Background: Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival. Methods: We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the "OM cohort," to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed.

Breast cancer is responsible for most ophthalmic metastases (OM) to the orbit and periorbit. OM are associated with poor prognosis, as 95% of affected patients subsequently die of breast cancer. Previous studies have demonstrated an increased propensity for invasive lobular carcinoma (ILC) to spread to the eye compared to invasive ductal carcinoma (IDC). ILC is less common than IDC, and it can exhibit an unusual pattern of metastatic spread, including to sites such as the ovaries and GI tract. We herein report our single academic institution experience with OM from breast cancer with respect to anatomical presentation, histology (lobular vs. ductal), treatment and survival. We used the natural language processing platform TIES (Text Information Extraction System) to identify OM caused by primary breast cancer in a database of over 2.3 million patients with electronically stored pathology and radiology reports at the University of Pittsburgh Medical Center. Search terms in TIES were translated into ontologies consisting of the NCI Metathesaurus’ synonyms and abbreviations. The search was thus not reliant on specific words. We then reviewed clinical notes, pathology reports, radiology reports, therapeutic regimens, and outcome data for the cases identified through TIES. Data from the patients identified through TIES was also compared to a large institutional database featuring 1,366 patients with metastatic breast cancer (MBC). Histological slides from 3 patients were analyzed. We identified 28 patients diagnosed with primary breast cancer between 1995 and 2016 and subsequent OM. Median age at diagnosis was 54, with a range of 28 to 77. ER, PR, and HER2neu status from the 28 patients with OM did not differ from other patients with MBC in our institutional database. The relative proportion of patients with ILC was significantly higher in the patient cohort with OM (32.1%) than in the metastatic institutional database (11.3%, p=0.007). Median OS in the OM cohort was 78.4 months; distant metastasis free survival (DMFS) was 34.2 months. These survival times did not differ significantly from those patients in the large institutional metastatic database. DMFS tended to be longer (35.05 months) for patients with ILC compared to IDC (23.34 months), supporting a tendency for late relapse. Additionally, after a diagnosis of first metastasis, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.2 months) (p=0.03). OM were the second most frequent site of first metastasis in the OM cohort after bony metastases. Median time to first OM was 46.7 months. Of the 9 patients who developed bilateral OM, 4 had ILC, 1 had IDC, 2 had a mixed ILC/IDC, and 2 had an unknown histology. We observed a significant co-occurrence of OM and central nervous system (CNS) metastases (p=0.018). Of 14 patients that developed OM and CNS metastases, only 3 were diagnosed with ILC compared to 9 patients diagnosed with IDC. 57.1% of the patients with OM received radiation therapy to the eye, and 25 patients received at least one line of systemic therapy. The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM. To our knowledge, our report of 28 patients is the largest analysis of the histological subtype of breast cancer OM. Through our focus on anatomical presentation, histological subtype, treatment, and survival we provide a broad overview of this rare complication of breast cancer. Our data suggests that OM from breast cancer can often impact both eyes, can be associated with CNS metastases, and are more frequent in patients with ILC than IDC. Citation Format: Martin Blohmer, Li Zhu, Jennifer M Atkinson, Sushil Beriwal, Joshua L. Rodriguez-Lopez, Margaret Rosenzweig, George C Tseng, Peter C Lucas, Adrian V Lee, Steffi Oesterreich, Rachel C Jankowitz. Breast cancer orbital and periorbital metastases can be bilateral, are associated with invasive lobular histology, and can co-occur with brain metastases [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-01-12.