Breast Cancer Treatment De-escalation Benefits Patients, Health Care Systems

From radical mastectomy to sentinel lymph node mapping, and systemic approaches such astamoxifen and targeted immune therapies, the options for treating breast cancer have undergone evolution after evolution. Although extensive therapies for breast cancer can be effective, not all patients will derive the most benefit due to toxicities related to treatment. That’s why the next leap forward in breast cancer is identifying patients who would best benefit from a treatment de-escalation approach through the use of precision medicine.

The success of [breast cancer treatment de-escalation] relies on the continued advocacy and education of doctors and researchers, medical technology innovation, legislators, insurance companies, and administrators.

The goal of de-escalation is reduced morbidity, decreased risk of adverse effects (AEs) and complications, and, most importantly, a higher quality of life post-treatment without compromising oncologic outcomes. Other benefits go beyond the patient directly, and include more efficient workflows, flexibility in scheduling, and cost effectiveness. The success of this movement relies on the continued advocacy and education of doctors and researchers, medical technology innovation, legislators, insurance companies, and administrators.

Systemic De-escalation

Breast cancer management can be described under categories: systemic (e.g., chemotherapy), local (e.g., surgery or radiation of the breast), and regional (e.g., surgery or radiation of the nodes). As an example, systemic de-escalation includes the now common practice of approaching tumors as being estrogen receptor (ER) positive vs ER negative.

At the beginning of my career, if we were dealing with a large tumor and positive nodes, we turned to chemotherapy. Since then, we’ve learned that not all ER-positive tumors need chemotherapy; for example, endocrine therapy is less toxic than chemotherapy and may give a patient adequate advantage.

Now, we have even more precise ways to interrogate a tumor; with products such as MammaPrint and BluePrint,¹ we can create a full genomic profile allowing us to apply the best possible therapy for that tumor specifically. That has led to a new NCCN Guideline, as the MammaPrint and BluePrint tests can detect ultra-low risk cases that may not require systemic therapy (and its accompanying AEs) after the tumor is removed.²

Surgical De-escalation

From a surgical perspective, de-escalation has meant going from nearly assured mastectomy in the 1970s and 1980s to breast conservation—how I was trained—to oncoplastic approaches that are now the standard of care. A good surgeon knows how to operate; an excellent surgeon knows when not to operate. Precision medicine is making us all more excellent surgeons. For the patient, this is an incredibly positive shift.

I recently had a case in which the tumor was so extensive that the patient was offered a mastectomy because, given the location and the size of the tumor, there was not a cosmetic way to save this breast. She saw me as a second opinion because she felt so strongly that if mastectomy was the only option, she would choose not to treat the cancer, and “leave it with God.”

I have been using a technology called MOLLI^®, a wire-free localization method with the smallest markers available. I could use MOLLI markers to define the extent of the tumor and evaluate her images with the radiologist to know how precisely I could excise it. We were able to give her a breast lift and reduction, and in less operating time. Because of precision medicine and technologies, I know exactly where the tumor is, and exactly what needs to be removed (and what doesn’t) so I can save as much tissue as possible, and leave patients with a cosmetically acceptable breast. It’s a good treatment that yields positive outcome.

Quality of life is a much higher priority for patients like this when I can offer them a lumpectomy and combine it with radiation. And even with radiation, we’ve noticed not everybody needs whole breast radiation within the last decade; some women may not need radiation at all. Partial breast radiation is less toxic, faster, and less expensive, and has allowed us to de-escalate on a localized therapy.

De-escalation Beyond Surgery

The latest de-escalation strategy I’m involved with is to skip surgery entirely. I am now using cryoablation techniques, a well-tolerated outpatient procedure, to treat very small, low-risk tumors.³ There is also radiofrequency ablation, radiation ablation, microwave ablation, and ultrasound ablation techniques available to de-escalate treatment, so some women can avoid going to the operating room entirely.

In my own career, going from modified radical mastectomy as the standard of care to techniques like cryoablation is exciting and gives me a lot of hope for patients in the next decades. The negative impact of therapy on patients is decreasing, and it takes less time and costs less money to get them the results they need, which is a relief for other systems within health care, too.

System Challenges: Education and Advocacy

With these tremendous advances come sizable challenges. Speaking for myself, the way I work now is not the way I was trained. Delivering de-escalation benefits to patients requires a coordinated approach that includes education and advocacy from the scientists who are developing technologies, the physician scientists who are embracing the technologies, and the public, as represented by policy makers, insurance providers, and administrators.

