bims-preonc 2024-11-24 papers

bims-preonc

Biomed News

on Precision oncology

Issue of 2024–11–24
thirteen papers selected by
Ankita Daiya, OneCell Diagnostics Inc.

Circulating Tumor DNA: A Pan-Cancer Biomarker in Solid Tumors with Prognostic and Predictive Value.
Bespoke ctDNA for longitudinal detection of molecular residual disease in high-risk melanoma patients.
ctDNA-guided adjuvant immunotherapy in colorectal cancer.
Integrating Machine Learning-Predicted Circulating Tumor Cells (CTCs) and circulating tumor DNA (ctDNA) in Metastatic Breast Cancer: a proof of principle study on endocrine resistance profiling.
Prognostic value of circulating tumor DNA in different cancer types detected by ultra-low-pass whole-genome sequencing. A systematic review and patient-level survival data meta-analysis.
Genomic profiling and expanded use of targeted anticancer drugs in solid cancers with exhausted evidence-based treatment options (PRECODE): study protocol of a prospective, non-randomized, cohort study.
Detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients.
Combined analysis of circulating tumor DNA and tumor tissue to overcome osimertinib resistance (OSIRIS); the second line osimertinib cohort.
Challenges in using tumor mutational burden as a post-treatment biomarker.
Dynamically monitoring minimal residual disease using circulating tumour cells to predict the recurrence of early-stage lung adenocarcinoma.
New Abdominal Mass After Surgery for Gastrointestinal Stromal Tumor: Desmoid-Type Fibromatosis Difficult to Distinguish from Mesenchymal Tumor - A Case Report.
Analysis of Concordance Between Next-Generation Sequencing Assessment of Microsatellite Instability and Immunohistochemistry-Mismatch Repair From Solid Tumors.
ER + HER2- early-stage breast cancer: association of HER2 expression, tumor characteristics, and outcomes.

Annu Rev Med. 2024 Nov 21.

Circulating Tumor DNA: A Pan-Cancer Biomarker in Solid Tumors with Prognostic and Predictive Value.

Nadia Hitchen, Adel Shahnam, Jeanne Tie.

Circulating tumor DNA (ctDNA), often referred to as a liquid biopsy, represents a promising biomarker in the management of both localized and advanced solid tumors. It has garnered significant attention due to its potential to inform prognosis and guide therapeutic decisions. The clinical utility of ctDNA spans early cancer detection, minimal residual disease identification, recurrence surveillance, treatment monitoring, and precision oncology treatment decision-making in the advanced setting. Unlike conventional radiological assessments, the short half-life of ctDNA allows for more timely insights into disease dynamics. Several technological approaches are available to measure ctDNA, including next-generation sequencing and droplet digital polymerase chain reaction, although their clinical accuracy depends on multiple biological and technical factors. This review evaluates current evidence surrounding ctDNA's utility in early and advanced solid tumors.

DOI: https://doi.org/10.1146/annurev-med-100223-090016
ESMO Open. 2024 Nov 15. pii: S2059-7029(24)01748-4. [Epub ahead of print]9(11): 103978

Bespoke ctDNA for longitudinal detection of molecular residual disease in high-risk melanoma patients.

S Genta, D V Araujo, K Hueniken, C Pipinikas, R Ventura, P Rojas, G Jones, M O Butler, S D Saibil, C Yu, A Easson, A Covelli, M B Sauder, C Fournier, Z Saeed Kamil, P Rogalla, D P Arteaga, O Vornicova, P Spiliopoulou, T P Muniz, L L Siu, A Spreafico.

