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.

     

Sentinel Node Biopsy Before Neoadjuvant Chemotherapy Spares Breast Cancer Patients Axillary Lymph Node Dissection

Background Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Methods Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Results Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Conclusions Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.     

Clinical Significance of Axillary Microresiduals After Neoadjuvant Chemotherapy in Breast Cancer Patients with Cytologically Proven Metastases

Background  Neoadjuvant chemotherapy (NAC) has been widely accepted for advanced breast cancer patients, and pathological complete remission (pCR) was revealed to be an important prognostic factor. The pCR status of cytologically proven axillary metastases (ALN-pCR) offers a more powerful prognostic predictor than pCR of the main tumor. This study evaluated the clinical significance of residual micrometastases and discusses screening methods after NAC in patients with cytologically proven axillary metastases. Methods  Eighty patients with a diagnosis of cytologically proven axillary metastases received NAC. All dissected lymph nodes were evaluated using multislice sectioning and cytokeratin immunohistochemistry, and categorized into four groups: no metastases (ALN-pCR), and with metastases ≤0.2 mm (ALN-itc), >0.2 mm but ≤2 mm (ALN-mic), and >2 mm (ALN-mac). Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan–Meier method based on the status of residual metastases. Results  DFS in patients with ALN-pCR and ALN-itc was significantly longer than that with ALN-mic (P = 0.007, P = 0.045, respectively). OS with ALN-pCR was significantly longer than that with ALN-mic (P = 0.004). There was no significant difference in DFS or OS between ALN-mac and ALN-mic. These data showed the clinical significance of microresidual metastases >0.2 mm after NAC in patients with cytologically proven axillary metastases. Conclusions  Using multislice sectioning, screening for ALN-mic after NAC was clinically important, and that for ALN-itc was not clinically essential.     

Touch Imprint Cytology of the Sentinel Lymph Nodes Might Not Be Indicated in Early Breast Cancer Patients with Ultrasonically Uninvolved Axillary Lymph Nodes

Background  Touch imprint cytology (TIC) is a fast, cheap and specific intraoperative examination of the sentinel lymph nodes (SLNs) in early breast cancer patients. The results of TIC in patients with ultrasonically (US) uninvolved axillary lymph nodes are not known. The objective of our study was to compare the results of TIC in the patients with US uninvolved axillary lymph nodes (US group) and those with only clinically uninvolved axillary lymph nodes (non-US group). Methods  A total of 470 patients were included in the study, 257 in the US group and 213 in the non-US group. TIC results were compared to the definite histology, and the sensitivity of TIC was calculated for both groups of patients. A subgroup analysis of TIC findings with regard to the primary tumor size was performed. Results  Overall sensitivity and sensitivity for detecting macrometastases was significantly lower in the US group compared with the non-US group. In the US group, TIC results changed the course of treatment in 9% of patients, while in the non-US group, the course of treatment was changed in 22% of patients. In the non-US group, the proportion of positive TIC results increased with increasing tumor size, whereas in the US group it did not. Conclusion  The sensitivity of TIC is lower in the patients with US uninvolved axillary lymph nodes compared to those with only clinically uninvolved axillary lymph nodes. TIC might not be indicated in patients with US uninvolved axillary lymph nodes as it changes the course of treatment in only 9% of patients.     

The Evaluation and Optimization of Intraoperative Touch Imprint Cytology for Sentinel Lymph Nodes in Early-stage Breast Cancer in China

Background  

Accurate intraoperative diagnosis of sentinel lymph node (SLN) metastasis reduces the need for additional surgery in patients with involved nodes. The present study evaluates the clinical value of multiple cross-sectional touch imprint cytology (TIC) as an intraoperative assessment for the diagnosis of SLN metastasis.     

Role of Intra-Operative Touch Imprint Cytology in the Treatment of Breast Cancer

Objectives : A prospective study was carried out to evaluate the role of intra-operative touch imprint cytology (TIC) in the assessment of sentinel lymph node (SLN) involvement for staging and treatment of early-stage, clinically node-negative breast carcinoma.

