|
1
|
Salahi‐Niri A, Zarand P, Shojaeian F, Mansouri N, Yazdani O, Esbati R, Safavi‐Naini SAA, Jahanbin B. Proliferative Markers in Breast Cancer and Chemotherapy Implications: A Comprehensive Review. Health Sci Rep 2025; 8:e70626. [PMID: 40201702 PMCID: PMC11976874 DOI: 10.1002/hsr2.70626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 02/26/2025] [Accepted: 03/09/2025] [Indexed: 04/10/2025] Open
Abstract
Background and Aims Breast cancer is the most common cancer and a leading cause of cancer-related death among women globally. Determining which patients will benefit from chemotherapy remains challenging. Proliferative markers such as Ki-67, mini chromosome maintenance (MCM) proteins, and proliferating cell nuclear antigen (PCNA) offer valuable insights into tumor growth and treatment response. This review evaluates their clinical roles, with a focus on chemotherapy implications and emerging digital pathology techniques for marker quantification. Methods A narrative review was conducted by searching PubMed, Scopus, and Google Scholar for studies related to Ki-67, MCM, PCNA, breast cancer, and chemotherapy. Studies were thematically categorized into five areas. A bibliometric analysis of publications from 2000 to April 2023 was performed using the Bibliometrix R package and VOSviewer to assess research trends and thematic evolution. Results Eighty studies were included in the narrative synthesis. Ki-67 is the most commonly used marker, particularly useful in predicting response to neoadjuvant chemotherapy (NAC). MCM proteins show promise for identifying proliferative potential across tumor grades, while PCNA is associated with aggressive tumor features and poor prognosis. Post-chemotherapy changes in Ki-67 levels are linked to survival outcomes. Bibliometric analysis revealed a shift in research focus from basic mechanisms to clinical applications and digital quantification. Conclusion Proliferative markers play an essential role in breast cancer management. Ki-67 remains a key predictor of chemotherapy response, while MCM and PCNA offer complementary prognostic insights. Integration of these markers with digital pathology and AI-driven tools may enhance diagnostic accuracy and personalized treatment strategies. Standardization of assessment methods is crucial for broader clinical application.
Collapse
Affiliation(s)
- Aryan Salahi‐Niri
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research, Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Paniz Zarand
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research, Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Fatemeh Shojaeian
- Sidney Kimmel Comprehensive Cancer Research CenterJohns Hopkins School of MedicineBaltimoreMarylandUSA
| | - Negar Mansouri
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research, Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Omid Yazdani
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research, Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Romina Esbati
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research, Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Seyed Amir Ahmad Safavi‐Naini
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research, Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
- Division of Data‐Driven and Digital Medicine (D3M)Icahn School of Medicine at Mount SinaiNew YorkUSA
| | - Behnaz Jahanbin
- Cancer Institute, Pathology Department, Imam Khomeini Hospital ComplexTehran University of Medical SciencesTehranIran
| |
Collapse
|
|
2
|
Ohnstad HO, Blix ES, Akslen LA, Gilje B, Raj SX, Skjerven H, Borgen E, Janssen EAM, Mortensen E, Brekke MB, Falk RS, Schlichting E, Boge B, Songe-Møller S, Olsson P, Heie A, Mannsåker B, Vestlid MA, Kursetgjerde T, Gravdehaug B, Suhrke P, Sanchez E, Bublevic J, Røe OD, Geitvik GA, Halset EH, Rypdal MC, Langerød A, Lømo J, Garred Ø, Porojnicu A, Engebraaten O, Geisler J, Lyngra M, Hansen MH, Søiland H, Nakken T, Asphaug L, Kristensen V, Sørlie T, Nygård JF, Kiserud CE, Reinertsen KV, Russnes HG, Naume B. Impact of Prosigna test on adjuvant treatment decision in lymph node-negative early breast cancer-a prospective national multicentre study (EMIT-1). ESMO Open 2024; 9:103475. [PMID: 38838499 PMCID: PMC11190479 DOI: 10.1016/j.esmoop.2024.103475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 04/15/2024] [Accepted: 04/24/2024] [Indexed: 06/07/2024] Open
Abstract
