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Cracking the Code

The Edith Sanford Breast Cancer Foundation is committed to funding transformational genomics research to ensure patients benefit from breast cancer treatment that is personalized and precise.

For many years cancer research has revolved around a powerful, elusive word: cure. We’ve been raising funds, wearing pink, and walking miles for a cure; we’ve been waiting, praying, hoping for a cure. The focus has been on one single solution to the big, deadly problem of cancer, but as we now know, the answer is far more complex.

Recently, the language and the mission of cancer research has shifted as we understand more about how cancer develops and grows. Scientists have learned more about the unique way that cancer manifests in each person, driven by genetic mutations and the interaction of multiple genes within the complex code that makes up our individual DNA. This knowledge has fueled the current commitment among researchers to crack these codes to reveal additional lifesaving genetic information and to develop treatments that target the genetic changes that cause cancer cells to grow.

This new approach to research has led to a transformational shift in how we think about treating cancer: instead of finding one cure, we are cracking a code to deliver many different highly personalized treatments that can and will save lives.

Genetics vs. Genomics

You’ve probably heard of genetic testing for cancer susceptibility, but the more recent and broader field of genomics is beginning to dramatically change our understanding of what cancer is and how it can be treated.

    • Genetics is the study of single genes and their effects. For example, certain inherited mutations in the BRCA1 or BRCA2 genes greatly increase a woman’s risk of breast and ovarian cancer. If a woman tests positive for a BRCA mutation, there are steps that she can take to reduce her cancer risk or to detect cancer at an early stage. Mutations may also be spontaneous, which unlike inherited mutations, means that they occur for other reasons during your lifetime.
  • Genomics generally refers to the study of the entire genome (all of the DNA in an organism). Genomics can consider multiple genes and how they interact with each other and the environment to affect health. Genomic information is already guiding treatment decisions for certain types of cancer—including breast cancer—and the field is expanding at a rapid rate.

 

It Starts With DNA

The story begins with DNA (deoxyribonucleic acid)—chemical information that is stored in the nucleus of each of our cells. You can think of DNA as being made up of two connected strands of letters. The way in which these letters are ordered and grouped to form words and sentences controls how our bodies are made and maintained.

Within each cell, DNA is packaged into several separate pieces called chromosomes. Each chromosome, in turn, consists of many genes. A gene is a stretch of DNA that has a particular function; usually, this function is to make a protein. Proteins form the basis for the structure and function of our bodies.

DNA Sequencing

By sequencing DNA—gathering information about the letters of the code within cancer cells and normal cells—scientists have begun to identify genomic changes that characterize certain types of cancer. This is expanding our understanding of the tremendous variability of cancer, and is also pointing the way toward better diagnostics and treatment.

As the tools for DNA sequencing have improved, it’s become possible to evaluate much more of the genome. Rather than looking at only a single gene or a small number of genes, it’s now possible to evaluate the entire genome. Whole exome sequencing and whole genome sequencing are examples of this broader approach to DNA sequencing.

    • Whole exome sequencing: The exome refers to all of the pieces of DNA that provide instructions for making proteins. This makes up roughly one percent of the genome. This type of sequencing is an efficient way to look for many of the currently known disease-causing mutations. A limitation of this approach, however, is that it misses DNA variations that occur in other parts of the genome.

 

  • Whole genome sequencing: Whole genome sequencing overcomes the limitation of whole exome sequencing by collecting information about all of the letters in an individual’s genetic code. This expands the number and types of genetic variations that can be detected.

Once genetic changes are identified, it’s important to determine whether and how they affect health. This research is ongoing.

Breast Cancer and Genomics

What is breast cancer?

breast cancer infographicBreast cancer is the most commonly diagnosed cancer in U.S. women, with more than 232,000 cases diagnosed each year. Survival has improved over recent decades, but the disease continues to kill roughly 40,000 women each year. (See our infographic to learn more.)

Breast cancer usually starts with the abnormal growth of cells in the ducts or lobules of the breast. As the cancer grows, these cells can invade nearby normal tissue and can also spread to other parts of the body.

Today we understand how complex breast cancer is at every level. It’s not a single disease, but many different diseases with tremendous variability in how they grow and respond to certain types of treatment. Currently, breast cancers are commonly tested for characteristics such as estrogen receptor (ER) status, progesterone receptor (PR) status, and HER2 status. These characteristics provide information about some of the pathways that drive the growth of the cancer, and also help guide decisions about the use of hormonal therapies and HER2-targeted therapies.

How is genomics changing our understanding of breast cancer?

For research purposes, breast cancers are often divided into at least four broad categories. These categories describe breast cancers that show different patterns of growth and behavior.

  • Luminal A: Hormone receptor-positive, HER2-negative, low Ki67
  • Luminal B: Hormone receptor positive and HER2-positive (or HER2-negative with high Ki67)
  • Basal-like/triple negative: Hormone receptor-negative and HER2-negative
  • HER2 type: Hormone receptor-negative, HER2-positive

These categories will likely undergo additional refinement based on ongoing genomic research. The ability to focus on more narrowly defined categories of breast cancer allows researchers to better understand the factors that drive the growth of each type. This, in turn, can point the way toward new, more effective, and more individualized types of treatment. Progress in this area will be particularly important for the subtypes of breast cancer that currently have a poor prognosis and few treatment options, such as triple negative breast cancer.

How is genomics changing care for breast cancer?

As noted above, several breast cancer characteristics have long played a role in treatment decision making. More comprehensive genomic testing, however, will provide more detailed information about tumor behavior.

Researchers recognize that patterns of gene activity within a tumor can provide information about how aggressive a tumor is likely to be. Rather than assessing only a single characteristic of the tumor, gene expression tests can evaluate several genes at the same time. For example, for women with early-stage, estrogen receptor-positive breast cancer, this type of testing can provide information about the likelihood of cancer recurrence and the likely benefit of chemotherapy. Use of this type of testing is likely to expand.

There’s Still Work to Do

Although genomics is already changing the way in which breast cancer is classified and managed, there is still a tremendous amount that we don’t know. Rapid progress is being made, however, offering the hope of evermore individualized treatment and longer, cancer-free survival.

References:

  1. National Human Genome Research Institute. Frequently Asked Questions About Genetic and Genomic Science. Available at: http://www.genome.gov/19016904 (Accessed September 18, 2013).
  2. Gray J, Druker B. The breast cancer landscape. Nature. 2012;486:328-329.
  3. Balko JM, Stricker TP, Arteaga CL. The genomic map of breast cancer: which roads lead to better targeted therapies? Breast Cancer Research. 2013;15:209.
  4. Genetics Home Reference. What advances are being made in DNA sequencing? Available at: http://ghr.nlm.nih.gov/handbook/genomicresearch/sequencing. Accessed September 30, 2013.
  5. American Cancer Society. Cancer Facts & Figures 2013.
  6. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor–positive breast cancer. J Clin Oncol. 2006;24:3726-3734