Lacrimal Gland Metastasis and Recurrence after Breast Cancer Remission: A Case Report

Abstract

Ocular and adnexal metastatic involvement is a rare occurrence in cancer patients, accounting for approximately 4 to 8% of the cases of orbital neoplasia, and it is more commonly associated with breast neoplasia, accounting for approximately 40% of the cases. Despite this, ocular metastasis can occur at any stage of the disease, with the orbit being the most affected site, followed by the choroid, the anterior segment, the optic nerve, and, less frequently, the lacrimal glands. The most commonly involved oncological subtypes are invasive ductal carcinoma and invasive lobular carcinoma, with the former presenting a lower prevalence in the context of breast neoplasia compared to the latter, accounting for 50 to 70% of the cases, while lethality, lack of response to treatment, and association with metastases are more relevant in cases of invasive lobular carcinoma, which are approximately 5 times more likely to present ocular metastases than cases of invasive ductal carcinoma. The present is a qualitative, descriptive, and observational study based on the collection of data from the electronic medical records and complementary exams of a patient with recurrent breast cancer 15 years after the diagnosis of a primary tumor, with a rare case of metastasis to the lacrimal gland, who was followed by the Clinical Oncology team of a university hospital.

Keywords

breast neoplasms - neoplasm metastasis - recurrence - lacrimal apparatus - case reports

Introduction

With the exception of non-melanoma skin tumors, breast cancer is the main primary site of neoplasia in women worldwide, accounting for 1 in 6 women who die from neoplasia. Breast neoplasia is classified according to histological type and immunohistochemical (IHQ) profile. Regarding histology, infiltrating ductal carcinoma (IDC) represents approximately 50 to 70% of the cases, while infiltrating lobular carcinoma (ILC) represents 10 to 33% of the cases.[1] The IHQ profile is classified by the positivity of estrogen receptor (ER) and progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Kiel antigen 67 (Ki-67) protein expression, with classifications stipulated as luminal A and B, HER-2-positive, and triple negative.[2] The most common IHQ subtype is the hormone receptor-positive, followed by the triple negative, and HER-2-positive.[2] [3] [4] The most relevant tumors to assess recurrence are those of the luminal subtypes, which are differentiated by their IHQ profile: luminal A (high expression of ER and PR +, HER-2 -, low Ki-67) and luminal B (reduced expression of ER and PR +, HER-2 + or -, high Ki-67).

Hormone receptor-positive tumors with Ki-67 levels higher than 14% are associated with shorter disease-free and overall survivals, as well as an increased risk of local recurrence and metastasis. Some studies[5] [6] have also shown that most cases of late recurrence occur in luminal-B tumors, particularly those that are HER-2+ and ER + , when compared to HER-2- tumors.

The main metastatic sites of breast cancer involve the brain, lungs, liver, and bones. The incidence of metastasis to a given organ varies mainly according to the IHQ profile, as occurs in triple-negative and HER-2 tumors, which present high rates of metastasis to the brain. Orbital and adnexal metastases are rarer events, with an incidence of 4 to 12%.[3] [7]

Orbital metastases account for 1 to 8% of all ocular tumors and occur in 2 to 5% of patients with systemic malignancy. The main primary sites for ocular metastases are the breast, representing 20 to 60% of cases, followed by the lung, melanocytes, prostate, and kidney, each accounting for approximately 15 to 20%. The increasing incidence of ocular metastases from diverse and unusual primary sites is related to the earlier detection of breast cancer.[2] [3] [4] [7]

Ocular metastasis can occur at any stage of the neoplastic disease, even at the time of diagnosis, as a single metastasis or in systemic progression, the latter being the most common. However, in approximately 25 to 40% of the cases, ocular manifestations arise as an initial symptom of breast cancer.[1] [4] [8] In general, involvement is unilateral, and the prediction for one eye presents divergence in the literature, with some articles reporting no statistically significant prevalence of one side compared to the other, while others report almost 50% of cases in the left eye, and it may be bilateral in up to 10 to 25% of the cases.[1] [8] The average time until the occurrence of ocular metastasis in the studies was of 2 to 8.5 years, but cases of up to approximately 30 years have been reported. The most common anatomical site affected by ocular metastases is the choroid, followed by associated involvement of the orbit and lacrimal gland, and, in third place in prevalence, mixed infiltrating lesions. One of the ocular adnexa with the lowest incidence of metastasis is the extrinsic ocular musculature, probably due to constant movement, which makes secondary tumor implantation difficult.[2] [4]

The prevalence of ILC (15%) in metastatic orbital tumors is higher than that of IDC (3%), which appears to be associated with the infiltrative nature of ILC, which has a worse prognosis and tends to be less responsive to neoadjuvant therapy, resulting in a 50% higher mortality in 10 years compared to IDC. Infiltrating lobular carcinoma is five times more likely to metastasize to the orbit compared to IDC. The most common metastatic sites of ILC are the orbit (25%), followed by the stomach and rectum. The literature[9] has shown that other less frequent histological types, such as noninvasive ductal adenocarcinoma and phyllodes tumor, individually account for 9% of the cases.

