00:00:00.000Hey, everyone. Welcome to the Drive podcast. I'm your host, Peter Atiyah. This podcast,
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00:01:04.200Welcome to a new episode of The Drive. Today, we're diving into breast cancer screening,
00:01:09.940why women are still dying from breast cancer despite effective screening tools,
00:01:15.100where current screening strategies fall short, and how to think about personalizing your own
00:01:19.760screening. This episode is really about one central question. How do you give yourself the
00:01:25.200best possible chance of not dying from breast cancer? As we consider this to be a really
00:01:31.280important public service announcement, the full episode and the detailed show notes for this
00:01:37.080discussion will be available to everyone, regardless of whether or not you're a premium
00:01:41.020subscriber. So without further delay, please enjoy this episode of The Drive.
00:01:49.760Most of us have heard that terrible statistic. About one in eight women will develop invasive
00:01:57.560breast cancer over the course of their lifetime. In the United States, roughly 42,000 women die0.58
00:02:04.000every year from this disease. That makes it one of the leading causes of cancer death behind only0.51
00:02:10.560lung, colorectal, and pancreatic. And yet, despite how common and consequential this disease is,
00:02:17.820Many women have questions about screening, including when it should start, how often to do it, and what factors actually matter.
00:02:26.100Even women who have looked at the guidelines often come away more confused than before because the guidance differs between organizations, and it's also shifted over time.
00:02:35.780And that confusion has real consequences because breast cancer screening works.
00:02:40.740Cancers found through screening are more likely to be caught early, before they've spread, when treatment is easier and outcomes are better.
00:02:47.820And that stage shift, as it's called, matters enormously. When breast cancer is caught at
00:02:53.620stage one, the 10-year survival is over 96%. By stage four, five-year survival is only around
00:03:03.50030%. It's no surprise then that women who screen regularly are up to 40% less likely to die from
00:03:11.380the disease. Now, of course, screening is not without trade-offs. For example, over-diagnosis
00:03:16.500of lesions that would never progress to cancer can increase healthcare burden with no real benefit
00:03:21.740and remains an area of ongoing uncertainty. We'll get into these considerations later,
00:03:27.180but they do not negate the core point. Screening is one of the most effective tools we have for
00:03:32.680reducing breast cancer mortality. And if you're optimizing for your individual risk of dying from
00:03:38.460breast cancer, not population efficiency, not total societal cost, but your own outcome,
00:03:43.960the default should be to err on the side of more effective screening, and certainly not less.
00:03:49.780Which raises the obvious question. If screening works so well, why are so many women still dying0.99
00:03:56.620from breast cancer every year? Part of the answer is biology. Some breast cancers are simply more0.96
00:04:03.380aggressive than others. They grow quickly, they spread early, and can be difficult to intercept,
00:04:08.780even with a very good screening system. Some back of the napkin math suggests that somewhere
00:04:15.220around 7 to 10 percent of cases are the ones we are unlikely to catch even with perfect screening.
00:04:24.080But those biologically aggressive cases are not the only reason this disease is still taking so
00:04:30.820many lives. A major and much more solvable part of the problem is far more mundane. We are still
00:04:37.920under screening. And I don't just mean that some women never get a mammogram, though that is
00:04:43.520certainly part of it. Even among women who have been screened before, screening may be inconsistent.
00:04:50.640Roughly a third of women over 40 have not had a mammogram in the past two years. And even among
00:04:57.860women aged 50 to 74, where the evidence is most universally agreed upon, about 20% are not up to
00:05:07.240date. Underscreening has two layers. The first is pretty basic. Most women are not even getting
00:05:14.620routine mammography at the right time. But the second is more nuanced. Some women are getting1.00
00:05:20.920screened, but not with the right strategy for their risk profile. This is one statistic that
00:05:27.020I think captures this perfectly. According to the criteria laid out by major screening guidelines,
00:05:33.460at least 9% of women meet the threshold for breast MRI as part of their screening protocol.
00:05:42.180And yet the actual utilization rate is just 0.4%. It's not that MRI is unproven or controversial
00:05:50.600for these women. This is a pure execution failure. We already know who these high-risk women are,1.00
00:05:58.560and we already have a tool that materially improves detection. We're simply not connecting
00:06:04.020the two. So what I want to do today is not simply tell you to get screened. You already know that.
00:06:10.220I want to give you a practical framework for smarter screening, one that starts with understanding
00:06:15.860your actual risk and helps you make informed decisions about when to start, how often to
00:06:21.980screen, and what imaging to use. Population guidelines form a great starting point, but
00:06:28.020they're not the finish line. But to get there, we need to start with the guidelines themselves.
00:06:33.720What do the major organizations actually recommend, and how should we talk about personalizing them?
00:06:39.720If you're confused about breast cancer screening, you're not alone. A recent survey found that
00:06:45.660roughly 50% of women aren't sure when to start mammography. And frankly, that confusion is
00:06:52.540understandable. The guidance has shifted multiple times over the past two decades, most recently
00:06:57.800in 2024. There are several organizations that publish screening recommendations, and they do
00:07:04.360not all agree. Rather than walking through all of them individually, let me first give you the
00:07:09.900composite picture of the most rigorous guidelines. We'll include a full comparison table in the show
00:07:15.520notes. Here's the big picture. Every woman should have a formal risk assessment by about the age of
00:07:22.54025. If you are average risk, annual mammography should begin at 40. If you are high risk, and I'll0.81
00:07:31.060define that in a minute, you may need an MRI and eventually mammography much earlier, and screening
00:07:37.960should continue for as long as you would be willing to pursue treatment if cancer were found.
