While it means that your cancer has spread from the original tumor to other parts of your body, this subtype of invasive breast cancer tends to grow slowly and be less aggressive than other subtypes, according to Adam Brufsky, MD, PhD, codirector of the Comprehensive Breast Cancer Center at the University of Pittsburgh. And new therapies are helping patients live longer than ever before. To help you regain a sense of control over your health and make the treatment decisions that are best for you, we gathered answers to some of the most pressing questions people have about HR-positive/HER-2-negative metastatic breast cancer.
1. What does HR-positive/HER-2-negative mean?
Although breast cancer is often thought of as one disease, there are more than 20 subtypes that differ in presentation, response to treatment, and outcomes, according to the American Cancer Society (ACS). A breast cancer is classified as HR-positive if its cells have receptors for the hormones estrogen and progesterone, which suggests the cancer cells receive signals from these hormones that promote their growth. It also means your treatment can include drugs designed to affect hormone production. Roughly two out of three breast cancers test positive for hormone receptors, the ACS says. Cancer tissue is also tested for HER-2 proteins, or receptors, that help control the growth and repair of breast cells. An overexpression of HER-2 proteins causes a marked increase in the reproduction of breast cells, a situation referred to as HER-2-positive. HER-2-negative breast cancers, on the other hand, have cells that contain little to no HER-2 protein, so they tend to grow more slowly and have a better outlook than HER-2-positive cancers, explains Dr. Brufsky. A HER-2-negative diagnosis also means your cancer won’t benefit from therapies that target the HER-2 protein. “Roughly half of metastatic breast cancers are both HR-positive and HER-2-negative,” says Brufsky. “About 70 percent of the time, this subtype of breast cancer spreads to the bone. It’s also commonly found in soft tissue like lymph nodes. It’s sometimes seen in organs like the lungs or liver, and it’s occasionally found in skin.”
Ovarian suppression For premenopausal women with metastatic breast cancer of this type, hormone therapy almost always begins with ovarian suppression by means of surgery to remove the ovaries (oophorectomy) or drugs, such as goserelin or leuprolide, that stop the ovaries from producing hormones, says Brufsky. Ovarian suppression lowers hormone levels in the body so the tumor can’t get the estrogen it needs to grow.Aromatase inhibitors (AIs) Postmenopausal women — and premenopausal women who have undergone removal or suppression of their ovaries — are often treated with AIs, such as anastrozole, exemestane, and letrozole. These drugs block the activity of the enzyme aromatase, which the body uses to make estrogen in the adrenal glands and fat tissue. This means less estrogen is available to stimulate the growth of HR-positive breast cancer cells, according to the National Cancer Institute.CDK4/6 inhibitors These drugs, which include palbociclib, ribociclib, and abemaciclib, block proteins in the cell known as cyclin-dependent kinases (CDKs). CDKs regulate cell proliferation and growth and are often elevated in breast cancer, fueling uncontrolled growth of cancer cells. “They are typically used in combination with AIs as a first-line treatment for HR-positive/HER-2-negative metastatic breast cancer,” Brufsky says.
In addition, you may receive treatments that target specific areas of the body that are affected. Cancer that has spread to the bones, for instance, can be treated with bone-modifying therapy. Chemotherapy may also be part of the initial treatment for those struggling with serious symptoms of metastatic breast cancer, such as difficulty breathing.
3. What are the side effects of treatment?
“Generally, the side effects of hormonal therapies tend to be mild and fairly well tolerated,” says Brufsky. The most common side effects are menopausal symptoms (such as hot flashes), achiness in the joints and bones, and fatigue. “AIs can cause some bone loss (osteoporosis), but that can typically be well controlled with bone-modifying medications,” Brufsky notes. CDK4/6 inhibitors may cause low white blood cell counts as well as some nausea and diarrhea.
4. How can I tell if my treatment is working?
“One way you’ll know is if your pain starts going away,” Brufsky says. Your doctor will also monitor your progress every few months with a variety of assessments, which may include a physical exam, blood tests to check for tumor markers, and imaging tests: X-ray, CT scan, PET scan, or bone scan. The results of these tests, combined with the symptoms you report, will help your cancer team understand whether your treatment is helping to control tumor growth, according to Breastcancer.org. Treatment is typically continued if it’s working and your side effects are manageable, but if the treatment is no longer working or the side effects are problematic, your doctor may switch you to a different drug. “We expect that just about every treatment we choose will work for a period of time and then likely stop working as the cancer develops resistance,” Brufsky says. “Fortunately, we have many treatments that are effective with HR-positive/HER-2-negative metastatic breast cancer.”
5. Should I enroll in a clinical trial?
Clinical trials are definitely worth considering, according to the Susan G. Komen organization. They offer the chance to try and possibly benefit from new treatments. The best time to join a trial is before starting treatment or, if your provider is considering changing treatments, before you switch to a new treatment. Ask your doctor if there are any trials that would suit your circumstances. You can also search the clinical trial database at ClinicalTrials.gov or use the Susan G. Komen Metastatic Trial Search, a personalized tool to match you with clinical trials.
6. Will I ever be cured?
Oncologists don’t talk about curing stage 4 breast cancer as much as managing it as you would other chronic diseases, according to Brufsky. “We’re not likely going to get rid of every single bit of cancer, but we’re learning that people can live with this disease and be asymptomatic for years and years,” he explains. “While the mean survival of patients with HR-positive/HER-2-negative metastatic breast cancer is now over five years, it’s hard to say what the future holds for a woman diagnosed with the disease today. The field is changing so quickly and dramatically that in two or three years, this will be a different conversation.”