BACKGROUND EMIT-1 is a national, observational, single-arm trial designed to assess the value of the Prosigna, Prediction Analysis of Microarray using the 50 gene classifier (PAM50)/Risk of Recurrence (ROR), test as a routine diagnostic tool, examining its impact on adjuvant treatment decisions, clinical outcomes, side-effects and cost-effectiveness. Here we present the impact on treatment decisions. PATIENTS AND METHODS Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative pT1-pT2 lymph node-negative early breast cancer (EBC) were included. The Prosigna test and standard histopathology assessments were carried out. Clinicians' treatment decisions were recorded before (pre-Prosigna) and after (post-Prosigna) the Prosigna test results were disclosed. RESULTS Of 2217 patients included, 2178 had conclusive Prosigna results. The pre-Prosigna treatment decisions were: no systemic treatment (NT) in 27% of patients, endocrine treatment alone (ET) in 38% and chemotherapy (CT) followed by ET (CT + ET) in 35%. Post-Prosigna treatment decisions were 25% NT, 51% ET and 24% CT + ET, respectively. Adjuvant treatment changed in 28% of patients, including 21% change in CT use. Among patients assigned to CT + ET pre-Prosigna, 45% were de-escalated to ET post-Prosigna. Of patients assigned to ET, 12% were escalated to CT + ET and 8% were de-escalated to NT; of those assigned to NT, 18% were escalated to ET/CT + ET. CT was more frequently recommended for patients aged ≤50 years. In the subgroup with pT1c-pT2 G2 and intermediate Ki67 (0.5-1.5× local laboratory median Ki67 score), the pre-Prosigna CT treatment decision varied widely across hospitals (3%-51%). Post-Prosigna, the variability of CT use was markedly reduced (8%-24%). The correlation between Ki67 and ROR score within this subgroup was poor (r = 0.25-0.39). The median ROR score increased by increasing histological grade, but the ROR score ranges were wide (for G1 0-79, G2 0-90, G3 16-94). CONCLUSION The Prosigna test result changed adjuvant treatment decisions in all EBC clinical risk groups, markedly decreased the CT use for patients categorized as higher clinical risk pre-Prosigna and reduced treatment decision discrepancies between hospitals.
Collapse
Affiliation(s)
- H O Ohnstad
- Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Oslo
| | - E S Blix
- Department of Oncology, University of North Norway, Tromsø; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø
| | - L A Akslen
- Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen; Department of Pathology Haukeland University Hospital, Bergen
| | - B Gilje
- Department of Haematology and Oncology, Stavanger University Hospital, Stavanger
| | - S X Raj
- Department of Oncology, St Olavs Hospital, Trondheim
| | - H Skjerven
- Department of Breast Surgery, Vestre Viken Hospital Trust, Drammen
| | - E Borgen
- Department of Pathology, Division of Laboratory Medicine, Oslo University Hospital, Oslo
| | - E A M Janssen
- Department of Pathology, Stavanger University Hospital, Stavanger; Department of Chemistry, Bioscience and Environmental Engineering, Stavanger University, Stavanger, Norway; Menzies Health Institute Queensland and Griffith University, Southport, Australia
| | - E Mortensen
- Department of Pathology, University of North Norway, Tromsø
| | - M B Brekke
- Department of Pathology, St Olavs Hospital, Trondheim
| | - R S Falk
- Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo
| | - E Schlichting
- Department of Oncology, Breast and Endocrine Surgery Unit, Division of Cancer Medicine, Oslo University Hospital, Oslo
| | - B Boge
- Department of Oncology, Hospital of Southern Norway, Kristiansand
| | | | - P Olsson
- Department of Breast Surgery, Innlandet Hospital Trust, Hamar
| | - A Heie
- Department of Breast Surgery, Haukeland University Hospital, Bergen
| | - B Mannsåker
- Department of Oncology, Nordland Hospital, Bodø
| | - M A Vestlid
- Department of Breast Surgery, Telemark Hospital Trust, Skien
| | - T Kursetgjerde
- Department of Oncology, Møre og Romsdal Hospital Trust, Ålesund
| | - B Gravdehaug
- Department of Breast Surgery, Akershus University Hospital, Lørenskog
| | - P Suhrke
- Department of Pathology, Vestfold Hospital Trust, Tønsberg
| | - E Sanchez
- Department of Oncology, Haugesund Hospital, Haugesund
| | - J Bublevic
- Department of Oncology, Førde Central Hospital, Førde
| | - O D Røe
- Department of Oncology, Levanger Hospital, Levanger
| | - G A Geitvik
- Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo
| | - E H Halset
- Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Oslo