History of breast cancer and ophthalmologic manifestations may lead to suspicion of recurrence of breast carcinoma or metastasis. The most common symptoms are reduced visual acuity, pain, amaurosis, ptosis, diplopia, blepharitis, altered ocular mobility, edema, and palpable orbital masses. Mechanical blepharoptosis due to unilateral involvement of the upper eyelid in metastatic orbital disease in young patients is rare. In addition, imaging tests and biopsy contribute to clarifying the diagnosis of metastasis through tissue analysis and IHQ, since metastases have the same characteristics as the primary tumor.[1] [8] [10]

Treatment can be local or systemic, with the following options: chemotherapy, hormonal therapy (HT), radiotherapy (RT), and surgery. However, this treatment has little impact on patient survival within the expected 2 to 34 months. The therapeutic modalities have been divided into monotherapy and multimodal therapy, with surgery being the most common monotherapy, followed by HT. As for the multimodal treatment, the most commonly cited was RT associated with chemotherapy and HT, with a prevalence of approximately 40%.[8] [11]

Given the rarity of this presentation, there is a paucity of studies on orbital tumors and breast carcinoma metastases to the lacrimal gland, with only a few cases reported to date. The current study aims to present the case of a patient with recurrent breast cancer 15 years after the diagnosis of the primary tumor, featuring an unusual metastasis to the lacrimal gland, documented with the patient's informed consent. The research was submitted to and approved by the institutional Ethics Committee under submission number 84911424.5.0000.0103.

Case Report

We herein present the case of a 50-year-old female patient who was admitted to the emergency room after being referred by the Neurology Department for an ophthalmological investigation due to periorbital pain and right-sided blepharoptosis, with no neurological alterations to justify the clinical picture. She had previously undergone treatment for periorbital cellulitis with amoxicillin and clavulanate, without success. She reported a history of luminal-B breast cancer in the superolateral and inferolateral quadrants of the right breast, 15 years before, and had undergone neoadjuvant therapy with chemotherapy, quadrantectomy of the right breast with axillary dissection, chemotherapy and adjuvant RT, and tamoxifen for 5 years. A physical examination of the breasts revealed an ulcerated nodule adhered to deep planes in the lateral quadrants. An ophthalmological evaluation revealed total eyelid ptosis and dermatochalasis, with no other alterations.

Contrast-enhanced cranial computed tomography (CT) scans of the orbits showed a heterogeneous lesion with irregular contours, measuring approximately 30 × 19 mm in the axial plane, in the superolateral aspect of the right orbit, with high contrast uptake ([Fig. 1]). The cranial CT showed no evidence of an intraparenchymal expansive process or other parenchymal, ventricular, or bone alterations. A chest CT showed a lesion affecting both lateral quadrants of the right breast, measuring approximately 33 × 26 mm; 2 8-mm nodules of similar morphology in the pectoralis major muscle on the right; focal thickening of the peribronchovascular bundle in the left lung apex and small pleural effusion bilaterally—questioned neoplastic infiltration—in addition to pulmonary nodules in the middle and right lower lobes. The radiological study also included cranial magnetic resonance imaging (MRI) scans, which corroborated the CT findings ([Fig. 2]).

Fig. 1 Computed tomography scans showing an expansile lesion in the region of the lacrimal gland.

Fig. 2 Magnetic resonance imaging scans showing the therapeutic response of the initial metastatic lesion. (A) Initial images of the metastatic lesion in 2023: (A1) axial T2-weighted image; (A2) axial T1-weighted image; (A3) sagittal view. (B) Images after treatment with paclitaxel followed by anastrozole for 1 year and 11 months (2025): (B1) axial T2-weighted image; (B2) axial T1-weighted image; and (B3) sagittal view.

The patient was admitted to the Gynecology Department, and an excisional breast biopsy was performed due to suspicion of local recurrence, confirmed by pathological examination as infiltrating breast adenocarcinoma not otherwise specified (NOS), poorly differentiated, nuclear grade 3, involving layers of the dermis and hypodermis, with compromised deep margin, with IHQ for luminal B (RP + , ER + , HER-2-, Ki-67+ in 40%). A biopsy of an intraorbital mass was performed, whose pathological examination corroborated the diagnosis of malignant epidermoid neoplasm infiltrating the lacrimal gland and fibroconnective tissue, with confirmation of metastatic origin from the breast by IHQ (ER + , RP + , HER-2-, cytokeratin 7+ [CK7 + ], cytokeratin 20- [CK20-], GATA3 +: GATA-binding protein 3 positive (indicates positive IHQ staining for the transcription factor GATA3), Ki-67 in 40%).

During outpatient follow-up by clinical oncology, chemotherapy treatment with paclitaxel 80 mg/m² weekly, totaling 120 mg, was instituted to control recurrence for 6 months, later replaced by HT with anastrozole due to neurotoxicity ([Fig. 3]), with improvement in visual acuity, ptosis, and retro-orbital pain.

