This transcript has been edited for clarity.
Lidia Schapira, MD: Hello. I'm Lidia Schapira, and I'm your host for this program, Medscape InDiscussion: Breast Cancer.
Before I introduce this episode's guest, I wanted to begin with a case study that we can return to talk about at the end. A 52-year-old, perimenopausal primary care physician consults with you after a recent biopsy showed a low-grade ductal carcinoma in situ (DCIS) that was detected after she had an abnormal screening mammogram. She has no known genetic risk or family history and is otherwise healthy. She met with a surgeon and radiation oncologist, and she comes to see you because she feels quite ambivalent about receiving treatment. She wants to know if she really must undergo local therapy now and consider endocrine therapy, or if it's safe to wait and see.
I can think of no better partner for this discussion than Dr Antonio Wolff, a professor of oncology and clinical trialist at Johns Hopkins. Dr Wolff's primary interest is in accelerating new treatments through trials designed to better understand the biology of breast cancer. But the breadth of his scholarship and publication extends to topics that address common management problems in breast cancer and delivery of care for cancer survivors.
Antonio, before we begin our discussion, can you share with our listeners what motivated you to become a medical oncologist and specifically to focus on breast cancer?
Antonio C. Wolff, MD: Thank you very much, Dr Schapira. It's really a treat to be with you today and with all the listeners of your podcast.
When we go around the table introducing ourselves at meetings, my usual response now is, "My name is Antonio Wolff, and I'm interested in anything related to breast cancer." And I think this goes back also to probably the decision that I made a long time ago, number one, to become a medical oncologist — and that actually was driven by my profound interest in internal medicine at large.
I think all of us who are medical oncologists recognize this is not a procedure-oriented specialty; this is a very cognitive type of patient care. There's a lot of thinking; there is a lot of discussion. There is a lot of the integrating the whole being: the patient, the care partners, their surroundings. And then the degree of science involved, the degree of biology involved. First and foremost, this is what attracted me to oncology. I was a good clinician, and I really loved patient care. Oncology is a very holistic specialty. And then breast cancer. It coincided with the mid 1990s, when I was doing my training. This is when BRCA1 and BRCA2 were identified. This is when the first Oxford overviews were coming out. I was inspired by the power of data, the power of evidence, and the conversations we have with our patients. So, to some degree, I think it was a natural attraction.
Schapira: You enjoy the science and clearly also the relational aspect of the work. Let me pick your brain now, and let's shift our attention to the topic for this episode. In a recent commentary that you published in the Journal of Clinical Oncology (JCO) as a senior author, you stated that "[t]he natural history of DCIS is poorly understood," and that clinicians and patients need to weigh possible benefits from such interventions as endocrine therapies with observation. How do you discuss this in your clinic with your patients, especially since the expectation of a patient who is referred to you for a medical oncology consultation is that she will leave with a prescription for treatment?
Wolff: Those conversations are among the longest conversations I have with patients. It's quite interesting: For a lot of patients who unfortunately have advanced disease, decisions are a little bit more clear-cut. The assumption is that you are going to do treatment; you're going to be as reasonably intensive and appropriate. I don't like to use the word "aggressive," but we're going to be deliberate, and we want to make sure that we don't second-guess having this opportunity to intervene, keeping in mind quality of life and all of the other issues.
With DCIS, I find those conversations to be among the longest conversations I have with my patients. It's almost like it's inversely proportional: The lower the stage of the cancer, the longer the conversations will be. And I think there is a significant degree of anxiety that we see in all patients with DCIS, and it's understandable if we are on the other side of the stethoscope and we're in their shoes. You've just been told that you have breast cancer. And even though we recognize that most patients with DCIS will not ultimately develop invasive disease — most patients with DCIS will live a full life and die of something else, such as old age and other comorbid issues, especially heart disease.
On top of that, we have seen with greater use of imaging screening, especially mammography screening, a significant increase in the frequency of detecting DCIS, which used to comprise about 10% of all breast cancer diagnoses and now accounts for upward of 30% of all breast cancer diagnoses. We would have expected that this would therefore translate in a lower frequency of invasive disease and improved survival, and we're not seeing that. So I think there's a major concern about the potential risk for overdiagnosis.
Schapira: Given that MRI has greater sensitivity for high-grade vs low-grade DCIS, is nearly 100% sensitive for invasive cancer, and is not affected by breast density, do you think MRI could be used to decrease the number of lesions that are biopsied and eventually treated?
Wolff: There are two parts to that. For those of you who are listening to this conversation, let's do a big disclaimer: I am a medical oncologist. This goes back to my comment before that I am, to a degree, interested in anything related to breast cancer treatment and management.