| | - M C Rypdal
- Department of Pathology, Division of Laboratory Medicine, Oslo University Hospital, Oslo
| | - A Langerød
- Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo
| | - J Lømo
- Department of Pathology, Division of Laboratory Medicine, Oslo University Hospital, Oslo
| | - Ø Garred
- Department of Pathology, Division of Laboratory Medicine, Oslo University Hospital, Oslo
| | - A Porojnicu
- Department of Oncology, Vestre Viken Hospital Trust, Drammen
| | - O Engebraaten
- Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Oslo; Institute of Clinical Medicine, University of Oslo, Oslo
| | - J Geisler
- Institute of Clinical Medicine, University of Oslo, Oslo; Department of Oncology, Akershus University Hospital, Lørenskog
| | - M Lyngra
- Department of Pathology, Akershus University Hospital, Lørenskog
| | - M H Hansen
- Department of Breast Surgery, University of North Norway, Tromsø
| | - H Søiland
- Department of Research, Stavanger University Hospital, Stavanger; Department of Clinical Science, University of Bergen, Bergen
| | - T Nakken
- User representative, Oslo University Hospital, Oslo
| | - L Asphaug
- Clinical Trials Unit, Oslo University Hospital, Oslo; Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo
| | - V Kristensen
- Institute of Clinical Medicine, University of Oslo, Oslo
| | - T Sørlie
- Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo; Institute of Clinical Medicine, University of Oslo, Oslo
| | | | - C E Kiserud
- National Advisory Unit for Late Effects after Cancer Treatment, Oslo University Hospital, Oslo, Norway
| | - K V Reinertsen
- Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Oslo; National Advisory Unit for Late Effects after Cancer Treatment, Oslo University Hospital, Oslo, Norway
| | - H G Russnes
- Department of Pathology, Division of Laboratory Medicine, Oslo University Hospital, Oslo; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo; Institute of Clinical Medicine, University of Oslo, Oslo
| | - B Naume
- Department of Oncology, Division of Cancer Medicine, Oslo University Hospital, Oslo; Institute of Clinical Medicine, University of Oslo, Oslo.
| |
Collapse
|
|
3
|
Bocklage T, Cornea V, Hickey C, Miller J, Moss J, Chambers M, Bachert SE. Ki-67 Testing in Breast Cancer: Assessing Variability With Scoring Methods and Specimen Types and the Potential Subsequent Impact on Therapy Eligibility. Appl Immunohistochem Mol Morphol 2024; 32:119-124. [PMID: 38450704 PMCID: PMC11996037 DOI: 10.1097/pai.0000000000001188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 01/26/2024] [Indexed: 03/08/2024]
Abstract
Abemaciclib was originally FDA approved for patients with ER-positive/HER2-negative breast cancer with Ki-67 expression ≥20%. However, there were no guidelines provided on which specimen to test or which scoring method to use. We performed a comprehensive study evaluating the variation in Ki-67 expression in breast specimens from 50 consecutive patients who could have been eligible for abemaciclib therapy. Three pathologists with breast expertise each performed a blinded review with 3 different manual scoring methods [estimated (EST), unweighted (UNW), and weighted (WT) (WT recommended by the International Ki-67 in Breast Cancer Working Group)]. Quantitative image analysis (QIA) using the HALO platform was also performed. Three different specimen types [core needle biopsy (CNB) (n=63), resection (RES) (n=52), and axillary lymph node metastasis (ALN) (n=50)] were evaluated for each patient. The average Ki-67 for all specimens was 14.68% for EST, 14.46% for UNW, 14.15% for WT, and 11.15% for QIA. For the manual methods, the range between the lowest and highest Ki-67 for each specimen between the 3 pathologists was 8.44 for EST, 5.94 for WT, and 5.93 for UNW. The WT method limited interobserver variability with ICC1=0.959 (EST ICC1=0.922 and UNW=0.949). Using the aforementioned cutoff of Ki-67 ≥20% versus <20% to determine treatment eligibility, the averaged EST method yields 20 of 50 patients (40%) who would have been treatment-eligible, versus 15 (30%) for the UNW, 17 (34%) for the WT, and 12 (24%) for the QIA. There was no statistically significant difference in Ki-67 among the 3 specimen types. The average Ki-67 difference was 4.36 for CNB vs RES, 6.95 for CNB versus ALN, and RES versus ALN (P=0.93, 0.99, and 0.94, respectively). Our study concludes that further refinement in Ki-67 scoring is advisable to reduce clinically significant variation.
