Correspondence *Sunnybrook Health Sciences Centre, Odette Cancer Centre, T2053–2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada

Email ellen.warner@sunnybrook.ca

The case

A 57-year-old woman presented to a medical oncology clinic complaining of blurred vision. She had first noticed distorted vision in her left eye approximately 1 month before presentation. However, her visual acuity had worsened considerably over the previous 3 days, to the point where she could no longer read with her left eye. On examination, her visual acuity was reduced to the ability to count fingers in her left eye at 30 cm. She had undergone a lumpectomy followed by an axillary lymph node dissection for a 1.1 cm infiltrating duct carcinoma of the right breast 6 years previously. She had no family history of breast or other cancers, and all fourteen lymph nodes were free of malignancy. The lesion was moderately differentiated with involvement of vascular spaces, and was both estrogen-receptor positive and progesterone-receptor positive. Radiation therapy was administered to the right breast, which consisted of 5,000 cGy in 25 fractions over 5 weeks, followed by a boost of 1,000 cGy in 5 fractions over 1 week because of close resection margins. Adjuvant oral tamoxifen 20 mg daily was given for a total of 5 years.

On ophthalmologic examination, the right eye was normal (Figure 1A); in the left eye, however, a choroidal mass was visible around the optic nerve head, with serous retinal fluid and serous retinal detachment that extended to the macula (Figure 1B). Ultrasonography showed a mass lesion that involved the optic nerve and a large proportion of the fundus, which was irregular in thickness and internal reflectivity, consistent with a metastatic lesion. Areas of serous retinal elevation could also be seen over the lesion and below the optic nerve. Fluorescein angiography showed hyperfluorescence and staining of the optic nerve, consistent with disc edema. Subretinal fluid was visible around the optic nerve head and extended into the macular region (Figure 1C). CT of the head showed a thickening in the posterior aspect of the left globe that was consistent with a choroidal metastasis. Other metastatic work-up, including chest X-ray, abdominal ultrasonography, bone scan, and bilateral mammography, was negative. The levels of carcinoembryonic antigen and CA15-3 (a tumor marker) were within normal limits. Radiation therapy, consisting of 3,750 cGy in 15 fractions, was administered over 19 days to the midplane of both eyes, because of the possibility of subclinical involvement of the right eye. By the sixth fraction, the patient reported an improvement in her vision. After the completion of radiotherapy her vision had returned to almost normal (20/30), and she was started on a 2.5 mg daily dose of letrozole. Her optic nerve returned to normal, with no subretinal fluid (Figure 2). Since then she has been followed semi-annually (medical oncology alternating with radiation oncology) and has continued to take letrozole (at the same dose and schedule as above). She has an excellent quality of life and has had no evidence of recurrence as of her last appointment in September 2008.

Figure 1 Pretreatment color retinal photographs and fluorescein angiograms.

(A) Retinal photograph showing normal right eye. (B) Retinal photograph of the affected left eye, showing optic nerve swelling and subretinal fluid. (C) Fluorescein angiogram of left eye showing optic nerve swelling and subretinal fluid. (D) Fluorescein angiogram of normal right eye.

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Figure 2 A post-treatment retinal photograph shows pigmentary changes after radiation, but normal optic nerve and no subretinal fluid.

The dark patch in the lower right corner is an artifact.

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At 8 years after her initial presentation to the medical oncology clinic with distorted vision and decreased visual acuity, she required bilateral cataract surgery, but has had no evidence of radiation retinopathy and no dry eye symptoms or other ocular sequelae of radiotherapy. The plan is to follow her at 6-monthly intervals and to keep her on letrozole indefinitely because of the suspicion of occult metastatic disease outside the eye.

Discussion of diagnosis

The choroid is the vascular, pigmented tissue layer between the retina and the sclera that provides the vascular supply to the outer part of the retina and forms the uveal tract, along with the iris and ciliary body. A choroidal metastasis is often an indicator of poor outcome,¹ and can represent the smallest clinically detectable metastasis; lesions as small as 1 mm can be detected by slit-lamp biomicroscopy and ophthalmoscopy.² The route of metastasis to the choroid is hematogenous, as intraocular structures have no lymphatic drainage.³ The iris is less frequently affected by metastatic disease,⁴ and metastatic tumors in the retina are extremely rare.³ The clinical presentation of choroidal metastases is usually blurred vision or decreased visual acuity, both of which were experienced by this patient.^{1, 2, 4} Other symptoms occur less frequently, but can include flashes and floaters, pain, metamorphopsia and scotomas.