Methods : Forty-five patients with early-stage, clinically node-negative breast cancer underwent a SLN biopsy with intra-operative TIC. The SLN was bisected if its width was less than 4 mm or sliced every 2 mm if it was more than 4 mm. The imprint specimens were stained with haematoxylin and eosin (H&E). Rapid immunochemistry (IH) was performed in case of equivocal cytological result. Permanent sections were evaluated with H&E and IH staining. The results of TIC were compared to histopathological results.

Results : The sensitivity, specificity and overall accuracy of TIC on a node basis were 65.5%, 96.3%, 85.5%, respectively. When calculated according to the size of SLN metastasis, the sensitivity of TIC for overt metastasis was 84.6%, while it was 62.5% for micrometastasis and 37.5% for sub-micrometastasis. The mean size of nodal metastasis was 5.08 mm and 1.25 mm for true positive and false negative results, respectively (P = 0.0236). Because of intra-operative TIC, 76.5% of the patients who needed further axillary lymph node dissection (ALND) could undergo this during the same operating time.

Conclusions : TIC is a rapid and reliable method for the intra-operative assessment of metastatic sentinel node involvement in patients with early-stage, clinically node-negative breast carcinoma. Despite a low sensitivity comparable to frozen section (FS) in detecting micro-and sub-micrometastases, the technique offers the advantage of full tissue preservation for subsequent histological analysis.     

Size of Residual Lymph Node Metastasis After Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients Is Prognostic

Background The prognostic significance of micrometastasis after neoadjuvant chemotherapy for locally advanced breast cancer is unknown. We examined the residual lymph node metastasis size in patients after treatment with neoadjuvant chemotherapy to determine the relevance of metastasis size on outcome. Methods Stage II/III breast cancer patients treated with neoadjuvant chemotherapy at our institution from 1991 to 2002 were included. We examined the relationship of postneoadjuvant chemotherapy lymph node metastasis size and number with distant disease-free survival (DDFS) and overall survival (OS). Results In 122 patients with a median follow-up of 5.4 years, we found not only that patients with an increasing number of residual positive nodes had progressively worse DDFS and OS (P < .0001 for both) compared with patients with negative nodes, but also that the size of the largest lymph node metastasis was associated with worse DDFS and OS (P < .0001 for both) in both univariate and multivariate analysis. Compared with negative nodes, even lymph node micrometastasis (<2 mm) was associated with worsened DDFS and OS (adjusted P = .02 and P = .005, respectively). Conclusions Residual micrometastatic disease in the axillary lymph nodes after neoadjuvant chemotherapy is predictive of worse prognosis than negative nodes. In this study, the lymph node metastasis size and the number of involved lymph nodes were independent powerful predictors of DDFS and OS.     

Axillary Dissection Versus No Axillary Dissection in Elderly Patients with Breast Cancer and No Palpable Axillary Nodes: Results After 15 Years of Follow-Up

Objective

To assess the long-term safety of no axillary clearance in elderly patients with breast cancer and nonpalpable axillary nodes.

Background

Lymph node evaluation in elderly patients with early breast cancer and clinically negative axillary nodes is controversial. Our randomized trial with 5-year follow-up showed no breast cancer mortality advantage for axillary clearance compared with observation in older patients with T1N0 disease.

Methods

We further investigated axillary treatment in a retrospective analysis of 671 consecutive patients, aged ≥70 years, with operable breast cancer and a clinically clear axilla, treated between 1987 and 1992; 172 received and 499 did not receive axillary dissection; 20 mg/day tamoxifen was prescribed for at least 2 years. We used multivariable analysis to take account of the lack of randomization.

Results

After median follow-up of 15 years (interquartile range 14–17 years) there was no significant difference in breast cancer mortality between the axillary and no axillary clearance groups. Crude cumulative 15-year incidence of axillary disease in the no axillary dissection group was low: 5.8% overall and 3.7% for pT1 patients.

Conclusions

Elderly patients with early breast cancer and clinically negative nodes did not benefit in terms of breast cancer mortality from immediate axillary dissection in this nonrandomized study. Sentinel node biopsy could also be foregone due to the very low cumulative incidence of axillary disease in this age group. Axillary dissection should be restricted to the small number of patients who later develop overt axillary disease.     

