New cancer drugs offer fresh hope with a side of new issues to manage | ASCO 2025

As new therapies have entered clinical practice in recent decades, physicians and their patients with breast cancer consider all options and collaborate on a treatment plan that balances the risks and benefits. For some people with cancer, the fear of treatment is as daunting as the disease itself: Will the treatment work and at what cost?

In a session at the 2025 annual meeting of the American Society for Clinical Oncology, expert physicians provided insight into the evolving landscape of breast cancer treatment side effects and how to manage them.

Antibody-drug conjugates

Examples: Datopotamab deruxtecan (Datroway), trastuzumab deruxtecan (Enhertu), ado-trastuzumab emtansine (Kadcyla), and sacituzumab govitecan (Trodelvy)

Antibody-drug conjugates (ADCs) have transformed treatment, providing hope to many people with cancer. Fifteen ADCs are approved for use in various cancers, and at least 150 more are being studied. This unique class of drugs comes with an unexpected side effect – eye and vision problems.

Tiny, cyst-like structures on the surface layer of the eye, called corneal pseudomicrocysts, can form where the blood vessels meet the cornea. They often develop within a few weeks of starting an ADC in as many as 70% of people taking these medicines. The symptoms include blurry vision and eye pain.

At their worst, these can be extremely hard to tolerate and lead to dose delays, dose reductions, or stopping the drug altogether. This side effect is reversible, but it can take up to six months to go away. It is a common side effect of datopotamab deruxtecan (Datroway), which was recently approved for metastatic HR+, HER2- breast cancer. It happens less often with trastuzumab deruxtecan (Enhertu), ado-trastuzumab emtansine (Kadcyla), and sacituzumab govitecan (Trodelvy).

Managing the side effects

Ophthalmologists and oncologists have worked together over time to develop a system to grade and screen for cancer treatment-related vision side effects. To avoid delays in care, eye doctors at the University of California at San Francisco routinely bring eye exams to the oncology clinic, screening multiple patients at a time.

Hormonal therapy

Examples: Tamoxifen, anastrazole, exemestane, letrozole

The side effects of hormonal therapy can be especially troubling for younger people with early-stage breast cancer who stay on the medicine for a long time.

Managing the side effects

As breast oncologists focus more on quality of life, new tools such as these become available to help people feel better.

• NK3 antagonists are a new class of drug that treat hot flashes by blocking the nerve cells that help create them. Fezolinetant already has FDA approval but involves frequent liver monitoring. Promising data on a second drug, elizanetant, are under review by the FDA. Symptoms disappeared within a week for people in the clinical trials, and liver monitoring is not needed. Gabapentin, oxybutynin, anti-depressants, and acupuncture are also effective.
• Vaginal estrogen is safe to use in small doses as a treatment for vaginal dryness. It is available as a three-month ring, a cream, or a tablet to be taken only twice/week (not daily as the label suggests).
• Duloxetine works against joint pain and stiffness caused by aromatase inhibitors (AIs), a common reason people stop this medication. Acupuncture and exercise are effective as well, but acupuncture may cost more out-of-pocket. In some cases, it may make sense to switch to another AI.
• Flibanserin is approved by the FDA to treat low sex drive in premenopausal women based on a small study. Flibanserin can trigger depression, and users should avoid alcohol. A larger randomized trial to look more closely at this drug is being planned.
• Bone loss is a common side effect of AIs. In early-stage breast cancer, measuring bone density, weight-bearing exercises, calcium, and vitamin D all play a role in managing bone health. Anti-resorptive therapy, such as zoledronate, can help slow down bone loss. This class of drugs also reduces the risk of fractures and cancer recurrence in the bones. A baseline dental exam is critical before starting these drugs.

Other common side effects

Skin side effects are associated with immunotherapy, ADCs, and therapies that target certain biomarkers or gene changes in breast cancer cells, such as HER2, PI3K, AKT and TROP. Most skin side effects respond to topical treatments, especially when caught early. Dermatologists can be helpful in providing accurate diagnoses and treatments. A short break from treatment is sometimes needed.

Cardiac side effects are less common but demand immediate attention when they do occur. Oncologists have become more aware of heart complications in recent years and increasingly consider the risk in treatment planning, especially when immunotherapies or targeted therapies may be used. It is important to monitor for heart-related side effects in all patients, but even more so in older people who may already have higher risk of heart disease based on age or other factors.

• An abnormal QT rate —a change in the heart rhythm marked by fast, chaotic heartbeats—has garnered attention recently in discussions of new targeted drugs.
• Checkpoint inhibitors are linked to myocarditis , a serious inflammation of the heart muscle that can be difficult to diagnose.

All side effects are better managed with strong doctor-patient communication before and during treatment, early identification, and involvement of specialists as needed.