So, number one, we need to be careful not to overdiagnose DCIS, but in a general sense, when you discuss this with breast imaging specialists, their increasing interest in MRI is the possibility that an MRI might be able to offer a better assessment of the extent of disease. It might better address a lack of calcification and so, if a decision has been made for someone who's been diagnosed with DCIS, perhaps an MRI could help better define the extent of disease and facilitate an increase in the number of patients that end up having a single procedure and reduce the amount of re-excision (which is still quite prevalent). Some data from the ECOG-ACRIN trial that our group conducted a number of years ago (E4112) showed that re-excision rates after patients are treated for DCIS with help from MRI appear to be significantly lower with the addition of MRI over traditional imaging. It's more about potentially improving, but once a decision has been made, you're going to intervene to improve the cosmetic outcome and reduce the number of surgeries that patients might need.
Schapira: It's another way of thinking about this as a way of becoming more precise in our diagnosis. Even though neither you nor I are imagers, as MRI techniques have evolved, there may be ways of doing the procedure in a way that are perhaps faster and easier and help us to distinguish some of these cases. But in the meantime, Antonio, what criteria do you use in practice to recommend MRI screening?
Wolff: More and more, I think we are thinking about MRI screening for patients who have a high baseline risk of developing breast cancer. This is especially prevalent in the population of individuals who belong to a high-risk family — in many cases of breast cancer or ovarian cancer, individuals who have been identified as being germline carriers for BRCA1, BRCA2, and PALB2. Those are the individuals who are likely to begin breast cancer screening at a younger age, in many cases around the age of 30. Those are the individuals. Those are the women who, because of age, are more likely to have dense breasts and mammography will have a lower sensitivity. So I think age is a big factor, especially for younger patients with a high-risk family history. I think that's all, in terms of screening, because then we have questions about the use of MRI after a cancer diagnosis and surveillance in the long run.
Schapira: If you want to make any comments about that, feel free to do that.
Wolff: This is a potentially even more challenging piece. And what I mean by that is: To all of us who are medical oncologists taking care of patients with a previous history — a previous diagnosis of breast cancer, in many cases stage 1 disease — a growing number of those individuals are being treated appropriately with breast conservation. Most of them will be a candidate for a lumpectomy and, in many cases, radiation therapy for completion of breast conservation. Now the question becomes, what's the best way to do long-term surveillance of the breast that has been treated and what's the best way to do screening for the contralateral breast that is not affected?
In this case, it's someone with a previous history of developing breast cancer, where we know the risk of developing contralateral breast cancer is about 0.5% that year, or about 5% up to 10 years. These patients, who have a preserved breast after early-stage diagnosis and breast cancer patients, soon after completion of the surgery, they often will have a BI-RADS 3 type of imaging. There will be postoperative changes. For both, radiation changes may take a while for things to settle down. The team will also be interested in confirming the stability of the imaging. Patients will have the images at 6 months and 12 months. And patients may go back to an annual surveillance schedule, but often many of these, especially young women, have more dense breasts. Then you see that infamous statement, which is understandable, by the radiologists that MRI should be considered or could be considered.
Those are tough statements to put in the report because once you say something could be considered, you could argue that a lot of things could be considered. And it becomes very difficult for the clinicians, the surgeon, the medical oncologist, and the radiation oncologist sometimes to advise the patient. The patient may come to you and say, "Dr Wolff, I saw this on my report that MRI could be considered. Should I do it?" And the answer is, "Well, you could consider it." But once a decision is made to begin MRI surveillance, the question that I find most challenging is: When do you stop? And now you keep going. Many of these women will have annual MRIs for surveillance, plus annual mammography for surveillance — and what was supposed to be a surveillance every 12 months becomes an appointment with breast imaging twice a year. I find those conversations incredibly challenging.
I want to be fair to all the physicians involved in the care of those patients. I want to be fair to the patient as well. I cannot be the decision-maker, obviously, especially because I am a medical oncologist with opinions, of course. But I usually try to engage also both the radiation oncologist and the breast surgeon and, more important, the imaging specialists — the radiologists — so that we don't make a default decision, which is simply start something. And once you start something — this is behavioral economics 101 — there is something called "the endowment effect." It's very easy to start something, to acquire something. It becomes very difficult to stop or give up on something.
Schapira: That was a phenomenal discussion of a pain point, I think, for many of us, especially in the setting where you're not part of the initial team that got it started. You're pulled into the conversation later, and you want to start a conversation about stopping a practice when your patient reaches an age where it just doesn't make sense to do it. But she has been led to believe that this is now part of her standard of care.
Let me turn your attention now to the idea of observing women with DCIS without treatment. Can you talk a little bit about trials that are actually investigating this and are current?
Wolff: This is another fascinating topic. The disclosure is that, in most cases, the medical oncologist will not be involved in the decisions about observation after a diagnosis of DCIS because the usual standard would be to intervene. The question then becomes: Could we intervene with something other than surgery? It could be an intervention of nothing, or it could be an intervention of drug therapy because you have someone who has been diagnosed with low-grade DCIS, abnormal imaging, or biopsy. And again, this goes back to what we were discussing before, Lidia: knowing that not all DCIS lesions will evolve into invasive disease — some may actually disappear. Remember that we used to not find them as much as we find them today.
