Shining a Spotlight on Better Treatment Options for Metastatic ER-Positive/HER2-Negative Breast Cancer

Researchers are always seeking safer, more effective treatment options for breast cancer patients through clinical trials, with the hope that these new treatments could also be more tolerable. For people living with metastatic estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer, the hormone therapy fulvestrant is the standard treatment for those whose cancer has progressed on a combination of hormone therapy plus a CDK4/6 inhibitor as their initial treatment.

Fulvestrant works well as a second-line treatment, as it has been the standard of care for many years, but it’s not perfect. As Virginia Borges, M.D., a medical oncologist at the University of Colorado observes, this treatment can also greatly impact a patient’s quality of life.

“Fulvestrant is two big injections, once a month,” Dr. Borges says. “So, it has never been a particularly convenient drug for the person who has to have that happen on a monthly basis.”

Dr. Borges doesn’t believe in settling for the status quo when it comes to treating breast cancer and is committed to finding more and better options for her patients.

“We are never complacent when we have a drug that has demonstrated benefit and is FDA-approved,” she says. “We want to use science and chemistry and sophisticated drug design to say, ‘Okay, well this worked, but can we change the way it is affecting the cancer?’”

Palazestrant and the OPERA-01 Clinical Trial

Dr. Borges is an investigator for the OPERA-01 clinical trial. This is one of several phase 3 clinical trials aiming to bring the next generation of hormone therapies to patients with metastatic ER+/HER2- breast cancer. Phase 3 clinical trials compare new treatments with the best currently available treatment. The OPERA-01 clinical trial will compare the safety and effectiveness of an investigational hormone therapy, palazestrant (OP-1250), to fulvestrant. Palazestrant is being developed by Olema Oncology.

OPERA-01 will compare factors between these two drugs including how long patients stay on the treatment without their cancer getting worse (called progression-free survival), overall survival, how well the cancer responds to the treatment, general safety and how patients feel during their treatment.

In July 2022, the U.S. FDA granted Fast-Track designation to Olema Oncology for the development of palazestrant. Through a fast track, the FDA can help expedite the review of a drug to help treat serious medical conditions and fulfill an unmet need.

A New Treatment Approach

In early tests, palazestrant has shown promise in patients who have already tried many treatments, with manageable side effects and good results. Palazestrant is both a complete estrogen receptor antagonist (a next-generation CERAN) and a selective estrogen receptor degrader (SERD).

As Dr. Borges explains, palazestrant is building on the success of fulvestrant.

“Think of the estrogen receptor as almost a small little Lego set, and different pieces have to come together for it to have its action,” Dr. Borges explains. “Fulvestrant binds to the estrogen receptor in one place and causes it to break apart. The Lego block breaks into a bunch of pieces, so it can’t tell cancer cells to keep growing and spreading.”

In comparison, palazestrant blocks the estrogen receptor and the signals it sends, while also helping break down the estrogen receptor. OPERA-01 researchers hope this more complete approach will make this treatment work even better and last longer than the standard of care.

“Palazestrant binds in two places in the estrogen receptor, so in theory, that’s going to do a better job of causing the estrogen receptor to break apart and stop working,” Dr. Borges explains.

Benefits to Having More Tools in the Toolbox

OPERA-01 is one of many clinical trials building upon past discoveries to improve progression-free survival for people with metastatic ER+/HER2- breast cancer. As Dr. Borges explains, the goal is to ensure these patients run the longest “race” possible.

“You might think you’re signed up for the marathon and we want you doing the Iron Man, and living as long as possible with this disease,” she says. “In the treatment of ER+ breast cancer, my patient is now running an ultramarathon they didn’t sign up for. We need many, many supports along the way to get them through that ultramarathon and the bottom line is, the longer the ultramarathon, the better.”

Patients with metastatic ER+/HER2- breast cancer need additional treatment options that work better and are more tolerable. Thankfully, researchers are working tirelessly to find more options for these patients.

“We want more tools in the toolbox,” Dr. Borges says. “Every single drug that we bring to market that can improve the duration of progression-free survival means that patients are living longer. And that’s the goal ‒ getting them to have as many years as possible.”

