Can Targeted Chemotherapy Affect Your Heart? What Breast Cancer Patients Should Know

If you're starting a targeted chemotherapy, antibody-drug conjugates (ADC) such as Enhertu (trastuzumab deruxtecan) or Kadcyla (T-DM1) for HER2-positive breast cancer, here's the heart question worth asking before your first infusion. HER2 is a protein that fuels some breast cancers and is also what these drugs are built to target: they work like guided missiles, homing in on HER2-marked cancer cells to deliver a potent chemotherapy payload directly into the tumor. The catch is that healthy heart muscle cells rely on some HER2 signaling too, and the antibody, its linker, and the specific drug it's carrying can each affect the heart differently, which is part of why Enhertu and Kadcyla don't carry identical cardiac risk, and why Enhertu's payload also carries a separate risk of lung inflammation worth knowing about. In clinical trials, meaningful drops in your heart's pumping strength, called ejection fraction or LVEF (normally 53% to 65%), happen in a modest minority of patients and are usually caught on a screening ultrasound before you'd feel anything. None of this is a reason to avoid these life-saving treatments; it's a reason for routine heart monitoring alongside them, planned jointly by your oncology and cardiology teams rather than managed by either specialist alone.

Key Findings & Takeaways

• Why Enhertu and Kadcyla aren't identical for your heart: Both target HER2, which healthy heart cells also rely on in small amounts, but each drug delivers a different chemotherapy payload directly into cells. Enhertu's payload is linked to a higher and more variable rate of pumping-function decline than Kadcyla's, and separately to a lung-inflammation risk that's specific to that drug.
• What raises your risk: Prior chemotherapy with anthracyclines (like doxorubicin), existing heart conditions such as high blood pressure, coronary artery disease, or prior heart failure, and previous radiation to the left breast or chest wall can all make your heart more vulnerable to these effects.
• How we monitor you: Your team typically orders a baseline echocardiogram, a simple ultrasound of the heart, before your first infusion, then repeats it periodically during treatment. Many of these echocardiograms also measure something called global longitudinal strain, which looks at how well your heart muscle squeezes and stretches with each beat rather than just the overall percentage of blood pumped out. Strain can flag subtle changes weeks before ejection fraction itself starts to drop, giving your team an earlier warning sign. The exact schedule varies by drug, dose, and your individual risk factors, so ask your own team what they recommend for you.
• If your numbers change: A meaningful drop in pumping function usually means temporarily pausing the cancer drug and starting heart-protective medications like ACE inhibitors or beta-blockers, then resuming cancer treatment once your heart recovers, which it usually does. These decisions are always made jointly between your oncology and cardiology teams and tailored to your case, not a one-size-fits-all protocol.
• Symptoms to call about between scans: New or worsening shortness of breath (especially lying flat or on stairs), swelling in your ankles or legs, a racing or irregular heartbeat, unusual fatigue, or new dizziness. Routine ultrasounds catch most problems before you'd feel anything, but don't wait for a scheduled scan if something feels off.
• Questions worth bringing to your next oncology visit: "Will my treatment include an antibody-drug conjugate like Enhertu or Kadcyla?" "Do I have a baseline echocardiogram scheduled before my first cycle?" "Based on my heart history, how often should we recheck my heart function?" "Who should I contact if I notice swelling or shortness of breath between visits?"

Reference Source: American College of Cardiology — JACC: CardioOncology Primer Examines CV Toxicity of ADCs in Breast Cancer

Journal Article: JACC: CardioOncology — Cardiovascular Toxicity of Antibody-Drug Conjugates in Breast Cancer: Current Evidence and Evolving Considerations