Internal Mammary Sentinel Lymph Node Research Articles

Development and validation of a nomogram for predicting internal mammary sentinel node metastasis in breast cancer patients

ObjectiveInternal mammary nodes are important in breast cancer prognosis, but their diagnosis is often missed in clinical practice, leading to inaccurate staging and treatment. We developed a validated nomogram to predict the presence of internal mammary sentinel nodes (IMSN) metastasis. MethodsA total of 864 sequential IMSN biopsy procedures from a prospective studies database of 1505 cases were used for model development and validation. Multivariable logistic regression was performed on 519 sequential IMSN biopsy procedures from multi-center data between August 2018 and July 2022 to predict the presence of IMSN metastasis. A nomogram was developed based on the logistic regression model and subsequently applied to 345 sequential IMSN biopsy procedures from single-center data between November 2011 and July 2018. The model's discrimination was assessed using the area under the receiver operating characteristic curve. ResultsThe overall frequency of IMSN metastasis was 17.0% in our study. A predictive model for IMSN metastasis was constructed using tumor size, tumor location, lymphovascular invasion, the number of positive axillary nodes (P < 0.05 for all variables in multivariate analysis), and histological grade (P < 0.05 only in univariate analysis). The nomogram was accurate, with a concordance index of 0.84 in the bootstrapping analysis and an area under the receiver operating characteristic curve of 0.80 in the validation population. ConclusionOur nomogram provides an accurate and validated multivariable predictive model for estimating the individual likelihood of having IMSN metastasis. This may be useful for personalized treatment decisions regarding internal mammary radiotherapy in breast cancer patients.

Abstract P2-14-06: Prospective, multicenter, clinical validation study of the repeatability and accuracy of internal mammary sentinel lymph node biopsy with modified injection technique (CBCSG026/CBCSG027)

Abstract Background: As a first-echelon nodal drainage site of breast cancer, the status of axillary lymph nodes (ALN) and internal mammary lymph nodes (IMLN) is both valuable for regional staging and treatment choice. The internal mammary sentinel lymph node biopsy (IM-SLNB) may provide minimally invasive staging, and guide individual IMLN radiation. Modified technique (periareolar intraparenchymal, high volume and ultrasound guidance) got a high internal mammary sentinel lymph nodes (IM-SLN) visualization rate of 71.1% in single center, and the prospective multicenter study was designed to verify its repeatability (CBCSG026, NCT03541278). High visualization rate and low false negative rate are prerequisites for the widespread of IM-SLNB. The question arises as to whether IM-SLN detected with the modified technique should be considered as “true” IM-SLN. The prospective, multicenter, clinical validation study of IM-SLNB followed by internal mammary lymph node dissection (IM-LND) was designed to verify the accuracy of IM-SLNB in patients with ALN positive breast cancer (CBCSG027, NCT03024463). Methods: While CBCSG026 trial enrolled patients with both axillary negative and positive breast cancer, CBCSG027 trial only enrolled axillary positive patients receiving mastectomy (either biopsy proving cN+ disease or cN0 with positive axillary SLN). The 1st to 3rd intercostal IM-LND was performed immediately after IM-SLNB to verify its accuracy in the CBCSG027 trial. Result: From May 2018 to June 2022, 600 and 264 patients were enrolled in the CBCSG026 and CBCSG027 trial from seven centers in China, respectively. Among the 600 recruited patients in the CBCSG026, the IM-SLN visualization rate was 65.0% (390/600), which was significantly related to patient’s age, body mass index, radiotracer intensity and interval time between injection and IM-SLN identification (all P&amp;lt; 0.05). The IM-SLNB successful rate was 97.4% (380/390), and the complication was 6.9%. The median number of IM-SLN was 1. The overall IM-SLN metastases rate was 18.9% (72/380), with 33.0% (65/195) and 3.8% (7/185) in ALN positive and negative patients, respectively. Multivariate analysis showed that the tumor size (P=0.028), the tumor location (P&amp;lt; 0.001) and the number of positive ALNs (P&amp;lt; 0.001) were independent predictors of IM-SLN metastasis. Those variables were included in a novel nomogram (Table 1), which was significantly better than the probability based on the number of metastatic ALNs alone according to the current guidelines (area under the curve: 0.860 vs. 0.804, P&amp;lt; 0.001). Of the 264 patients enrolled in the CBCSG027 trial, 185 patients (70.1%) had IM-SLN visualization (included 107 with cN+ disease and 78 with positive axillary SLN). The median number of IM-SLN and IM-nSLN was 2 (1~4) and 3 (1~9), respectively. The positive rate of IMLN and IM-SLN was 37.8% (70/185) and 36.8% (68/185), respectively, yielding the false negative rate of IM-SLNB 2.9% (2/70), the accuracy of 98.9% (183/185) and the sensitivity of 97.1% (68/70). The false negative rate of patients with cN+ disease and patients with positive axillary SLN was 4.8% (2/42) and 0, respectively. The positive IM-SLNs were the only positive IMLNs identified in 51.4% (36/70) patients. IM-SLNB can change the pN stages of 37.2% (68/183) patients. IMLN irradiation could be avoided in 72.7% (80/110) patients with axillary pN1 and 46.7% (35/75) with pN2/N3 disease in the study. Conclusions: The modified technique of radiotracer injection (periareolar intraparenchymal, high volume, and ultrasound guidance) can significantly improve the detection rate of IM-SLN with very low false-negative rate with the prospective, multicenter validation results, providing minimally invasive staging and guiding individual IMLN radiation. When there is no IM-SLN visualization, the nomogram can predict the risk of IMLN metastasis and guide IMLN radiation. The nomogram which can predict the risk of IMLN metastasis The nomogram which can predict the risk of IMLN metastasis Citation Format: Yong-Sheng Wang, Qing Lu, Shi-Guang Zhu, Wen-He Zhao, Guang-Lun Yang, Yuan-Xi Huang, Hong Zhong, Xiao Sun, Pengfei Qiu. Prospective, multicenter, clinical validation study of the repeatability and accuracy of internal mammary sentinel lymph node biopsy with modified injection technique (CBCSG026/CBCSG027) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-06.

