Breast Cancer

Anne Marie: Most recommending groups don't actually recommend self breast exams anymore. There have been some trials done that show it doesn't really move the dial in terms of mortality, which is what we want to see in screening tests for tumors. That being said, being aware of changes in your breast is very important.

Brent: Welcome to Death Clock. I am your host, Brent Franson. Today we speak with Doctor Anne Marie McCarthy about breast cancer prevention. We spend the majority of the time talking about screening: when to screen, how often to screen, and the different types of screens that are available. Like so many other cancer screening recommendations, there is a lot of nuance.

Brent: Your family history matters, your genetics matter, and the types of screens you get matter. There are false positive rates, which are basically ambiguous results, so there are some tough decisions to make on whether or not to biopsy, along with different types of side effects. It's very much a strategy of being as educated as you can so you can make the best decisions for you.

Brent: I think she does a great job of walking us through this for breast cancer specifically. I hope you enjoy.

Brent: Doctor Anne Marie McCarthy, welcome to the show.

Anne Marie: So nice to be here. Thanks for the invitation, Brent.

Brent: Of course. You have built your career and your research around studying breast cancer prevention, spending your time there, so I'm excited to dive in. Before we get into that, give us a sense of your bio and background.

Anne Marie: I was born and raised in Philadelphia, Pennsylvania. I unfortunately experienced cancer at a very young age—my cousin died of ovarian cancer when she was 24, and I was five when that happened. It's one of my earliest memories. From that time on, I was always really interested in why this happened to her specifically.

Anne Marie: And why does cancer happen more broadly? That was always in the back of my mind. I think that really led me into science. I worked in a lab for a while as a biology major at the University of Pennsylvania for undergrad. I really liked working in the lab, but I wanted to do something a little bit more applied.

Anne Marie: I really wanted to do something that impacted people, and that's how I found the fields of public health and epidemiology. Epidemiology literally means the study of epidemics. Many epidemiologists study infectious diseases like COVID, but I study cancer and the epidemic of cancer—what we can do at the population level to prevent it and reduce its burden.

Brent: So you knew at five years old. That trajectory started really early.

Anne Marie: It did. That was such a central memory of mine. Unfortunately, my mom's family suffered from cancer often. I had three aunts die from cancer, and my mom beat cancer twice. It was very much part of the fabric of our family—how cancer affects not just individuals, but their loved ones as well.

Anne Marie: It was definitely something I felt really passionate about, wanting to spend my career improving conditions for people.

Brent: Let's start with the genetic and familial association. Can you share a little bit about the BRCA genes and the role of genetics in someone's risk for breast cancer?

Anne Marie: Of course. Our estimate now is that about 5 to 10% of breast cancers have a clear genetic cause. As you mentioned, BRCA1 and BRCA2 are probably the best-known breast cancer genes, identified in the '90s. The genes are relatively rare in the population, but if you have that mutation, your risk of both breast and ovarian cancer goes way up.

Anne Marie: An average woman has about a 12% risk of developing breast cancer over her lifetime, whereas for a woman with a BRCA mutation, it's anywhere from a 60 to 80% lifetime risk. Because of that, women with genetic mutations are encouraged to take more proactive preventive measures, which we can discuss.

Anne Marie: Up until now, we mostly thought about genetic risk based on family history. Women who have a family history of breast cancer, ovarian cancer, or both should talk to their doctors about whether genetic counseling and testing make sense for them. There are other genes we know about now besides BRCA1 and BRCA2 that increase risk.

Anne Marie: There are other genes, like PALB2 and CHEK2, that we're learning increase your risk of breast cancer.

Brent: Is BRCA the common reference? I tend to pronounce it "BRCA," or do people say "B-R-C-A"?

Anne Marie: I hear both.

Brent: Can those be picked up on a standard genetic profile like 23andMe or an equivalent?

Anne Marie: You have to be careful with 23andMe and similar tests because they don't always test for every possible mutation in the genes. At one point, 23andMe was testing a specific set of typical founder mutations. The best course is to talk to your doctor and a genetic counselor to ensure comprehensive testing.

Anne Marie: There are differences between a test you buy directly versus clinical genetic testing ordered by a doctor.

Brent: Over-the-counter versus prescribed.

Anne Marie: Yes. I don't want to generalize that all over-the-counter tests are wrong, but if you test positive on one, or if you test negative despite a strong family history, you should follow up.

Anne Marie: Go talk to a geneticist or medical oncologist to make sure you are properly covered in terms of testing.

