How to Enhance Early-Stage Breast Cancer Survivorship

ASCO Daily News

Drs. Hope Rugo, Diana Lam, Sheri Shen, and Mitchell Elliott discuss key strategies and emerging technology in early-stage breast cancer survivorship, including mitigating risk through lifestyle modification, surveillance for distant recurrence, and optimization of breast imaging.

TRANSCRIPT

Dr. Hope Rugo: Hello, I'm Dr. Hope Rugo, your guest host of the ASCO Daily News Podcast today. I'm a professor of medicine and director of breast oncology and clinical trials education at the University of California San Francisco's Comprehensive Cancer Center. I'm also an associate editor of the ASCO Educational Book.

There are currently about 4 million breast cancer survivors in the United States, according to the American Cancer Society, and this number is expected to rise as more women are being diagnosed at early stages of this disease, thanks to advances in early detection and the delivery of more effective adjuvant and neoadjuvant treatment leading to successful outcomes.

In today's episode, we'll be discussing current and emerging clinical strategies for the survivorship period, focusing on a multidisciplinary approach. Joining me for this discussion are Drs. Mitchell Elliott, Sherry Shen, and Diana Lam, who co-authored, along with others, a recently published article in the 2024 ASCO Educational Book titled, “Enhancing Early-Stage Breast Cancer Survivorship: Evidence-Based Strategies, Surveillance Testing, and Imaging Guidelines.”

They also addressed this topic in an Education Session presented at the recent ASCO Annual Meeting. Dr. Elliott is a drug development fellow and clinician scientist trainee at the Princess Margaret Cancer Center in Toronto, Canada. Dr. Sherry Shen is a breast oncologist and assistant attending at the Memorial Sloan Kettering Cancer Center in New York. Dr. Diana Lam is a breast radiologist and associate professor at the University of Washington Fred Hutchinson Cancer Center in Seattle.

Our full disclosures are available in the transcript of this episode.

It's great to have you all on the podcast today. Thank you for being here.

Dr. Mitchell Elliott: Thank you so much.

Dr. Sherry Shen: Thank you.

Dr. Hope Rugo: Let's go into the meat of the article now and try to provide some interesting answers to questions that I think come up for clinicians all the time in practice. Your article points out that addressing the challenges in early-stage breast cancer survivorship requires a comprehensive, patient-centered approach, focusing on mitigating risk through lifestyle modification, surveillance for distant recurrence, and optimization of breast imaging.

Dr. Shen, surveillance can facilitate the early detection of recurrence, but ultimately the goal is to prevent recurrence. Lifestyle modifications are a key component of survivorship care, and there are many interventions in this context. Could you summarize the best approaches for mitigating risk of breast cancer recurrence through lifestyle modification and how we might accomplish that in clinical practice?

Dr. Sherry Shen: Absolutely. This is a question that we get asked a lot by our breast cancer patients who are so interested in what changes they can make within their lifestyle to improve their breast cancer outcomes. I always tell them that there are three main things, three main lifestyle factors that can improve their breast cancer outcomes.

Firstly, enough physical activity. So the threshold for physical activity seems to be around 150 minutes of a moderately vigorous level per week. So moderately vigorous means something that gets the heart rate up, like walking quickly on rolling hills, for example. Or patients can do a vigorous level of physical activity for at least 75 minutes per week. Vigorous meaning playing a sport, swimming, for example, running, something that really gets the heart rate up.

The second really important lifestyle modification is limiting alcohol use. Keeping alcohol to less than 4 to 7 drinks per week is particularly important for breast cancer outcomes, especially in women who are postmenopausal and have hormone receptor positive diseases. That's where the strongest connection is seen.

Lastly, maintaining a healthy weight. We know that women who gain more than 5% to 10% of their diagnosis body weight have a higher risk of breast cancer recurrence and worse breast cancer outcomes. That, of course, is easier said than done, and it's primarily through dietary modifications.

I always tell women that in terms of specific things in the diet, it's really hard to study at a population level because diets vary so much between patients. But what is really important is consuming a plant-forward whole foods diet that prioritizes nutrients and the quality of the diet. A little bit more specifically, it's important to limit the amount of red and processed meats in the diet, really limit the amount of sugar sweetened beverages, ideally to cut that out of the diet entirely, and to consume an appropriate amount of dietary fiber in the range of 20 to 30 grams per day. Those are more specific things that have been associated with breast cancer outcomes.

Dr. Hope Rugo: This is such helpful, practical information for clinicians and for patients. Thank you.

But let's move on to another area, surveillance testing for distant recurrence, an area of great interest, in fact highlighted in a special session at ASCO 2024. In clinic, we've seen that many cancer survivors expressed surprise at the less intensive approach to surveillance testing for recurrence, with the whole idea that if you detected it earlier, the outcome would be better. But it does raise an important question. What is the optimal strategy for monitoring for recurrence? And importantly, can early detection through surveillance testing impact outcome?

