Is There a Role for Primary Surgery in Stage IV Breast Cancer?

Breast cancer is the most common cancer in American women after skin cancers. There is about a 1 in 8 chance that a woman will develop breast cancer during her lifetime. While incidence rates are rising, death rates have dropped dramatically over the last 30 years.¹

Breast cancer treatments are generally local (surgery or radiation) or body-wide (systemic drugs). The treatment depends on the diagnosis. There are various subtypes of breast cancer, which respond differently to specific treatments. Over time, experts have developed new treatments to target the various forms of breast cancer.²

Stage 4 (IV) breast cancer treatment

Stage 4 occurs when the disease has spread to one or more areas of the body beyond the breast. It is also known as metastatic breast cancer. Areas of spread may include the bones, liver, lungs, or brain. Spread often occurs through the lymph system or bloodstream.^2,3

The typical treatment for stage 4 breast cancer has been systemic therapy. But local treatment may also be an option in certain cases.^2,3

Systemic therapy

Drug treatment has been the main approach for most people with stage 4 breast cancer. Hormone therapy, chemotherapy, targeted drug therapy, and immunotherapy are generally prescribed alone or together to attack the cancer. Types of drugs used for stage 4 breast cancer depend on several factors, including:^2,4

• The hormone receptor status of the cancer
• The human epidermal growth factor receptor 2 (HER2) status of the cancer

One example of a specific breast cancer subtype involves tumors that make too much HER2 protein on the surface of the cancer cells. This type is called HER2-positive. Systemic therapies to treat certain forms of HER2-positive breast cancer include:^4,5

• Antibody drug conjugates like Kadcyla® (ado-trastuzumab emtansine)
• Targeted drug therapies like Perjeta® (pertuzumab) and trastuzumab (and trastuzumab biosimilars), in combination with chemotherapy
• Kinase inhibitors like Tykerb® (lapatinib), Nerlynx® (neratinib), and Tukysa® (tucatinib)

Other breast cancer subtypes include triple-negative breast cancer and HER2-low breast cancer. HER2-low cancer is a subset of breast cancer that accounts for about half of all breast cancers. Some drugs are making progress in treating certain forms of these types of breast cancer. These drugs include:^4-7

• Immunotherapy like Keytruda® (pembrolizumab) to treat certain forms of triple-negative breast cancer
• Antibody drug conjugates (ADCs) like:
  • Trodelvy® (sacituzumab govitecan-hziy), the first ADC approved for certain forms of triple-negative breast cancer
  • Enhertu® (fam-trastuzumab deruxtecan-nxki), the first drug approved to treat certain forms of HER2-low breast cancer

Systemic therapy has had positive outcomes for many people with metastatic breast cancer. But metastatic breast cancer usually cannot be cured.^4,5

Local treatment options

Surgery, like radiation, is considered a local treatment for stage 4 breast cancer. Surgery is not a cure for breast cancer that has spread to other parts of the body. But it can be useful in some cases. For example, it can be done to help relieve symptoms caused by the spread of cancer.⁸

A 2020 study suggests that surgery may result in longer survival when used with targeted therapy and other treatment methods. Researchers looked at the effect of removing the primary tumor on survival in women with HER2-positive stage 4 breast cancer. They examined outcomes for about 3,200 cases from the National Cancer Database.⁹

Although earlier studies saw mixed results, the most recent findings showed that women with metastatic HER2-positive breast cancer lived longer if they had surgery for the primary tumor. Results from the study found that the median overall survival time after the surgery was 25 months. Without the surgery, it was 18 months.⁹

More research is needed

Research shows that surgery on the primary site in people with metastatic HER2-positive breast cancer may help them live longer. However, more research is needed to know for sure. Future studies of surgery for stage 4 breast cancer may look at the effect that timing has on different therapies.