph node biopsy as an alternative to the evaluation of the entire axilla in patients with breast cancer makes the first-time detailed evaluation for micrometastases practically feasible. In this review the different methods of detecting micrometastatic disease in the axilla and the significance of such findings are discussed. ▪     

Impact of Clinicopathological Factors on Sensitivity of Axillary Ultrasonography in the Detection of Axillary Nodal Metastases in Patients With Breast Cancer

Background: Ultrasonography and fine-needle aspiration (FNA) are used to evaluate the breast and regional nodes in breast cancer patients. We sought to identify factors influencing the sensitivity of ultrasonography for detection of nodal metastasis.Methods: Patients with a clinically negative axilla who underwent axillary ultrasonography and sentinel lymph node biopsy were included.Results: Of 208 patients, axillary ultrasonography was negative in 180 (86%) and suspicious or indeterminate in 28 (14%). FNA was performed in 22 patients whose findings were indeterminate or suspicious, and 3 were positive for malignancy. Final pathological examinations revealed positive nodes in 53 patients: 39 (22%) of 180 with negative ultrasonographic findings and 14 (50%) of 28 with indeterminate or suspicious ultrasonographic findings (P = .001). Excisional biopsy was more common for patients with indeterminate or suspicious findings on preoperative ultrasonography (P = .038). There were no significant differences in tumor size, histological features, size of nodal metastasis, or number of positive nodes between patients whose ultrasonography findings were negative and those whose findings were indeterminate or suspicious.Conclusions: Ultrasonographically suggested nodal metastasis is associated with the finding of nodal disease on final pathological examination. No significant clinicopathologic criteria were found to impact sensitivity of ultrasonography; however, excisional biopsy for diagnosis may be a confounding variable in subsequent axillary ultrasonography.     

Disease Recurrence in Sentinel Node-Positive Breast Cancer Patients Forgoing Axillary Lymph Node Dissection

Background

Clinically node-negative breast cancer patients usually undergo sentinel lymph node (SLN) biopsy. When metastasis is identified, completion axillary lymph node dissection (CALND) is recommended. Newer data suggest that CALND may be omitted in some women as it does not improve local control or survival.

Methods

Women with a positive SLN diagnosed between 1999 and 2010 were included in this review and were stratified according to whether they did or did not undergo CALND. Primary endpoints included recurrence and breast cancer-specific mortality. Differences between the groups and in time to recurrence were compared and summarized.

Results

Overall, 276 women were included: 206 (79?%) women who underwent CALND (group 1) and 70 (21?%) women in whom CALND was omitted (group 2). Group 1 patients were younger, had more SLN disease, and received more chemotherapy (P?P?>?0.05 for each). Median follow-up was 69 (range 6?C147) and 73 (range 15?C134) months for groups 1 and 2, respectively. Five (2?%) women in group 1 and three (4?%) women in group 2 died of breast cancer (P?=?0.39). Local?Cregional or distant recurrence occurred in 20 (10?%) group 1 patients and in 10 (14?%) group 2 patients (P?=?0.39). On multivariate analysis, only estrogen receptor negativity and lymphovascular invasion predicted for recurrence.

Conclusions

Omission of CALND in women with SLN disease does not significantly impact in-breast, nodal, or distant recurrence or mortality. Longer-term follow-up is needed to verify that this remains true with time.     

Favorable Outcome of Secondary Axillary Dissection in Breast Cancer Patients with Axillary Nodal Relapse

Purpose

Little evidence can be found about the long-term outcome of breast cancer patients after axillary lymph node recurrence (ALNR) and its survival benefit after different kinds of management. The present study intends to evaluate the risk factors associated with axillary recurrence after definite surgery for primary breast cancer. The prognosis after ALNR and particularly outcome of different management methods also were studied.

Methods

We retrospectively reviewed data from 4,473 patients who were diagnosed with primary breast cancer and received surgical intervention in a single institute from January 1990 to December 2002. Medical files were reviewed and data on survival were updated annually. Risk factors and prognosis of patients with axillary recurrence were analyzed. Breast–cancer-specific survival of patients with ALNR and outcomes after different management methods also were studied.

