Welcome to our interview with Dr. Jana de Boniface, a renowned surgeon and researcher specializing in breast cancer. In this conversation, we delve into her inspiring journey, groundbreaking research, and collaborative efforts that have led to significant advancements in breast cancer treatment.

Robert Szulkin (RS):  Jana, you’ve just published a paper on “Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases” in the New England Journal of Medicine (NEJM) [1]. Congratulations! This project was completed in cooperation with Cytel’s Real-World Evidence team, and we’d love to discuss the process that made this project a reality. But first, a brief introduction. You are a surgeon specializing in oncoplastic breast surgery as well as a Professor in the Department of Medical Epidemiology and Biostatistics at the Karolinska Institute in Sweden. I’d like to ask a bit about your background.
What inspired you to become a scientist and a surgeon?

Jana de Boniface (JdB): I began my journey as a scientist during my university years in Berlin, and that was just a completely different topic, it was psycho-oncology. When I moved to Sweden to train as a surgeon, I didn’t have a specific moment of inspiration. However, a fantastic senior colleague, Leif, approached me early in my training and encouraged me to pursue research. He must have seen something in me—perhaps my curiosity and perseverance. Since then, what drives me to continue with research is the patients and seeing them in situations where I cannot say why I am doing what I am doing. I need to have evidence for the treatments I recommend. For instance, if I tell a patient they need a mastectomy or need lymph nodes removed and I know it’s going to hurt the patient in the long term, I want to be certain that these actions are necessary. It’s basically this unhappy feeling in the clinic when I just don’t know if I’m doing the right thing.

About how I became a surgeon, I was going to become a psychosomatic doctor, which is a combination of internal medicine, psychology, and psychotherapy in Berlin. Everything was planned: exams, research, post-doc work. Then, during my final obligatory year as a student, I decided to go to Sweden for my mandatory surgical training, as my best friend Michaela had moved there. During these three or four months at the clinic, I just felt like I was home. The hands-on nature of surgery, the immediate impact of the work, and the ability to cure people felt incredibly appealing. My mother, a psychologist, once told me, ‘ You can’t cure people with a knife’ but I believe you can!

RS: That’s interesting. I thought you always wanted to be a surgeon. I’ve seen you perform surgery, and it was incredibly inspiring. What was the first research question you began to investigate in your career, and how has this changed over time?

JdB: My initial research in Berlin was completely different—it was a study on the treatment of hepatitis C. However, I set that aside. My first projects involved sentinel lymph node biopsy in breast cancer, around the early 2000s. At that time, we still performed many axillary clearances, so we started implementing sentinel lymph node biopsies while still performing clearances to ensure the sentinel nodes weren’t giving false-negative results. That’s how I started. We were still discussing the performance and accuracy of sentinel lymph node biopsy in large tumors as a different project. I also delved into tumor immunology, studying the immune response in lymph nodes, which was quite exciting.

RS: So, you’ve been doing axillary surgery research for almost 25 years now. That’s quite impressive. I guess you know the subject very well after all this time.

JdB: Yes, I’ve been deeply involved in it for many years.

RS: Let’s talk about our recent publication, which is a very hot topic right now. The results have been presented worldwide. The research conducted aims to reduce the burden of surgery in breast cancer patients, such as the invasiveness of surgery and potential complications. And now this research has resulted in the first surgical paper to have been published in NEJM in the last 17 years. The SENOMAC trial started back in 2015; how did you come up with the idea to start this study?

JdB: It was of course not just my idea, but we were a team from the beginning. When we started the study, we thought it would just confirm the results of two previous studies conducted in the US and the Netherlands, which had shown similar outcomes. But, those studies faced a lot of criticism, especially the US one, due to their small sample sizes and lack of statistical power. They weren’t convincing enough. Back then, I argued against continuing axillary dissections but the Swedish National Guidelines committee deemed the data too weak to support stopping them. So, we kept performing axillary dissections, which felt frustrating. We were then a small group of people who decided we’d try to start a trial adding more data to the area and broadening the population characteristics to also embrace new questions. For me, this research was a tool to reduce the number of dissections because if guidelines don’t allow you to do less, you need to research to prove the point, and at the same time, research allows patients to get access to a more modern approach.

Before our study was complete, the Swedish guidelines changed, allowing the omission of axillary dissections for certain patients, and replacing it with radiotherapy. So, I  didn’t expect our study to have such a significant impact. While it doesn’t change the Swedish guidelines, it significantly influenced guidelines in other countries. I’ve received many inquiries about the inclusion criteria, such as whether we included patients with extra-nodal extension and if our findings apply to various patient types. And then I noticed that people have probably not just used these older trial data in their full scale, but they’ve used it for some subgroups. They still hesitate to omit axillary dissection in certain types of patients. And I think our study, because it’s so large and has full statistical power, is the first to provide definitive answers to these questions. That’s fantastic and it’s gratifying to see its impact.