99mTc-rituximab tracer injection for guiding internal mammary sentinel lymph nodes biopsy in primary breast cancer: A prospective observational study.

To explore the use of 99mTc-rituximab tracer injection for internal mammary sentinel lymph node (IM-SLN) detection in patients with primary breast cancer. This prospective observational study enrolled female patients with primary breast cancer between September 2017 and June 2022 at Fujian Provincial Hospital. The participants were divided into the peritumoral group (two subcutaneous injection points on the surface of the tumor), two-site group (injections into the glands at 6 and 12 o'clock around the areola area), and four-site group (injections into the gland at 3, 6, 9, and 12 o'clock around the areola area). The outcomes were the detection rates of the IM-SLNs and axillary sentinel lymph nodes (A-SLNs). Finally, 133 patients were enrolled, including 53 in the peritumoral group, 60 in the two-site group, and 20 in the four-site group. The detection rate of the IM-SLNs in the peritumoral group (9.4% [5/53]) was significantly lower than in the two-site (61.7% [37/60], P<0.001) and four-site (50.0% [10/20], P<0.001) groups. The detection rates of A-SLNs among the three groups were comparable (P=0.436). The two-site or four-site intra-gland injection of 99mTc-rituximab tracer might achieve a higher detection rate of IM-SLNs and a comparable detection rate of A-SLNs compared with the peritumoral method. The location of the primary focus has no impact on the detection rate of the IM-SLNs.

A Clinical-Radiomics Model of Preoperative Prediction IMN Status of Breast Cancer Patients

