Metastasis to central nervous system (CNS) by breast cancer is a very well-known entity, and the clinically distinct situations are multiple brain metastases (78%), solitary brain metastasis (14%), and leptomeningeal metastases (8%). CNS metastases are found in 10%–16% of Stage IV carcinoma of breast patients.
Triple negative breast cancer (TNBC) patients usually develop CNS metastasis earlier than those with other receptor subtypes, and those who develop CNS metastases particularly have a dismal prognosis. Initial presentation of an isolated cranial nerve involvement without any symptoms pertaining to carcinoma of breast has not yet been documented in the literature. Paraneoplastic neuropathy could be the cause of the cranial nerve involvement, but not consistent with our patient's presentation, given initial brain magnetic resonance imaging (MRI) findings. Hence, we felt that reporting this rarest case report to the medical literature will be fruitful academically.
A 52-year-old postmenopausal woman presented with a 2-month history of headache, tingling sensation, and sharp shooting pain over the left face initially followed by left facial paresthesia with pain over the maxillary region. She consulted a local physician and diagnosed clinically as trigeminal neuralgia and managed symptomatically with carbamazepine and analgesics. With some initial improvement of symptoms, her neurologic symptoms upheld, and she underwent a brain MRI scan. She was not having any previous history of nipple discharge, breast pain and lump in the breast, infection, or trauma. She reached her menarche at the age 13 years and had first child when she was at the age of 27 years. She reached menopause at the age of 46 years. She did not require any oral contraceptive pills or hormone replacement therapy during her life time. Her past medical and family history was unremarkable.
On general physical examination, she was fairly built and nourished, with her height, weight, and body mass index within the normal range. Breast examination in the supine and upright position revealed a mass of 2.5 cm × 2 cm in the right upper outer quadrant, which was mobile, was nontender, and was firm to hard in consistency, without any underlying chest wall fixity. There was no nipple discharge or peau d'orange or axillary lymphadenopathy. Neurological examination revealed hyperesthesia to touch over the left maxillary and mandibular facial region. The rest of the neurologic examination was normal clinically.
MRI scan revealed presence of enplaque altered signal intensity soft-tissue lesion along the left 5th nerve from its origin at pons, through the left foramen ovale reaching up to the left parapharyngeal space. The left 5th nerve was not seen separately from the lesion. The lesion appeared to be of heterogeneous mixed intensity on T1- and T2-weighted images and showed postcontrast enhancement. The lesion was bulky and caused lateral bulge of the left Meckel's cave [Figures 1 and 2].
A positron emission tomography with concurrent computed tomography showed a 2.9 cm × 2.6 cm intensely 18F-fluorodeoxyglucose (FDG)-avid breast mass, in the upper outer quadrant of the right breast. No other hypermetabolic FDG-avid lesions were noted except the right breast mass.
A diagnostic mammogram with breast sonography was done which revealed a spiculated mass with microcalcifications and significant architectural distortion. The size of the mass was 3.2 cm × 2.6 cm in the upper outer quadrant of the right breast. Ultrasound-guided core-needle biopsy from the breast lump revealed infiltrating ductal carcinoma with Bloom Richardson score of 8. Her estrogen receptor, progesterone receptor, and Her2-neu (1 by immunochemistry) analysis suggested triple-negative breast cancer (TNBC). Her serum biochemical reports such as renal function tests and liver function tests were within normal limits. Her serum CA-15.3/27.29 and CA-125 were within the normal range. Lumbar puncture was performed to look for leptomeningeal spread, and cerebrospinal fluid cytology did not demonstrate any malignant cells. Her baseline echocardiography was normal.
In view of her neurological symptoms, she was offered palliative whole-brain radiation therapy. 30 Gy of radiation therapy was given at a dose of 3 Gy per fraction over 14 days. In the context of TNBC and good performance status, she was offered palliative FEC (5-flurouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) chemotherapy at an interval of every 21 days. Along with chemotherapy, she was advised to take analgesics, gabapentin, carbamazepine, and antiemetic drugs. She tolerated chemotherapy very well without any significant toxicity. After three cycles of chemotherapy, there was partial response in the right breast mass according to the Response Evaluation Criteria in Solid Tumor criteria, and there was dramatic improvement in her neurological symptoms. In view of good subjective and objective response with tolerable toxicity profile, she was advised to continue chemotherapy till six cycles. At the end of six cycles, mammography showed 1 cm × 1 cm mass and brain MRI scan was normal. She was asymptomatic for her neurologic symptoms at the end of five cycles. After discussing with the patient and family members, we advised her to take oral capecitabine 1000 mg/m2 with 2 weeks on and 1 week off, in view of bad biology of the disease and residual mass.
The patient responded very well to radiotherapy and chemotherapy with complete improvement in her neurological symptoms and now she is under regular follow-up for chemotherapy for 8 months without any subjective or objective progression of the disease.
Brain metastases are the most common intracranial malignancy, and breast cancer is the second most common cancer to metastasize to the brain. Brain metastasis is a significant cause of morbidity in breast cancer patients, with cognitive impairment detected on neuropsychological testing in up to 67% of patients. Breast carcinoma accounts for 12%–20% of brain metastases, second only to lung cancer. Breast cancer as with other cancers has a predilection for brain regions with the highest perfusion, as 80% of metastases occur in the cerebral hemispheres, 15% are located in the cerebellum, and 5% occur in the brainstem. The various mechanisms of brain metastasis in breast cancer are interaction of the brain endothelial cells with breast cancer cells through adhesins and breast cancer cell adaptation to the brain microenvironment.
TNBC is not a biologically homogeneous subgroup; it does not help to select a particular treatment and its overall prognosis is worse. While a subset of patients with triple-negative breast cancer can be cured with the addition of adjuvant chemotherapy, others relapse quickly despite such treatment mainly because of the inhomogeneity in the disease biology. Triple receptor-negative breast cancer (TNBC) patients usually develop CNS metastasis earlier than those with other receptor subtypes, and those who develop CNS metastases particularly have a dismal prognosis.
Metastasis to CNS by breast cancer is a very well-known entity, and the clinically distinct situations are multiple brain metastases (78%), solitary brain metastasis (14%), and leptomeningeal metastases (8%). CNS metastases are found in 10%–16% of Stage IV carcinoma of breast patients. An isolated cranial nerve involvement from a distant primary tumor is rare but has been reported, particularly for trigeminal neuropathy in lung cancer, lymphoma, and colorectal cancer. Isolated trigeminal cranial nerve involvement in patients with metastatic breast cancer has been rarely documented in the literature. However, isolated trigeminal mononeuropathy presenting as an early sign of breast cancer has been documented in only one case report. Similar to the reported case, our patient presented initially with left trigeminal neuralgia, with improvement in symptoms after local and systemic therapy. Paraneoplastic neuropathy could be the cause of the cranial nerve involvement, but not consistent with our patient's presentation, given initial brain MRI findings. Hence, we felt that reporting this rarest case report to the medical literature will be fruitful academically.
In conclusion, even though trigeminal nerve involvement in metastatic breast cancer has been documented, its presence as an early sign of breast cancer is not yet been documented except one case report.
Learning points/take-home messages
- Isolated cranial neuropathy may be an early harbinger of metastatic breast cancer, so we should search for the primary malignancy
- TNBC is associated with early CNS metastasis because of heterogeneity in the biology of the disease
- Whole-brain radiotherapy and palliative chemotherapy are the best available treatment modalities.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient and the caretaker have given consent for the images and other clinical information to be reported in the journal. The patient and the caretaker understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
All authors acknowledge the patient for her speedy recovery and good health.
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