Predicting Pathological Complete Response in Breast Cancer After Two Cycles of Neoadjuvant Chemotherapy by Tumor Reduction Rate: A Retrospective Case-Control Study / 한국유방암학회지

Purpose@#We aimed to identify effectiveness-associated indicators and evaluate the optimal tumor reduction rate (TRR) after two cycles of neoadjuvant chemotherapy (NAC) in patients with invasive breast cancer. @*Methods@#This retrospective case-control study included patients who underwent at least four cycles of NAC at the Department of Breast Surgery between February 2013 and February 2020. A regression nomogram model for predicting pathological responses was constructed based on potential indicators. @*Results@#A total of 784 patients were included, of whom 170 (21.68%) reported pathological complete response (pCR) after NAC and 614 (78.32%) had residual invasive tumors. The clinical T stage, clinical N stage, molecular subtype, and TRR were identified as independent predictors of pCR. Patients with a TRR > 35% were more likely to achieve pCR (odds ratio, 5.396; 95% confidence interval [CI], 3.299–8.825). The receiver operating characteristic (ROC) curve was plotted using the probability value, and the area under the ROC curve was 0.892 (95% CI, 0.863–0.922). @*Conclusion@#TRR > 35% is predictive of pCR after two cycles of NAC, and an early evaluation model using a nomogram based on five indicators, age, clinical T stage, clinical N stage, molecular subtype, and TRR, is applicable in patients with invasive breast cancer.

Discussion on the indications of internal mammary sentinel lymph node biopsy in breast cancer in the era of precision medicine / 中华肿瘤杂志

Objective@#To determine the clinical benefits of internal mammary sentinel lymph node biopsy (IM-SLNB) acquired by breast cancer patients with clinically positive axillary lymph node (ALN), and further optimize the IM-SLNB indications.@*Methods@#All primary breast cancer patients with clinically positive ALN from February 2014 to September 2017 were prospectively recruited in this study. IM-SLNB was performed under the guidance of the modified injection technique. The success rate and visualization rate of IM-SLNB, metastatic rate of internal mammary sentinel lymph node (IMSLN) and its related factors were analyzed, and the clinical benefits were accessed according to the current guidelines.@*Results@#Among 126 patients, all of 94 patients (74.6%) who showed internal mammary drainage successfully underwent IM-SLNB. The incidence of internal mammary artery bleeding and pleural lesion were 4.3%(4/94) and 9.6%(9/94), respectively. The metastatic rate of IMSLN was 38.3% (36/94), which was significantly associated with the number of positive ALN (P<0.001) and tumor size (P=0.024). The lymph node staging of 94 patients who underwent IM-SLNB was more accurate. Among them, 36 cases with positive IMSLN underwent internal mammary radiotherapy (IMRT), while the other 58 cases with negative IMSLN avoided radiotherapy.@*Conclusions@#IM-SLNB should be routinely performed in patients with positive ALN. IM-SLNB can provide more accurate staging and guide tailored IMRT to benefit more breast cancer patients.

Murine Model Study of a New Receptor-Targeted Tracer for Sentinel Lymph Node in Breast Cancer / 한국유방암학회지