Choroidal metastases should be suspected in any patient with a history of cancer, particularly one with known metastatic disease, who presents with progressive visual symptoms. A choroidal lesion is, however, rarely the presenting sign for a previously undetected primary malignancy. The diagnosis is generally made with slit-lamp biomicroscopy and ophthalmoscopy.⁵ On ophthalmoscopic examination, the choroidal metastasis is described as 'a creamy yellow subretinal mass, often with a secondary retinal detachment'.⁴ The clinical appearance of the lesion is often pathognomonic of metastatic disease and requires an accompanying systemic work-up if suspected. Fluorescein angiography and ultrasonography can be helpful in diagnosis, and fine-needle aspiration biopsy with cytologic or even histologic evaluation can be used in difficult cases that cannot be established with less-invasive methods.⁵ In this patient the diagnosis was made on ophthalmoscopy and was supported by the findings on ultrasonography and fluorescein angiography. A neurological examination and CT of the brain (as undertaken in this patient), or preferably MRI if available, should also be performed as the likelihood of brain metastases increases with the advent of choroidal metastases.² Although the choroid is a rare site of metastases from any cancer, in most studies, breast cancer represents the most common primary site of choroidal metastases, followed by lung cancer.^{4, 6} The true incidence of choroidal metastases is difficult to determine as studies that were unselected for visual symptoms are rare. In clinical, nonautopsy case series, the frequency of choroidal metastasis in patients with metastatic breast cancer ranged from 0 to 9.2%.^{1, 7, 8, 9} The study by Mewis and Young¹ included both symptomatic and asymptomatic patients, and 9 (9.2%) of 98 asymptomatic patients with disseminated disease had choroidal metastases. The potential role of screening patients with metastatic breast cancer who have no ocular symptoms was investigated in three studies: the frequencies of asymptomatic choroidal metastases were 5%⁷, 0%⁸, and 0%.⁹ Interestingly, the frequency of choroidal metastases from breast cancer seems to be decreasing with time. One possible explanation for this decrease is the greater and prolonged use and aggressiveness of adjuvant systemic therapy (both chemotherapy and hormonal therapy), which might be particularly effective in the eradication of tiny micrometastases in a well-vascularized environment such as the choroid. Screening asymptomatic patients for choroidal metastases is, therefore, probably unnecessary.

Treatment and management

As the current patient's choroidal metastasis extended to the macula, urgent radiation therapy was initiated in the hope that some of the rapid visual deterioration and macular involvement might be due to edema, which would be likely to be reversible. The traditional treatment for choroidal metastases from breast cancer is external-beam radiation therapy, which results in improvement of functional vision in the majority of patients.^{1, 10, 11} Timely initiation of radiation therapy is critical, and contributed to the good recovery of vision in this patient. Radiation therapy should begin as soon as possible after the diagnosis is made. In the series by Mewis and Young,¹ of 52 irradiated eyes in patients with choroidal metastases, 94% had stabilization or improvement in vision. Treatment consisted of 2.5–3.0 Gy delivered through a lateral portal in 10 fractions. In a larger series by Rudoler and colleagues,¹⁰ 57% of 155 eyes assessed demonstrated improved visual function or maintenance of navigational vision (defined as best corrected visual acuity of 20/60–20/200) after radiation therapy. The ideal treatment, however, depends partly on other patient-related factors, such as systemic involvement. Case reports exist of choroidal metastases that have regressed on chemotherapy,¹² hormonal therapy,¹³ and combination chemotherapy with trastuzumab.¹⁴

A case series in which aromatase inhibitors (anastrazole, letrozole and exemestane) alone were used in the treatment of choroidal metastases showed promising results; 10 (59%) of 17 patients showed regression after an average of 20 months (range 4–48 months) on medication.¹⁵ In this case series, one of the patients had also been previously treated with a lumpectomy, radiation to the breast and tamoxifen, and the isolated choroidal metastasis regressed with treatment. However, questions still remain as to whether aromatase inhibitors by themselves should be the sole treatment; seven patients did not respond, three of whom ultimately required external-beam radiation therapy. In addition, follow-up was limited to 20 months.¹⁷ The paper did not report whether visual acuity deteriorated, stabilized, or improved over the time to regression, and no details of ultimate visual outcome were presented. The choice of hormone therapy (rather than chemotherapy) for our patient was based on the desire to maintain quality of life in a patient with no clinical or radiologic evidence of metastatic disease outside the eye, while still providing systemic therapy in the hope of delaying the progression of statistically probable, occult metastases. The choice of letrozole over other aromatase inhibitors was somewhat arbitrary.

This patient's outcome is remarkable because the prognosis of patients with breast cancer and choroidal metastases is generally poor.^{1, 2, 12} Given that the patient has been on empiric, 'adjuvant' hormonal therapy with letrozole since the diagnosis of her solitary metastasis, this highlights the potential role of hormonal therapy in the treatment and secondary prevention of choroidal metastases. Whether hormonal therapy should be used as an adjunct to radiation therapy, or can be used as the sole agent, is still open to question.

Conclusions

In this Case Study, we present a patient treated for an isolated, choroidal metastasis 6 years after the original diagnosis of breast cancer, and who has now been free from disease for 9.5 years. To the best of our knowledge, this report is the first to document such prolonged, disease-free survival. Awareness needs to be raised among oncologists about this treatable complication of breast cancer, as most literature on choroidal metastases is published in ophthalmology journals.

Acknowledgments

Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

The authors would like to thank the patient for agreeing to this case report. Written consent for publication was obtained from the patient. We would also like to thank Doug Nicholson and the administrative staff in the Ophthalmology Clinic (Sunnybrook Health Sciences Centre) for helping us to obtain the retinal images.

References

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Subject areas under which this article appears: Radiotherapy