Collapse
Affiliation(s)
| | | | | | | | - Jessica Moss
- Departments ofInternal Medicine, Medical Oncology, University of Kentucky, Lexington, KY
| | - Mara Chambers
- Departments ofInternal Medicine, Medical Oncology, University of Kentucky, Lexington, KY
| | - S. Emily Bachert
- Department of Pathology, Brigham & Women’s Hospital and Harvard Medical School, Boston, MA
| |
Collapse
|
|
4
|
Curigliano G, Burstein HJ, Gnant M, Loibl S, Cameron D, Regan MM, Denkert C, Poortmans P, Weber WP, Thürlimann B. Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer 2023. Ann Oncol 2023; 34:970-986. [PMID: 37683978 DOI: 10.1016/j.annonc.2023.08.017] [Citation(s) in RCA: 79] [Impact Index Per Article: 39.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Accepted: 08/23/2023] [Indexed: 09/10/2023] Open
Abstract
The 18th St Gallen International Breast Cancer Conference held in March 2023, in Vienna, Austria, assessed significant new findings for local and systemic therapies for early breast cancer with a focus on the evaluation of multimodal treatment options. The emergence of more effective, innovative agents in both the preoperative (primary or neoadjuvant) and post-operative (adjuvant) settings has underscored the pivotal role of a multidisciplinary approach in treatment decision making, particularly when selecting systemic therapy for an individual patient. The importance of multidisciplinary discussions regarding the clinical benefits of interventions was explicitly emphasized by the consensus panel as an integral part of developing an optimal treatment plan with the 'right' degree of intensity and duration. The panelists focused on controversies surrounding the management of common ductal/no special type and lobular breast cancer histology, which account for the vast majority of breast tumors. The expert opinion of the panelists was based on interpretations of available data, as well as current practices in their professional environments, personal and socioeconomic factors affecting patients, and cognizant of varying reimbursement and accessibility constraints around the world. The panelists strongly advocated patient participation in well-designed clinical studies whenever feasible. With these considerations in mind, the St Gallen Consensus Conference aims to offer guidance to clinicians regarding appropriate treatments for early-stage breast cancer and assist in balancing the realistic trade-offs between treatment benefit and toxicity, enabling patients and clinicians to make well-informed choices through a shared decision-making process.
Collapse
Affiliation(s)
- G Curigliano
- Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
| | - H J Burstein
- Medical Oncology, Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston, USA.
| | - M Gnant
- Comprehensive Cancer Center, Medical University of Vienna, Vienna; Austrian Breast and Colorectal Cancer Study Group, Vienna, Austria
| | - S Loibl
- Center for Hematology and Oncology Bethanien, Frankfurt; German Breast Group, Neu-Isenburg, Germany
| | - D Cameron
- Edinburgh Cancer Research Centre, University of Edinburgh and NHS Lothian, Edinburgh, UK
| | - M M Regan
- International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - C Denkert
- Institut für Pathologie, Philipps-Universität Marburg und Universitätsklinikum Marburg, Marburg, Germany
| | - P Poortmans
- Department of Radiation Oncology, Iridium Netwerk, Wilrijk-Antwerp; University of Antwerp, Faculty of Medicine and Health Sciences, Wilrijk-Antwerp, Belgium
| | - W P Weber
- Department of Surgery, University Hospital Basel, Basel, Switzerland; Faculty of Medicine, University of Basel, Basel, Switzerland
| | - B Thürlimann
- SwissBreastCare, Bethanienspital, Zürich, Switzerland; SONK Foundation, St. Gallen, Switzerland
| |
Collapse
|
|
5
|
Li Y, Chen T, Du F, Wang H, Ma L. Concordance of RT-qPCR with immunohistochemistry and its beneficial role in breast cancer subtyping. Medicine (Baltimore) 2023; 102:e35272. [PMID: 37746948 PMCID: PMC10519502 DOI: 10.1097/md.0000000000035272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 07/12/2023] [Accepted: 08/28/2023] [Indexed: 09/26/2023] Open
Abstract
This study was to compare the concordance of transcription-quantitative polymerase chain reaction (RT-qPCR) with immunohistochemistry (IHC) in determining estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and tumor proliferation index (Ki67) status in breast cancer, and to assess the prognosis based on different subtypes. Totally 323 breast cancer patients were selected, including 216 in the training set and 107 in the validation set. Logistic regression models were constructed using 5-fold cross-validation with the mRNA expression of each biomarker as the predictor and the corresponding IHC expression level as the binary response variable. Receiver operating characteristic curve was used to determine the cutoff value. When the thresholds of ER, PR, HER2, and Ki67 were 0.764, 0.709, 0.161, and 0.554, there existed high concordance rates between IHC and RT-qPCR in ER (94.4%), PR (88.0%) and HER2 (89.4%) and a medium concordance rate in Ki67 (67.8%), which were further confirmed in the validation set (ER: 81.3%, PR: 78.3%, HER2: 80.4%, and Ki67: 69.1%). Based on the subtyping stratified by RT-qPCR, the 5-year recurrence-free interval rates of patients with luminal, HER2-enriched, and triple-negative subtypes were 88% (95% CI: 0.84-0.93), 82% (95% CI: 0.73-0.92) and 58% (95% CI: 0.42-0.80), respectively, which were similar to those assessed by IHC (88%, 78% and 47%). RT-qPCR may be a complementary method to IHC, which can not only provide additional useful information in clinic, but also show more advantages over IHC in determining certain subtypes of breast cancer.
