Breast Cancer in 2012: Not Your (Grand)Mother’s Disease
Guest blog from Kelly Graham-Seyed, Susan G. Komen for the Cure Scientific Grants Manager
In the 1970’s, breast cancer was a disease that no one talked about, and doctors found very difficult to treat. The methodology used to identify estrogen receptor (ER) status was just being developed, and not commonly used. Fast forward 20 years, to the 1990s, and testing for the estrogen receptor was optimized and widely used in pathology labs to split breast tumors into ER+ and ER- types and help doctors to offer treatments that would be most effective in specific patients. In the late 1990s, recommendations from the American Society of Clinical Oncology to test for the HER2 receptor led to an additional division of breast cancer types. The early 2000s brought the analysis of breast tumor types to a genetic level, with the identification of 5 distinct subtypes of breast tumors based on the genes present in individual tumors’ genetic fingerprints. The year 2012 has further defined (and thus subdivided) breast tumor types, providing us with a better understanding of breast cancer, a roadmap to personalized medicine, and revealing more questions to answer in the years to come.
One important study this past year came from The Cancer Genome Atlas Network (TCGA), a collaborative effort of more than 150 researchers from nearly 100 institutions, departments, and centers from around the globe. This project is the first comprehensive genetic analysis of breast cancer, combining information from six different technologies used to study the tumor genome. The study revealed four major types of breast cancer which can be further divided by alterations in the tumor’s genetic makeup. These alterations represent potential Achilles heels in the tumor’s biological processes, providing targets for new therapies. The data also showed similarities between basal-like breast cancers (which are mostly triple-negative) and high-grade ovarian cancers.
The significance of this project extends well beyond the science. First, it demonstrates the advantage of a collaborative research environment: science is not a “silo” and the breast cancer research community must rally around the cause to make major advances. Second, it shows that individual breast tumors are defined by much more than their ER and HER2 status, providing the rationale for making personalized medicine a reality. Lastly, the study demonstrates molecular commonalities in breast cancer and other types of cancer. The importance of this key finding means therapies already approved for treating other cancers may be available to implement in the breast cancer setting, making clinical trials more streamlined.
Genetic Studies of Breast Cancer
Other work that advanced our knowledge of breast cancer and its complexities in 2012 included a novel study from the Cancer Genome Project used methods similar to those used to determine the age and relationship between different species of animals to look back in time at the step-wise accumulation of genetic mutations in breast tumor samples. The take-home message from this study is that the mutations present in of the heterogeneous population of cells in a breast tumor occur when a tumor is starting to form and continues to evolve over time, resulting in unique genetic fingerprints for each breast tumor.
Another paper co-authored by Komen Scholar Judy Garber and Komen Grantee Kornelia Polyak and colleagues echoed these findings, suggesting that some BRCA1-associated breast tumors may not be initiated and driven by BRCA1 mutations, but may instead have other genetic mutations that drive the tumor’s growth, with BRCA1 mutations occurring later in the tumor’s life cycle.
This year, researchers took a long, hard look at mammary stem cells (MASCs) that contribute to mammary gland development during key physiological changes (puberty and pregnancy). Scientists hypothesize that breast cancers arise when the biological processes in MASCs are deregulated. Komen Scholar Geoff Wahl studied fetal mammary gland development in mice and found striking similarities between the molecular pathways expressed in fetal MASCs and basal-like breast cancers, which may provide promising biomarkers for patient prognosis and targets for therapy development. Other studies focusing on adult breast stem cells unveiled a molecular mechanism for determining a mammary stem cell’s commitment to becoming a specific breast cell type. The genes that regulate these processes have been implicated in tumor development and metastasis, and may provide targets for future therapies and diagnostic tests.
New Approaches to Understanding Breast Cancer Treatment
Research efforts in 2012 have also advanced our understanding of breast cancer treatment. Many studies sought to understand the biology behind a tumor’s resistance to breast cancer therapy. Komen grantee Gary Johnson and his team at the University of North Carolina School of Medicine identified key signaling pathways involved in drug resistance, providing insight for developing more effective drug combinations to fight breast cancer, particularly in triple negative breast cancer, which is notoriously difficult to treat.
In other work, Komen Scholars Joan Brugge and Gordon Mills studied drug resistance in 3D breast cell cultures, which more closely resemble what occurs in the breast. They found that a combination of drugs that target cell survival pathways and cell proliferation pathways at the same time was more effective than treatment with a single drug.
Komen grantee Trey Westbrook and his team at Baylor have been using a technology, called functional genomics, to study genes that play a role in cancer. Using this technology, Dr. Westbrook identified a gene that is related to the propensity for a tumor to metastasize, which may provide doctors with a new drug target to prevent metastases.
A Look Towards the Future
The new technologies and research advances of 2012 have enhanced our understanding of the complex biology of breast cancer and provided the foundation for testing possible new therapies. In years to come, researchers will build upon these advances to move us closer to a world without breast cancer. When we achieve that vision, we will have today’s (and yesterday’s) scientists to thank for sending us in the right direction with their research and perseverance.
About the author
Nancy G. Brinker promised her dying sister, Susan G. Komen, she would do everything in her power to end breast cancer forever. In 1982, that promise became Susan G. Komen for the Cure and launched the global breast cancer movement. Today, Komen for the Cure is the world’s largest grassroots network of breast cancer survivors and activists fighting to save lives, empower people, ensure quality care for all and energize science to find the cures. Thanks to events like the Komen Race for the Cure®, we have invested more than $1.9 billion to fulfill our promise, becoming the largest source of nonprofit funds dedicated to the fight against breast cancer in the world.