Dr. Elliott, your research has focused on ctDNA surveillance and the evolving role of minimal residual disease, or MRD. Can you comment on the current surveillance guidelines for distant recurrence, and then, how we really define true MRD?

Dr. Mitchell Elliott: Those are excellent questions, and I think leaving that Education Session at ASCO left us with even more questions than answers with the current role of MRD in this setting. I think a lot of this comes from wanting to help patients and trying to identify the patients at highest risk of cancer recurrence, with the goal of intervening with effective targeted therapy to prevent metastatic relapse.

Current international guidelines in the United States done by ASCO and the NCCN, as well as ESMO guidelines in Europe and even our local Canadian guidelines, do not suggest that patients undergo routine screening in asymptomatic individuals, whether it be blood work or routine radiographic imaging, as there were some studies that were done in the late 1990s and early 2000s that didn't actually show benefit and actually maybe favored a little bit of harm in these situations. So these recommendations are based on these initial studies. However, we know that in the last 10, 15 years, even 20 years, that breast cancer and the landscape of breast cancer has changed significantly with the introduction of our typical standard classification of breast cancer, the emergence of HER2 positive breast cancer, and thus triple negative breast cancer, which was not actually routine standard testing at the time of these studies, and also the most effective therapies we have to date, including immunotherapy, HER2 targeted therapy and the advent of antibody drug conjugates. We're at prime time right now to potentially revisit this question, but the question is, do we have the right technology to do so? And this is where the circulating tumor DNA has really emerged as a potential option, given its minimally invasive opportunity with a standard blood test to actually identify tumor specific DNA that is highly predictive of distant metastatic recurrence or patient recurrence in general.

The evolving role – we still have a lot of questions in this setting. There have been a lot of retrospective analyses of cohort studies and clinical trials that have shown that modern fit for purpose MRD based tests actually have a high positive predictive value at identifying patients with imminent risk of breast cancer recurrence. The most important thing in this setting is that there are different fit for purpose tests. The initial ctDNA assays were actually genotyping based assays, which look for the presence of mutations in the blood. But we know that the sensitivity of these assays is quite challenging at the level of ctDNA required to actually diagnose patients with very small amounts of residual disease. So the fit for purpose MRD assays are now emerging on the market. And we have several that are in clinical development, several that are in research development, but the high specificity in the setting is very important, which we're seeing some evolving and emerging technologies in this setting. We really don't have the data about if these interventions, so if we were to effectively deploy these MRD based ctDNA assays prospectively in patients, if they will actually improve patient outcomes, and how do we correct and address lead time bias, which might potentially affect study results?

Also, the important thing to think about in this setting is if we are able to find something, we also should have an effective therapy to actually intervene for patients, because the outcome in these trials will actually be dependent not only on identifying early breast cancer occurrence, but also delivering the best targeted intervention for that individual patient, which currently we don't understand fully.

Another really interesting thing is there was a trial, the ZEST trial, as many of our listeners may know, that was randomizing patients with patients with ctDNA detected in the adjuvant setting were randomized through either intervention or standard follow up. And going forward, is it actually an opportunity, or is it possible to actually randomize patients knowing that they have a near 100% likelihood of breast cancer recurrence to observation? So these are several ongoing questions that we have to address as we move forward to deploying this technology in the clinical space.

Dr. Hope Rugo: Really fascinating, and thanks for sharing that. I think really broad and helpful information on these ctDNA [assays] and also our surveillance guidelines, which I think really suggests that you only do surveillance for cause, other than looking for local recurrence and new cancers with breast imaging. So it is really an interesting time where we're seeing evolving technologies and evolving understanding of how we can best do this kind of testing when there are so many different assays out there. I think it's going to take a little while. And also understanding, as you pointed out, trying to target treatments when patients have emerging ctDNA to mutations. And we just have no idea yet if we're going to ultimately change outcomes. This is really helpful, and I think we'll give people a good understanding of where to think about this right now, what to look for in the future.

Now, of course, it's a nice segue into the idea of breast imaging for early breast cancer survivors because that's where we do have data. Dr. Lam, let's talk about how we optimize breast imaging in early-stage breast cancer survivors, because there's such a wide variation in breast cancer imaging survival protocols between different centers and different countries. And of course, here our group is representing two countries and really a broad geographic area. So some of the variations are when to do imaging in terms of frequency, when to start imaging and what kind of examination to do, screening versus diagnostic, MRI versus mammogram. And of course, there are some emerging imaging techniques as well. Could you tell us a little bit about the variation in imaging surveillance protocols in survivors, and the challenges and what you recommend?