   BACKGROUND: Locally advanced melanoma has a variable prognosis. Currently, there are no reliable criteria to stratify the risk of disease relapse and identify those patients who will benefit the most from adjuvant therapies. Circulating tumor DNA (ctDNA) is an emerging biomarker measuring the presence of tumor-derived DNA in blood.
PATIENTS AND METHODS: We used a bespoke, tumor-informed assay (RaDaR®, NeoGenomics, Inc.) to detect ctDNA in 276 prospectively collected plasma samples from 66 melanoma patients receiving definitive treatment. Collection time points included landmark (after completion of local treatment) and every 3-6 months for up to 2 years.
RESULTS: ctDNA was detected in at least one plasma sample in 19 patients (29%), including 6/65 (9%) at landmark (post-surgical sample). Positive ctDNA at landmark was associated with shorter overall survival (OS; median OS 22.7 months versus not reached, log-rank P value = 0.01) and a trend towards a shorter relapse-free survival (RFS; median RFS 15.7 months versus not reached, log-rank P value = 0.07). In 10 patients, ctDNA detection preceded disease relapse by a median of 128 days (range 8-406 days).
CONCLUSIONS: Our data indicate that ctDNA detection after surgery can identify patients with worse prognosis, and serial ctDNA measurements may enable earlier identification of disease recurrence.

Keywords:  biomarker; circulating tumor DNA; liquid biopsy; melanoma; molecular residual disease

DOI:  https://doi.org/10.1016/j.esmoop.2024.103978
Immunotherapy. 2024 Nov 17. 1-6

ctDNA-guided adjuvant immunotherapy in colorectal cancer.

Nicholas Burley, Yurhee Lee, Louisa Liu, Alexandra Gangi, Yosef Nasseri, Katelyn Atkins, Karen Zaghiyan, Zuri Murrell, Arsen Osipov, Andrew Hendifar, Megan Hitchins, Jun Gong.

  Circulating tumor DNA (ctDNA) represents a powerful measure of minimal residual disease (MRD) in colorectal cancer (CRC). Although immunotherapy has been widely established in metastatic CRC that is mismatch repair deficient or microsatellite instability-high (dMMR/MSI-H), its role in non-metastatic CRC is rapidly evolving. In resected, dMMR/MSI-H stage II CRC, adjuvant fluoropyrimidine has no benefit and is not recommended. There is growing evidence to suggest diminished benefit from neoadjuvant chemotherapy and chemoradiation in localized CRC that is dMMR/MSI-H. We present two cases of dMMR/MSI-H stage III CRC treated with definitive surgery wherein adjuvant oxaliplatin-based chemotherapy led to a failure to clear postoperative plasma ctDNA levels, prompting a change to immune checkpoint blockade with pembrolizumab and resultant ctDNA clearance. We illustrate that chemotherapy may achieve suboptimal disease control in localized colon cancer that is dMMR/MSI-H, while plasma ctDNA offers a window of opportunity to gauge the efficacy of oxaliplatin-based adjuvant chemotherapy to clear microscopic disease in resected, dMMR/MSI-H stage III colon cancer. These findings are important to contextualize given that relapse is inevitable with failure to clear MRD in the postoperative stage I-III CRC setting whereby chemotherapy remains the standard adjuvant therapy in resected, dMMR/MSI-H stage III colon cancer.

Keywords:  Colorectal cancer; adjuvant therapy; ctDNA; immunotherapy; microsatellite instability; mismatch repair deficient

DOI:  https://doi.org/10.1080/1750743X.2024.2430941
Cancer Lett. 2024 Nov 20. pii: S0304-3835(24)00720-1. [Epub ahead of print] 217325

Integrating Machine Learning-Predicted Circulating Tumor Cells (CTCs) and circulating tumor DNA (ctDNA) in Metastatic Breast Cancer: a proof of principle study on endocrine resistance profiling.

Lorenzo Gerratana, Andrew A Davis, Lorenzo Foffano, Carolina Reduzzi, Tania Rossi, Arielle Medford, Katherine Clifton, Ami N Shah, Leslie Bucheit, Marko Velimirovic, Sara Bandini, Charles S Dai, Firas Wehbe, William J Gradishar, Amir Behdad, Paola Ulivi, Cynthia X Ma, Fabio Puglisi, Aditya Bardia, Massimo Cristofanilli.

