For patients living with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, the future is looking more hopeful thanks to new treatments. According to Wade Smith, MD, a medical oncologist specializing in breast cancer, “We have more ways to control this cancer and help people live longer than we did a decade ago.”
Over the past 10 years, advancements in targeted therapies, biomarker testing, and personalized treatment strategies have expanded treatment options for HR+/HER2- advanced breast cancer. These options are helping many people live longer and maintain a better quality of life.
Dr. Smith noted that when breast cancer has spread to distant organs, it is generally treatable rather than curable. However, many people live for years with treatment, and the goal is to give patients more time while helping them feel well and continue their daily activities.
Progress in Breast Cancer Treatment
Progress is not limited to metastatic breast cancer. According to the American Cancer Society, breast cancer death rates have fallen steadily since 1989, dropping by 44% through 2023. This decline is due to the advancements being made in breast cancer treatment.
One of the biggest advances has been combining hormone therapy with targeted drugs. Dr. Smith explained that hormone therapy combined with targeted medicines can often slow the growth of cancer and delay the need for chemotherapy.
A key group of targeted drugs is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Dr. Smith said that CDK4/6 inhibitors, used with hormone therapy, have been a major advance, helping control cancer longer and extending survival in some cases.
New Therapies and Treatment Options
The MONALEESA-2 trial found that postmenopausal women who received the CDK4/6 inhibitor ribociclib (Kisqali) with letrozole as their first treatment for advanced disease lived a median of 63.9 months, compared to 51.4 months for those who received letrozole alone.
These include oral selective estrogen receptor degraders (SERDs), such as elacestrant (Orserdu), and antibody-drug conjugates (ADCs), such as sacituzumab govitecan (Trodelvy).
Dr. Smith highlighted the importance of biomarker testing in determining which treatment may be right for a patient. He explained that testing, previous treatments, and side effects all factor into choosing a treatment that fits a patient’s cancer and daily life.
The definition of HER2-low breast cancer has also become important, as newer treatments have made it possible to identify smaller amounts of the HER2 protein. Dr. Smith noted that HER2-low disease is still classified as HER2-negative, but some patients with HER2-low metastatic breast cancer may be eligible for targeted treatments like trastuzumab deruxtecan (Enhertu).
According to the National Cancer Institute, HER2-low tumors account for about 50% to 60% of all breast cancers. This means that some patients whose cancer was previously described as HER2-negative may now have another treatment option.
George W. Sledge Jr., MD, executive vice president and chief medical officer of Caris Life Sciences, said that metastatic HR+ breast cancer has become a chronic illness that can be managed over the long term. While there is no cure, many patients can live well with cancer, and the focus should be on quality of life as well as length of life.
Dr. Sledge recommended that patients take practical steps, such as getting a second opinion and searching for clinical trials, to explore new treatment options.
As research continues to advance, new treatments are being developed for HR+/HER2- breast cancer. More antibody-drug conjugates are in clinical trials, and additional hormone therapies are being tested. The FDA is expected to decide on the approval of giredestrant, an oral SERD, in combination with everolimus for ESR1-mutated advanced breast cancer.
This decision is anticipated by December 18, 2026.