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Ductal carcinoma in situ -

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Norman Swan: Today on the Health Report, the Black Death. It makes a comeback in the most populous state of the richest country in the world.

And a huge debate of massive importance to women: the diagnosis of early breast cancer through mammography screening. What are the benefits and what are the downsides if you choose treatment?

A major study has been published into the most common finding when healthy women have a screening mammogram and they're told they have cancer: it's called ductal carcinoma in situ, DCIS, cancer cells which have not moved out of the duct designed to carry breast milk to the nipple.

It turns out that DCIS may not be what cancer specialists have thought it is.

The research leader was Professor Steven Narod of the University of Toronto.

Steven Narod: It was thought not to be a full-blown cancer because it was believed it was a precursor lesion, but the research that we present led me and my colleagues to believe that in fact it's a cancer. The only reason it's different from other cancers is it's smaller. The reason that the mortality rate from DCIS is small, that is 97% of the women are cured, I think is not because of where the cancer cells are but just because they are small cancers.

Norman Swan: So in other words people thought that DCIS was a bit like the breast equivalent of the polyp in bowel cancer or the precancerous lesion on a cervix for cervical cancer. In other words, the track to a more serious form of tumour. And what this research suggests is that's actually not necessarily true. What was the study that you did?

Steven Narod: Well, we compiled information that had already been recorded in the United States on 108,000 women who had been diagnosed with ductal carcinoma in situ over I think 20 years. We asked when they were diagnosed, what age, were they white or black, how were they treated? And in the 20 years that followed we asked did they die, did they die of breast cancer? We came to the conclusion it was 3.3% out of the women died of breast cancer at 20 years, and we came to the conclusion that the three treatments that they were given were equivalent no difference: whether you had a lumpectomy, removal of the ductal carcinoma; whether they had a lumpectomy followed by radiotherapy, typically 20 courses; or whether they had a complete breast removed, which is a mastectomy, the outcome was the same, about 3% of the women died of breast cancer.

Norman Swan: And it has to be said that that's one of the issues here, is that women are exposed to a variety of treatments including, as you say, a mastectomy.

Steven Narod: Right. I mean, I do want to emphasise that they all received some kind of treatment. We had no control group that had no treatment. I suspect if we had such a group where they just watched them and saw the course of the disease, the risk of dying would be higher than the 3.3% we saw. I'm not sure how much higher it would be and no one knows but I'm suspecting it would be higher, but we can't really have the data to comment on that.

But certainly if we compare the women with the mastectomy to those women who had a lumpectomy, those women that had a mastectomy, all the breast removed, had far fewer recurrences, cancers coming back in the breast was reduced greatly by the mastectomy, but there was no reduction in the number of breast cancer deaths.

Norman Swan: And this is something that is hard for women and for anybody to get their head around, is that in fact recurrence of a cancer in breast cancer, a lot of the treatment is to prevent the recurrence in that breast, and it doesn't necessarily relate, do you any good in terms of your overall survival.

Steven Narod: That's perfectly put, you said it as well as I could say it. Most of treatment in fact for DCIS over the past 20 years has been developed and has been evaluated with the sole goal, the entire purpose of preventing recurrence. Why? Because it is relatively common. You know, you can get up to 20% of patients who will have a recurrence. However, to study death, only 3% of the patients died within 20 years. We had to study 100,000 patients in order to make a story about DCIS and deaths from breast cancer, so…

Norman Swan: So what you're suggesting is the benefits are rather dilute.

Steven Narod: Well, it's good, as we get more and more advanced, to some extent one of the benefits to society is we are willing to invest more and more energy and money in order to reduce the cancer burden by smaller and smaller amounts. In order to get a benefit from this we have invested lots of money in screening for breast cancer. Let's remember, these DCIS cancers is a modern phenomena, they didn't exist 30 years ago, they were very, very rare.

That's why they call them stage 0 breast cancers because when they invented breast cancer classifications they went from stage 1, 2, 3 and 4. Then mammography came along and they realised there was cancers that were even smaller and didn't fit into the traditional classification so they created a new number for them, stage 0. So it was created to accommodate the new cancers that were being identified through this widespread mammography screening.

