6 Questions About HR-Positive/HER2-Negative Metastatic Breast Cancer, Answered

2. How Is This Cancer Treated?

Fortunately, newer therapies are helping people with HR-positive/HER2-negative breast cancer live longer than ever before. “It doesn’t really matter which therapy you have; most of the trials right now suggest an overall survival in excess of 60 months — like 65 to 67 months,” Brufsky says.

Your treatment plan will depend on where the cancer has spread, the extent of the disease, other medical conditions you have, and your age and menopause status. Common therapies include CDK 4/6 inhibitors, ovarian suppression, and aromatase inhibitors (AIs). Brufsky says that, in general, people with metastatic HR-positive/HER2-negative breast cancer can typically expect to live without their cancer getting worse for about two to two and a half years after starting their initial treatment. Overall, their chance of surviving beyond five years is good, even if the cancer has spread to other parts of the body.

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, explains Brufsky. Ovarian suppression lowers hormone levels in the body so the tumor can’t get the estrogen it needs to grow.

Aromatase Inhibitors (AIs)

Post-menopausal 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/HER2-negative metastatic breast cancer,” Brufsky says.

The most common therapy for metastatic HR-positive, HER2-negative breast cancer is a CDK 4/6 inhibitor along with endocrine therapy as the first line of treatment, notes Brufsky. He says the specific inhibitor doesn’t make a big difference, as many recent trials suggest an overall survival of around 65 to 67 months, regardless of the therapy approach.

Still, one study from 2023

found that initial treatment without CDK4/6 inhibitors keeps the cancer from progressing for a few months to over a year, but adding these inhibitors extends this time by 9 to 14 months, lasting over 25 months. Another study from 2022

followed more than 5,600 patients for about 3.5 years and saw that the group using abemaciclib along with hormone therapy had a better chance of staying cancer-free than those only on hormone therapy. After four years, more people in the abemaciclib group were free of cancer (about 86 percent) compared with those on hormone therapy alone (about 79 percent).

After any of these first-line treatments, Brufsky says, “Most people within a couple years will progress and go on to second line therapy, but I have had patients on these therapies for nine years. Generally, [treatment] is indefinite.”

But if your cancer has spread, you will most likely also receive treatments that target specific areas of the body affected. For example:

  • If your cancer has spread to your bones, you will most likely receive bone-modifying therapy. Medications such as denosumab and zoledronic acid decrease bone turnover at the cancer-bone interface, preventing lesions, bone weakness, and fractures. The goal of bone-modifying therapy is to reduce common side effects like bone fractures and elevated calcium levels in the blood, which, according to the Mayo Clinic,

    can cause fatigue, nausea, constipation, excessive thirst, frequent urination, and confusion. But Brufsky says both medications can cause some reactions, as well. “About 10 to 20 percent of people will get achiness and a flu-like reaction that lasts a day or two.” Brufsky also says both medications carry a rare side effect called osteonecrosis of the jaw, which means these drugs can interfere with bone healing in situations like invasive dental procedures.

  • If you are struggling with serious symptoms of metastatic breast cancer, such as difficulty breathing, chemotherapy may also be part of your initial treatment. It can help target the cancer cells causing these symptoms.

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.

CDK 4/6 inhibitors, such as ribociclib, are associated with lowering the body’s neutrophil count. Neutrophils are white blood cells that help the body fight off infections. Ribociclib specifically also carries a risk of irregular heartbeats and liver function abnormalities. Abemaciclib, another CDK 4/6 inhibitor, has side effects like diarrhea, lung inflammation, and an increased risk of blood clotting.

In the context of advanced disease, certain medications, particularly aromatase inhibitors, can result in achiness and joint pain. “AIs can cause some bone loss (osteoporosis), but that can typically be well controlled with bone-modifying medications,” Brufsky notes. Meanwhile, Faslodex, a chemotherapy injected into the buttocks, can cause pain in the injection site.

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 various assessments, including a physical exam, blood tests to check for tumor markers, and imaging tests: X-ray, CT scan, PET scan, or bone scan. According to,

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.

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 try a different approach. “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/HER2-negative metastatic breast cancer.”

5. Should I Enroll in a Clinical Trial?

Clinical trials are worth discussing with your care team, 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 or use the Susan G. Komen Metastatic Trial Search, a personalized tool to match you with clinical trials.

6. Will I Ever Be Cured?

Brufsky says oncologists don’t talk about curing stage 4 breast cancer as much as managing it, just as you would any other chronic disease. “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/HER2-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.”

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