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Vol 102 Issue 10 Interview Transcript

Molly Wetterschneider: Welcome to the JNCI podcast, a production of the Journal of the National Cancer Institute. I’m Molly Wetterschneider. Mammography is an x-ray examination of the breast. Physicians use mammography both for screening purposes, to detect breast cancer early at a stage when it is easier to treat, and also for diagnostic purposes, to evaluate women who have concerning symptoms of breast cancer, such as a palpable mass. Studies looking into the performance of mammography for screening purposes have given controversial results. The discussion centers on which age groups can benefit from mammography screening and what the recommended guidelines should be. A study published in Issue 10 of the Journal of the National Cancer Institute looks at the performance of mammography screening specifically in women who are younger than 40 years of age. For insight into this topic I spoke with Rebecca Smith-Bindman, a professor of Radiology, Epidemiology and Biostatistics at the University of California San Francisco. Thank you for speaking with me Dr. Smith-Bindman.

Rebecca Smith-Bindman: My pleasure.

Molly Wetterschneider: Could you please tell me a little bit about the study? What did the researchers find?

Rebecca Smith-Bindman: Absolutely. The group, led by Dr. Yetkaskas [ph?] and using data from a large mammography registry called the Breast Cancer Surveillance Consortium, looked at the utilization and performance of mammography in women younger than age 40. And this research group told us about the performance of mammography, how does mammography perform in these women, does it find cancer if it’s there, does it lead to unnecessary procedures when it’s not there. And what they found is not terribly surprising. They found that the performance of mammography is not very good in these younger women. Partly it’s not very good ‘cause there’s not very much cancer to find, it’s like looking for a needle in a haystack. It’s also not very good because there’s so much active glandular breast tissue it’s very hard to find those few needles that are out there. And so they basically characterized the accuracy of mammography in these women. And there are lots of different ways to characterize the accuracy of a test, lots of different statistics that can be thrown out there, but I couldn’t put it in the few ways that I think helps to make clear why mammography is not very good. One of them is how many women would you have to do mammography in to find a cancer?

Rebecca Smith-Bindman: And based on their study, which is really very large, that number’s about 650. So you’d have to do mammograms in 650 women to find that one cancer. When you’re doing that you’d also lead to lots of additional tests and procedures and biopsies in women who don’t have cancer. And that number’s 145 unnecessary procedures, including more mammograms in women who don’t have cancer. So the summary understanding is you’d have to do lots of tests in these younger women, you wouldn’t find very much cancer, but you’d lead to lots and lots of other tests.

Molly Wetterschneider: Okay, so there are drawback of mammography including the other tests that you mentioned. Are there any others?

Rebecca Smith-Bindman: Well, yes. There’s several drawbacks as well as several reasons to question whether the benefits even in finding those cancers would be real. Let me talk about whether the benefits would be real. Fortunately there is not very much breast cancer in younger women. But it turns out the cancers that do occur in very young women turn out to be very aggressive. And it’s not clear that finding one of those cancers early really will improve outcomes, unfortunately.

Rebecca Smith-Bindman: And so even the benefit, which I pointed out as very small, I’m not sure it’s real. There haven’t been any studies that have included women to learn about whether there’s any value. But there is a very serious side affect that, again, is small, but I think really needs to be considered. Mammograms deliver x-rays. They’re low dose x-rays and in women in their 40s, 50s, 60s we’ve found that the benefit of finding cancer early is worth the small risk of that radiation. And the risk of that radiation is that radiation is associated with the development of cancer. It turns out there’ve been two recent scientific studies that have addressed the question about whether doing mammograms in young women could potentially increase the risk of cancer. One of these studies was published in the Journal of the National Cancer Institute last February, led by a researcher at the National Cancer Institute named Dr. Barrington deGonzales. [ph?] She looked at the risk of mammograms in very young women who were at an increased risk of breast cancer based on having BRCA mutations. So they’re at increased risk of breast cancer based on genetic mutations, then they undergo mammography. They found that having early and repeated mammograms in these young women, women in their 20s and 30s, could increases their risk of breast cancer.

Rebecca Smith-Bindman: A second study, led by Dutch investigators presented this last November at the RS&A meeting, pooled data from six prior studies to look at exposure to mammograms and chest x-rays in young women. And they also found that women who had been exposed to radiation from chest x-rays or early mammograms were at increased risk of getting breast cancer. So the risk of the radiation induced cancers, I would say, is very low, but greater than the benefit of having those mammograms early. So there’s very little benefit of mammography, and there’s this concern that exposing women at a young age to mammograms could increase rather than decrease their risk of breast cancer. So I think the whole collection of literature would suggest, for me, that this really is not good practice to do mammography in younger women, either women who are at average risk or women who are at increased risk of breast cancer due to a family history, given the overall benefits and risks of doing those tests.

