• 20 Apr, 2025
• Dr. Steven Narod

Challenging Breast Cancer Beliefs: Professor Steven Narod on Early Detection, Screening, Genetics & Treatment

Magazica: Welcome to Magazica. Today we have the honor of speaking with Professor Steven Narod, a leading voice in breast cancer research.

For over three decades, Professor Narod has dedicated his career to understanding and combating this disease. His work at the University of Toronto’s Institute of Medical Science has challenged conventional wisdom and offered new perspectives on breast cancer. His recent book, A Fair Trial, is already sparking essential conversations. We are here to explore his insights, his journey, and what they mean for us all.

Professor Narod, welcome to Magazica.

Dr. Steven Narod: Thank you for inviting me.

Magazica: You have dedicated three decades of your career to breast cancer research. That’s a remarkable commitment. What initially sparked your interest in this field, and what keeps you driven after so many years?

Dr. Steven Narod: I started my training in mathematics at the University of British Columbia back in 1971. Then, I went into medical school in 1975 and graduated in 1979 at age 24. I was deeply interested in science and my mathematical background influenced my understanding of how research works.

I specialized in public health in Ottawa and later moved to the University of Toronto to work with Dr. Tony Miller, an expert in cancer epidemiology. We began the Canadian National Breast Screening Study in 1983, and we published the final report in 2014 after 30 years of work.

My interest in the genetics of cancer emerged when I started exploring whether chemicals in the environment, which we call mutagens, contribute to cancer. This led me to further study of genetics at Sick Children’s Hospital in 1985. Over time, I became fascinated with the idea that mutations in some genes, inherited rather than caused by environmental exposures, could influence cancer risk as well. The technology at that time offered the potential to identify these genes and help individuals at high risk.

I continued this journey at the International Agency for Research on Cancer with Gilbert Lenoir in Lyon, France. My project there focused on identifying a breast cancer gene. Since 1987, I’ve worked alongside a great team. One of our key collaborators was Henry Lynch in Omaha, Nebraska, who had collected extensive family histories and blood samples. With this data, we analyzed which parts of the chromosomes correlated with cancer risk.

In 1994, I was a member of the team that discovered the BRCA1 gene, followed by the BRCA2 gene in 1995. These were pivotal moments. Using my training as an epidemiologist and mathematician, I then delved into questions about risk factors, prevention strategies, and the overall risk of various cancers.

The risk of breast cancer in BRCA1 and BRCA2 carriers is about 80%. But can we reduce this? Yes, we can reduce it by understanding which risk factors contribute. We can reduce it through better screening, perhaps with an anti-cancer pill, or even preventive surgery. Since 1995, I’ve been collecting data from approximately 18,000 women worldwide who have BRCA1 or BRCA2 mutations.

We gather information every couple of years, asking questions about the hormones they’re taking, the screenings they’ve undergone, and the surgeries they’ve had. Over time, we’ve gained a solid understanding of how to lower the cancer risk from 80% closer to the population risk. This has been a productive part of my career, and it’s what I’m best known for—although I’ve also expanded my research into ovarian, and prostate cancers.

Magazica: That’s a fascinating journey. You’ve encapsulated it beautifully. Let’s turn to your book A Fair Trial: The Foundations of Breast Cancer. In your 2024 edition, I understand it challenges some long-held beliefs about breast cancer. Could you explain one or two key concepts from the book for our readers, many of whom don’t have a medical background?

Dr. Steven Narod: I hope it’s easy to grasp. While the ideas may challenge the medical establishment, my aim is to make them understandable for non-specialists. My observations often seemed paradoxical, conflicting with conventional views on breast cancer.

For instance, our study on breast cancer screening in Canada, conducted from 1983 to 2014 with Tony Miller, revealed that annual breast cancer screenings did not reduce mortality. While mammography improved survival rates for cancers found early, it did not decrease overall deaths – compared to women who didn’t undergo screening. How can that be? This puzzled me and made me question why mammography failed to provide the expected benefit.

Another significant discovery involved early-stage breast cancer. Surprisingly, while we could prevent second breast cancers in many women, it didn’t necessarily prevent death. For example, our 2024 publication focused on second breast cancer. If you develop breast cancer in your left breast, your chance of getting it in your right breast over 20 years is about 10%. Having a second breast cancer increases the risk of dying from breast cancer—from 11% to 18%.

Many women who opted for bilateral mastectomies—removing both breasts—effectively prevented second breast cancer. Yet, this preventive measure had no impact on mortality rates. This paradox, that prevention doesn’t lead to increased survival, mirrors findings from the 1980s by Bernard Fisher regarding invasive recurrences following breast cancer in the same breast.