<h3>Purpose/Objective(s)</h3> To establish a prediction model based on clinicopathological factors and dynamic contrast enhanced (DCE)-MRI radiomics features, and to make a non-invasive prediction of IMN metastasis risk before operation. <h3>Materials/Methods</h3> The DCE-MR images and clinicopathological data of 124 breast cancer patients who had undergone internal mammary sentinel lymph node biopsy and / or internal mammary lymph node (IMN)dissection with IMN negative on preoperative images from January 2013 to December 2019 were obtained. All patients received plain breast scan and dynamic contrast-enhanced MR in Shandong Cancer Hospital before operation. In this study, three types of predictive models were established, which are based on clinicopathological risk factors, DCE-MRI imaging features and the combination of the two: 1) Clinical model: a logistic regression model based on clinicopathological factors was developed to predict ALN status. 2) Radiomics model: radiomics model based on radiomics score (RS) score is developed. 3) Clinical-radiomics model: combining the imaging features with the independent risk factors for independent prediction of IMN status, the multiple logistic regression method was used to establish a nomogram for predicting the risk of IMN metastasis. All models were evaluated by ROC and AUC, and clinical decision analysis curves was used to evaluate the clinical application value of the model. <h3>Results</h3> Three variables including primary tumor location, PR status and axillary lymph node metastasis status were included in the clinical model, and the AUC was 0.913. 150 imaging features were extracted from DCE-MRI images of primary tumors. Finally, 4 imaging features were selected to participate in the development of RS. Finally, the AUC of the imaging model combined with DCE-MRI imaging features of IMN was 0.831. The clinical-radiomics model with an AUC of 0.964. Delong test showed that, there was no significant difference in ROC curve between clinical model and radiomics model (p=0.1337) , but there were significant differences in ROC curve between clinical model and clinical-radiomics model, and between clinical model and clinical-radiomics model (p<0.05). DCA curve analysis shows that the application of clinical-radiomics model has the greatest net benefit, optimal predictive efficiency and better distinguishing ability, which is better than clinical model and radiomics model. <h3>Conclusion</h3> Clinical-radiomics model is helpful to evaluate the IMN metastasis status of breast cancer patients before operation.

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%.

Risk assessment of internal mammary lymph node metastasis and choice of irradiation of internal mammary lymphatic drainage area in breast cancer patients with negative internal breast lymph nodes on imaging

Objective: To explore the independent risk factors of internal mammary lymph nodes (IMN) metastasis and the risk assessment method of IMN metastasis preoperatively in breast cancer patients with negative IMN in imaging examination, and guide the radiotherapy of IMN in patients with different risk stratification of IMN metastasis. Methods: The clinical and pathological data of 301 breast cancer patients who underwent internal mammary sentinel node biopsy(IM-SLNB) and/or IMN dissection in Shandong Cancer Hospital with negative IMN on CT and/or MRI from January 2010 to October 2019 were analyzed retrospectively. The independent risk factors were analyzed by univariate and multivariate logistic regression, and the independent risk factors of IMN metastasis were used to risk stratification. Results: Among the 301 patients, 43 patients had IMN metastasis, and the rate of IMN metastasis was 14.3%. Univariate analysis showed that vascular tumor thrombus, progesterone receptor (PR) expression, T stage and N stage were associated with IMN metastasis. Multivariate logistic regression analysis showed that tumor located in medial quadrant, positive PR and axillary lymph node metastasis were independent risk factors for IMN metastasis. The risk of IMN metastasis was assessed according to the independent risk factors of the patients: low-risk group is including 0 risk factor, medium-risk group is including 1 risk factor, and high-risk group is including 2-3 risk factors. According to this evaluation criteria, 301 patients with breast cancer were divided into low-risk group (with 0 risk factors), medium-risk group (with 1 risk factor) and high-risk group (with 2-3 risk factors). The IMN metastasis rates were 0 (0/34), 4.3% (6/140) and 29.1% (37/127), respectively. Conclusions: The risk stratification of IMN metastasis according to three independent risk factors of IMN metastasis including tumor located in medial quadrant, positive PR and axillary lymph node metastasis in breast cancer patients can guide the radiotherapy of IMN in newly diagnosed breast cancer patients. For N1 patients, radiotherapy of IMN is strongly recommended when the primary tumor is located in the medial quadrant and/or PR positive.

Atlas of sentinel lymph nodes in early breast cancer using single-photon emission computed tomography: implication for lymphatic contouring.