Can Breast MRI Predict Axillary Lymph Node Metastasis in Women Undergoing Neoadjuvant Chemotherapy

Background  

Axillary lymph node status provides important staging information. We sought to evaluate the predictive value of breast magnetic resonance imaging (MRI) in detecting axillary lymph node metastases prior to initiation of neoadjuvant chemotherapy (NAC) and in detecting residual lymph node metastases after NAC in women found to be node positive prior to NAC.     

Intraoperative Frozen Section Analysis of Sentinel Lymph Node in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Background Recently, many studies have demonstrated the feasibility and accuracy of sentinel lymph node (SLN) biopsy for patients treated with neoadjuvant chemotherapy (NAC). However, no studies have been conducted to evaluate the accuracy of frozen section (FS) analysis of SLN in NAC-treated patients. The aim was to evaluate the accuracy of intraoperative FS analysis of SLNs in breast cancer patients treated with NAC in comparison with that in those not treated. Methods Patients with primary breast cancer either treated with NAC (n = 62) or not treated (n = 301) were included in this study. Intraoperatively, the largest cut surface (2-mm thickness) of the SLN was subjected to FS analysis. Remainders of the SLN were formalin-fixed, serially sectioned at 2-mm thickness, and subjected to H&E staining and immunohistochemistry. The largest diameter of metastases in the SLN was measured. Results The sensitivity, specificity, and accuracy of FS analysis of SLNs were 74, 100, and 88%, respectively, for NAC-treated patients, similar to the corresponding values of 71, 99, and 90% for non-NAC-treated patients. The sensitivity of FS analysis for macrometastases was lower for NAC-treated patients (76%) than for non-NAC-treated patients (91%), while that for micrometastases and isolated tumor cells was higher for NAC-treated patients (67%) than for non-NAC-treated patients (31%). However, neither of these differences was statistically significant. Conclusions Intraoperative FS analysis of SLNs is as accurate for NAC-treated as for non-NAC-treated patients, indicating that FS analysis of SLNs is a clinically acceptable method for those receiving NAC.     

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy Is Accurate in Breast Cancer Patients with a Clinically Negative Axillary Nodal Status at Presentation

Background In breast cancer, neoadjuvant chemotherapy (NAC) is widely used in order to enable a conservative surgery. In patients treated with NAC, the use of sentinel lymph node (SLN) biopsy, which is a good predictor of the axillary nodal status in previously untreated patients, is still discussed. The aim of our study was to determine clinicopathological factors that may influence the accuracy of SLN biopsy after NAC. Methods Between March 2001 and December 2006, 129 patients with infiltrating breast carcinoma were studied prospectively. Preoperatively, all of them underwent NAC. At surgery, SLN biopsy followed by axillary lymph node (ALN) dissection was performed. Lymphatic mapping was done using the isotope method. Results The SLN identification rate was 93.8% (121/129). Fifty-six out of the 121 successfully mapped patients had positive ALN. Eight out of these 56 patients had tumor-free SLN (false-negative rate of 14.3%). The false-negative rate was correlated with larger tumor size (T1-T2 versus T3; P = 0.045) and positive clinical nodal status (N0 versus N1-N2; P = 0.003) before NAC. In particular, the false-negative rate was 0% (0/29) in N0 patients and 29.6% (8/27) in N1-N2 patients. Clinical and pathological responses to NAC did not influence the accuracy of SLN biopsy. Conclusion Our results show that clinical nodal status is the main clinicopathological factor influencing the false-negative rate of SLN biopsy after NAC for breast cancer. SLN biopsy after NAC can predict the ALN status with a high accuracy in patients who are clinically lymph node negative at presentation.     

The Role for Sentinel Lymph Node Dissection after Neoadjuvant Chemotherapy in Patients who Present with Node-Positive Breast Cancer

Background

Sentinel lymph node (SLN) dissection has been investigated after neoadjuvant chemotherapy and has shown mixed results. Our objective was to evaluate SLN dissection in node-positive patients and to determine whether postchemotherapy ultrasound could select patients for this technique.

