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CORRESPONDENCE
Year : 2019  |  Volume : 15  |  Issue : 3  |  Page : 722-724

A rare case: Branch retinal vein occlusion associated with the use of tamoxifen


1 Department of Medical Oncology, Ankara Numune Training and Research Hospital, Ankara, Turkey
2 Department of Ophthalmology, Ankara Numune Training and Research Hospital, Ankara, Turkey

Date of Web Publication29-May-2019

Correspondence Address:
Dr. Nebi Serkan Demirci
Department of Medical Oncology, Ankara Numune Training and Research Hospital, 06100 Altindag, Ankara
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.204888

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 > Abstract 


Tamoxifen-induced ocular complications including cataracts, keratopathies, retinopathy, impaired visual acuity, ocular irritation, optical neuritis, and retinal vein occlusion are uncommonly reported in the literature. Herein, we report on a premenopausal patient with right-side breast carcinoma who received adjuvant tamoxifen therapy (20 mg/day) for 1.5 years and developed sudden visual loss. Fundal examination revealed an obstruction in the branch of the retinal vein. The diagnosis was confirmed by fluorescein angiography and optical coherence tomography. Thus, tamoxifen was switched to an aromatase inhibitor. Tamoxifen-induced ocular complications should be kept in mind when visual symptoms are seen in patients undergoing tamoxifen therapy. In such cases, a complete ocular examination should be performed.

Keywords: Breast cancer, ocular toxicity, retinal vein occlusion, tamoxifen therapy


How to cite this article:
Demirci NS, Erdem GU, Uçgun N&, Bozkaya Y, Ozdemir NY, Dogan M, Zengin N. A rare case: Branch retinal vein occlusion associated with the use of tamoxifen. J Can Res Ther 2019;15:722-4

How to cite this URL:
Demirci NS, Erdem GU, Uçgun N&, Bozkaya Y, Ozdemir NY, Dogan M, Zengin N. A rare case: Branch retinal vein occlusion associated with the use of tamoxifen. J Can Res Ther [serial online] 2019 [cited 2019 Jun 24];15:722-4. Available from: http://www.cancerjournal.net/text.asp?2019/15/3/722/204888




 > Introduction Top


Breast cancer is one of the leading causes of cancer-related deaths among women between the ages of 20 and 59 years.[1] Sixty percent of premenopausal breast cancer patients test positive for estrogen receptor (ER+).[2] Estrogen may induce carcinoma cell proliferation in such cases. Tamoxifen, a selective modulator of the ER, is used as adjuvant therapy in ER+ breast cancer patients, reducing mortality and recurrence by up to 30% and 39%, respectively.[3] Despite exhibiting a variety of side effects, tamoxifen is generally well tolerated. Fatigue, vasomotor instability, insomnia, headache, depression, altered menses, fluid retention, nausea, skin rash, ovarian cysts, pain (bone or musculoskeletal), endometrial cancer, pulmonary emboli, stroke, and deep vein thrombosis are some of the systemic side effects.[4] Tamoxifen-induced ocular complications are rare (0.6%) and include cataracts, keratopathies, retinopathy, impaired visual acuity, ocular irritation, and optical neuritis.[5]

Herein, we present a case of branch retinal vein occlusion (BRVO) in a patient who developed sudden visual loss secondary to tamoxifen use.


