Pathologic Axillary Lymph Node Status Research Articles

Predicting pathological axillary lymph node status with ultrasound following neoadjuvant therapy for breast cancer

PurposeHigh-performing imaging and predictive markers are warranted to minimize surgical overtreatment of the axilla in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT). Here we have investigated whether axillary ultrasound (AUS) could identify axillary lymph node (ALN) metastasis (ALNM) pre-NACT and post-NACT for BC. The association of tumor, AUS features and mammographic density (MD) with axillary-pathological complete response (axillary-pCR) post-NACT was also assessed.MethodsThe NeoDense-study cohort (N = 202, NACT during 2014–2019), constituted a pre-NACT cohort, whereas patients whom had a cytology verified ALNM pre-NACT and an axillary dissection performed (N = 114) defined a post-NACT cohort. AUS characteristics were prospectively collected pre- and post-NACT. The diagnostic accuracy of AUS was evaluated and stratified by histological subtype and body mass index (BMI). Predictors of axillary-pCR were analyzed, including MD, using simple and multivariable logistic regression models.ResultsAUS demonstrated superior performance for prediction of ALNM pre-NACT in comparison to post-NACT, as reflected by the positive predictive value (PPV) 0.94 (95% CI 0.89–0.97) and PPV 0.76 (95% CI 0.62–0.87), respectively. We found no difference in AUS performance according to neither BMI nor histological subtype. Independent predictors of axillary-pCR were: premenopausal status, ER-negativity, HER2-overexpression, and high MD.ConclusionBaseline AUS could, to a large extent, identify ALNM; however, post-NACT, AUS was insufficient to determine remaining ALNM. Thus, our results support the surgical staging of the axilla post-NACT. Baseline tumor biomarkers and patient characteristics were predictive of axillary-pCR. Larger, multicenter studies are needed to evaluate the performance of AUS post-NACT.

Abstract OT3-02-03: Radiomics multi-parametric MRI of before and after neoadjuvant chemotherapy associated with axillary lymph node metastasis and prognostic in patients with breast cancer: A multicenter RBC-002 study

Abstract Background: Axillary lymph node metastasis is a vital factor of prognosis in patients with invasive breast cancer. However, sensitivity and noninvasive for prediction of lymph node metastasis and survival after neoadjuvant chemotherapy is limited. This study aims to develop radiomics combining multi-parametric MRI before and after neoadjuvant chemotherapy to predict axillary lymph node metastasis and prognosis, as well as investigate the relationship between the radiomics and tumor microenvironment in invasive breast- cancer. Methods: RBC-02 is a multicenter, ambispective cohort study proposes to build a clinical predictive model to predict axillary lymph node metastasis and prognosis in invasive-breast- cancer patients who received neoadjuvant chemotherapy. Patients are recruited from Sun Yat-sen Memorial Hospital of Sun Yat-sen University (training cohort), Sun Yat-sen University Cancer Center (validation cohort), and Tungwah hospital of Sun Yat-sen University (validation cohort) in China. Invasive breast cancer patients undergo multi-parametric MRI at baseline, then undergo multi-parametric MRI after received neoadjuvant chemotherapy for at least 4 cycles as planned. After the surgery, responses to neoadjuvant chemotherapy are determined according to the histopathologically examination of the surgically resected specimens. The model is built based on breast MRI signatures extracted and analyzed via deep machine- learning algorithm methods. The correlation between radiomics features and tumor microenvironment is also planned to investigate. Decision curve analysis was performed with the combined training and validation set to estimate the clinical usefulness of the radiomics nomogram, which is built with a multivariate logistic regression model. The primary endpoint is disease-free survival. Secondary endpoints include pathological complete response, pathological axillary lymph node status, and overall survival. The trial is registered with ClinicalTrials.gov, number NCT04004559, and Chinese Clinical Trail Registry, number ChiCTR1900024113. Citation Format: Herui Yao, ChenChen Li, Yunfang Yu, Chuanmiao Xie, Jie Ouyang, Yujie Tan, Nian Lu, Ying Wang, Jianli Zhao, Kai Chen, Jiafan Ma. Radiomics multi-parametric MRI of before and after neoadjuvant chemotherapy associated with axillary lymph node metastasis and prognostic in patients with breast cancer: A multicenter RBC-002 study [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 OT3-02-03.