Physician Challenge

Keeping up with new information and using it to change the way you work is a challenge for everyone in almost every profession. For physicians, it can be a struggle to get out of the comfort zone of one’s training. Typically, larger academic centers are more likely to push the envelope, so people who are part of those systems may have an advantage in that way. That means patients with the same tumor in a rural vs urban location may not be able to access the same treatment options. And, as expertise goes deeper rather than broader, subspecialty training has increased. That’s where technological advancement is more rapidly embraced.

In addition to keeping up-to-date with the latest technologies and procedures, physicians must also prioritize research and assessment of these new approaches. For a new test or therapy to gain approval by insurance companies, it must undergo many peer-to-peer reviews. Physicians must collect data to enhance credibility, report on those findings, ensure quality, and publish them.

Technological Challenge

I often say technology is a good servant but it's a bad master. Just because something is new doesn’t mean it is good or effective. For example, we've gone through a lot of different technological solutions for working up a nipple discharge.

While I was training, the buzz was about a tiny ductoscope that would allow visualization of lesions within the duct system of a breast. It was expensive, very precise, and required special training to use. But it couldn’t rule cancer in or out, so surgery was required either way. The bang for the buck, if you will, was not there. When we push technology, we always have to match it with evidence to see that it works.

Not all change is progress.

It’s our job as physicians to be good stewards, so that if resources are going into new technologies, they are used in the best possible ways. As new technology comes with a capital cost, there needs to be good communication and understanding about the return on that investment. Why is it best for patients? Why is it the best use of funds? Administration and chief executive officers need this information so they can put up the capital for physicians to embrace technologies that help de-escalate breast cancer therapy.

Each technology, though expensive in its own right, is helping to bring down the total cost of health care because it treats patients precisely on an individualized basis to derive maximum benefit instead of treating everyone with the same surgery or systemic approach, which scales the expense. The more precise we become in choosing the best care for the best cause and the best outcomes, the more cost effective we can be.

Patient Challenge

Another angle is the patient's perceptionof treatment. Some patients are much more comfortable with the treatments they’ve heard of or experienced indirectly that are backed up by a deeper wealth of data. Some are, by their nature, excited about participating in newer strategies, trials, and research studies. That’s why public education and community awareness are important parts of a physician’s role. At the same time, the ethics of “do no harm” mean we need to be mindful that new approaches and technologies always have less data than established ones. It’s a needle we must tread carefully to advance care without compromising safety.

Physicians must also prioritize communication with their patients. Patients are often overwhelmed with the complexity of their treatment options, and physicians must ensure that they have a clear understanding of the risks and benefits, as well as the potential AEs.

From the patient to legislators and healthcare insurance providers, there are many levels of education in place. The ultimate stakeholder—for the legislators, doctors, and insurance companies—is the patient. And many times when these decisions are being made, the patient is not at the table. That’s why advocacy is an important part of being a physician in this system.

Quality of Life in the Future

Until now, survival and quality of life have been the driving force behind how we treat cancer. But we understand better that it’s not just about adding days to life but adding life to days. If a patient lives longer but suffers from depression, chronic pain, or she’s not perceiving herself as a normal looking woman, have we served that patient? On paper, that question has no answer because no two patients and no two cancers are alike. That’s why the future of cancer treatment must be about delivering the best possible individualized care using precision medicine at all levels from diagnostics to therapy.

Oncology is a team sport. No one person can do everything, and communication is crucial between all of the complex systems involved: technology, healthcare delivery, insurance, and legal. We’ve come a long way in the last few decades from new drugs to new technologies, and new research. But there is much more to do.

References

1. Schuler E, Uygun S, Mittempergher L, et al. Equivalence of NGS-based MammaPrint 70-gene signature risk of recurrence and BluePrint 80-gene signature of molecule subtyping test to the centralized microarray tests. Ann Oncol. 2022;33(suppl 3):S232-S237. doi:10.1016/j.annonc.2022.03.256
2. Updated NCCN® guidelines recognize MammaPrint® UltraLow risk result, highlighting its clinical utility for women with early-stage breast cancer who can safely forgo toxic treatments with excellent survival rates. News release. Agendia. February 13, 2023. Accessed May 10, 2023. https://bit.ly/44IAhlr
3. Regan-Tuero HC, Ward RC, Sikov WM, Littrup PJ. Cryoablation and immunotherapy for breast cancer: overview and rationale for combined therapy. Rad: Imag Can. 2021;3(2). doi:10.1148/rycan.2021200134