We've invested in the mammography screening, and as a consequence we have found three times more small breast cancers now than we did 30 years ago. We haven't reduced the numbers of large breast cancers, and having all these DCIS cancers we've now got more and more of these small cancers, to which the benefit of treatment becomes smaller and smaller. There is a benefit in return but it becomes marginally smaller and smaller as the cancers get smaller.

Norman Swan: What percentage of these women with DCIS were actually diagnosed by screening? Because it does make a difference, doesn't it?

Steven Narod: We don't have the data, but certainly those cancers which are diagnosed by feeling a lump…I would agree with you entirely, those cancers that are due to DCIS and come to your attention because somebody felt them, either the patient herself or a doctor, probably do a lot worse than the ones that are mammographically detected only. And the case in point is if you read our paper carefully, those women who had a DCIS diagnosed under the age of 35 did particularly poorly. That could be because of the age, but it also could be because we don't recommend treating mammography to women at 35. Those cancers, probably the majority of them, were felt as a lump.

Norman Swan: What was the extent, do you believe, of over-diagnosis? Because this is a major issue when we come to the screening debate.

Steven Narod: Well, our study didn't address specifically over-diagnosis. If you ask me the question how many cancers are due to over-diagnosis, I would say, well, we have to be a bit more specific. Out of those cancers that are diagnosed in a mammography program I would say 30% are over-diagnosed. Out of those cancers that are diagnosed in a mammography program and that you can't feel, that the only way that they came to the attention of the doctor was through the mammogram and the woman had no signs or symptoms and you couldn't feel anything, 50% of those are over-diagnosed.

Norman Swan: And are those all DCIS, these ductal carcinoma in situ?

Steven Narod: No, but they tend to be…it's quite interesting, people say we don't know what they are, we know very much what they are, they are either DCIS or they are what we call luminal A breast cancers. They are called luminal A breast cancers if a breast cancer…if you can feel a breast cancer, it's not over-diagnosed, it needs treatment. If the breast cancer has positive lymph nodes, it's not over-diagnosed, it needs treatment. If the breast cancer is oestrogen receptor negative, it's an aggressive breast cancer, it needs treatment. If the breast cancer is HER2 positive, it's aggressive, it needs treatment…

Norman Swan: Just before you go on, just to explain to the audience, what you're talking about here are hormone and growth factor lock-and-key mechanisms which if the breast doesn't have a lock-and-key mechanism to oestrogen, it is more aggressive, and if it is this HER2, which is a chemical messenger which promotes growth, if it's positive for that, then it is more aggressive.

Steven Narod: Right, very well said. There are several categories of breast cancer. If you go by categories, the majority of the categories—the BRCA1 positive, the ER negative, the HER2 positive, the palpable, the node negative—are all categories which are certainly aggressive, intervention is imperative, those needs treatment. Now, I could say the only ones that I think are likely to go away is this small category, what we call luminal A, which is oestrogen receptor positive particularly or progesterone receptor positive, non-palpable, detected only by the mammogram, and those are low grade.

Norman Swan: But you wouldn't put DCIS in that category?

Steven Narod: Or DCIS, DCIS is a similar thing. Those ones I think are mostly over-diagnosed. Having said that, even though it is one category of many, it comprises the majority of breast cancers diagnosed through mammography alone.

Norman Swan: And the other thing which you alluded to earlier that you find in this study is that a lot of the woman who died, even though they were small numbers, of DCIS, didn't appear to develop an invasive breast cancer. So they seems to go direct to spread of their cancer from the ductal carcinoma in situ, which was thought to be a precursor, and which is why you say it might actually be a breast cancer in its own right.

Steven Narod: That's exactly true. People have accused me of giving a mixed message because I say these are low risk, only 3% died, so it's not a real threat, but it's high risk because they have a metastatic potential from the beginning. Both are true. I call them cancers but I also at the same time say we should redefine our notion of cancer to include very small cancers. I think the fact that they can metastasise without being invasive means they are cancers. I can see no other interpretation.

Norman Swan: So the question is do they all need treatment?

