Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer

Abstract

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with early breast cancer were updated and published online in 2023, and adapted, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with early breast cancer. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with breast cancer representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and KSMO. The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with early breast cancer across the different regions of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling, as well as the age and stage at presentation. Attention is drawn to the disparity in the drug approvals and reimbursement strategies, between the different regions of Asia.

Keywords: ESMO; Pan-Asian; early breast cancer; guidelines; treatment.

Figure 1

EBC treatment overview. Burgundy box: general categories or stratification; blue boxes: systemic anticancer therapy; turquoise boxes: combination of treatments or other systemic treatments; white boxes: other aspects of management. ALN, axillary lymph node; c, clinical; ChT, chemotherapy; CPG, Clinical Practice Guideline; DCIS, ductal carcinoma in situ; EBC, early breast cancer; ET, endocrine therapy; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; N, node; OFS, ovarian function suppression; RT, radiotherapy; T, tumour; TNBC, triple-negative breast cancer. ^aSee Figure 2 for management of ALN involvement and Figure 3, Figure 4, Figure 5 for systemic therapy according to breast cancer subtype. Recommendations for special situations (elderly patients, male breast cancer and DCIS) are described in the CPG text and in Table 1. ^bBisphosphonates are approved for bone metastases and osteoporosis and not for prevention of relapse. ^cIf ChT is indicated, it may be given in the neoadjuvant setting.

Figure 2

Management of ALN involvement in EBC. Burgundy box: general categories or stratification; orange boxes: surgery; blue box: systemic anticancer therapy; dark green boxes: radiotherapy; turquoise box: combination of treatments or other systemic treatments; white boxes: other aspects of management. ALN, axillary lymph node; ALND, axillary lymph node dissection; c, clinical; ChT, chemotherapy; CT, computed tomography; EBC, early breast cancer: i, imaging; ITC, isolated tumour cell; LN, lymph node; MDT, multidisciplinary team; MRI, magnetic resonance imaging; N, node; p, pathological; PET, positron emission tomography; PST, primary systemic therapy; RT, radiotherapy; SLN, sentinel lymph node; SLNB, sentinel lymph node biopsy; TAD, targeted axillary dissection; US, ultrasound. . ^aDiscuss in MDT whether number of LNs is important for systemic therapy allocation. ^bSee Figure 1 for an overview of primary surgery and neoadjuvant therapy indications. ^cImaging (axillary US is preferred but MRI and PET–CT may be used in specific cases where more detailed imaging is required). ^dRefers to ACOSOG-Z0011 trial eligibility criteria. ^eRefers to AMAROS trial eligibility criteria. OTOASOR trial criteria can also be considered. ^fInflammatory breast cancer and patients with N2 or N3 stage disease should receive ALND unless otherwise defined in a clinical trial. ^gIf ITCs are detected, consider axillary and locoregional RT as an alternative to ALND if an impact on adjuvant systemic treatments is not anticipated.

Figure 3

Management of HR-positive, HER2-negative EBC. Burgundy box: general categories or stratification; blue boxes: systemic anticancer therapy; turquoise boxes: combination of treatments or other systemic treatments; white boxes: other aspects of management; dashed line: optional recommendation. ChT, chemotherapy; CPS+EG, pretreatment clinical stage and post-treatment pathological stage, estrogen receptor and tumour grade; EBC, early breast cancer; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of molecular Targets; ESMO, European Society for Medical Oncology; ET, endocrine therapy; FDA, Food and Drug Administration; gBRCA1/2; germline BRCA1/2; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; m, mutation; MCBS, ESMO-Magnitude of Clinical Benefit Scale; N, node; pCR, pathological complete response; wt, wild type. ^aSee Figure 1 for the role of surgery in HR-positive, HER2-negative EBC. ^bStage N1 with primary tumour >5 cm, and/or grade 3 and/or Ki-67 ≥20%. ^cESMO-MCBS v1.1 was used to calculate scores for new therapies/indications approved by the EMA or FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms). ^dIf gBRCA1/2 testing is appropriate and feasible. ^ePatients with HR-positive tumours and non-pCR after neoadjuvant ChT require a CPS+EG score ≥3 to receive olaparib. ^fESCAT scores apply to alterations from genomic-driven analyses only. These scores have been defined by the guideline authors and assisted as needed by the ESMO Translational Research and Precision Medicine Working Group.

