# Brain Metastases From HER2 Breast Cancer That Achieved Complete Response With Trastuzumab Deruxtecan Without Any Local Treatment

## TL;DR

A patient with brain metastases from HER2-positive breast cancer achieved complete response using trastuzumab deruxtecan without local treatment.

## Contribution

Demonstrates the effectiveness of T-DXd in treating brain metastases without local therapy.

## Key findings

- The patient achieved complete response in brain metastases after six cycles of T-DXd.
- T-DXd was effective without causing neurological symptoms or requiring local therapy.
- T-DXd may be a safe alternative for patients avoiding cognitive decline from local treatments.

## Abstract

The blood-brain barrier (BBB) prevents high molecular weight drugs from reaching the brain, and only some low molecular weight drugs have been effective against brain metastases (BMs) from breast cancer. Therefore, local therapy, such as surgery or radiotherapy, has been the first choice and the standard treatment for BMs. However, trastuzumab deruxtecan (T-DXd), which has recently been introduced, demonstrates a high penetration rate into BM lesions and is believed to be highly effective. We herein present a case of complete response to T-DXd alone, without local therapy, in a patient with BMs from human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The patient was a 56-year-old premenopausal woman with estrogen receptor-positive, progesterone receptor-positive, HER2(+) left breast cancer; left axillary, left cervical, and left submandibular lymph node metastases; and multiple BMs. Lymphedema of the left upper limb was observed. However, no cerebral neurological symptoms were noted. She refused local therapy for BMs because her job required advanced calculations, and she could not afford the possibility of cognitive decline. She chose trastuzumab + pertuzumab + docetaxel (TPD) triweekly as the first-line therapy, and at the end of six cycles, the BMs were stable and the metastatic lesions in the body showed a complete response; however, peripheral sensory neuropathy due to docetaxel appeared. Therefore, docetaxel was discontinued, and tamoxifen (TAM) was started instead. Trastuzumab + pertuzumab (TP) was continued. At the end of six cycles of TP-TAM (a total of 12 cycles of TP), because BM appeared to be progressive on imaging tests, TP-TAM was discontinued, and T-DXd was introduced; however, no neurological symptoms were observed. At the end of the six cycles, BMs had disappeared. Although local therapy is the standard for BMs, the National Comprehensive Cancer Network guidelines state that systemic therapy can be prioritized before local therapy in the absence of active neurological symptoms. T-DXd is an antibody-drug conjugate that penetrates the BBB disrupted by metastasis and is thought to exert its effectiveness by penetrating the lesion through a bystander effect. Furthermore, it is thought to be a safe treatment option for patients with unacceptable complications of local therapy, as in our case.