00:07:44.300That composite comes from groups like the American Cancer Society, the National Comprehensive Cancer
00:07:50.560Network and the American College of Radiology. The one notable outlier is the U.S. Preventive
00:07:57.140Service Task Force, or USPSTF, whose guidance tends to inform insurance coverage decisions.
00:08:05.980The USPSTF currently recommends mammography only every other year for average-risk women
00:08:12.880aged 40 to 74, with no explicit recommendation for high-risk women. Now, these are population-level
00:08:21.440guidelines. They're created by looking at large studies and evaluating the optimal strategy for
00:08:28.180maximizing cancer detection while minimizing false positives across millions of women. And
00:08:33.760of course, they take into account the societal cost of screening. But when you move from populations
00:08:40.640to actual people, personalization matters. When we think about how to personalize screening,
00:08:48.520for any cancer, the first question we need to start with is what is my baseline risk? Then,
00:08:56.000given that risk, how much false positive burden am I willing to tolerate in exchange for potentially
00:09:03.120earlier detection? And third, which screening plan, both modality and frequency, best match
00:09:11.640both of these objectives? This is not about trying to outsmart the guidelines. It's about deciding
00:09:18.520whether the default plan actually fits you. For some women, it will, but for others, it will fall0.99
00:09:24.940short. The aim is not to get as much imaging as possible. It's to land on a strategy most likely
00:09:32.540to help someone with your particular risk profile. So let's start with the first question. What
00:09:38.960actually determines your baseline risk? While most people immediately think of BRCA level risk when
00:09:45.420they think about breast cancer, most women who develop breast cancer do not have one dramatic
00:09:51.000obvious risk factor. It is far more common to have several smaller risk factors that together
00:09:58.000add up to a higher risk. So we are not just looking for the rare woman with the obvious red0.97
00:10:04.540flag. We want to identify the women whose overall risk is meaningfully above average. However,
00:10:11.700risk assessment is only useful if it happens early enough to change the plan. You do not want to find
00:10:19.080out at age 42 that you should have been the patient who started MRI years earlier. That is
00:10:25.680why some groups recommend formal risk assessment by age 25, not because everyone needs imaging at
00:10:31.96025, but because by then you want to know whether or not you are truly average risk or not. I think
00:10:39.280this is exactly right. A risk assessment should be done in your mid-20s. So what are the risk
00:10:44.700factors we need to consider? The most basic are the ones we don't usually think of as risk factors,
00:10:50.980sex, and age. Breast cancer is overwhelmingly more common in women, one versus eight versus
00:10:56.000one in about 750 for men. So keep in mind, men can develop this as well. Then there's age,
00:11:02.620which is one of the strongest breast cancer risk factors overall. The median age of diagnosis is
00:11:08.540around 62, and the vast majority of breast cancers are diagnosed after age 40. While age alone is an
00:11:15.760imperfect guide, it is important to keep in mind that risk accumulates over time. But once you get
00:11:20.940past these two obvious risk factors, the most obvious high-impact category is genetics. Mutations
00:11:28.180in genes like BRCA1 and BRCA2 are the most recognized inherited breast cancer risk factors,
00:11:34.300and for good reason. They can substantially increase risk and often shift that risk earlier
00:11:39.900in life. But these mutations are actually much rarer than people tend to think. In the general
00:11:46.320population, only about 1 in 400 people carry a pathogenic mutation in BRCA1 or BRCA2,
00:11:54.180though prevalence is higher in some groups, including people of Ashkenazi Jewish ancestry.
00:12:00.100There are also other important genes, but the broader point is that inherited mutations matter
00:12:06.460a great deal for screening, even if they account for a minority of breast cancer cases.
00:12:12.780And genetics ties directly into the next factor, family history.
00:12:17.180I separate these because family histories capture more than just the known single gene mutations.
00:12:24.060Yes, family history is a proxy for high-impact mutations like the BRCA mutations,
00:12:28.720but it also reflects the cumulative effect of lower penetrant genetic variants,
00:12:35.460shared environmental exposures, and other inherited factors that no single genetic test currently covers.
00:12:42.420Having multiple first or second degree relatives, parents, siblings, grandparents, aunts, with breast cancer can substantially increase your risk.
00:12:52.420But keep in mind that lack of family history does not automatically equate to low risk.
00:12:57.180Some families are small, some relatives may have died young of other causes, and, importantly, some mutations that increase breast cancer risk can show up in the family as other cancers, like prostate or pancreatic cancer, rather than an obvious pattern of breast cancer.
00:13:15.920So family history matters, but it should be interpreted thoughtfully, and the absence of a family history of breast cancer does not guarantee that you are of average risk.
00:13:25.160In addition, ancestry-related differences can influence both risk and tumor biology.