A couple of studies have been attempted. Another one is ongoing. These are studies of observation for low-risk DCIS. There are two studies in Europe: one is called LORIS, and the other one is LORD, a similar idea. These studies closed prematurely because of issues with accrual, highlighting the challenges again. Once you diagnose something that you call "cancer," patients ask, "Doctor, are we going to just watch? Aren't you going to do something about it?" So those are not easy conversations to have.
Another possibility, instead of just observation, might be early intervention with drug therapy instead of surgery. There is in the US the COMET study, which is the comparison of operation vs monitoring with or without endocrine therapy for low-grade DCIS. These patients, instead of having an immediate intervention, will be given drug therapy with an anti-estrogen oral medication for a period of several months. Then you're going to be watching these individuals carefully with imaging and the possibility that some of these images may regress and may potentially even disappear. That could provide another way to deal with these patients or help these physicians deal with their issues.
In some cases, even if these patients already develop DCIS, they could be at risk for developing another breast cancer event in the future — ipsilateral or contralateral disease. And maybe these are the best patients to consider for primary risk reduction in this case, who already have a diagnosis of DCIS.
The challenge in some cases becomes that for many patients with low-risk DCIS, if you're going to make a decision to intervene with something, some could argue that a small surgical procedure is a one-time thing and you are done. Some of these patients may indeed have low-grade DCIS. It may not require radiation, so you do your outpatient surgical procedure and nothing else. And you don't commit them to radiation, which in some women can be associated with low-grade residual inflammation in the breast and with discomfort, or expose them to drug therapy, which could have quality of life issues related to the use of anti-estrogens. You will find different schools of thought.
I think at the end of the day, it's not that you have one approach that is a better approach or a more efficacious approach, especially when you're dealing with a disease that is unlikely to metastasize and is unlikely to have an impact on long-term outcomes in terms of survival. A lot of these decisions are quality-of-life decisions. And perhaps what I like about having all of these options on the table and learning about them through clinical research is that actually, different options will be good options for different patients. I think the more information we have on different types of intervention vs observation, the better off we will be in helping patients make a decision that is right for them.
Schapira: You've talked about observation, surveillance, wide excision alone, the use of local radiation or omission, and the use of endocrine therapies. Lots of things to think about.
As we finish this section, again I have a very focused question for you, because I so admire the time you take to explain things to patients. I wonder how you have these conversations and have the patient leave you feeling confident about their ability to make a decision that is right for them. Because you and I know, Antonio — and there's plenty of literature to support this fact — often the perception of risk is highly exaggerated for women with DCIS. We've both, I'm sure, seen so many women who are distressed, who have psychological morbidity and what we would think of as an almost an exaggerated fear of cancer recurrence for what we, as oncologists, consider a low-risk problem. How do you handle it? What tips do you have for listeners?
Wolff: The problem is that we are human beings. Patients are human beings. Doctors are human beings. We all bring to the consultation room our life experiences and our past experience with good and bad decisions we made, with regrets or a lack of regret of various decisions we have made. And we humans don't deal well — forget about healthcare issues — we don't deal well with risks. I remember watching Jaws in 1975 and the next day going to the beach, and you can imagine what how fearful I was of a shark attack on the beaches of Rio de Janeiro, where a shark attack has never happened in history. The point is, we don't do a good job at assessing risk. And now in the age of COVID, we see that on a daily basis.
I think there's a lot in terms of telling the patients what you're going to tell them. Tell them, and then tell them again. Try to be balanced in the presentation of evidence. Try to remind them that no one is absolute in their knowledge. Try to remind them that our data are imperfect. Evidence is imperfect, and crystal balls are very cloudy.
I think this is actually one of the most important things that I tell patients: We need to make decisions today based on the available information we have today, and we make the best decision we can. We do this every day. We do this when we decide to buy a house here vs there, or to marry one person vs another at some point. You may change your mind, or you may regret the decision you made, but you don't live in fear that you made a bad decision.
The challenge here is that obviously you're talking about health issues, and health issues trigger a huge amount of emotion. But I try to, when I meet with patients, ask them for a moment to see whether they can put that on the side. And let's make today a decision that feels good to you. My job is not to give them the menu of a restaurant so that they can choose à la carte what they want for dinner.
They came to us because we are the experts, so I think we don't have the right to sit on the fence and tell patients, "It's your choice." That is not fair to them. I think we can tell them what we think they should do, but to try to explain the different possibilities and what to expect and allow them to make the best possible decision. And we can tell them, "Do not second-guess your decision, because it's not going to be fair to you and to your loved ones if you do that."
Schapira: This concludes part one of my conversation with Dr. Antonio Wolff on DCIS and lower-risk early-stage breast cancer. The rest of our conversation with Dr. Wolff on higher-risk forms of early-stage breast cancer will be available as episode 3 of this podcast. Thanks for joining us.
Feasibility of a Prospective, Randomised, Open-label, International Multicentre, Phase III, Non-inferiority Trial to Assess the Safety of Active Surveillance for Low Risk Ductal Carcinoma In Situ – The LORD Study
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Cite this: DCIS and Low-Risk, Early-Stage Breast Cancer - Medscape - Mar 15, 2022.