For the past 20 years, people with early estrogen receptor-positive (ER+) breast cancer have received a standard treatment, including hormone therapies like aromatase inhibitors or tamoxifen. While these patients generally have good outcomes after this treatment, they are still at risk for recurrence. As researchers seek more targeted and effective treatments for people with early ER+ breast cancer, they are changing the game with promising new hormone therapies that could offer better outcomes to these patients.
In this episode of Breast Cancer Breakthroughs, we speak with Komen grantee Sean Fanning, Ph.D., assistant professor of cancer biology at Loyola University Chicago about how hormone therapies work and where improvements are still needed. We also speak with Priya Rastogi, M.D., medical oncologist at the University of Pittsburgh School of Medicine about how new clinical trials are bringing improved hormone therapies to people with early ER+ breast cancer.
Expanding the Treatment Arsenal for Early ER+ Breast Cancer
Hormone therapies work by directly targeting the estrogen receptors in cancer cells. Estrogen can attach to these receptors and cause them to divide and grow. When a hormone therapy drug blocks the estrogen receptor of a cancer cell, it stops the signals that it needs to keep growing.
Three different types of hormone therapies are approved by the Food and Drug Administration (FDA). Aromatase inhibitors stop the production of estrogen and selective estrogen receptor modulators (SERMs) like tamoxifen prevent estrogen from binding to the receptor. A third type, known as selective estrogen receptor degraders (SERDs), damage the estrogen receptor and cause the cell to throw it away.
The first FDA-approved SERD called fulvestrant (Faslodex) offered promising results in treating metastatic breast cancer (MBC), especially if a person’s cancer became resistant to other types of hormone therapies. However, the drug has some pitfalls; it’s too weak to be given as a pill and needs to be given as an injection into the buttocks.
“This was the first real need for an oral SERD, to develop something that was pharmaceutically better and easier on the patient,” Dr. Fanning says.
Fulvestrant and elacestrant (Orserdu) are currently only used to treat MBC, but several clinical trials are looking at whether these SERDs could be used to treat people with early ER+ breast cancer.
Balancing Risk and Treatment
For people with early ER+ breast cancer who are at higher risk for their breast cancer coming back, minimizing this risk often comes with the burden of more treatment. Currently, those with higher risk of recurrence are prescribed 5-10 years of hormone therapy after their initial treatment, which is usually a combination of radiation and surgery, plus chemotherapy or CDK4/6 inhibitors, depending on their treatment plan.
Today, researchers are working to find new treatments for these patients that will reduce the risk of recurrence. In this episode, Dr. Rastogi describes four phase 3 clinical trials in progress that are evaluating new oral SERDs for people with early ER+ breast cancer who are at an increased risk of recurrence based on their tumor’s characteristics.
Two of these trials are testing two different approaches for the new oral SERD camizestrant. Dr. Rastogi is involved in the CAMBRIA-1 trial, which is investigating whether switching hormone therapy to camizestrant after 2-5 years of standard treatment can effectively reduce the risk of recurrence compared to standard hormone therapy. The CAMBRIA-2 trial is also testing the impact of camizestrant on breast cancer recurrence when it is given up front, instead of standard hormone therapy.
“What I think is really important with all these studies, if the [results] show that there are improvements in outcomes for patients who receive it, is there’s more treatment options available to patients,” Dr. Rastogi says.
More Options Means More Decisions
Komen Scientific Advisory Board Member, Sandra Finestone, Psy.D., has seen incredible progress in breast cancer research over the last 30 years, including the evolution of hormone therapies. Hormone therapies were not an option when Finestone was first diagnosed with breast cancer, when the common treatment was a single or double mastectomy. “The advances that have been made in the 30 years since I was diagnosed have been unbelievable,” she says.
Hormone therapy options for early ER+ breast cancer continue to expand as new clinical trials present more effective and tolerable drugs like oral SERDs. While a larger variety of treatments is a good thing, it can also mean new challenges for people with early ER+ breast cancer.
“I tell patients when I meet with them, the good news is you have options,” Finestone says. “The bad news is you have options, because you as a patient are expected to make those decisions.”
Some of these decisions include, can I live with these side effects? Will I remember to take a pill every day, or would it be better for me to have a scheduled treatment like a shot? Patients also face the decision of, do I want as much treatment as possible, or do I trust my doctor if they say I can have less?
According to Finestone, the best way for patients to make informed decisions is to have the best information possible, delivered in a language they can understand.
“Having someone there like Komen, like the navigators that can help bring that language into understandable proportions and meaning for a patient is huge, huge beyond what the patient appreciates and understands,” Finestone says. “And that’s certainly what this community needs.”
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If you’d like more information about choosing a clinical trial, BreastCancerTrials.org, in collaboration with Susan G. Komen®, offers a custom matching service to help find clinical trials that fit your needs.
To learn more about Komen patient navigators and the support they provide, visit: https://komen.org/patientcarecenter
To speak with a Komen navigator, call (877) 465-6636 or email helpline@komen.org
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