A Canadian national guideline on the neoadjuvant treatment of invasive breast cancer, including patient assessment, systemic therapy, and local management principles

Abstract

Purpose The neoadjuvant treatment of breast cancer (NABC) is a rapidly changing area that benefits from guidelines integrating evidence with expert consensus to help direct practice. This can optimize patient outcomes by ensuring the appropriate use of evolving neoadjuvant principles. Methods An expert panel formulated evidence-based practice recommendations spanning the entire neoadjuvant breast cancer treatment journey. These were sent for practice-based consensus across Canada using the modified Delphi methodology, through a secure online survey. Final recommendations were graded using the GRADE criteria for guidelines. The evidence was reviewed over the course of guideline development to ensure recommendations remained aligned with current relevant data. Results Response rate to the online survey was almost 30%; representation was achieved from various medical specialties from both community and academic centres in various Canadian provinces. Two rounds of consensus were required to achieve 80% or higher consensus on 59 final statements. Five additional statements were added to reflect updated evidence but not sent for consensus. Conclusions Key highlights of this comprehensive Canadian guideline on NABC include the use of neoadjuvant therapy for early stage triple negative and HER2 positive breast cancer, with subsequent adjuvant treatments for patients with residual disease. The use of molecular signatures, other targeted adjuvant therapies, and optimal response-based local regional management remain actively evolving areas. Many statements had evolving or limited data but still achieved high consensus, demonstrating the utility of such a guideline in helping to unify practice while further evidence evolves in this important area of breast cancer management.

Evolving Role of Risk Tailored Therapy in Early Stage HER2-Positive Breast Cancer: A Canadian Perspective

“…From the first preoperative chemotherapy studies, the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 and B-27 trials, preoperative chemotherapy was shown to be equivalent to adjuvant chemotherapy [ 24 , 25 ]. Although initially reserved for patients with locally advanced or inflammatory breast cancer, neoadjuvant therapy (NAT) has become the standard for patients with clinical stage 2 disease, particularly those with HER2-positive and triple-negative breast cancer (TNBC) [ 26 , 27 ]. Here, NAT allows patients to be risk-stratified based on their response to upfront systemic therapy, where patients with residual disease at the time of surgery can benefit from additional systemic therapy due to their higher risk of recurrence and death.…”

“…From a Canadian perspective, the two TRAIN2 regimens with their nine cycles of chemotherapy are not used in the standard practice, but the ones studied in BCIRG-006 are commonly administered. Overall, guidelines now support a move away from the routine use of anthracyclines in HER2-positive EBC, which has also been commonly incorporated into the Canadian practice [ 27 , 43 ].…”

Neoadjuvant chemotherapy for triple negative and Her2+ve breast cancer: striving for the standard of care

“…Conversely, identi cation of residual disease after NAC for TN and HER2 breast cancers is also critical, as new adjuvant (post-operative) therapies (capecitabine and TDM-1, respectively) have emerged as important contributors to improving survival outcomes in eligible patients [8,9]. In summary, the contemporary use of NAC in breast cancer is complex and multipurpose, impacting potential surgical management, prognostication, and response-driven adjuvant treatments, especially in higher risk subtypes of breast cancer International evidence-based consensus guidelines now recommend that NAC be considered for most TN and HER2 breast cancers, speci cally those 2cm or larger (cT2) and/or with involved lymph nodes (N1-3) [10][11][12][13]. As such, early referral to medical oncology is an essential component of multimodality treatment planning [10].…”

“…In summary, the contemporary use of NAC in breast cancer is complex and multipurpose, impacting potential surgical management, prognostication, and response-driven adjuvant treatments, especially in higher risk subtypes of breast cancer International evidence-based consensus guidelines now recommend that NAC be considered for most TN and HER2 breast cancers, speci cally those 2cm or larger (cT2) and/or with involved lymph nodes (N1-3) [10][11][12][13]. As such, early referral to medical oncology is an essential component of multimodality treatment planning [10]. Despite these recommendations, we suspected there was a low use of NAC for patients with TN and HER2 breast cancers based on previous work in Canada and other countries, but that the overall rates of NAC use may be increasing over time given the newer evidence for post-NAC adjuvant therapies [14][15][16][17][18][19].…”

Access to Neoadjuvant Pertuzumab for HER2 Positive Breast Cancer in Canada: A Dilemma Increasingly Difficult to Explain

“…Based on this data, and the accepted importance of pCR internationally, funding guidelines from Europe (ESMO), the US (ASCO) and the UK (NICE) have all recommended neoadjuvant pertuzumab for patients with high-risk HER2 positive disease [ 15 , 16 , 17 , 18 ]. A recent Canadian Consensus Guideline also highlighted the importance of pertuzumab in NAT for HER2+ disease [ 19 ]. This guideline also noted the lack of public access which has now become entrenched due to the second negative, and final, funding decision from CADTH [ 5 ].…”