Pre-operative Conventional Ultrasound and Sonoelastography Evaluation for Predicting Axillary Lymph Node Metastasis in Patients with Malignant Breast Lesions

The objective of our study was to evaluate the association between the sonoelastography features of breast tumor and axillary lymph node metastasis (ALNM) in patients with breast cancer. In a cohort of 106 women with breast cancer, the conventional ultrasound features and elasticity parameters by elasticity imaging and Virtual Touch Tissue Imaging & Quantification (VTIQ) were retrospectively analyzed. Ultrasound and elastography findings were compared with pathologic axillary lymph node status. Receiver operating characteristic curve analysis was used to evaluate diagnostic performance. Pathologically, the overall incidence of ALNM was 39.6% (42/106) in the final analysis. ALNM was significantly more frequent in tumors with elasticity imaging scores >4.5, maximal shear wave velocity values (Smax) >6.42 m/s and mean shear wave velocity values (Smean) >5.66 m/s, respectively. The sensitivity, specificity and accuracy were 78.6%, 54.7% and 64.2% for elasticity imaging score; 85.7%, 54.7% and 67.0% for Smax; and 59.5%, 79.7% and 71.7% for Smean, respectively Elastography features, including elasticity imaging score and VTIQ, can be used to supplement conventional ultrasound to predict ALNM in patients with breast cancers.

Phase-Transition Nanodroplets for Real-Time Photoacoustic/Ultrasound Dual-Modality Imaging and Photothermal Therapy of Sentinel Lymph Node in Breast Cancer

Pathological status of lymph nodes (LNs) plays a critical role in staging and treatment for the patients with breast cancer. Sentinel lymph node biopsy has become the standard method in determining pathological status of axillary LNs. Therefore, the determination of sentinel lymph nodes (SLNs) and therapy of metastatic LNs are highly desirable in clinic. Herein, an unprecedented carbon nanoparticles (CNs)-incorporated liquid-gas phase-transition nanodroplets (CNPs) with strong near-infrared (NIR) absorption, good biocompatibility, excellent photoacoustic (PA) and ultrasound (US) contrast, and high photothermal-conversion efficiency are reported in this study. Upon laser irradiation, liquid-gas phase transition of the CNPs has been demonstrated to provide excellent contrasts for PA/US dual-modality imaging both in vitro and in vivo. Additionally, the CNPs are capable of staining lymph nodes, which can contribute significantly to the identification of LNs with naked eyes. With increased laser energy, the CNPs exhibit the high performance in killing the breast cancer cells both in vitro and in vivo, due to the photothermal effect induced from the CNs within CNPs. These results suggest that the developed multifunctional phase-transition nanodroplets have high potential to act as the theranostic agents in both SLNs detection and therapy of metastatic LNs.

Efficacy of adjuvant endocrine therapy in breast cancer patients with a positive-to-negative switch of hormone receptor status after neoadjuvant chemotherapy

Objective: To evaluate the efficacy of adjuvant endocrine therapy (AET) in breast cancer patients with a positive-to-negative switch of hormone receptor status after neoadjuvant chemotherapy (NAC). Methods: One hundred and six patients who presented with hormone receptor (HR)-positive breast cancer at diagnosis and turned to HR-negative after NAC during December 2000 and December 2013 in Jiaxing Maternity and Child Health Care Hospital were retrospectively identified. Kaplan-Meier analysis and log-rank test were used for univariate analyses of factors related to disease free survival (DFS) and overall survival (OS). Multivariate analysis was carried out using the Cox proportional hazards model in patients with DFS and OS. Results: All the patients were categorized into two groups on the basis of the administration of AET:61 AET-administered patients (57.5%) and 45 AET-naïve patients (42.5%). After a median follow-up of 68 months (range 14-103 months), human epidermal growth factor receptor 2 (HER-2) status, initial clinical stage, pathological axillary lymph node status and the use of AET were identified as the variables affecting DFS and OS (all P<0.05). Patients treated with AET had a significantly improved 5-year DFS rate when compared with that without AET (77.1% vs 53.5%,P<0.05). The 5-year OS of AET-administered patients was also better than that of AET-naïve patients (80.9% vs 71.0%,P<0.05). Cox regression analysis showed that AET-administered or not was the independent predictor for 5-year DFS (HR=2.096, 95% CI:1.081-4.065, P<0.05). Conclusion: Patients with HR altered from positive to negative after NAC may still gain benefit from AET.