PurposeTo determine the localization of sentinel lymph nodes (SLNs) in a large cohort of patients with breast cancer and validate the European Society for Therapeutic Radiology and Oncology (ESTRO), Radiation Therapy Oncology Group (RTOG), and Radiotherapy Comparative Effectiveness (RADCOMP) guidelines on regional lymph node clinical target volume (CTV-LN) delineation.Materials and MethodsA total of 254 women with cT1-3N0-1M0 breast cancer underwent single-photon emission computed tomography (SPECT-CT) visualization of SLNs after intra- and peritumoral injection of 99mTc-radiocolloids. All SPECT-CT images were fused with reference simulation computed tomography. A 3D atlas of SLNs was created and used for evaluation of CTV-LN defined by contouring guidelines.ResultsSPECT-CT visualized 532 SLNs that were localized in axillary level I in 67.5%, level II in 15.4%, level III in 7.3%, internal mammary in 8.5%, and supraclavicular in 1.3% cases. The majority of level II–IV and internal mammary SLNs were inside the recommended CTV-LN. Axillary level I SLNs were covered by ESTRO and RTOG contours in 85% and 85% cases, respectively. “Out of contours” SLNs were mostly detected in lateral subgroup of level I LN (18.5%), while 98%–99% of anterior pectoral and central axillary SLNs were covered by CTV-LN. Internal mammary SLNs were visualized in 33 cases and were outside ESTRO and RTOG contours in 3 and 6 observations, respectively.ConclusionSPECT-CT atlas of SLNs demonstrated that in most cases ESTRO and RTOG guidelines correctly represented CTV-LNs with the exception of lateral subgroup of SLNs.

Abstract P1-20-14: Prospective, multicenter, clinical validation study of internal mammary sentinel lymph node biopsy followed by internal mammary lymph node dissection with the modified injection technique (CBCSG026/27)

Abstract Purpose: As a first-echelon nodal drainage site of breast cancer, the status of axillary lymph nodes (ALN) and internal mammary lymph nodes (IMLN) is valuable both for regional staging and treatment choice. The internal mammary sentinel lymph node biopsy (IM-SLNB) might provide minimally invasive staging and guide individual IMLN radiation and systemic therapy. In our earlier study, we have tried injecting radiotracer with a modified technique (periareolar intraparenchymal, high volume and ultrasound guidance), and got a high IMSLN visualization rate at 71.1%, which laid a technical feasibility for the further study and clinical application of IM-SLNB. A prospective multicenter study was designed to verify the repeatability of this high IMSLN visualization rate with the modified injection technique (CBCSG026, NCT03541278). High visualization rate and low false negative rate are prerequisites for the widespread of IM-SLNB. The question arises as to whether IMSLN detected with the modified technique should be considered as “true” IMSLN. The prospective, multicenter, clinical validation study of IM-SLNB followed by internal mammary lymph node dissection (IM-LND) was designed to verify the accuracy of IM-SLNB in patients with ALN positive breast cancer (CBCSG027, NCT03024463). Methods and Materials: CBCSG026 trial enrolled patients with both axillary negative and positive breast cancer. It was assumed that the visualization rate of IMSLN was 65% and the success rate of IM-SLNB was 90%. At the 5% significance level, a minimum of 350 patients were required to reach a power of 95% (two-sided test). CBCSG027 trial only enrolled axillary positive (cN+ with biopsy proving or cN0 with positive axillary SLN) breast cancer patients receiving mastectomy. IM-LND of the 1st to 3rd intercostal was performed immediately after IM-SLNB to verify its accuracy. At the 5% significance level and a power of 95% (two-sided test), at least 40 patients with positive IMLN were required (110~140 patients with the visualization of IM-SLN were scheduled for the enrollment.) Results: Seven centers in China enrolled more than three quarters patients before April 30, with 286/350 (81.7%) in CBCSG026 and 34/40 (85.0%) in CBCSG027. The overall IMSLN visualization rate is 68.2% (195/286) with a success rate of IM-SLNB of 94.9% (185/195). The overall IMLN positive rate is 42.0% (34/81) wih a false negative rate of 2.9% (1/34). Conclusion: Modified technique of radiotracer injection (periareolar intraparenchymal, high volume, and ultrasound guidance) could significantly improve the detection rate of IMSLN with very low false negative rate with the prospective, multicenter validation results, providing minimally invasive staging and guiding individual IMLN radiation and systemic therapy. Citation Format: Yongsheng Wang, Qing Lu, Shiguang Zhu, Wenhe Zhao, Guanglun Yang, Yuanxi Huang, Jiong Wu, Yanbin Liu, Xiao Sun, Pengfei Qiu. Prospective, multicenter, clinical validation study of internal mammary sentinel lymph node biopsy followed by internal mammary lymph node dissection with the modified injection technique (CBCSG026/27) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-14.

