Internal Mammary Node Metastases Research Articles

A novel nomogram and survival analysis for different lymph node status in breast cancer based on the SEER database

IntroductionThe axillary lymph node status (ALNS) and internal mammary lymph nodes (IMLN) expression associated with breast cancer are closely linked to prognosis. This study aimed to establish a nomogram to predict survival at 3, 5, and 10 years in patients with various lymph node statuses.MethodsWe obtained data from patients with breast cancer between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER database). Chi-square analysis was performed to test for differences in the pathological characteristics of the groups, and Kaplan–Meier analysis and the log-rank test were used to plot and compare the correlation between overall survival (OS) and breast cancer specific survival (BCSS). The log-rank test was used for the univariate analysis, and statistically significant characteristics were included in the multivariate and Cox regression analyses. Finally, Independent factor identification was included in constructing the nomogram using R studio 4.2.0; area under curve (AUC) values were calculated, and receiver operating characteristic (ROC) curve, calibration, and decision curve analysis (DCA) curves were plotted for evaluation.ResultsA total of 279,078 patients were enrolled and analysed, demonstrating that the isolated tumour cells (ITC) group had clinicopathological characteristics similar to those of micrometastases (Mic). Multivariate analysis was performed to identify each subgroup's independent risk factors and construct a nomogram. The AUC values were 74.7 (95% CI 73.6–75.8), 72.8 (95% CI 71.9–73.8), and 71.2 (95% CI 70.2–72.2) for 3-, 5-, and 10-year OS, respectively, and 82.2 (95% CI 80.9–83.6), 80.1 (95% CI 79.0–81.2), and 75.5 (95% CI 74.3–76.8) for BCSS in overall breast cancer cases, respectively. AUC values for 3-, 5-, and 10-year OS in the ITC group were 64.8 (95% CI 56.5–73.2), 67.7 (95% CI 62.0–73.4), and 65.4 (95% CI 60.0–70.7), respectively. For those in the Mic group, AUC values for 3-, 5-, and 10-year OS were 72.9 (95% CI 70.7–75.1), 72.4 (95% CI 70.6–74.1), and 71.3 (95% CI 69.6–73.1), respectively, and AUC values for BCSS were 77.8 (95% CI 74.9–80.7), 75.7 (95% CI 73.5–77.9), and 70.3 (95% CI 68.0–72.6), respectively. In the IMLN group, AUC values for 3-, 5-, and 10-year OS were 75.2 (95% CI 71.7–78.7), 73.4 (95% CI 70.0–76.8), and 74.0 (95% CI 69.6–78.5), respectively, and AUC values for BCSS were 76.6 (95% CI 73.0–80.3), 74.1 (95% CI 70.5–77.7), and 74.7 (95% CI 69.8–79.5), respectively. The ROC, calibration, and DCA curves verified that the nomogram had better predictability and benefits.ConclusionThis study is the first to investigate the predictive value of different axillary lymph node statuses and internal mammary lymph node metastases in breast cancer, providing clinicians with additional aid in treatment decisions.

Tumor Contact With Internal Mammary Perforator Vessels as Risk Factor for Gross Internal Mammary Lymph Node Involvement in Patients With Breast Cancer

ImportanceThe identification of internal mammary lymph node metastases and the assessment of associated risk factors are crucial for adjuvant regional lymph node irradiation in breast cancer patients. The current study aims to investigate if tumor contact with internal mammary perforator vessels is associated with gross internal mammary lymph node involvement. MethodsWe included 297 patients with primary breast cancer and gross internal mammary (IMN+) and/or axillary metastases (AXN+) as well as 230 patients without lymph node metastasis. Based on pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DE-MRI), we assessed contact of the tumor to the internal mammary perforating vessels (IMPV). Results59 patients had ipsilateral IMN+ (iIMN+), 10 patients contralateral IMN+ (cIMN+) and 228 patients had ipsilateral axillary metastases without IMN. 230 patients had node negative breast cancer. In patients with ipsilateral IMN+, 100% of tumors had contact with ipsilateral IMPV with 94.9% (n=56) classified as major contact. In iIMN- patients on the other hand, major IMPV contact was observed in only 25.3% (n=116) and 36.2% (n=166) had no IMPV contact at all. Receiver operating characteristic (ROC) analysis revealed that “major IMPV contact” was more accurate in predicting ipsilateral IMN+ (AUC 0.85) compared to a multivariate model combining grade of differentiation, tumor site, size and molecular subtype (AUC 0.65). Strikingly, among patients with contralateral IMN+ (cIMN+), 100% of tumors had contact to a crossing contralateral IMPV, whereas in contralateral IMN- (cIMN-) patients, IMPVs to the contralateral side were observed in only 53.4% (iIMN+) and 24.8% (iIMN-), respectively. ConclusionTumor contact with the IMPV is highly associated with risk of gross IMN involvement. Further studies are warranted to investigate whether this identified risk factor is also associated with microscopic IMN involvement and whether it can assist in the selection of breast cancer patients for IMNI.

