Designing an Individually Tailored Cancer Treatment Utilizing Advanced CTC Molecular Analysis
By Steven Nemeroff, ND
For decades, traditional medicine has made cancer treatment decisions based on the “one size fits all” approach—in which everyone with a particular cancer received the same treatment. Tragically, this approach has failed to benefit the vast majority of women with breast cancer who received standard chemotherapy protocols.
This approach has refused to acknowledge the individual differences inherent in the cancer that could have affected treatment. Now, exciting new advances in circulating tumor cell (CTC) technology can allow medical science to finally move away from this outdated approach and towards an individually tailored cancer treatment program.
The basic circulatory tumor cells (CTC) test you learned about in the previous article measures the number of CTC in the bloodstream.
In this article, we’ll examine an even more advanced circulating tumor cell test available in Europe that measures the genetic characteristics of circulating tumor cells and makes specific conventional and natural treatment suggestions based on the individual patient’s CTC profile. This technology offers great potential to optimally design an individualized treatment, targeting the specific weaknesses of these potential metastatic cancer cells.
Exposing the Flaws of the “One Size Fits All” Approach
When a person is prescribed a treatment for their cancer, they might assume that the treatment was chosen based on the uniqueness of their cancer. For instance, when a woman with early-stage breast cancer is told that her chemotherapy treatment regimen will consist of the drugs Adriamycin®, Cytoxan®, and Taxol®, (ACT), she might think this treatment was individually tailored for her cancer. In actuality, ACT is a standard chemotherapy protocol given to breast cancer patients. This “one size fits all” approach to breast cancer treatment would work well if superior results were obtained from this routine practice. Sadly, this has not been the case. The “one size fits all” approach to prescribing chemotherapy has failed to improve survival for the vast majority of women with breast cancer. In a shocking study of women with breast cancer over the age of 50 who had cancer present in their lymph nodes, standard chemotherapy regimens were shown to increase 10-year survival by only 3%.1
In a related study of breast cancer patients receiving tamoxifen, researchers at the Dana-Farber Cancer Institute in Boston determined that those over age 50 with cancer in their lymph nodes did not receive any statistically significant survival benefits from receiving generic chemotherapy regimens compared to tamoxifen alone!2
A critical flaw of the “one size fits all” approach rests in treating all breast cancers as if they are one and the same. Although traditional oncology does make distinctions in a few obvious qualities, such as size of the cancer, lymph node status, and estrogen receptor status, we now know there can be substantial individual differences in cancer cell genetics among those with “similar” breast cancers. These differences can dramatically affect the response to treatment.
A powerful illustration of the lack of appreciation for individual differences in cancer treatment was clearly revealed in a landmark study published in the New England Journal of Medicine in 2007. Researchers compared women with lymph node-positive breast cancer who received ACT chemotherapy to those who did not receive chemotherapy. Their HER2 status was also determined—which refers to a genetic characteristic of the cancer. The researchers discovered that the group of women who were HER2 negative and estrogen receptor positive did not benefit at all from taking Taxol®!3 The ramifications of this study are immense, as approximately two thirds of women with breast cancer fall into this category. In recognition of the failure of Taxol® to benefit this large group of women with breast cancer, oncologist Anne Moore, MD, Professor of Clinical Medicine at the Weill Medical College of Cornell University in New York stated, “The days of ‘one size fits all’ therapy for patients with breast cancer are coming to an end.”4
A further indictment of the “one size fits all” approach was prominently displayed in a study published in the Journal of the National Cancer Institute in 2008. In this investigation, scientists measured the effectiveness of an anthracycline-based chemotherapy regimen in 5,354 women with early-stage breast cancer. Anthracyclines are a class of chemotherapy drugs of which Adriamycin® is a key member. The scientists determined that women with early-stage breast cancer who were HER2 negative derived absolutely no benefit from taking Adriamycin® or other anthracycline drugs!5 Given that approximately 80% of breast cancers are HER2 negative,4 then only 1 of 5 women with breast cancer can benefit from these drugs that have considerable toxicity associated with their use. In one study, 7% of patients treated with Adriamycin® developed congestive heart failure.6
Another fundamental flaw of the current cancer treatment model is the exclusive focus on the primary tumor. However, it is the spread of cancer to other parts of the body that is very often lethal. Once the primary tumor has been surgically removed, then chemotherapy will often be prescribed in an attempt to kill any cancer cells remaining in the body that could potentially form metastases.
The choice of the appropriate chemotherapy agent to target the metastatic cancer cells is usually based on the characteristics of the primary tumor—which assumes that the metastatic cancer cells are genetically identical to the primary tumor. This assumption might be ill-advised as research has demonstrated that metastatic cancer cells can be genetically dissimilar from the primary tumor.
In an illuminating study conducted with metastatic breast cancer patients, researchers compared the genetic composition of the cancer cells that had formed distant metastasis to the genetic composition of the corresponding cancer cells in the primary breast tumor. The findings were alarming—in 31% of the comparisons, the genetic composition of the metastatic cancer cells differed almost completely from that of the primary breast tumors!7 Amazingly, further analysis revealed that none of the pairs of primary breast tumors with its corresponding metastatic cancer were identical. Based on these findings, the authors remarked that “because metastatic cells often have a completely different genetic composition, their phenotype [biological behavior], including aggressiveness and therapy responsiveness, may also vary substantially from that seen in the primary tumors,” leading to their conclusion that “the resulting heterogeneity [genetic variability] of metastatic breast cancer may underlie its poor responsiveness to therapy...”
To further support the evidence that metastatic cancer cells can vary genetically from the primary tumor, two additional studies8,9 with breast cancer patients have demonstrated that CTC can be HER2 positive while the primary breast tumor can be HER2 negative!
Tailoring Cancer Treatment for the Individual
Clearly, this old-fashioned approach of prescribing the same treatment for everyone with a particular cancer needs to be succeeded by a more enlightened paradigm which tailors treatment towards the individual uniqueness of the cancer. Furthermore, this “person-centered” model places emphasis on directing treatment decisions towards the distinguishing characteristics of the potential metastatic CTC. One of the most exciting applications of CTC technology is its use to facilitate the design of a treatment program that is truly customized to the genetic attributes of the person’s cancer. Given that CTC can be the seeds that eventually form metastatic disease, then CTC analysis provides medical science with an excellent opportunity to examine the genetic features of these cancer cells before metastasis occurs, when treatment is far more likely to be successful.
In addition to detecting the presence and quantity of CTC in the bloodstream, recent advances in technology now allows the examination of CTC for a large number of tumor cell markers and genetic expressions. In essence, CTC testing constructs a genetic fingerprint of these potential metastatic cancer cells. The information obtained from this analysis can provide vital insight as to which chemotherapy drugs are best suited to exploit the genetic weaknesses of the CTC, as well as which chemotherapy agents are likely to be powerless against the genetic strengths of the CTC.