Molly Wetterschneider: So how should physicians respond to these results?

Rebecca Smith-Bindman: So this study describes current practice, and most of the women who got mammograms in this study were undergoing it as a screening test, a test looking for cancer in an asymptomatic woman. And so to look at that group there’s no evidence that there’s any screening test that should be done for women in their 30s to look for breast cancer. If the question is what should happen in women who are symptomatic, that’s a completely different question. If a woman has a symptom, meaning she has a lump, then she absolutely needs some further evaluation, and I personally believe the best place to start that evaluation is with a careful physician examination and then a tissue sampling, like a fine needle aspiration, to further evaluate it, or with ultrasound to see if it’s a solid or cystic lesion. And then there’s a role for mammography in some settings as well. The last group of women are not women who are symptomatic but women who are at increased risk of breast cancer, either because they’re BRCA 1 or 2 mutation carriers or because they have a strong family history. And in that group it’s a group that’s terribly concerned about breast cancer, for good reason. They have an increased risk of breast cancer so they want any possible screening test. I think this study suggests to us that mammography doesn’t seem to be that test.

Rebecca Smith-Bindman: It doesn’t perform very well. But there is a lot of investigation into the role of MRI as a screening test in young women who are at high risk of breast cancer. As a test in those women it will find breast cancer. It will lead to a lot of false positives. So there’s ongoing debate about what to do in that group. But that would be the alternative, and possibly a good test in young BRCA 1 or 2 mutation carriers or those with a strong family history in order to find breast cancer early.

Molly Wetterschneider: So MRI is Magnetic Resonance Imaging.

Rebecca Smith-Bindman: That’s right.

Molly Wetterschneider: And can you describe that briefly?

Rebecca Smith-Bindman: MRI is another technology to evaluate the breast. Unlike mammography it doesn’t involve exposure to radiation, so it doesn’t have that small associated harm of mammography. There’ve been several studies that have looked at MRI. It basically gives very detailed information both about the anatomy of the breast, but more importantly about blood flow and patterns of blood flow to the breast, and those detect subtle findings that can reflect cancer earlier than mammography would. So it has a higher sensitivity, meaning it finds a larger proportion of breast cancers than mammography. The down side of MRI is it has large numbers of false positives. And what that means is large numbers of women who undergo MRI, and this number’s really very, very high, will have these bright spots on the exam. And we can’t tell if they’re cancer or not cancer. It’s tricky to evaluate those lesions ‘cause they’re very difficult to target for biopsy. We need to follow them up with repeat imaging and repeat surveillance and yet we will definitely find a high proportion of cancer. So as a test it has very high detection rates. It unfortunately has very high false positive rates, and we haven’t fully evaluated how to use this as a screening test to improve outcomes in women who have an elevated risk of breast cancer due to the known factors that are associated with breast cancer.

Molly Wetterschneider: So how should women respond to this study? Should they fear mammography?

Rebecca Smith-Bindman: So I don’t want in any way to suggest that mammography is not a safe exam in the groups where we recommend it should be used or where it makes sense to use it. So the amount of radiation from mammography is really very low, and the benefit of mammography, for example, in women in their 50s, 60s, even women in their 40s, is very clear, that the benefit outweighs the harm. When we begin to use that test in women in their 20s and 30s, where the benefit becomes so low, then the harm becomes a concern. Every test we do is a balancing act. We can’t think of any test as being a sort of free ride, giving us some value without any cost. And we have to balance them. And I think for mammography the balance is very clear for women 50s and 60s. I think the balance is much more subtle for women in their 40 and thus it’s an area that we discuss quite a lot. For women in their 30s and 20s the balance is also clear. And it weighs towards believing that this test is harmful rather than helpful. And I want to emphasize it’s not that I’m not sympathetic with wanting a screening test for younger women. This just doesn’t seem to be it.

Molly Wetterschneider: Well thank you so much for your insight.

Rebecca Smith-Bindman: Absolutely. A pleasure speaking with you.

Molly Wetterschneider: That was Dr. Smith-Bindman of the University of California San Francisco. Find out more about the performance of mammography in younger women by reading the study and an accompanying editorial in issue 10 of JNCI. You’ve just enjoyed another edition of the JNCI podcast. Please check back in two weeks for our next audio update and a new issue of JNCI. Until then, we’d love to hear from you. Send an email to podcasts@oxfordjournals.org and let us know how we’re doing. In the meantime, you can find even more information on today’s topic, as well as news and commentary about cancer research, online at JNCI.oxfordjournals.org. Also, for the latest cancer news and studies, follow us on Twitter at JNCI_now. I’m Molly Wetterschneider. Thanks for listening.