The study explored endocrine resistance by leveraging machine learning to establish the prognostic stratification of predicted Circulating tumor cells (CTCs), assessing its integration with circulating tumor DNA (ctDNA) features and contextually evaluate the potential of CTCs-based transcriptomics. 1,118 patients with a diagnosis of luminal-like Metastatic Breast Cancer (MBC) were characterized for ctDNA through NGS before treatment start, predicted CTCs were computed through a K nearest neighbor algorithm. Differences across subgroups were analyzed through chi square or Fisher's exact test according to sample size and corrected for False Discovery Rate. Differences in survival were tested by log-rank test and uni- and multivariable Cox regression. CTCs transcriptomics was performed through RNAseq after sorting with DEPArray NxT. Univariable and multivariable analysis adjusted for ctDNA alterations revealed a significant impact of CTCs predictive stratification on both progression-free survival (PFS) and overall survival (OS). Alterations in RTK and ER pathways were significantly correlated with predicted-Stage IVaggressive. The combined impact of CTCs stratification and RTK/ER pathway alterations influenced patient outcomes, with predicted-Stage IVaggressive having a negative impact on PFS regardless of the mutational status. The pilot exploratory CTCs transcriptomics analysis showed transcriptional changes linked to cell proliferation such as under expression of MALAT1 and overexpression of GREM1, GPR85 and OCM. Our data underline the potential of an integration between ctDNA and CTCs, both through quantification and transcriptomic analysis, for a deeper understanding of tumor biology and treatment response in HR-positive, HER2-negative MBC.

DOI: https://doi.org/10.1016/j.canlet.2024.217325
Carcinogenesis. 2024 Nov 16. pii: bgae073. [Epub ahead of print]

Prognostic value of circulating tumor DNA in different cancer types detected by ultra-low-pass whole-genome sequencing. A systematic review and patient-level survival data meta-analysis.

Miguel Sogbe, Daniel Aliseda, Paloma Sangro, Manuel de la Torre-Aláez, Bruno Sangro, Josepmaria Argemi.

  Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5× coverage) of plasma cell-free DNA (cfDNA) has emerged as a low-cost promising tool to assess circulating tumor DNA (ctDNA) fraction. This meta-analysis aims to summarize the current findings and comprehensively investigate the prognostic value of baseline ctDNA detected by ULP-WGS in solid tumors. A systematic review was carried out by searching PubMed/MEDLINE and Scopus databases to identify eligible studies conducted between January 2014 and January 2024. Inclusion criteria comprised studies with reported overall survival (OS) and progression-free survival (PFS) outcomes across therapy-naïve patients with different solid tumors. All patients underwent baseline ULP-WGS of plasma cfDNA and were categorized as ctDNA positive (tumor fraction ≥10%) or negative (tumor fraction <10%). A one-stage meta-analysis was performed using patient-level survival data reconstructed from published articles. A Cox proportional hazards model with shared frailty was used to assess the difference in survival between arms. A total of six studies, comprising 620 patients (367 negative ctDNA and 253 positive ctDNA), were included in the OS analysis, while five studies, involving 349 patients (212 negative ctDNA and 137 positive ctDNA), were included in the PFS analysis. The meta-analysis showed that patients with baseline positive ctDNA had a significantly higher risk of death (HR = 2.60, 95% CI: 2.01-3.36) and disease progression (HR = 2.28, 95% CI: 1.71-3.05) compared to those with negative ctDNA. The presence of a positive ctDNA at baseline is associated with increased risk of death and progression in patients with same stage cancer.

Keywords:  Circulating tumor DNA; Whole Genome Sequencing; overall survival; patient level meta-analysis; progression-free survival

DOI:  https://doi.org/10.1093/carcin/bgae073
BMC Med Genomics. 2024 Nov 21. 17(1): 274

Genomic profiling and expanded use of targeted anticancer drugs in solid cancers with exhausted evidence-based treatment options (PRECODE): study protocol of a prospective, non-randomized, cohort study.