These insights shaped treatments like lumpectomies, which involve removing the tumor while preserving the breast. Before, mastectomies were standard practice, removing the entire breast. Fisher’s findings showed that preventing local recurrence via mastectomy didn’t improve survival rates, which explains the shift toward lumpectomies. Women who have a lumpectomy have a higher risk of recurrence, but it doesn’t affect their survival.

These were two observations that seemed symmetrical. You can develop a new breast cancer in the same breast or the opposite breast, and while this significantly increases your chance of dying, preventing it through preventive surgery doesn’t reduce your chance of dying from breast cancer.

This struck me as very similar to the idea of mammography. If detecting cancers through screening when they’re small is beneficial, then why isn’t preventing them altogether better? For instance, while a bilateral mastectomy can prevent cancer, it doesn’t reduce mortality. So why would screening for the second breast cancer be more effective?

For example, many women who have had breast cancer undergo annual mammograms to check for recurrence. However, we’ve shown that preventing recurrence doesn’t reduce mortality, so it raises the question of why finding it early would improve outcomes. These are controversial ideas. Women willingly undergo mammograms for peace of mind, but it’s worth examining whether it truly changes outcomes. Recently, a Lancet paper compared outcomes of having mammograms every three years after breast cancer compared to annual ones, and found survival rates were the same. This leads me to question whether mammograms after breast cancer are beneficial at all.

No study has conclusively shown that post-breast cancer screening mammography reduces mortality. While I could go on, I encourage readers to explore these ideas in my book, A Fair Trial. I could be wrong—nothing in science is beyond challenge or replacement with better evidence and insights. But I think that these are important discussions.

Breast cancer starts in the breast, but women die because it spreads. Cancer that spreads to the lungs, liver, brain, or bones (metastatic) is ultimately what causes death. I propose that breast cancer in the breast and metastatic breast cancer might be two separate processes. The conventional model suggests breast cancer begins in the breast and then spreads. Thus, removing it should prevent metastasis and reduce mortality. My model, however, suggests these processes might happen independently.

For instance, we can completely remove a breast cancer through surgery, yet 10 to 20% of women die from it nevertheless. This is because, for them, the metastasis may already have spread before the cancer is removed. For these unfortunate women, metastatic spread at diagnosis is ultimately the cause of death. Understanding and addressing this is key to improving outcomes for breast cancer patients in 2025.

Magazica: When reading Part 4 of your book, titled “Dormancy and Activation,” it discussed how long cancer remains dormant and when it becomes active or visible. For a breast cancer patient, understanding the period between dormancy and activation feels critical—especially regarding early detection. Could you elaborate on how this impacts your research and what guidelines you might offer readers for successful early detection?

Dr. Steven Narod: When I speak of tumor dormancy, I refer to cancer cells that have already left the breast and entered metastatic sites like the lung, brain, or bones. Dormancy describes the time between breast cancer diagnosis and recurrence, which can span over 20 years.

For instance, we’ve discovered that for women with low-risk breast cancers—like ER-positive, small, well-differentiated tumors—the risk of recurrence remains constant throughout their lifetime. Remarkably, the chance of recurrence in the second year after diagnosis is the same as in the 18th year.

We can accurately predict the likelihood of recurrence, but predicting when it will occur remains elusive. Breast cancers primarily fall into two categories: triple-negative and ER-positive. In 2007, Rebecca Dent and I co-authored a paper showing how these types differ in the timing of recurrence timing. Triple-negative breast cancers typically recur within two years, and by six years, the likelihood of recurrence is nearly nonexistent. Conversely, ER-positive breast cancers carry recurrence risks for at least 20 years.

I believe this difference stems from tumor dormancy. ER-positive cancer cells can remain dormant for years, even decades, while triple-negative cancers tend to recur more rapidly. Advances in blood tests, like ctDNA, now help predict whether dormant cancer cells remain in the body. Positive results indicate a high likelihood of recurrence, while negative results suggest a lower risk. However, what to do after a positive test remains unclear—no studies have yet shown that early intervention prevents recurrence.

Patients often ask me whether they should undergo these tests, which may not be government-funded. While the results provide valuable and accurate information, the lack of proven therapies following a positive test makes the decision personal. I advise some patients to wait until more interventions are available.

I’m optimistic that, over the next five years, research will identify effective treatments—whether new or existing chemotherapies—to prevent progression after a positive ctDNA test. My statistical approach to studying dormancy has revealed fascinating insights, though predicting recurrence remains a challenge.