Brent: What is the prevalence of BRCA mutations in women?

Anne Marie: It's around 1 in 400.

Brent: Would you recommend that all women be tested for that genetic mutation? In a perfect world, should 100% of women see a genetic counselor for a prescribed screening?

Anne Marie: Current recommendations for genetic testing are mostly based on family history or personal risk of cancer. We don't recommend general population screening at this point because the mutations are relatively rare, but whether we should move toward population-wide testing is an active area of debate.

Anne Marie: We might miss genetic mutations if a patient doesn't have a strong family history. I think about this often now that family sizes are shrinking. Decades ago, people had multiple aunts and uncles on both sides, making family patterns obvious.

Anne Marie: If someone only has one sibling who is male, you might not have a flagged family history that prompts testing. We're in an area with a growing push for wider genetic testing, but for right now, it remains mostly family history-based.

Brent: That's a really good point. With smaller families, the odds of seeing something show up in relatives are much lower, which increases the need for proactive screening.

Brent: I never thought about that. That's really interesting.

Anne Marie: Having a first-degree relative—a mother or sister—with breast cancer is more concerning than a second-degree relative like a cousin, aunt, or grandmother. Second-degree history is still considered, but first-degree relatives present the highest risk.

Brent: Is there a strong argument against screening at the individual level? Insurance math compares the cost of prevention versus treatment across a population, but at the individual level, knowing you have a 60 to 80% risk allows for early detection and better outcomes.

Brent: If we set economics aside and assume everyone can afford it, is there any reason for a woman without a family history not to be screened?

Brent: If you're just a woman, even if you don't have it in your family.

Anne Marie: Economics are a major driver. If testing were free, the case for universal screening would be much stronger. However, genetic testing isn't just a simple positive-or-negative result.

Anne Marie: There are also variants of unknown significance. We know certain BRCA mutations are clearly pathogenic and significantly increase risk. But if we screen the general population broadly, we will find many genetic variations where we aren't sure of the impact.

Anne Marie: Some mutations might be in non-coding regions or might not alter amino acids, making it unclear whether they raise risk to the same degree as known pathogenic variants.

Anne Marie: There is ongoing research modeling these unknown variants to determine if they cause elevated risk. That potential uncertainty is the main downside to widespread testing.

Anne Marie: Getting an inconclusive result can be stressful for patients. For known BRCA carriers, we recommend intense screening with mammograms and MRIs starting in their 30s, as well as considering prophylactic surgeries like mastectomies or removing ovaries after having children.

Anne Marie: We want to ensure those major interventions are fully warranted, which isn't clear with variants of unknown significance.

Anne Marie: To summarize: there's a huge difference between having a BRCA mutation (60-80% risk) and not having one (12% average risk). Those with the mutation follow an intensive track with earlier screenings and potentially preventive surgeries. Those without mutations follow standard screening without those drastic measures.

Anne Marie: And with some of these variants of unknown significance, we don't know that it's warranted.

Brent: Determining which track you belong on comes down to family history of breast or ovarian cancer.

Brent: If there is significant history, you should strongly consider genetic counseling and testing.

Brent: Is there a lot of ovarian cancer in the family? Is there a lot of breast cancer in the family? If there is, you're going to be much more heavily considering going to the genetic counselor and looking for those genetic mutations.

Anne Marie: That's right. The age of diagnosis in your family is also key. Diagnosis in their 40s is much more concerning than a relative diagnosed at 80, as hereditary cancers tend to appear earlier.

Anne Marie: Younger breast cancer diagnoses in the family are a major red flag.

Brent: If you don't have a family history but want to check for BRCA mutations, you can explore over-the-counter options or talk to a counselor. However, the risk with broad testing is similar to full-body scans: ambiguous results that create psychological distress and force decisions about invasive follow-up procedures like biopsies, which carry their own risks.

Brent: You can go talk to a genetic counselor and and try to get referred. The risk of that is the same risk that we have with over screening in other areas. This comes up with full body scans and liquid biopsies, sometimes referred to as false positives. I think that that's misleading. It's ambiguous results. So you are told, hey, you have a mutation that might make your risk higher and that carries to risk one, there's the psychological impact of that would just like, oh, do I have something that's concerning?

Brent: And maybe you do, maybe you don't. But now you didn't have that question before. And then too, there's the subsequent question that you have to ask, which is what do I do? Okay. Am I going to go do some kind of biopsy? Am I going to do something that's more intrusive? So is that second piece also there that we see in the full body scans, which is and there's risks associated with a biopsy.

