Thank you all of you so much for being here. I'm really happy to have this chance to have a conversation about alcohol use and breast cancer. I'm going to begin by introducing our wonderful panelists. We have Dr.Sharima Rasanayagam who is the Director of Science, she's also a doctor at breast cancer prevention partners, it's a leading science-based non-profit organization that does science-based environmental health policy and advocacy work. They're based in Northern California. We also have Dr. Peggy Reynolds, who is a cancer epidemiologist and Professor at the Department of Epidemiology and Biostatistics at the University of California at San Francisco. She's also a member of the Helen Diller family Comprehensive Cancer Center. We also have Dr.Ritu Aneja who's a professor of cancer biology and a distinguished university professor at the Department of Biology at Georgia State University. She's also Director of the Molecular Basis of Disease Program and she founded the International Consortium for Advancing Research on Triple Negative Breast Cancer. We have Dr. Raime Eck who is past president and advocacy committee, co-chair of the Maryland Public Health Association. She's also a former cancer research training award fellow at the National Cancer Institute and founder and principal of Sonrisa Solutions. I'm Dr. Priscilla Martinez. I'm a scientist at the Alcohol Research Group, a Program at the Public Health Institute in Northern California. I also had a very happy experience of being the principal investigator of the drink less for your breast program with Dr. Peggy Reynolds. We're going to share what we know about alcohol and breast cancer. We're going to begin by covering some of the evidence that shows that this link is real, get into some of the details of that link, talk a little bit about the awareness of this link generally and what that means for alcohol policies, and then move a little bit beyond talking about alcohol use as a risk factor for breast cancer and talk a little bit about what we know about alcohol's impact when you get a breast cancer diagnosis. To kick things off, let's start with Dr. Rasanayagam. Can you tell me a little bit about what we know about the evidence showing that alcohol use increases the risk of breast cancer? Hi. Thank you, Priscilla, and thank you to everybody for inviting me here. At breast cancer prevention partners, we did an analysis of the scientific literature as part of our 2020 report, cost of prevention. We looked at all of the peer review papers published on the link between alcohol and breast cancer up till 2019. What we found from that, there is a large body of evidence with multiple studies which show that women who drink alcohol are more likely to be diagnosed with breast cancer than those who do not and that the more that you drink, the higher your risk. Now while some studies show that drinking any alcohol increases a woman's risk, others suggest that consuming over 10 grams of alcohol a day increases risk. For context of five ounce glass of wine contains about 14 grams of alcohol, even a small glass of wine, that's a small glass of wine by most people's standards, can significantly increase your risk by small amount, but a significant increase. Sounds like there's really clear evidence that this is true. One of the questions that I often follow is when we, I think, say that alcohol can increase a woman's risk of breast cancer is how does it do it? What do we know about the physiological mechanisms that might be driving this risk? I know that's really important to know. There's three main ways that we think that alcohol increases risk for breast cancer. First of all, when we drink alcohol, our body breaks it down into what we call metabolites. The most concerning one is acetaldehyde and that is an actual carcinogen. Acetaldehyde has been found to cause cancer in a variety of studies. There's that carcinogen, the alcohol is broken down to in our own bodies. Also with breast cancer, specifically, drinking alcohol also increases the estrogen levels in our body and the higher levels of estrogen in a woman had been linked to an increased risk of breast cancer. There's these two mechanisms, the general carcinogen mechanism plus this specific to breast cancer estrogen mechanism. Then there's also a concern that drinking alcohol makes it more difficult for you to absorb folate from your diet which can lead to lower folate levels in people who drink a lot of alcohol. Folate is important for DNA synthesis and maintenance of DNA health and low levels can increase DNA damage and also be a risk for cancer. Those are the three main mechanisms we think are at play. That's great. Really clearly there are ways that this actually happens. When I talk about this with women, even after I'll say everything you just said, they'll say, so is there any safe level of drinking? Is even a little bit? I only drink occasionally. Does that increase my risk? Dr. Reynolds, I'd like you to answer that