Results

After a median follow-up of 70.2 months, axillary recurrence developed in 0.8% of patients. Factors associated with ALNR included: age younger than 40 years, medial tumor location, no initial standard level I &; II axillary dissection, and not receiving hormonal therapy. The 5-year breast–cancer-specific survival after ALNR was 57.9%. For patients who received further axillary dissection, the 5-year survival rate was 82.5% compared with 44.9% for patients who did not receive further dissection.

Conclusions

ALNR is a rare event in treating breast cancer. Young age at diagnosis and medially located tumor are associated with higher risk, but standardized initial axillary dissection to level II and adjuvant hormonal therapy is protective against ALNR. In patients with ALNR, the outcome is not dismal and survival may be improved if further axillary dissection is given.     

乳腺癌腋窝淋巴结B超检查特异性回顾性分析

目的 探讨各辅助检查方法对乳腺癌腋窝淋巴结转移的诊断价值。方法 对天津医科大学附属肿瘤医院2009年3月至2009年6月253例经手术病理证实乳腺癌病人术前B超与钼靶、MRI、PET-CT资料进行回顾性分析,比较灵敏度、特异度、阳性及阴性预测值和准确性。结果 B超（253例）灵敏度,特异度,阳性及阴性预测值,准确性为70.6%,87.4%,84.8%,75.0%和79.1%;钼靶（220例）为14.6%,100%,100%,53.9%和57.3%;MRI（27例）为50.0%,100%,100%,71.4%,77.8%;PET-CT（23例）为90.0%,92.3%,90.0%,92.3%,91.3%。B超与病理对照的Kappa值为0.581,与病理的一致性一般;高年资组B超医师的灵敏度、特异度、准确性为与低年资组比较差异有统计学意义（P＜0.05）。结论 判断乳腺癌腋窝淋巴结转移状况B超优于其他检查,而且超声检查者的经验影响诊断结果。     

Axillary Ultrasonography to Detect Recurrence After Sentinel Node Biopsy in Breast Cancer

Background Sentinel node biopsy (SNB) for breast cancer has a false-negative rate of approximately 5%. Initial reports of follow-up show lower axillary recurrence rates than expected. We performed axillary ultrasonography to determine whether occult recurrences could be detected. Methods In a community hospital setting, 289 patients who had SNB for breast cancer in a single surgeon’s practice underwent axillary examination by the surgeon followed by axillary ultrasonography by a dedicated breast radiologist. Ultrasonography was performed one time from 4 to 79 months (median, 25 months) after surgery. Five patients with suspicious nodes had ultrasound-guided fine-needle aspiration, and one had a core biopsy. Results No patient had suspicious nodes on clinical examination. Only six patients had ultrasound findings that warranted intervention. Five patients had benign cytological characteristics, and one had a benign core biopsy result. No evidence of axillary recurrence was found in any patient. Conclusions Axillary ultrasonography did not detect occult metastases in any patient and is not recommended for routine follow-up after SNB. The lack of ultrasound evidence of metastasis suggests that the recurrence rate is likely to remain low.     

Identification of the Sentinel Node by Ultrasonography in Patients with Breast Cancer

Background

Identification of the sentinel node (SN) in patients with breast cancer is done by tracking a radioactive tracer, a vital dye, or both, as the marker(s) reach the axilla. Replacing this method with ultrasonographic (US) recognition of the SN could eventually spare patients the need for systemic anesthesia, permit minimally invasive outpatient biopsy of the node, and allow the formulation of a precise therapeutic plan before a definitive surgical procedure.

Methods

Eighty-eight axillae of 84 patients with a histologic diagnosis of breast cancer were studied by injecting the subareolar area of the affected breast(s) with technetium 99 and an iron preparation before the planned surgical procedure and SN biopsy. An axillary US scan was performed in all patients before the injection of the markers. After induction of anesthesia, the SN was identified, needle-localized, and extracted under US guidance. Confirmation that the SN was retrieved was established by concordance with the audible gamma signal, unless there was none. All extracted nodes had iron stains performed.

