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  • Dr. Robert A. Nagourney, MD

Aggressive Prostate Cancer: A Life-Saving Opportunity Nearly Missed

A 42 year old gentleman presented in 2003 with an aggressive prostate cancer. He underwent surgery, radiation, hormones, chemotherapy, immunotherapy and both 2nd and 3rd line androgen ablation (male hormone reduction), yet his disease progressed.

When we first met, his 2012 PET scan was strongly positive and his PSA was rising. I succeeded in controlling his disease for 3 years until the growth of pelvic lymph nodes led to a biopsy in November of 2015.

We used our EVA-PCD assay to explore his tumor’s drug sensitivity but found his cancer to be drug resistant, that is, with the exception of sensitivity to platinum drugs. With his diagnosis at a young age (42) and this new found platinum sensitivity, known to be characteristic of BRCA gene mutations, I wondered whether he might be a BRCA patient.

The BRCA genes discovered in 1990 found a direct link between BRCA mutations and the early onset of breast and ovarian cancer. BRCA patients have a 30-80% lifetime risk.

Widespread BRCA testing has shown that 5-10% of all patients with breast and ovarian cancers carry a “germ line” BRCA mutation that is passed down from generation to generation. And it has now been shown that BRCA mutations can increase the risk of a wide variety of other cancers.

I referred the patient to a genetic counselor who performed a blood-test for the BRCA mutation. The result returned negative.

He did not have a “germ-line” BRCA mutation. As a result he would not qualify for treatment with the new and very effective PARP inhibitors that have been FDA-approved exclusively for BRCA positive patients.

I was puzzled: Young age, aggressive disease and a high degree of platinum sensitivity in our laboratory analysis. The results did not add up. No matter what his gene profile found, I had evidence from platinum sensitivity that he was BRCA mutated.

I decided to send the patient's actual tumor tissue (not his blood) for BRCA analysis. Lo and behold, despite the negative “germ line” analysis, his tumor, did carry a BRCA2 mutation, entirely consistent with our laboratory’s platinum-sensitive result.

How could this be?

We now recognize that some people with BRCA abnormalities do not have the familial form. For them the terms “BRCA-ness” or “BRCA-like” are applied. Despite negative family histories these patients develop their own unique BRCA mutations within their tumors that are every bit as dangerous.

These are known in the scientific literature as “somatic” mutations, from the Greek soma, for body.

Our perseverance and laboratory insights paid off as this patient is now a candidate for the PARP inhibitors that target his BRCA gene and I anticipate a good response.

We learn once again that each patient’s cancer is unique and that we must be prepared to use each patient’s tissue to identify active treatments. There is much to learn about human cancer, much more it would seem than can be found through the use of generic gene profiles.

As always, I welcome your questions 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

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