Clinicopathological characteristics and outcomes of patients with HER2-low breast cancer: 6-year ambispective cohort study from India.
Authors: Melemadathil Karthika Remeshchandra , Pai Ananth , Udupa Karthik , Mailankody Sharada , Sekaran Mangaiyarkarasi , Pamidi Kavya Siva Keerthana 
Published: June 2024

e23260 Background: Patients with low HER2-positive breast cancers are treated like those who are entirely HER2-negative. The DESTINY-Breast trials have proven Trastuzumab deruxtecan's benefit in the low HER2 subset. In Literature, limited data is available regarding the characteristics and outcomes of patients with low HER2 positivity from India. This study is done to address this research gap. Methods: This was an ambispective cohort study where we analysed the patients with carcinoma breast who were treated at our institute in the last 6 years. Out of 1845 patients, 243 were identified to have low HER2 expression. Patients were classified as Low HER2 positive if they had HER2 1+ or 2+ by IHC and negative by FISH. The clinical and pathological characteristics, progression-free survival (PFS) and overall survival (OS) of HER2 low subset, Estrogen Receptor (ER) positive and negative HER2 low cohorts and Metastatic (MBC) HER2 low patients were analysed separately. Results: A total of 243 patients were analysed. Of which 157 had HER2 2+ and 86 had 1+ expression. 240 were females. 79.8% were ER+ and 20.2% were ER negative among the total patients. 76.7% and 81.5% were ER+ in HER2 1+ and 2+ cohorts respectively. 78.2% were non-metastatic and 21.8% had MBC. 34.6% were treated with Neoadjuvant chemotherapy (NACT) and 42.4% with adjuvant chemotherapy (CT). 4.5% of patients treated with NACT attained PCR. 53.1% had T2, 16.8% had T4 disease. Most of the patients had N0 (35.4%) and N1(37%) disease. The OS of all low HER2+ patients were 4.97 years 95%CI(4.72-5.22). The OS in HER1+ and 2+ cohorts were 4.08 years and 5.04 years respectively. The PFS in low HER2+ patients was 5.01 years 95%CI(4.74-5.27) and 4.29 years and 4.89 years in HER2 1+ and 2+ cohorts. In the ER+ and negative cohorts, 31.4% of ER+ were treated with NACT and 45.4% of ER+ patients were treated with adjuvant CT. Most of ER+ low HER2 patients were of T2 stage (53.6%, p = 0.037). 36.6% were N0 and 34% were N1. 14.4% of ER+ low HER2 were MBC and 16.3% ER negative low HER2 were MBC. The OS of ER+ lowHER2+ cohort was 4.44 years and ER- HER2+ cohort was 4.43 years. Patients with MBC had a larger tumour size and nodal positivity (T4 43.4%, N1 37.8%,p = 0.001). The PFS and OS in MBC were 3.42 and 3.07 years compared to 5.29 years and 5.37 years in non-metastatic patients. Patients who were treated with NACT had an OS and PFS of 4.24 and 4.20 years and those who were treated with adjuvant CT had an OS of 5.39 years. Conclusions: The data on low HER2-positive patients is scarce in the Indian population. The low HER2+ patients had a PFS of 4.97 years and an OS of 5.01 years. Most of the patients had a T2 and N1 disease. The research gap low HER2+ subset is significant, especially considering the recent approval of trastuzumab deruxtican in India. With ongoing trials in MBC and non-metastatic settings, the benefit from this newer option may become clearer, particularly in ER+ low HER2 subset.