Definition of Internal Mammary Node Target Volume Based on the Position of the Internal Mammary Sentinel Lymph Nodes Presented on SPECT/CT Fusion Images.

Purpose: Mapping the distribution of internal mammary sentinel lymph nodes (IM-SLNs) presented on single photon emission computed tomography in conjunction with computed tomography (SPECT/CT) images to explore the value of IM-SLN to guide tailored clinical target volume (CTV) delineation of postoperative prophylactic IMNI.Materials and methods: Ninety-seven patients who underwent preoperative lymphoscintigraphy by SPECT/CT and had imaging of IM-SLN were selected in this study. The imaging IM-SLNs on SPECT/CT of eligible patients were projected onto corresponding anatomical positions of a representative axial CT image. The IMN CTVs were delineated on the representative axial CT images according to the Radiation Therapy Oncology Group (RTOG) and Danish Breast Cancer Cooperative Group (DBCG) guideline, and defined as CTVRTOG and CTVDBCG. The location of the IM-SLNs was compared with the RTOG and DBCG guidelines of IMN target volume delineations, respectively. The intercostal space distribution of IM-SLNs was recorded. The distances from the CTVRTOG and CTVDBCG to the IM-SLNs were measured, respectively.Results: The total number of imaging IM-SLNs was 136. IM-SLNs were mostly found in the first intercostal space (40.4%), with 30.2, 24.3, 4.4, and 0.7% of IM-SLNs in the second, third, fourth, and fifth intercostal space, respectively. The average distance from the edge of the CTVRTOG and the edge of CTVDBCG to the central points of the IM-SLNs was 4.10 mm (SD, 3.3 mm) and 1.60 mm (SD, 2.6 mm), respectively (t = 16.640, P = 0.000). The average distance from the edge of CTVRTOG and the edge of CTVDBCG to the lateral border IM-SLN was 6.40 mm (SD, 3.5 mm) and 3.34 mm (SD, 3.3 mm), respectively (t = 19.815, P = 0.000). Only 18.4% of IM-SLN central points were included in the CTVRTOG, and 60.3% of IM-SLN central points were included in the CTVDBCG. When covering 90 and 100% of the IM-SLN center points, the CTVRTOG needs to expand 8 and 15 mm, respectively, and the CTVDBCG needs to expand 5 and 13 mm, respectively.Conclusion: Neither the RTOG nor DBCG consensus guideline about the delineation of IMN CTV was sufficient to cover 90% of IM-SLNs. For 90% coverage of IM-SLN central points, CTVRTOG needed to be expanded by 8 mm, and CTVDBCG needed to be expanded by 5 mm.

Research progress of sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer

The feasibility and safety of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) for breast cancer are still controversial in clinical practice. SLNB after NAC is feasible and safe for patients with clinically node-negative (cN0) breast cancer, while those with clinically node-positive (cN+ ) should be carefully considered. In addition to methylene blue and 99mTc-sulfur colloid tracing, some other tracing methods have been proposed in clinical studies, such as carbon nanoparticles and indocyanine green fluorescence tracing. The axillary lymph node (ALN) state of SLNB patients after NAC was associated with molecular subtyping, response to chemotherapy, residual breast tumor size, etc. Therefore, a number of factors should be considered to determine whether ALN dissection is needed. The false negative rate of SLNB after NAC can be reduced by some measures such as placing clips prior to surgery and preoperative tattooing with sterile black carbon suspension. Besides ALN, internal mammary lymph nodes is another route for breast cancer metastasis. As a low-invasive diagnostic technique, internal mammary sentinel lymph node biopsy can complete lymph node staging and pathological staging to guide treatment. This review attempts to introduce the research progress of SLNB after NAC from multiple aspects such as feasibility and safety, tracer methods, assessment of ALN status and methods to reduce false negative rate. Key words: Breast neoplasms; Neoadjuvant therapy; Sentinel lymph node biopsy; Axillary lymph node dissection; Internal mammary sentinel lymph node biopsy

Internal Mammary Sentinel Lymph Node Biopsy in Clinically Axillary Lymph Node-Positive Breast Cancer: Diagnosis and Implications for Patient Management

