Hormone therapy treats advanced breast cancer
Treatment options for advanced breast cancer have become more effective and personalized, particularly for the most common subtype, hormone receptor-positive, HER2-negative breast cancer (HR+/HER2-). This type of cancer uses estrogen and sometimes progesterone to grow, but does not produce high levels of HER2. In advanced or metastatic disease, first-line treatment often includes hormone therapy combined with a CDK4/6 inhibitor.
The goal of this treatment is to control the disease, help patients live longer, and maintain quality of life, according to Dhvani Thakker, MD, director of women’s medical oncology at Mount Sinai South Nassau in Oceanside, New York. First-line treatment for advanced HR+/HER2- breast cancer depends on several factors, including a patient’s symptoms, disease burden, and prior therapies, said Madhurima Anne, MD, director of hematology/oncology at Hackensack Meridian Ocean University Medical Center.
Standard Treatment Approach
In many cases, the standard approach is a combination of an aromatase inhibitor and a CDK4/6 inhibitor, according to Dr. Thakker. Aromatase inhibitors are anti-estrogen treatments that reduce estrogen levels in HR+/HER2- breast cancer. CDK4/6 inhibitors block a pathway that helps breast cancer cells grow and divide. When paired with anti-estrogen therapy, they have been shown to improve response rates and help patients live longer.
Dr. Thakker explained that while aromatase inhibitors can work well at first, advanced breast cancer often becomes resistant to hormone therapy over time. Resistance can develop through several biological pathways, allowing cancer cells to keep growing and the disease to progress. However, other treatment options can help if the cancer becomes resistant to hormone therapy.
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CDK4/6 Inhibitors
Currently, there are three U.S. Food and Drug Administration (FDA)-approved CDK4/6 inhibitors for HR+/HER2- breast cancer: Ribociclib (Kisqali), Abemaciclib (Verzenio), and Palbociclib (Ibrance). No head-to-head trials have directly compared these three drugs against one another, Dr. Thakker noted, so there isn’t a single “best” option that fits everyone. Instead, the right choice depends on factors like overall health, medical history, and the side effects each drug may cause.
Dr. Thakker said Ribociclib (Kisqali) has shown the strongest overall survival benefit in the first-line setting. It does require liver function monitoring and EKG monitoring before and after treatment initiation for QTc prolongation. Abemaciclib (Verzenio) has an overall survival benefit in a second-line setting but has significant side effects of diarrhea requiring diarrhea management in addition to the risk of thromboembolism.
Palbociclib (Ibrance) is the only CDK4/6 inhibitor that has not demonstrated an overall survival benefit. Still, it may be an option for patients who cannot tolerate Ribociclib (Kisqali) or Abemaciclib (Verzenio). The choice of CDK4/6 inhibitor depends on individual patient factors.
In the context of HR+/HER2- breast cancer treatment, the use of CDK4/6 inhibitors has been a significant advancement. By blocking the CDK4/6 pathway, these inhibitors can help slow down cancer cell growth and improve treatment outcomes.
Testing for genetic mutations and biomarkers is also an essential part of the treatment process. Dr. Anne explained that patients with metastatic HR+/HER2- breast cancer are tested for mutations such as PIK3CA/AKT1/PTEN and ESR1 mutations. Knowing which mutations a tumor carries helps the care team create the best treatment plan.
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Patients carrying PIK3CA, AKT1, or PTEN mutations are treated with endocrine therapy plus drugs that target the PI3K/AKT pathway, such as capivasertib (Truqap), an AKT inhibitor, or alpelisib (Piqray), a PI3K inhibitor. The presence of these mutations can significantly impact the treatment approach and outcome for patients with HR+/HER2- breast cancer.
Dr. Anne noted that oral selective estrogen receptor degraders (SERDs) have been approved for metastatic breast cancer after they have become resistant to first-line therapies, if the tumor has been found to carry the ESR1 mutation. The available oral options include elacestrant (Orserdu), imlunestrant (Inluriyo), and vepdegestrant (Veppanu). These oral SERDs offer a new treatment option for patients who have developed resistance to hormone therapy.
Antibody-drug conjugates (ADCs) are another class of cancer treatments that combine monoclonal antibodies with chemotherapy. Dr. Anne explained that ADCs are designed to recognize specific targets on cancer cells and deliver the treatment more precisely to the tumor. Approved options include sacituzumab govitecan (Trodelvy), fam-trastuzumab deruxtecan (Enhertu), and datopotamab deruxtecan (Datroway).
Dr. Anne noted that the treatment of HR+/HER2- breast cancer is constantly evolving. New treatments and combination therapies are being developed, and the use of genetic testing and biomarkers is becoming more widespread.
