Mutations do matter in Cancer: Dr. Nilesh D. Mehta

Mutations do matter in Cancer: Dr. Nilesh D. Mehta

 Surgeons realized decades ago that breast cancer is not a disease that they can cure all the time. It had to be a multipronged and intelligent attack on cancer cells. There are oncogenic drivers involved in malignant transformation and eventually leading to the spread of cancer. If a patient with breast cancer is not diagnosed at an early stage (I or II), then the likelihood of a cure diminishes substantially.

Genomic studies have revealed that breast cancer is a complicated and heterogeneous disease that includes many targetable genomic alterations. Where it gets confusing is that there are specific oncogenic drivers that propagate the cell growth leading to a worsening condition of the patient. Scientists are studying these genetic alterations in an attempt to provide breast cancer patients with a reasonable crack at precision medicine in metastatic disease. These genomic alterations include PIK3CA mutations, CCND1 amplifications, FGFR1 amplifications, AKT1 mutations, and ERBB2 amplifications. In breast cancer, it is certainly not a “one size fits all” concept. The main reason for this phenomenon is the innate ability of cancer cells to develop mutations rendering previous treatments ineffective. It is like a car that runs out of petrol in the tank and then still run flawlessly with diesel. Or perhaps, even better, develop mutations that would allow the car to run without any fuel whatsoever.

 

The current armamentarium from a treatment perspective revolves around hormonal therapy, chemotherapy, and drugs targeting the HER2 gene. All these treatments have withstood the test of time and have worked exceedingly well. Despite these advances in the last five decades, patients with breast cancer continue to relapse and die from their disease. In an extremely complicated an intricate cellular environment, scientists are trying to elucidate pathways that have therapeutic implications in managing patients with stage IV breast cancer. However, not all stage IV patients with this disease are alike, in fact there is tremendous diversity depending on their tumor make-up. Rather than give chemotherapy to all breast cancer patients, it is becoming increasingly common to “study” the tumor in great detail and then design an attack just for that patient. This would become possible if all the targetable genomic alterations were understood properly. The new “wave” of research is geared towards molecularly analyzing the tumor characteristics using next-generation sequencing technologies from Foundation Medicine. So, imagine a patient who has metastatic breast cancer and wants her treatment. Both breast and lung cancers have served as models for the development of tailored cancer care for our patients. A patient’s oncologist would want to accurately study her tumor characteristics at a molecular level through newer and innovative technology like next-generation sequencing and then cater treatment depending on the report of this smart technology. Gone will be the days where an oncologist will recommend a treatment based on his or her personal bias. It would be a “designed” approach rather than a “bulk” approach. What does this mean for our patients? This is a step in the right direction; however, we are not quite there yet. Clinical trials like SAFIR01 and MOSCATO trials are just beginning to expand our horizons in this important field of breast cancer research. Progress in cancer genomics have raised hopes of increased precision in the identification of patients suitable for targeted therapies tailored to their genotypes.

 

This will be an ongoing medical challenge since science needs proof that this concept that sounds valid has practical implications in treating our patients. Shifting from a one size fits all to individually tailored therapy will require commitment from patients, families, research institutions, academic centers, physicians, scientists, and government support. To answer the question, “are we there yet?”  We most certainly are not. However, the destination is clear and the journey is well on its way. With the continued commitment and dedication of breast cancer researchers, we will soon see many advances in cancer care.

 

Results from the upcoming  50^th anniversary of ASCO (American Society for Clinical Oncology) meeting in Chicago will be awaited by the scientific community.