BackgroundRoutine performance of internal mammary sentinel lymph node biopsy (IM-SLNB) remains a subject of debate due to no clinical relevance in breast cancer, because it was performed only in clinically axillary lymph node (ALN)-negative patients. In this study, IM-SLNB was performed in clinically ALN-positive patients, and its impact on nodal staging and therapeutic strategy were subsequently analyzed.MethodsClinically ALN-positive patients who underwent IM-SLNB were enrolled in this prospective study. Statistical analysis was performed using Chi square test, Mann–Whitney U and logistic regression models with a significance level of 0.05.ResultsAmong the 352 recruited patients, the internal mammary sentinel lymph node (IMSLN) visualization rate of patients who received initial surgery and neoadjuvant systemic therapy (NST) was 71.9% (123/171) and 33.1% (60/181), respectively. The 183 patients who underwent IM-SLNB successfully had the average time duration of 7 min and the median IMSLN number of 2. There were 87 positive IMSLNs in all the 347 removed IMSLNs, which were mainly concentrated in the second (50.6%) and third (34.5%) intercostal space. The IMSLN metastasis rate was 39.8% (initial surgery) and 13.3% (NST), respectively. All of the 183 IM-SLNB patients received more accurate nodal staging, 57 of whom had stage elevated, which might have prompted modifications to the therapeutic strategy.ConclusionsIM-SLNB should be routinely performed in clinically ALN-positive patients, and thus more accurate nodal staging and perfect pathologic complete response definition could be put forward. The identification of IMLN metastases by IM-SLNB might potentially influence therapeutic strategies.

Discussion on the indications of internal mammary sentinel lymph node biopsy in breast cancer in the era of precision medicine

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.

Predictive risk factors for sentinel lymph node nonvisualization on planar lymphoscintigraphy using an intratumoral injection in patients with primary breast cancer.

Lymphoscintigraphy is considered a useful tool to optimize sentinel lymph node (SLN) identification. Nonvisualization of the SLN is associated with a lower SLN identification rate. The aim of this study was to identify preoperative factors associated with SLN nonvisualization on lymphoscintigraphy. A total of 2050 consecutive SLN procedures were evaluated from clinically node-negative breast cancer patients. Planar lymphoscintigraphy was performed at 3 h after an intratumoral injection of technetium-99m-nanocolloid. This technique was used for extra-axillary SLN identification. Patient, tumor, and treatment characteristics were analyzed for association with SLN nonvisualization. Factors with a P-value less than 0.1 in univariate analysis were included in a multivariate logistic regression model. The SLN visualization rate was 86.7%. In multivariate logistic regression, age of at least 70 years [odds ratio (OR): 3.24; 95% confidence interval (CI): 2.14-4.91)], BMI of at least 30 (OR: 1.93; 95% CI: 1.39-2.69), T3/T4-tumors (OR: 2.70; 95% CI: 1.37-5.32), medially/centrally located tumors (OR: 1.52; 95% CI: 1.17-1.99), previous mantle field radiation (OR: 4.04; 95% CI: 1.74-9.35), nonpalpable tumors (OR: 1.88; 95% CI: 1.36-2.60), and presence of iodine seeds (OR: 1.35; 95% CI: 1.02-1.78) were associated significantly with nonvisualization on lymphoscintigraphy. Nonvisualization was the strongest independent predictor of unsuccessful intraoperative SLN identification (P<0.001). Overall, the SLN identification rate was 97.7% because of the use of additional imaging and blue dye. This study reports new tumor and treatment-related risk factors for nonvisualization on lymphoscintigraphy by using an intratumoral injection in primary breast cancer. We recommend a periareolar subcutaneous injection to improve SLN visualization in patients with limited prognostic and therapeutic relevance of internal mammary chain SLN identification.

