Triple negative breast cancer (TNBC) represents a distinct form of breast cancer that does not express estrogen receptors (ER), progesterone receptors (PR) or the Her2/neu protein, hence triple negative.
These cancers are aggressive, disseminate rapidly and do not always respond to standard chemotherapy. Some are associated with BRCA gene mutations. TNBC tends to occur in younger women with a predisposition for African-Americans. Some TNBCs reveal exquisite sensitivity to Platinum-based treatments.
In October 2015, I consulted with a 50-year-old patient with a very large left-sided triple negative breast cancer. The MRI and PET/CT scans confirmed the disease to be localized with no evidence of distant spread. The patient was familiar with our work and expressed interest in having a tissue sample sent to our laboratory for functional profiling.
As the patient’s HMO did not contract with our office, I referred her to a colleague who participated in her insurance plan so he could obtain tissue for our analysis. After she met with the HMO physician, he recommended against our analysis. Once the patient got over her surprise, as it was I who had referred her to this physician in the first place, she declined follow-up with that office, opting instead to pay out-of-pocket at our institution for the biopsy and her first cycle of treatment, while she set about changing her insurance.
With the biopsy performed, my expectation, based upon my original work with triple negative breast cancer (J Clin Oncol 2000) was that Carboplatin plus Gemcitabine would be the most effective. Many investigators consider this to be a gold standard in triple negative breast cancer treatment and I was fully prepared to administer this combination if our laboratory analyses were not available.
Results of the functional profile provided an interesting and very instructive lesson.
Despite my belief in and use of Carboplatin plus Gemcitabine in triple negative breast cancer treatment, this particular patient was much more sensitive to Carboplatin plus Taxotere. Contrary to my expectations, the assay results proved my assumptions wrong.
Based upon our findings she began treatment with Carboplatin and Taxotere. In a single cycle the tumor virtually disappeared. By the second cycle neither the patient nor I could feel the previously large mass. By the fourth cycle there was nothing to be found and with six cycles, restaging revealed only the gold bead placed at the time of initial biopsy. Surgery confirmed a pathologic complete remission with the lymph nodes, tumor and the resected breast all free of disease.
There are a number of lessons from this case.
The first is the exquisite sensitivity of triple negative breast cancer to the right treatment. The second is that functional analyses beat clinical experience, published literature and personal assumptions every time. The third lesson is that patients know best. This patient insisted that we give her the best treatment based upon the functional profile and no opinion, recommendation or outside advice would sway her from that position.
No amount of clinical experience, literature support or big data can replace the predictive validity of human tissue analyses.
This case is an example of cell biology superseding other considerations, as her cancer behaved exactly as the EVA/PCD analysis.