00:13:32.420In the U.S., for example, black women are more likely to be diagnosed younger and with more
00:13:37.700aggressive subtypes, which has implications for how early and how aggressively screening should
00:13:43.540be considered. Another important category is prior chest radiation. The classic example is
00:13:50.360radiation treatment for Hodgkin's lymphoma in adolescence or early adulthood. Cumulative high
00:13:56.160dose exposure, particularly around the time when breast tissue is still developing, carries the
00:14:01.720greatest risk. Now, to be clear, this does not mean you should avoid a diagnostic x-ray if your
00:14:06.600doctor recommends one. A single chest x-ray or CT delivers a tiny fraction of the dose used in
00:14:13.020cancer treatments, and the evidence that the occasional routine chest imaging study meaningfully
00:14:18.240increases. Breast cancer risk is very weak at best. Then there's breast density, which is important
00:14:24.180for two separate reasons. First, dense breasts are associated with a somewhat higher baseline risk of0.97
00:14:30.840breast cancer. But just as importantly, dense tissue makes mammograms harder to interpret0.98
00:14:36.600because both dense tissue and tumors appear white on the image. So density is not just a biological
00:14:43.420risk factor. It is also one of the main reasons our most common screening test becomes less
00:14:49.740effective. And this is where things get a little tricky. You usually cannot actually know your
00:14:56.460breast density until you've had an imaging study, which for most otherwise average risk women does0.85
00:15:02.140not happen until screening begins at around age 40. This creates a bit of a catch-22. Density
00:15:08.280matters for screening decisions, but you often do not learn until it's potentially too late.
00:15:14.520There's a partial workaround though. Breast density is fairly heritable, roughly 60 to 70%.
00:15:20.200So if your mother or grandmother was told she had dense breasts, that's worth knowing. It is just
00:15:26.340not something most women tend to think about. Density matters enough that the FDA now requires1.00
00:15:32.340imaging centers to notify women of it. That is typically reported with the BIRADS density
00:15:38.640category. A and B are considered non-dense, while C and D are considered dense. While density
00:15:47.300declines with age, about 50% of screening age women have dense breast tissue. Then there are1.00
00:15:54.580the reproductive and hormonal factors, which tend to be more cumulative in nature. In general,
00:16:00.680the factors that point toward higher risk include earlier onset of menstruation, later menopause,
00:16:07.660never having had a full-term pregnancy, or having a first pregnancy after age 40 and not breastfeeding.
00:16:14.580Individually, none of these risk factors typically change the screening plan on its own,
00:16:18.740but they do contribute slightly to overall risk, especially when several are present together.
00:16:25.120The same is true, of course, of modifiable risk factors such as alcohol use,
00:16:29.160obesity, poor metabolic health, and physical inactivity. You don't need to change your
00:16:35.560screening protocol based on these alone, but they can shift risk and are factors you should
00:16:41.840actually do something about. So the big picture here is that risk is usually not one thing. It is
00:16:48.320the sum of multiple inputs, some large, some small, that together determine whether someone
00:16:54.760is truly average risk, somewhat above or below average, or clearly high risk.
00:17:02.320And because no one is going to accurately estimate all of that in their head, this is
00:17:10.940Calculators like Tyra Cusick combine family history, personal risk factors, and breast
00:17:16.940density to estimate 10-year and lifetime risk.
00:17:20.280These models are not perfect, but they are much better than guessing, and they help
00:17:24.320identify women whose risk is high enough to justify earlier or more intensive screening.
00:17:30.160Most screening guidelines classify lifetime risk above 20% as high risk, though factors such as
00:17:36.460ancestry may shift that threshold. You can find these calculators online, but we're going to link
00:17:40.960to one in the show notes. And it's a good idea to complete one so you can get a more concrete
00:17:46.120understanding of where your risk falls. So if you take anything away from this, know your risk and
00:17:51.920know it early enough that you still have time to act on it. But risk alone doesn't tell you what
00:17:57.740to do. The next question is, given that risk, how aggressively do you want to be screening?
00:18:03.620Because every time you push screening towards higher sensitivity, that is, finding more cancers,
00:18:09.920you also accept more downside, more false positives, and more follow-up testing,
00:18:15.360not to mention the anxiety that can come with those. In a perfect world, screening would find
00:18:20.500every meaningful cancer early and spare everyone the downside of a false alarm. But in the real
00:18:26.420world, the balance is never that straightforward. In the U.S., about 10% of screening mammographies
00:18:33.180lead to a callback for additional testing. But only about 5% of those callbacks end in a cancer
00:18:40.980diagnosis. In other words, for every thousand women who undergo a screening mammogram, about
00:18:48.020100 will be called back because something looked abnormal, but about 95 of those 100 will not
00:18:54.720actually have cancer. And those numbers add up over time. More than half the women screened annually
00:19:02.300for 10 years will experience at least one false positive result. The most common harms from breast
00:19:09.320cancer screening are not major physical injuries from the test itself, but the anxiety and
00:19:14.960uncertainty that comes from a return visit for more imaging. When a callback leads to an earlier
00:19:21.460cancer diagnosis, it's obviously worthwhile. But when most callbacks do not end in cancer,
00:19:27.620we need to think carefully about what screening strategy makes sense for each individual woman.1.00
00:19:33.560So how should a woman think about that trade-off? The higher your baseline risk, the easier it is1.00
00:19:38.020to justify accepting more false positives in exchange for finding more cancer earlier. If
00:19:44.000you're very high risk, say you carry a BRCA mutation or have a combination of factors that
00:19:49.020pushes your lifetime risk well above average, then a more aggressive strategy is easy to defend.