Factors such as myocardial infarction can accelerate recurrence, and there’s evidence that aspirin and vitamin D might reduce risk. Drugs like tamoxifen, widely used for ER-positive cancers, extend dormancy by keeping cancer cells in a quiet state. While tamoxifen reduces recurrence risk during use, stopping the drug may elevate risk again. The debate continues on whether it should be taken for five, seven, or ten years. While longer durations show some benefits, we must balance these against potential side effects.

Magazica: You’ve already answered many of my follow-up questions, but one thing that stands out is the type of research you do—data-based, statistics-driven, often involving longitudinal studies. These are incredibly long and tedious processes for a layperson like us. How do you keep yourself motivated during all this?

Dr. Steven Narod: That’s a really good question. Take the breast cancer study I mentioned earlier with BRCA carriers—I started that in 1995. Some of the patients enrolled back then are still doing well 30 years later. They continue to fill out questionnaires, and occasionally, I have the pleasure of speaking with them. Many are doing well and are grateful—that really motivates me.

The breast cancer screening study I did with Dr. Miller is another example. We started it in 1983 and published it in 2014. Every patient in that study was followed for 30 years to assess the outcome of mammography.

Currently, my research is focusing on various treatment options for breast cancer, particularly for young women and those with genetic mutations like BRCA1, BRCA2, and PALB2. In the past five years, we’ve ramped up efforts to investigate optimal treatments for these patients. For some, we use retrospective techniques, reviewing the medical records of individuals diagnosed 10 or 15 years ago to understand outcomes.

Collaboration has played a big role in my work. I’ve been fortunate to work with excellent colleagues at Women’s College Hospital, including Mohamed Akbari, Joanne Kotsopoulos, David Lim, Kelly Metcalfe and Vasily Giannakeas. Many of them have been part of the team for 20 years. Together, we’ve used large-scale databases to answer critical questions. For instance, American data from the SEER Registry covers nearly half of U.S. breast cancer cases and has provided us insights for numerous papers, some based on close to a million breast cancer cases.

However, existing databases can’t always answer detailed questions. For specific studies—like examining the impact of breastfeeding duration, hormone replacement therapy, contraceptive use, or MRI screenings—we go directly to the patients. One ongoing effort involves 1,500 women diagnosed with breast cancer before age 40. This Canadian study, now running for five years, is comprehensive: we gather medical histories, conduct genetic tests, and collect blood samples to better understand how we can help these young patients.

So what keeps me motivated? Honestly, the answers aren’t out yet. With every study, there’s hope that we’ll uncover valuable insights in the next few years. That hope drives me forward. I believe our efforts can genuinely help patients. Beyond that, I’m passionate about sharing my model of breast cancer as described in my book A Fair Trial. I’d love to see it generate more dialogue among researchers, patients, and leaders in the cancer field.

There’s been remarkable progress recently. New tests can define individual risk and assess recurrence likelihood. Advances in chemotherapy, both for patients with and without genetic mutations, show promise. Knowing that we’re making strides motivates me to keep going.

Magazica: So there’s a lot to go. In your book, I noticed in Chapter 15 that you mention “the mammogram debate continues.” With your vast experience in the field, and given this ongoing debate, what do you believe are the most promising areas of breast cancer research right now? What gives you hope for the future?

Dr. Steven Narod: Most progress in reducing breast cancer mortality over the past 10–15 years has come from advancements in treatment, particularly chemotherapy. There are new drugs targeting estrogen receptor-positive and receptor-negative breast cancers that have made a difference. While the incremental benefits of these drugs on mortality may seem small individually, when combined and personalized—through testing the tumor and the blood—they significantly improve outcomes.

Tamoxifen, introduced in the 1980s, has been incredibly beneficial, and newer developments build on that success. I aim to explore ways to target chemotherapy toward metastasized cells rather than focusing solely on cancer cells within the breast. This requires understanding the burden of chemotherapy and how it interacts with breast cancer. It’s important to remember that chemotherapy reduces mortality risk by one-third. For example, among 100 women with early stage breast cancer, we’d expect about 20 to die within 10–15 years. Chemotherapy can reduce that number to 14, preventing six deaths.

We give chemotherapy to all 100 women because we can’t yet identify the 20 at higher risk. If we could identify those 20, we could avoid giving chemotherapy to the other 80, eliminating unnecessary side effects. This de-escalation is a major goal of current research—identifying patients at risk through blood tests and tumor analysis to personalize treatments. While de-escalating chemotherapy improves quality of life by removing side effects, it doesn’t directly reduce the number of deaths. Targeting metastatic cells and understanding the cancer’s unique biology—both in the woman and in the tumor—are crucial.

