The future of breast cancer treatment: 5 promising approaches

According to the World Health Organization (WHO), breast cancer was the most common cancer in women in 157 countries out of 185 in 2022, with incidence rates found to be rising by 1% per year overall – and 1.4% per year for women under the age of 50. Fortunately, however, deaths from breast cancer have dropped by around 10% in the past decade. There is a direct link between this statistic and the wide array of new breast cancer treatments that have become available on the market.

In fact, when Phesi released the results of its annual global analysis of all clinical trials conducted in 2024, it showed that breast cancer was once again the world’s most studied disease for the fourth consecutive year, demonstrating the interest in this indication from big pharma and biotech companies. 

In this article, we explore the overall breast cancer treatment landscape, with a particular focus on several biotech companies that have received positive results in the last year for their respective therapies. 

Breast cancer: A broad treatment landscape with an established market

Breast cancer is a heterogeneous disease that encompasses a number of different subtypes defined by distinct molecular profiles, behaviors, and responses to treatment. 

In breast cancer, the cancer cells can either have estrogen receptors (ER) or progesterone receptors (PR), which basically means that the cells have receptors that allow them to use either estrogen or progesterone to grow. Approximately 75% of breast cancers are estrogen receptor-positive (ER+). 

In addition to this, the cancer can either be HER2-positive or HER2-negative; HER2 is a protein that helps breast cancer cells grow quickly. Meanwhile, triple-negative breast cancer means the cancer cells do not have ER or PR receptors, and also do not make any or too much HER2. This type of breast cancer tends to grow or spread faster and comes with fewer treatment options. 

This diversity has led to a complex treatment landscape, with companies adopting several different approaches to tackling breast cancer. 

There are already a variety of approved products on the market to tackle the challenges of this diversity, with several of these therapies now forming the cornerstone of breast cancer treatment. Targeted treatments like Roche’s trastuzumab (Herceptin) have transformed outcomes for patients with HER2-positive breast cancer. Similarly, Pfizer’s palbociclib (Ibrance), a CDK4/6 inhibitor, has become a standard for managing HR+, HER2-negative advanced breast cancer, and AstraZeneca’s olaparib (Lynparza), a poly ADP-ribose polymerase (PARP) inhibitor, provides an option for patients with inherited breast cancer gene (BRCA) gene mutations. 

Nevertheless, many companies are still working toward bringing even more new therapies to the market in an effort to broaden the treatment landscape further, in turn providing a vast array of options for patients – even those who find their cancers resistant to treatment with current standard of care therapies. 

New technologies related to breast cancer

AstraZeneca moves ahead in big pharma race to develop SERD therapies for breast cancer 

In late February 2025, AstraZeneca moved ahead in the race between some big pharmas to bring their Selective Estrogen Receptor Degradation (SERD) therapies to the market, as the company’s drug, camizestrant, demonstrated a highly statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival in HR-positive breast cancer patients when tested in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor in a phase 3 trial. This made it the first and only next-generation oral SERD and complete estrogen receptor (ER) antagonist to demonstrate first-line benefit in combination with widely approved CDK4/6 inhibitors.

The study also featured a novel design that reflected an unmet need in the indication, whereby physicians monitored circulating tumor DNA to spot ESR1 mutations. If a mutation was found before disease progression, patients switched to camizestrant and stayed on the CDK4/6 drug.

SERD therapies are endocrine therapies that bind to and break down ERs, which are found inside the cells of female reproductive tissue, breast tissue, other types of tissue, and some cancer cells. These drugs keep the hormone estrogen from binding to the ERs inside the cells and block the effects of estrogen in the body, stopping the cancer cells from growing.

The first-ever approval for an oral SERD for breast cancer came in 2023 when the FDA approved Menarini’s Orserdu (elacestrant) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. 

Since then, big pharma has been competing with each other to bring more effective SERD therapies to the market. Eli Lilly also reported phase 3 data late last year on its oral SERD, imlunestrant, in patients who progressed on an aromatase inhibitor. Although the results were generally positive, it may need some extra help to reach a broad patient population with ER-positive, HER2-negative breast cancer. Meanwhile, Roche is aiming to have data on its own challenger giredestrant, sometime from mid-2025 onward.

