Survey of clinicians on the use of adjuvant therapy for premenopausal women with breast cancer

PLOS ONE RESEARCH ARTICLE Survey of clinicians on the use of adjuvant therapy for premenopausal women with breast cancer Young-Won Lee ID1, Sei-Hyun Ahn2☯, Young-jin Lee1☯, Tae-Kyung Yoo1☯, Jisun Kim1☯, Il Yong Chung1☯, Hee Jeong Kim1☯, Beom Seok Ko1☯, Jong Won Lee1☯, Byung Ho Son1☯, Sae Byul Lee ID1* 1 Division of Breast Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea, 2 Department of Surgery, Ewha Womans University College of Medicine, Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 ☯ These authors contributed equally to this work. * Abstract Purpose OPEN ACCESS Citation: Lee Y-W, Ahn S-H, Lee Y-j, Yoo T-K, Kim J, Chung IY, et al. (2023) Survey of clinicians on the use of adjuvant therapy for premenopausal women with breast cancer. PLoS ONE 18(8): e0290174. https://doi.org/10.1371/journal. pone.0290174 Editor: Daniele Ugo Tari, Local Health Authority Caserta: Azienda Sanitaria Locale Caserta, ITALY Received: March 29, 2023 Accepted: August 3, 2023 Considering prognostic and anatomic stages in early-stage premenopausal patients with breast cancer, clinicians decide on performing the multigene assay, adjuvant chemotherapy, or ovarian function suppression (OFS). This decision is also based on genetic information related to hormone receptor-positive and human epidermal growth factor receptor 2 negative results. We aimed to determine the tendency to use adjuvant therapy in clinical practice. Methods From April to May 2022, clinicians of the Korean Breast Cancer Society responded to a web-based survey. The survey included 62 multiple-choice questions mainly on decisionmaking under different pathologic conditions. Published: August 17, 2023 Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting information files. Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Results Among 92 responding clinicians, 91.3% were breast surgeons. For 35-year-old patients (pT2N0 and Ki-67 50% profile), 96.8% of clinicians selected chemotherapy, whereas 50.7% selected chemotherapy for patients with pT1N0, Ki-67 10%, and without Oncotype Dx (ODX). Only 35.6% selected chemotherapy for 47-year-old patients with the same profiles, while 84.3% and 49.1% chose chemotherapy with ODX recurrence score 21 and 16, respectively. More clinicians selected tamoxifen (TMX) plus OFS than aromatase inhibitor (AI) plus OFS for 5 years of endocrine therapy in patients with adjuvant chemotherapy regardless of genomic and clinical risks. However, for the same patients without adjuvant chemotherapy, more clinicians selected AI plus OFS. A longer duration of additional OFS and TMX was selected in patients with high clinical and genomic risks, and the duration of OFS was relatively shorter in older patients. PLOS ONE | https://doi.org/10.1371/journal.pone.0290174 August 17, 2023 1 / 13 PLOS ONE Clinicians’ survey on adjuvant therapy for premenopausal breast cancer patients Conclusion The decision regarding adjuvant therapy should be made considering clinical and genomic risks and age, and clinicians should consult with patients about adverse effects and compliance. Introduction At the turn of the century, a ground-breaking study described the gene expression-based subgroup classification of breast cancer [1]. Furthermore, a series of studies provided clarity that breast cancer can be categorized into at least five subtypes based on gene expression patterns. A tendency of individualized decisions for each group has been observed among clinicians for the treatment. Considering the changes in data presented in the last 40 years at St. Gallen Consensus Conferences, the main breast cancer treatment has transformed from surgical methods (based on anatomical information) to medical therapies (based on biological information) [2] This implied that the biological information of patients with breast cancer is now recognized as the primary concern. In the 8th edition of the American Joint Committee on Cancer (AJCC) in 2017, in addition to the anatomic stage, the importance of biology was included in the prognostic stage. Biological markers, such as histological grade, estrogen-receptor (ER), progesterone-receptor (PR), human epidermal growth factor receptor 2 (HER2), and nuclear protein Ki-67 status, have been used for tumor staging. Moreover, the expression levels of genes, such as hormone receptor (HR) -positive, are included [3]. According to the National Comprehensive Cancer Network (NCCN) guidelines version 3 in 2022, clinicians can decide to perform adjuvant chemotherapy or include ovarian function suppression (OFS) using the results of Oncotype Dx (ODX) assay for premenopausal patients with pathological node 0 (pN0) and tumor size >0.5 cm [4]. Clinicians can consider a similar approach even in pN positive (pN1) patients, while deciding the optimal treatment for the extension of the endocrine therapy for the following 5 years. Hence, each clinician needs to decide on treatment modalities, such as performing the multigene assay and adjuvant chemotherapy or adding OFS, considering adverse effects and risk of recurrence on switching or extending adjuvant endocrine therapy. While current guidelines offer predefined options, yet the inclusion of the term "consider" acknowledges the existence of certain conditions where making definitive decisions becomes challenging. Due to the complexities associated with adjuvant endocrine therapy in recent times, clinicians can select various other available options by evaluating the clinical and genomic risks and potential benefits of each treatment. The Adjuvant! Online tool suggests the clinical risks using the information of histologic grade, the status of nodal metastases, and tumor size, and the genomic risk information can be obtained from prior studies, such as TAILORx, MINDACT, and RxPONDER trials [5–7]. Previous studies have demonstrated no benefit of additional adjuvant chemotherapy in postmenopausal women or patients over 50 years of age, whereas a 5–6% benefit was observed in premenopausal women or patients below 50 years of age. However, whether a combination of OFS with an aromatase inhibitor (AI) can be used in place of adjuvant chemotherapy (with ODX recurrence score [RS] of 16 or 21, to 25) in premenopausal women or patients with a low risk in the MammaPrint (MMP) test remains unclear. Therefore, in this study, a survey was conducted to obtain the opinion of clinicians regarding the progress of decision-making on adjuvant t (...truncated)