Interstate Oncology: Breast Cancer Patient On the Run

Repost: https://www.nagourneycancerinstitute.com/blog/interstate-oncology-breast-cancer-patient-on-the-run

Of the one million new breast cancer patients diagnosed each year worldwide, approximately 170,000 of these cases are triple negative.

The term applies to patients who do not express the hormone receptors for estrogen or progesterone and are also HER2 negative. About 75% of these patients are of the basal type and the diagnosis is more common in young woman and the black population. Triple negative breast cancer is a distinct subtype of breast cancer and requires its own unique approaches.

Case: Triple Negative Breast Cancer

In August of 2017, I met a delightful 50-year-old British woman who had traveled to California from her home in Saratoga Springs, Utah. The patient was seen by her local physician for palpable mass in the right breast. A biopsy confirmed high grade triple-negative breast cancer. Staging identified eight positive axillary lymph nodes.

The patient was referred to a prestigious research center and obtained an opinion from a breast cancer oncologist. Despite the high-grade disease, high risk presentation, and triple negative finding, she was offered the standard chemotherapy combination of Cytoxan/Adriamycin followed by Taxol.

As a young woman and mother of six children, this patient had no intention of taking “off the shelf therapy.” She drove the many hours from Utah to California for an opinion.

I referred the patient to one of my skilled surgeons who conducted a biopsy in August and the tissue was evaluated in our laboratory.

Her Functional Profiling Results

The results were striking. Every platinum-based regimen killed virtually every cell. The other more standard regimens were less effective.

I suggested to the patient that a modification in the pre-operative (neoadjuvant) chemotherapy regimen would be warranted. In the interim, the patient was evaluated at the molecular level and found positive for the BRCA1 mutation.

At this point, everything fit together, the triple negative finding, the exquisite sensitivity to Cisplatin-based therapies, and the BRCA1 mutation are all “peas in a pod” for triple negative breast cancer. It was evident that a platinum-based regimen was essential.

With the recent memory of her interaction with the cancer center physician, the patient made a decision. She was going to commute to California for care.

Treatment Begins

In August, we began Carboplatin-based therapy and the tumor disappeared. Within two cycles, the large tumor and axillary nodes were gone.

Several cycles later, they were undetectable by radiographic means. With PET scan confirming a complete remission, and the BRCA1 mutation identified, the patient underwent bilateral mastectomies and was referred for future evaluation and prophylactic hysterectomy with oophorectomy.

Complete Remission Achieved

Now two years since diagnosis, the patient is in complete remission and having undergone the necessary surgical procedure to address any additional risks associated with the BRCA1 mutation is now living a normal life.

Her story is the subject of a recent breast cancer blog posting and serves as an interesting example of patients following their instincts as they seek the best possible and potentially curative therapy for their own individual cancers.

Conclusion

Although the patient was sensitive to several forms of chemotherapy and might have benefited from standard treatment, the therapies that she received were exactly right for her and provided immediate benefit with the least toxicity. Adriamycin-based treatments, widely used in this disease, are both less active than the platin and demonstrably more toxic.

We are delighted that the patient received exactly the right treatment for her, that she tolerated it well, and she gives us a call occasionally on her way from a soccer game or band practice with her six children in the car – a victory for intelligent cancer therapy.

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

There’s Something Sweet About Evolutionary Biology

Repost: https://www.nagourneycancerinstitute.com/blog/something-sweet-about-evolutionary-biology

Humans evolved around their food supply. The foods we eat, the herbs we consume, our sources of nutrition, indeed everything that makes it possible for us to meet our caloric needs can be traced through evolution. A new study examining the enzyme amylase has now traced the origin of this carbohydrate metabolizing enzyme through 47 different species.

Amylase, critical for the digestion of carbohydrates, hydrolyzes starch into sugars. It is found in the pancreas and in some species in the saliva. The authors examined duplication of the amylase gene which allows for multiple copies to produce more of the enzyme, allowing carbohydrates to be consumed in the diet and shows how evolution drives #nagouradaptation.

Species that live in close proximity to humans develop higher levels of amylase.

In fact, wild dogs have virtually no amylase, while domesticated species have high quantities of amylase in their saliva. Thus, adaptation to the human diet through table scraps drove the production of amylase. Monkeys that store food in their cheeks have large quantities of amylase, while mountain lions have none.

But what has this got to do with cancer?

Possibly quite a lot. Investigators in the UK have begun to apply evolutionary principles to cancer therapy. Under Dr. Charles Swanton the clinical trial TRACERx (Tracking Cancer Evolution through Therapy) is using liquid biopsies to examine how cancer cells evolve and become resistant to therapy.

The similarity between the amylase study and cancer are interesting.

For one, amylase levels reflect a specific environmental pressure that provides an advantage to species with higher levels. Secondly, the evolutionary process is relatively rapid, as the domestication of dogs and the infestation of rats and mice in the human environment is historically comparatively recent. Thirdly, the adaptation is not driven by mutations, per se, but instead up-regulation of an existing normal gene.

If we consider cancer adaptation to the stressors that we call therapy, we can imagine that the process of evolution is accelerated as cells divide and live comparatively short periods of time compared to dogs and humans that proliferate comparatively slowly and live a rather long time. By condensing evolutionary adaptation, cancers can outdo our best therapies quickly.

In oncology, patients who show brilliant responses to initial therapy, breast cancer to estrogen withdrawal or prostate cancer to androgen deprivation, generally become resistant within two or three years as selective pressures lead to an outgrowth of resistant clones.

What are the lessons?

Among them is the growing thought that cancer therapy should not be continuous but instead episodic or intermittent. This may offer the opportunity to avoid selective pressures.

This approach has been utilized successfully in prostate cancer and may apply in other diseases. Unfortunately, most oncologists are afraid to find out, as removing therapy could result in progression even death. At least that is a very real fear.

Where the principle has been applied, however, it has shown some early signs of success. Among them is the use of chemotherapy in diseases like small cell cancer and even non-small cell cancer of the lung for defined periods of time with cessation or low-dose maintenance as the subsequent treatment.

One widely used approach in colon cancer is dubbed OPTIMOX which stops patient treatments after FOLFOX and observes them until recurrence, only then reinstating treatments. Survivals have been similar with improved tolerance for those patients who stop active treatment.

There are several questions that remain unanswered. For the amylase study, did amylase arise first and animals then seek starch or did the accessibility of starch render the expression of amylase an evolutionary advantage? Similarly, for those patients with relatively indolent cancers, does the introduction of therapy, particularly mutagenic chemotherapy set in motion the very process of resistance that we seek to avoid?

The field of evolutionary biology will provide extraordinary insights into cancer once we begin to apply its principles. Scientists around the world are beginning to take new looks at the way we think about and treat cancer. It will be refreshing to get the input of physicists, mathematicians, and biochemists in a field that has been uniformly managed by genomic scientists.

The future could be bright, maybe even sweet, as we move in these new directions.

As always, I appreciate your thoughts and comments.