PURPOSE: Sentinel lymph node biopsy (SLNB), a critical staging and treatment step, has replaced axillary lymph node (LN) dissection as the standard staging procedure for early stage breast cancer patients with clinically negative axillary LNs. Hence, using a murine sentinel lymph node (SLN) model, we investigated the localization effect of the new receptor-targeted tracer, indocyanine green (ICG)-rituximab, on breast cancer SLNB. METHODS: After establishing the murine SLN model, different doses of ICG-rituximab were subcutaneously injected into the hind insteps of BALB/c mice to determine the optimal dose and imaging time using continuous (> 3 hours) MDM-I fluorescence vasculature imaging. To explore the capacity of ICG-rituximab for sustained SLN localization with the optimal dose, MDM-I imaging was monitored at 6, 12, and 24 hours. RESULTS: The popliteal LN was defined as the SLN for hindlimb lymphatic drainage, the iliac LN as the secondary, and the para-aortic or renal LN as the tertiary LNs. The SLN initial imaging and optimal imaging times were shortened with increased ICG-rituximab doses, and the imaging rates of the secondary and tertiary LNs increased accordingly. The optimal ICG dose was 0.12 μg, and its optimal imaging time was 34 minutes. After 24 hours, the SLN imaging rate remained 100%, while those of the secondary and the tertiary LNs increased from 0% (6 hours) and 0% (6 hours) to 10% (12 hours) and 10% (12 hours) to 20% (24 hours) and 10% (24 hours), respectively. CONCLUSION: ICG-rituximab localized to the SLN without imaging from the secondary or tertiary LNs within 6 hours. The optimal ICG dose was 0.12 μg, and the optimal interval for SLN detection was 34 minutes to 6 hours post-injection. This novel receptor-targeted tracer is of great value to clinical research and application.

Target definition for internal mammary lymph node irradiation based on distribution of internal mammary sentinel lymph node developed on SPECT/CT fusion imaging / 中华放射医学与防护杂志

Objective To explore the target definition for internal mammary lymph nodes ( IMLNs) irradiation based on the distribution of internal mammary sentinel lymph nodes ( IM-SLNs ) developing on SPECT/CT fusion imaging. Methods A total of 709 breast cancer patients who underwent preoperative SPECT/CT fusion imaging examination in IM-SLN from 2014 to 2018 were selected. All of the selected patients were first diagnosed and did not receive neoadjuvant treatment before SPECT/CT examination. Finally, totally 97 patients with 136 positive imaging IM-SLNs were included in this study. The clinical target volumes ( CTVs) were delineated according to the consensus guidelines from RTOG and DBCG and defined as CTVRTOG and CTVDBCG , respectively. The positional relationship of CTVRTOG , CTVDBCG and IM-SLNs were determined. Results The number of IM-SLNs from the first to fifth intercostal spaces were 55, 40, 33, 6 and 1, respectively. And the number of IM-SLNs in the first three intercostal spaces accounted for 94. 85％ of the total. The average distance from the edge of CTVRTOG to the centre points and the edges of IM-SLNs were 4. 10 mm ( 95％CI 3. 54-4. 65 mm) and 6. 40 mm ( 95％CI 5. 81-6. 98 mm), respectively (t=-30. 486,P<0. 05). For the CTVDBCG, the average distance was 1. 60 mm ( 95％CI 1. 16-2. 05 mm) and 3. 34 mm ( 95％CI 2. 78-3. 89 mm) , respectively ( t=-16. 364,P<0. 05) . The average distances from the edge of CTV to the centre points and the edge of IM-SLNs for CTVRTOG were all significantly greater than those for CTVDBCG(t=16. 640, 19. 815, P<0. 05). The rate of covering IM-SLN center points for CTVRTOG and CTVDBCG were 18. 4％ and 60. 3％, respectively. In order to cover 90％or 100％ of the IM-SLN center points, the edge of CTVRTOG should be expanded by 8 or 15 mm, respectively, and the edge of CTVDBCG should be expanded by 5 or 13 mm, respectively. If the diameter of IM-SLN was assumed as 5 mm, the edge of CTVRTOG needed an expansion of 11 or 17 mm to contain 90％or 100％ of IM-SLNs, respectively, while the edge of CTVDBCG needed 7 or 16 mm to cover 90％ or 100％of IM-SLNs, respectively. Conclusions It is reasonable to include the first three intercostal spaces IMLNs for prophylactic irradiation based on the distribution of IM-SLNs. However, CTVs based on the two guidelines are both insufficient to cover 90％ of IM-SLNs.