Assessing internal mammary lymph node metastasis by breast magnetic resonance imaging in breast cancer.

The internal mammary lymph nodes (IMLNs) are a main pathway of metastasis in breast cancer, and breast magnetic resonance imaging (MRI) plays an important role in staging that disease. We investigated the MRI parameters that can predict metastatic IMLNs and evaluated their diagnostic performance by comparing the breast MRI findings for metastatic and benign IMLNs. From January 2016 to December 2020, 474 cases of enlarged IMLNs on breast MRI were identified. By cytopathology or integrated positron emission tomography/computed tomography (PET/CT), 168 IMLNs were confirmed as metastatic, and 81 were confirmed as benign. Breast MRIs were reviewed by 2 radiologists, and various parameters (node axes, fatty hilum, necrosis, margin characteristics, restricted diffusion, and involved levels; primary tumor location and skin involvement) were assessed. Independent t-tests, receiver operating characteristic (ROC) curve analyses, chi-square tests, and Fisher exact tests were performed to compare and evaluate the diagnostic accuracy of the imaging findings. Significant differences in the breast MRI findings for the short and long axes, fatty hilum, necrosis, margin characteristics, diffusion restriction, and tumor location were observed between benign and metastatic IMLNs. Compared with the long axis and the ratio of the axes, the short axis had the best diagnostic value (higher area under the ROC curve) for predicting metastatic IMLNs. In conclusion, breast MRI parameters such as short axis, presence of fatty hilum, necrosis, margin characteristics, and diffusion restriction can be used to evaluate and differentiate benign from metastatic IMLNs, offering valuable insights to improve diagnosis and treatment planning in breast cancer.

Analysis of factors influencing the pathological complete remission (ipCR) in patients with internal mammary lymph node metastasis after neoadjuvant chemotherapy.

To investigate the factors impacting pathological complete remission (ipCR) of the internal mammary lymph nodes in patients with internal mammary lymph node metastasis (IMLN) after adjuvant chemotherapy. Sixty-five cases of primary breast cancer (BC) with IMLN metastasis who had received neoadjuvant chemotherapy (NAC) were retrospectively analyzed. Postoperative pathology was used to divide the patients into ipCR and non-ipCR groups. Univariate and multivariate analyses were performed on ipCR after NAC. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the factors related to ipCR and a Kaplan-Meier curve was used to analyze prognosis. Twenty-nine (44.62%) of the 65 female patients received ipCR after NAC. Significant differences in hormone receptor (HR) negative and axillary pathological complete response (apCR) rates between the ipCR and non-ipCR group (P<0.05). Multivariate logistic regression analysis showed that HR (OR = 2.698) and apCR (OR = 4.546) were the most significant factors that influenced ipCR (P<0.05). The ROC curves showed that the area under the curves (AUC) for HR and apCR for the prediction of ipCR were 0.744 and 0.735 respectively. The AUC for the combined detection was 0.905. The average disease free survival (DFS) for patients in the ipCR group was 94.0 months which was significantly longer compared to patients in the non-ipCR group (64.2 months) (χ2 = 4.265, P=0.039). No significant difference in OS was detected between the two groups (P>0.05). ipCR after NAC is correlated with HR and apCR. HR combined with apCR has value in predicting ipCR. ipCR has prognostic value in patients with IMLN metastasis and may have the potential to inform clinical decision-making. Further validation of these findings is required through larger-scale prospective studies.

Risk factors of breast cancer recurrence in pathologic complete response achieved by patients following neoadjuvant chemotherapy: a single-center retrospective study.