Methods

Between 1994 and 2010, 150 patients with biopsy proven axillary metastasis underwent SLN dissection after chemotherapy and 121 underwent axillary lymph node dissection (ALND). Clinicopathologic characteristics were analyzed before and after chemotherapy. Statistical analyses included Fisher??s exact test for nodal response and multivariate logistic regression for factors associated with false-negative events.

Results

Median age was 52?years. Median tumor size at presentation was 2?cm. The SLN was identified in 93?% (139/150). In 111 patients in whom a SLN was identified and ALND performed, 15 patients had a false-negative SLN (20.8?%). In the 52 patients with normalized nodes on ultrasound, the false-negative rate decreased to 16.1?%. Multivariate analysis revealed smaller initial tumor size and fewer SLNs removed (<2) were associated with a false-negative SLN. There were 63 (42?%) patients with a pathologic complete response (pCR) in the nodes. Of those with normalized nodes on ultrasound, 38 (51?%) of 75 had a pCR. Only 25 (33?%) of 75 with persistent suspicious/malignant-appearing nodes had a pCR (p?=?0.047).

Conclusions

Approximately 42?% of patients have a pCR in the nodes after chemotherapy. Normalized morphology on ultrasound correlates with a higher pCR rate. SLN dissection in these patients is associated with a false-negative rate of 20.8?%. Removing fewer than two SLNs is associated with a higher false-negative rate.     

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.     

Relationship Between Breast and Axillary Pathologic Complete Response in Women Receiving Neoadjuvant Chemotherapy for Breast Cancer

Annals of Surgical Oncology - We aim to delineate the relationship between breast and axillary pathologic complete response (pCR) in patients receiving neoadjuvant chemotherapy for breast cancer....     

Role of Sentinel Lymphadenectomy Combined with Intraoperative Ultrasound in the Assessment of Locally Advanced Breast Cancer After Neoadjuvant Chemotherapy

Background Sentinel node (SN) biopsy for patients with locally advanced breast cancer after neoadjuvant chemotherapy results in a lower detection rate and higher false-negative rate. The aims of the study were to explore the role of SN biopsy in these patients in Taiwan and to assess the role of intraoperative ultrasound examination of the non-SN level. Methods We used a blue dye to identify the SNs in 127 patients with T3 locally advanced breast cancer initially treated with neoadjuvant chemotherapy. After SN biopsy, we used intraoperative ultrasound to explore the non-SN region for additional lymph nodes, followed by at least level II axillary dissection. All the SNs were evaluated histologically and immunohistochemically with anticytokeratin antibodies. All the non-SNs were examined by routine histology. Results SNs were identified in 116 (91.3%) of 127 procedures. SN metastases were found in 64 cases (55.2%). Subsequent axillary dissection revealed tumor involvement of non-SNs in 40 (62.5%) of 64 cases. SN biopsy results had a sensitivity of 92.8%, a specificity of 100%, and a false-negative rate of 9.6%. Furthermore, intraoperative ultrasound detected suspicious malignant nodes in the non-SN level in 39 out of 40 cases, and detected 5 cases with non-SN metastases that had false-negative SN mapping. This technique decreased the false-negative rate of SN mapping from 9.6% to only 1.39% for these cases. Conclusions SN biopsy results combined with intraoperative ultrasonography can accurately assess the non-SN status and help breast surgeons to decide whether subsequent axillary dissection is warranted after SN biopsy has been performed.     

Omission of Axillary Dissection after a Positive Sentinel Node Dissection may Influence Adjuvant Chemotherapy Indications in Operable Breast Cancer Patients

Background

This study was designed to evaluate how the omission of axillary dissection would have altered the indication for adjuvant chemotherapy (ACT) in patients with early breast cancer submitted to conservative surgery with one or two positive sentinel lymph nodes (SLNs).