Karin Holmskov Hansen, Maria Bibi Lyng, Annette Raskov Kodahl, Jon Thor Asmussen, Arman Arshad, Henrik Petersen, Lotte Krogh, Sidse Ehmsen, Thomas Kielsgaard Kristensen, Henrik J Ditzel.

   BACKGROUND: Genomic profiling of advanced solid cancer in patients with no further evidence based standard treatment options is a novel approach to identify potential experimental treatment options based on specific genomic alterations. Due to the expected short survival of these patients timely assessment of potential druggable targets is critical to minimize the risk of deterioration during the analysis. The primary objective of this prospective study is to evaluate the turnaround time for genomic profiling and the clinical investigational procedures. The secondary objectives are to investigate how often genomic alterations in tumor tissue gives rise to a matched treatment offer and evaluate the clinical outcome.
METHODS: The PRECODE study is a prospective, non-randomized, single-center cohort study conducted at Departments of Oncology and Pathology, Odense University Hospital, Denmark. Enrollment between March 1, 2019 and December 31, 2024. Eligibility criteria are age ≥ 18 years, written informed consent, advanced solid tumors, exhausted treatment options, ECOG performance status 0-2, adequate organ function and life expectancy ≥ 3 months. A core needle biopsy is analyzed by next generation sequencing using a pan-cancer comprehensive panel. Results are discussed weekly at institutional/local and national multidisciplinary tumor boards.
DISCUSSION: Strategies and methods for genomic profiling of advanced solid cancers differ. Rapid analysis and interpretation of sequencing data are key to avoiding delays in initiation potential experimental treatments, as these late-stage patients may quickly deteriorate. Although a highly optimized setup with fast-track clinical evaluation and genomic profiling has been established a subset will not be offered a targeted treatment due to deterioration. Local and national multidisciplinary teams have been established to optimize individualized treatment decisions. After genomic profiling a subset of patients will take part in clinical trials, which will constrain the reporting of overall survival or progression free survival.
TRIAL REGISTRATION: Danish Ethics Committee, Projekt-ID: S-2018014, date of approval: 27- FEB- 2019) Danish Data Protection Agency (Journal no: 18/58329, date of approval: 23-NOV-2018).
CLINICALTRIALS: gov Identifier: NCT05385081 (retrospectively registered).

Keywords:  Genomic profiling; Next generation sequencing; Solid cancers; Tumor agnostic therapy

DOI:  https://doi.org/10.1186/s12920-024-02033-z
Acta Neuropathol Commun. 2024 Nov 20. 12(1): 177

Detection of diagnostic somatic copy number alterations from cerebrospinal fluid cell-free DNA in brain tumor patients.

Svenja Klinsing, Julia Beck, Katharina J Weber, Kirsten Bornemann-Kolatzki, Mareike Dettki, Hans Urban, Bastian Roller, Kai U Chow, Henning Reis, Peter J Wild, Ekkehard Schuetz, Philipp Euskirchen, Joachim P Steinbach, Michael W Ronellenfitsch, Patrick N Harter, Pia S Zeiner.

  The gold standard for precise diagnostic classification of brain tumors requires tissue sampling, which carries relevant procedural risks. Brain biopsies often have limited sensitivity and fail to address tumor heterogeneity, because small tissue parts are being examined. This study aims to explore the detection and quantification of diagnostically relevant somatic copy number aberrations (SCNAs) in cell-free DNA (cfDNA) extracted from cerebrospinal fluid (CSF) in a real-world cohort of patients with defined brain tumor subtypes. A total of 33 CSF samples were collected from 30 patients for cfDNA extraction. Shallow whole-genome sequencing was conducted on CSF samples containing > 3ng of cfDNA and corresponding tissue DNA from nine patients. The sequencing cohort encompassed 26 samples of 23 patients, comprising 12 with confirmed CNS cancer as compared to 11 patients with either ambiguous CNS lesions (n = 5) or non-cancer CNS lesions (n = 6). After mapping and quality filtering SCNAs were called by depth-of-coverage analyses with a binning of 5.5 Mbp. SCNAs were exclusively identified in CSF cfDNA from brain tumor patients (10/12, 83%). In tumor patients, SCNAs were detectable in cfDNA from all patients with, but also in five of seven patients without tumor cells detected by CSF cytopathology. A substantial number of shared SCNAs were traceable between tissue and CSF in matched pair analyses. Additionally, some SCNAs unique to either CSF or tissue indicating spatial heterogeneity or tumor evolution. Also, diagnostically relevant genomic alterations as well as essential and desirable SCNAs as implemented in the current WHO classification of CNS tumors for certain primary brain tumor subtypes were traceable. In summary, this minimally invasive cfDNA-based LB approach employing shallow whole genome sequencing demonstrates potential for providing a molecularly informed diagnosis of CNS cancers, mapping tumor heterogeneity, tracking tumor evolution, and surveilling tumor patients. Further prospective trials are warranted.