Abstract P1-01-22: Which cytologically proven node-positive breast cancer patients can avoid axillary lymph dissection after neaodjuvant chemotherapy?

Abstract BACKGROUND: It is still controversial whether axillary lymph node dissection can be omitted after negative sentinel lymph node biopsy in breast cancer patients with clinically positive axilla at presentation treated with neoadjuvant chemotherapy (NAC). The aim of this study was to analyze whether SLN biopsy could be useful in these patients. METHODS: After NAC of 112 patients with cytology-proven axillary node metastasis at the time of diagnosis, SLNB using radioisotope and blue dye was performed including completion node dissection between 2008 and 2012. The results of SLNB and clinicopathological characteristics were analyzed for correlation with pathological axillary lymph node status. RESULTS: SLN was successfully identified in 107 (95.5%) patients. Tumor nonresponse and extensive residual nodal disease were found to be significantly associated with detection failure of sentinel nodes. Axillary status was predicted with 94% accuracy and a false negative rate of 8.7%. Axillary nodal status before NAC (cN2 versus cN12) was associated with higher false-negative rates (p = 0.02). Conversion to node-negative disease was achieved in 38 (35%) patients: 23% of patients with the luminal A subtype, 12% of patients with the luminal B, 39% of patients with the HER2-enriched, and 26% of patients with the triple-negative breast cancer subtype. The tripple negative and HER2-enriched breast cancer subtypes had a significantly better false negative rate and accuracy. CONCLUSIONS: SLNB was found to be technically feasible, but its routine use was not recommended for LABCs after NAC. However, acceptable performance was noted for tripple negative and HER2-enriched breast cancer patients presented with N1 axillary status in the beginning of NAC, and thus SLNB might be safely considered in these selected patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-01-22.

Diagnostic performance of fluorodeoxyglucose-positron emission tomography/computed tomography combined with ultrasonography-guided fine needle aspiration cytology for identifying axillary lymph node status in patients with breast cancer

AimThe aim of this study was to assess the diagnostic performance of fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in combination with ultrasonography-guided fine needle aspiration cytology (US-guided FNAC) for the preoperative diagnosis of axillary lymph node (ALN) metastases in patients with breast cancer. Materials and methodsA total of 318 patients with breast cancer were recruited retrospectively. Some of the cases that underwent neoadjuvant chemotherapy (NAC) were included. The sensitivity and specificity of FDG-PET/CT were calculated. We assessed the relationship between the combined results for US-guided FNAC with FDG-PET/CT and the pathological ALN status. ResultsA total of 271 patients underwent FDG-PET/CT. Of these patients, 41 underwent US-guided FNAC. The sensitivity and the specificity of FDG-PET/CT for the cases without NAC were 18.5%, 97.1%, respectively. The sensitivity in cases with NAC was 68.2%. As a whole, the sensitivity was 40.8%.ALN metastasis was detected using US-guided FNAC in a case with a negative FDG uptake in the ALN. The T stage was T2 in the case and the FDG uptake at the primary site was poor. ConclusionFDG-PET/CT has a good specificity for ALN metastasis, although its sensitivity is limited, especially in early-stage cases. In cases with a negative FDG uptake in the ALN, US-guided FNAC may play a role in the detection of lymph node metastasis when the primary tumor size is large and the FDG uptake in the primary tumor is low.

