It was on the checklist that day. My yearly screening mammogram was scheduled at 7am on September 1, 2015.
The first patient slot assures a departure time of 7:30am. I would arrive at work by 8am, giving me just enough time to stop for a coffee on the way. I had a full day planned – two Zoom meetings, neuroradiology imaging studies, a 6pm Peloton class, and finally a walk with my two best friends and our dogs.
Little did I know that by 7:16am that day, my life would change. Typically, following my scan on the way to check out, I sit for five minutes with the radiologist – my roommate from medical school – and catch up on life. This time, however, there would be no small talk. I needed an emergent ultrasound and biopsy for a mass deep near the chest wall. Neither of us could even feel it on physical exam.
This was not on my checklist.
Now four years out from treatment with surgery, chemotherapy, and radiation, I consider myself to be one of the lucky ones. I have recovered from my treatment, but no one knows about the persistent heaviness or multiple episodes of cellulitis in my dominant right arm, following the removal of 21 lymph nodes. No one knows the feeling of having two kettle bells as breasts.
My radiation burns have healed. My hair has grown back to its normal length and texture. On the outside I have healed, but on the inside, I have scars. But, still, I am one of the lucky ones.
The Current Landscape
Improved survival rates after breast cancer diagnosis are due to many factors. Better and more frequent screening procedures have led to earlier treatments. Advances in systemic therapies, such as hormonal, targeted and immunotherapies, mean that we can treat later-stage diseases.
The mainstay surgical procedures such as lumpectomies and mastectomies have been performed for decades with some technical improvements, but still, local complications remain. Radiation has been used for decades, and some medications can now minimize the burn, but still, local complications remain. Many of the chemotherapy agents have also remained the same but are better tolerated with the use of other medicines to decrease side effects, but still, systemic complications remain. Despite progress, there is still significant pain, suffering, and disability.
Over the past several years, focused ultrasound – a noninvasive, early-stage therapeutic technology – has gained traction in the medical community due to its ability to treat tissue with no needles or skin incisions, thus minimizing the risk of skin deformity, bleeding, or infection. There are more than 130 clinical indications at various stages of research for focused ultrasound, and 6 FDA approved applications, so it is no surprise that breast cancer is an interesting and potentially promising target for the technology. In fact, the use of focused ultrasound for the treatment of some types of breast cancers already has regulatory approval in Europe, Russia, and China, and there have been more than 20,000 total treatments worldwide.
How it Works
Focused ultrasound is a novel technology that precisely focuses beams of ultrasound on targets in the body without damaging surrounding tissue or tissue along the beam path. At the focal point where the beams converge, the ultrasound energy can create a variety of biological effects enabling the treatment of breast cancer. The primary mechanism that has been employed for focused ultrasound treatment of breast tumors is called thermal ablation. During this technique, the focused ultrasound beams generate high temperatures within the targeted tissue, which induces cell death.
An analogy that most of us can remember from childhood is using a magnifying glass to focus the sun’s rays on a leaf, creating heat and a small fire. In this same way, focused beams of ultrasound can kill the targeted tissue with submillimeter precision. And because focused ultrasound is an image-guided therapy, both MRI and ultrasound can be used as guidance systems to target and monitor the treatment in real time. There are clinical trials in Switzerland, the Netherlands, and France that are exploring the use of focused ultrasound-induced thermal ablation for primary breast cancer masses.
Immunotherapy and Chemotherapy
More recently, the biological effect of focused ultrasound to activate an anti-tumor immune response and focused ultrasound’s potential to enhance the delivery of immunotherapy drugs are areas being explored in clinical trials and preclinical laboratory studies. The hypothesis is that when focused ultrasound beams disrupt cancer cells, specific proteins called antigens are released and become detectable by the body’s immune system. This may then lead to the activation of T cells that can infiltrate and destroy tumor cells.
In addition, it has been shown that focused ultrasound enhances the effects of immunotherapy drugs in other ways, the exact mechanisms of which are still under investigation. At the University of Virginia, a clinical trial exploring the use of focused ultrasound combined with an immunotherapy drug (Keytruda) to treat metastatic breast cancer is under way. This is the first-in-the-world clinical trial using a combination of the two therapies to treat breast cancer.
Additionally, focused ultrasound can also increase the concentration of medications to breast cancer metastases through increased blood flow and increased permeability of the vasculature. Trials in Norway and the Netherlands are exploring the potential of focused ultrasound to enhance drug delivery to breast cancer liver metastases, and in patients with stage 4 breast cancer, respectively. The scientists hope that focused ultrasound will increase drug delivery to the tumor and decrease total body drug concentration, resulting in fewer systemic side effects.
Focused ultrasound can also be used to safely and temporarily open the blood-brain barrier, which can increase transport of therapeutics such as chemotherapy and immunotherapy drugs directly to target sites within the brain. A clinical trial for targeted drug delivery and blood-brain barrier opening in patients with HER2 positive breast cancer metastases to the brain has begun enrolling patients in Canada.
Although the use of focused ultrasound for the treatment of breast cancer is quite promising, multiple challenges exist which are being addressed in the above clinical trials. Defining the best patient population to treat, including the stage of the cancer and the optimal tumor size, need to be determined. There are several technical issues to overcome, such as the inability of current machines to safely target cancers less than one centimeter from the skin surface. Further, long-term follow-up of patients is costly, and surveillance measures to ensure lack of recurrence are not yet standardized. Ongoing research will also help us determine which mechanisms of action – such as thermal ablation, targeted drug delivery, or immune activation – are best, whether alone or in combination, to fight breast cancer.
The Focused Ultrasound Foundation will continue to support breast cancer research, and perhaps focused ultrasound will prove to be an integral tool in the armamentarium of breast cancer therapies.
My checklist is now growing again – and reprioritized. Number 1: My dedication to breast cancer research with focused ultrasound.
Help us revolutionize treatment for breast cancer by funding studies that will develop strategies for both early-and later-stage disease.
See the case statement >
Focused Ultrasound for Breast Cancer
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Suzanne LeBlang, MD, is the Director of Clinical Relationships at the Focused Ultrasound Foundation.