Figure 4

Management of HER2-positive EBC. Burgundy box: general categories or stratification; blue box: systemic anticancer therapy; turquoise box: combination of treatments or other systemic treatments; white boxes: other aspects of management. c, clinical; ChT, chemotherapy; EBC, early breast cancer; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of molecular Targets; ESMO, European Society for Molecular Oncology; ET, endocrine therapy; FDA, Food and Drug Administration; HER2, human epidermal growth factor receptor 2; HP, trastuzumab–pertuzumab: HR, hormone receptor; MCBS, ESMO-Magnitude of Clinical Benefit Scale; N, node; p, pathological; pCR, pathological complete response; RT, radiotherapy; T, tumour; T-DM1, trastuzumab emtansine. ^aTumours <2 cm can be considered for neoadjuvant therapy. ^bESMO-MCBS v1.1 was used to calculate scores for new therapies/indications approved by the EMA or FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms). ^cESCAT score I-A if HER2 gene amplification by FISH/chromogenic in situ hybdidisation. ESCAT scores apply to alterations from genomic-driven analyses only. These scores have been defined by the guideline authors and assisted as needed by the ESMO Translational Research and Precision Medicine Working Group.

Figure 5

Management of early TNBC. Burgundy box: general categories or stratification; blue box: systemic anticancer therapy; turquoise box: combination of treatments or other systemic treatments; white boxes: other aspects of management; dashed line: optional recommendation. AC, doxorubicin–cyclophosphamide; c, clinical; ChT, chemotherapy; CPG, Clinical Practice Guideline; EC, epirubicin–cyclophosphamide; EMA, European Medicines Agency; ER, estrogen receptor; ESCAT, ESMO Scale for Clinical Actionability of molecular Targets; ESMO, European Society for Molecular Oncology; ER; estrogen receptor; ET, endocrine therapy; FDA, Food and Drug Administration; gBRCA1/2, germline BRCA1/2; gBRCA1/2m, germline BRCA1/2; mutation; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; ICI, immune checkpoint inhibitor; m, mutation; MCBS, ESMO-Magnitude of Clinical Benefit Scale; N, node; p, pathological; pCR, pathological complete response; PgR, progesterone receptor; RT, radiotherapy; T, tumour; TNBC, triple-negative breast cancer; wt, wild type. ^aSee the ESMO CPG for risk reduction and screening of cancer in hereditary breast–ovarian cancer syndromes. ^bHER2– tumours with 1%-9% ER and/or PgR expression (ER-low/PgR-low) are a heterogeneous group, some of which behave biologically similarly to TNBC; therapeutic strategies should be adjusted to this specific situation since this might lead to a higher response to ChT and to reduced efficacy of ET, compared with classical HR+ breast cancer [II, B]. ^cThese evidence-based regimens without ICIs are sequential: anthracycline-based therapy followed by a taxane or taxane–carboplatin or vice versa. ^dAccording to OlympiA inclusion criteria. ^eESMO-MCBS v1.1 was used to calculate scores for new therapies/indications approved by the EMA or FDA. The scores have been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee (https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-evaluation-forms). ^fIndicated as adjuvant therapy for patients with gBRCA1/2m tumours and non-pCR or _pT2 or _pN1 if treated with initial surgery. ^gESCAT scores apply to alterations from genomic-driven analyses only. These scores have been defined by the guideline authors and assisted as needed by the ESMO Translational Research and Precision Medicine Working Group. ESCAT applicable if HER2 gene amplification by FISH. ^hOnly if pembrolizumab was given preoperatively. ⁱOnly for ICI-naïve patients.

Figure 6

Management of adjuvant endocrine therapy in HR-positive EBC. Burgundy box: general categories or stratification; blue boxes: systemic anticancer therapy; turquoise box: combination of treatments or other systemic treatments; white boxes: other aspects of management. AI, aromatase inhibitor; EBC, early breast cancer; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; OFS, ovarian function suppression. ^aSee Figure 1 for the role of surgery in HR-positive, HER2-negative EBC. ^bTamoxifen can be given for lower-risk tumours or if AIs are not tolerated [I, A].