00:19:55.360If you're truly average risk or even lower than average risk, the decision is based largely on
00:20:00.900preference. That does not necessarily mean less screening. It means being thoughtful about how
00:20:07.020much extra testing you're willing to accept for what may be smaller incremental benefits.
00:20:12.120And that's really the key here. More screening is not automatically better screening. The right
00:20:18.260question is not how much imaging can I get, but which strategy is most likely to help someone
00:20:23.980with my risk profile and am I comfortable with the trade-offs that come with that? There's no
00:20:28.940universal answer to that question, of course. It depends on the person. But once you know your
00:20:33.180baseline risk and you have a sense of your tolerance for false positives, you're ready
00:20:37.180for the next piece. Which screening tools actually exist and how should you think about choosing
00:20:41.820between them. When we talk about breast cancer screening, it's often treated as if breast imaging
00:20:46.840were just one thing, but it's not. Breast imaging is a toolkit consisting of different varieties of
00:20:53.400mammography, MRI, and ultrasound. Some of these are best for routine screening, while others are
00:20:58.980more appropriate for follow-up on an abnormal finding or as a supplemental option in higher
00:21:04.400risk women. We'll go through each of these here, and I'll also place in the show notes a detailed
00:21:09.420comparison table. The foundation of screening, of course, is the mammography. Mammograms use
00:21:14.820low-dose x-rays to look for breast cancer, and for most average-risk women, they remain
00:21:19.360the starting point. One important strength of mammography is that it is particularly good at
00:21:25.060detecting calcifications, such as those seen in ductal carcinoma in situ, or DCIS. DCIS is
00:21:32.600sometimes called stage 0 breast cancer. The abnormal cells are still confined to the ducts0.69
00:21:38.400rather than invading surrounding tissue. If left untreated, estimates suggest that somewhere
00:21:43.960between 25 and 60% of DCIS cases may eventually become invasive cancer, a wide range that reflects
00:21:51.020how much we still don't know about the natural history of DCIS. But that uncertainty is precisely
00:21:57.300why early detection matters, and mammography is well-suited for finding it. That said,
00:22:03.020not all mammograms are the same. In 2000, the FDA approved the first full-field digital mammography
00:22:10.380system, and this is what most of us are thinking of when we hear mammogram. Standard digital
00:22:17.500mammography, sometimes called 2D mammography, is the technology that many research studies have
00:22:23.760historically used. Most recently, in 2011, digital breast tomosynthesis, or DBT, commonly referred to
00:22:32.060as 3D mammography was rolled out. DBT takes multiple images from different angles to create
00:22:40.080a more layered view of the breast. This results in better cancer detection with lower recall rates,0.51
00:22:46.440particularly for women with dense breasts. Not every imaging center offers DBT, however, and
00:22:52.940sometimes there is still an added cost. However, this is the version of mammography I would
00:22:57.880prioritize, again, especially for women with dense breasts. Mammography is the right foundation for0.61
00:23:04.140virtually everyone, but for women at higher risk, mammography alone may not be sensitive enough.
00:23:09.480This is where MRI comes in. While not a complete replacement for mammography, MRI is an important
00:23:16.100supplemental option. MRI uses magnetic fields and intravenous gadolinium-based contrast to detect
00:23:24.200abnormal blood flow or tissue behavior that mammography can miss, making it the most sensitive
00:23:29.720screening tool available. It is better for detecting very small invasive tumors and atypical cancers
00:23:35.780than any other imaging modality. But it's not perfect for everything. Mammography still does
00:23:41.000a better job with certain calcifications, so MRI is generally used in addition to, but not instead
00:23:48.400of mammography. The downsides are cost, access, and the use of IV contrast, along with a higher
00:23:56.300callback burden because of the higher sensitivity. But if your goal is maximum cancer detection,
00:24:02.940MRI's sensitivity tends to outweigh these downsides. The full breast MRI is what most
00:24:09.680very high-risk women are recommended for initial screening and may also be used for diagnostics0.99
00:24:15.360after an abnormal test. More recently, many patients are opting for the abbreviated breast0.99
00:24:21.920MRI, which in my mind is the most underutilized tool we have. Based on current diagnostic accuracy
00:24:29.960data, the abbreviated protocol preserves nearly all of the sensitivity of the full exam, but takes
00:24:36.220only 10 to 15 minutes compared to 30 to 60 minutes for the full exam. That makes it cheaper, faster,
00:24:42.580and more scalable while still providing dramatically better cancer detection than
00:24:47.480mammography alone. For women with extremely dense breasts, adding MRI after a negative mammogram0.76
00:24:53.960cut the rate of interval cancers, meaning cancers found between screens, in half from 5 per 1,000
00:25:00.980to 2.5 per 1,000 with mammography alone. So for women who are high risk, have dense breasts,
00:25:07.920or simply want a more sensitive complement to mammography, MRI is the strongest option we have.
