Hormone receptor-positive (HR+)/HER2-negative breast cancer is the most common type of breast cancer. As you and your doctor decide on treatment, a key piece of the picture will be whether your breast cancer has certain gene mutations in genes such as PIK3CA, ATK1, or PTEN.
Knowing your mutations and how various treatments affect it is the first step in personalizing your treatment plan.
Here's a breakdown of treatment options for HR+/HER2- breast cancer with common mutations.
Endocrine Therapy
Despite your cancer’s genetic mutation status, endocrinetherapy (hormone therapy) is still the standard treatment for HR+/HER- breast cancer. You may have these treatments in combination with medication specific to certain genetic mutations.
Endocrine therapy includes several options:
Aromatase inhibitors
Aromatase inhibitors are pills you take by mouth. They stop your body from making the amount of estrogen it typically does. This is a common option for people who have already gone through menopause. Before menopause, most estrogen is made by your ovaries. But after menopause (or if certain treatments or other circumstances mean your ovaries aren’t working) your body makes estrogen in body fat by an enzyme called aromatase. Aromatase inhibitors stop this process.
There are three aromatase inhibitor options:
- Anastrozole (Arimidex)
- Exemestane (Aromasin)
- Letrozole (Femara)
Tamoxifen
Tamoxifen is a pill you take once or twice a day with food. This drug is a selective estrogen receptor modulator (SERM). It works by blocking estrogen’s access to cancer cells. When estrogen is kept away from the cancer cells, it can’t tell them to grow and divide.
This drug may be a good option for women who have not gone through menopause yet.
These drugs block estrogen from connecting to the cancer cells and telling them to grow and divide. Even though they have anti-estrogen effects in your breast cells, they act like estrogen in other tissues, like the uterus and the bones, which helps reduce the effects of low estrogen in the body.
Fulvestrant (Faslodex)
Fulvestrant (Faslodex) is in a class of drugs called selective estrogen receptor degraders (SERDs). These drugs also attach to estrogen receptors, like tamoxifen does. But they bind so tightly that they break down the receptors. Unlike tamoxifen, fulvestrant causes anti-estrogen effects in your whole body.
This drug tends to be best for women who are past menopause. If your doctor considers it as a treatment before menopause, you’ll take it in combination with luteinizing-hormone releasing hormone (LHRH) to turn off your ovaries.
You get this drug as a shot in your bottom. First you get them once every two weeks, and then move to once a month.
Special considerations for PTEN mutations
If you have a PTEN mutation, your cancer cells may become resistant to endocrine therapy drugs more quickly than cancer with other mutations. Because of this, your doctor may suggest starting targeted therapy early in your treatment.
CDK4/6 Inhibitors Plus Endocrine Therapy
These drugs that you take in pill form by mouth block proteins in cancer cells called cyclin-dependent kinases (CDKs). The CDKs they focus on are CDK4 and CDK6. This process stops HR+ breast cancer cells from dividing and can slow cancer growth.
CDK4/6 Inhibitors include:
- Abemaciclib (Verzenio)
- Palbociclib (Ibrance)
- Ribociclib (Kisqali)
Your doctor may prescribe these in combination with an aromatase inhibitor or fulvestrant.
Targeted Treatment for PIK3CA Mutations
HR+/HER2- breast cancer that also has a mutation in the PIK3CA gene has two key targeted therapies that can be especially helpful:
Alpelisib (Piqray) is a pill you take by mouth once a day. The FDA approved it in 2019. You’ll likely take it in combination with fulvestrant (Faslodex).
Inavolisib (Itovebi) is a tablet you take by mouth. The FDA approved it in 2024. Your doctor may combine it with fulvestrant (Faslodex) and palbociclib (Ibrance) for treatment of advanced PIK3CA-mutated breast cancer.
These drugs are in a class called kinase inhibitors. This means they block the action of enzymes called kinases in your body. Kinases control processes like cell growth, division, and signalling. When you “turn off” certain kinases with drugs, it can help stop cancer cells from growing.
Both alpelisib (Piqray) and inavolisib (Itovebi) are PI3K inhibitors, which means they specifically block PI3K. This is the pathway affected by mutations in the PI3KCA mutation.
mTOR Inhibitor
If PIK3CA-targeted therapy isn’t an option for you or your disease has progressed after you’ve tried aromatase inhibitors, your doctor may recommend a different targeted treatment that comes as a combination:
Everolimus (Afinitor) is a pill you take once a day. It blocks mTOR, a protein in cells that typically helps them grow and divide. It may also slow down tumor growth by stopping new blood vessels from growing. Studies show everolimus (Afinitor) seems to help hormone therapy drugs (like exemestane, or sometimes fulvestrant) work better.
Targeted Treatment for AKT Mutations
For HR+/HER2- breast cancer with a mutation in the AKT gene, one targeted treatment is available. Your doctor may also choose this treatment in combination with fulvestrant (Faslodex) if you have PIK3CA or PTEN mutations:
Capivasertib (Truqap) is an AKT inhibitor the FDA approved in 2023. You take it as a pill by mouth twice a day for four days followed by three days off each week. The drug blocks the AKT protein, which is part of a signaling pathway inside cells (including cancer cells) that can help them grow.
Chemotherapy
Doctors typically turn to chemotherapy if your disease is particularly aggressive or hormonal and targeted therapies aren’t working anymore. You may get chemotherapy by mouth or as an injection into your vein (intravenously).
Because chemotherapy drugs travel through your bloodstream, the side effects can be more intense than targeted treatment side effects.
Common chemotherapy drugs include:
- Capecitabine
- Doxorubicin
- Paclitaxel
Your doctor may use chemotherapy alongside targeted therapies.
Questions for Your Doctor
As you weed through the different options for treating your HR+/HER2-, come to your appointments with questions to better understand your treatment options and recommendations. You can ask your doctor:
- What are my gene mutations and how do they affect my treatment options?
- What treatment do you recommend I start with?
- What are the goals of my treatment?
- How do I take this treatment?
- What side effects should I expect with my treatment?
- Are there clinical trials I might be qualified for?
Show Sources
Photo Credit: iStock/Getty Images
SOURCES:
ESMO Open: “How I treat endocrine-dependent metastatic breast cancer.”
American Cancer Society: “Targeted Drug Therapy for Breast Cancer,” “Chemotherapy for Breast Cancer.”
Nature: “A retrospective analysis suggests PTEN expression is associated with favorable clinicopathological features of breast cancer.”
FDA: “FDA approves alpelisib for metastatic breast cancer,” “FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer,” “FDA approves capivasertib with fulvestrant for breast cancer.”
National Cancer Institute: “Kinase inhibitor.”
Medscape: “Inavolisib (Rx).”
