YO1 - Trastuzumab deruxtecan and Stereotactic radiosurgery (SRS) in HER2-positive (HER2+) breast cancer with brain metastases (BM)

Case summary

Advanced HER2+ breast cancer presents a 25-50% risk of brain metastasis (BrM). Previous treatments had limited intracranial impact. T-DXd, an antibody-drug conjugate, shows significant extracranial and potential intracranial effects. SRS is a key BrM therapy, with systemic therapy improving survival. ctDNA monitoring can help predict BrM progression. A HER2+ breast cancer case with BrM, treated with T-DXd and SRS, guided by ctDNA, led to longer survival and better QoL.

A 42-year-old premenopausal Asian female presented with a palpable right breast mass in 2011. Ultrasound revealed a 4x5 cm mass, and pathology confirmed grade 2 invasive ductal carcinoma.Immunohistochemical analysis indicated that the tumor was estrogen receptor and progesterone receptor positive, with human epidermal growth factor receptor 2 negativity. She underwent adjuvant chemotherapy (docetaxel, pirarubicin) and extended endocrine therapy(tamoxifen, anastrozole). PET-CT identified multiple bone metastases, with subsequent biopsy showing ER (10%), PR (20%), HER2 (3+). A ctDNA test later indicated increased tumor load (5.0%). In 2022, she developed neurological symptoms; MRI detected multiple brain lesions, the largest in the right parietal lobe (3.3x3.2 cm), confirming brain metastasis. After an additional five cycles of T-DXd treatment, the intracranial lesions further reduced to 2.5 x 2.1 cm. Concurrently, intracranial edema and ventricular compression were reduced, and the patient's headache symptoms gradually subsided.SRS was administered in 2023, targeting multiple brain sites, resulting in further lesion shrinkage. Follow-up imaging showed stable disease with no significant lesion growth, and the patient's intracranial symptoms improved markedly.

This case study details a premenopausal, initially HR+/HER2- patient with subsequent HER2+ brain metastasis. Post-treatment with T-DXd and SRS, the patient exhibited controlled disease and high QoL. PET-MRI confirmed SRS's efficacy, with a PFS of 25 months and no new brain lesions, suggesting potential for extended survival with T-DXd and SRS in central nervous system metastases.

Clinical trial identification

Editorial acknowledgement