Learn more about the OPERA-01 trial.

Visit our clinical trials page to learn more about clinical trials and read about our other featured clinical trials.

Did you know? Komen has invested in more than 700 new discoveries and over 400 potential treatments in the research pipeline for MBC.

Trial Fact Sheet

Olema Oncology is a sponsor for the Spotlight on Clinical Trials series and the sponsor of OPERA-01.

Shining a Spotlight on Better Treatment Options for Metastatic ER-Positive/HER2-Negative Breast Cancer

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2024-08-09

Twin Sisters Undergo Breast Cancer Together

Aleta and Alicia Sayas are identical twins. They’ve always done everything together – but going through breast cancer at the same time is something neither of them ever expected. And now that they’re finished with treatment, the twins are ready to advocate on behalf of others with breast cancer.

In 2022, two months after passing a physical and clinical breast exam by her family doctor, Aleta felt a lump in her breast. Aleta reached out to her doctor, who ordered a series of tests. She was diagnosed with triple negative and invasive ductal carcinoma. “Learning I had breast cancer was devastating,” Aleta said. During her first appointment with a breast surgeon, Alicia went along for moral support.

“I asked the surgeon, since we’re twins, what does Aleta’s diagnosis mean, since we share the same genetic material,” Alicia explained, adding that she had recently had a 3D mammogram with normal results. “He said since we were identical twins, I needed to get an MRI.”

Alicia’s MRI revealed a spot, and she was sent for a biopsy. Just four weeks after Aleta’s diagnosis, Alicia learned she also had triple negative breast cancer like her sister. “It was a double whammy,” said Aleta. “It’s like I didn’t have time to process my own diagnosis. It was so unexpected. I was emotional. I was angry. I felt like Alicia’s mammogram and the medical community had failed her.”

Alicia was also overwhelmed. “I remember speaking with the oncologist and she mentioned a lot about possible side effects,” Alicia said. “One of them was death. I was in disbelief. It was a frightening experience.”

While there is not a history of breast cancer in the twins’ family, they did undergo genetic testing. Neither tested positive for a BRCA inherited gene mutation. Aleta’s treatment included chemotherapy and surgery and she’s currently on an anti-estrogen medication. Alicia had immunotherapy, surgery, chemotherapy and radiation therapy.

Aleta and Alicia have always been advocates for their health, but this experience propelled them to want to do more. They recently attended Komen’s Advocacy Summit, which has inspired them to advocate on behalf of people with breast cancer. “Breast cancer affects everyone. It doesn’t discriminate,” Alicia said. “And cancer is not free. Between wait times, the lack of affordable healthcare and insurance denials, people are dying.”

“The summit really instilled hope in me, listening to survivors and learning how important it is to continue this fight,” said Aleta. “It’s not going to take one person to fight breast cancer. It has to take everybody in order to find a cure.”

“We wanted to make sure our voices were going to be heard as it relates to the policymakers, the people who regulate, the government regulators,” Alicia added. “There are disparities in breast cancer health.” The sisters do breast cancer awareness at local homeless shelters as a way to get important breast health information to those who may have the least access to it.

“Now that we’ve gone through breast cancer ourselves, we feel like we are in a better position to raise our voices and be part of the solution,” Alicia said.

Learn more about Komen’s advocacy work.

2024-08-28

Komen Ambassador Andy Grammer’s Breast Cancer Connection

Andy Grammer is a multi-platinum recording artist, husband and father to two young girls – and an advocate for breast cancer, a cause close to his heart.

In 2009, when Andy was just 25, he lost his mother Kathy to breast cancer. “Her cancer was diagnosed late, and it happened really quickly. It was a very hard time.”

Losing his mother has influenced the way Andy lives his life and how he approaches his music. Growing up, Kathy was a driving force in Andy’s life and his biggest champion. “She was an incredible mother,” he said. “She was a community builder and a champion of other women.

