In early September of 2018, I consulted with a 51-year-old patient with heavily pre-treated, extremely advanced metastatic breast cancer. Diagnosed 5 years earlier, the tumor was managed by targeting the HER-2 oncogene identified in her surgical biopsy.
After initial success, the cancer began to rapidly progress. Desperate to control a disease that had nearly replaced her liver, she traveled to Austria in the spring of 2018 to receive liver-directed therapy known as trans-arterial chemoembolization (TACE).
A Chance Meeting
While offering a brief reprieve, upon return to California her cancer progressed and treatment options became very limited. With her oldest daughter beginning college she and her husband traveled to San Diego for her move into the dormitory on campus.
As luck would have it, one of my patients was also enrolling her son at the same school and the same dormitory.
My patient, now well and fully recovered, looked across the room at this slender, pale woman and sensed a dilemma.
It’s a sixth sense that cancer patients have akin to “it takes one to know one”. She approached the woman and gleaned that she was suffering from advanced breast cancer.
One week later I was looking across my desk at the patient as she provided a detailed history of her disease and treatment.
Her Fight with Breast Cancer
Her story was long and complex.
Beginning five years earlier she had presented with high grade breast cancer found HER2 positive.
She underwent a combination of Carboplatin, Taxotere, Herceptin and Perjeta. After completing her pre-operative chemotherapy, she had surgery and then remained on maintenance Herceptin plus Perjeta.
By the third year her disease was progressing.
Attempts at chemotherapy were largely unsuccessful leading her to travel to Europe for TACE therapy to address massive hepatic (liver) progression.
A Tough Diagnosis
An August, 2018 CT scan confirmed diffuse bone metastasis and a compression fracture of thoracic vertebra 4, extensive liver metastases and lung nodules.
With tumor markers rising astronomically, weight loss and abdominal pain she was rapidly failing.
Of interest, the HER-2 FISH (fluorescence in situ hybridization) test on the most recent biopsy was no longer positive.
Confronting liver failure with a deteriorating performance status and the risk of spinal cord compression, I wondered whether there was anything that I could do.
Not Giving Up
As a mother of two, one in college and the other still in high school she made it clear that she wasn’t giving up and requested a liver biopsy to allow us to perform an (EVA/PCD) functional profiling analysis.
I must admit that I had hesitation, as the extent of her disease, particularly the thoracic vertebra compression, gave me pause. Our surgeon scheduled her immediately but the biopsy wasn’t done until late September, fully two weeks after we had first met.
The delay at was her request.
As sometimes happens in patients with such advanced cancer, they begin to “bargain” with their disease. Increasingly convinced of the likelihood of failure, they postpone or even forgo interventions in order to attend one more birthday party, a christening or in this case a “parent’s weekend” at the University.
I awaited the biopsy with bated breath.
Based on what we already knew, I studied drugs active against the HER2 target but they were utterly ineffective. We also examined drugs that target the pathways associated with androgen receptor, epidermal growth factor and mTOR but these were equally inactive.
Her Functional Profiling Results
The EVA/PCD findings revealed exquisite sensitivity to drugs that damage DNA and those that inhibit its repair.
This triple-negative-like biology dubbed “BRCA-ness” is similar to BRCA mutations. Even though she was known not to carry BRCA or related mutations, her biology was typical of “BRCA-ness" and we began the selected treatments immediately.
Treatment Begins
During her first visit to the infusion suite a week later, I saw her across the room looking pale and I felt concerned. With all that she’d been through there was good reason for concern.
In the weeks since we had first met her tumor markers and liver function tests had tripled, now in the 1000s. We were late to the game and it was clearly in overtime.
Results from Her Treatment
At follow up 2 weeks later, she arrived with a spring in her step.
Sitting comfortably, she said that she had not felt this well in years. “I am better, I know I am better”. I inquired how she’d done.
"Oh, it was a cinch," she said, "one of the easiest I've taken."
After another cycle the results were dramatic with the tumor markers falling by 50% every two weeks. She’d gained weight and was tolerating treatment almost without side effects.
By every measure she was better, much better.
At week 5 the tumor markers were down by 90%. I now look forward to our every visit to see just how much better the results will be.
Treating “Untreatable” Cancers
Many of my patients present with extremely advanced diseases.
Some have cancers that are considered "untreatable" based on tumor-type like rare sarcoma or advanced pancreatic, others are based on prior therapy and the exhaustion of treatment options.
In these patients, responses can be particularly gratifying as the results can be so dramatic and unanticipated.
This patient was just such as an example.
Had we not met the moment of our first encounter; had my other patient not been at the University; had the patient not pursued the biopsy, I fear that we would have lost her.
I wasn’t expecting so good an outcome.
Fearing for her well-being I had considered not treating her at all as the benefits seemed so uncertain. I worried about the biopsy, her extensive disease and bone involvement.
In retrospect, it is so fortunate that we moved forward.
Valuable Lessons to be Learned
There are lessons to be learned.
The first is that biology supersedes genomics. Regardless of HER2 or other features, the laboratory cultures carried the day over other diagnostic considerations.
Secondly, each patient's cancer is unique with a biology driven by the tumor’s capacity to survive. As cellular survival defines cancer, our ability as therapists reflects little more than the use of drugs and combinations that successfully undermine cancer cell survival.
Thirdly, the EVA/PCD laboratory platform is a window on human tumor biology that informs us of the drugs and combinations that most effectively “kill” each patient’s cancer cells.
Finally, we cannot rely upon serendipity and chance to save the lives of patients.
Cancer patients must be made aware of and avail themselves of the tools they need to address the unique biology of their own disease.
They must go beyond genomic (DNA) analyses, standard protocols, NCCN guidelines and generic regimens if they are to find the treatments that work best for them.
As always, I appreciate your thoughts and comments.
Dr. Robert Nagourney, has been internationally recognized as a pioneer in cancer research and personalized cancer treatment for over 20 years. He is a TEDx speaker, author of the book Outliving Cancer, a practicing oncologist and triple board certified in Internal Medicine, Medical Oncology and Hematology helping cancer patients from around the world at his Nagourney Cancer Institute in Long Beach, California. For more info go to NagourneyCancerInstitute.com