ESMO 2025 Breast Cancer Research Takeaways

The European Society for Clinical Oncology (ESMO) Congress 2025 is taking place Oct. 17-21 in Berlin. Thousands of people have gathered to share and learn about the latest research on cancer care.

The ESMO 2025 Breast Cancer meeting, a companion conference focused on breast cancer, took place May 14-17 in Munich.

We’re bringing you the top breast cancer research highlights from both meetings.

Two studies suggest that Enhertu, also called T-DXd, may lead to better outcomes in people with early-stage HER2-positive breast cancer.

In the DESTINY-Breast11 study, researchers compared people who received Enhertu (chemical name: fam-trastuzumab deruxtecan-nxki) plus THP chemo regimen (Taxol, Herceptin, and Perjeta) with those who received the standard AC chemo regimen (Adriamycin and Cytoxan) plus THP chemo before surgery. The Enhertu regimen was more effective, as measured by pCR.

Doctors judge how well pre-surgery treatments work by looking at the tissue removed during surgery to see if any actively growing cancer cells are present. If no active cancer cells are present, doctors call it a “pathologic complete response” or pCR. The pCR rates were 67% for Enhertu and THP, compared to 53% for AC and THP.

The Enhertu-THP regimen also caused fewer severe side effects and could be a new standard treatment before surgery for early-stage HER2-positive disease.  

The DESTINY-Breast05 study also showed promising results for early-stage disease. For this study, researchers focused on people who had remaining cancer after neoadjuvant treatment (treatment before surgery). They found that Enhertu was better than Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine) at treating these leftover cancer cells. After three years of follow-up, 92% of people who received Enhertu were alive with no recurrence, compared to 83.5% of people who received Kadcyla.

As Paolo Tarantino, MD, PhD, a breast medical oncologist at Dana-Farber Cancer Institute, said in a press release, “[T]hese two studies establish T-DXd as a critical treatment option for early-stage HER2-positive breast cancer … once considered the most aggressive subtype of breast cancer, and which today represents the one with the highest chance of cure.”

As a first treatment, Trodelvy improved progression-free survival — how long people live without the cancer growing — by three months compared to standard chemotherapy in people with metastatic triple-negative breast cancer who were ineligible for the PD-L1 inhibitor immunotherapy medicine Keytruda. The results of the ASCENT-03 study were also published in The New England Journal of Medicine. Right now, Trodelvy (chemical name: sacituzumab govitecan-hziy) isn’t approved as a first treatment for this type of cancer; it’s only approved for metastatic triple-negative disease that has been treated with at least two lines of chemotherapy. 

“Seeing this improvement in [progression-free survival] does establish [Trodelvy] as a potential new first-line standard of care treatment for this patient population,” Sara Tolaney, MD, MPH, chief of the Division of Breast Oncology at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, said in a video post on X.

Sacituzumab tirumotecan, a new antibody-drug conjugate, led to better progression-free survival — how long people live without the cancer growing — than a doctor’s choice of chemotherapy in people with metastatic hormone receptor-positive, HER2-negative breast cancer that grew during CDK4/6 inhibitor treatment. After six months of treatment, 61% of people who received sacituzumab tirumotecan were alive without the cancer growing, compared to about 26% of people who received chemotherapy. The chemotherapies included in the study were Halaven (chemical name: eribulin), Navelbine (chemical name: vinorelbine), Xeloda (chemical name: capecitabine), and Gemzar (chemical name: gemcitabine).

A new targeted therapy called gedatolisib may help slow the progression of metastatic hormone receptor-positive, HER2-negative breast cancer that grew during treatment with a CDK4/6 inhibitor. When used in combination with Faslodex (chemical name: fulvestrant), with or without Ibrance (chemical name: palbociclib), gedatolisib improved progression-free survival — how long a person lives without the cancer growing — compared to Faslodex alone. Progression-free survival was two months with Faslodex alone; about 7.5 months with gedatolisib and Faslodex; and slightly more than nine months with gedatolisib, Ibrance, and Faslodex. 

Five years of follow-up show that younger women diagnosed with early-stage, hormone receptor-positive breast cancer who paused hormonal therapy to try to become pregnant didn’t have higher rates of the cancer coming back (recurrence) than women who didn’t pause hormonal therapy. These are the latest results from the POSITIVE trial (previous data from the trial focused on recurrence rates after about 3.5 years of follow-up). The recurrence rate in women who paused hormonal therapy was about 12%, which was similar to the 13% recurrence rate seen in the SOFT and TEXT trials, two studies where women took hormonal therapy continuously for five years. Many of the women who temporarily stopped treatment delivered healthy babies: 69% had one or more children.

Combining giredestrant, a new oral selective estrogen degrader (SERD), with Afinitor (chemical name: everolimus) may be a new treatment option for people with metastatic hormone receptor-positive, HER2-negative breast cancer with an ESR1 mutation that’s stopped responding to a CDK4/6 inhibitor. Compared to the standard treatment of hormonal therapy and Afinitor, the combination of giredestrant and Afinitor nearly doubled progression-free survival — how long people lived without the cancer growing — from five months to nearly 10 months. Up to 40% of metastatic estrogen receptor-positive breast cancers develop an ESR1 mutation during treatment. Besides making the cancer resistant to certain hormonal therapy medicines, ESR1 mutations also can make the cancer more likely to grow and spread. The most common side effects of the giredestrant-Afinitor combination were mouth sores, diarrhea, and nausea.

