For those living with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, recent advancements in treatment offer new reasons for hope. Over the past decade, targeted therapies, biomarker testing, and personalized treatment strategies have significantly expanded options for managing this condition.
Wade Smith, MD, a medical oncologist specializing in breast cancer and director of research at City of Hope Newport Beach, stated, “We have more ways to control this cancer and help people live longer than we did a decade ago.” While advanced breast cancer is generally treatable rather than curable, Dr. Smith emphasized that many patients live for years with effective treatment.
How New Therapies Are Extending Survival
One significant breakthrough is the combination of hormone therapy with targeted drugs. This approach slows cancer growth and delays chemotherapy. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, paired with hormone therapy, have proven particularly effective.
The MONALEESA-2 trial, published in The New England Journal of Medicine, found postmenopausal women receiving the CDK4/6 inhibitor ribociclib (Kisqali) alongside letrozole as initial treatment lived a median of 63.9 months, compared to 51.4 months for letrozole alone.
Survival statistics often reflect older data from before many current treatments were available. Given rapid advancements, current outcomes may be significantly better.
Latest Treatments for HR+/HER2- Advanced Breast Cancer
Recent years have introduced innovative treatments targeting specific features of breast cancer. Dr. Smith highlighted key developments:
Oral selective estrogen receptor degraders (SERDs), such as elacestrant (Orserdu), target the estrogen receptor directly. These drugs are effective for cancers with ESR1 gene mutations resistant to earlier hormone therapies. Four SERDs have received FDA approval since 2023, with camizestrant approved most recently in September 2026.
Capivasertib (Truqap), combined with fulvestrant, targets a growth pathway in cancers with PIK3CA, AKT1, or PTEN gene alterations. This combination was FDA-approved in 2023.
Inavolisib (Itovebi), paired with palbociclib (Ibrance) and fulvestrant, is an option for certain PIK3CA-mutated cancers recurring during or after hormone therapy. The FDA approved it in 2024.
These advancements, along with antibody-drug conjugates (ADCs) like sacituzumab govitecan (Trodelvy) and datopotamab deruxtecan (Datroway), offer new hope. Biomarker testing helps determine the most effective treatment for each individual.
HER2-Low Breast Cancer and Treatment Options
Biomarker testing plays a key role in determining suitable treatments for patients. HER2-low breast cancer, characterized by a small amount of HER2 protein, is still classified as HER2-negative. Trastuzumab deruxtecan (Enhertu) is a targeted treatment that delivers chemotherapy directly to cancer cells with HER2 protein.
The FDA has approved Enhertu for certain individuals with HER2-low metastatic breast cancer who have received prior treatment. This approval expands treatment options for patients whose cancer was previously described as HER2-negative. Additionally, those with even lower HER2 levels, known as HER2-ultralow, may also be eligible for this treatment.
Managing Metastatic HR+ Breast Cancer Long-Term
George W. Sledge Jr., MD, executive vice president and chief medical officer of Caris Life Sciences, explains “chronic” can describe a disease persisting over time or one that persists without causing death.
Emerging Treatments and Patient Actions
More antibody-drug conjugates (ADCs) are in clinical trials, building on the success of Enhertu for HER2-low disease.
Additional hormone therapies are in development. The FDA is expected to decide by December 18, 2026, on approving giredestrant, an oral SERD, combined with everolimus for ESR1-mutated advanced breast cancer.
Patients are encouraged to ask questions and discuss with their care team how advancements may impact their treatment and quality of life. The National Cancer Institute reports HER2-low tumors account for 50% to 60% of breast cancers, potentially expanding treatment options for many.