RS: Where is this already implemented? What kind of impact will this research have?

JdB: Before the study, I believed that many countries already omitted axillary dissection. The big question was regarding mastectomy patients, those undergoing removal of the entire breast, because we lacked data on that group. The impact of our study is significant here.

Some large countries had already implemented omitting axillary clearance, but they didn’t apply it to patients where metastasis had grown outside the lymph node. After our study, they began to include these patients as well, seeing similar outcomes. Many guidelines adapted these older trials with specific limitations, and I think our study helped to remove those limitations. While I don’t know every single country’s guidelines, I believe many were already moving towards reducing axillary dissection for more subgroups.

In the US, the first trials on omitting axillary clearance in breast-conserving surgery were conducted around 2011-2012. They allowed the omission of axillary clearance in these cases but not in mastectomy patients. It appears their guidelines suggest considering it, but it wasn’t standard practice. Our study is now providing the necessary evidence to support broader implementation, including for mastectomy patients.

RS: How would you describe the results of your research to a non-clinician, such as a patient? What kind of impact could this research have on them?

JdB: For a patient, I would explain it like this: Normally, if we don’t see any signs that cancer has spread to the armpit, we remove something called a sentinel lymph node. This is the first lymph node in the armpit which receives lymphatic fluid from the breast, and sometimes, cancer cells if the tumor spreads. We typically remove one, two, or three of these nodes. And then, if we find signs of metastasis in these nodes, previously, we used to perform an additional operation to remove more lymph nodes from the armpit—usually more than 10. This often led to problems with the arm, such as swelling, pain, and restricted movement in the arm, which could last a long time.

Now, our research shows that removing more lymph nodes does not improve survival rates or reduce the risk of cancer recurrence. So, we can safely leave the remaining lymph nodes in place even if the disease may be present in these nodes. This makes a big difference in the patient’s recovery and quality of life.

RS: You participate actively in real-world evidence studies, observational studies, and clinical trials. Why do you think that is important? Can they complement each other, and what’s your view on that?

JdB: In my field, many questions will never be addressed in randomized trials. For example, deciding whether to perform a mastectomy or a lumpectomy, or whether or not to have an immediate breast reconstruction, can’t be left to a coin toss today. Patients need to be involved in the decision-making process, weighing the pros and cons to make informed choices.

For issues like breast conservation versus mastectomy, new randomized trials beyond those performed in the 70s and 80s are unlikely. Instead, we rely on high-quality, population-based databases with comprehensive and reliable data. These databases allow us to adjust for all these confounders that we know we have and provide insights that randomized trials cannot. There are many similar questions where patient choice is paramount, such as whether to undergo breast reconstruction.

Prospective cohort studies also play a crucial role. If there’s evidence suggesting a new method might be better, but the existing trials are not conclusive enough, we can implement this method in a prospective cohort study. This allows us to monitor patients closely and ensure they receive modern treatment while still being able to assess the method’s effectiveness. If the method turns out to be suboptimal, we can identify this and adjust accordingly.

RS: As I mentioned earlier, this project was completed in cooperation with Cytel’s Real-World Evidence team. Why did you choose to partner with us on this project?

JdB: We specifically chose to work with you because our colleague, Anna Johansson, and I discussed the idea of breast conservation versus mastectomy. When we needed someone for the hands-on statistical analysis, Anna recommended you because of the previous positive experience and partnership we have had.

Before we started our collaboration, I mostly did statistics myself. However, with increasing study sizes and the need for randomized trials, I felt the quality had to be completely watertight, and you provided that. I also quite like our collaborative discussions and your proactive ideas. You’re not just executing tasks; we have a dialogue and we brainstorm our options and come up with solutions to the problems that arise throughout the process. Our team, including Anna, shares a commitment to timelines and schedules, making us very effective. When we wrote the articles, we successfully streamlined the process and ensured everyone contributed and helped.

RB: I agree. Our close collaboration and communication work very well. You explain the clinical aspects clearly, and I can, most of the time, explain the statistical context of everything. Even tasks like data cleaning and checks, which could be tedious, were smooth due to our excellent communication. It’s wonderful to have a good working relationship with sponsors, and it’s been a great experience working with you and Anna.

Interested in learning more about Cytel’s Real-World Evidence solutions? Read more.

Note:

[1] Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases | New England Journal of Medicine (nejm.org)

Share Via