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      Which Patients Need Chemotherapy? From Pathological Risk Factors to Gene Signatures and Evaluation of Endocrine Response

      review-article
      Breast Care
      S. Karger AG
      Early breast cancer, Prognosis, Chemotherapy, Gene expression signatures, Endocrine response

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          Abstract

          Background

          Chemotherapy, used either before or after surgery, has significantly improved survival in early breast cancer. Accurate risk assessment is essential to avoid both overtreatment and undertreatment. This review provides an overview of the evolution of chemotherapy as well as risk factors for tailored systemic therapies in early breast cancer – from pathologic risk factors to gene expression signatures to endocrine response assessment.

          Summary

          Chemotherapy has improved dramatically in recent decades from its beginnings with conventionally dosed cyclophosphamide plus methotexate plus 5-fluorouracil to dose-dense anthracycline- and taxane-containing regimens. Similarly, risk assessment has evolved starting from traditional pathologic risk factors such as tumor size, axillary nodal status, and grading. In recent decades, gene expression signatures have improved prognostic accuracy with a high level of evidence. In turn, these signatures can be further improved by incorporating the aforementioned pathologic factors. As an important step away from this static assessment, dynamic assessment of proliferation factor Ki-67 after short-term preoperative endocrine treatment has gained interest to improve risk assessment in early hormone receptor-positive breast cancer.

          Key Message

          This review highlights advances in chemotherapy and risk assessment in early breast cancer, from pathologic risk factors for recurrence to gene expression signatures and endocrine response assessment. These developments are leading to better risk stratification and thus better adaptation of therapies.

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          Most cited references42

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          Molecular portraits of human breast tumours.

          Human breast tumours are diverse in their natural history and in their responsiveness to treatments. Variation in transcriptional programs accounts for much of the biological diversity of human cells and tumours. In each cell, signal transduction and regulatory systems transduce information from the cell's identity to its environmental status, thereby controlling the level of expression of every gene in the genome. Here we have characterized variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. These patterns provided a distinctive molecular portrait of each tumour. Twenty of the tumours were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumours were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumour samples from the same individual were almost always more similar to each other than either was to any other sample. Sets of co-expressed genes were identified for which variation in messenger RNA levels could be related to specific features of physiological variation. The tumours could be classified into subtypes distinguished by pervasive differences in their gene expression patterns.
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            Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

            The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.
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              20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.

              The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment.
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                Author and article information

                Journal
                Breast Care (Basel)
                Breast Care (Basel)
                BRC
                BRC
                Breast Care
                S. Karger AG (Basel, Switzerland )
                1661-3791
                1661-3805
                25 April 2023
                December 2023
                : 18
                : 6
                : 422-427
                Affiliations
                [1]Department of Obstetrics and Gynecology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
                Author notes
                Correspondence to: Marcus Schmidt, marcus.schmidt@ 123456unimedizin-mainz.de
                Article
                530818
                10.1159/000530818
                10730099
                38125921
                280c81b4-a362-4581-8fb0-5715bda63c89
                © 2023 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY) ( http://www.karger.com/Services/OpenAccessLicense). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher.

                History
                : 12 March 2023
                : 20 April 2023
                : 2023
                Page count
                Tables: 2, References: 42, Pages: 6
                Funding
                None.
                Categories
                Review Article

                early breast cancer,prognosis,chemotherapy,gene expression signatures,endocrine response

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