 > Case Report Top


A 49-year-old perimenopausal woman was diagnosed with invasive lobular carcinoma in her right breast. Modified radical mastectomy was performed 3 years prior. Her pathological staging was T3N3M0, ER-positivity was 10%, progesterone receptor-positivity was 60%, and Cerb-B2 status was negative. Four cycles of adjuvant cyclophosphamide (600 mg/m 2 i.v.), doxorubicin 60 mg/m 2 i.v.), and 5-fluorouracil (600 mg/m 2 i.v. on day 1) (CAF) and four cycles of Taxotere (100 mg/m 2 on day 1) chemotherapy, followed by radiotherapy, were applied. Then, the patient was prescribed oral tamoxifen 20 mg/day and a luteinizing hormone-releasing hormone analog 3.6 mg/month. In her second year of adjuvant tamoxifen therapy, she was admitted to the hospital with a complaint of sudden vision loss in the right eye. Her past medical history was unremarkable in terms of the use of any other drug, comorbid disease, alcohol consumption, smoking, and trauma. A physical examination was normal; her arterial blood pressure was 100/60 mmHg. She was screened for hypercoagulopathy. Her protein C, protein S, factor V Leiden, antithrombin 3, and homocysteine levels were within normal ranges, as was the extent of prothrombin gene mutation. She had no signs of local or systemic infection or vasculitis. On ocular examination, visual acuity (measured using a Snellen chart) was 0.4 for the right eye and maximal for the left eye. Fundal examination of the right eye revealed cystoid macular edema (CME) and retinal hemorrhage. The intraocular pressures in the right and left eyes were 16 and 17 mmHg, respectively. Biomicroscopic examination of the anterior segment was normal. Funduscopic examination of the right eye revealed an obstruction in the inferior temporal vein [Figure 1]. The central macular thickness as measured by optical coherence tomography (OCT) was 367 μm for the right eye and 208 μm for the left eye [Figure 2]. Tamoxifen treatment was terminated and anastrozole (1 mg/day; a nonsteroidal aromatase inhibitor) was initiated. It was expected that the retinal hemorrhages and retinal edema associated with BRVO would regress spontaneously within 3 months. The patient was followed up at 2 months, at which time the findings were as follows. The visual acuity of the right eye was 0.5 and was maximum for the left eye. The macular thicknesses of the right and left eyes were 458 μm and 214 μm upon OCT examination, respectively. Focal laser therapy was applied to the right eye because of an increase in the extent of macular edema. At month 8, the visual acuity of the right eye was 0.4 and maximum for the left eye. The macular thicknesses of the right and left eyes were 424 μm and 211 μm, respectively. As the right eye still exhibited CME and retinal hemorrhage, bevacizumab was injected intravitreally. At month 11, the visual acuity of the right eye was 0.4 and the central macular thickness was 272 μm. The hemorrhage and macular edema had regressed. At month 13, the visual acuity of the right eye was 0.8 and the central macular thickness was 284 μm. Hydration was suggested. The complaints further regressed during later follow-up.
Figure 1: Fundus photograph of the right eye showing a branch retinal vein occlusion involving the superior retina with marked hemorrhage and nerve fiber layer infarction

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Figure 2: Optical coherence tomography scan of the right eye showing macular edema due to branch retinal vein occlusion

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 > Discussion Top


The procoagulant mechanism of action of tamoxifen remains unclear. Although tamoxifen is principally an antiestrogenic drug, it also possesses a weak estrogenic effect that may contribute to prothrombogenic activity. Tamoxifen may trigger acquired hypercoagulability because the drug reduces the levels of natural anticoagulant proteins.[6],[7] Women heterozygous for the Factor V mutation are at 5-fold increased risk for thrombosis when taking tamoxifen.[8] However, tests for hemostatic parameters in patients on tamoxifen have yielded conflicting results and thus such tests are not sufficiently reliable to guide daily practice.[9],[10]

The Early Breast Cancer Trialists' Collaborative Group and two comprehensive studies on breast cancer found that the risk of venous thrombosis is increased by tamoxifen use, particularly during the first 2 years. When tamoxifen is added to preexisting chemotherapy, the procoagulant effect becomes predominant.[3],[11],[12],[13] Earlier case studies have reported retinal vein occlusion caused by thrombotic angiopathy during adjuvant tamoxifen treatment.[14],[15]

Retinal vein occlusion is the second most common cause of visual impairment and blindness (the first is diabetic retinopathy). The pathogenesis is multifactorial and remains unclear. Typical risk factors are increased age, cigarette smoking, diabetes, hypertension, and hyperlipidemia.[16] The prevalence of venous disease in patients with BRVO is 3%.[17]

As we found no other cause that might have contributed to the pathogenesis of the present thrombosis, the BRVO of our case is thought to have developed secondarily to tamoxifen use.

