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Breast Disease 34 (2014) 173–176 DOI 10.3233/BD-140367 IOS Press

Case Report

An unusual orbital metastasis of breast cancer Lorenzo Rossi∗, Serena Zancla, Liana Civitelli and Ersilia Ranieri Azienda Policlinico Umberto I, Centro Prevenzione e Diagnosi Tumori, Palazzo Baleani, Rome, Italy

Abstract. In this paper we report the clinical case of a 84 year old female patient with a history of breast cancer diagnosed 14 years before, treated only with hormone therapy for 10 years and with subsequent follow-up oncology which always demonstrated negative results. 14 years after the first diagnosis, the patient presented with an increase in mass markers (CEA), and progressive symptoms of the right eye (diplopia). A CT scan and an MRI of the orbits confirmed the presence of an expansive neoplastic formation of the right orbit of 16 × 9 mm. The orbital metastases are rare locations of metastatic breast cancer which pose problems of differential diagnosis and require prompt and multimodal treatment (chemotherapy, hormone therapy, radiation therapy) aimed at improving the quality of life of the patient. Keywords: Orbital metastases, unusual breast carcinoma metastases

1. Introduction Breast cancer is a disease characterized by high rates of incidence and increasing long-term survival rates. The improvement of adjuvant therapies and diagnostic techniques has allowed for an increase in the number of long-term survivors, and has consequently prolonged the time of the appearance of local or distant recurrence, which can often appear many years after the first diagnosis of breast cancer in patients who become elderly or in unusual sites. The orbital structures are unusual sites for the appearance of secondary tumors, which account for between 2 to 11% of all orbital neoplastic lesions [1, 2]. The presence of a secondary orbital lesion presents many difficulties of differential diagnosis and treatment, which must be as timely as possible and aim for rapid improvement of the quality of life of the patient.

∗ Corresponding author: Lorenzo Rossi, Centro Prevenzione e Diagnosi dei Tumori, Palazzo Baleani, Corso Vittorio Emanuele II, 244, 00188 Rome, Italy. Tel.: +39 06 49978675; Fax: +39 06 49978678; E-mail: [email protected]

2. Case report We submit the clinical case of a female patient 84 years of age, without significant comorbidity but with a positive oncologic history of infiltrating ductile breast cancer diagnosed 14 years earlier, at the age of 70. At the time of diagnosis, the original lesions were found in the upper-external quadrant of the right breast, and appeared to be approximately x centimeters in size. The patient was treated quickly with surgery (breast quadrantectomy and ipsilateral axillary lymph node dissection with removal of 19 lymph nodes); histological examination confirmed the presence of infiltrating ductal breast cancer without metastases in all 19 lymph nodes removed, pT1c pN0, M0, stage Ia. The receptors for estrogen and progesterone were positive (ER 20%, PgR 40%), the Ki-67 was 30%, the c-erb B2/neu had not been assessed. The patient was subjected to complementary radiotherapy and also, in consideration of the presence of positive hormone receptors, to hormone therapy with Tamoxifen for a period of 10 years. The subsequent follow-up, consisting of imaging tests (annual chest x-ray, abdominal ultrasound, totalbody bone scintigraphy for the first 5 years, and later after longer intervals) and laboratory tests (standard

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L. Rossi et al. / An unusual orbital metastasis of breast cancer

Fig. 1. CT Scan of orbits with the presence of orbital metastasis that displaces the optic nerve.

Fig. 2. CT Scan of Mediastinum with the presence of metastatic lymphadenopathy.

Fig. 3. CT frontal reconstruction with the presence of hilar and mediastinal lymphadenopathy.

blood and tumor markers such as Ca 15-3, CEA, Ca 125, TPA) always resulted negative until October 2012, when an increase in CEA and Ca 15-3 with TPA was noted, always within the norm. TPA always result in the standard. Due to this increase of tumor markers, a complete restaging was requested with a negative chest X-ray for pulmonary metastases, complete abdominal ultrasound which resulted negative for metastases in examined visceral sites, and a bone scan with a dubious result for the presence of bone metastases in the spine (indicate where); a subsequent X-ray examination of the spine was negative. In a short time the patient presented with ocular symptoms characterized by diplopia without evident exophthalmus upon clinical examination, and a progressive lymphoedema of the

