BCRF’s singular focus on research distinguishes it from any other breast cancer foundation in the U.S. This year alone, BCRF has committed $63 million to support nearly 300 researchers conducting breast cancer research across 14 countries.
Each October BCRF welcomes its researchers to New York City and hosts two events in their honor: a scientific conference followed by a public symposium and awards luncheon.
This year’s symposium, held at the New York Midtown Hilton, featured a panel discussion with 2018 Jill Rose awardee, Dr. Hedvig Hricak, and BCRF investigators, Dr. Ben Park and Dr. Joseph Sparano. BCRF Co-Scientific Directors Dr. Larry Norton and Dr. Judy Garber moderated the discussion and directed questions from the audience to relevant experts on the panel or seated among the BCRF investigators in the audience.
Key takeaways from the discussion:
Changing how we treat metastatic breast cancer
Dr. Hricak, who was being honored for her contributions in merging imaging with advances in molecular biology, described how radiology has evolved from screening to advanced molecular imaging. Working with a team of experts in radiation and medical oncology, she has developed techniques that converge imaging with molecular biology and is using this technology to better understand metastatic breast cancer.
She described how molecular imaging is being used to identify new tumor targets in metastatic breast cancer and differentiate regions of the tumor that may respond to particular therapies. This work is helping to explain why single therapies often do not destroy all the tumor cells and how combinations can more effectively target the diverse drivers of tumor growth and survival. Precision therapy for early-stage breast cancer
Using blood to monitor response to treatment and to predict recurrence
Dr. Ben Park described how DNA mutations in cancer cells drive growth and the spread of the tumor. By looking for these mutations in the blood of patients, researchers can determine whether the cancer is still present throughout the course of therapy. The hope is that the liquid biopsy can be used to identify breast cancers before they are clinically detectable or to augment imaging diagnostics. In this approach, a suspicious mammogram result can be confirmed by a liquid biopsy before a surgical biopsy is performed.
Dr. Park emphasized that liquid biopsy for early detection is complicated and there are significant hurdles to overcome before it will be ready for clinical applications. He stressed, however the promise of using multiple modalities: radiology, molecular imaging, genomic tests, artificial intelligence etc., to develop precision screening guidelines for each individual.
Dr. Sparano described how liquid biopsy may also be able to predict risk of recurrence. In a study supported by BCRF, Dr. Sparano and his team measured circulating tumor cells in the blood of women diagnosed with early-stage, estrogen receptor-positive breast cancer, who had been taking anti-estrogen therapy for five years. They followed the study participants for a median of 10 years and found that those who had one or more circulating tumor cell after five years of therapy had a much higher risk of late recurrence. His group is launching a clinical trial to test whether they can prevent breast cancer in those they identify at high risk using the blood biopsy.
Precision prevention: the new frontier
Dr. Judy Garber explained that while we have made great progress in our understanding of the molecular underpinning of cancer, less progress has been made in being able to predict individual risk of breast cancer or how to prevent it.
This is the focus of a new prevention initiative BCRF will launch in 2019 Dr. Garber highlighted efforts being made to utilized genetic information in the form of SNPs – singular changes in DNA that may or may not be important to gene function. Scientists are finding that while individual SNPs have very little effect on risk, combinations of SNPs can be used as a signature of risk. In precision prevention, this information will be used with other known risk factors, including breast density to personalize risk assessment.
We know that breast density is associated with increased risk of breast cancer but having dense breasts does not mean you are going to get breast cancer. There is a lot we don’t understand about the risk associated with breast density and clinical trials are needed to study this further. Dr. Laura Esserman is conducting a trial called the WISDOM study to develop better ways to screen for breast cancer, including understanding the role of breast density.
The future of precision oncology: knowing when to treat and not to treat.
Many early breast cancers have a very low risk of becoming life threatening. We don’t yet have the knowledge or the tools to know which ones will progress and those that won’t. Dr. Hricak stated that in the future, doctors will be able to know at diagnosis how aggressive a tumor will be and determine whether patients need therapy or not. Citing her experience in prostate cancer, she believes that some breast cancer patients with early-stage disease will be monitored until the cancer progresses, while others will know from diagnosis that they need more aggressive treatments.
Dr. Sparano agreed with this prediction citing three different studies around the world that are testing a similar “watch and wait” approach that is used for the majority of low-risk prostate cancers in women with low-risk, early-stage breast cancer.
Dr. Garber used the example of how surgery for breast cancer has become progressively less invasive as an example of the success of a “less is more” approach for breast cancer treatment. She emphasized that as precision medicine advances we will know what kind of treatment and how much treatment is appropriate for every breast cancer.
Dr. Park added that liquid biopsy can also be used to monitor levels of DNA mutations in patients in a watch and wait scenario. He explained that “by measuring DNA mutations levels in the blood over time, we can detect changes that could signal a change in the cancer.”
As example of how we are learning who to treat and who not to treat, Dr. Sparano cited a BCRF-supported study that focused on identifying patients who will most likely benefit from chemotherapy and spare those who don’t need it. He described recent results from the TAILORx study, which showed that most women with early stage, estrogen-positive breast cancer can forgo chemotherapy. This means that anti-estrogen therapy will be sufficient to treat their cancer. Using a gene test called Onctotype Dx® doctors can better predict which patients will benefit from chemotherapy and spare those who won’t.
Immunotherapy in breast cancer
Dr. Norton called on Dr. Leisha Emens in the audience to describe recent progress in immunotherapy in breast cancer patients. She highlighted recent results from a clinical trial in which she is the lead investigator. The trial showed a significant benefit in overall survival in patients with metastatic triple negative breast cancer who received immunotherapy in addition to standard chemotherapy. The drug called atezolizumab targets a protein on the surface of immune cells called PD-L1. Patients whose tumors contained high amounts of PD-L1 protein responded dramatically better than patients whose tumors had low or no PD-L1. Dr. Emens emphasize that the results demonstrate that PD-L1 may be a useful marker in identifying patients most likely to respond to the anti-PD-L1 drug. Until now, response to immunotherapy in breast cancer has been poor.
BCRF investigator, Dr. Hope Rugo, a co-investigator on the clinical trial explained how important it is to have a marker for triple negative breast cancer.
“Unlike the majority of breast cancers that are estrogen receptor-positive,” she said, “there has not been a marker to identify patients who are most likely to respond to a targeted therapy.”
The challenge moving forward is to convert “cold” cancers – those that don’t respond to immunotherapy, to “hot” cancers that will. Dr. Rugo described efforts by her team to test combinations of immunotherapy and to see if treating breast cancers with immunotherapy early – before they can become resistant to therapy – will improve response.
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