Clinical relevance of biomarker discordance between primary breast cancers and synchronous axillary lymph node metastases (original) (raw)
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Applied Immunohistochemistry & Molecular Morphology, 2017
Background: We aimed to demonstrate that in breast carcinomas the tumor profile is not stable during the metastatic process, with impact on therapeutic decisions. Materials and Methods: We analyzed the estrogen receptor (ER), progesterone receptor (PR), and HER2 status and Ki67 index in 41 primary unifocal (PU) and 37 primary multiple (PM) breast carcinomas with identical immunohistochemical profiles among multiple tumor foci and the matched axillary lymph node metastases. We defined as concordant cases in which the primary tumor (PU or PM) and lymph node metastases displayed identical positivity or negativity for ER, PR, HER2, Ki67 and as discordant cases in which there was a mismatch in at least 1 biological parameter among PU and PM tumor and lymph node metastases. Moreover, we defined as concordant cases in which the molecular profile (based on the immunohistochemical evaluation of ER, PR, HER2, and Ki67) was concordant among PU and PM tumors and lymph node metastases and mismatch cases as those in which the molecular profile of the primary tumor differs from one of the lymph node metastases in at least 1 lymph node. Results: The positivity for the biological markers is not stable during the metastatic process. In this study the total rate of discordant cases was 92.7% in PU tumors and 75.7% in PM homogenous tumors (P = 0.058, odds ratio = 0.245, 95% confidence interval, 0.06-0.991). The total rate of shifted cases was 64.9% in PM tumors and 82.9% in PU tumors. The highest rate of shifting was encountered from Luminal B-like to Luminal Alike. In 11 out of 37 (29.7%) PM and in 17 out of 41 (41.5%) PU cases the subtype shifted to a poorer one with respect to prognosis. Conclusions: The patients in whom the primary tumor is hormone receptor and/or HER2 negative but is positive for these markers in the axillary lymph nodes could become eligible for hormonal treatment and/or trastuzumab treatment, which may significantly improve the patient's outcome.
Clinical Breast Cancer, 2015
Estrogen receptor (ER), progesterone receptor (PR), and HER2/neu are the most important tissue markers in the management of breast cancer, in the adjuvant setting and in the setting of metastatic disease. Many studies have demonstrated a discordance of expression between primary breast cancer, synchronous axillary metastases, and metastatic sites. The aim of this article is to review studies on discordance of expression of these predictive parameters to better understand the importance of a reassessment of biomolecular status to modify treatment strategies. We performed a literature review to identify studies that assessed ER, PR, and HER2 discordance between primary breast cancer, synchronous axillary lymph node metastasis, and other metastatic sites. We reviewed these data related to (1) relevance of discordance rates in clinical practice and (2) therapeutic consequences of discordance rate. Results were analyzed qualitatively. Changes in ER and particularly in PR are observed in locoregional and in distant metastases reaching a rate of 10% to 30% for ER and 20% to 50% for PR. The loss of PR is more frequent than ER loss. High HER2 concordance between primary tumors and axillary lymph node or distant metastases has been demonstrated in many studies; in the discordant cases, it is more frequent to have HER2-positive metastases with negative primary tumors than the opposite. A reassessment of biomolecular status in residual tumors after neoadjuvant treatment or in metastatic sites is advisable, whenever it is possible, to correct/modify the treatment schedule and to estimate the actual prognosis.
Predictive markers in primary breast cancer compared with lymph node and bloodspread metastases
International journal of physiology, pathophysiology and pharmacology, 2009
High levels of HER2 expression identify those patients who might benefit from treatments that target HER2. Among women with metastatic breast cancer, the predictive markers may be different from the primary tumor. We compared predictive markers: Estrogen Receptor (ER), Progesterone Receptor (PR) and HER2 of primary breast carcinomas with those of lymph node (LN) and blood spread metastases (BM). ER, PR and HER2 status were compared between the primary breast tumor and the LN metastasis and blood spread metastasis. ER, PR and HER2 were performed on primary tumor core biopsies and available FNA cell blocks and on metastatic lesions using FDA approved antibodies and HercepTest (Dako). ER and PR were positive when >/=10%. Her2 was positive (amplified/expressed) when 3+ >30% by immunostain or >2.2 by FISH. Sixty four metastatic breast cancer patients were included in this analysis. Forty-eight patients had LN metastases (35 [73 %] diagnosed by FNA) and twenty seven patients had ...