00:25:14.720In many screening settings, an abbreviated MRI is likely sufficient, while the full protocol
00:25:20.480may be more useful for diagnostic workup and select edge cases. If MRI is not feasible,
00:25:27.640the next best modality is contrast-enhanced mammography, or CEM. CEM is a newer modality
00:25:35.660introduced in 2011 that is basically mammography plus intravenous iodine-based contrast. It gives
00:25:43.380more functional information than a standard mammogram and can be a very reasonable alternative
00:25:49.300when MRI is unavailable or contraindicated. This technology isn't yet widely available,
00:25:56.460but I do think it will become more popular in the future. Then there's ultrasound. Ultrasound
00:26:01.360uses sound waves rather than radiation or magnetic fields to create images of breast tissue as with
00:26:07.600the other imaging modalities ultrasound comes in different flavors handheld where a technician or
00:26:13.360radiologist moves the probe manually and automated where the machine acquires images more systematically
00:26:20.560both are more operator dependent than mammography or mri and both carry a higher false positive
00:26:26.560burden than you would see in those modalities. Ultrasound can be useful as a supplemental
00:26:32.120imaging modality, but its value is highly dependent on two things. Who performs the
00:26:38.280ultrasound and what baseline imaging you are adding it to. In one study, adding physician-performed
00:26:46.600handheld ultrasound to a standard 2D mammography increased the rate of cancer detection by 4.2
00:26:54.780per 1,000 women screened. A second study paired technician performed ultrasound with DBT,
00:27:02.580the more sensitive mammogram, and the detection boost was much smaller, only about 1.1 per 1,000.
00:27:10.140So when the base imaging is better or the technician is less experienced, the incremental
00:27:16.040benefit of ultrasound shrinks. That doesn't mean it's not worth doing, but it does mean its benefits
00:27:22.420are more variable than what we see when adding MRI to mammography. So where does ultrasound best
00:27:29.100fit into practice? Because handheld ultrasounds allow for real-time visualization, they're an
00:27:34.920excellent option for getting more clarity on something suspicious seen on other imaging or
00:27:39.680guiding biopsies. And while ultrasound can boost cancer detection over mammography alone,
00:27:45.900it's not going to do it to the same extent seen with adding MRI. Ultimately, ultrasound is a
00:27:52.080viable tool. But for average risk women, it is not a substitute for mammography. And for high risk0.89
00:27:57.840women, it's not a substitute for MRI. So how do we actually pull all of this together in a way
00:28:04.640that is useful? At a practical level, the hierarchy looks like this. The foundation for all women is
00:28:10.820mammography, ideally digital breast tomosynthesis or DBT. If your risk is elevated or if dense
00:28:19.020breast tissue is likely to reduce the sensitivity of mammography, MRI is the most effective
00:28:24.600supplemental tool. If MRI is not feasible due to cost, access, or contraindication,
00:28:30.480contrast-enhanced mammography is the next best option. Ultrasound can add incremental detection,
00:28:36.980but its benefit is more variable and highly dependent on operator skill and on, of course,
00:28:43.240baseline imaging that it's paired with. The key point is that these tools are not
00:28:48.280interchangeable. They have a clear hierarchy in terms of sensitivity and consistency. And your
00:28:53.460goal is to choose the combination that best matches your risk. But regardless of the screening tool
00:28:59.340you decide on, keep in mind that where you get screened matters. Not every imaging center offers
00:29:05.100every modality, and not every center has the same level of experience with the tests it offers.
00:29:11.100Simply having imaging done is not the same thing as having high-quality imaging done.
00:29:16.380For mammography, positioning and complete tissue capture matter. MRI and CEM are more standardized,
00:29:25.100but they still depend on good protocol execution, contrast timing, and experienced interpretation.
00:29:31.620For the reasons I discussed a moment ago, ultrasound is the most operator-dependent
00:29:35.580modality. So a routine mammogram can usually be done well in many places, but the quality of
00:29:42.260imaging and interpretation still varies. High-volume centers and dedicated breast imaging centers
00:29:47.780tend to have more experience, better protocols, and more consistent interpretation.
00:29:53.080If you are pursuing more advanced imaging, such as MRI or contrast-enhanced mammography,
00:29:58.500or even ultrasound in dense breast tissue, you should strongly consider going to a center that
00:30:03.760performs these studies frequently and has specialized expertise. The difference is not
00:30:09.300trivial, and in some cases, it can directly affect whether a cancer is detected or not.
00:30:14.700Bottom line here is that each imaging modality has strengths and weaknesses,
00:30:18.900and which one or which option you choose is a personal choice based on your risk,
00:30:24.660your preferences, and your access. Once you think about imaging in that way,
00:30:28.780the next question becomes, how often should you screen? As I mentioned previously, the USPSTF
00:30:35.500recommends biennial mammography for average risk women aged 40 to 74. Most other groups recommend
00:30:42.140annual mammography starting around the age of 40 or a hybrid approach with annual screening
00:30:48.320from 45 to 54 and biennial screening thereafter, though I've never really understood that given
00:30:54.580that risk is always going up with age. It's worth acknowledging up front that no randomized
00:31:00.380control trial has ever directly compared annual versus biennial screening with mortality as its
00:31:07.400primary endpoint. Every interval recommendation we have is based on modeling studies and
00:31:13.060observational data. That does not mean we're flying blind, but it does mean we are working
00:31:17.600with a slightly different kind of evidence than we have for, say, the question of whether screening
00:31:22.200reduces mortality at all. The most important modeling data come from the Cancer Intervention
00:31:28.880and Surveillance Modeling Network, or CISNET, a consortium of independent modeling groups
00:31:34.940funded by the National Cancer Institute. CISNET has been commissioned three times to run
00:31:40.740simulations for the USPSTF, and the task force has leaned heavily on these models to justify
00:31:48.520biennial mammography recommendations. Interestingly, other cancer and radiology groups
00:31:54.140have looked at the same CISNET data to conclude that annual screening is better. So which is it?