Keywords:  Brain tumor; Cell-free DNA; Cerebrospinal fluid; Liquid biopsy; Next-generation sequencing

DOI:  https://doi.org/10.1186/s40478-024-01887-9
Lung Cancer. 2024 Sep 28. pii: S0169-5002(24)00506-3. [Epub ahead of print]198 107972

Combined analysis of circulating tumor DNA and tumor tissue to overcome osimertinib resistance (OSIRIS); the second line osimertinib cohort.

J W T van der Wel, M Jebbink, D van den Broek, L C Steinbusch, W S M E Theelen, G Ruiter, W Buikhuisen, J A Burgers, P Baas, M Vermeulen, V van der Noort, S M S Hashemi, L J W Bosch, K Monkhorst, E F Smit, M C Boelens, A J de Langen.

   INTRODUCTION: Osimertinib resistance inevitably occurs in EGFR mutated NSCLC. We aimed to identify resistance mechanisms (RM) using paired plasma and tumor samples in patients that progressed on 2nd/3rd line osimertinib.
METHODS: From 09 - 2019 to 02 - 2021, 51 patients were enrolled. Plasma sequencing used AVENIO Expanded Panel (research use only), tumor biopsies underwent DNA and RNA sequencing and histological evaluation. Sequencing was regarded successful when the driver mutation was confirmed with a variant allele frequency of ≥0.10%. Concordance between modalities was calculated for the driver mutation and RMs covered in both modalities. The Molecular Tumor Board formulated a treatment advice.
RESULTS: The driver mutation was detected in 42/51 plasma samples (82%) and in 50/51 tumor samples (98%), concordance rate was 80%. In 41/51 (80%) patients ≥1 RM was identified. Thirty-two RMs covered in both modalities were found in plasma (61.5%), 39 in tumor (75%), nineteen in both. RM concordance rate was 36.5%.
CONCLUSION: Combined analysis of plasma and tumor samples post 2nd/3rd line osimertinib identifies additional RMs regardless of the comparative approach used. Plasma sequencing identified 61.5% of RMs, tumor analysis identified 75%. Combined, they provide a superior overview of osimertinib resistance, enabling more tailored treatment options.

Keywords:  Biopsy; Drug resistance; EGFR; NSCLC; Osimertinib; ctDNA

DOI:  https://doi.org/10.1016/j.lungcan.2024.107972
ESMO Open. 2024 Nov 18. pii: S2059-7029(24)01769-1. [Epub ahead of print]9(12): 103999

Challenges in using tumor mutational burden as a post-treatment biomarker.

H Taban, Y Ergun.

DOI: https://doi.org/10.1016/j.esmoop.2024.103999
J Hematol Oncol. 2024 Nov 21. 17(1): 114

Dynamically monitoring minimal residual disease using circulating tumour cells to predict the recurrence of early-stage lung adenocarcinoma.

Qi Zhang, Xiaoli Zhang, Zhuoheng Lv, Huandong Huo, Ligong Yuan, Duo Wan, Peipei Xie, Shujun Cheng, Kaitai Zhang, Wen Zhang, Yousheng Mao.

  Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related deaths worldwide, with a 5-year survival rate of approximately 19%. With the advent of screening and diagnostic techniques such as low-dose spiral CT and liquid biopsy, the detection rate of early stage LUAD is increasing. Even in stage I LUAD, the cumulative 5-year recurrence rate after radical surgical resection is 17.9%. This may be related to the presence of microscopic residual disease (MRD), a potential source of recurrence and metastasis. Circulating tumour cells (CTCs) are key biomarkers in liquid biopsies, but the ability of dynamic CTC detection to monitor MRD and warn of recurrence in patients with early LUAD has not been validated. Here, we conducted a prospective study using the telomerase reverse transcriptase-based CTC detection method (TBCD) to evaluate perioperative and follow-up CTC levels for dynamic monitoring to evaluate its clinical efficacy in predicting postoperative recurrence in early-stage LUAD. By longitudinal dynamic monitoring of CTC, we accurately predicted recurrence within 2 years after surgery, with an AUC of 0.9786, demonstrating the clinical values of CTC in predicting recurrence. The median lead time from positive detection of CTC to radiological recurrence was 183 days, with the earliest CT recurrence predicted 354 days in advance. Taken together, our study demonstrates that longitudinal monitoring of CTC is effective in early warning of LUAD recurrence and provides valuable information on early detection and intervention strategies for the management of LUAD.

Keywords:  Circulating tumour cells; Lung adenocarcinoma; Microscopic residual disease; Recurrence

DOI:  https://doi.org/10.1186/s13045-024-01637-3
Int Med Case Rep J. 2024 ;17 965-969

New Abdominal Mass After Surgery for Gastrointestinal Stromal Tumor: Desmoid-Type Fibromatosis Difficult to Distinguish from Mesenchymal Tumor - A Case Report.

Xiaodong Wang, Chunhui Shou, Kankai Zhu, Weili Yang, Jiren Yu.

  A new lump in patients with a history of gastrointestinal stromal tumor (GIST) may indicate resistance to medication and recurrence. It is important to monitor for recurrence or metastasis after surgery for GIST, especially in cases of high-risk GIST, as it determines the subsequent treatment. However, it is difficult to differentiate between GIST and DF by imaging. Tissue biopsy and final diagnosis through pathological analysis are usually required. Here, we report 2 cases of primary diagnosis with high-risk GIST and suspected tumor recurrence during Imatinib treatment. The mass was not located where the previous GIST lesion had been. After the complete excision of the mass through laparoscopic surgery, the pathological findings revealed that it was not a recurrence of GIST, but a desmoid-type fibromatosis.

Keywords:  GIST; imatinib; lumpectomy; pathological diagnosis

DOI:  https://doi.org/10.2147/IMCRJ.S488459
JCO Precis Oncol. 2024 Oct;8 e2300648

Analysis of Concordance Between Next-Generation Sequencing Assessment of Microsatellite Instability and Immunohistochemistry-Mismatch Repair From Solid Tumors.

Rouba Ali-Fehmi, Harris Benjamin Krause, Robert T Morris, John J Wallbillich, Logan Corey, Sudeshna Bandyopadhyay, Mira Kheil, Leana Elbashir, Fadi Zaiem, M Ruhul Quddus, Evi Abada, Thomas Herzog, Anthony N Karnezis, Emmanuel S Antonarakis, Pashtoon Murtaza Kasi, Shuanzeng Wei, Jeffrey Swensen, Andrew Elliott, Joanne Xiu, Jaclyn Hechtman, David Spetzler, Jim Abraham, Milan Radovich, George Sledge, Matthew J Oberley, David Bryant.