Brent: And there are side effects of those things.

Anne Marie: It's all about the risk-to-benefit ratio. There are risks to almost everything in life, so the goal is learning how to weigh those risks against the benefits.

Brent: It seems like a personal philosophy question. Some people prefer having maximum information despite potential risks, while others prefer sticking strictly to standard recommendations.

Brent: So it does feel like there's some, I don't know, philosophical touch.

Anne Marie: Yes, there's a lot of personal preference involved there.

Brent: Can you describe genetic counseling? When people hear "counselor," they might think of mental health. Is a genetic counselor primarily helping you interpret complex genetic results?

Anne Marie: It comes from evaluating personal preferences and weighing risks versus benefits. Genetic testing results can be complex because they deal with future risk, which carries major health implications for both you and your family.

Anne Marie: When facing impactful choices like prophylactic surgery, a genetic counselor helps lay out the benefits, risks, and options specific to your family history.

Anne Marie: You start by filling out a detailed questionnaire on your family history, which the counselor evaluates to see if there is significant reason for concern.

Anne Marie: They guide you on which specific panel to test, as there are tests for breast, colorectal, and other cancer genes. Timing is also key; for instance, we wouldn't test a 12-year-old child for a BRCA mutation because medical action wouldn't be taken for decades, avoiding unnecessary anxiety.

Anne Marie: Genetic counselors combine expertise in genetics with counseling to help individuals make the right decisions at the right time.

Brent: If someone without family history wants to get tested out of an abundance of caution, what does that process and cost look like?

Anne Marie: The cost of BRCA testing has decreased significantly, though multi-gene panel testing can vary based on what you are looking for.

Anne Marie: If you have a known mutation in your family or targeted ancestry like Ashkenazi Jewish lineage, targeted testing for specific founder mutations can be less expensive.

Anne Marie: Genetic testing used to cost thousands, but prices have dropped. Some companies offer options around $300 out-of-pocket.

Anne Marie: I recommend starting with your physician to see if insurance will cover it based on your history, which typically requires some personal or family history of cancer for coverage.

Anne Marie: Because costs are dropping, explore your options, but always consult your doctor first.

Brent: It's worth noting that while rare, men can also get breast cancer or pass along mutations to daughters. Should men approach this with a similar mindset?

Anne Marie: Men can get and die from breast cancer, though it is much less common than in women. Men can also carry BRCA mutations, which elevated risks for prostate and pancreatic cancers.

Anne Marie: A history of breast or prostate cancer among male relatives can indicate a genetic cause. Men with a family history of BRCA or female relatives with cancer should consider speaking to a genetic counselor.

Brent: Stepping away from genetics, let's discuss basic screening methods: self-exams, mammograms, and MRIs. Can you walk through each of those?

Brent: And then the second would be the mammogram and the third would be an MRI. Can you speak to each of those.

Anne Marie: Most guidelines no longer recommend routine self breast exams, as clinical trials show they don't significantly lower mortality rates. However, overall breast self-awareness remains crucial.

Anne Marie: Rather than strict monthly exams, women should pay attention to symptoms like new lumps, pain, nipple discharge, dimpling, or changes in how the nipple looks or feels.

Anne Marie: All of those symptoms should be evaluated by a doctor promptly.

Brent: Why did organizations stop recommending structured self-exams?

Anne Marie: Normal hormonal fluctuations during the menstrual cycle cause temporary lumpiness and tenderness, leading to high rates of false positives and unnecessary follow-up imaging or biopsies.

Anne Marie: For women getting regular mammograms, structured monthly self-exams add minimal benefit while increasing unnecessary procedures. In areas without access to mammography, self-exams play a larger role.

Anne Marie: Then I think self breast exam might be more important, but that's part of it. It's again, it's about the weighing the balance, the risks and benefits of over screening and under screening.

Brent: Anecdotally, we often hear about individuals finding a lump early through self-exams that saved their lives, even if group data doesn't reflect a broad mortality benefit.

Brent: That there do seem to be these individual anecdotes where some finding the lump when somebody's found it, you know, may have saved their life versus the downside side of, you know, the monthly screening is not ever death, right? So it's like, okay, maybe there's a little bit of psychological damage or there's an unnecessary biopsy, which is not good, but it's not.

Brent: Since self-exams carry no direct physical danger beyond anxiety or follow-ups, is that perspective flawed?

Anne Marie: It isn't wrong. On an individual level, some women do benefit. However, on a population level, teaching routine self-exams doesn't shift overall mortality rates compared to mammography.