00:32:00.680The answer depends on your question. If the question is how to maximize efficiency across
00:32:06.980an entire population, balancing cost, false positives, and resource utilization,
00:32:12.880biennial screening is a defensible answer. But if the question is what gives an individual woman0.98
00:32:19.200the best chance of avoiding death from breast cancer, the answer is different. And that
00:32:24.720distinction is critical for everything that I'm about to say. The argument for biennial mammography
00:32:31.100traces back to the original 2009 CISNET analysis, which found that biennial screening retained
00:32:38.060about 81% of the mortality benefit of annual screening with roughly half as many false
00:32:44.460positives. This was done using data from film-based mammography, the technology that came before
00:32:50.680digital mammography and certainly before DBT was introduced. The conclusion from this modeling
00:32:56.260study was not that biennial mammography was best for mortality, but that it offered the best
00:33:02.280trade-off between benefit and resource use at a population level. In 2024, CISNET published its
00:33:10.420most comprehensive analysis using multiple models and imaging strategies, including both
00:33:16.080two-dimensional digital mammography and DBT. A secondary analysis of those results showed,
00:33:22.640in essence, that annual screening is better for saving lives. When compared to no screening,
00:33:28.780annual screening of women aged 40 to 79 produced a 42% mortality reduction, while biennial screening
00:33:36.220produced only a 30% mortality reduction. In absolute numbers, this corresponded to 230 life
00:33:45.660years gained per thousand women for annual screening versus 165 for biennial. The cumulative
00:33:54.000number for false positives is higher for annual screening, as we would expect, given that we're
00:33:58.760performing twice as many tests. However, the rate of false positives and benign biopsies per exam
00:34:05.360is actually lowest with annual screening, likely because the radiologist has a more recent image
00:34:12.080to compare to, making it easier to distinguish cancerous changes from normal variation. I think
00:34:18.340this is a very important statistic that gets overlooked. The bottom line is that the case
00:34:23.700for biennial screening rests on population-level efficiency, not on maximizing the benefits for
00:34:29.260any individual woman. If the question is what gives you the best chance of not dying from breast
00:34:34.640cancer, CISNET's own data answers it clearly, screen annually. The observational data tell a
00:34:42.640similar story. Among women aged 40 to 84 who develop breast cancer, those screening annually
00:34:49.440had far fewer interval cancers, 11% versus 38% for biennial screeners, and were more likely to
00:34:57.780have an early stage diagnosis, 76% stage one with annual screening versus 56% with biennial.
00:35:06.520Taken together, the modeling and observational data, the conclusion is straightforward. If your
00:35:11.600goal is to maximize your chances of avoiding death from breast cancer as an individual,
00:35:16.800annual mammography is the better strategy. But all of these studies have focused entirely on
00:35:23.240mammography. What about when to add in other imaging modalities such as MRI? The most common
00:35:29.740approach in clinical practice is to alternate the two tests every six months, say mammography in
00:35:36.760January, MRI in July, rather than stacking them at the same time. The logic is kind of intuitive.
00:35:42.740By spacing them out, you're effectively creating a six-month screening interval instead of a 12-month
00:35:48.240one, which in theory gives the fastest growing cancers less time to develop between the screens.
00:35:55.740But the evidence here is thinner than you might expect, in large part because these studies are
00:36:00.500genuinely hard to do well. When two tests are given at two different times, it becomes very
00:36:05.500difficult to fairly credit a cancer detection to one test versus the other, which makes comparing
00:36:11.240the two scheduling approaches unreliable. One small study found that the combined sensitivity
00:36:17.340of MRI plus mammography was higher than either test alone, while another found no significant
00:36:23.480difference between stacking and alternating. Neither is definitive. For ultrasound plus
00:36:29.040mammography, the timing question has essentially never been studied directly. All major ultrasound
00:36:34.260trials performed both tests simultaneously and annually. Any rationale for staggering ultrasound
00:36:40.380is purely extrapolated from the already limited MRI literature. The bottom line on multi-modality
00:36:47.400scheduling is rather unsatisfying. We do not yet have compelling evidence to favor one
00:36:53.300schedule over another. I might lean towards the alternating schedule for high-risk women1.00
00:36:59.420who are more likely to develop rapidly growing cancers, but until better prospective data exists,
00:37:05.400the scheduling decision is really more about logistics and personal preference.
00:37:09.380To summarize the practical takeaway here, all women should screen annually with mammography.
00:37:14.380If you are high risk and you are getting multiple imaging modalities, alternating them every six
00:37:20.740months is reasonable, but the evidence is not strong enough to insist on that schedule.