right arm. A CT scan of the orbits was then immediately requested which showed an expansive oval formation of 16 × 9 mm in diameter in the right orbital cavity with an apparent manifestation from the external rectus muscle slightly displacing the optic nerve medially (Fig. 1); an skull MRI scan which confirmed the presence of an expansive formation of regular contours on the right side which slightly displaces the optic nerve medially, probably developing from the rectus muscle, with isointense signals to muscle tissue in T1 and T2 and with homogeneous enhancement of the signal after infusion of contrast medium, predominantly in the peripheral area; a PET-CT with FDG which showed intense and non-homogeneous hyperaccumulation of the metabolic tracer (SUV max 12:43) in a tissue formation in the right retro-orbital area infiltrating the right lateral rectus and displacing the optic nerve, and hyper-accumulation in metabolic tracer in the right axilla, in the anterior mediastinum, in the hilar and parahilar areas, and in a small polylobed nodule in the left basilar pulmonary area; a total-body CT scan showed an expansive formation with precise margins in the right orbit attached to the lateral rectus muscle, with a maximum diameter of approximately 2 cm, which exerts compression on the optic nerve, medially displaced; expansive swelling in the right axilla, solid, plurinodulare, with non-homogeneous contrast and internal liquefactive areas; numerous enlarged lymph nodes in the mediastinum and bilateral hilar and para-aortic (Figs 2, 3); two non-homogeneous focal abnormalities of approximately 2 cm adjacent to the pleural layer and spleen; other non-homogeneous nodular formations in the left paracardiac area and the lower tract of the retro-aortic area, and a pseudo-nodular area in the left lung, irregular, maximum diameter 1.8 cm. During this interval of about 5 months, we have seen a progressive deterioration of the lymphoedema in the left arm and of the ocular symptoms, and the appearance of a persistent cough. The Ca 15-3 marker has always remained negative as well as the Ca-125, while the CEA and TPA were altered but stable (see the values of CEA and TPA). A cytological sputum test was also performed with a negative result, as with the assessment of NSE. The presence of a single pulmonary nodular lesion concerning the ipsilateral iliac lymph nodes and normal levels of the Ca 15-3 marker raise the suspicion of a primary pulmonary tumor (eg: small cell pulmonary carcinoma) with unilateral metastasis on the orbit; on the other hand, the oncological medical history positive for breast cancer and the lymphoedema

L. Rossi et al. / An unusual orbital metastasis of breast cancer

on the same side of the operated breast were compatible with a metastatic lesion from breast cancer, despite 14 years of negative follow-up. The presence of pulmonary lesions, reduced respiratory function and the advanced age of the patient contraindicated the general anesthesia necessary for biopsy of the orbital lesion. An ultrasound of the right axilla was performed which showed a hypoechogenic non-homogeneous formation of irregular margins, with rear attenuation of the ultrasonic beam, with a maximum diameter of approximately 10 mm. The patient, who was properly informed, then underwent surgery under local anesthesia in our facility for a histological exam on which would be based a systemic therapy. The histological examination showed a relapse of breast cancer with moderate positive results of hormone receptors (ER and PgR 55%), ki-67.9%, c-erb B2-neu negative (IHC 0%). The patient quickly underwent chemotherapy with an oral capecitabine dosage of 1250 mg/mq per day for 15 days every 3 weeks (with a 1 week suspension); the patient exhibited gastrointestinal toxicity with nausea and diarrhea G2, both controlled with appropriate supporting therapy, and grade G1/G2 hand-foot syndrome grade G1/G2 controlled with the customary rules of hygiene. In addition, due to the presence of hormone receptors, the patient began hormone therapy with aromatases inhibitors (letrozole). The orbital lesion, on which it was not possible to obtain a useful histological sample but was assumed to be a metastasis from breast cancer, will also be treated with targeted radiotherapy (indicate Gy and the distribution method), though at this time the patient already shows significantly reduced tumor mass and disappearance of the symptoms.

3. Discussion The longer survival rate in patients with breast cancer has allowed for a longer follow-up period and, at the same time, allows the examination of local and remote recurrences also at quite long intervals with regards to the first diagnosis. Moreover, the breast tumors may metastasize in virtually every site, but as has been noted, the most frequent sites are the lung, liver, bone and, less frequently, the brain. The orbital metastases are much less frequent: the literature reports incidences of orbital metastasis from 2 to 11% of all orbital tumors [3,4]. The tumors that most frequently metasta-

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size to the orbit are breast, pulmonary, gastrointestinal, prostate, kidney and melanoma carcinomas, with variable frequency. The period of time between detection of the primary tumor and orbital metastasis varies from an average of 2 months (pulmonary) and an average of 34 months (breast). The more frequent clinical manifestations of orbital metastatic tumors are diplopia and local tenderness, and those less frequent are exophthalmos and decreased central visual acuity [5–8]. The diagnosis should always be histological using a sample obtained by open biopsy of the orbit, however, this is not feasible in every case. Differential diagnosis must be performed on the primary orbital tumors (rhabdomyosarcoma, lymphoma, tumors of the lachrymal glands) with extension of intraocular tumors (uveal melanoma), with benign and malignant tumors of the optic nerve, bone localizations in the orbital cavity of prostate or thyroid cancer, or non-neoplastic lesions (e.g., vascular abnormalities). The presence of a progressively worsening unilateral lesion with a positive oncological history raises a strong suspicion of distant recurrence [9]. In the clinical case presented here, all imaging techniques were compatible with the hypothesis of a secondary orbital lesion, but the presence of a single pulmonary nodule with lymphadenopathy of the ipsilateral pulmonary hilar and the negative result of the Ca 15-3 led to suspicions of, besides the metastases from breast cancer, the presence of a primary pulmonary lesion. A bronchoscopy was inappropriate, also considering the age and condition of the patient, but a sputum cytology was negative. The appearance of lymphoedema steered us towards immediate execution of an ultrasound of the right axilla, at practically no cost, which revealed the presence of an area with ultrasound features compatible with local recurrence. A simple surgical procedure under local anesthesia for open biopsy of the lesion in the axilla has allowed us to obtain quickly and without high risks for the patient histological examination on the basis of which to plan an intervention (hormone therapy, chemotherapy with or without treatment organic anti-HER2). The presence of multiple metastatic sites (assuming a recurrence of breast disease), the presence of a high Ki-67 (30%), the negativity of hormone receptors and HER2 (triple negative cancer) indicated the use of chemotherapy. The advanced age of the patient and her refusal of treatment with major side effects led us to the use of oral capecitabine. In light of current knowledge, capecitabine is, along with taxanes and anthracyclines, one of the most effec-

