When you have HER2-negative advanced (metastatic) breast cancer, treatment usually focuses on managing your disease, not curing the cancer. The goal is to help you live longer and have a better quality of life.
This type of cancer is most often treated with systemic therapy. These drugs go into your bloodstream to send treatment to cells and organs throughout your body. Systemic therapies include:
- Hormonal treatments
- Chemotherapy
- Targeted therapy
- Immunotherapy
Some women also have surgery or radiation to prevent or treat symptoms.
Hormonal Therapies
Hormonal therapy is often the first treatment doctors use for women with HER2-negative advanced breast cancer that's "hormone receptor positive."
Some 67% to 80% of breast cancers are hormone receptor positive. That means your hormones, like estrogen or progesterone, help the cancer grow.
Hormonal or endocrine therapies help to block this process. Some drugs lower your levels of estrogen. Others stop estrogen from connecting to cancer cells so they can’t multiply.
Hormonal therapies have a lower risk of serious side effects than chemotherapy. So you may have a better quality of life during treatment. You can take them as pills or in a shot.
Hormonal therapies include:
- Aromatase inhibitors (AIs) like anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara)
- Fulvestrant (Faslodex)
- Tamoxifen (Nolvadex, Soltamox)
- Toremifene (Fareston)
- Imlunestrant (Inluriyo)
- Camizestrant (Etcamah)
- Drugs that stop your body from making estrogen, like goserelin (Zoladex) and leuprolide (Lupron)
Chemotherapy
Chemotherapy or "chemo" is medicine that kills cancer cells. You can take it as pills or get them through an IV.
Many different chemotherapy drugs are used, either alone or in combination, to treat HER2-negative breast cancer. Your doctor will prescribe a chemo drug based on:
- Your past treatments
- Your preferences
- Any other conditions you have
- Your risk of side effects
Categories of chemo drugs called taxanes and anthracyclines are often used to treat this cancer.
Often, you get chemo drugs in cycles of two to three weeks. Between cycles, you have a rest period so your body can recover from the drug's effects.
Targeted Therapies
Targeted therapies block certain proteins or molecules that drive the growth and spread of cancer cells. Those molecules are the "targets" of the drugs.
There's a lot of research into targeted therapies for cancer. These drugs are also called precision medicine. That's because your doctor prescribes a certain drug based on your genes or the proteins associated with your specific cancer.
Targeted therapies for HER2-negative advanced breast cancer include:
PARP inhibitors like olaparib (Lynparza) and talazoparib (Talzenna). These drugs stop a protein known as poly-ADP ribose polymerase (PARP) from repairing cancer cells, so the cells die. They're given to women who have a mutation in the BRCA gene and HER2-negative breast cancer.
Capivasertib (Truqap). This drug blocks some types of the AKT protein. It can be used if the cancer cells have changes in any of the AKT1, PIK3CA, or PTEN genes.
Everolimus (Afinitor). This drug blocks a protein called mTOR, which helps cancer cells grow and multiply. It may also stop tumors from making blood vessels that fuel their growth.
CDK4/6 inhibitors like abemaciclib (Verzenio), palpociclib (Ibrance), and ribociclib (Kisqali). These block proteins called cyclin-dependent kinases and slow the cancer’s growth.
In September 2026, the FDA approved abemaciclib (Verzenio) with imlunestrant (Inluriyo) for adults with ER-positive, HER2-negative advanced or metastatic breast cancer that worsened after at least one hormone therapy. An FDA-authorized test must confirm an ESR1 gene change (mutation).
Alpelisib (Piqray) withcapivasertib (Truqap). This drug blocks some types of the AKT protein. It can be used if the cancer cells have changes in any of the AKT1, PIK3CA, or PTEN genes. Up to 40% of women with breast cancer have a mutation in the PI3KCA gene.
Gedatolisib (Revtorpyk). This targeted therapy blocks the PI3K and mTOR pathways. It is used with fulvestrant, with or without palbociclib, for adults with locally advanced or metastatic HR-positive, HER2-negative breast cancer without a detected PIK3CA mutation. It may be used after the cancer progresses during or after at least one endocrine therapy for metastatic disease.
Antibody-drug conjugates (ADCs). This type includes drugs like sacituzumab govitecan-hziy (Trodelvy)and daptopotamab deruxtecan (Datroway). It targets a protein called Trop-2 to bring chemo drugs directly into your cancer cells.
Vepdegestrant (Veppanu). The first FDA-approved proteolysis targeting chimera (PROTAC) is a targeted protein degraderfor people with estrogen receptor-positive (ER+) HER2-, estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer, whose disease has progressed after at least one prior hormone (endocrine) therapy. An FDA-authorized test confirming ESR1 mutation must be given before starting treatment.
Immunotherapy
Immunotherapy uses the power of your immune system to fight cancer. Drugs called immune checkpoint inhibitors can be used to treat certain types of advanced breast cancer.
Immune "checkpoints" are proteins. They help your immune system tell the difference between healthy cells and dangerous ones. But cancer cells sometimes use them to hide from your immune system.
Pembrolizumab (Keytruda) stops the checkpoint protein PD-1 from attaching to another protein, PD-L1, that sits on the surface of T cells. T cells are immune cells that circulate through your body to fight disease. But when PD-1 binds with PD-L1, the T cells can’t do their job. Pembrolizumab (Keytruda) stops these proteins from linking up. This lets your T cells find and kill your cancer.
It only works on breast cancer that is PD-L1-positive.
Palliative Care
Once you’re diagnosed with HER2-negative advanced breast cancer, you may also consider starting palliative care. Palliative therapies treat pain, anxiety, and other issues that can come along with cancer.
You can get palliative care from:
- Your cancer doctor
- Nurses
- Therapists
- Social workers
- Psychologists
- Dietitians
- Your pastor, if you choose
Clinical Trials
You may want to enroll in a clinical trial to try a drug that isn’t yet approved for advanced breast cancer. Your doctor can tell you more about clinical trials and whether you qualify for one.