Collapse
Affiliation(s)
- Yilun Li
- Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | | | - Furong Du
- State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics CO., Ltd., Nanjing, China
- Department of Medicine, Nanjing Simcere Medical Laboratory Science Co., Ltd., Nanjing, China
| | - Huimin Wang
- State Key Laboratory of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics CO., Ltd., Nanjing, China
- Department of Medicine, Nanjing Simcere Medical Laboratory Science Co., Ltd., Nanjing, China
| | - Li Ma
- Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| |
Collapse
|
|
6
|
Li W, Lu N, Chen C, Lu X. Identifying the optimal cutoff point of Ki-67 in breast cancer: a single-center experience. J Int Med Res 2023; 51:3000605231195468. [PMID: 37652458 PMCID: PMC10478558 DOI: 10.1177/03000605231195468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 08/01/2023] [Indexed: 09/02/2023] Open
Abstract
OBJECTIVE Ki-67 is associated with breast cancer subtypes, but the optimal cutoff point of Ki-67 has not been established in our center. We evaluated the cutoff point of Ki-67 in breast cancer and analyzed the associations among Ki-67, clinicopathological features, and prognosis. METHODS The clinicopathological data and prognostic information of patients with breast cancer treated in our center were retrospectively collected, and the optimal cutoff point of Ki-67 was determined by univariate and multivariate survival risk analyses. The cutoff point was used to group the patients, and the differences in the clinicopathological features and prognosis were analyzed between the two groups. RESULTS In total, 609 patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative primary breast cancer were enrolled. The mean Ki-67 value was 22.3% ± 15.4%, the median was 20%, and a cutoff point of 30% was an independent factor influencing recurrence-free survival. When 30% was used as the cutoff point, patients with a Ki-67 value of ≤30% had a better prognosis and lower tumor malignancy. CONCLUSION The optimal cutoff point of Ki-67 in breast cancer in our center is 30%.
Collapse
Affiliation(s)
- Wang Li
- School of Graduate, Bengbu Medical College, Bengbu, China
- Department of Breast Surgery, Affiliated Hospital of Jiaxing University (the First Hospital of Jiaxing), Jiaxing, China
| | - Ning Lu
- Department of Pathology, Affiliated Hospital of Jiaxing University (the First Hospital of Jiaxing), Jiaxing, China
| | - Caiping Chen
- Department of Breast Surgery, Affiliated Hospital of Jiaxing University (the First Hospital of Jiaxing), Jiaxing, China
| | - Xiang Lu
- School of Graduate, Bengbu Medical College, Bengbu, China
| |
Collapse
|
|
7
|
Licata L, Cosentini D, De Sanctis R, Iorfida M, Caremoli ER, Vingiani A, Simoncini EL, Pruneri G, Munzone E, Bianchini G, Zambelli A, Tondini C. Multigene signatures for early breast cancer in clinical practice: A report of the Lombardy genomic assays for breast cancer working group. Front Oncol 2023; 13:1081885. [PMID: 36950554 PMCID: PMC10025563 DOI: 10.3389/fonc.2023.1081885] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 02/15/2023] [Indexed: 03/08/2023] Open
Abstract
The increasing understanding of breast cancer biology has provided the basis for the development of multigene signatures aimed to improve the capability of clinicians to assess patients' prognostication and risk stratification. Incorporating these tools in clinical practice has profoundly impacted on the decision-making process for the adjuvant therapy of patients with ER+/HER2- early breast cancer and the results from prospective adjuvant trials have strengthened the clinical utility of multigene signatures in this setting. In July 2019, Lombardy was the first Region in Italy to reimburse genomic testing for patients with ER+/HER2- early breast cancer. Three years later, a group of investigators from six referral Cancer Centers in Lombardy convened to debate the use of multigene signatures in clinical practice and share their own experience with the tests after reimbursement. Here, we reviewed relevant data on the role of multigene signatures in tailoring adjuvant chemotherapy for patients with ER+/HER2- early breast cancer and discussed about the optimal use of these assays in current clinical practice. As the treatment landscape of early breast cancer evolves and novel questions about the possible additional applications of multigene assays arise, we also provide our viewpoint on the potential implementation of the assays in the evolving scenario ER+/HER2- early breast cancer treatment.
