In his book, The Emperor of All Maladies, author Siddhartha Mukherjee, MD, PhD, gives a face to “The Big C.” He traces our understanding of it and efforts to eradicate it—from Hippocratic “karkinos” (~400 B.C.) to the myriad of malignancies we now lump together as cancer.1 Breast cancer is just one of these. It is the most common malignancy among women worldwide, and it strikes women in their prime.
Mukherjee’s book is punctuated by stories of brave, often brash men and women who dared to challenge the status quo. Often not popular among their colleagues, these pioneers doggedly pursued ideas and approaches that now form the basis of modern cancer biology and clinical oncology. Breakthroughs frequently result from the pursuit of something that is generally believed to be impossible. This editorial is the story of such a breakthrough. It was made not by the research community, but by women themselves who sought to accelerate the path to a cure for breast cancer.
In his “biography of cancer,” Dr. Mukherjee points out that “prevention is the cure.” But how can we prevent something if we don’t understand what causes it? Unlike lung cancer, there is no obvious carcinogen to be avoided with breast cancer. During the past century, our knowledge of “what makes us tick” has grown on a logarithmic scale. We now have an ever-expanding understanding of the molecular triggers, switches, and brakes that together make us who and what we are. We also have the tools that enable us to drill down to the most intricate of cellular mechanisms.
Dr. Mukherjee notes that cancer is “a distorted version of our normal selves.” If breast cancer is “a distorted version” of the “normal” breast, it stands to reason that to understand breast cancer, we must first understand the normal breast. But what is the normal breast?
Defining the ‘Normal Breast’
The human breast is one of the body’s most dynamic organs. During a typical lifetime it constantly changes—from preadolescence to puberty to pregnancy, lactation, involution, and eventually menopause. In any premenopausal nongravid month, it even changes between the two parts of the menstrual cycle. Yet surprisingly little is known about the molecular signals that dictate normal breast physiology. One reason for this is so basic it’s alarming: there has been no source of well-characterized and preserved normal breast tissue. Investigators have used poor substitutes, including tissue from reduction mammoplasties and adjacent “normal” tissue near the malignancy in surgical specimens. Recent work has demonstrated that even at a histologic level, reduction mammoplasty is not “normal.”2 Molecular biology common sense tells us that tissue that is 2-5 cm from a malignancy has experienced the same “field effect” as the malignancy itself.
Now, through the grassroots efforts of the breast cancer advocacy community, a source of breast tissue from healthy female volunteers without breast cancer exists.
The Susan G. Komen® Tissue Bank at the IU Simon Cancer Center (Komen Tissue Bank) became a reality because women want to see breast cancer become a disease of historical curiosity. All we had to do was ask, and more than 3,200 women have come forward to have core breast biopsies, demonstrating that some minor discomfort was a small price to pay for being able to materially contribute to the eradication of this disease.
The Komen Tissue Bank
The Komen Tissue Bank is the world’s only repository of biologic specimens from women not known to have breast cancer. Since its founding in 2007, it has collected breast tissue specimens from 3,200 healthy donors and blood from more than 9,000 individuals. Blood is stored as whole blood (primarily for DNA extraction), as well as serum and plasma. Generally, three to four core biopsies are obtained; one is formalin-fixed and paraffin-embedded, and the others are snap-frozen in liquid nitrogen.
The samples are collected, processed, and stored following stringent standard operating procedures modeled from the National Cancer Institute’s Office of Biorepositories and Biospecimen Research Best Practices for Biospecimen Resources and from the International Society of Biological and Environmental Repositories Best Practices for Biospecimen Resources. Each sample is linked to detailed clinical annotation, including height, weight, menstrual and reproductive history, family history, and a detailed listing of comorbidities and medications.
This unique and critically valuable resource is available to researchers worldwide through a straightforward application found on the website (komentissuebank.iu.edu). From the “Researchers” page, prospective applicants can search the database to ascertain whether the Komen Tissue Bank has the specific samples their work requires. The proposals are reviewed, and once approved, the specimens are released on the condition (as per a Material Transfer Agreement) that the data are returned once publication and/or patent application has been completed. Data will be uploaded into a “Virtual Tissue Bank,” thus informing other researchers and allowing them to build onto earlier results. By avoiding needless repetition and promoting data dissemination and sharing, the hope is to accelerate the path to better treatment strategies and, ultimately, prevention strategies.
For the first time ever, the Komen Tissue Bank allows researchers to compare healthy breast cells to malignant ones and thus decipher the key mechanisms of malignant transformation. For example, understanding the signaling pathways by which the normal breast changes in response to normal hormone fluctuation will inform our understanding of estrogen’s influence on breast malignancies. Detailed annotation of risk, paired with DNA, RNA, and protein analyses, will help us understand the influence of risk factors at a molecular level in healthy tissues and how these contribute to carcinogenesis. Ultimately, it is the identification and modification of key pathways—key “targets”—that will lead to breast cancer prevention.
Importantly, the Komen Tissue Bank has also changed the research paradigm. The tissue donors are not simply subjects in a study. They are participants and partners in research. Together we will find a cure.