Personalized Medicine is a rapidly evolving approach to patient care that incorporates an individual’s genetic information into a customized prevention or treatment plan.  Mapping a person’s total genetic makeup or whole genome sequencing has created mountains of data about variations in our human genetic code.  As this experience has grown, some of these variations have been linked to risks for certain diseases, or in some cases the likelihood that a person will respond to a particular treatment.  Individuals may now submit a DNA sample and obtain their genetic sequence with accompanying risk association analysis for a few hundred dollars.  Can this technology however be harnessed to drive better outcomes for patients diagnosed with cancer?  Many clinicians and scientists argue that we are not there yet.

In breast cancer, survival rates have significantly improved with better means of early diagnosis and treatment, however a consistent proportion of women continue to develop recurrence and die of their disease (450,000 worldwide annually).  In spite of our growing understanding of breast cancer biology, the majority of women continue to receive approximately the same chemotherapy and in some cases hormonal therapy.  This treatment algorithm is the product of decades of rigorous clinical trials defining the best therapy for “the majority of patients”.  We are now entering the era of genomic medicine where doctors and patients alike will demand the best therapy for the individual.

A striking development ushering in this new era of personalized medicine for cancer treatment was the OncotypeDX assay from Genomic Health.  This assay tests a panel of 21 genes within breast tumors to indicate whether a patient will benefit from chemotherapy based on the likelihood of cancer recurrence.  Now widely used in clinical oncology practices this assay offers a tailored approach to treatment for the individual patient, allowing some patients to avoid chemotherapy that will not be helpful for their particular tumor.  Whole tumor genome sequencing, namely sequencing all genes within a tumor cell (25-30,000), intends to elevate this concept to the next level.  In fact The Cancer Genome Atlas project (2012) recently published results of genome sequencing of breast cancers revealing 4 major subtypes, or molecular classifications.  Numerous studies have indicated that significant diversity exists in terms of genetic changes from one tumor to the next.  Consequently, researchers are now using tumor sequencing information to determine personalized cancer therapy.  A recent pilot study from the University of Michigan (Roychowdhury et al) is one of the first examples to explore use of tumor whole genome sequencing for treatment decision making.  Four patients with advanced stage cancer underwent sequencing.  Next an expert panel of doctors and scientists convened to review the specific mutations found in each tumor, and review potential treatment implications.  The study concluded that this approach was feasible and a useful tool in connecting patients with clinical trials examining new drugs for their unique tumor mutations.  It also however defined a significant need for more knowledge connecting the true significance of mutations with individual tumor behavior and treatment response.  Further studies are underway and will no doubt add valuable experience in developing genome based assays to enhance personalized cancer therapy.

Hank Schmidt, MD PhD, is a Surgical Oncologist at the Dubin Breast Center