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tive agents for breast tumors, and is frequently used in the metastatic setting for monotherapy or in combination therapy [10–12]. The randomized study of Stockler [13] has shown that capecitabine is better than classic CMF in controlling the disease for over 6 months, with a better toxicity profile and quality of life, also thanks to the oral form. The study of Bajetta [14] conducted on older women (average age 73), affected with advanced or metastatic breast cancer showed response rates for capecitabine in monotherapy of 34.9 to 36.7% and a TTP of approximately 4 months. In addition to the systemic treatment of orbital metastases from breast cancer, it is very useful to utilize radiation therapy with a dose of 20–40 Gy for 1 or 2 weeks. Unfortunately, the prognosis is not favourable, with an average in such cases of 22 to 31 months. The goal of the treatment is not recovery but mitigation of symptoms and improvement in the quality of life.

Conflicts of interest The authors declare no conflicts of interest related to this article.

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Milman T, Pliner L, Langer PD. Breast carcinoma metastatic to the orbit: an unusually late presentation. Ophthal Plast Reconstr Surg. 2008; 24: 480–2. [4] Surace D, Piscioli I, Morelli L et al, Orbital metastasis as the first sign of “Dormant” breast cancer dissemination 25 years after mastectomy, Jpn J Ophthalmol. 2008 Sep-Oct; 52(5): 423-5. doi: 10.1007/s10384-008-0555-5. Epub 2008 Nov 11. [5] Reeves D, Levine MR, Lash R. Nonpalpable breast carcinoma presenting as orbital infiltration: case presentation and literature review. Ophthal Plast Reconstr Surg. 2002; 18: 84–8. [6] Spitzer SG, Bersani TA, Mejico LJ. Multiple bilateral extraocular muscle metastases as the initial manifestation of breast cancer. J Neuroophthalmol. 2005; 25: 37–9. [7] Dieing A, Schulz CO, Schmid P, et al. Orbital metastases in breast cancer: report of two cases and review of the literature. J Cancer Res Clin Oncol. 2004; 130: 745–8. [8] Kuo SC, Hsiao SC, Chiou CC, et al. Metastatic carcinoma of the breast: A case with the unusual presentation of unilateral periorbital oedema. Jpn J Ophthalmol. 2008; 52: 305–7. [9] Peckham EL, Giblen G, Kim AK, et al. Bilateral extraocular muecle metastasis from primary breast cancer. Neurology. 2006; 65: 74. [10] Gelmon K, Chan A, Harbeck N. The role of capecitabine in first-line treatment for patients with metastatic breast cancer. Oncologist 2006; 11 (Suppl. 1): 42-51. [11] Ershler WB. Capecitabine use in geriatric oncology: An analysis of current safety, efficacy, and quality of life data. Crit Rev Oncol Hematol 2006; 58: 68-78. [12] Nolè F, Catania C, Munzone E, et al. Capecitabine/vinorelbine: An effective and well-tolerated regimen for women with pretreated advanced-stage breast cancer. Clin Breast Cancer 2006; 6: 518-24. [13] Stockler MR, Harvey VJ, Francis PA, Capecitabine versus classical cyclophosphamide, methotrexate, and fluorouracil as first-line chemotherapy for advanced breast cancer, J Clin Oncol. 2011 Dec 1; 29(34): 4498-504. doi: 10.1200/JCO.2010.33.9101. Epub 2011 Oct 24. [14] Bajetta E, Procopio G, Celio L et al, Safety and efficacy of two different doses of capecitabine in the treatment of advanced breast cancer in older women, J Clin Oncol. 2005 Apr 1; 23(10): 2155-61. Epub 2005 Feb 14.

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An unusual orbital metastasis of breast cancer.

In this paper we report the clinical case of a 84 year old female patient with a history of breast cancer diagnosed 14 years before, treated only with...
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