A Novel Combined Approach for Metastatic Breast Cancer with Dural and Leptomeningeal Disease with an Impressive Clinical Outcome : A Case Study

Concurrent dural and leptomeningeal metastatic carcinomatosis are very rare and have a poor prognosis. Here we present a woman with advanced estrogen receptor (ER) positive and progesterone receptor (PR) positive breast cancer who presented with leptomeningeal disease. Patient underwent multi targeted epigenetic therapies applied in a protocol called MTET. She continued to respond to the interval treatment, which consisted only of the nutraceutical agents. Here we discuss her case in detail and we believe that such an example might be applied to other patients in this situation resulting clinical improvement and less toxicity.


Introduction
If the tumor is small in size (less than 3 cm), Gamma knife stereotactic radiosurgery (GKRS) is an option.Gammaknife survival rates are similar to surgery plus whole brain radiation or whole brain radiation alone and are generally ineffective.The majority of patients progress despite systemic therapy and die in less than 6 months [1]- [7].
Here we present a woman with advanced estrogen receptor (ER) positive and progesterone receptor (PR) positive breast cancer who presented with left facial paralysis, numbness to the chin and scalp, double vision, and severe headaches, then diagnosed with metastatic duraland leptomeningeal disease with possible intraparenchymal disease and involvement of the cavernous sinus, cranial fossa and microinvasion to brain parenchyma by the tumor.

Methods
The patient underwent combined systemic therapy by receiving a patented series of neutroceutical infusions consisting of called MTET (multi-targeted epigenetic therapy), along with GKRS, and minimal oral chemotherapy.She experienced a surprising overall improved physical response and radiological findings; all together it created a meaningful clinical response to the minimally toxic treatment.
With the MTET alone, she continued to respond to the interval treatment, which consisted only of the neutroceutical agents.

Discussion
Here we discuss her case in detail and we believe that such an example might be applied to other patients in this situation resulting clinical improvement and less toxicity.The patient reported improved quality of life after the very first day of treatment and continued to improve clinically.Her ECOG score improved from 3 to  The serum Her 2 level continued to drop to 28 from 124.1 at baseline (please see Figure 1).

Case Study
On 4/6/17 while patient has been off ANY conventional therapies for over 6 months, her labs showed significant improvement on MTET therapy.Her CA Concurrent dural and leptomeningeal metastatic carcinomatosis are very rare and have a poor prognosis.In the literature, advanced breast carcinomas, bone-to-dura spread has been hypothesized to arise from dissemination of tumor cells from the bone, especially the vertebral bodies, with retrograde reflux of tumor cells into veins, venousplexi, and subsequently the dura.Conventional intrathecal infusions of cytotoxic agents have failed to improve survival in majority of patients.Data from the Cleveland Clinic, Humboldt University in Berlin, and Karolinska Hospital in Stockholm have shown a median survival ranging from 4.2 to 6.5 months despite radiation therapy (RT) to the brain.J. Taguchi et al.DOI: 10.4236/jct.2018.93025275 Journal of Cancer Therapy

A
forty-seven year-old woman with an initial diagnosis of stage 2A ER-positive, PR-weak positive, HER2 negative multifocal ductal carcinomas of the left breast declined adjuvant tamoxifen and RT after a left lumpectomy and negative sentinel node biopsy.The OnctoypeDx Recurrence Scores of both tumors were 27 and 33.This patient used alternative therapies including GcMAF, an injectable immune modulator with dietonly to discover 5 months later with increasing hip pain, she harbored extensive bony metastases on her PET scan.The bony lesions were diffuse and destructive in all areas involving the thoracic and lumbar spine.She required a left hip replacement.The patient accepted taking 10 mg of Tamoxifen with monthly injections of Denosumab (XGEVA) andlater stopped the Denosumab due to the side effects of prolonged bone pain and reactions.Her oncologist referred her for evaluation and therapy since the patient wished to avoid cytotoxic chemotherapy.The patient's main complaint was pain and inability to walk due to progressive disease in the bones.Her initial labs 7/12/16 prior to the therapy showed very high tumor marker levels (CA 15.3, 27.29 and CEA), elevated LDH and alkaline phos-DOI: 10.4236/jct.2018.93025276 Journal of Cancer Therapy phatase, and positive circulating tumor cell DNA (c tDNA) with Guardant 360 testing for PI3K and FGFR1.The serum showed abnormally high HER2 positivity.Thrombocytopenia (platelets = 71,000) and calcium of 12.4 were assumed due to extensive bony metastases.Treatments and results: She started IV epigenetic therapies with the MTET protocol, which she received on daily basis for two weeks, then tapered to twice a week.MTET protocol consists of patented combination of polyphenols formulated to modify the histone deacetylases along with DNA demethylating effect.
Xa: PET diffuse mets to bone; Xb: Significant reduction in SUV activity of nearly all boney mets.Xc: PET neg FDG; diffuse blastic changes in bone; low attenuation liver lesions-neg FDG.Xd: MRI brainbaseline-left paramedial enhancement.No intracranial mets; skull mets.Xe: MRI brain; diffuse dural metastatic disease, involving superior sagittal sinus, left cavernous, and right temporal ovale, with possible right temporal and left parietal microinvasion.Xf: MRI brain-reduction in duralmass.Xg: MRI brain-continued reduction of dural mass.MTET: Multi-targeted epigenetic therapy.DOI: 10.4236/jct.2018.93025277 Journal of Cancer Therapy