Trends and outcomes in patients receiving neoadjuvant chemotherapy for breast cancer in Ontario: A population-based study.

person Matthew Castelo University of Toronto, Toronto, ON, Canada info_outline Matthew Castelo, Lena Nguyen, Amanda Roberts

Authors person Matthew Castelo University of Toronto, Toronto, ON, Canada info_outline Matthew Castelo, Lena Nguyen, Amanda Roberts Organizations University of Toronto, Toronto, ON, Canada, ICES Central, Toronto, ON, Canada, Sunnybrook Health Sciences Centre, Toronto, ON, Canada Abstract Disclosures Research Funding Canadian Cancer Society Challenge Grant, Sunnybrook AFP Association through Innovation Fund of the Alternative Funding Plan Background: Modern neoadjuvant chemotherapy (NAC) regimens in breast cancer offer higher rates of pathologic complete response, an ability to guide further adjuvant treatment, and may de-escalate surgery. However, the utilization of NAC has been heterogeneous in Ontario. This study aimed to describe trends in NAC use in Ontario, report survival outcomes, and explore factors associated with overall survival in these patients. Methods: This was a population-based cohort study using linked health administrative data in Ontario, Canada. From the Ontario Cancer Registry, we identified women ≥18 years who underwent neoadjuvant chemotherapy followed by surgery for operable (cT1N1, cT2-3N0, or cT2-3N1) breast cancer between 2012 and 2020. Patients were divided by receptor subtype (triple negative breast cancer [TNBC], ER+/HER2-, ER+/HER2+, ER-/HER2+) and characteristics were compared using standardized mean differences (SMDs). Five-year overall survival (OS) and breast cancer-specific survival (BCSS) were determined and reported for each subtype. Associations with OS and BCSS were calculated for patient and disease characteristics using univariate and multivariable Cox proportional hazards models and Fine and Gray models, respectively. Results: 3,804 women underwent NAC for cT1N1, cT2-3N0, or cT2-3N1 breast cancer in Ontario between 2012 and 2020. The largest contributing subtype was ER+/HER2- patients (39.3%) followed by those with HER2+ disease (ER-/HER2+ 13.8%, ER+/HER2+ 23.4%), and TNBC (23.5%). The median age was 50 years (IQR 42-59 years). Most patients were clinically node-positive (2,736; 71.9%), and underwent mastectomy (2,397; 63.0%). There was a significant increase in the number of patients receiving NAC in Ontario, from 217 in 2012 to 667 in 2019 ( p <0.001), with a greater increase among patients with TNBC or HER2+ disease. Compared to those with ER+/HER2- disease, TNBC patients were treated for smaller tumours (28.6% T3 vs. 39.8%; SMD = 0.24), and were more likely to be node-negative (39.1% N0 vs. 22.1%; SMD = 0.38). Similar trends for nodal status were found for patients with ER-/HER2+ (26.7% N0) and ER+/HER2+ cancer (27.9% N0). 5-year OS for the entire cohort was 88.1% (95% CI 87.1 – 89.2%). Survival was highest for ER+/HER2+ patients (94.2%, 95% CI 92.6 – 95.8%) and lowest for TNBC patients (80.1%, 95% CI 77.5 – 82.8%). Similar patterns were seen for BCSS. Factors associated with OS in a multivariable model included older age (increase in 5 years HR 1.1, 95% CI 1.07 – 1.14), N1 status (HR 1.99, 95% CI 1.61 – 2.47), larger tumour size (T3 HR 1.83, 95% CI 1.34 – 2.5), mastectomy (HR 1.45, 95% CI 1.2 – 1.75), and TNBC (versus ER+/HER2- HR 1.9, 95% CI 1.56 – 2.32). Conclusions: The use of NAC has increased in Ontario, particularly among TNBC and HER2+ patients. Women with TNBC have worse outcomes compared to those with ER+/HER2- disease, despite being treated for less advanced disease.