Pathologic complete response (pCR) of breast cancer after neoadjuvant chemotherapy (NAC) is highly related to molecular subtypes. Patients who achieved tumor pCR after NAC have a better prognosis. However, despite of better prognosis, pCR patients have a potential for recurrence. There is little evidence of risk factors of recurrence in patients with pCR. We aim to analyze factors associated with tumor recurrence in patients who achieved pCR. This study retrospectively reviewed the data of patients diagnosed with breast cancer who achieved pCR after receiving NAC between January 2009 and December 2018 in Samsung Medical Center. pCR was defined as no residual invasive cancer in the breast and axillary nodes even if there is residual ductal carcinoma in situ (ypT0 or ypTis with ypN0). Breast cancers are classified into 4 subtypes based on hormone receptors (HR) and human epithelial growth factor receptor 2 (HER2) status. Patients who had bilateral breast cancer, ipsilateral supraclavicular or internal mammary lymph node metastasis, inflammatory breast cancer, distant metastasis, unknown subtype, and histologically unique case were excluded from the study. In total 483 patients were included in this study except for patients who corresponded to the exclusion criteria. The median follow-up duration was 59.0 months (range, 0.5-153.3 months). Breast cancer recurred in 4.1% of patients (20 of 483). There was a significant difference in clinical T (P = 0.004) and clinical N (P = 0.034) stage in the Kaplan-Meier curve for disease-free survival. Molecular subtypes (P = 0.573), Ki67 (P = 1.000), and breast surgery type (P = 0.574) were not associated with tumor recurrence in patients who achieved pCR after NAC. In the clinical T stage and clinical N stage, there was a significant difference between recurrence and no-recurrence groups (clinical T stage; P = 0.045, clinical N stage; P = 0.002). Univariable Cox regression revealed statistical significance in the clinical T stage (P = 0.049) and clinical N stage (P = 0.010), while multivariable Cox regression demonstrated non-significance in the clinical T stage (P = 0.320) and clinical N stage (P = 0.073). Results in this study showed that clinical T, clinical N stage, and molecular subtypes were not statistically significant predictors of recurrence in patients who achieved pCR after NAC. In spite of that, pCR after NAC may be more important than clinical staging and molecular subtype in early breast cancer. In addition, escalated treatments for patients with HER2 + or triple-negative tumors would be considered with a strict patient selection strategy to prevent over-treatment as well as achieve pCR.

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.

Chest complications in autologous breast reconstruction

Complications from autologous free flap reconstruction of the breast can present with both common surgical complications and unique complications at the chest recipient site. This review covers complications at the chest recipient site, including chest wall deformity, chronic pain, mastectomy skin flap necrosis, infection, pyoderma gangrenosum, bleeding complications, pneumothorax, chyle leak, and positive internal mammary lymph node metastasis.

Effectiveness of PET/CT and VATS for detecting and treating internal mammary lymph node metastasis: a case series.

We occasionally observed internal mammary lymph node metastases of breast cancer in a clinical setting. However, unlike a standard treatment in axillary metastasis, surgical resection for internal mammary lymph node metastasis is not prevalent because of unclear safety and benefits. Thus, we aimed to evaluate the diagnostic ability and clinical outcomes of positron emission tomography/computed tomography and video-assisted thoracoscopic surgery. We retrospectively investigated 34 patients with breast cancer with abnormal 18F-fluorodeoxyglucose uptake in internal mammary lymph nodes, at a single centre, between January 2015 and June 2022 and identified 11 female patients (mean age±SD, 51.5±12.9years) who underwent video-assisted thoracoscopic surgery resection. Positron emission tomography/computed tomography was used to determine the clinical stage. We reviewed the surgical pathology of eleven and two patients who underwent direct-view internal mammary lymph node resection to calculate the positive predictive value of positron emission tomography/computed tomography. Ipsilateral fluorodeoxyglucose accumulation was observed, with an average maximum standardized uptake value of 8.9 (range, 3.1-24.0). No perioperative complications occurred, and all patients who underwent video-assisted thoracoscopic surgery alone were discharged from the hospital on post-operative day 2 or 3. The estimated positive predictive value was 80%. All patients were alive, and seven of nine patients with metastasis were relapse-free, at a mean follow-up period of 17.9months (range, 1-51). However, two patients had recurrence at 16 and 14months after surgery for internal mammary lymph node relapse. Radiotherapy is the standard treatment for suspected internal mammary lymph node metastasis detected using positron emission tomography/computed tomography; however, we could safely perform minimally invasive video-assisted thoracoscopic surgery resection, leading to a definite pathological diagnosis.

