Educated Patient® Metastatic Breast Cancer Summit Estrogen Receptor-Positive Presentation: June 11, 2022

Hormone-positive breast cancer (where the disease relies on hormones to grow) is the most common subtype of the disease and has a wide array of treatment options — even for those with metastatic disease, according to Dr. Suchita Pakkala.

Pakkala, assistant professor in the Department of Hematology and Medical Oncology at the Emory University School of Medicine, presented on hormone-positive metastatic breast cancer at the CURE® Educated Patient® Metastatic Breast Cancer Summit.

“Hormone-positive and HER2-negative breast cancer represents the majority of breast cancers diagnosed, at 68%,” Pakkala said in her presentation.

When patients with hormone-positive, HER2-negative breast cancer experience disease metastasis (meaning that it spread to other parts of the body), surgery is rarely used, as the cancer has spread to multiple places and may not be able to be effectively taken out. Similarly, radiation use is limited in this setting, too, as cancer may be in symptomatic areas that can cause pain or bleeding, according to Pakkala.

That said, medications are the mainstay treatment for patients with this type of metastatic breast cancer.

“The goal of treatment is to control cancer and to help prevent symptoms and to help people live longer,” Pakkala said.

Upfront Endocrine Therapy

Hormone-positive breast cancer relies on estrogen and other hormones to thrive, so in patients who have not undergone menopause yet, surgical ovary removal or using drugs to stop estrogen production may be a treatment option offered to these patients, known as LHRH agonists.

For patients who have already gone through menopause, Pakkala explained that the ovaries are no longer producing estrogen and, instead, most of the hormone is made in the fat. Drugs called aromatase inhibitors help to block estrogen in this population of patients. Aromatase inhibitors can be given with or without CDK4/6 inhibitors, which block a protein that is needed for cancer to grow.

Additionally, instead of blocking estrogen itself, another treatment approach for hormone-positive HER2-negative metastatic breast cancer includes blocking the estrogen receptor.

“Cancer cells need the estrogen to grow and stimulate growth,” Pakkala said. “And that interaction is through the receptor.”

Most commonly, tamoxifen is used to block estrogen receptors, and can be given with or without an injection to make the estrogen receptors less available.

However, treatment decisions can largely rely on whether a patient underwent menopause.

“When we first see a patient, we want to decide if they’re menopausal or post-menopausal, because that determines what treatments we’re going to give them,” Pakkala said. “If you’re pre-menopausal, we would give you tamoxifen, which is a pill medication or an LHRH agonist, which suppresses your ovaries and makes you menopausal. Then, we can give a postmenopausal medication such as an aromatase inhibitor.”

Side Effects from Hormone Therapy

With the blocking of estrogen comes menopausal side effects, Pakkala explained. This can include vaginal dryness, hot flashes, irregular periods or blood clots.

LHRH is typically well-tolerated, though since it is given via injection, it can cause pain at the injection site or result in mood changes, mild nausea or muscle aches.

“Aromatase inhibitors, however, are more commonly associated with joint or muscle aches in probably about a third of patients,” Pakkala said. “It is also associated with increased cholesterol levels, which may need to be monitored and treated.”

Additionally, CDK4/6 inhibitors have been commonly associated with gastrointestinal issues, such as diarrhea, nausea, vomiting and abdominal pain.

“So with any patient who we’re treating for metastatic breast cancer, patients are going to continue treatment as long as they’re tolerating it, and until disease progresses or gets worse,” Pakkala said.

Second-Line Therapy

“Oftentimes, these patients who are on therapy can have a response initially but will eventually develop some type of resistance where their cancer may progress,” Pakkala noted. “And when this happens, or if they’re intolerant to a therapy, we have to switch their therapy to something else — that’s called second-line therapy.”

Pakkala explained that about 30 to 40% of patients have a PI3 kinase mutation, which is another protein that causes cancer cells to grow. These patients may be offered a regimen of the targeted drug Piqray (alpelisib) plus Faslodex (fulvestrant), a chemotherapy agent.

For those who do not have a mutation, standard of care consists of Afinitor (everolimus), an mTOR inhibitor plus endocrine therapy.

These second-line therapies also come with side effects that patients should be aware of, too, such as increase in blood sugar or rash. Piqray can cause severe increases in blood pressure, while Afinitor is associated with mouth sores and diarrhea.

“As we discussed, for any patient who is on metastatic therapy, we want to follow along with scans about every three months to make sure that they’re responding,” Pakkala said.

PARP Inhibition

About 5% to 10% of patients in the overall breast cancer population harbor a BRCA mutation, and a type of drug called PARP inhibitors has been widely used to treat this patient population.

PARP inhibitors affect the mechanism on how a patient’s cancer cells can repair their DNA that results in cell death.

“PARP inhibitors are often given after initial therapy, and responses can be seen in up to 60% of patients, and at least half of them will respond for at least six months,” Pakkala said. “This is tolerated better than chemotherapy, as is the other endocrine therapies and targeted therapies that we discussed as well. So these are favored as upfront therapy prior to considering chemotherapy.”

Chemotherapy

Chemotherapy is typically offered after endocrine or targeted therapies, but may be used upfront if a response is needed quickly. When determining a potential chemotherapy treatment, patients and clinicians consider any medical problems the patient has, as well as the potential side effects the individual may experience.

“Generally speaking, we go one chemotherapy at a time but sometimes we do (use) combination chemotherapy, depending on the situation or if we need a quick response,” Pakkala said. “Side effects may include but are not limited to low blood counts who again risk for infection, hair loss, fatigue, some cases nausea and vomiting.”

Ultimately, hormone-positive, HER2-negative breast cancer is the most common subtype of the disease and tends to have better outcomes than other metastatic breast cancers thanks, in part, to the breadth of treatments that are available for the disease.

“Just a few words on things that patients can do: if you are undergoing treatment for metastatic breast cancer, other things that are important, are eating well sleeping well,” Pakkala said. “Making sure that you're taking your medications appropriately, remaining active and as healthy as possible, and talking to your doctor about any symptoms or side effects that you have so that we can address them.”

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