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Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy.

ABSTRACT: Background: Breast cancer (BC) is a heterogeneous disease made up of clones with different metastatic potential. Intratumoral heterogeneity may cause metastases to show divergent biomarker expression, potentially affecting chemotherapy response. Methods: We investigated the immunohistochemical (IHC) and FISH profile of estrogen receptors (ER), progesterone (PR) receptors, Ki67, and HER2 in a series of BC-matched primary tumors (PTs) and axillary lymph node (ALN) metastases in pre-operative core needle biopsies (CNBs). Phenotypical findings were correlated to morphological features and their clinical implications. Results: Divergent expression between PTs and ALNs was found in 10% of the tumors, often involving multiple biomarkers (12/31, 39%). Most (52%) displayed significant differences in ER and PR staining. HER2 divergences were observed in almost three-quarters of the cases (23/31, 74%), with five (16%) switching from negativity to overexpression/amplification in ALNs. Roughly 90% of disparities reflected significant morphological differences between PTs and ALN metastases. Less than half of the discrepancies (12/31, 39%) modified pre/post-operative treatment options. Conclusions: We observed relevant discrepancies in biomarker expression between PTs and metastatic ALNs in a noteworthy proportion (10%) of preoperative BC CNBs, which were often able to influence therapies. Hence, our data suggest routine preoperative assessment of biomarkers in both PTs and ALNs in cases showing significant morphological differences.

SUBMITTER: Marletta S

PROVIDER: S-EPMC10854870 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy.

Marletta Stefano S Giorlandino Alexandra A Cavallo Enrico E Dello Spedale Venti Michele M Leone Giorgia G Tranchina Maria Grazia MG Gullotti Lucia L Bonanno Claudia Lucia CL Spoto Graziana G Falzone Giusi G Tornabene Irene I Trovato Carmelina C Baron Marco Maria MM Di Mauro Giuseppe G Falsaperna Lucia L Angelico Giuseppe G Pafumi Sarah S Rizzo Antonio A

Diagnostics (Basel, Switzerland) 20240125 3

<b>Background</b>: Breast cancer (BC) is a heterogeneous disease made up of clones with different metastatic potential. Intratumoral heterogeneity may cause metastases to show divergent biomarker expression, potentially affecting chemotherapy response. <b>Methods</b>: We investigated the immunohistochemical (IHC) and FISH profile of estrogen receptors (ER), progesterone (PR) receptors, Ki67, and HER2 in a series of BC-matched primary tumors (PTs) and axillary lymph node (ALN) metastases in pre-o ...[more]

PMID: 38337775

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Project description:Whether the expression status of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) receptor and Ki-67 show concordance between the primary tumors and the synchronous axillary lymph node (ALN) metastases has been discussed in numerous studies. However, to date, the results of these studies remain controversial. Therefore, the present study aimed to investigate whether the expression of ER, PR, HER-2 and Ki-67 was in concordance between the primary tumors and synchronous ALN metastases in patients with operable breast cancer (BC). A total of 60 tissue samples were collected from patients with primary operable BC diagnosed with primary tumors and synchronous ALN metastases. The expression levels of the four biomarkers, ER, PR, HER-2 and Ki-67, were assessed in primary lesions and synchronous ALN metastases samples using immunohistochemistry. The cut-off values were set to 10% for ER and PR, while the labeling index of Ki-67 was set to 14%. The immunostaining intensity of ER and PR was scored as negative (?), 1+, 2+ and 3+. The criteria for HER-2 testing in BC were implemented according to the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) guidelines. The concordance rates for ER, PR and HER-2 were 96.7 (58/60), 96.7 (58/60) and 90% (54/60), respectively. In addition, the kappa values of consistency in the primary lesions and the synchronous ALN metastases were 0.773 for ER, 0.654 for PR and 0.785 for HER-2. Furthermore, the P-values of ER, PR and Ki-67 numerical variables between the two groups were 0.393, 0.400 and 0.331, respectively, as demonstrated using a non-parametric Wilcoxon signed rank test. The findings of the present study demonstrated a high degree of concordance between the expression of ER, PR, HER-2 and Ki-67 in the primary tumors and that in the synchronous ALN metastases, suggesting that the BC primary tumor biomarkers may be used for the prognosis of synchronous ALN metastases in patients with operable BC.

