Part I: Consensus Statements and Expert Recommendations for HER2-Negative Early Breast Cancer in the Asia-Pacific Region: Diagnosis and Risk Assessment

Soo Chin Lee^1*Yeon Hee Park²Christian Singerr³Judith Balmaña⁴Rebecca Alexandra Dent⁵Veronique Kiak-Mien Tan⁵Nadia Ayu Mulansari⁶Mastura Md⁷Frances Victoria F Que⁸Yen-Shen Lu⁹Napa Parinyanitikul​¹⁰Cam Phuong Pham¹¹Aishah Taib¹²Sun-Young Kong¹³Yoland Antill¹⁴Hee Jeong Kim¹⁵

• ¹Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
• ²Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
• ³Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria
• ⁴Vall d'Hebron University Hospital, Barcelona, Catalonia, Spain
• ⁵National Cancer Centre Singapore, Singapore, Singapore
• ⁶Ciptomangunkusumo National General Hospital/Universitas Indonesia, Jakarta, Indonesia
• ⁷Pantai Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
• ⁸St Luke’s Medical Center, Quezon City and Global City, Manila, Philippines
• ⁹National Taiwan University Hospital, Taipei, Taiwan
• ¹⁰King Chulalongkorn Memorial Hospital, Bangkok, Thailand
• ¹¹bachmai hospital, Hanoi, Vietnam
• ¹²UM Cancer Research Institute, Kuala Lumpur, Malaysia
• ¹³National Cancer Center, Goyang-si, Republic of Korea
• ¹⁴Monash University, Melbourne, Victoria, Australia
• ¹⁵Asan Medical Center, College of Medicine, University of Ulsan, SONGPA-GU, Seoul, Republic of Korea

Introduction: In the Asia-Pacific region, there is increasing contention on the practical challenges involved in managing human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (eBC). This modified Delphi consensus explores gaps in genetic counselling (GC) and genetic testing (GT), and clinical risk assessment for HER2-negative eBC.Methods: An expert panel of 16 Asia-Pacific medical oncologists, geneticists, and breast cancer surgeons arrived at 33 statements. The level of statement consensus was considered high at ≥75%. A survey of 134 healthcare practitioners (HCPs) (breast cancer surgeons, geneticists, oncologists, molecular biologists/pathologists) explored the real-world practices in this region.Results: A consensus was reached for 88% of the statements (29/33) and aligned with international guidelines. Experts reached 100% consensus on offering pretest GC, obtaining consent before GT, considering first diagnosis of breast cancer (BC) as ideal time for GT, offering reflex testing for patients with likely/pathogenic germline BRCA variant, and considering patients with germline BRCA mutant early triple-negative breast cancer (TNBC) patients who do not achieve pathological complete response after neoadjuvant treatment to be at high risk of recurrence. Over 90% of experts supported germline GT for BRCA for TNBC patients irrespective of age at diagnosis or family history and prioritized tumour size and nodal status as prognostic factors for cancer recurrence. Experts reached 80%-90% consensus for using genetic risk assessment tools in low/under-resourced healthcare systems and considering patients with likely/pathogenic variants in BRCA for risk reduction surgery. Significant gaps existed between real-world practices and recommendations, particularly in offering pretest GC to patients with suspected hereditary BC and to blood relatives of patients with BRCA germline pathogenic variant BC, ideal time for GT, considering GT for early TNBC patients irrespective of age, offering post-test GC for positive results, utilizing risk assessment tools, and streamlining GC through non-geneticist HCPs.Conclusion: GT and pretest GC should be mainstreamed at the first diagnosis of BC. Risk assessment for disease recurrence should be performed at diagnosis and post-surgery for HER2-negative eBC patients. These recommendations would help standardize GC and improve GT access for clinical decisions.