Methods

We identified 321 women in our institutional database who fulfilled the characteristics. All underwent completion axillary lymph node dissection (AD). Each case was blindly reviewed by our breast team in two rounds, and the total number of positive lymph nodes was disclosed only in the second. At each round, the panel chose between: (1) recommend, (2) discuss, (3) do not recommend ACT. Changes between round 1 and 2 were studied by the marginal homogeneity test. Exploratory logistic regression analyses were performed to study predictors of non-SLN involvement and of changes in the indication for ACT.

Results

AD revealed non-SLNs metastases in 96 patients (30?%). Fifty-two patients (16?%) had their initial indication changed at round 2 (p?<?0.001). Most of the changes were toward ACT (83?%), and all except two occurred in patients with immunohistochemically defined luminal A and luminal B/HER2-negative tumors. In these two subgroups, a Ki67 above the median value (21?%) was the only independent predictor of no change in the indication to ACT at round 2.

Conclusions

Omission of AD in patients with one or two positive SLNs may change the indication to ACT in a significant proportion of patients with hormone receptor-positive/HER2-negative tumors. All implications should be taken into account before abandoning AD, including a possible biologically tailored surgical approach.     

Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Patients with Cytologically Proven Node-positive Breast Cancer at Diagnosis

Background

The performance of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NCT) was investigated in patients with locally advanced breast cancer (LABC).

Methods

After NCT of 178 patients with cytology-proven axillary/supraclavicular nodes metastasis at the time of diagnosis, SLNB using radioisotope was performed including completion node dissection between 2008 and 2011. The detection rate, sensitivity, false negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were analyzed.

Results

SLNB was successfully performed in 169 (94.9 %) patients. Tumor nonresponse and extensive residual nodal disease were found to be significantly associated with detection failure of sentinel nodes. Sensitivity, FNR, NPV, and accuracy of SLNB were 78.0, 22.0, 75.8, and 87.0 %, respectively, and a greater number of retrieved SLNs increased all four of these performance measures. Conversion to node-negative disease was achieved in 69 (40.8 %) patients: 24 % of patients with the luminal A subtype, 51.6 % of patients with the luminal B, 51.7 % of patients with the HER2-enriched, and 58.5 % of patients with the triple-negative breast cancer (TNBC) subtype. Luminal B, HER2-enriched, and TNBC subtypes showed comparable responses to NCT; however, the TNBC subtype had a significantly better FNR and accuracy.

Conclusions

SLNB was found to be technically feasible, but its routine use was not recommended for LABCs after NCT. However, acceptable performance was noted for locally advanced TNBCs, and thus SLNB might be safely considered in these selected patients.     

乳腺癌新辅助化疗后局部区域外科处理进展

目的探讨乳腺癌新辅助化疗后对局部区域的外科处理策略。方法对近年来有关乳腺癌新辅助化疗降期后保乳治疗、同侧乳房复发的相关因素、原发肿瘤病理退缩模式以及前哨淋巴结活检等局部区域的外科处理的相关文献进行综述。结果①新辅助化疗可使乳腺原发肿瘤降期,提高保乳手术的比率,但通过新辅助化疗降期后保乳手术患者可能存在较高的同侧乳腺肿瘤复发风险。目前比较趋于一致的影响新辅助化疗降期后保乳治疗的同侧乳腺肿瘤复发率的相关因素为残余肿瘤呈多中心模式、残余肿瘤直径〉2cm。新辅助化疗后原发肿瘤病理退缩模式及相关因素尚不明确。②新辅助化疗前、后前哨淋巴结活检（SLNB）均是可行的并获得指南与专家共识的认可,初始腋窝淋巴结阴性患者更能从新辅助化疗后SLNB中获益,初始腋窝淋巴结阳性患者新辅助化疗转阴性后行SLNB替代ALND的前景可期,但需要获得临床认可的成功率和假阴性率及与ALND相似的局部区域复发率及总生存率。结论无论乳腺癌新辅助化疗的临床和影像学疗效如何,外科处理仍然是目前降低局部区域复发风险的重要治疗手段。分子分型时代,我们可以依据乳腺癌初始分期及新辅助化疗的疗效对乳腺癌患者施行个体化的局部区域外科处理