Dr. Diana Lam: First off, I want to say that surveillance mammography saves lives and annual intervals are uniformly recommended among both national and international guidelines. However, we know that in practice there are variations in imaging surveillance protocols, with approximately 40% of sites performing imaging at more frequent or six-month intervals for at least one to two years. In addition, there's variation in what type of mammogram someone gets in terms of the indication. They might be getting initial diagnostic mammograms for a short period of time or screening mammograms. However, overall, there is limited evidence in improved outcomes in women getting a diagnostic versus a screening exam for asymptomatic surveillance. In addition, there is limited evidence in increased frequency of surveillance, for example, every six months versus one year.

The real difference between a screen and a diagnostic mammogram, if someone is asymptomatic in the surveillance population, primarily has to do with workflow. For screening examinations, the imaging is generally viewed after a patient leaves the facility, and it might actually take days, maybe even weeks, for the results to be delivered to the patient. In addition, if more imaging is needed, the patient will need to return back to the facility, which does diagnostic imaging work for us to work up this finding. And this practice approach causes diagnostic delays in care. It also disproportionately affects Black and Hispanic women. For diagnostic mammography surveillance, there's generally real time interpretation with immediate results. However, there are both access and scheduling limitations, as not all facilities actually perform these types of examinations. There may also be out of pocket costs which are increased due to the diagnostic indication of this exam.

So what we found, which is an approach that can aid in minimizing patient costs and decreasing these health disparities, is to provide immediate interpretations of these screening mammography surveillance exams, or so-called online screens where diagnostic workup and potential biopsy can be performed on the same day.

Dr. Hope Rugo: This is all very interesting, but what do we tell our patients? How do we, as oncologists, decide on how frequently to get mammograms? Should we be getting diagnostic or screening? And do we sequence MRI with mammograms for everybody or just for certain patients? And then some patients will say, “Well, my doctor does an ultrasound to mammogram.” We don't do that for screening. When do you recommend that?

Dr. Diana Lam: We do know that compared to people without a personal history of breast cancer, surveillance mammography is actually less sensitive. It's only about 70% versus 87% or so percent sensitive with over four times more interval cancers or cancers diagnosed after a negative surveillance mammogram compared to the general screening population without a personal history of breast cancer. In addition, about 35% of invasive second breast cancers are actually interval cancers or those not detected by surveillance mammography. However, there is currently no guideline consensus on supplemental breast imaging or additional imaging beyond surveillance mammography. Contrast-enhanced breast MRI is most often recommended, particularly for patients who are already at high risk for breast cancer, such as those with genetic mutations, or patients who have had primary breast cancer diagnosed at a younger age to less than 50 years old, or those patients who have dense breast tissue on mammography.

There is a question about whole breast ultrasound and this is generally not specified or recommended unless the patient is unable to undergo breast MRI. This is primarily due to the number of false positive examinations or findings that are seen that do not amount to breast cancer. We do have the opportunity here to tailor surveillance imaging by selecting people who are at high risk for interval second breast cancers in order to decrease harms and improve patient outcomes. We know that there are a number of factors such as primary breast cancer subtype which affects second breast cancer risk. We know that women who have ER negative and/or hormonal negative breast cancers have significantly higher recurrence rates within the five years of treatment with no significant difference after that 5 years. We also know that there are certain factors such as imaging factors where patients are more likely to develop an interval second cancer with mammography surveillance only. And these are factors such as if their primary breast cancer was hormone negative, if they had an interval presentation to start, or if they had breast conservation without radiation therapy. So, in terms of the future of local breast imaging surveillance, this can be improved with upfront risk prediction and stratification based on the patient, primary breast cancer and treatment factors, as well as looking at imaging test performance to optimally guide the modality and frequency of surveillance imaging.

Dr. Hope Rugo: Really interesting.

Well, thank you all three of you for sharing your valuable insights. This has been so interesting and a great addition to the ASCO Daily News Podcast. I would encourage everyone to actually read the article as well because there's some really great tables and interesting information there that of course we don't have time to cover, but thank you, all three of you.

Dr. Diana Lam: Thank you.

Dr. Mitchell Elliott: Thank you for having us.

Dr. Hope Rugo: And thank you to our listeners for joining us today. You'll find a link to the article that you can read and look at and cut out the tables discussed today in the transcript of this episode. I encourage all of our listeners also to check out the 2024 ASCO Educational Book where there is an incredible wealth of useful information. Finally, if you value the insights that you've heard today and here on ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Thanks again.

Disclaimer:

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinion of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.

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Dr. Hope Rugo 

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@MitchElliott18

Dr. Sherry Shen

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Disclosures:  

Dr. Hope Rugo: 

Honoraria: Mylan/Viatris, Chugai Pharma

Consulting or Advisory Role: Napo Pharmaceuticals, Puma Biotechnology, Sanofi

Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffmann-LaRoche AG/Genentech, Inc., Stemline Therapeutics, Ambryx

Dr. Diana Lam:

No relationships to disclose

Dr. Sherry Shen:

Honoraria: MJH Life Sciences

Research Funding (Inst.): Merck, Sermonix Pharmaceuticals

Dr. Mitchell Elliott:

No relationships to disclose