Collapse
Affiliation(s)
- Luca Licata
- Department of Medical Oncology, San Raffaele Hospital, Milan, Italy
- Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, Milan, Italy
- *Correspondence: Luca Licata,
| | - Deborah Cosentini
- Medical Oncology Unit, ASST Spedali Civili of Brescia, Brescia, Italy
| | - Rita De Sanctis
- Medical Oncology and Hematology Unit, IRCCS - Humanitas Research Hospital, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Monica Iorfida
- Division of Medical Senology, IEO, European Institute of Oncology, Milan, Italy
| | | | - Andrea Vingiani
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
- Faculty of Medicine and Surgery, University of Milan, Milan, Italy
| | | | - Giancarlo Pruneri
- Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
- Faculty of Medicine and Surgery, University of Milan, Milan, Italy
| | - Elisabetta Munzone
- Division of Medical Senology, IEO, European Institute of Oncology, Milan, Italy
| | - Giampaolo Bianchini
- Department of Medical Oncology, San Raffaele Hospital, Milan, Italy
- Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, Milan, Italy
| | - Alberto Zambelli
- Medical Oncology and Hematology Unit, IRCCS - Humanitas Research Hospital, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Carlo Tondini
- Oncology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
| |
Collapse
|
|
8
|
Burstein HJ, Curigliano G, Thürlimann B, Weber WP, Poortmans P, Regan MM, Senn HJ, Winer EP, Gnant M. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol 2021; 32:1216-1235. [PMID: 34242744 PMCID: PMC9906308 DOI: 10.1016/j.annonc.2021.06.023] [Citation(s) in RCA: 470] [Impact Index Per Article: 117.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/22/2021] [Accepted: 06/27/2021] [Indexed: 12/12/2022] Open
Abstract
The 17th St Gallen International Breast Cancer Consensus Conference in 2021 was held virtually, owing to the global COVID-19 pandemic. More than 3300 participants took part in this important bi-annual critical review of the 'state of the art' in the multidisciplinary care of early-stage breast cancer. Seventy-four expert panelists (see Appendix 1) from all continents discussed and commented on the previously elaborated consensus questions, as well as many key questions on early breast cancer diagnosis and treatment asked by the audience. The theme of this year's conference was 'Customizing local and systemic therapies.' A well-organized program of pre-recorded symposia, live panel discussions and real-time panel voting results drew a worldwide audience of thousands, reflecting the far-reaching impact of breast cancer on every continent. The interactive technology platform allowed, for the first time, audience members to ask direct questions to panelists, and to weigh in with their own vote on several key panel questions. A hallmark of this meeting was to focus on customized recommendations for treatment of early-stage breast cancer. There is increasing recognition that the care of a breast cancer patient depends on highly individualized clinical features, including the stage at presentation, the biological subset of breast cancer, the genetic factors that may underlie breast cancer risk, the genomic signatures that inform treatment recommendations, the extent of response before surgery in patients who receive neoadjuvant therapy, and patient preferences. This customized approach to treatment requires integration of clinical care between patients and radiology, pathology, genetics, and surgical, medical and radiation oncology providers. It also requires a dynamic response from clinicians as they encounter accumulating clinical information at the time of diagnosis and then serially with each step in the treatment plan and follow-up, reflecting patient experiences and treatment response.
