How is Metastatic Breast Cancer Treated?
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Metastatic breast cancer, also known as stage 4 breast cancer, is diagnosed when the cancer has spread outside the breast to other organs, most commonly the bones, brain, liver, and lungs, according to the American Society of Clinical Oncology (ASCO).
“While [metastatic breast cancer] is not traditionally considered to be curable – meaning that we make it go away and it never comes back again – it is very treatable,” says Dr. Tiffany Troso-Sandoval, MD, a breast oncologist at Memorial Sloan Kettering Cancer Center. “Patients can live with certain types of metastatic breast cancer for many, many years.”
While someone with a metastatic breast cancer diagnosis can’t currently be cured of the disease, many treatments can help slow the spread of the cancer or keep it from progressing, manage pain and other symptoms and side effects, and improve quality of life, according to the ACS.
Metastatic breast cancer is most commonly treated using hormone therapy, chemotherapy, immunotherapy, targeted drugs, or a combination of these treatments, per the ACS.
Radiation therapy and surgery are not as commonly used to treat breast cancer that has metastasized, though radiation may be used as part of palliative care to help relieve pain.
The type of treatment you receive will largely depend on how far the cancer has spread, where it has spread to, and the form of disease you were diagnosed with.
Breast Cancer: Types and Subtypes
The overwhelming majority (75-80 percent) of breast cancers arise from the milk ducts and are referred to as invasive ductal carcinoma. The second most common type of breast cancer is invasive lobular carcinoma (up to 15 percent), which arises from the milk lobules. There are also other less common types of breast cancer also.ASCO.
Beyond where the cancer originated in the breast, breast cancer is further classified into subtypes. Subtypes are based on the types of receptors that appear on the surface of the cells. Knowing a cancer’s subtypes helps doctors select treatments each subtype is sensitive to.
Common breast Cancer Subtypes:
- Hormone receptor-positive Many breast tumors–up to 75 percent–contain receptors for estrogen and progesterone, the female hormones, on their surface. If a tumor is hormone positive, it means it carries these receptors, and that the tumor will grow in the presence of these hormones. Many treatments for this subtype are designed to block the hormones or interfere with their production. It’s very common for breast cancers to be “positive” for these hormones.
- HER2-positive HER2 is a common receptor found in many areas of the body. But in some cancers, including breast cancer, the HER2 receptor can be present to an abnormal degree. About 20 percent of breast tumors are positive for HER2 receptors, also known as being “HER2 positive.” There are drugs that target this receptor.
- Triple-negative These breast cancers don’t carry receptors for progesterone, estrogen, or HER2. As a result, they are considered more difficult to treat because, without these receptors, they are more difficult to target with treatments.
Treating Metastatic Hormone Positive Breast Cancer
Hormone Therapy
Because hormone receptor-positive breast cancers grow in response to estrogen and progesterone, treating this type of cancer is most commonly done using drugs that block the hormone pathway, says Dr. Kelly McCann, MD, breast oncologist at UCLA Health in Beverly Hills, California.
These typically take the form of oral medications – or aromatase inhibitors – which decrease hormone levels.
The most commonly used aromatase inhibitors are:
Estrogen helps the body maintain bone density, so one complication that can arise from blocking it is a decrease in bone density, says Dr. McCann. Other side effects of these drugs may include arthralgia, or aching of the bones and joints, and menopausal symptoms, such as hot flashes or vaginal dryness, says McCann.
For this reason, your doctor may combine your prescription with a class of drug called CDK 4/6 inhibitors.
CDK 4/6 Inhibitors
CDK 4/6 inhibitors are a class of drugs that stop cancer cells from multiplying by targeting the CDK 4/6 protein found on the surface of breast cancer cells. Some research suggests that using a combination of CDK 4/6 inhibitors with aromatase inhibitors may be better at slowing cancer spread than if the therapies are used individually.
The most commonly used CDK 4/6 inhibitors are:
Though this type of drug is tolerable for most people, side effects may include fatigue, low blood counts, and a decrease in appetite, says Troso-Sandoval,
Chemotherapy
Targeted therapies like aromatase inhibitors and CDK4/6 inhibitors tend to be first go-tos when treating those with metastatic hormone receptor-positive breast cancer because they tend to be more effective and have fewer side effects than older options like chemotherapy, says McCann. But chemotherapy may still be used, particularly if a patient has widespread disease, and it’s either progressing despite the other therapies or they’re experiencing intolerable side effects from them.