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.

Outcomes of Radiotherapy Boost in Breast Cancer Patients with Undissected Supraclavicular and/or Internal Mammary Lymph Node Metastasis

<h3>Purpose/Objective(s)</h3> To evaluate the outcomes in breast cancer patients with clinically significant undissected supraclavicular (SCF) nodes and/or internal mammary lymph nodes (IMN) with or without nodal boost. <h3>Materials/Methods</h3> A retrospective study of 89 patients with clinically positive SCF and/or IMN metastasis treated with curative intent from January 2002 to December 2018 was done. Female breast cancer patients with no distant metastasis, previous history of any cancers, or any synchronous cancer were included. Clinically positive SCF and/or IMN metastasis was defined as radiological significant lymph node seen on imaging, including ultrasound and computed tomography scan, with or without biopsy confirmation. All patients received either neoadjuvant or adjuvant chemotherapy, and all patients underwent either mastectomy or breast conserving surgery, with axillary clearance. Post-operative RT to chest wall or whole breast and nodes included 50 Gy/25# or 40 Gy/15#, with or without a boost of 6-18 Gy. <h3>Results</h3> 89 patients were analyzed; 28 had IMN and 62 had SCF node involvement on diagnosis. 70 patients received neoadjuvant chemotherapy while 19 patients received adjuvant chemotherapy. 80 patients underwent mastectomy and 9 patients had breast conserving surgery. All patients received radiotherapy of which 40 patients had RT boost and 49 had no RT boost. After a median follow-up of 65 months, there were 30 (33.7%) deaths which were all breast cancer related. 32 patients had disease recurrence of which 14 patients had RT boost and 18 did not have RT boost. Of the 14 relapsed patients with RT boost, 7 (50%) patients had locoregional recurrence of which 3 (21%) were boost in-field recurrences. Of the 18 patients without RT boost with disease recurrence, 10 (56%) patients had locoregional recurrence. The 5-year overall survival (OS), disease free survival (DFS) and locoregional free survival (LRFS) rates of patients with RT boost compared to no RT boost were 57.9% vs 51.1% (p = 0.99), 42.1% vs 34.0% (p = 0.46) and 47.4% vs 38.3% (p = 0.66) respectively. Sub-group analysis of patients with SCF boost vs no SCF boost showed a 5-year OS, DFS and LRFS of 56.7% vs 48.3% (p = 0.70), 40% vs 31% (p = 0.64) and 43.3% vs 34.5% (p=0.52) respectively, while patients with IMN boost vs no IMN boost had a 5-year OS, DFS and LRFS of 62.5% vs 52.6% (p = 0.71), 50.0% vs 36.8% (p = 0.95) and 62.5% vs 42.1% (p = 0.33) respectively. <h3>Conclusion</h3> In patients with undissected SCF and/or IMN metastasis, there was a high rate of breast cancer related death. Of 40 patients who received RT boost, only 3 experienced in-field recurrence. We demonstrated a signal of better locoregional control for RT boost in clinically significant IMN or SCF nodes in breast cancer patients, although no statistical significance is achieved likely due to low rates of locoregional recurrences. Further study with a larger cohort is warranted.

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.

Clinical practice guidelines for endoscopic breast surgery in patients with early-stage breast cancer: Chinese Society of Breast Surgery (CSBrS) practice guidelines 2021.

Clinical practice guidelines for endoscopic breast surgery in patients with early-stage breast cancer: Chinese Society of Breast Surgery (CSBrS) practice guidelines 2021.

Contrast enhanced mammography (CEM) versus magnetic resonance imaging (MRI) for staging of breast cancer: The pro CEM perspective

In women with newly diagnosed breast cancer, preoperative staging is required to assess disease extent, enabling us to decide on the most optimal treatment strategy. For locoregional staging, assessment of intramammary tumor extent and presence of axillary and perhaps also internal mammary lymph node metastases is required. Due to the similarity in the underlying principle, contrast-enhanced mammography is increasingly considered instead of breast MRI for this purpose. When considering the combination of CEM and US as a single appointment imaging strategy for preoperative staging of breast cancer, there is only limited room for an additional benefit of breast MRI. For tumor size measurements, equal performance of both CEM and MRI are observed. Sensitivity of both techniques for detecting breast cancer is comparable, meaning that both techniques are capable of detecting additional ipsilateral or contralateral tumor foci. However, specificity is in favor of CEM, meaning that there is a slightly lower chance of having false positive findings in preoperative staging of the breast. Axillary US can be performed during the same appointment as CEM, with equal performance and limitations as evaluation of the axilla on standard breast MRI examinations. Finally, there is no need to actively pursue the detection of IMLN metastases, meaning that additional MRI to do so is not required. This review provides a ‘pro-CEM’ perceptive on the arguments why breast MRI is hardly necessary when CEM in combination with US has been performed as a single appointment imaging strategy in breast cancer patients.

