Exploring Breast Cancer Research at ESMO 2025 With Jasmin Hundal, MD, MS, MPH

Early Hormone Receptor (HR)–Positive Breast Cancer

Early breast cancer discussions at ESMO centered around CDK4/6 inhibitors, which have moved into the adjuvant space alongside endocrine therapy.

Dr. Hundal highlighted the monarchE trial as practice‑shaping. High‑risk, early‑stage, HR-positive, node‑positive patients or those with other high‑risk features received 150 mg abemaciclib twice daily for two years. “This produced a statistically significant overall survival (OS) benefit—the first OS benefit we’ve seen in the adjuvant hormone receptor–positive setting,” she noted. The absolute OS difference was 2%, with curves continuing to separate at seven years, reinforcing the durability of benefit. Tolerability remains manageable with experience. “We do know with abemaciclib that the concern is diarrhea,” Dr. Hundal said, “but most clinicians now are comfortable with using dose‑escalation strategies to improve tolerability.”

Updated data from NATALEE also drew attention. Three years of ribociclib maintained invasive disease‑free survival separation at five years, though overall survival is not yet mature. “Ribociclib is increasingly used for lower‑risk or node‑negative patients or for patients who cannot tolerate abemaciclib,” Dr. Hundal explained. Together, these trials underscore that CDK4/6 inhibition in early disease is here to stay, but “patient selection is definitely going to be key.”

Metastatic HR-Positive Disease

In the metastatic setting, ESMO’s focus shifted from first‑line CDK4/6 to new endocrine‑targeted strategies. The two trials that stood out were combination approaches involving oral selective estrogen receptor degraders (SERDs) and mTOR inhibition.

A trial of giredestrant plus everolimus versus standard endocrine therapy plus everolimus demonstrated a hazard ratio of 0.38 for progression‑free survival, which Dr. Hundal described as very exciting,” particularly given that giredestrant is especially active in ESR1‑mutated tumors. This adds “another option to our existing options for our patients,” pending regulatory decisions and further readouts.

The VICTORIA‑1 trial similarly impressed with a targeted agent delivered alongside palbociclib and endocrine therapy, achieving a hazard ratio of 0.24 for progression-free survival. However, toxicity vigilance remains crucial. “With this medication we just have to be very wary about stomatitis,” Dr. Hundal cautioned, emphasizing proactive management if and when such regimens enter routine use.

HER2‑Positive Disease

The HER2 space was marked by multiple DESTINY‑Breast trials evaluating trastuzumab deruxtecan (T‑DXd) across the continuum of care.

DESTINY‑Breast11 evaluated T‑DXd in the neoadjuvant setting for high‑risk (T3 or N1) patients, with four cycles of T‑DXd followed by THP emerging as “a potential new standard.” Anticipated concerns around interstitial lung disease (ILD) were tempered by the data: “You might say you may be worried about ILD, but the rates were low at 4.4% in both groups, which is very reassuring,” Dr. Hundal reported.

In DESTINY‑Breast05, T‑DXd was compared with trastuzumab emtansine (T‑DM1) in patients with residual disease after neoadjuvant therapy. “This significantly improved invasive disease‑free survival with a hazard ratio of 0.47 and also reduced central nervous system (CNS) recurrence, which is very exciting and interesting,” she said. Nonetheless, “ILD still remains a key toxicity” and will require careful monitoring as T‑DXd moves into earlier lines.

Finally, DESTINY‑Breast09 suggested that T‑DXd plus pertuzumab could be a first‑line option in HER2‑positive disease. While data are still maturing, Dr. Hundal is “looking forward to that data as well to see how it matures,” particularly in the context of current paclitaxel/trastuzumab/pertuzumab standards.

Communicating Emerging Data to Patients

Beyond efficacy and safety, Dr. Hundal stressed the communication challenges that arise when robust data precede approvals. “Whenever data comes out and FDA approval is not granted yet, patients always have that question—how are we going to use it? Will I be losing out from what I received instead?” she said. Patients diagnosed months or years earlier may fear they were “suboptimally treated.”

For clinicians, she believes “the key is really patient‑centered communication.” That includes reassuring patients that “we treated them with the best option that we had at that given time,” clarifying what new results mean for their specific case, and distinguishing between data that are promising versus data that are practice‑changing and FDA‑approved. With rapid advances in early, metastatic, and HER2‑positive disease, she finds it reassuring to emphasize that “there are more and more options available” as patients progress through their disease course.

Key Takeaways

• Adjuvant HR-positive disease: Abemaciclib (monarchE) shows a sustained OS benefit with ongoing curve separation at seven years; ribociclib (NATALEE) supports extended IDFS benefit, particularly in lower‑risk or node‑negative settings.
• Metastatic HR+ disease: Giredestrant plus everolimus and other targeted combinations show marked PFS improvements (hazard ratios ~0.24-0.38), especially relevant for ESR1‑mutated tumors, but require close toxicity monitoring (eg, stomatitis).

• HER2‑positive disease: T‑DXd is pushing into neoadjuvant and post‑neoadjuvant settings, improving invasive disease–free survival and reducing CNS recurrence with manageable ILD rates, and may move toward first‑line use in combination with pertuzumab.
• Clinical practice today: Many regimens are not yet FDA‑approved; treatment decisions should balance current standards with emerging evidence while avoiding therapeutic nihilism about past care.
• Patient communication: Transparent, empathetic discussions about evolving data, regulatory status, and individualized applicability are essential to mitigate anxiety and maintain trust as the therapeutic landscape rapidly expands.

About Dr. Hundal

Jasmin Hundal, MD, MS, MPH, is a second-year Hematology/Oncology Fellow at the Cleveland Clinic in Cleveland, Ohio. Previously, she completed her Internal Medicine Residency at the University of Connecticut. Dr. Hundal’s main area of interest is the overlap between cardiometabolic health and cancer, particularly for breast cancer patients and survivors. Outside of work, she enjoys traveling, cooking, and hiking.