Prior to his Kathy’s death, Andy had not experienced a lot of tragedy in his life, but found her passing helped ground his art in a way that was important for him. “When you lose someone, you have to get to a place where you learn from it. I had no understanding that people were going through this level of difficulty,” he said. “It became very important for me as someone who sings songs about lifting people to have empathy for what I’m singing about.”

As a way to honor his mother and give back to the breast cancer community, Andy has partnered with Komen “I miss my mom every day, but I’m grateful for what I got from that situation,” Andy said. “It’s helped me see that people are going through pain all the time in all different aspects of life, and there can be a lot of beauty that comes from that.”

Learn more about the ways Andy is giving back and raising awareness for breast cancer. Listen to Andy share his story here.

2024-08-28

4 Reasons Why Your Breast Cancer Experience Isn’t One-Size-Fits-All

If you’ve just been diagnosed with breast cancer, you’re not alone. Since 1 in 8 women in the U.S. will be diagnosed with breast cancer in their lifetime, each diagnosis is as unique as the person receiving it; breast cancer isn’t one-size-fits-all. Your breast cancer experience will not be the same as your aunt’s, friend’s or friend-of-a-friend.

Because of incredible advances in our understanding of breast cancer over the past several decades, treatment for breast cancer is more personalized than ever before. As a 30-year breast cancer survivor, Komen Scientific Advisory Board Member Dr. Sandra Finestone has witnessed these advances first-hand. While treatments have improved, she explains that a breast cancer diagnosis is just as overwhelming now as it was 30 years ago.

“I tell patients when I meet with them, the good news is you have options. The bad news is you have options because you as a patient are expected to make those decisions. But you take someone who’s not been in this arena before and drop them in and the amount of information that’s available is as overwhelming as the diagnosis, and they feel this urgency to make a decision as well,” says Finestone.

As a patient advocate for more than 25 years, Dr. Finestone is a firm believer that patients need access to information about their diagnosis that they can easily understand.

According to Finestone, “I just feel very, very strongly that patients need the information they need, not all of the information, but they need the information that’s particular to their diagnosis.”

Komen is aiming to meet this need through our Know More series. We’ll explain the basic concepts of breast cancer so that you’ll feel confident to dig deeper into our other breast cancer information and be empowered to discuss your concerns with your doctor. Breast cancer is not one disease, but a family of diseases. Below you’ll find the top 4 factors that make your breast cancer as unique as you are.

Biomarkers. Biomarkers are molecules that can be measured in your body – and they can tell your oncologist a lot about your breast cancer. Researchers have discovered three key biomarkers that ultimately determine the types of treatment you’ll receive. The three main breast cancers that are defined by these biomarkers are: hormone receptor-positive, HER2-positive, and triple negative. Everyone diagnosed with breast cancer will fall into one or more of these categories, and your doctor can tell you what biomarkers your cancer contains.

Mutations. Mutations are a type of biomarker, and there are some key mutations your doctor may look for to further customize your treatment plan. Some mutations can be inherited from your mother or father, but most happen spontaneously. In addition, some mutations may also be found in the tumor itself. Genetic testing can be used to identify which treatments might be right for you.

Biology. Doctors are getting better and better at predicting the behavior of your tumor. In addition to looking at individual biomarkers, doctors sometimes use tumor profiling tests to look at how your tumor cell’s genes work together to make them grow, divide and spread. This can give your doctor important information about your risk of recurrence or how likely you are to respond to certain treatments.

If you’re facing a breast cancer diagnosis and not sure where to begin, you’ve come to the right place. Our Know More series will continue to help educate you and arm you with the tools you’ll need to feel empowered to advocate for yourself through your experience.

Hormone receptor status

HER2 status

Triple negative breast cancer

Contents of a pathology report

Hear More:

Watch Breast Cancer Breakthroughs to learn about the latest breast cancer advancements for patients.

Read and listen to our Spotlight on Clinical Trials Series.

More Actions You Can Take:

Questions to ask your doctor if you’ve been diagnosed with breast cancer

Visit Komen’s Patient Care Center for support.

Join ShareForCures. ShareForCures is Komen’s Breast Cancer Research Registry that will be answering some of the most pressing questions in breast cancer. Anyone over age 18 in the United States is eligible to participate.