Results

All except three of the SNs were identified with US after the iron marker was injected, and all except six were identified by their radioactive signal. One of the SNs undetected on US was identified by its radioactive tracer, and the other two, although seen on US, had neither a gamma signal nor concordant iron deposits. All other SNs identified with US had a concordant audible signal when there was one, and all had concordant iron deposits on microscopy. Of the six SNs without a gamma signal, three without preincision activity were identified with US; three with neither a preincision nor an ex vivo signal were seen with US, but two of these were the SNs without a concordant iron deposit.

Conclusions

Using an iron preparation, the SN in patients with breast cancer can be identified with US with an accuracy equal to and perhaps better than that achieved with a radioactive tracer. These findings may change the current diagnostic model and affect the therapeutic algorithm of breast cancer patients.     

A Predictive Tool to Estimate the Risk of Axillary Metastases in Breast Cancer Patients with Negative Axillary Ultrasound

Background

Sentinel node biopsy (SNB) is the “gold standard” in axillary staging in clinically node-negative breast cancer patients. However, axillary treatment is undergoing a paradigm shift and studies are being conducted on whether SNB may be omitted in low-risk patients. The purpose of this study was to evaluate the risk factors for axillary metastases in breast cancer patients with negative preoperative axillary ultrasound.

Methods

A total of 1,395 consecutive patients with invasive breast cancer and SNB formed the original patient series. A univariate analysis was conducted to assess risk factors for axillary metastases. Binary logistic regression analysis was conducted to form a predictive model based on the risk factors. The predictive model was first validated internally in a patient series of 566 further patients and then externally in a patient series of 2,463 patients from four other centers. All statistical tests were two-sided.

Results

A total of 426 of the 1,395 (30.5 %) patients in the original patient series had axillary lymph node metastases. Histological size (P < 0.001), multifocality (P < 0.001), lymphovascular invasion (P < 0.001), and palpability of the primary tumor (P < 0.001) were included in the predictive model. Internal validation of the model produced an area under the receiver operating characteristics curve (AUC) of 0.731 and external validation an AUC of 0.79.

Conclusions

We present a predictive model to assess the patient-specific probability of axillary lymph node metastases in patients with clinically node-negative breast cancer. The model performs well in internal and external validation. The model needs to be validated in each center before application to clinical use.     

Treating Positive Axillary Disease in Elderly Breast Cancer Patients: The Impact of Age on Radiation Therapy

IntroductionBreast cancer is the second most common cause of cancer death in females, and 30% of these patients are over the age of 70 years. Studies have shown deviation from the standard treatment paradigms in the elderly, especially in regard to radiation treatment.MethodsWe performed a retrospective chart review on 118 patients over the age of 70 years diagnosed with breast cancer and pathologically proven axillary disease over an 8-year period at an urban academic hospital to examine which patient factors influenced radiotherapy.ResultsIncreasing patient age was associated with a decrease in the probability of receiving radiotherapy, while HER2-negative patients were more likely to receive radiation. Neither race, number of coexisting medical conditions, or insurance status showed any influence on radiation treatment.ConclusionPatient age has a significant influence if elderly patients with axillary disease receive radiotherapy. Further investigation and validation are needed to understand why chronological age rather than biological age influences treatment modalities.     