00:37:24.960Right now, the bigger issue is not whether the tests are staggered. It's whether both tests are
00:37:29.800getting done consistently each year. Okay. At this point, we know we should do a risk assessment in
00:37:36.680mid-20s and we know how often to screen and which imaging modalities make sense, the next question
00:37:44.820is when should we actually start screening? I saved this for last because this is the area
00:37:49.800where we have the least concrete data beyond the whole scheduling thing. The intuitive assumption
00:37:54.980is that if screening saves lives, then starting earlier should save more of them. But whether
00:38:00.800earlier screening actually helps depends on many factors, and the answer is more nuanced than you
00:38:05.520might expect. First, the risk for developing breast cancer before age 40 is genuinely low.
00:38:12.160Only about 5% of breast cancer diagnoses occur in women under 40. The cumulative risk through age
00:38:17.88090 is about 13%, which is where that familiar 1 in 8 statistic comes from. But the cumulative
00:38:23.400risk through age 40 is less than 1%. Now the obvious next question, how do we know incidence
00:38:30.700is actually low if we're not routinely screening women under 40. Maybe we're just not finding
00:38:36.240cancers that are there. But these data come from cancer registries, which capture all diagnosed
00:38:42.540cancers, including cancers found symptomatically and cancers caught in women who began screening
00:38:48.020earlier because of elevated risk. On top of that, the age incidence curves rise smoothly and
00:38:54.960continuously through the 30s and 40s. We've included a figure in the show notes so you can
00:39:00.340take a look at this for yourself. But there is no sharp spike at age 40, which is what you would
00:39:05.740expect to see if screening were suddenly uncovering a large hidden backlog of disease. So the low
00:39:12.560incidence under 40s appears to be real, not an artifact of under-detection. But low risk does
00:39:19.740not mean no risk. So could there still be a case for screening before 40? This is where we run into
00:39:26.660the limits of evidence. We have no randomized trials and no mortality data on screening average
00:39:32.680risk women under 40. The best study we have looked at about 6 million mammograms from facilities
00:39:39.840across the U.S. About 12% of these mammograms were from women under 40. And the researchers
00:39:46.340compared cancer detection rates across age groups, broken down by whether a woman had at least one
00:39:52.540risk factor, defined as a personal history of breast cancer, a family history, and a first-degree
00:39:56.920relative or dense breasts. Among women aged 35 to 39 with at least one risk factor, the cancer
00:40:04.440detection rate was 2.1 per 1,000 women screened. For average risk women in the same group with no
00:40:11.880family history, no personal history, and non-dense breasts, the rate was just 0.59 per 1,000. This is
00:40:20.080about a three and a half full difference driven by risk factors, not age alone. And here's where
00:40:26.380the comparison gets especially interesting. For average risk women age 40 to 44, the detection
00:40:32.660rate was only 0.71 per thousand. In other words, women in their late 30s with risk factors were
00:40:42.260being diagnosed with cancer at roughly three times the rate of average risk women who were screening
00:40:49.240in their 40s. Those risk factors are not just nudging the needle. They are effectively shifting
00:40:56.580a woman's screening profile forward by a decade. Once you get to women 45 and older, incidence
00:41:04.020rises enough that detection rates exceed what we would see in women under 40, regardless of risk.
00:41:10.860But below that threshold, risk factors may matter more than age. This brings us back to the point
00:41:17.720I've made throughout this discussion. Knowing your baseline risk is what makes the difference.
00:41:23.280The age 40 cutoff for screening makes sense on average, but for women with one or more of these
00:41:29.760three risk factors we've just discussed, earlier screening may be the right call. And the women who
00:41:35.560are diagnosed with breast cancer in their 20s and 30s are not a random cross-section of the
00:41:41.320population. They are disproportionately women who could have been identified as above average risk
00:41:47.180earlier on. On top of this, breast cancer doesn't look the same in younger women as it does in
00:41:53.060older women. Younger women are much more likely to develop aggressive subtypes. About 20% of
00:42:00.040breast cancer in women under 40 are the so-called triple negative, the most aggressive form,
00:42:06.560compared with roughly 6 to 12% in women over 40. And these tumors grow fast. Triple negative
00:42:14.120cancers can double in size in under four months, which means even annual screening may not catch
00:42:19.800them in time. On the other end of the spectrum, the slower growing cancers that screening is best
00:42:25.520at detecting, the ones with doubling times closer to a year, make up only about a third of cases in
00:42:31.860women under 40, compared to well over a half in older women. For high-risk women, this biology
00:42:38.900has direct implications for which screening tool to use. Mammography alone may not be enough.1.00
00:42:46.380Consider how risk from a BRCA1 mutation plays out over a lifetime. It's not spread evenly. It's
00:42:52.700heavily front-loaded. A woman in her late 20s carrying a BRCA1 mutation has a breast cancer
00:42:59.620risk roughly 100 times that of a non-carrier. By her 30s, it's about 44 times. And by her 60s,
00:43:08.140it drops to about three times. In other words, these mutations don't just increase risk,
00:43:13.720they shift the entire risk curve earlier. And because the cancers that develop in these younger
00:43:20.560high-risk women tend to be fast-growing and harder to see in mammography, MRI is the more
00:43:26.400appropriate screening tool for this group. There is one more practical consideration worth
00:43:32.320mentioning. One of the three risk factors in the study I just discussed was breast density. And as
00:43:38.740I mentioned to you earlier, you cannot know your breast density without imaging, at least
00:43:42.900definitively. About half of women have dense breasts and density is higher in younger women
00:43:48.960than older women. So there's a reasonable argument for getting a single baseline mammogram in your
00:43:54.72030s, not primarily to find cancer, but to establish whether you have dense breasts. If you do, that
00:44:01.780changes your risk profile and may change your screening strategy. To be clear, this is less
00:44:07.140about cancer detection and more about risk stratification. And while there is no direct
00:44:12.400evidence supporting this approach, it's something that I think is worth considering. So when should
00:44:18.100you start screening? As with everything else we've talked about, it depends on your risk.
