Multi-Study Secondary Analysis of Radiation Therapy Outcomes in Patients with Locally Advanced or Metastatic Triple Negative Breast Cancer

Breast cancer is one of the most common cancers affecting women worldwide. A specific and aggressive type, called triple-negative breast cancer (TNBC), does not respond to common treatments that target three key molecular features commonly found in other breast cancer subtypes.

Most breast cancers are tested for hormone receptors, which are special proteins—called estrogen receptors (ER) and progesterone receptors (PR)—that allow tumor cells to use the body's natural hormones to grow. Cancers that express these receptors can be treated with hormone therapy, which blocks or lowers hormone levels to slow cancer growth. Another important protein tested in breast cancer is HER2 (human epidermal growth factor receptor 2). In certain subtypes of breast cancer, tumor cells produce an excessive amount of this protein, thereby enabling and accelerating growth. These HER2-positive cancers can be treated effectively with targeted therapies, such as trastuzumab or pertuzumab, that specifically block HER2.

In contrast, TNBC lacks all three of these features, it is ER-negative, PR-negative, and HER2-negative. Without these molecular targets, treatments like hormone therapy or HER2-targeted drugs are ineffective, making TNBC especially challenging to treat. TNBC accounts for about 10–15% of all breast cancer cases and tends to grow and spread more quickly than other types. It often affects younger women and has fewer treatment options, especially once it has spread to other parts of the body—a stage known as metastatic cancer.

Unfortunately, once TNBC becomes metastatic, the outlook for patients is usually poor. Most people in this stage are treated with systemic therapy, which is treatment that travels through the bloodstream to reach cancer cells throughout the body. While progress has been made in improving systemic therapy for TNBC, we still need better ways to improve survival and quality of life for patients.

Recent studies suggest that radiotherapy—a treatment that uses high-energy rays to kill cancer cells—might help certain patients with TNBC, even after the cancer has spread. This could include treating the original tumor or small numbers of cancer spots (called oligometastases) elsewhere in the body. However, there is not enough strong evidence yet to know how helpful radiotherapy is in these cases.

In this project, we will study data from past clinical trials involving patients with metastatic TNBC. We will analyze whether adding radiotherapy to their treatment was linked to longer survival or delayed cancer progression. Our goal is to create real-world evidence that will help doctors decide when radiotherapy might be beneficial for people with this aggressive cancer. This research may also guide the design of future clinical trials and ultimately improve care for patients with metastatic TNBC.