Sentinel lymph node biopsy after neoadjuvant chemotherapy predicts pathological axillary lymph node status in breast cancer patients with clinically positive axillary lymph nodes at presentation

It is still controversial whether axillary lymph node (ALN) dissection (ALND) can be omitted after negative sentinel lymph node (SLN) biopsy (SLNB) in breast cancer (BC) patients with clinically positive ALNs at presentation treated with neoadjuvant chemotherapy (NAC). The study aim was to analyze whether SLNB could be useful in these patients. In a retrospective study, eligible patients were women with invasive BC with clinically positive ALNs at presentation, treated with NAC then a total or partial mastectomy, with an intraoperative histological examination of SLNs and non-SLNs suspicious for metastasis followed by ALND. Non-SLNs suspicious for metastasis were defined as hard or large nodes located in the same level of the axilla where clinically positive ALNs had been initially identified. The results of SLNB and clinicopathological characteristics were analyzed for correlation with pathological ALN status. In a consecutive series of 105 women with 107 BC cases, 81 (75.7 %) had at least 1 SLN, and the remaining 26 (24.3 %) had at least 1 non-SLN suspicious for metastasis. The intraoperative (or final) histological examination of these nodes revealed that the false-negative (FN) rate and accuracy were 8.2 (or 6.3) % and 95.1 (or 96.3) %, respectively. Estrogen receptor status at presentation, pathological tumor response, lymphovascular invasion after NAC, and NAC regimen were correlated with pathological ALN status. The histological examination of SLNs and that of non-SLNs suspicious for metastasis are useful for predicting pathological ALN status in BC patients with clinically positive ALNs at presentation who are treated with NAC.

Pathological Axillary Lymph Node Status in HER-2 Receptor Positive and Negative Breast Cancers

Pathological Axillary Lymph Node Status in HER-2 Receptor Positive and Negative Breast Cancers

Outcomes in breast cancer patients relative to margin status after treatment with breast-conserving surgery and radiation therapy: the University of Pennsylvania experience

Purpose: To evaluate the significance of final microscopic resection margin status on treatment outcomes in women with early breast cancer who are treated with breast-conserving surgery and definitive breast irradiation.Methods and Materials: An analysis was performed of 1021 consecutive women with clinical Stage I or II invasive carcinoma of the breast treated with breast-conserving surgery and definitive breast irradiation. Complete gross excision of tumor was performed in all cases, and an axillary staging procedure was performed to determine pathologic axillary lymph node status. The 1021 patients were divided into four groups based on the final microscopic margin from the tumor excision or from the re-excision if performed. These four groups were: (a) 518 patients with negative margins; (b) 124 patients with focally positive margins; (c) 96 patients with focally close margins (≤ 2 mm); and (d) 283 patients with unknown margins.Results: Local failure was not significantly different in patients with negative, focally positive, focally close or unknown final pathologic margins of resection at 8 years (8% vs. 10% vs. 17% vs. 16%, respectively, p = 0.21). The 8-year outcome also was not different among the four groups for overall survival (86% vs. 83% vs. 88% vs. 81%, respectively, p = 0.13), cause-specific survival (89% vs. 86% vs. 88% vs. 83%, respectively, p = 0.14), no evidence of disease survival (81% vs. 73% vs. 86% vs. 77%, respectively, p = 0.09), and freedom from distant metastases (85% vs. 75% vs. 86% vs. 79%, respectively, p = 0.08).Conclusion: These results demonstrate that selected patients with focally positive or focally close microscopic resection margins can be treated with breast-conserving surgery and definitive breast irradiation with 8-year local control rates and survival rates that are similar to those seen in breast-conservation patients with negative or unknown final resection margins.

Early-stage bilateral breast cancer treated with breast-conserving surgery and definitive irradiation: The university of pennsylvania experience