Internal Mammary Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer / 한국유방암학회지

PURPOSE: The definition of nodal pathologic complete response (pCR) after a neoadjuvant chemotherapy (NAC) just included the evaluation of axillary lymph node (ALN) without internal mammary lymph node. This study aimed to evaluate the feasibility of internal mammary-sentinel lymph node biopsy (IM-SLNB) in patients with breast cancer who underwent NAC. METHODS: From November 2011 to 2017, 179 patients with primary breast cancer who underwent operation after NAC were included in this study. All patients received radiotracer injection with modified injection technology. IM-SLNB would be performed on patients with internal mammary sentinel lymph node (IMSLN) visualization. RESULTS: Among the 158 patients with cN+ disease, the rate of nodal pCR was 36.1% (57/158). Among the 179 patients, the visualization rate of IMSLN was 31.8% (57/179) and was 12.3% (7/57) and 87.7% (50/57) among those with cN0 and cN+ disease, respectively. Furthermore, the detection rate of IMSLN was 31.3% (56/179). The success rate of IM-SLNB was 98.2% (56/57). The IMSLN metastasis rate was 7.1% (4/56), and all of them were accompanied by ALN metastasis. The number of positive ALNs in patients with IMSLN metastasis was 3, 6, 8, and 9. The pathology nodal stage had been changed from pN1/pN2 to pN3b. The pathology stage had been changed from IIA/IIIA to IIIC. CONCLUSION: Patients with visualization of IMSLN should perform IM-SLNB after NAC, especially for patients with cN+ disease, in order to complete lymph nodal staging. IM-SLNB could further improve the definition of nodal pCR and guide the internal mammary node irradiation.

Molecular subtypes and axillary downstaging surgery after neoadjuvant chemothera-py for breast cancer / 中国肿瘤临床

Objective:To determine the optimal time to perform sentinel lymph node biopsy(SLNB)in patients with clinically node-negative disease and assess clinically node-positive patients who would acquire greater benefits from axillary downstaging surgery af-ter neoadjuvant chemotherapy(NAC).Methods:From October 2010 to November 2017,206 patients with breast cancer who under-went surgery after NAC were included in this retrospective study in Shandong Cancer Hospital Breast Cancer Center.Their clinicopatho-logic data were collected to discuss the correlation between axillary node pathologic complete response(apCR)and different molecu-lar subtypes.Results:Among 206 patients who received NAC,183 patients had clinically node-positive disease.The frequency of apCR after NAC was 33.3%(61/183),which was significantly higher in patients with human epidermal growth factor receptor 2(HER-2)-posi-tive subtype[with targeted therapy,62.1%(18/29);without targeted therapy,34.5%(10/29)]and triple-negative breast cancer(TNBC) (41.0%)(16/39)than in patients with HER-2-negative luminal subtype breast cancer[19.8%(17/86)](P<0.001). Among 23 patients with Cn0 tumors,the rate of positive sentinel lymph nodes after NAC was 26.1%(6/23);this rate was 36.4%(4/11),25.0%(1/4),and 12.5% (1/8)among patients with HER-2-negative luminal subtype breast cancer,TNBC,and HER-2-positive subtype breast cancer,respective-ly.Conclusions:Molecular subtypes could predict the chance of achieving apCR.For patients with clinically node-negative disease,it would be preferable to perform SLNB prior to NAC for patients with HER-2-negative luminal subtype breast cancer.SLNB after NAC for those with TNBC and HER-2-positive subtype breast cancer could decrease the chances of axillary lymph node dissection.For patients with initial clinically node-positive disease converting to clinically node-negative disease after NAC,especially in TNBC and HER-2-posi-tive subtype breast cancer,these patients might benefit more from axillary downstaging surgery after NAC.