After its own positive results, AstraZeneca plans to share the interim phase 3 data with global regulatory authorities.

BioNTech provides evidence that its bispecific breast cancer treatment can unseat Keytruda

Through its $800 million acquisition of Biotheus, BioNTech gained full control of a candidate that has the potential to unseat Merck’s checkpoint inhibitor Keytruda to become the new standard of care in multiple cancer indications, including breast cancer. The acquisition followed a strategic partnership with Biotheus in 2023, in which BioNTech paid $55 million upfront for the rights to the candidate outside of greater China. 

The candidate in question is a bispecific antibody called BNT327 that targets both PD-L1 and VEGF-A. Essentially, it combines PD-L1 checkpoint inhibition, which is aimed at restoring the T cells’ ability to recognize and destroy tumor cells, with the neutralization of VEGF-A. The blocking of VEGF-A is aimed at reversing the tumor’s immuno-suppressive effect in its microenvironment and cutting off the blood and oxygen supply that feeds tumor cells, with the intention of preventing tumor growth and proliferation. 

When Akeso and Summit Therapeutics’ own PD-1xVEGF-A candidate ivonescimab beat Keytruda in September last year, it spearheaded the belief that this new class of drug can be more effective than traditional checkpoint inhibitors and replace several blockbuster therapies that are currently the mainstay in many cancer regimens. The possibilities presented by this are likely what increased BioNTech’s willingness to bet even further on BNT327 in its acquisition of Biotheus. 

In December 2024, BioNTech added to the evidence that these bispecifics really can unseat Keytruda, reporting positive results from a trial run by Biotheus in patients with locally advanced or metastatic triple-negative breast cancer who took BNT327 and nab-paclitaxel as a first-line therapy. Researchers shared the first look at overall survival data from the trial at the San Antonio Breast Cancer Symposium, showing an 18-month overall survival rate of 69.7%. This was compared to Merck’s KEYNOTE-355 trial, which reported an estimated overall survival at 18 months of 47.8% in triple-negative breast cancer patients who received Keytruda and chemotherapy. 

Although the Keytruda study was a much larger phase 3 trial and we will need to see more data from later-stage studies of BNT327 to be able to properly compare the two, the currently available evidence does suggest that breast cancer patients may live longer on BioNTech’s bispecific. 

Relay Therapeutics’ PI3Kα inhibitor could challenge AstraZeneca’s Truqap 

Relay Therapeutics’ candidate for breast cancer treatment is a phosphoinositide 3-kinase alpha (PI3Kα) inhibitor called RLY-2608 that is designed to target and inhibit only the mutant form of PI3Kα so that it spares the normal enzyme in the hope of minimizing off-target effects and reducing toxicity.

The reason that Relay is targeting PI3Kα is because it is a critical enzyme involved in cancer cell growth and survival. Mutations in the PIK3CA gene – which encodes the PI3Kα enzyme – are some of the most common genetic alterations in HR+, HER2-negative metastatic breast cancer, leading to hyperactivation of the PI3K pathway, in turn driving tumor proliferation and resistance to standard therapies. 

In September 2024, Relay Therapeutics reported that, according to interim data from a phase 2 trial, it had beaten its survival goal for RLY-2608. The study, which is testing the candidate in combination with Pfizer’s Faslodex (fulvestrant), demonstrated a median progression-free survival of 9.2 months in patients with heavily pre-treated PI3Kα-mutated, HR+/HER2- metastatic breast cancer. 

Relay used a subgroup of AstraZeneca’s Truqap study as its benchmark for the phase 2 study of RLY-2608. Again, although cross-trial comparisons can be unreliable, the almost four-month difference between the progression-free survival reported between RLY-2608 and Truqap means that Relay’s candidate could become a challenger to Truqap if it continues to demonstrate the same kind of data in later pivotal trials.  

Relay plans to initiate phase 3 trials for its PI3Kα inhibitor later this year. 

