Iris metastasis from breast cancer successfully treated with Abemaciclib and Letrozole

Abstract

Purpose:

To describe a patient with an unusual presentation of iris metastasis from breast cancer and her response to systemic therapy.

Methods:

Retrospective chart review of one patient.

Results:

A 57-year-old woman presented with a superonasal translucent vascularized iris stromal mass with fish egg-like structures budding from the surface. High frequency anterior segment ultrasonography demonstrated a solid iris stromal mass measuring 6.0 × 3.3 × 1.9 mm. On optical coherence tomography, the egg-like structures appeared as hyperreflective spheres, some of which were detached from the main iris stromal tumor. Oncologic evaluation revealed metastatic breast cancer involving the brain and lung. She was treated with oral abemaciclib and letrozole, as well as external beam radiotherapy to the brain. The iris mass had completely regressed within 4 months and remained undetectable through 8 months follow-up. The other metastatic lesions responded well to therapy.

Conclusion:

We report a case of iris metastasis as the presenting sign of cancer dissemination that was successfully treated with targeted systemic therapy without ocular radiotherapy.

Introduction:

Breast cancer is the most common source of uveal metastasis in women¹ and comprises 37% to 49% of all uveal metastases. ^2,3 Choroid is the most common site of uveal metastasis from breast cancer, with iris accounting for only 3% of such cases.¹

Case Report:

A 57-year-old woman presented with mild redness and blurred vision in the right eye (OD). Her best corrected visual acuity was 20/25 OD and 20/20 in the left eye (OS), and intraocular pressures were normal. Anterior segment examination OD revealed an irregular, translucent vascularized iris stromal mass occupying 2 clock hours superonasally and associated with fish egg-like structures budding from the surface (Figure 1A–B). High-resolution ultrasonography showed a solid iris stromal mass with an irregular bumpy surface, involving the pupillary sphincter and measuring 6.0 × 3.3 × 1.9 mm (Figure 1C). By optical coherence tomography (OCT), the egg-like structures appeared as hyperreflective spheres, some of which were detached from the main iris stromal tumor (Figure 1D). The remainder of the ophthalmic examination in both eyes was unremarkable. Past medical history was significant for stage II estrogen receptor/progesterone receptor (ER/PR)-positive / human epidermal growth factor receptor 2 (HER2)-negative breast cancer treated seven years earlier with bilateral mastectomy. Tamoxifen was recommended at that time, but she declined. She was promptly referred for oncologic evaluation and found to have metastatic breast cancer involving the brain and lungs. Mediastinal lymph node biopsy confirmed the diagnosis and revealed that the cancer was still ER/PR-positive/HER2- negative. She was started on oral abemaciclib (150mg twice daily) and letrozole (2.5mg once daily), and she received globe-sparing external beam radiotherapy (EBRT) to the brain. Four months later, the iris lesions had completely regressed (Figure 2) and remained undetectable though 8 months of follow-up. Systemic imaging showed partial regression and loss of metabolic activity of the lung lesions at 3 months and complete regression of the brain lesions at 5 months after initiating therapy.

Figure 1:

(A) Slit lamp photograph of the anterior chamber shows a flesh-colored, vascularized iris stromal lesion in the superonasal quadrant of the right iris. There are round aggregations of tumor cells with a fish-egg like appearance budding from the main lesion and extending past the pupillary margin.

(B) Slit lamp gonioscopy photograph of the anterior chamber angle in the quadrant of the iris where the tumor is located. The tumor partially extends into the angle and the round aggregations of tumor cells budding form the main lesion are seen extending past the pupillary margin.

(C) High-resolution ultrasonography (Aviso, Quantel Medical, Poland) illustrates a solid iris stromal mass measuring 6.0 × 3.3 mm in diameter and 1.9 mm thick.

(D) Optical coherence tomography (Heidelberg Engineering, Germany) through the iris lesion shows multiple, round, hyperreflective lesions that appear to be distinct from and surrounding the main tumor in the iris stroma.

Figure 2:

Slit lamp photograph of the anterior segment at four months after the start of treatment with letrozole and abemaciclib. The tumor and the fish-egg like aggregations of tumor cells have completely regressed. There is a small area of posterior synechiae that remains in the area where the mass was previously located.

Discussion:

This case provides a striking clinical presentation of iris metastasis from breast cancer and demonstrates the potential effectiveness of targeted systemic therapy. The irregular shape, infiltration of the iris stroma, intratumoral vascularization, and lack of inflammation were consistent with a metastatic process, the suspicion for which was increased by her history of breast cancer. Treatment options for uveal metastasis from systemic cancer include external beam and plaque radiotherapy, systemic chemotherapy, hormone therapy, immunotherapy, surgical resection, and enucleation.^1,4,5 Intravitreal bevacizumab may be useful in patients with secondary neovascular complications.^4,5 Iris metestasis in our patient responded to systemic treatment.

Letrozole is a non-steroidal aromatase inhibitor, and abemaciclib is an inhibitor of cyclin dependent kinases (CDK) 4 and 6, which have been implicated in breast carcinogenesis.^6,7 Binding of estrogen to its receptor activates cyclin D1, which interacts with CDK4 and CDK6 to drive proliferation by inhibiting the retinoblastoma protein.⁷ Pharmacologic blockade of CDK4 and CDK6 by abemaciclib results in cell apoptosis and senescence.^6,7 MONARCH 3, a double-blind, randomized, phase III study of patients with advanced ER/PR-positive / HER2-negative breast cancer without previous systemic therapy, showed that abemaciclib combined with a non-steroidal aromatase inhibitor like letrozole increased progression free survival compared to placebo plus a non-steroidal aromatase inhibitor.^6,7 In our patient, oral abemaciclib and letrozole resulted in excellent systemic response and complete resolution of the iris metastasis without requiring ocular radiotherapy or other ocular treatments.

Summary Statement:

A 57-year-old woman with a history of breast cancer presented with an iris lesion consistent with metastasis. Work up revealed additional metastases to the lungs and brain. Systemic abemaciclib and letrozole yielded excellent response.