00:44:22.600If you are truly average risk, beginning annual mammography at 40 is well supported, though you
00:44:29.040may want to consider getting a baseline mammogram in your 30s at a minimum to establish your breast
00:44:34.340density. If you are above average risk, there is a small amount of evidence that mammography in
00:44:41.020your 30s can be worthwhile. And if you're clearly high risk, a known BRCA carrier, a strong family
00:44:46.800history, or prior chest radiation, the conversation is different entirely and more aggressive screening
00:44:51.700protocol should be started in your 20s or early 30s. Now everything we have discussed so far is
00:44:57.880about routine screening, finding cancer before it causes symptoms. But there's one type of breast
00:45:04.180cancer that does not follow those rules, and I want to make sure we address it before we wrap up.
00:45:09.740Inflammatory breast cancer is a rare type of cancer, roughly 1 to 5 percent of all breast
00:45:15.140cancers, but it is aggressive and it does not present the way most people expect breast cancer
00:45:20.500to present. There is often no discrete lump. Instead, what you may notice is rapid swelling
00:45:26.100or heaviness of the breast, redness or rash, warmth, or changes in skin texture or thickness.
00:45:32.900Because these symptoms can look like skin irritation or something else relatively benign,
00:45:37.980diagnosis is frequently delayed. And this is the key point. Normal screening mammography does not
00:45:44.160rule out inflammatory breast disease. These cancers may not be visible on mammography,
00:45:48.840so a diagnostic workup is necessary. This is an important reminder that screening tests are
00:45:54.940designed for women without symptoms. If you notice something new, a lump, skin changes, nipple
00:46:00.940discharge, pain that does not resolve, do not wait for your next scheduled screening. A recent
00:46:07.700normal screen does not guarantee everything is fine. Go and get evaluated in person by your
00:46:13.620doctor. And this applies to men too. I have focused this discussion on women because the vast majority
00:46:19.260of breast cancers occur in women, but men do develop breast cancer. Because we do not routinely
00:46:25.420screen men, symptoms are typically the only path to diagnosis. A new symptom in a man should not0.60
00:46:31.560be dismissed. It should be evaluated just as it would be in a woman. All right, so where does all0.99
00:46:37.440of this leave us? We started this episode with a question. If screening works so well, why are 42,000
00:46:45.960women still dying from breast cancer every year? Part of the answer is biology. Some cancers are
00:46:51.260aggressive enough that they will evade even the best screening. But the far larger part, and the
00:46:56.820one that we can actually do something about right now, is that we are not screening intelligently
00:47:02.040enough. A quarter of eligible women are not up to date on basic mammography. The vast majority of1.00
00:47:09.280women who qualify for MRI are not getting it, and most women have never had a formal risk assessment.
00:47:15.960The science here is not the bottleneck. The tools exist. The evidence is strong. What is missing is
00:47:23.460the bridge between what we know and what women are actually doing. And to be clear, this is not an0.93
00:47:29.580individual failure. Access to MRI is limited in many areas. Insurance coverage is often tied to
00:47:36.100the USPSTF recommendations, which do not fully address high-risk populations. Imaging quality
00:47:42.940varies across centers. All of these system-level factors contribute to underscreening and suboptimal
00:47:49.080screening. But there is still a great deal that is within your control. So if you take nothing else
00:47:56.160from this episode, let it be this. First, complete a risk assessment using a validated risk calculator
00:48:02.800like the one we'll link to in the show notes, so you have a quantitative sense of your baseline risk.
00:48:08.960Second, find out your breast density from prior imaging or plan to establish it when you begin screening.
00:48:16.240Third, choose a cancer screening strategy, both modality and frequency, that matches your level of risk and your tolerance for false positives.
00:48:25.360And fourth, execute that plan consistently over time.
00:48:30.800None of these steps are complicated, but taken together, they are what separates passive
00:48:35.860screening from intentional, personalized screening.
00:48:39.200With the current technology, we cannot reduce breast cancer deaths to zero, but far too
00:48:45.500many lives are still being lost because we are applying the right tools too late, too
00:48:50.080inconsistently, or to the wrong people.
00:48:53.000At least at the individual level, this problem is more solvable than most people realize.
00:48:57.960If risk is assessed, the right screening strategy is chosen and the screening is actually carried out.
00:49:04.980Thank you for listening to this week's episode of The Drive.
00:49:08.420Head over to peteratiyamd.com forward slash show notes if you want to dig deeper into this episode.
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