Abstract P3-03-06: Internal mammary chain sentinel nodes in early stage breast cancer patients: Towards selective removal

Abstract Background Internal mammary chain (IMC) sentinel nodes (SN) are visible in 1 out of 5 breast cancer patients on lymph scintigraphy after intra- or peritumoral injection of a radiopharmaceutical. The IMC SN status affects prognosis and treatment of breast cancer and IMC radiotherapy improves survival in selected patients. In contrast to the axillary SN, removal of the IMC SN is not routinely performed and often technically challenging. This study aims at determining the effect of IMC SN biopsy on recurrence-free survival (RFS) and overall survival (OS) and the identification of predictive factors for the development of IMC- and distant metastases. Methods All patients with IMC SNs were selected from a prospective database from 1999 to 2007. Following intratumoral injection of technetium-99m, conventional lymphoscintigraphy was performed. Sentinel nodes were removed in all regions with lymphatic drainage on scintigraphy. The RFS and OS were calculated for the total group and subgroups with tumor-positive, tumor-negative or non-removed IMC SN. Predictive factors were identified for tumor-positive IMC SN and for distant metastasis by regression analysis. Results Internal mammary chain SN biopsy was performed in 287 out of 336 patients (85%). The IMC SN was tumor-positive in 38 patients (13%). Patients with IMC metastasis had poorer OS compared to patients without IMC metastasis or a non-removed IMC SN (57%, 82% and 59% 10- year OS, respectively, p = 0.002). These patients also had worse RFS, mainly due to by the development of distant metastases (68%, 84% and 61% RFS, respectively, p = 0.002). Multivariable predictive for tumor-positive IMC SN were axillary metastases (PPV = 38.5%). Predictive factors for distant metastasis were tumor-positive IMC SN (HR 2.5, 95% CI; 1.0 - 5.8, p = 0.04), not removed IMC SN (HR 2.3, 95% CI; 1.0 - 5.1, P = 0.05), tumor diameter &amp;gt;1.5cm (HR 3.5, 95% CI; 1.6 - 8.4, p &amp;lt; 0.00) and age &amp;gt;65 years (HR 3.1, 95% CI; 1.2 - 7.7, p = 0.02, reference &amp;lt;50 years). Conclusion Breast cancer patients with tumor-positive IMC SN have worse 10- year survival than patients with tumor-negative IMC SN, mainly due to the development of distant metastasis. The clinically relevant predictive factor for distant metastasis is tumor size &amp;gt;1.5cm. Radiotherapy of the IMC can improve survival. However, the cardiotoxicity of parasternal radiotherapy must be weighed against the expected survival benefit. Therefore, our current protocol is to perform IMC SN biopsy in patients younger than 70 years with a tumor diameter &amp;gt;1.5cm. Citation Format: van Loevezijn AA, Bartels SA, van Duijnhoven FH, Heemsbergen WD, Bosma SC, Elkhuizen PH, Donswijk ML, Rutgers EJ, Oldenburg HS, Vrancken Peeters M-JT, van der Ploeg IM. Internal mammary chain sentinel nodes in early stage breast cancer patients: Towards selective removal [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-06.

ASO Author Reflections: A Reappraisal of Internal Mammary Chain Sentinel Node Biopsy in Breast Cancer Patients: Recommendations for Clinical Practice.

ASO Author Reflections: A Reappraisal of Internal Mammary Chain Sentinel Node Biopsy in Breast Cancer Patients: Recommendations for Clinical Practice.

The Lymphatic Drainage Pattern of Internal Mammary Sentinel Lymph Node Identified by Small Particle Radiotracer (99mTc-Dextran 40) in Breast.

PurposeThe purpose of this study was to detect the lymphatic drainage pattern of internal mammary area and verify the concept of internal mammary sentinel lymph node (IM-SLN) in breast.Materials and MethodsA small particle radiotracer (99mTc-Dextran 40) was prepared and tested. 99mTc-Dextran 40 was injected into intraparenchyma at the sound breast by a modified radiotracer injection technique. Subsequently, dynamic single-photon emission computed tomography (SPECT), computed tomography (CT), and SPECT/CT combination images were performed to identify the radioactive lymph vessels and internal mammary lymph nodes (IMLNs). The direction of lymph drainage and the location of the IMLNs were identified in the SPECT/CT imaging.ResultsThe radiochemical purity of 99mTc-Dextran 40 was > 95%. 99mTc-Dextran 40 could drainage into first, second, and third lymph node and the radioactive lymph node could be detected by the γ detector in the animal experiment. After 99mTc-Dextran 40 injecting into intraparenchyma, 50.0% cases (15/30) were identified the drainage lymphatic vessels and radioactive IMLNs by SPECT. The drainage lymphatic vessel was found from injection point to the first IMLN (IM-SLN) after 10.5±0.35 minutes radiotracer injection, and then 99mTc-Dextran 40 was accumulated into the IM-SLN. The combination imaging of SPECT/CT showed the second IMLN received the lymph drainage from the IM-SLN. The lymphatic drainage was step by step in the internal mammary area.ConclusionThe lymph was identified to drain from different regions of the breast to IM-SLN, and then outward from IM-SLN to other IMLN consecutively. It demonstrated the concept of the IM-SLN and provided more evidences for the application of internal mammary sentinel lymph node biopsy.

