New treatment options for generalized HER2-positive breast cancer in higher-line systemic palliative therapy

Czech version

Authors: J. Špaček
Authors‘ workplace: Onkologická klinika 1. LF UK a VFN v Praze
Published in: Klin Onkol 2025; 38(1): 58-62
Category: Case Reports
doi: https://doi.org/10.48095/ccko202558

Overview

Background: HER2-positive breast cancer occurs in about 15–20 % of all breast cancers. It is both a prognostic and predictive biomarker and the introduction of anti-HER2 therapy over the last 20 years has significantly improved outcomes in this subset of patients, so that they are now comparable to or better than those of patients with HER2-negative tumors. Approximately 5–10% of patients are diagnosed with metastatic breast cancer. It was good news for these patients when, on April 17, 2020, the FDA approved tucatinib in combination with trastuzumab and capecitabine for adult patients with advanced unresectable or metastatic HER2-positive breast cancer who had received one or more prior anti-HER2-based regimens in the metastatic setting. The efficacy of the regimen was demonstrated in the HER2CLIMB trial, which enrolled 612 patients with HER2-positive metastatic breast cancer who had previously been treated with trastuzumab, pertuzumab, and/or trastuzumab emtansine. Median overall survival for patients in the tucatinib arm was 21.9 months (95% CI 18.3–31.0) compared with 17.4 months (95% CI 13.6–19.9) for patients in the control arm (HR 0.66; 95% CI 0.50–0.87; P = 0.00480). Case: Our patient is a middle-aged woman without visceral metastatic involvement, but with extensive nodal involvement, skeletal metastatic involvement and left breast almost completely consumed by tumor. This woman had a more or less successful three lines of anti-HER2 therapy and the fourth line of one-year-long systemic treatment with the cytostatic eribulin. The inclusion of tucatinib with trastuzumab and capecitabine in the fifth line of systemic therapy achieved a very nice partial regression of the primary tumor without significant toxicity. Conclusion: In this case report, we describe the case of a highly pretreated patient with HER-2 positive metastatic breast cancer.

Keywords:

breast cancer – HER2 positivity – palliative biotherapy – highly pretreated patient

Sources

1. Swain SM, Miles D, Kim SB et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol 2020; 21 (4): 519–530. doi: 10.1016/S1470-2045 (19) 30863-0.

2. Hurvitz SA, Hegg R, Chung W-P et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet 2023; 401 (10371): 105–117. doi: 10.1016/S0140-6736 (22) 02420-5.

3. André F, Hee Park Y, Kim S-B et al. Trastuzumab deruxtecan versus treatment of physician’s choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial. Lancet 2023; 401 (10390): 1773–1785. doi: 10.1016/S0140-6736 (23) 00725-0.

4. Curigliano G, Mueller V, Borges V et al. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol 2022; 33 (3): 321–329. doi: 10.1016/j.annonc.2021.12.005.

5. Agostinetto E, Curigliano G, Piccart M et al. Emerging treatments in HER2-positive advanced breast cancer: Keep raising the bar. Cell Rep Med 2024; 5 (6): 101575. doi: 10.1016/j.xcrm.2024.101575.

6. Frenel JS, Zeghondy J, Guerin C et al. Efficacy of tucatinib+trastuzumab+capecitabine (TTC) after trastuzumab-deruxtecan (T-DXd) exposure in Her2-positive metastatic breast cancer: a French multicentre retrospective study. [online]. Available from: https: //ascopubs.org/doi/pdfdirect/10.1200/JCO.2023.41.16_suppl.1014.