Significance of Axillary Lymph Node Metastasis in Primary Breast Cancer
Journal of Clinical Oncology
PURPOSE: Axillary lymph node status is the single most important prognostic variable in the management of patients with primary breast cancer. Yet, it is not known whether metastasis to the axillary nodes is simply a time-dependent variable or also a marker for a more aggressive tumor phenotype. The purpose of this study was to determine whether nodal status at initial diagnosis predicts outcome after relapse and therefore also serves as a marker of breast cancer phenotype. PATIENTS AND METHODS: Survival experience after first relapse in 1,696 primary breast cancer cases was analyzed using Cox proportional hazards regression. The following explanatory variables and their first-order interactions were considered: number of axillary lymph nodes involved (zero v one to three v four or more), hormone receptor status (any estrogen receptor [ER] negativity v ER negativity/progesterone receptor positivity v other ER positivity), primary tumor size (< 2 cm v 2 to 5 cm v > 5 cm), site ...
The Oncologist, 2013
Background. The primary aim of this retrospective study was to investigate intraindividual correlation of estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status between primary breast cancer and metastatic breast cancer (mBC). Secondary aims included patients' characteristics, overall survival, feasibility of histopathological evaluation in the metastatic setting, and predictive factors associated with receptors status discordance. Methods. Patients with either biopsy of metastatic relapse or surgery of metastasis were identified. Demographics, tumor characteristics, treatment characteristics, and ER, PR, and HER2 statuses were retrospectively obtained in patients' reports. Receptors statuses were assessed by immunohistochemistry with a positivity cutoff of more than 10% for ER and PR. HER2 was considered as positive if overexpression was scored at 3+ in immunohistochemistry or if amplification ratio was >2 in fluorescent in situ hybridization. ...
Archives Breast Cancer, 2021
Background: Axillary lymph node metastasis (ALNM) is one of the important prognostic factors of breast cancer. The objective of this study was to assess the risk of ALNM in different molecular subtypes determined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (her2neu) of breast cancer. Methods: This retrospective study was conducted on patients who had undergone upfront breast conserving surgery (BCS) or modified radical mastectomy (MRM). Patients were classified as HR (hormone receptor) +/ her2neu-(ER or PR positive and her2neu negative), HR+/her2neu+ (ER or PR positive and her2neu positive), HR-/her2neu-(ER, PR and her2neu negative or triple negative or basal type), and HR-/her2neu+ (ER or PR negative and her2neu positive). The association between clinicopathological variables and ALNM was evaluated in logistic regression analyses. Results: In this study, 476 patients met the inclusion criteria, and had 67.2% ALNM at diagnosis. ALNM was statistically significantly correlated with age ≤ 40 years (p=0.026), tumor grade (p=0.007), pathological tumor size (P<0.001), estrogen receptor (P=0.045), molecular subtypes (P=0.021), LVI (P<0.001), and PNI (P<0.001). Post Hoc test revealed that HR-/her2neu+ subtypes of breast cancer had the highest and HR+/her2neu-had the lowest risk of ALNM. Conclusion: ALNM may be predicted by molecular subtypes of breast cancer. The risk of ALNM is less in TNBC although it is clinically more aggressive. These findings may play an important role in gauging the individualized axillary management in breast cancer.
Asian Pacific journal of cancer prevention : APJCP, 2015
BACKGROUND Prognostic biomarkers in breast cancer are routinely investigated in the primary tumors to guide further management. However, it is proposed that the expression may change during the disease progression, and may result in a different immune profile in the metastatic nodes. This work aimed to investigate the expression of breast prognostic biomarkers in primary tumors and in its axillary nodal metastasis, to estimate the possible discordant expression. MATERIALS AND METHODS 60 paired primary and axillary nodal metastasis samples were collected from patients with primary breast cancer with positive nodal deposits, diagnosed at the Maadi Military Hospital, Cairo, Egypt, during the year 2013. ER, PR and HER2 expression was assessed by immunohistochemistry in all samples RESULTS 48.3% of the included cases showed concordant results for both ER and PR receptors between the primary tumor and its nodal metastasis while 51.7% showed discordant results and the discordance level was...