Oncolytics Biotech announces favorable results for immuno-oncolytic virus for breast cancer treatment

Oncolytics Biotech specializes in the development of immuno-oncolytic viruses for cancer and is currently developing pelareorep, an intravenously delivered immuno-oncolytic virus derived from the naturally occurring, unmodified reovirus, as a potential breast cancer treatment. 

The candidate works by exploiting a key vulnerability in cancer cells, in which many tumors lack the ability to defend against viral infections due to defective antiviral signaling pathways. The virus selectively infects and replicates within these cancer cells, causing them to burst and die. Consequently, this releases tumor-associated antigens into the microenvironment and allows the immune system to recognize the cancer cells and kill them. On top of this, pelareorep also stimulates an anti-tumor immune response by activating dendritic cells and T cells, further helping the body to recognize and attack the cancer more effectively. 

Oncolytics is evaluating pelareorep in a phase 2 trial assessing pelareorep in combination with chemotherapy drug paclitaxel in patients with HR+, HER2-negative metastatic breast cancer. In September 2024, the company announced favorable results from this trial, which the company said reinforced the path to funding a registration-enabling study for pelareorep in metastatic breast cancer. The results showed that the two-year survival rate for patients in the pelareorep and paclitaxel combination arm was 64% compared to 33% for paclitaxel monotherapy patients, and the overall response rate was 37.5% for the pelareorep and paclitaxel combination, compared to just 13.3% for paclitaxel on its own.

Oncolytics said in October 2024 that the strong efficacy results from this trial will provide the foundation for a large phase 2 study designed to support accelerated approval from the FDA and that the company is planning to submit a request for this in early 2025. 

Olema Pharmaceuticals presents promising new breast cancer treatment data for small molecule OP-1250 

Olema Pharmaceuticals is a breast cancer-focused biotech company whose lead candidate, OP-1250 (palazestrant), is a small molecule that works as both a complete estrogen receptor antagonist (CERAN) and a selective estrogen receptor degrader. The dual mechanism here is designed to inhibit and degrade the estrogen receptor, with the aim of effectively blocking the estrogen signaling pathways that drive the growth of ER-positive, HER2-negative breast cancer cells.

After sharing positive phase 1b/2 interim data in May 2023 for OP-1250 showing that it exhibited favorable pharmacokinetics, tolerability, and preliminary anti-tumor activity in patients with recurrent, locally advanced, or metastatic ER-positive, HER2-negative breast cancer, Olema presented more promising new data in May 2024 at the European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress that showed its potential as a monotherapy and in combination with other agents for the treatment of ER-positive, HER2-negative breast cancer.

The new data demonstrated that, across 50 treated patients, a combination of OP-1250 and ribociclib was well tolerated with no new safety signals or increased toxicity and no clinically meaningful impact on drug exposure of either therapy. Plus, an 85% clinical benefit rate was observed across all eligible patients. 

Just this week, the company said that a pivotal phase 3 trial of OP-1250 in combination with ribociclib in patients with frontline metastatic breast cancer is on track for initiation this year, enabled by a new collaboration with Novartis and a $250 million equity private placement. Furthermore, another pivotal phase 3 trial of OP-1250 as a monotherapy in patients with 2/3L metastatic breast cancer is on track for topline data in 2026.

Breast cancer: A challenging indication 

As touched upon previously, the sheer diversity of breast cancer and its different subtypes represents some serious challenges for biotech companies. 

Resistance to endocrine therapies, targeted therapies, and chemotherapy continues to limit long-term efficacy for many patients. Furthermore, triple-negative breast cancer remains a critical unmet need due to the lack of hormone or HER2 targets, making it a more aggressive and difficult-to-treat subtype that results in more deaths. 

Having said that, the future of breast cancer treatment is a hopeful one, as more and more therapies with varying targets and functionality work their way toward regulatory approval. Additionally, the potential of certain combination therapies means that carefully put together treatment regimens should be able to tackle the heterogeneity of breast cancer. 

Ultimately, the goal is for patients with any subtype of breast cancer to have a fighting chance of kicking their disease into remission.

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