Collapse
Affiliation(s)
- H J Burstein
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.
| | - G Curigliano
- European Institute of Oncology, University of Milan, Milan, Italy.
| | | | - W P Weber
- University of Basel, Basel, Switzerland
| | | | - M M Regan
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - H J Senn
- St. Gallen Oncology Conferences (Foundation SONK), St. Gallen, Switzerland
| | - E P Winer
- Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - M Gnant
- Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
9
|
ESR1, PGR, ERBB2, and MKi67 mRNA expression in postmenopausal women with hormone receptor-positive early breast cancer: results from ABCSG Trial 6. ESMO Open 2021; 6:100228. [PMID: 34371382 PMCID: PMC8358421 DOI: 10.1016/j.esmoop.2021.100228] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Revised: 06/28/2021] [Accepted: 07/07/2021] [Indexed: 11/20/2022] Open
Abstract
Background The purpose of this study was to assess the concordance of real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) detection of ESR1, PGR, ERBB2, and MKi67 messenger RNA (mRNA) in breast cancer tissues with central immunohistochemistry (IHC) in women treated within the prospective, randomized Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 6. Patients and methods We evaluated ESR1, PGR, ERBB2, and MKi67 mRNA expression by Xpert® Breast Cancer STRAT4 (enables cartridge-based RT-qPCR detection of mRNA in formalin-fixed paraffin-embedded tissues) and estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 protein expression by IHC [in situ hybridization (ISH) for HER2 IHC 2+] in 1115 surgical formalin-fixed paraffin-embedded specimens from patients of ABCSG Trial 6. Overall percent agreement (concordance), positive percent agreement (sensitivity), and negative percent agreement (specificity) between STRAT4 and IHC were determined for each marker. The primary objective of the study was concordance between STRAT4 mRNA measurements of ESR1, PGR, ERBB2, and MKi67 with central reference laboratory IHC (and ISH for HER2 IHC 2+ cases). Time to distant recurrence was analyzed by Cox models. Results All performance targets for ER, PR, and Ki67 were met. For HER2, the negative percent agreement target but not the positive percent agreement target was met. Concordance between STRAT4 and IHC was 98.9% for ER, 89.9% for PR, 98.2% for HER2, and 84.8% for Ki67 (excluding intermediate IHC 10%-20% staining). In univariable and multivariable Cox regression analyses, all four biomarkers tested by either STRAT4 RT-qPCR or by central IHC (ISH) had a comparable time to distant recurrence indicating similar prognostic value. Conclusions With the exception of HER2, we demonstrate high concordance between centrally assessed IHC and mRNA measurements of ER, PR, and Ki67 as well as a high correlation of the two methods with clinical outcome. Thus, mRNA-based assessment by STRAT4 is a promising new tool for diagnostic and therapeutic decisions in breast cancer.
Immunohistochemistry is the clinical gold standard for assessing ER, PR, HER2, and Ki67 expression in breast cancer. RNA expression assays provide an alternative approach to measuring these biomarkers. We demonstrate high concordance of STRAT4 mRNA detection in comparison to central immunohistochemistry. The STRAT4 assay is a promising new tool which can be carried out in <2 h and with lower costs. STRAT4 may be a cost-effective alternative to obtain standardized diagnostic results for breast cancer patients.
Collapse
|
|
10
|
Chang MC, Mrkonjic M. Review of the current state of digital image analysis in breast pathology. Breast J 2020; 26:1208-1212. [PMID: 32342590 DOI: 10.1111/tbj.13858] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 11/05/2019] [Indexed: 01/10/2023]
Abstract
Advances in digital image analysis have the potential to transform the practice of breast pathology. In the near future, a move to a digital workflow offers improvements in efficiency. Coupled with artificial intelligence (AI), digital pathology can assist pathologist interpretation, automate time-consuming tasks, and discover novel morphologic patterns. Opportunities for digital enhancements abound in breast pathology, from increasing reproducibility in grading and biomarker interpretation, to discovering features that correlate with patient outcome and treatment. Our objective is to review the most recent developments in digital pathology with clear impact to breast pathology practice. Although breast pathologists currently undertake limited adoption of digital methods, the field is rapidly evolving. Care is needed to validate emerging technologies for effective patient care.
Collapse
Affiliation(s)
- Martin C Chang
- University of Vermont Cancer Center, Burlington, VT, USA.,Department of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, VT, USA
| | - Miralem Mrkonjic
- Sinai Health System, Toronto, ON, Canada.,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| |
Collapse
|