Breast Cancer Research and Treatment, 2013
Molecular profiles of asynchronous breast cancer metastases are of clinical relevance to individual patients' treatment, whereas the role of profiles in synchronous lymph node metastases is not defined. The present study aimed to assess individual biomarkers and molecular subtypes according to the St Gallen classification in primary breast tumours, synchronous lymph node metastases and asynchronous relapses and relate the results to 10-year breast cancer mortality (BCM). Tissue microarrays were constructed from archived tissue blocks of primary tumours (N = 524), synchronous lymph node metastases (N = 147) and asynchronous relapses (N = 36). The samples were evaluated by two independent pathologists according to oestrogen receptor (ER), progesterone receptor (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and in situ hybridisation. The expression of biomarkers and molecular subtypes in the primary tumour was compared with that in the synchronous lymph node metastases and relapses, and related to 10-year BCM. Discordances were found between primary tumours and relapses (ER: p = 0.006, PR: p = 0.04, Ki67: p = 0.02, HER2: p = 0.02, St Gallen subtypes: p = 0.07) but not between primary tumours and metastatic lymph node. Prognostic information was gained by the molecular subtype classification in primary tumours and nodal metastases; triple negative subtype had the highest BCM compared with the luminal A subtype (primary tumours: HR 4.0; 95 % CI 2.0-8.2, p \ 0.001, lymph node metastases: HR 3.5; 95 % CI 1.3-9.7, p = 0.02). When a shift in subtype inherence between primary tumour and metastatic lymph node was identified, the prognosis seemed to follow the subtype of the lymph node. Molecular profiles are not stable throughout tumour progression in breast cancer. Prognostic information for individual patients appears to be available from the analysis of biomarker expression in synchronous metastatic lymph nodes. The study supports biomarker analysis also in asynchronous relapses.
Frontiers in Oncology, 2021
Breast cancer (BC) remains a significant healthcare challenge. Routinely, the treatment strategy is determined by immunohistochemistry (IHC)-based assessment of the key proteins such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. However, it is estimated that over 75% of deaths result from metastatic tumors, indicating a need to develop more accurate protocols for intertumoral heterogeneity assessment and their consequences on prognosis. Therefore, the aim of this preliminary study was the identification of the expression profiles of routinely used biomarkers (ER, PR, HER2, Ki-67) and additional relevant proteins [Bcl-2, cyclin D1, E-cadherin, Snail+Slug, gross cystic disease fluid protein 15 (GCDFP-15), programmed death receptor 1 (PD-L1), and phosphatase of regenerating liver 3 (PRL-3)] in breast primary tumors (PTs) and paired synchronous axillary lymph node (ALN) metastases. A total of 67 tissue samples met the inclusion criteria for the study. The expression status of biomarkers was assessed in PTs and ALN metastases using tissue microarrays followed by IHC. In 11 cases, the shift of intrinsic molecular BC subtype was noticed between PTs and paired ALN metastases. Moreover, a significant disproportion in E-cadherin presence (p = 0.0002) was noted in both foci, and the expression status of all proteins except for HER2 demonstrated considerable variance (k = 1, p < 0.0001). Importantly, in around 30% of cases, the ALN metastases demonstrated discordance, i.e., loss/gain of expression, compared to the PTs. Intertumoral synchronous heterogeneity in both foci (primary tumor and node metastasis) is an essential phenomenon affecting the clinical subtype and characteristics of BC. Furthermore, a greater understanding of this event could potentially improve therapeutic efficacy.
OncoTargets and Therapy, 2014
Background: Human epidermal growth factor receptor 2 (HER2) is considered to be a therapeutic and prognostic marker in the management of breast carcinoma (BC), although discordance rates between primary and metastatic or locally recurrent lesions have been reported. Methods: One hundred and forty-eight paraffin-embedded BC tissues from patients of mean age 59.27 (33-96) years and corresponding synchronous lymph node metastases were collected and retrospectively studied using immunohistochemistry and fluorescence in situ hybridization to evaluate HER2 status. Fleiss-Cohen weighted k statistics were used to assess the concordance rate between HER2 status of the primary BC and the synchronous metastatic lesions. Results: The overall concordance rate for HER2 was 95.28%. Eighty-nine cases were concordantly HER2-negative in primary BC and nodal metastases, and 52 cases were HER2-positive in both primary and metastatic tumors. Changes in HER2 status between primary BC and corresponding synchronous metastases were observed in seven (4.72%) cases. Three of the discordant cases were HER2-negative in the primary tumor and HER2-positive in the metastases, while four cases were HER2-positive in the primary BC and HER2-negative in the metastases. No significant correlations were identified between HER2 status and expression of hormone receptors, growth fraction (Ki-67), or other histopathological parameters (pT, pN, grade). Conclusion: Simultaneous determination of HER2 in BC and corresponding metastatic lymph nodes is not mandatory, but may strongly influence the therapeutic management. It was demonstrated that loss of HER2 amplification results in worse post-relapse survival and overall survival in BC patients and, on the other hand, a gain in HER2 expression in metastatic lymph nodes of BC may allow the possibility of a targeted treatment. Thus, our opinion is that significant prognostic information may be obtained by simultaneous assessment of HER2 status in both primary and synchronous metastatic BC.