Steven Narod: We did not address the question do they all need treatment. So by treatment…I would defer to the conservative that they all need a surgical prevention. I would recommend, until we have research to say otherwise, that all women with DCIS, one should remove the basic DCIS cells through a lumpectomy. Whether one wishes to do more treatment, particularly a mastectomy, should depend on the wishes of the patient, whether they are fearful of experiencing another breast cancer, knowing that the more extensive treatment will not improve their survival, will not save their life, but maybe allow them to forego another event and more treatment. I think there is much less inclination in my position to recommend radiotherapy. It doesn't eliminate their chance of recurrence and it doesn't really reduce the fear of recurrence.

Norman Swan: For women who've had ductal carcinoma in situ diagnosed in one breast, is there an increased risk in the other breast?

Steven Narod: Yes, probably the risk is doubled in the other breast. So I can't remember the exact number, think it was about 5% of women had a breast cancer in the opposite breast over 20 years, I would expect that to be twice as high as we would expect with women without DCIS. Having said that, is the risk high enough to recommend for a bilateral mastectomy? I don't think so. In women with a BRCA1 mutation, we estimate the same risk over 20 years to be in the neighbourhood of 40% to 50% with a BRCA1 mutation for the opposite breast. For DCIS, about 4% or 5%.

If the woman has a BRCA1 mutation we do recommend now in our clinic that the surgery includes a bilateral mastectomy because the risk of getting that second breast cancer in the opposite breast is so high. And furthermore we've shown that it reduces the number of deaths. If the risk is only 5% over 20 years, the risk of dying is probably in the neighbourhood of 1%, I don't think generally surgeons consider a reduction in the risk of breast cancer deaths by 1% to justify a bilateral mastectomy. Let's put it another way why that makes sense. If we would justify a bilateral mastectomy for a woman with a 1% risk of dying of breast cancer, we would recommend it to every woman in Australia, and we don't…

Norman Swan: Because that's the background risk.

Steven Narod: Right. It's very, very interesting, what we call heuristics or what Lisa Rosenthal calls the effective nature of risk perception, this gets more and more interesting as we go along. If you take two women, one who has had breast cancer and one who hasn't had breast cancer, and you say to them, 'A bilateral mastectomy will reduce your chance of dying of breast cancer by 2%,' the woman with breast cancer will take you up on the offer, the woman without breast cancer will think you are crazy.

Norman Swan: Do the findings of this study shake your confidence or belief in breast cancer screening?

Steven Narod: I've never been considered to be an advocate of breast cancer screening. I was the senior author on the recent Canadian National Breast Cancer Screening Study, you may not be aware, in which we studied 90,000 women over 30 years, and we found no reduction in breast cancer deaths from screening. In that study, which I thought was the best study for breast cancer screening, we saw 150 new breast cancers diagnosed by mammography that were small and they were non-palpable, and those women are all alive today, and those women all attribute their life span to the fact that the cancers were caught on mammography. Yet there was no reduction in the cancer deaths. I think this is a complementary study which supports the idea that we really need to re-evaluate our assumptions about the value of early diagnosis per se as a way of conquering breast cancer.

Norman Swan: So what's the alternative? Because you did show that mortality went down…

Steven Narod: Well, I think the alternative to some extent is taking life as it comes. If I say to a woman, 'You have a 3.3% risk of dying of breast cancer,' some will find that to be terrible news, some will find that assuring. I would propose to you that if you went down to the streets of Sydney and asked the next 20 women walking along the street, 'What do you think your chance is of dying of breast cancer in the next 20 years is?' Half of them will give you a number higher than 3%, they are quite comfortable in their shoes. In other words, I think we have created the idea that a 3% chance of dying of breast cancer is an unacceptable number.

Gladly I'd love to have it smaller. It's hard to study rare events, and the psychological response that people have, given a 97% cure rate I would have to think that that's overwhelmingly good news. If the patient thinks the 97% prognosis cure rate as bad news, I think we have been over-medicalising our society, I think we've given them an unrealistic optimistic notion of what medical research can and cannot do.

Norman Swan: Professor Steven Narod of the University of Toronto.