Dutch molecular biologist Dr. Laura van ’t Veer. Photo: Karen Shuster.
Dutch molecular biologist Dr. Laura van ’t Veer is a pioneer in the field of personalized medicine and one of the world’s leading innovators in cancer diagnostics. She is the leader of the Breast Oncology Program and Director of Applied Genomics at the University of California San Francisco, and her work is having a major impact on the field, for which she has received many awards, including the European Inventor Award in 2015.
She was listed by 24/7 Wall Street as one of the 32 Amazing Women Inventors who have succeeded in fields dominated by men.
Dr. van ’t Veer is the inventor of MammaPrint, a gene-based test that predicts the chances of recurrence in early-stage breast cancer patients, sparing women who will derive little or no benefit from chemotherapy.
Chemotherapy is often recommended after surgery to decrease the risk of cancer recurrence. Yet, the side effects of chemotherapy are harsh, and, as Dr. van ’t Veer’s work shows, it might not be needed for every patient. In fact, her studies show that 46 percent of patients with early stage breast cancer who are recommended chemotherapy can safely forego chemotherapy.
Instead of one treatment for all, Dr. van ’t Veer’s revolutionary work is paving the way to change treatment approaches to target a person’s specific tumor. Her goal is to increase each person’s chance of surviving breast cancer using this individualized approach.
Breast cancer: not one disease
DNA and genes have fascinated Dr. van ’t Veer since she was a high school student. She began studying biology at the University of Amsterdam in the late 1970s and worked as an undergraduate at the Netherlands Cancer Institute). There she became acquainted with research on DNA and cancer, which was an innovative new field in the early 1980s.
“From early on I was interested in understanding the gene mutations in breast cancer and how it could help to identify what kind of disease somebody has. Breast cancer is not one disease, but there are many different types,” Dr. van ’t Veer said.
She completed her Ph.D. at Leiden University in the Netherlands and then pursued postdoctoral training at Harvard Medical School in Boston. Dr. van ’t Veer found Harvard intense and inspiring. At her first cancer meeting in Boston, she said she was surrounded by 500 experts from different disciplines.
“They were all interested in understanding the biology of cancer and using this knowledge to develop new drugs and to understand the diagnosis,” she said. “I had never experienced this. My experience at Harvard further defined what I was going to do.”
Following her postdoctoral fellowship, Dr. van ’t Veer returned to Amsterdam, where she started working for the Netherlands Cancer Institute. She was the first molecular biologist to work in both the institute’s Antoni van Leeuwenhoek hospital and research department. She became head of molecular pathology and set up the molecular pathology diagnostics lab in the institute’s hospital. Leading a multidisciplinary team, she studied the risk of recurrence of breast cancer in women.
“If you understand the risk for recurrence in a patient, you can adjust the patient’s treatment,” she said.
To prevent recurrence after surgery, doctors have recommended chemotherapy for many breast cancer patients based on factors such as the age of the patient, the size of the tumor, and the number of lymph nodes and dividing cells.
“These factors give some indication, but are far from perfect,” Dr. van ’t Veer said. Some tumors look high-risk but in fact are not and the result is overtreatment.
Dr. van ’t Veer and her team took a different approach and looked at the breast tumor’s genes to see if the biology of the tumor could reveal if the cancer is aggressive.
By looking at the activity in the genes of the tumor, they discovered 70 cancer-specific genes which, if switched on, indicate a high risk for recurrence. If these genes are not switched on, the risk for recurrence is low.
Understanding the breast cancer tumor in this way allows for a more tailored approach to treatment.
“If the disease is aggressive with chance of early recurrence, you want to give all of the necessary therapy to prevent this. However, if the disease is very slow growing and the chance of recurrence is low, there is no need to give all of the drugs. Possibly you can even omit chemotherapy,” Dr. van ’t Veer said.
From research to market
Dr. van ’t Veer and her team developed their research finding into a robust diagnostic test to analyze the activity of the 70 genes in the breast cancer tissue and called it MammaPrint, the culmination of years of research and clinical studies.
The test’s validation came from a large clinical trial run by the European Organization for Research and Treatment of Cancer. This trial involved nearly 7,000 women with early-stage breast cancer from nine countries and 100 hospitals.
Recognizing the potential for widespread impact for patients, she wanted to bring MammaPrint to market, so patients outside the Netherlands Cancer Institute’s hospital could benefit from it. For this she needed funding.
To pursue this funding, Dr. van ’t Veer and co-inventor Dr. René Bernards set up a company in 2003 called Agendia. Today, Agendia is a medium-sized company with more than 150 employees, based in Amsterdam and Irvine, California.
At Agendia’s laboratories, a sample of the patient’s tumor is analyzed using MammaPrint. The result shows if a patient is high risk or low risk and recommends who should receive chemotherapy and who can safely forego it.
Today MammaPrint is approved by the US Food and Drug Administration, recommended in national and international clinical practice guidelines, and covered by Medicare and most private insurance companies.
For women who are identified by MammaPrint as high risk, standard chemotherapy is still an option. Yet, standard chemotherapy will only prevent recurrence in one out of five patients, and is thus not always effective.
“If somebody has a high risk for recurrence, you want to do better than 20 percent results. You want to bring it up to 100 percent,” Dr. van ’t Veer said. She is tackling this challenge in an innovative clinical breast cancer trial, I-SPY, at the University of California San Francisco.
Through I-SPY, Dr. van ’t Veer is testing new drugs for patients who have a high risk for early recurrence to study which drug or combination of drugs is most effective given the patient’s breast cancer type.
To access the thousands of new targeted drugs that are emerging, Dr. van ’t Veer joined forces with Dr. Laura Esserman, the principal investigator of the trial and breast surgeon at the University of California San Francisco, to set up a unique consortium of 10 pharmaceutical companies, 20 academic institutions, and six biotech companies.
“To fully understand when to use a specific drug for whom, requires a collaboration with all stakeholders,” Dr. van ’t Veer said. “Everybody has a piece of the knowledge. If we work together, it will go faster. It is this particular collaboration that made me decide to come to UCSF.”
Whereas standard chemotherapy in high-risk patients will only prevent recurrence 20 percent of the time, the I-SPY study has already demonstrated that matching new, emerging drugs to the biology of a patient’s cancer, in addition to standard chemotherapy, has a success rate of 40 percent, and for some tumors it is up to 60 percent.
These findings show that understanding the biology of a patient’s breast cancer can help healthcare providers and patients choose the most optimal treatment for the best results.
“You do not want to give a certain drug to a patient who does not respond to that specific drug,” Dr. van ’t Veer said. “Besides this, these treatments are often $50,000 or more, so also to reduces costs, you just want to give it to those patients who will have a response. We have come a long way.”