Purpose : To determine whether patients with early-stage bilateral breast cancer can be treated with definitive irradiation following breast-conserving surgery with acceptable survival, local control, complications, and cosmesis. Methods and Materials : During the period 1977–1992, 55 women with State 0, I, or II concurrent ( n = 12) or sequential ( n = 43) bilateral breast cancer were treated with definitive irradiation following breast-conserving surgery. The records of these 55 patients with 110 treated breasts were reviewed for tumor size, histology, pathologic axillary lymph node status, first and overall site(s) of failure, and adjuvant chemotherapy or hormonal therapy. Curves for survival, local control, and regional control were determined. Cosmetic outcome, complication rates, and matching technique were analyzed. The median total radiation dose delivered was 64 Gy *range 42–72) using tangential whole-breast irradiation followed by an electron or iridium implant boost. The tangential fields were matched with no overlap in 40 patients (73%); there was overlap on skin of up to 4 cm in 14 patients. (25%); and the matching technique was unknown in 1 patient (2%). The median follow-up for the 12 women with concurrent bilateral breast cancer was 4.0 years. The median follow-up for the other 43 women with sequential cancer was 9.3 and 4.9 years, respectively, after the first and second cancers. Results : For the overall group of 55 patients, the 5- and 10-year overall survival rates were 96% and 94%, respectively, after treatment of the first cancer, and 96% and 92%, respectively, after treatment of the second cancer. The 5- and 10-year actuarial relapse-free survival rates were 90% and 75%, respectively, after treatment of the first cancer, and 83% and 72%, respectively, after treatment of the second cancer. For the 110 treated breast cancers, th 5- and 10-year actuarial local failure rates were 5% and 15%, respectively. Complication rates were: 28% breast edema, 8% arm edema, 4% pneumonitis, 3% cellulitis, 1% rib fracture, and 1% brachial plexopathy; no patients developed matchline fibrosis. For patients with a minimum of 3 years of relapse-free follow-up, the rate of excellent or good cosmetic outcome for 104 treated beasts was 85%. Conclusion : Definitive irradiation after breast-consercing surgery is technically feasible for selected patients with concurrent or sequential early-stage bilateral breast cancer. Survival, local control, complication rates, and cosmetic outcomes appear comparable to historical reports of breast conservation treatment for unilateral disease. Bilateral definitive breast irradiation after breast-conservation surgery should be considered an acceptable alternative treatment to bilatera; mastectomy for selected patients with concurrent or sequential early-stage bilateral breast cancer.

Predictors of axillary lymph node metastases in patients with impalpable breast cancer

To define a subgroup of patients in whom axillary lymph node dissection could be omitted, 111 patients with an impalpable invasive breast carcinoma were studied. The records of these patients were reviewed for pathological axillary lymph node status, age, menopausal status, clinical nodal status, findings on mammography and tumour characteristics such as tumour size, tumour grade, mitotic activity index, receptor status, and lymphatic and blood vessel invasion. Twenty-two per cent of the patients had lymph node metastases. Age and tumour size were significantly correlated to pathological nodal status.

The significance of the pathology margins of the tumor excision on the outcome of patients treated with definitive irradiation for early stage breast cancer

To evaluate the significance of the pathology margins of the tumor excision on the outcome of treatment, an analysis was performed of 697 consecutive women with clinical Stage I or II invasive carcinoma of the breast treated with breast-conserving surgery and definitive irradiation. Complete gross excision of the primary tumor was performed in all cases, and an axillary staging procedure was performed to determine pathologic axillary lymph node status. The 697 patients were divided into four groups based on the final pathology margin from the primary tumor excision or from the re-excision if performed. These four groups were: (a) 257 patients with a negative margin (>2 mm), (b) 57 patients with a positive margin, (c) 37 patients with a close margin (⪯2 mm), and (d) 346 patients with an unknown margin. The patients with positive final pathology margins were focally positive on microscopic examination. Patients with grossly positive margins or with diffusely positive microscopic margins were treated with conversion to mastectomy. There was a significant difference in the total radiation dose for the four groups (median dose of 6000 vs 6500 vs 6400 vs 6240 cGy, respectively; p < .0001). There was no significant difference among the four groups for 5-year actuarial overall survival (p = .19), no evidence of disease (NED) survival (p = .95), or relapsefree survival (p = .80). There was no significant difference among the four grous for five year actuarial local or regional control (all p ≥ .29). Subset analyses did not identify any poor outcome subgroups. These results have demonstrated that selected patients with focally positive or close microscopic pathology margins can be adequately treated with definitive breast irradiation. Patient selection and the technical delivery of radiation treatment including a boost may have been important contributing factors to the good outcome in these patients.