乳腺癌腋窝淋巴结转移危险因素的研究

目的探讨导致乳腺癌腋窝淋巴结转移的相关危险因素,为制定更合理的个体化治疗方案提供参考依据。方法以2014年1月至2016年6月间住院治疗的94例乳腺癌患者为研究对象,收集患者临床病理特征,包括年龄、肿瘤大小、前哨淋巴结状态、脉管浸润、病理类型等,检测ER、PR、HER2、AR、Bcl-2蛋白表达情况,采用单因素与多因素结合分析筛选腋窝淋巴结转移相关危险因素。应用SPSS17.0软件进行统计学处理,采用χ~2检验逐个进行单因素分析,筛选出有意义的因素纳入Logistic回归模型进行多因素分析,P0.05表示差异有统计学意义。结果 94例患者中,发生腋窝淋巴结转移61例(64.9%)。单因素分析结果显示,乳腺癌腋窝淋巴结转移与肿瘤大小(直径)、有无前哨淋巴结转移、有无脉管浸润及AR、Bcl-2蛋白表达相关,差异有统计学意义(P0.05)。多因素Logistic回归分析结果显示,肿瘤大小、前哨淋巴结转移、脉管浸润是乳腺癌患者腋窝淋巴结转移的危险因素,AR阳性为保护因素。结论肿瘤直径≥2 cm、有前哨淋巴结转移及脉管浸润是乳腺癌患者腋窝淋巴结转移的高危因素,AR表达情况是预测腋窝淋巴结转移风险较佳的生物学因素。     

Supraclavicular and Contralateral Axillary Lymph Node Involvement in Breast Cancer Patients

Annals of Surgical Oncology - Ipsilateral supraclavicular disease was reclassified from Stage IV, distant metastatic disease, to Stage IIIC, locally advanced breast cancer 20 years ago. Treatment...     

Decreasing Use of Axillary Dissection in Node-Positive Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Background

Neoadjuvant chemotherapy (NAC) may downstage axillary disease in node-positive breast cancer. Several clinical trials have shown that sentinel lymph node (SLN) surgery after NAC is feasible for these patients. We sought to evaluate the use of SLN surgery and ALND in cN1 patients undergoing NAC.

Methods

We identified all patients with biopsy-proven cN1 breast cancer treated with NAC at our institution between January 2009 and December 2017. Approximated biologic subtype was determined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. Cochran–Armitage trend and Chi square tests were used for statistical analysis.

Results

Of 430 cN1 patients treated with NAC, 93 (22%) underwent SLN surgery only, 100 (23%) underwent SLN and ALND, and 237 (55%) underwent ALND only. The use of SLN surgery (±?ALND) increased from 28% in 2009 to 86% in 2017 (p?<?0.001), while the performance of ALND decreased from 100% in 2009 to 38% in 2017 (p?<?0.001). Among SLN+ patients who underwent ALND, disease was limited to the SLNs in 25/73 (34%) patients. The nodal pathologic complete response rate was 46% and varied by tumor subtype (p?<?0.001). Among patients undergoing SLN surgery, ALND was avoided in 48% of patients overall and varied by biologic subtype: 55% ER?/HER2+, 61% ER+/HER2+, 62% ER?/HER2?, and 31% ER+/HER2? (p?=?0.001). With short-term follow-up, no nodal recurrences have occurred in patients without ALND.

Conclusions

We observed a significant shift in axillary surgery for cN1 breast cancer patients treated with NAC, with increasing use of SLN surgery to assess nodal treatment response, and decreasing use of ALND.

     

Axillary Staging in Breast Cancer Patients with Exclusive Lymphoscintigraphic Drainage to the Internal Mammary Chain

Background  

The aim of this study was to evaluate the need of axillary staging in breast cancer patients showing exclusive lymphatic drainage to the internal mammary chain (IMC).     

前哨淋巴结活检在早期乳腺癌手术中的意义

目的探讨前哨淋巴结活检在早期乳腺癌外科治疗中决定乳腺切除范围的意义.方法278例乳腺癌患者,利用γ-探测仪定位前哨淋巴结(SLN),切下的SLN和腋窝淋巴结(ALN)行HE染色和免疫组织化学染色(IHC),观察前哨淋巴结病理结果,预测腋窝淋巴结转移的准确性.结果278例前哨淋巴结,检出率91.73%(255/278).248例进行腋窝淋巴结清扫,HE染色86例腋窝淋巴结转移,87例前哨淋巴结转移;IHC染色显示腋窝淋巴结转移91例,前哨淋巴结转移88例.60例前哨淋巴结活检阴性的早期乳腺癌保乳治疗后,随访3～5年影像学检查均未发现局部复发或腋窝淋巴结转移,保乳保腋窝组和保乳未保腋窝组远期疗效无区别.结论前哨淋巴结活检用于指导腋窝淋巴结清扫,是一种相对可靠的客观指标,活检阴性可作为保留腋窝的安全指标,但术后仍需监测腋窝淋巴结的增多或增大现象,必要时进行淋巴结活检.     