A nomogram for the intraoperative prediction of non-sentinel lymph node metastasis in breast cancer patients / 中国癌症杂志

Background and purpose: When patients have positive sentinel lymph node (SLN), axillary lymph node dissection (ALND) is usually performed, but most of them have no metastasis in the non-sentinel lymph node (nSLN). It is of great significance to predict metastasis of nSLN precisely. The aim of the study was to establish a nomogram for the intraoperative prediction of nSLN metastasis in breast cancer patients using one-step nucleic acid amplification (OSNA) techniques and to direct the subsequent therapy for breast cancer effectively. Methods: Of 552 breast cancer patients who underwent SLN biopsy in the 2010 OSNA clinical trial, 103 with SLN metastasis treated with ALND were assessed to establish a nomogram for intraoperative prediction of nSLN based on the molecular diagnosis. A validation cohort of 61 patients who met the similar criteria in the 2015 OSNA clinical trial subsequently validated it. Results: Primary tumor size, total tumor load, the number of positive SLNs and negative SLNs were associated with the presence of nSLN metastasis based on the multivariable logistic regression results, and a nomogram was established with these variables. Its area under the ROC curve was 0.814 for the predictive model and it was 0.842 in the re-validation cohort. The tumor size assessed by the postoperative histological examination was replaced by the size evaluated by the imaging examination, and the area under the ROC curve was 0.838. There was no statistically significant difference in the accuracy compared with the former validation data (P=0.7406). Conclusion: The predictive nomogram based on the molecular diagnosis can predict the nSLN metastases intra/post-operatively. It appears to be obviously superior to other predictive models and may help to guide the axillary management and to make decisions about radiation target region.

Validation study of the modified injection technique for internal mammary sentinel lymph node biopsy in breast cancer / 中华内分泌外科杂志

Objective To verify the accuracy of the modified technique for internal mammary sentinel lymph node biopsy ( IM-SLNB) in breast cancer .Methods In the validation study , the radiotracer was injected with the modified technique , and fluorescence tracer was injected into the peritumoral breast tissue .The radioac-tive IM-SLN was identified by preoperative lymphoscintigraphy and γprobe.The radioactive IM-SLN received bi-opsy during operation .The status of the fluorescence tracer was identified by the fluorescence imaging system . Results A total of 162 patients were enrolled from Sep .2013 to Dec.2014.IM-SLNB was performed in 110 pa-tients.The radiotracer and the fluorescence tracer were identified in the same IM-SLN in 94 cases, and the con-cordance rate was 85.5%(Case-base, Spearman coefficient correlation 0.823, P<0.001).Conclusion Dif-ferent tracers injected into the different sites of the intra-parenchyma can reach the same IM-SLN, proving the ac-curacy of the modified technique and the hypothesis of IM-SLN lymphatic drainage pattern ( IM-SLN receives not only the lymphatic drainage from the primary tumor area but the entire breast parenchyma ) .

Internal mammary sentinel lymph node biopsy in breast cancer pa-tients with clinically positive axillary lymph nodes / 中国肿瘤临床

Objective:This study was conducted to evaluate the roles of internal mammary sentinel lymph node biopsy (IM-SL-NB) in the treatment of breast cancer patients with clinically positive axillary lymph nodes. Methods:This study is a one-armed clini-cal research conducted from June 2013 to October 2014. A total of 64 breast cancer patients from Shandong Cancer Hospital with clini-cally positive axillary lymph nodes were enrolled in the study. All patients underwent axillary lymph node dissection. Meanwhile, IM-SLNB was performed in all patients using the new injection method of radiotracer. Results:Among the 64 enrolled patients, the visual-ization rate of internal mammary lymph node was 59.4%(38/64). For the 38 patients who were subjected to visualization of the internal mammary node, the detection rate was 100%(38/38), and the incidence of complications was 7.9%(3/38). The metastasis rate of inter-nal mammary lymph node was 21.1%(8/38). Patients with upper inner quadrant tumors and metastasis of more axillary lymph nodes had a significantly higher chance of developing sentinel lymph node metastasis (P<0.001 and P=0.017, respectively) than the other pa-tients. The clinical benefit rate of the above mentioned treatment was 59.4%. Among the patients, 12.5%(8/64) received extra internal mammary radiotherapy, whereas 46.9%(30/64) patients avoided the unnecessary internal mammary radiotherapy. Conclusion:IM-SL-NB should be performed in breast cancer patients with clinically positive axillary lymph nodes because IM-SLNB could provide the ac-curate indication of radiation to the internal mammary area, especially for the patients with upper inner quadrant tumors and those with a suspiciously high level of axillary lymph node metastasis.

