MARGARET’S STORY

The Case of Margaret 

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Patient Presentation
Margaret was a 64 year old woman from BC, Canada whom was originally treated for estrogen receptor (ER) positive breast cancer 10 years ago and had been on anti-estrogen therapy until her disease progressed. The MRI and CT imaging scans that Margaret’s public system oncologist had ordered showed that she had new metastasis in her bones and lungs, and that her prognosis was dismal.

Since she had endured surgery, multiple rounds of chemotherapy, radiation therapy and many years of anti-estrogen therapy, her oncologist told her that they had run out of treatment options and she was offered palliative care with a chemotherapeutic drug called capecitabine, which was unlikely to provide her with any benefits. She was told to get her affairs in order.

Margaret wasn’t ready to just accept this and so she reached out to us.

How we helped Margaret using our 5 step system

1. Introduced Advanced Diagnostics
Firstly, we obtained a sample of Margaret’s tumor tissue and sent it for tumor DNA sequencing. We looked for cancer causing mutations in the DNA of over 340 genes involved in breast cancers.

Secondly, we asked Margaret to contact an independent community oncologist near her home town that we had experience working with, and suggested that she get a PET-CT to establish the exact state of her disease.

PET-CT, which unlike other forms of medical imaging, is able to identify active tumors at a very small size, based on the biological activity of the tumor.

While most forms of imaging look at the density of the tumor and compare it to the surrounding tissues, PET-CT uses a harmless radioactive isotope that is bound to a sugar molecule.

Since tumor cells are constantly growing and therefore highly metabolic, they drink up more of the sugar-isotope solution than the surrounding tissues and any tumor will glow like a Christmas tree light.

Since only live tumors will drink the sugar-isotope solution, PET-CT can tell if a tumor is alive or if it has been affected (killed) by a specific treatment. No other form of imaging can reveal this essential information!

Furthermore, since the amount of the sugar-isotope solution a specific tumor drinks depends on how fast it is growing, a PET-CT can determine how aggressive a specific tumor is compared with other tumors in the body. This can allow doctors to focus on the tumors that are most likely to metastasize.

2. Conducted Patient Specific Research
We uncovered extensive data indicating that a newly approved drug called afinitor, was providing significant increases in disease free and overall survival rates for postmenopausal women with metastatic ER positive breast cancer that have failed all other options.

We also identified clinical trial data that a specific type of drug used to prevent bone loss called zometa, also had cancer fighting properties and provided a survival benefit for post-menopausal women with ER positive breast cancers. The drug that she was currently taking for bone loss called clodronate, had no such benefits.

3. Interim Treatment Support
Next, we researched the British Columbia Cancer Agencies (BCCA) treatment guidelines for advanced breast cancers and identified provisions in the guidelines to treat patients such as Margaret with afinitor.

We immediately wrote up patient report for Margaret’s new health care treatment team, and her community oncologist was able to get the costs of both a PET-CT and the cost of the afinitor covered by BCCA.

However, Margaret had to pay out of pocket for zometa.

4. Genetic Testing During Treatment
During the course of her treatment, Margaret’s DNA sequencing results indicated that her cancer would potentially be sensitive to a variety of targeted therapies including a recently approved drug called palbociclib, which was providing superior survival benefits to breast cancer patients.

Since recent data was showing that a new class of immunotherapy drugs called PD-1 inhibitors was also showing significant benefits to women with breast cancer whose tumors were PD-1 positive, we performed a liquid biopsy RNA sequencing (blood test) test to identify if any of Margaret’s tumors were PD-1 positive.

We decided on the liquid biopsy because not all tumors will express the PD-1 at the same time and the expression of it varies between different tumor sites and single biopsy based PD-1 testing has been not an accurate predictor of responses to PD-1 inhibitors.

Testing all of the body’s tumors at the same time using liquid biopsies is much more accurate in determining if there is a potential for responses to these drugs.

5. Clinical Trial Support and Advocacy
Since Margaret’s PD-1 liquid biopsy test came back as positive, she will be able to enter a local clinical trial using PD-1 inhibitors if she chooses. Additionally, she can access the drugs via her community private oncologist.

6. Outcome
Afinitor is working very well for Margaret over the last 6 months, and is known to delay disease progression significantly, reduce hospital visits, and increase her comfort as it is a non-chemotherapy targeted drug. Importantly, Margaret is able to continue working.

Since this drug was approved and covered by her local cancer agency, she got the treatment she needed with much less stress and financial strain.

Furthermore, when afinitor stops working, she has a variety of other targeted therapies that have the potential of providing her with more time, without the damaging side effects of standard chemotherapy.

7. Update

Recently, Margaret’s tumor markers started to rise and a recent PET-CT showed that she was becoming resistant to afinitor and that her cancer was progressing.

We went back to her F1 tumor sequencing panel and with some extra research, identified a drug called votrient that would target the mutations in her FGFR signalling pathway. The FGFR signalling pathway has recently been found to be associated with certain forms of breast cancer and there is some new evidence that shows inhibition of this pathway can slow the growth of breast cancers. We suggested that Margaret take this drug in conjunction with a newer estrogen inhibitor that we have been using for years called fulvetsrant.

While most estrogen inhibitors target the aromatase pathway, which is involved in the synthesis of estrogen, fulvetsrant works by irreversibly binding to and degrading the actual estrogen receptors on the surface of cancer cells, which is what estrogen binds to and which is responsible for the oncogenic growth of estrogen receptor (ER) positive  cancers. This results in a much stronger inhibition of estrogen negative tumor promoting activity while preserving the function of normal estrogen signalling.

Since estrogen is responsible for a variety of functions in the body, and since fulvetsrant does not directly affect it, Margaret will not have to suffer from the harsh effects of estrogen deprivation.

We contacted her doctor and he was able to arrange for funding for fulvetsrant. We also wrote up a white paper for funding of votrient, which unfortunately was denied.

Currently, Margaret is responding well to this new combination of drugs and her tumor markers continue to fall.

Conclusions

As you can see, CTOAM’s advanced diagnostics , records review and consultations can result in significant benefits to a patient’s outcome. Having access to a team of knowledgeable scientists, doctors and patient advocates that WORK FOR YOU and NOT THE MEDICAL SYSTEM, can make all the difference in the outcome of your disease!

If you or a loved one is fighting cancer, give us a call so we can do a brief review of your medical records. It is important to be sure that you KNOW that you are doing all you can, and that you have access to the best treatments for your own unique case. (778) 999-5463