Implicaciones de la biopsia selectiva de ganglio centinela en cadena mamaria interna sobre la radioterapia adyuvante en mujeres con cáncer de mama sin invasión axilar

ObjectiveTo determine the role of internal mammary sentinel lymph node (IM-SLN) biopsy in adjuvant radiotherapy in female patients with early-stage breast cancer when axillary lymph node biopsy is not performed. Patients and methodsRetrospective cohort study of female patients with early-stage breast cancer diagnosed between January 2008 and December 2016. Only patients with an indication for SLN biopsy and migration of the radiotracer into the internal mammary nodes were included. Data were recorded and analysed on the patients’ clinical features, tumour histology, surgical treatment, adjuvant treatment, locoregional recurrence and overall survival. ResultsA total of 2,622 invasive breast carcinomas were diagnosed. Twenty-three (2.2%) patients had exclusive drainage to the internal mammary nodes. IM-SLN was detected in 65.2% (15/23) of patients, with a mean of 1.61 nodes harvested per patient. Seventy-five per cent of patients receiving adjuvant radiation therapy received it on the internal mammary chain. Chemotherapy and endocrine therapy were administered to 52.2% (12/23) and 87% (20/23) of patients, respectively. A statistically significant association was found between IM-SLN identification and radiotherapy to the internal mammary chain (P<.003), as well as between IM-SLN involvement and radiotherapy to the internal mammary chain (P<.006). One patient developed breast cancer recurrence and another patient developed bone metastases. The median follow-up was 60 months. No deaths were reported. ConclusionsBoth IM-SLN identification and involvement modify the rate of radiotherapy to the internal mammary chain in patients with early-stage breast cancer.

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

PurposeThe 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.MethodsFrom 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.ResultsAmong 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.ConclusionPatients 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.

Research progress in internal mammary lymph node irradiation for breast cancer

Internal mammary lymph node irradiation (IMLNI) could reduce local recurrence and distant recurrence and improve survival. The NCCN Guidelines have updated the recommends in IMLNI. However, the relative toxicities of IMLNI to the heart and lungs should be carefully considered by clinicians, so individualized indications for IMLNI are needed. Internal mammary sentinel lymph node biopsy (IM-SLNB) could be an accurate technique to guide IMLNI with minimally invasive staging, and provide more survival benefits to patients. This article reviews the benefits of IMLNI, controls of the side effect, and discussion of IMLNI guided by IM-SLNB. Key words: Breast neoplasms/radiotherapy; Internal mammary lymph node/irradiation; Progress

Internal mammary lymph nodes radiotherapy of breast cancer in the era of individualized medicine.

Inclusion internal mammary lymph nodes as a part of regional nodal irradiation have a potential to reduce local recurrence, distant recurrence, and improve survival in breast cancer. However, the increased risk of cardiac toxicity and lungs injure associated with internal mammary lymph nodes irradiation has drew more and more attention. Estimating risk of metastasis in internal mammary lymph nodes based on axillary lymph nodes metastasis status is not always reliable: low-risk do not always mean negative in internal mammary lymph nodes and high-risk do not always indicate positive in internal mammary lymph nodes. Inaccurate prediction of in internal mammary lymph nodes metastasis might lead to over- or under-treatment of in internal mammary lymph node. Internal mammary sentinel lymph node biopsy is a minimally invasive technique which has a high potential to accurately evaluate the metastasis status in in internal mammary lymph nodes and improve accuracy of nodal staging. This technique might be a useful tool to guide individualized internal mammary lymph nodes irradiation.