Project description:PurposeSentinel lymph node biopsy (SLNB) alone following neoadjuvant chemotherapy (NAC) remains controversial in patients with breast cancer who are initially lymph node-positive. The present study aimed to evaluate the impact of SLNB and axillary lymph node dissection (ALND) on breast cancer recurrence and survival in patients who converted from lymph node-positive to pathological node-negative (ypN0) after NAC.MethodsThis single-center retrospective study included 223 patients who converted to axillary lymph node-negative status after NAC and underwent breast and axillary surgery between January 2006 and December 2015. This study compared the overall survival (OS), disease-free survival (DFS), ipsilateral axillary lymph node recurrence rates and incidence of postoperative complications, especially, arm lymphedema and shoulder stiffness between SLNB and ALND.ResultsThis study included 223 patients with axillary pathological complete response (pCR) after NAC and surgery. The SLNB and ALND groups included 94 and 129 patients, respectively. The median follow-up time was 57 (range, 6-155) in the SLNB group and 99 (range 2-159) months in the ALND group. The corresponding 5-year OS and DFS rates were 96.3% and 94.2% (p = 0.392), and 89.2% and 86.4% (p = 0.671), respectively. Four patients (4.3%) in the SLNB group and nine (7.0%) in the ALND group developed locoregional recurrences. Ipsilateral axillary lymph node recurrence and distant metastasis were observed in one (1.1%) and three (2.3%) patients, and in 10 (10.6%) and 11 (8.5%) patients, respectively. Patients in the ALND group were more likely than their SLNB counterparts to experience complications, such as shoulder stiffness (9 [7.0%] vs. 4 [4.3%] patients, p = 0.57). The rate of lymphedema in the ALND group was three times that in the SLNB group (35 [27.1%] vs. 8 [8.5%] patients, p < 0.001).ConclusionAs an alternative to ALND, SLNB has oncological safety in patients with axillary pathological complete response after NAC.

Project description:IntroductionThe axillary lymph node (ALN) status of breast cancer patients is an important prognostic indicator. The use of primary breast mass features for the prediction of ALN status is rare. Two nomograms based on preoperative ultrasound (US) images of breast tumors and ALNs were developed for the prediction of ALN status.MethodsA total of 743 breast cancer cases collected from 2016 to 2019 at the Second Affiliated Hospital of Harbin Medical University were randomly divided into a training set (n = 523) and a test set (n = 220). A primary tumor feature model (PTFM) and ALN feature model (ALNFM) were separately generated based on tumor features alone, and a combination of features was used for the prediction of ALN status. Logistic regression analysis was used to construct the nomograms. A receiver operating characteristic curve was plotted to obtain the area under the curve (AUC) to evaluate accuracy, and bias-corrected AUC values and calibration curves were obtained by bootstrap resampling for internal and external verification. Decision curve analysis was applied to assess the clinical utility of the models.ResultsThe AUCs of the PTFM were 0.69 and 0.67 for the training and test sets, respectively, and the bias-corrected AUCs of the PTFM were 0.67 and 0.67, respectively. Moreover, the AUCs of the ALNFM were 0.86 and 0.84, respectively, and the bias-corrected AUCs were 0.85 and 0.81, respectively. Compared with the PTFM, the ALNFM showed significantly improved prediction accuracy (p < 0.001). Both the calibration and decision curves of the ALNFM nomogram indicated greater accuracy and clinical practicality. When the US tumor size was ≤21.5 mm, the Spe was 0.96 and 0.92 in the training and test sets, respectively. When the US tumor size was greater than 21.5 mm, the Sen was 0.85 in the training set and 0.87 in the test set. Our further research showed that when the US tumor size was larger than 35 mm, the Sen was 0.90 in the training set and 0.93 in the test set.ConclusionThe ALNFM could effectively predict ALN status based on US images especially for different US tumor size.

Project description:BackgroundIn the last three decades, axillary lymph node dissection (ALND) has been replaced by sentinel lymph node biopsy (SLNB) in all clinically node-negative patients. However, when SLNB alone is performed in clinically node-positive patients who are rendered node-negative by neoadjuvant chemotherapy, the procedure has a high false-negative rate and other complementary procedures have been described to improve its reliability. Preoperative tattooing of the suspicious lymph node with India ink at the time of biopsy, in addition to sentinel lymph node biopsy, is a reasonable alternative. The objective of our study is to determine, in clinically node-positive patients, the feasibility of tattooing suspicious axillary lymph node at the time of percutaneous needle biopsy and its retrieval at the time of surgery.MethodsA prospective experimental study will be conducted divided into two phases-phases I and II. In phase I, 10 patients committed to undergo upfront surgery (without neoadjuvant chemotherapy) will have a suspicious lymph node tattooed by injecting India ink at the time of core needle biopsy. All patients will undergo a SLNB, during which the axilla will be inspected to determine if the tattooed lymph node can be visualized. Routine microscopic examination will follow, and concordance between the sentinel and tattooed node will also be established. In phase II, the process will be repeated for 30 patients who undergo surgery after neoadjuvant chemotherapy. The analysis will be performed in Stata version 12.DiscussionThere is a need to identify and test the techniques for the down-staged axilla in post-neoadjuvant chemotherapy patients, which are not only practical and limit the number of invasive procedures necessary but are representative of the new axillary status and help limit the extent of axillary surgery without negatively impacting outcomes. We propose that, for the patient undergoing neoadjuvant chemotherapy with a biopsy-proven disease in the axilla, this could be achieved by India ink which allows marking, identification, and retrieval of the biopsied lymph node. Retrieval of this previously biopsied lymph node along with sentinel nodes, if found to be representative of the status of the remainder of the axilla, could potentially eliminate the need for routine axillary lymph node dissection and thus limit morbidity.Trial registrationClinicalTrials.gov, NCT03939598. Retrospectively registered on 7 May 2019.

Dataset Information

Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy.

Publications

Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy.

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