Pertuzumab/Trastuzumab-Associated Corneal Melting In Her2+ Breast Cancer

Pertuzumab and trastuzumab are recombinant humanized monoclonal antibodies (mABs) designed to target human epidermal growth factor (EGF) receptors. Specifically, they focus on HER2, an EGF receptor protein that becomes overexpressed in breast cancer, significantly interfering with malignant cells’ survival and proliferation. EGF receptors, and HER2 in particular, are also present on the corneal, limbal, and conjunctival epithelia, where they play a major role in cell proliferation and migration. We describe corneal ulcer reactivation with stromal melting after successful treatment, shortly after pertuzumab/trastuzumab administration.

Corneal toxicity is frequent with the antibody-drug conjugate trastuzumab-emtansine (28%). However, corneal ulceration with trastuzumab monotherapy is rare, and our literature review found only 3 case reports. Severe pertuzumab-induced ocular adverse events have not been reported. In the era of immunotherapy, the ophthalmologist must be familiar with its side effects and discussion with the oncologist will determine the beneficial effects on cancer control vs. irreversible visual loss.

In this report, we present the case of a 57-year-old woman who presented at our clinic with acute left eye pain and photophobia following the use of contact lenses. The patient was undergoing treatment with pertuzumab/trastuzumab for stage 4 (cT2 N3a M1, HER2+) invasive ductal carcinoma of the left breast. Assessment of the anterior segment was performed using the Haag-Streit BQ 900® LED + IM 900® slit-lamp, and anterior segment optical coherence tomography (AS-OCT) was conducted using the Heidelberg Spectralis® system. Corneal swabs were obtained for direct examination and bacterial/fungal cultures.

A central corneal ulcer with stromal melting and a low-grade hypopyon were observed. Fortified ceftazidime/vancomycin drops, oral moxifloxacin, corticosteroids, doxycycline and vitamin C were started. Swab culture revealed the growth of Pseudomonas aeruginosa, susceptible to ceftazidime and ciprofloxacin, guiding antibiotic therapy. Topical corticosteroids were added after re-epithelialization. Four weeks later, the corneal ulcer resolved, leaving a central leukoma. However, 24 hours after pertuzumab/trastuzumab cycle stromal melting and hypopyon recurred, despite the absence of contact lens wear or trauma. A second swab confirmed the same pathogenic agent, prompting the reinstitution of successful treatment with antibiotics and steroids.

The paradoxical worsening of the corneal ulcer likely resulted from a recurrence of Pseudomonas, compounded by pertuzumab/trastuzumab-induced corneal toxicity. This conclusion is supported by the temporal correlation between the medication cycle and the exacerbation, along with the absence of other identifiable risk factors for this recurrence. This case underscores the potential for corneal toxicity and recurrent infectious keratitis as adverse effects of pertuzumab/trastuzumab. Enhanced prevention strategies and closer monitoring, possibly with extended antibiotic treatment, are warranted in such cases.