The immunotherapy Keytruda and chemotherapy are commonly used before surgery to treat early-stage triple-negative breast cancer with a high risk of recurrence. But Keytruda is expensive and may not be available or covered by insurance in all countries. A small study has found that adding even a very low dose of Keytruda to chemotherapy before surgery still seems to offer people with early-stage TNBC an advantage over chemotherapy alone. Doctors judge how well treatments before surgery work by looking at the tissue removed during surgery to see if any active cancer cells are present. If none of these are present, doctors call it a “pathologic complete response” or pCR. The pCR rates were 54% for low-dose Keytruda and chemotherapy compared to 40.5% for chemotherapy alone. The low dose of Keytruda was less than one-tenth of the current standard dose for early-stage TNBC. 

“There is an urgent unmet need to revisit the dose for immune checkpoint inhibitors [like Keytruda], as this can radically improve the access and decrease financial toxicity,” said Atul Batra, MBBS, MD, DM, assistant professor of medical oncology at the All India Institute of Medical Sciences, who presented the results.

When a new drug called culmerciclib was added to Faslodex (chemical name: fulvestrant) as a first treatment for advanced-stage hormone receptor-positive, HER2-negative breast cancer, people had better progression-free survival — how long they lived without the cancer growing — than Faslodex alone. After 18 months of follow-up, about 70% of people who received culmerciclib and Faslodex were alive with no cancer progression, compared to about 50% of people who received Faslodex alone. 

Culmerciclib is a medicine similar to the CDK4/6 inhibitors, but is a CDK2/4/6 inhibitor. Because culmerciclib also inhibits the CDK2 enzyme, which stops cells from dividing at a later stage, researchers think it may help stop cancers from becoming resistant to the medicine. “[The results] support this combination as a promising new therapeutic strategy,” said Erwei Song, MD, PhD, professor of breast surgery at Sun Yat-sen University, who presented the research.

Among more than 6,230 women with a BRCA mutation who were diagnosed with early-stage breast cancer while pregnant, one out of three went on to have another pregnancy, according to an analysis of information from a large international study. When compared with women who didn’t have another pregnancy, there were no differences in survival among the women. “No safety concerns emerged regarding material or fetal outcomes,” said Marta Perachino, MD, medical oncologist and clinical investigator at Vall d’Hebron Institute of Oncology, who presented the research.

Doctors have been wondering what the best treatments are for people diagnosed with advanced-stage estrogen receptor-positive, HER2-negative breast cancer that came back (recurred) or grew during or after treatment with a CDK4/6 inhibitor. Would another CDK4/6 inhibitor offer benefits? Should it be combined with another medicine?

The latest results from the EMBER-3 study show another CDK4/6 inhibitor can be effective. The combination of Verzenio (chemical name: abemaciclib), a CDK4/6 inhibitor, and imlunestrant, a new selective estrogen receptor downgrader (SERD), offers better progression-free survival (the amount of time a person lives without the cancer growing), (9.3 months), than imlunestrant alone (3.7 months) in people who previously received a CDK4/6 inhibitor (Ibrance, also known as palbociclib, in most cases).

Final survival results from the APHINITY study continue to show that adding Perjeta (chemical name: pertuzumab) to Herceptin (chemical name: trastuzumab) and chemotherapy after surgery for early-stage HER2-positive breast cancer reduces the risk of the cancer coming back (recurrence) and improves survival.

After 10 years of follow-up, overall survival rates were 91.6% with Perjeta, Herceptin, and chemo, compared to 89.8% with just Herceptin and chemo. Adding Perjeta also reduced the risk of recurrence. Ten-year disease-free survival rates (the percentage of people who were alive with no recurrence after 10 years) were 87.2% for people who received the three medicines and 83.8% for people who received only Herceptin and chemo.

No new heart side effects were seen with longer follow-up.

“After 10 years, the APHINITY trial clearly shows a statistically significant and clinically meaningful improvement of the overall survival,” said Sibylle Loibl, MD, PhD, chair of the German Breast Group who presented the research. “Adding Perjeta to a standard adjuvant treatment is most beneficial for people with HER2-positive breast cancer with lymph node-positive disease who are at high risk of recurrence.”

Gaining more than 5% of body weight after a breast cancer diagnosis increased the risk of dying from the disease for women living with healthy weight or overweight before diagnosis.

The results come from an analysis of more than 6,800 women in the Nurses’ Health Study.

The women were diagnosed between June 1978 and June 2018. They were followed for about four to 15 years.

Before diagnosis, women with a BMI of less than 25 (healthy weight) who gained more than 5% of their body weight had a 32% higher risk of dying from breast cancer than women who didn’t gain that much weight. Women with a BMI of 25-29.9 (overweight) before diagnosis had a 37% higher risk of dying from the disease if they gained more than 5% of their body weight. In contrast, women with obesity didn’t have a higher risk if they gained weight.

The researchers found that losing weight or gaining less than 5% of body weight didn’t affect the risk of dying from breast cancer. They’re not sure why this is.

“We aimed to identify specific weight gain thresholds associated with the risk of breast cancer mortality to provide guidance for professionals managing breast cancer patients,” said Sixten Harborg, MD, a physician and PhD fellow at Aarhus University Hospital in Denmark, who presented the research.

What is the future for young women with breast cancer? What are their unique needs and challenges? What questions do they have that older women don’t have? Anne Partridge, MD, MPH, addressed these issues during her keynote address, “A decade of BCY [Breast Cancer in Young Women]: What we have done and where we are going?”

Partridge is interim chair of the Department of Medical Oncology at the Dana-Farber Cancer Institute, where she also serves as director of the Adult Survivorship Program and co-founder and director of the Program for Young Adults with Breast Cancer.