Value of Ultrasound-Guided Biopsy in Evaluating Internal Mammary Lymph Node Metastases in Breast Cancer

ObjectivesThis retrospective study aimed to assess the value of a real-time, ultrasound-guided biopsy in evaluating internal mammary lymph nodes (IMLNs) in breast cancer. MethodsPatients who were diagnosed with breast cancer and underwent real-time, ultrasound-guided core-needle biopsy (CNB) or fine-needle aspiration (FNA) in suspected IMLN metastasis were retrospectively analyzed. Patient information and ultrasonographic images were reviewed and correlated with pathology results. ResultsOf the 164 IMLNs that were subjected to CNB, 131 were positive for metastasis by histopathologic confirmation, 8 were negative, and 25 were insufficient. By FNA, 84 IMLNs were regarded as positive for metastasis, 4 were negative, and 4 were insufficient. In total, there were 215 (83.98%) metastatic IMLNs, 12 benign IMLNs, and 29 unconfirmed by histopathology. There were statistically significant differences in the success of puncture sampling and detection of IMLN metastasis between the CNB and FNA groups (P < .05). There were no significant complications reported after FNA or CNB, including bleeding, nerve injury, infection, pneumothorax, or hemothorax. ConclusionsOur study showed that ultrasonography accurately detected nodes that were likely to be malignant IMLNs, and that real-time, ultrasound-guided CNB and FNA are accurate and valuable techniques for the determination of status in breast cancer patients. Moreover, performing ultrasound-guided CNB and FNA on suspicious IMLN metastasis does not have additional severe complications.

Staging for Breast Cancer With Internal Mammary Lymph Nodes Metastasis: Utility of Incorporating Biologic Factors.

PurposeTo validate the 8th edition of the American Joint Committee on Cancer (AJCC) pathological prognostic staging system for breast cancer patients with internal mammary lymph nodes (IMN) metastasis (N3b disease, stage IIIC in 7th AJCC anatomical staging).MethodsBreast cancer patients with IMN metastasis diagnosed between 2010 and 2014 were retrieved from the Surveillance, Epidemiology, and End Results program. Chi-squared test, Log-rank test, Kaplan-Meier method, and Cox proportional hazard analysis were applied to statistical analysis.ResultsWe included 678 patients with N3b disease in this study. Overall, 68.4% of patients were downstaged to IIIA and IIIB diseases from the 7th anatomical staging to 8th pathological prognostic staging. The new pathological prognostic staging system had better discriminatory value on prognosis prediction among IMN-metastasized breast cancer patients, with a 5-year breast cancer-specific survival (BCSS) of 92.7, 77.4, and 66.0% in stage IIIA, IIIB, and IIIC diseases, respectively (P<0.0001), and the 5-year overall survival (OS) rates was 85.9, 72.1, and 58.7%, respectively (P<0.0001). The results of the multivariate prognostic analysis showed that the new pathological prognostic staging was the independent prognosis related to BCSS and OS, the 8th AJCC pathological prognostic stages showed worse BCSS and OS with gradually increased hazard ratios.ConclusionThe 8th AJCC pathological prognostic staging system offers more refined prognostic stratification to IMN-metastasized breast cancer patients and endorses its use in routine clinical practice for this specific subgroup of breast cancer.

The value of ultrasound in diagnosing metastatic internal mammary lymph nodes in preoperative breast cancer.

