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. 2020 Nov 5;6(1):26.
doi: 10.1186/s40959-020-00081-9.

Clinical impact of interruption in adjuvant Trastuzumab therapy in patients with operable HER-2 positive breast cancer

Sagar Sardesai  1   2 , Jasmine Sukumar  3   4 , Mahmoud Kassem  3   4 , Marilly Palettas  5 , Julie Stephens  5 , Evan Morgan  3   4 , Daniel Addison  6 , Ragavendra Baliga  6 , Daniel G Stover  3   4 , Jeffrey VanDeusen  3   4 , Nicole Williams  3   4 , Mathew Cherian  3   4 , Maryam Lustberg  3   4 , Robert Wesolowski  3   4 , Bhuvaneswari Ramaswamy  3   4
Affiliations

Clinical impact of interruption in adjuvant Trastuzumab therapy in patients with operable HER-2 positive breast cancer

Sagar Sardesai et al. Cardiooncology. .

Abstract

Background: Trastuzumab-induced cardiotoxicity (TIC) can lead to early discontinuation of adjuvant therapy, however there is limited evidence on long-term survival outcomes in patients with operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) experiencing treatment interruption or discontinuation.

Methods: The primary objective of the study was to evaluate disease-free survival (DFS) in non-metastatic, HER2-positive, female BC patients who experienced treatment interruption or early discontinuation of trastuzumab therapy. Clinical and histopathological data were collected on 400 patients at The Ohio State University, an NCI-designated comprehensive cancer center between January 2005 and December 2015. Treatment interruption was defined as any delay of ≥2 weeks during trastuzumab therapy, including permanent cessation prior to completing planned therapy. TIC was defined as LVEF < 50% or > 15 points decline from baseline as evaluated by 2D echocardiogram after initiation of (neo) adjuvant therapy. DFS was defined as the time from diagnosis to first recurrence (loco-regional or distant recurrence) including second primary BC or death. Overall survival (OS) was defined as the time from diagnosis to death or last known follow up. OS/DFS estimates were generated using Kaplan-Meier methods and compared using Log-rank tests. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHR) for OS/DFS.

Results: A total of 369 patients received trastuzumab therapy; 106 (29%) patients experienced treatment interruption at least once and 42 (11%) permanently discontinued trastuzumab prior to completing planned therapy. TIC was the most common reason for interruption (66 patients, 62%). The median duration of trastuzumab in patients with treatment interruption was 11.3 months (range: 0.5-16.9) with 24 (23%) patients receiving ≤6 months of therapy. This duration includes the time delay related to treatment interruption. Patients with any treatment interruption had worse DFS (aHR: 4.4, p = 0.001) and OS (aHR: 4.8, p < 0.001) after adjusting for age, stage, grade, ER, node status and TIC.

Conclusions: Treatment interruption or early discontinuation of trastuzumab therapy in early HER2-positive BC, most often from TIC, is an independent prognostic marker for worse DFS and OS in operable HER2-positive BC. Future prospective studies should consider targeting at-risk populations and optimizing cardiac function to avoid interruption in trastuzumab therapy.

Keywords: Breast cancer; Cardio-oncology; Chemotherapy; HER2; Trastuzumab.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Kaplan Meier curve showing the disease free survival between patients on trastuzumab and patients who had interruption (unadjusted log-rank results)
Fig. 2
Fig. 2
Kaplan Meier curve showing the overall survival between patients on trastuzumab and patients who had interruption (unadjusted log-rank results)
See this image and copyright information in PMC

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