If ocular problems or visual complaints develop in patients on tamoxifen, a complete ocular examination should be performed. If a diagnosis of BRVO is confirmed by fundoscopy, angiography, and OCT, switching to an aromatase inhibitor is the most reasonable strategy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29.  Back to cited text no. 1
    
2.
Pujol P, Daures JP, Thezenas S, Guilleux F, Rouanet P, Grenier J. Changing estrogen and progesterone receptor patterns in breast carcinoma during the menstrual cycle and menopause. Cancer 1998;83:698-705.  Back to cited text no. 2
    
3.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Davies C, Godwin J, Gray R, Clarke M, Cutter D, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: Patient-level meta-analysis of randomised trials. Lancet 2011;378:771-84.  Back to cited text no. 3
    
4.
Fritsch M, Wolf DM. Symptomatic side effects of tamoxifen therapy. In: Jordan VC, editor. Long-term Tamoxifen Treatment for Breast Cancer. Madison (WI): University of Wisconsin Press; 1994. p. 23555.  Back to cited text no. 4
    
5.
Gianni L, Panzini I, Li S, Gelber RD, Collins J, Holmberg SB, et al. Ocular toxicity during adjuvant chemoendocrine therapy for early breast cancer: Results from International Breast Cancer Study Group trials. Cancer 2006;106:505-13.  Back to cited text no. 5
    
6.
Anderson JA, Weitz JI. Hypercoagulable states. Clin Chest Med 2010;31:659-73.  Back to cited text no. 6
    
7.
Jones AL, Powles TJ, Treleaven JG, Burman JF, Nicolson MC, Chung HI, et al. Haemostatic changes and thromboembolic risk during tamoxifen therapy in normal women. Br J Cancer 1992;66:744-7.  Back to cited text no. 7
    
8.
Garber JE, Halabi S, Tolaney SM, Kaplan E, Archer L, Atkins JN, et al. Factor V Leiden mutation and thromboembolism risk in women receiving adjuvant tamoxifen for breast cancer. J Natl Cancer Inst 2010;102:942-9.  Back to cited text no. 8
    
9.
Mamby CC, Love RR, Feyzi JM. Protein S and protein C level changes with adjuvant tamoxifen therapy in postmenopausal women. Breast Cancer Res Treat 1994;30:311-4.  Back to cited text no. 9
    
10.
Mannucci PM, Bettega D, Chantarangkul V, Tripodi A, Sacchini V, Veronesi U. Effect of tamoxifen on measurements of hemostasis in healthy women. Arch Intern Med 1996;156:1806-10.  Back to cited text no. 10
    
11.
Cuzick J, Forbes JF, Sestak I, Cawthorn S, Hamed H, Holli K, et al. Long-term results of tamoxifen prophylaxis for breast cancer – 96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst 2007;99:272-82.  Back to cited text no. 11
    
12.
Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 1998;90:1371-88.  Back to cited text no. 12
    
13.
Hernandez RK, Sørensen HT, Pedersen L, Jacobsen J, Lash TL. Tamoxifen treatment and risk of deep venous thrombosis and pulmonary embolism: A Danish population-based cohort study. Cancer 2009;115:4442-9.  Back to cited text no. 13
    
14.
Onder HI, Kilic AC, Kose SA, Karatas A, Kaya E, Kaya M, et al. Branch retinal vein occlusion associated with tamoxifen use. Semin Ophthalmol 2013;28:88-90.  Back to cited text no. 14
    
15.
Schlich B, Heidrich H, Keuch R, Bleckmann H. Occlusion of finger arteries and thrombotic angiopathy of the retina during adjuvant tamoxifen therapy of a mammary carcinoma. Dtsch Med Wochenschr 1997;122:783-6.  Back to cited text no. 15
    
16.
Lattanzio R, Torres GA, Battaglia-Parodi M, Bandello F. Retinal vein occlusion: Current treatment. Ophthalmologica 2011;225:135-43.  Back to cited text no. 16
    
17.
Fraenkl SA, Mozaffarieh M, Flammer J. Retinal vein occlusions: The potential impact of a dysregulation of the retinal veins. EPMA J 2010;1:253-61.  Back to cited text no. 17
    


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