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Pulmonary Hypertension Following the Use of Trastuzumab Biosimilars
Timi Ojo1, Kory Cablay2, Neveen Emara3
1University of South Carolina School of Medicine Greenville, Greenville, South Carolina, USA, sc.edu.
Background:
HER2-positive breast cancer comprises 14%-20% of breast cancer cases and was previously linked with aggressive progression. Trastuzumab and its biosimilars have improved survival significantly, but their pulmonary toxicities remain underrecognized. While left ventricular dysfunction is a well-documented adverse effect, pulmonary hypertension, pulmonary arterial hypertension (PAH), and right heart failure are rarely reported.
Case Presentation:
We report the case of a 53-year-old woman with Stage IV HER2-positive invasive ductal carcinoma and well-controlled HIV who presented with shortness of breath, edema, and weakness. She previously completed five cycles of trastuzumab biosimilars (trastuzumab-anns or trastuzumab-dttb), Perjeta (pertuzumab), and Taxotere (docetaxel) and then transitioned to maintenance therapy with just trastuzumab-anns and pertuzumab for one cycle due to neuropathy. Pretreatment and interim echocardiograms showed preserved left ventricular and right ventricular function. Shortly after her last trastuzumab dose, she was hospitalized with severe anasarca, bilateral pleural effusions, and respiratory failure. Right heart catheterization revealed severe precapillary pulmonary hypertension (mPAP 40 mmHg [normal < 20 mmHg], PAWP 8 mmHg [normal ≤ 15 mmHg]), consistent with WHO Group I PAH. Despite aggressive diuresis and respiratory support, her condition deteriorated, and she elected for comfort-focused care.
Discussion:
Although rare, pulmonary vascular complications such as PAH have been linked to HER2-targeted therapies. Reports from clinical trials, FAERS data, and national registries have documented cases of trastuzumab-associated PAH, suggesting a possible vascular mechanism, potentially through ACVRL1 pathway involvement. This case highlights the importance of considering pulmonary hypertension as a potential adverse event in patients on trastuzumab, particularly those with pulmonary metastases.
Conclusion:
Clinicians should be aware of pulmonary complications in patients receiving HER2-targeted therapies, even when left ventricular function is preserved. Early recognition and monitoring of right-sided pressures in high-risk patients may improve outcomes. This case adds to emerging evidence on trastuzumab's pulmonary risks.
Insights
Trastuzumab, used for HER2-positive breast cancer, can cause pulmonary hypertension, a rare but serious side effect. This case highlights the need for awareness and monitoring of pulmonary complications in patients receiving this therapy.
Area of Science:
- Oncology
- Cardiology
- Pulmonology
Background:
- HER2-positive breast cancer is aggressive but treatable with trastuzumab.
- Trastuzumab improves survival but carries risks of pulmonary toxicity.
- Pulmonary hypertension and right heart failure are underrecognized side effects.
Purpose of the Study:
- To report a case of severe pulmonary hypertension in a patient treated with trastuzumab.
- To highlight the potential pulmonary risks associated with HER2-targeted therapies.
- To emphasize the importance of monitoring for pulmonary complications.
Main Methods:
- Case report of a 53-year-old woman with Stage IV HER2-positive breast cancer.
- Patient received trastuzumab biosimilars, pertuzumab, and docetaxel.
- Diagnosis of pulmonary hypertension confirmed by right heart catheterization.
Main Results:
- Patient developed severe precapillary pulmonary hypertension (mPAP 40 mmHg) after trastuzumab treatment.
- Echocardiograms showed preserved left and right ventricular function initially.
- Condition deteriorated despite aggressive treatment, leading to comfort-focused care.
Conclusions:
- Pulmonary vascular complications like PAH are rare but linked to HER2-targeted therapies.
- This case underscores the need for clinical awareness of trastuzumab-associated pulmonary hypertension.
- Early recognition and monitoring of right-sided pressures are crucial for high-risk patients.
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