Management of Occult Breast Cancer with Axillary Involvement

Occult breast cancer (OBC), which is defined as clinically recognizable axillary metastatic carcinoma from an undetectable primary breast tumor, accounts for less than 1% of all patients who present with breast cancer (BC). Although criticized for high false positive rate (FPR) in routine BC diagnosis, the role of magnetic resonance imaging (MRI) is crucial in the diagnosis of OBC. The standard treatment for OBC, initially, was blind modified radical mastectomy, but one third of patients who undergo blind mastectomy, will have no histopathological findings of carcinoma. Current evidence supports the use of whole breast radiotherapy (WBRT) and axillary nodes clearance (ANC) as the locoregional treatment for patients with OBC. Management of the axilla does not differ from that of patients with BC with clinically palpable axillary lymph nodes (LNs) and ANC, which remains the gold standard, should be used for staging and loco-regional control. Neo-adjuvant chemotherapy (NACT) could reduce ANC by 43%, and for patients who undergo NACT with complete radiological response, a more conservative surgical approach, with a minimum of 3 sentinel lymph node biopsies (SLNBs), together with targeted dissection of the involved LNs could be considered as an option. This offers adequate staging and loco-regional control, combined with significantly less comorbidities than ANC. Overall, the prognosis of OBC is equal to or better than that of other BCs with metastasis to the axillary LNs. Progesterone receptor (PR) expression should be taken into account when evaluating the prognosis of OBC because PR-positive patients achieve better overall survival and have a lower risk of local recurrence. Surveillance should include breast MRI and mammography.     

Axillary Padding without Drainage after Axillary Lymphadenectomy - a Prospective Study of 299 Patients with Early Breast Cancer

BACKGROUND: After lymphadenectomy for early breast cancer, seroma formation is a constant event requiring a suction drainage. This drainage is the strongest obstacle to reducing the hospital stay. Axillary padding without drainage appears to be a valuable option amid the various solutions for reducing the hospital stay. METHODS: We conducted a comparison between 114 patients with padding and 185 patients with drainage. Data were obtained from 2 successive prospective studies. RESULTS: The mean hospital stay was 2.4 days (range 1-4) in the padding group and 4.2 days (range 2-9) in the drainage group (p < 0.05). There were fewer needle aspirations for seroma in the padding group (8.8 vs. 23%, p < 0.05). At 6 weeks, only 28% (32/114) of the patients in the padding group reported pain versus 51% (94/185) in the drainage group. The mean pain intensity at 6 weeks was 3 and 4.3 respectively (p < 0.0001). CONCLUSION: Axillary padding without drainage was associated with a better post-operative course than suction drainage in this historical comparison, and the hospital stay was significantly shortened. There are only few series published on this new technique but they all indicate good feasibility and good tolerance. A large randomised multicentric evaluation is now warranted.     

乳腺癌腔镜前哨淋巴结活检83例临床分析

目的探讨染料法腔镜腋窝前哨淋巴结活检在乳腺癌中的可行性和临床意义。方法应用亚甲蓝染色法对83例Ⅰ、Ⅱ期乳腺癌行腔镜前哨淋巴结活检(ESLNB),然后行腔镜腋窝淋巴结清扫(EALND)。对获取的全部淋巴结行病理检查,评价前哨淋巴结检出率、准确率及假阴性率。结果83例中73例检出前哨淋巴结,检出率87.9%(73/83)。ESLNB准确率97.3%(71/73),灵敏性88.2%(15/17),特异性100.0%(56/56)。结论染料法腔镜腋窝前哨淋巴结活检临床可行,能够对早期乳腺癌进行准确分期,但体重指数高、肿瘤部位在内侧、术前肿瘤切除活检、腔镜技术欠熟练等是影响前哨淋巴结检出的主要因素。