Internal mammary lymph nodes (IMLNs) metastasis is of great significance for patients with breast cancer (BC), but the diagnosis of metastasis is difficult. The purpose of this study was to explore the characteristics of metastatic internal mammary lymph nodes visualized on breast ultrasound (US) in preoperative breast cancer. Between March 2014 and May 2020, a total of 278 patients with primary BC were enrolled in a retrospective study and were divided into a metastatic group (n=224) and a non-metastatic group (n=54) according to IMLN status. Medical records, US findings, and especially IMLN status (long and short diameter, cortical thickness, blood flow) were reviewed, analyzed, and correlated with pathologic results. There were significant differences in long diameter, short diameter, numbers, intercostal space (ICS) distribution, and structure type of IMLN between the two groups (P<0.05), but no statistical difference in the ratio of long to short diameter and blood flow (P>0.05). The best cutoff values of size for differentiating IMLN metastasis from benign LNs were 10.5 mm (long diameter), 4.5 mm (short diameter), and 1.9 mm (cortical thickness), with sensitivities of 62.9%, 71.4%, and 91.4%, respectively and specificities of 90.7%, 77.8%, and 86.7%, respectively. The sensitivity and specificity of long and short diameter combined with structure type of IMLN were 74.1% and 83.3%, respectively. US is an important tool to evaluate the status of IMLN in patients with BC. US features of metastatic IMLNs include thickened cortex (≥1.9 mm), absent fatty hilum, multiple (n≥2). The size (long or short diameter) combined with structural types of IMLN had good efficacy for diagnosing IMLN metastasis.

Imaging and Management of Internal Mammary Lymph Nodes.

Internal mammary lymph nodes (IMLNs) account for approximately 10%-40% of the lymphatic drainage of the breast. Internal mammary lymph nodes measuring up to 10 mm are commonly seen on high-risk screening breast MRI examinations in patients without breast cancer and are considered benign if no other suspicious findings are present. Benign IMLNs demonstrate a fatty hilum, lobular or oval shape, and circumscribed margins without evidence of central necrosis, cortical thickening, or loss of fatty hilum. In patients with breast cancer, IMLN involvement can alter clinical stage and treatment planning. The incidence of IMLN metastases detected on US, CT, MRI, and PET-CT ranges from 10%-16%, with MRI and PET-CT demonstrating the highest sensitivities. Although there are no well-defined imaging criteria in the eighth edition of the American Joint Committee on Cancer Staging Manual for Breast Cancer, a long-axis measurement of ≥ 5 mm is suggested as a guideline to differentiate benign versus malignant IMLNs in patients with newly diagnosed breast cancer. Abnormal morphology such as loss of fatty hilum, irregular shape, and rounded appearance (which can be quantified by a short-axis/long-axis length ratio greater than 0.5) also raises suspicion for IMLN metastases. MRI and PET-CT have good sensitivity and specificity for the detection of IMLN metastases, but fluorodeoxyglucose avidity can be seen in both benign conditions and metastatic disease. US is helpful for staging, and US-guided fine-needle aspiration can be performed in cases of suspected IMLN metastasis. Management of suspicious IMLNs identified on imaging is typically with chemotherapy and radiation, as surgical excision does not provide survival benefit and is performed only in rare cases.

Optimal radiotherapy for patients with internal mammary lymph node metastasis from breast cancer

BackgroundThis study aimed to determine the optimal radiotherapy (RT) regimen for patients with clinical metastasis to the internal mammary lymph node (cIMN+) from breast cancer.MethodsWe retrospectively reviewed the medical records of 84 patients with cIMN+ breast cancer treated with curative surgery, taxane-based chemotherapy, and postoperative RT between January 2009 and December 2014. Postoperative RT was administered to the whole breast or chest wall using 50 Gy in 2 Gy fractions. Boost RT to the internal mammary lymph node (IMN) was administered at the physician’s discretion. We categorized patients into two groups according to the IMN dose as follows: low-dose IMN RT (50.0–63.5 Gy) and high-dose IMN RT (63.6–70.4 Gy).ResultsAfter a median follow-up of 58 months (range, 12–111 months), IMN recurrence was observed in 2 patients (2.4%), and all IMN recurrences developed simultaneously with distant metastases. The 5-year locoregional recurrence-free survival, disease-free survival (DFS), and overall survival rates were 89.1, 72.0, and 81.2%, respectively. The triple-negative subtype, IMN size ≥1.0 cm, old age, and low-dose IMN were significantly associated with poor DFS. Among the patients with IMN size ≥1.0 cm, the 5-year DFS was significantly higher in those treated with high-dose IMN RT than in those treated with low-dose IMN RT (69.3% vs. 33.3%, p = 0.019).ConclusionsIMN RT without IMN dissection resulted in favorable outcomes in cIMN+ breast cancer. For patients with a large IMN, a higher IMN radiation dose might be needed for disease control.