Anne Marie: Mammograms remain the far more effective tool for population screening.

Anne Marie: The main downside of self-exams is simply the increased rate of false positives.

Brent: How should women approach mammography in terms of starting age and frequency?

Anne Marie: A mammogram is a low-dose X-ray and remains the gold standard for catching early-stage breast cancer before a physical lump develops. Detecting tumors depends heavily on breast size and tissue composition.

Anne Marie: Randomized controlled trials prove mammograms reduce mortality. The US Preventive Services Task Force recently updated its guidelines in 2023 to recommend starting screening at age 40, lowering it back down from 50.

Anne Marie: This change reflects rising cancer rates at younger ages and addresses disparities, such as Black women developing breast cancer earlier on average than white women.

Anne Marie: Additionally, while breast cancer in your 40s is relatively uncommon, tumors that develop pre-menopausally can be more aggressive due to circulating estrogen fueling hormone-sensitive cancers.

Anne Marie: The USPSTF currently recommends screening every two years, whereas some medical organizations and insurance policies support annual screening starting at 40.

Anne Marie: For women at elevated risk, breast MRIs are increasingly used as a supplemental tool alongside mammograms because they offer higher sensitivity in detecting tumors.

Anne Marie: While effective, mammograms are not 100% perfect. If you notice a new symptom or lump shortly after a normal mammogram, you must still have it clinically evaluated.

Anne Marie: Mammograms detect roughly 85% of breast cancers, which means some cancers can still be missed.

Anne Marie: A negative result means no cancer was detected on that image, not a absolute guarantee that cancer is absent.

Anne Marie: For high-risk individuals, such as those with BRCA mutations or strong family histories, earlier screening in their 30s with both mammograms and breast MRIs is standard.

Brent: Risk assessment models also factor in prior benign high-risk biopsy results like atypical hyperplasia or LCIS.

Anne Marie: Why aren't breast MRIs used universally if they offer higher clarity?

Brent: Breast MRIs require IV contrast dye, take longer, cost more, and carry higher false-positive rates of around 10% leading directly to biopsies without intermediate re-imaging.

Brent: There are also system-wide equipment and capacity constraints, making MRIs appropriate primarily for women with a lifetime risk over 20% or extremely dense breasts.

Anne Marie: Dense breast tissue makes cancers harder to detect on standard mammograms, dropping sensitivity down into the 60% range, while also independently increasing breast cancer risk up to fourfold.

Anne Marie: The FDA now requires mammogram reports to explicitly inform patients of their breast density level so high-density patients can discuss supplemental screening with their doctor.

Brent: What are the primary side effects or concerns associated with unnecessary biopsies following false positives?

Anne Marie: While physical complications like infection are relatively rare compared to other procedures, unnecessary biopsies cause psychological distress, financial burdens, missed work, and risks of overdiagnosis.

Anne Marie: About 20% of detected breast cancers are Ductal Carcinoma in Situ (DCIS), a non-invasive Stage 0 condition. Because current science cannot reliably differentiate which DCIS cases will progress versus remain harmless, many women undergo aggressive treatments unnecessarily.

Anne Marie: What are your thoughts on emerging commercial screenings like full-body MRIs or multi-cancer early detection blood tests?

Anne Marie: Blood-based liquid biopsies are promising future developments, but comprehensive trial data on whether they provide more overall benefit than harm across populations is still pending.

Anne Marie: Beyond individual choices, we must consider system constraints and equity: over-screening low-risk individuals can consume limited healthcare appointments and delay access for higher-risk individuals.

Anne Marie: Lastly, what lifestyle factors impact breast cancer risk?

Anne Marie: Post-menopausal obesity and higher alcohol consumption both clearly increase risk, while regular physical activity serves a protective role. Additionally, long-term menopausal hormone replacement therapy increases risk, so women should weigh those risks against severe menopausal symptoms with their physician.

Anne Marie: Where can people find out more information about your work?

Anne Marie: You can look me up through the University of Pennsylvania. For general information, the American Cancer Society provides excellent evidence-based resources and patient guides.

Anne Marie: Doctor Anne Marie McCarthy, thank you so much for joining us and for all the work that you do.

Brent: Thanks so much. Great talking to you, Brent.

Anne Marie: Death Clock is recorded in Boulder, Colorado, and San Francisco, California. Produced by Patrick Gudino, music by Patrick Lee, and hosted by yours truly, Brent Franson, founder and CEO.