PURPOSE: The new CAP guideline published in August 2022 recommends using immunohistochemistry (IHC) to test for mismatch repair defects in gastroesophageal (GE), small bowel (SB), or endometrial carcinoma (EC) cancers over next-generation sequencing assessment of microsatellite instability (NGS-MSI) for immune checkpoint inhibitor (ICI) therapy eligibility and states there is a preference to use IHC over NGS-MSI in colorectal carcinoma (CRC).
METHODS: We assessed the concordance of NGS-MSI and IHC-MMR from a very large cohort across the spectrum of solid tumors.
RESULTS: Of the over 190,000 samples with both NGS-MSI and IHC-MMR about 1,160 were initially flagged as discordant. Of those samples initially flagged as discordant, 50.9% remained discordant after being reviewed by an additional pathologist. This resulted in a final discordance rate of 0.31% (590/191,767). Among CRC, GE, SB and EC, 55.4% of mismatch repair proficient/MSI high (MMRp/MSI-H) tumors had at least one somatic pathogenic mutation in an MMR gene or POLE. Mismatch repair deficient/microsatellite stable (MMRd/MSS) tumors had a significantly lower rate of high tumor mutational burden than MMRp/MSI-H tumors. Across all solid tumors, MMRd/MSI-H tumors had significantly longer overall survival (OS; hazard ratio [HR], 1.47, P < .001) and post-ICI survival (HR, 1.82, P < .001) as compared with MMRp/MSS tumors. The OS for the MMRd/MSS group was slightly worse compared to the MMRp/MSI-H tumors, but this difference was not statistically significant (HR, 0.73, P = .058), with a similar pattern when looking at post-ICI survival (HR, 0.43, P = .155).
CONCLUSION: This study demonstrates that NGS-MSI is noninferior to IHC-MMR and can identify MSI-H tumors that IHC-MMR is unable to detect and conversely IHC-MMR can identify MMRd tumors that NGS-MSI misses.

DOI: https://doi.org/10.1200/PO.23.00648
Breast Cancer Res Treat. 2024 Nov 19.

ER + HER2- early-stage breast cancer: association of HER2 expression, tumor characteristics, and outcomes.

Hadar Goldvaser, Rinat Yerushalmi, Raz Mutai, Iryna Kuchuk, Margarita Toker, Shani Paluch-Shimon, Karen Drumea, Ella Evron, Amir Sonnenblick, Einav Gal-Yam, Gil Bar- Sela, Ayelet Shai, Rotem Merose, Avital Bareket-Samish, Lior Soussan-Gutman, Salomon M Stemmer.

   PURPOSE: To evaluate the association between the HER2 score as provided by the Oncotype DX Recurrence Score (RS) assay, tumor characteristics, and outcomes in early-stage, ER + HER2-negative breast cancer (BC).
METHODS: All women insured by the Clalit Health Services, with early-stage, ER + HER2-negative BC who underwent RS testing between 2008 and 2011 were included. Patient/tumor characteristics and Kaplan-Meier estimates for distant recurrence-free survival (DRFS) and overall survival (OS) were compared by HER2 category, based on the HER2 score provided by the RS assay: lower HER2 score group representing the lower third of the HER2 score range (≤ 8.5); higher HER2 score group representing the upper 2 thirds of the HER2 score range (8.6-10.7).
RESULTS: 1535 patients were included (948 node negative, 587 node positive); 330 (21.5%) were categorized as lower HER2 score and 1205 (78.5%) as higher HER2 score. Compared to the higher HER2 score group, the lower score group included a significantly higher proportion of patients with RS ≥ 26 in both node-negative (41% vs. 13.6%, P < .001) and node-positive diseases (36% vs. 19.4%, P < .001). Compared to the higher HER2 score group, the lower score group had significantly lower Oncotype ER and PR scores and lower proportion of lobular disease. Age and tumor size were comparable between the HER2 score groups. Within each RS category, DRFS and OS were not associated with the HER2 score.
CONCLUSION: Lower HER2 score was associated with higher RS results. Further study is desired to elucidate the role and significance of HER2 expression in early-stage, ER + HER2-negative.

Keywords:  HER2 mRNA; HER2-low; Oncotype; Recurrence score

DOI:  https://doi.org/10.1007/s10549-024-07549-7