We often focus on preventing recurrence or contralateral breast cancer as valid outcomes, but preventing recurrence in the breast doesn’t necessarily affect mortality. It’s essential to prevent metastasis or eliminate metastatic cells after they develop. The challenge lies in intervening before diagnosis, as once cancer is diagnosed, it either has or hasn’t metastasized—the primary tumor’s removal doesn’t change that.

Magazica: It’s fascinating to hear from someone so deeply involved in the field. Your insights are invaluable.

Dr. Steven Narod: Thank you. There are certainly differing opinions, and I encourage exploring other perspectives.

Magazica: Professor, you’ve made a remarkable impact on many lives through your research, insights, and your model in A Fair Trial. At the end of your book, you included ten thought-provoking questions about breast cancer, which I encourage all readers to explore. What do you hope your legacy will be? What message would you like to leave with our readers?

Dr. Steven Narod: I hope my legacy reflects my contribution to understanding breast cancer and improving patient care. My goal is to challenge assumptions and inspire better conversations among researchers, clinicians, and patients. The questions at the end of A Fair Trial aim to spark curiosity and critical thinking. If I’ve helped shift paradigms or encouraged new insights in breast cancer research, I’ll consider that a success.

Magazica: Above all, I want to leave readers with hope—hope that we’re making progress and that the future holds even greater promise for personalized medicine and improved outcomes.

Dr. Steven Narod: We aim for our studies to have a direct impact on the lives of women with breast cancer. For instance, last year we demonstrated that MRI, or magnetic resonance imaging, is highly effective at reducing deaths in BRCA1 carriers. Currently, we’re investigating some key questions, such as whether hormone replacement therapy (HRT) is suitable for women at high risk of breast cancer or those undergoing preventive oophorectomy. These women often have their ovaries removed at a relatively young age—in their thirties or forties—and there’s hesitation to prescribe HRT due to concerns it may increase the risk of cancer recurrence. We’re putting significant effort into determining the validity of these concerns.

Magazica: If I may interject, at the start of the interview, you mentioned researching four groups of women. Is this related?

Dr. Steven Narod: Yes, it’s connected to both young women and BRCA1 mutation carriers. Since 1896, studies—like one published by Beatson in the UK—have shown that oophorectomy, removing the source of hormones, can be therapeutic for breast cancer patients. While we now have drugs that can suppress ovarian function, our research shows that for BRCA1 carriers, removing ovaries at a young age significantly reduces mortality from both ovarian and breast cancer. However, we’re focused on improving their quality of life through HRT. We’re optimistic about producing impactful results, particularly for BRCA1 carrier studies.

When discussing quality of life, it involves addressing side effects of treatments. We aim to reduce these by appropriately managing them and avoiding chemotherapy for women who might not benefit. We strive to support quality of life by providing HRT for those experiencing menopause, whether induced by chemotherapy or oophorectomy. Additionally, proper surgery and reconstructive techniques contribute to maintaining a positive body image.

Patient-informed consent is central in 2025. Today, patients play a significant role in their treatment decisions. While this doesn’t extend much to chemotherapy, it’s evident in choices regarding surgery, radiotherapy, tamoxifen use, or screening. The advancements in patient engagement—particularly in Toronto and Canada—ensure women are involved in discussions about therapies, understanding potential benefits and side effects.

Magazica: You’ve also dedicated an entire chapter to the patient perspective in your book, which is fascinating.

Dr. Steven Narod: It’s an area worth exploring. For example, while doctors may advocate screening to detect cancer early and prevent death, patients often seek reassurance that they don’t have cancer. Surprisingly, many interventions—despite lacking promises of improved life expectancy—are sought for peace of mind. Mammograms are one such example, offering reassurance but not necessarily preventing death. After a normal mammogram your risk of dying of breast cancer goes down a lot.

Anxiety and depression also influence quality of life and should not be underestimated. For instance, our studies reveal those women with very early breast cancer diagnoses and low mortality risks, say below 5%, experience similar levels of anxiety as those with higher expected mortality risks, around 20-30%.

Magazica: Congratulations on your 2025 induction into the Canadian Medical Hall of Fame. We’re eagerly looking forward to more groundbreaking books and research from you. You’ve left an indelible mark on this field, and it’s been an honor having this conversation with you. Thank you for joining us.

Dr. Steven Narod: I appreciate it. Thank you very much for having me.