Fig. 3 Clinical presentation of ocular metastasis undergoing treatment with adjuvant radiotherapy. Note: Photographic record authorized by the patient, taken in January 2024.

Discussion

We herein report a case of late recurrence of a HER-2- luminal-B tumor with highly-positive Ki-67, consistent with the recurrence profile reported in the literature. The median time until late recurrence in these cases is of 112 months, while in our patient it occurred in 180 months.

The main metastatic sites of breast cancer are the brain, lungs, liver, and bones, and the predilection for each target organ varies according to the molecular subtype of the tumor. However, some topographies are less commonly affected, such as the orbit and its annexes. According to the recent literature,[8] [12] breast neoplasms are responsible for approximately 28 to 58% of the cases of orbital metastasis, with greater involvement of the choroid due to hematogenous dissemination, with a lower incidence (7.1%) of lesions to the lacrimal gland. Two large studies[3] [13] corroborate this incidence, demonstrating that masses in this topography represented 5 to 13% of the lesions to the lacrimal gland. In the analysis of 120 lesions in the lacrimal apparatus, Font et al.[3] identified only 3 cases of metastatic lesions, 2 of which originated from breast carcinomas.

Between 2015 and 2024, 11 reports of metastatic breast cancers to the lacrimal gland were found.[1] [7] [10] [14] [15] The median age at diagnosis of the glandular lesion was of 68.27 (range: 31–80) years, and only 2 patients were men.[14] Orbital metastases can occur at any stage of the neoplastic disease, being more common in situations of systemic progression. In 30% of the cases, ocular manifestations appear as an initial symptom of breast cancer,[1] which was not observed in the current case report. As for the aforementioned patient, the visual changes developed associated with systemic progression and more than 9 months after the onset of tumor recurrence, namely: decreased ocular mobility, retro-orbital pain, proptosis and right eyelid ptosis. In addition, reduced visual acuity, amaurosis, and eyelid edema are also common manifestations, usually with unilateral involvement.[8]

The clinical outcome was described in 7 of the reports, but only one showed clinical improvement.[1] In 4 cases,[10] [15] [16] all patients died within a period of 3 months to 1 year after the diagnosis of metastasis. Only in two cases[14] was there a longer survival, in which the patients continued follow-up with chemotherapy and RT for 3 and 6 years until death due to recurrence of the lesion.

Regarding treatment, the patient herein reported began chemotherapy with weekly paclitaxel in the right eye, which was switched to HT with anastrozol for maintenance, and the patient showed clinical improvement. This initial treatment was motivated by the need for rapid reduction of the tumor burden at the metastatic site, as TH requires a longer response time. The 2024 Sociedade Brasileira de Oncologia Clínica (SBOC),[6] 2024 National Comprehensive Cancer Network (NCCN),[17] and 2023 European Society of Medical Oncology[18] (ESMO) guidelines recommend chemotherapy in cases of imminent risk of organ failure and acute patient distress. It is worth noting that, because this is a rare presentation, there are no guidelines for the treatment of lacrimal-gland metastases. In most cases reported,[7] [9] [14] adjuvant RT was performed with or without chemotherapy.

The literature presents a good response to HT with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors for bilateral ocular metastases from hormone receptor-positive breast cancer.[19] However, in the public health context, the patient does not meet this indication due to previous chemotherapy and the absence of recurrence in the adjuvant therapy.[20] Due to the occurrence of neurotoxicity, the option to initiate anastrozole is supported by the 2023 ESMO,[17] 2024 NCCN,[18] and the 2024 Brazilian Ministry of Health guidelines.[20]

Conclusion

The importance of prolonged oncological surveillance and personalized, risk-based therapy, based on the patient's clinical, histological, and IHQ profiles, is emphasized for the early detection of recurrences. Furthermore, it is important to pay attention to ophthalmological symptoms in patients with a history of cancer, as such manifestations may indicate the onset or progression of tumor activity.

Furthermore, given the low incidence of metastases to the orbit and its adnexa, further studies on this topic are necessary to determine the best therapeutic approach for this location, as its outcome and prognosis remain uncertain.

Conflict of Interests

The authors have no conflict of interests to declare.

Authors' Contributions

GMO:– study conception and design, collection and assembly of data, data analysis and interpretation, writing – original draft, and writing – review & editing; ATM: collection and assembly of data, provision of study materials or patient care, data analysis and interpretation, writing – review & editing, final approval of the manuscript, and accountability for all aspects of the work; IPR: writing – original draft and writing – review & editing; CHZ and LSP: writing – original draft; LDV and APLL: collection and assembly of data, provision of study materials or patient care, and data analysis and interpretation; and MCFM: final approval of the manuscript and accountability for all aspects of the work.

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Publication History

Received: 10 May 2025

Accepted: 10 October 2025

Article published online:
22 December 2025