# Adjuvant Metronomic Chemotherapy After Surgery in pT1-T2 N0 M0 HER2-Positive and ER/PR-Positive Breast Cancer Plus Targeted Therapy, Anti-Hormonal Therapy, and Radiotherapy, with or Without Immunotherapy: A New Operational Proposal

## TL;DR

This paper proposes using low-dose, frequent chemotherapy after surgery for a specific type of breast cancer, combined with other treatments like targeted therapy and immunotherapy.

## Contribution

A new adjuvant treatment proposal for early-stage HER2- and hormone-positive breast cancer using metronomic chemotherapy alongside existing therapies.

## Key findings

- Metronomic chemotherapy may reduce side effects while being effective in early-stage breast cancer.
- Combining metronomic chemotherapy with targeted and anti-hormonal therapies could improve outcomes.
- Immunotherapy using PD-1 antibodies may further enhance treatment effectiveness in PD-1 positive cases.

## Abstract

Metronomic chemotherapy (MCTP) consists of frequently administering low doses of chemotherapy to reduce its side effects, without extended drug-free breaks. Here, its oral adjuvant use after surgery in combination with targeted therapy, anti-hormonal therapy, and radiotherapy is proposed in a variant of breast cancer smaller than 5 cm, not metastatic to the lymph nodes or elsewhere, and expressing both human epidermal growth factor receptor 2 (HER2) and hormone receptors. The possible improvement with immunotherapy using monoclonal antibodies against programmed death 1 (PD-1) is also considered.

Breast cancer is the most common and deadly female-specific malignancy in the world. Four immunohistochemical subtypes are distinguished: luminal A, luminal B, HER2-positive, and triple-negative. In turn, the HER2-positive subtype presents two variants depending on the status of the hormone receptors. The variant that expresses them can benefit from both anti-HER2 and anti-hormonal therapy. Today, MCTP finds application in maintenance therapy after standard of care and in advanced breast cancer when the patient’s clinical condition is already seriously compromised by metastatic disease; in this context, it is used as a first-line treatment, in pre-treated subjects, or as a rescue treatment. Here, the use of adjuvant oral MCTP after surgery at an early stage in HER-2 and hormone-positive local breast cancer is proposed, where effective treatment options are available, such as anti-HER2 therapy (e.g., trastuzumab, pertuzumab), anti-hormonal therapy (e.g., tamoxifen, letrozole), radiotherapy, and, in case of strong PD-1 positivity, immunotherapy.