A retrospective study of axillary and internal mammary sentinel lymph node biopsy in breast cancer patients after neoadjuvant chemotherapy / 中国癌症杂志

Background and purpose:Whether axillary sentinel lymph node biopsy (ASLNB) could replace axillary lymph node dissection (ALND) in patients who converted after neoadjuvant chemotherapy (NAC) from cN+ to ycN0 is still contentious, and the previous study only evaluated the pathological status of ALN without internal mammary lymph node (IMLN) condition. This study is to evaluate roles of ASLNB and internal mammary sentinel lymph node biopsy (IM-SLNB) in breast cancer patients after NAC.Methods:From Jan. 2012 to Dec. 2014, 60 breast cancer cT1-4N0-3M0patients who were scheduled for neoadjuvant chemotherapy (NAC) and agreed to accept surgery after NAC from our department were enrolled into the retrospective study. Patients with cN0 before NAC and ycN0 after NAC underwent ASLNB (group A). Patients with cN+ received NAC and ycN0 after NAC (group B) were treated with ASLNB and ALND. Only patients whose clinical nodal status remained positive (ycN+) after NAC underwent ALND without ASLNB (group C). All the patients received radiotracer injection and patients in group A and group B received blue dye injection additionally. Meanwhile, IM-SLNB would be performed for all patients with IM-SLN visualization.Results:The number of patients enrolled in group A, group B and group C was 6, 45 and 9 cases respectively. The accuracy rate of ASLNB in group A was 100% (6/6). Only one patient was axillary sentinel lymph node (ASLN) positive performed ALND. With combination of blue dye and radiolabeled colloid, the accuracy rate of ASLNB in group B was 100% (48/48) and the false negative rate (FNR) was 17.9% (5/28). The FNR in patients with 1, 2 and>2 SLNs examined was 27.3% (3/11), 20.0% (2/10) and 0% (0/7). All of the ALNs were positive in group C. The visualization rate of IM-SLN was 63.3% (38/60). The detection rate of IM-SLNB was 97.4% (37/38) and the metastasis rate was 8.1% (3/37). The incidence of complications was 5.3% (2/38).Conclusion:ASLNB can be performed either before or after preoperative chemotherapy for patients with cN0 disease. Among women with cN+ converted to ycN0 who had 3 or more SLNs examined, the FNR could return to be less than 10%. Those patients whose nodes are still ycN+ should perform ALND. IM-SLNB should be performed routinely in all breast cancer patients after NAC, for it might help to make clear of the nodal staging and the pathological status of IM-SLN and provide the accurate indication of radiation to the internal mammary area in case of under-stage and under-/over-treatment, expecting to develop the deifnition of pathological complete response (pCR).

Effects of different preparation methods and injection sites of 99Tcm-sulfur colloid on sentinel lymph node detection in breast cancer / 中华核医学与分子影像杂志