The most commonly used chemotherapy drugs include:
Side effects of chemotherapy include an increased risk of infection, anemia, bruising and bleeding, blood clots and nausea. Many of these side effects can be managed with the help of palliative care, a change in diet, and additional medication.
Treating Metastatic HER2-Positive Breast Cancer
Targeted Therapy
Metastatic HER2 positive breast cancers may also be hormone positive, so these patients may receive hormone therapy as well as therapy targeted for the HER2 receptor. (ACS)This type of treatment may also be combined with the same type of chemotherapy used for hormone positive metastatic breast cancers, McCann says.
The most common types of medications used to treat metastatic HER2-positive breast cancer, according to Troso-Sandoval, include:
Common side effects of this type of medication may include diarrhea, hair loss, nausea, fatigue, and rash on your skin. If you experience these symptoms, tell your provider. They may be able to prescribe additional medications or suggest lifestyle changes to help.
Chemotherapy
Chemotherapy treatment for HER2 cancers is very similar to other breast cancers. See above for more information.
New Drug Treatments
Advancements in research on metastatic HER2-positive breast cancer have led to the development of several new drugs. Those include:
- Tucatinib (Tukysa). Tucatinib is a small molecule inhibitor of HER2, meaning it slows progression of cancers that carry the HER2 receptor. It has been approved by the FDA when combined with trastuzumab and capecitabine.
- Trastuzumab emtansine (Kadcyla). Kadcyla works by binding to the HER2 receptor to stop growth of cancer cells. It has been approved by the FDA.
- Orserdu (Elacestrant). Orserdu was approved by the FDA in 2023. It’s a combination product that works to precisely deliver a drug to cancer cells by using an antibody (attached to the drug) to hone in on HER2 receptors. .
Side effects for these treatments may include nerve damage, nausea, and fatigue. Providers can address these issues with palliative care including medication and lifestyle changes.
Treating Metastatic Triple-Negative Breast Cancer
Triple-negative breast cancer, which comprises about 15 percent of all breast cancers, is defined by the absence of estrogen, progesterone and HER2 proteins, McCann says. It’s more difficult to treat because it lacks receptors to target.
Triple negative breast cancer (TNBC) is less common than the other subtypes, and is more commonly seen in Black women. TNBC is also associated with the BRCA1 genetic mutation, known to increase risk for breast cancer, but most people who get a diagnosis of TNBC will not have a genetic mutation.
Interestingly, research has shown that African-American women have rates of BRCA1 and BRCA2 (another genetic mutation associated with risk for breast cancer) genetic mutations that are very similar to women of Ashkenazi Jewish ethnicity, who are more commonly thought to be a high risk population. .
Chemotherapy
Because this form of breast cancer lacks hormone and HER2 receptors, therapies that target them are not used. Instead, metastatic triple-negative breast cancer is usually treated with chemotherapy, McCann says. This chemotherapy is similar to the chemotherapy treatment addressed above.
Immunotherapy
On top of chemotherapy, your provider may also opt to treat you with immunotherapy. Before trying this, doctors will usually examine tissue from the tumor to check it for expression of a biomarker called PD-L1, McCann says. Tumors that express this biomarker tend to be more responsive to a class of immunotherapy drugs known as PD-L1 inhibitors.
The most common immunotherapy drugs used to treat this form of metastatic breast cancer are:
- Abemaciclib (Verzenios)
- Atezolizumab (Tecentriq)
- Denosumab (Prolia, Xgeva)
- Pembrolizumab (Keytruda)
- Sacituzumab govitecan (Trodelvy)
- Trastuzumab (Herceptin, Herzuma, Ontruzant)
- Trastuzumab deruxtecan (Enhertu)
- Trastuzumab emtansine (Kadcyla)
Because tumors can grow and mutate quickly, one complication you may experience with immunotherapy treatment is developing resistance to these drugs, saysMcCann.
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