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      Response Predictivity to Neoadjuvant Therapies in Breast Cancer: A Qualitative Analysis of Background Parenchymal Enhancement in DCE-MRI

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          Abstract

          Background: For assessing the predictability of oncology neoadjuvant therapy results, the background parenchymal enhancement (BPE) parameter in breast magnetic resonance imaging (MRI) has acquired increased interest. This work aims to qualitatively evaluate the BPE parameter as a potential predictive marker for neoadjuvant therapy. Method: Three radiologists examined, in triple-blind modality, the MRIs of 80 patients performed before the start of chemotherapy, after three months from the start of treatment, and after surgery. They identified the portion of fibroglandular tissue (FGT) and BPE of the contralateral breast to the tumor in the basal control pre-treatment (baseline). Results: We observed a reduction of BPE classes in serial MRI checks performed during neoadjuvant therapy, as compared to baseline pre-treatment conditions, in 61.3% of patients in the intermediate step, and in 86.7% of patients in the final step. BPE reduction was significantly associated with sequential anthracyclines/taxane administration in the first cycle of neoadjuvant therapy compared to anti-HER2 containing therapies. The therapy response was also significantly related to tumor size. There were no associations with menopausal status, fibroglandular tissue (FGT) amount, age, BPE baseline, BPE in intermediate, and in the final MRI step. Conclusions: The measured variability of this parameter during therapy could predict therapy effectiveness in early stages, improving decision-making in the perspective of personalized medicine. Our preliminary results suggest that BPE may represent a predictive factor in response to neoadjuvant therapy in breast cancer, warranting future investigations in conjunction with radiomics.

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          New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

          Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.
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            Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update

            Purpose To update key recommendations of the American Society of Clinical Oncology/College of American Pathologists human epidermal growth factor receptor 2 (HER2) testing in breast cancer guideline. Methods Based on the signals approach, an Expert Panel reviewed published literature and research survey results on the observed frequency of less common in situ hybridization (ISH) patterns to update the recommendations. Recommendations Two recommendations addressed via correspondence in 2015 are included. First, immunohistochemistry (IHC) 2+ is defined as invasive breast cancer with weak to moderate complete membrane staining observed in > 10% of tumor cells. Second, if the initial HER2 test result in a core needle biopsy specimen of a primary breast cancer is negative, a new HER2 test may (not "must") be ordered on the excision specimen based on specific clinical criteria. The HER2 testing algorithm for breast cancer is updated to address the recommended work-up for less common clinical scenarios (approximately 5% of cases) observed when using a dual-probe ISH assay. These scenarios are described as ISH group 2 ( HER2/chromosome enumeration probe 17 [CEP17] ratio ≥ 2.0; average HER2 copy number < 4.0 signals per cell), ISH group 3 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 6.0 signals per cell), and ISH group 4 ( HER2/CEP17 ratio < 2.0; average HER2 copy number ≥ 4.0 and < 6.0 signals per cell). The diagnostic approach includes more rigorous interpretation criteria for ISH and requires concomitant IHC review for dual-probe ISH groups 2 to 4 to arrive at the most accurate HER2 status designation (positive or negative) based on combined interpretation of the ISH and IHC assays. The Expert Panel recommends that laboratories using single-probe ISH assays include concomitant IHC review as part of the interpretation of all single-probe ISH assay results. Find additional information at www.asco.org/breast-cancer-guidelines .
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              Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013

              The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy. It refined its earlier approach to the classification and management of luminal disease in the absence of amplification or overexpression of the Human Epidermal growth factor Receptor 2 (HER2) oncogene, while retaining essentially unchanged recommendations for the systemic adjuvant therapy of HER2-positive and ‘triple-negative’ disease. The Panel again accepted that conventional clinico-pathological factors provided a surrogate subtype classification, while noting that in those areas of the world where multi-gene molecular assays are readily available many clinicians prefer to base chemotherapy decisions for patients with luminal disease on these genomic results rather than the surrogate subtype definitions. Several multi-gene molecular assays were recognized as providing accurate and reproducible prognostic information, and in some cases prediction of response to chemotherapy. Cost and availability preclude their application in many environments at the present time. Broad treatment recommendations are presented. Such recommendations do not imply that each Panel member agrees: indeed, among more than 100 questions, only one (trastuzumab duration) commanded 100% agreement. The various recommendations in fact carried differing degrees of support, as reflected in the nuanced wording of the text below and in the votes recorded in supplementary Appendix S1, available at Annals of Oncology online. Detailed decisions on treatment will as always involve clinical consideration of disease extent, host factors, patient preferences and social and economic constraints.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                J Pers Med
                J Pers Med
                jpm
                Journal of Personalized Medicine
                MDPI
                2075-4426
                01 April 2021
                April 2021
                : 11
                : 4
                : 256
                Affiliations
                [1 ]Struttura Semplice Dipartimentale di Radiodiagnostica Senologica, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; d.laforgia@ 123456oncologico.bari.it
                [2 ]Unità Operativa Complessa di Radiologia–Senologia–P.O. San Paolo–ASL Bari, Via Caposcardicchio, 70123 Bari, Italy; angela.vestito@ 123456asl.bari.it (A.V.); m.lasciarrea@ 123456gmail.com (M.L.)
                [3 ]Struttura Semplice Dipartimentale di Fisica Sanitaria, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; mariac.comes@ 123456libero.it (M.C.C.); a.fanizzi@ 123456oncologico.bari.it (A.F.)
                [4 ]Struttura Semplice Dipartimentale di Chirurgia Senologica, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; sergiodiotaiuti@ 123456gmail.com
                [5 ]Unità Operativa Complessa di Oncologia Medica, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; francescogiotta@ 123456libero.it (F.G.); a.latorre@ 123456oncologico.bari.it (A.L.); vitolorusso@ 123456me.com (V.L.)
                [6 ]Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; gennaropalmiotti@ 123456hotmail.it (G.P.); l.rinaldi@ 123456oncologico.bari.it (L.R.)
                [7 ]Dipartimento di Chimica, Università degli Studi di Bari “Aldo Moro”, Via E. Orabona 4, 70125 Bari, Italy; rahel.signorile@ 123456gmail.com
                [8 ]Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, 81100 Naples, Italy; ggatta@ 123456sirm.com
                Author notes
                [* ]Correspondence: r.massafra@ 123456oncologico.bari.it ; Tel.: +39-080-5555111
                Author information
                https://orcid.org/0000-0002-3902-4523
                https://orcid.org/0000-0003-2903-4389
                https://orcid.org/0000-0003-0874-8294
                https://orcid.org/0000-0002-2729-9896
                Article
                jpm-11-00256
                10.3390/jpm11040256
                8065517
                1a39bdb1-3239-41e9-ae05-0c5acc855935
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 04 February 2021
                : 23 March 2021
                Categories
                Article

                background parenchymal enhancement,breast mri,breast cancer,neoadjuvant chemotherapy,fibro glandular tissue

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