Objective To prospectively investigate the optimal setting for sentinel lymph node biopsy (SLNB) in patients with breast cancer by comparing the effects of different preparation methods and injection sites of 99Tcm-SC in sentinel lymph node (SLN) mapping and detection.Methods Two batches of 99Tcm-SC were prepared by boiling for 3 min (radiotracer 1) and 5 min (radiotracer 2),respectively.Radioactive chemical purity (RCP) and size of colloid particles were measured at 10 min,1 h,2 h and 4 h after the preparation.One hundred and forty-seven patients with breast cancer were involved and randomly divided into 3 groups.Group A consisted of 40 patients with periareolar injection of radiotracer 1,group B of 40 patients with periareolar injection of radiotracer 2,and group C of 67 patients with peritumoral injection of radiotracer 2.Lymphatic mapping was performed for all patients using SPECT/CT preoperatively and blue dye was subdermally injected over the tumor.The detection rate of the axillary and internal mammary SLN was recorded.One-way analysis of variance,independent two-sample t and x2 tests were used to analyze the data.Results There was no significant difference of RCP between the two radiotracers at 10 min,1 h,2 h and 4 h after preparation (t =-0.267,-0.794,0.826 and-0.977,all P＞0.05).Compared with radiotracer 1,the percentage of particles smaller than 100 nm in radiotracer 2 reduced significantly ((73.72±2.36) ％ vs (65.25±3.56)％,t=6.436,P＜0.05) and the mean effective particle size was significantly larger ((45.27±6.42) nm vs (75.59t7.04) nm,t=7.315,P＜0.05).In groups A,B and C,the detection rate of the internal mammary SLN was 70.0％ (28/40),47.5％ (19/40) and 17.9％ (12/67),respectively,with significant difference (x2=29.525,P＜0.05).In groups A,B and C,the detection rate of the axillary SLN was 100％ (40/40),95.0％ (38/40) and 97.0％ (65/67),respectively,without significant difference (x2 =2.686,P＞ 0.05).Conclusion For SLNB of patients with breast cancer,the axillary and internal mammary SLN could be better detected by SPECT/CT lymphatic mapping using radiotracer prepared with a shorter boiling time,via periareolar injection,and combined with subdermal injection of blue dye.

Risk factors for sentinel lymph node metastasis and validation study of the MSKCC nomogram in breast cancer patients / 中华内分泌外科杂志

ObjectiveTo evaluate the risk factors for sentinel lymph node(SLN)metastasis,and assess the value of the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting SLN metastasis in breast cancer patients.Methods A sentinel lymph node biopsy(SLNB) database containing 1227 consecutive breast cancer patients(412 patients with a positive SLN)was retrospectively analyzed.The value of MSKCC nomogram was predicted by drawing the trend line and calculating the area under the curve(AUC) of receiver-operator characteristic(ROC). Meanwhile,the risk factors of SLN metastasis were evaluated. Results Tumor size,tumor location,histological grade,lymphovascular invasion,mulifocality,ER and PR status were correlated with SLN metastasis( all P ＜ 0.05 ).All the above factors but tumor location were significant independent predictors for SLN metastasis(all P ＜ 0.01 ).The MSKCC nomogram presented AUC value of 0.730 for ROC.Patients with predictive values lower than 16％ had the frequency of 0.9％ for SLN metastasis while patients with predictive values higher than 70％ had the frequency of 96.2％.ConclusionsThe risk factors of SLN metastasis in our study are consistent with those in MSKCC nomogram.MSKCC nomogram is a useful tool in predicting the probability of SLN metastasis for breast cancer patients.Axillary surgery can be avoided in patients with the predictive values lower than 16％,axillary lymph node dissection could be done in patients with the predictive values higher than 70％,and other patients should still undergo SLNB.

Research progress of internal mammary lymph node in breast cancer / 肿瘤研究与临床

The metastases status of internal mammary lymph node(IMLN) is an independent prognostic factor for breast cancer and it also is an important reference for neoplasm staging.The patients with IMLN metastases consistently have worse outcomes.The overall risk of IMLN metastases is 18 ％-33 ％.Metastases exclusively situated in the IMLN,without concurrent axillary metastases,occur in 2 ％-11％ of patients.Factors related to IMLN metastases include the status of axillary node,the age of patients,the localization and characteristics of primary tumor.Recently,with the development of sentinel lymph node biopsy(SLNB), internal mammary-SLNB may access the status of IMLN with a minimal risk. Internal mammary-SLNB procedure can improve the system for nodal staging of breast cancer,and it will contribute to the individualized treatment for breast cancer patients.