question, please. After that very exquisite explanation, I think you can see that there are a number of particular potential mechanisms of risk and just very briefly, I can say that the data suggests there is in fact no safe level. It's pretty well established that the risk increases with each unit of alcohol consumed per day. This is across many, many studies, and although public health messaging that we got from USDA, HHS, their definition of moderate drinking suggests that women should consume no more than a drink a day for a variety of public and health concerns, the fact is for breast cancer risk, less is better. It sounds like there isn't any "safe level" but the relationship is such that at very low levels, that increases huge, but it does increase as you increase the drinking. Yeah. Thank you. A little bit more, some of the details of the link between alcohol use and breast cancer. Dr. Reynolds, can you tell us a little bit about what we know about the effect of when you drink alcohol. As we know, the trajectory of alcohol use changes over the life course, oftentimes it's higher in younger ages, peaks in your 20s, and that's where levels off as you get older, although trends are changing over time. But what do we know about the age of consumption and how that affects breast cancer risk. We do know that for a number of cancer risk factors, particularly for chemical exposures and other exogenous exposures there's been very high interest in identifying windows of susceptibility during the life course. There may be especially important for cancer development and as you say, certainly drinking patterns in women vary during the lifespan and they could coincide with these important events. When women's breast tissue changes in both structure and function importantly during puberty, pregnancy, and menarche. Drinking at an early age cannot only map to changes in breast tissue but also other developmental and lifestyle challenges during this period of life. One of the more well-known studies, the Nurses' Health Study in which you say a large, a couple of large prospective studies from the Nurses' Health Study 2, the second Nurses Health Study included younger women than the original study. They were ages 24 and 44, an entry reported an 11 percent increase in breast cancer risk for every 10 grams of alcohol intake per day between menarche and first pregnancy. This was similar to the observed eight percent increase in risk from recorded earlier life consumption for 10 grams of alcohol from the Nurses' Health Study 1, which recruited women slightly older at baseline. Although this and other evidence suggest that starting drinking during adolescence and early adulthood may be associated with a higher risk than starting at a later age. The literature window of higher susceptibility is actually a little bit mixed. While younger women may be more vulnerable due to the sensitivity of breast tissue to external exposures during these important developmental windows. Alcohol consumption appears to be a fairly equal opportunity exposure across types of alcoholic beverage, the age started drinking, and menopausal status, and other life stages. Again, back to our original tenet the evidence says that there is evidence for a linear dose-response relationship to risk, so less is better or more is worse. Less is better, more is worst. Yeah, better. But it does sound like if you're drinking at a very young age, that is a window of susceptibility for alcohol use impacting the development of breast cancer and which is, I think something to remember and you hit on something that I want to quickly follow up on about type of alcoholic beverage because we've heard a lot about how red wine is good for us. For breast cancer risk, does the type of alcohol we drink matter? The evidence suggests that it doesn't. It's really the alcoholic content and different beverages provide different amounts of alcoholic content. There is this interesting hypothesis about reservatrol in red wine may be protective. But again, the literature is pretty mixed on that, and the more compelling evidence, is that it doesn't really matter when you start. It's really a dose-response. Yeah. Alcohol is also equal opportunity in terms of what you're drinking. It's just alcohol is alcohol to the body. That's pretty much what the evidence looks like. Great. Thank you. Thinking about risk, I'm going to move to Dr. Aneja. Alcohol can increase the risk of breast cancer, but not everybody who drinks is going to develop breast cancer. That opens up the question about who might be more vulnerable and when we think about vulnerability, oftentimes we think about genetic predispositions. Dr. Aneja, could you tell us a little bit about what we know about potential genetic factors that might confer more breast cancer risk in the context of alcohol use? Yeah, Priscilla. So far, I don't think there is any strong evidence that genetic factors can modify the association of alcohol consumption and breast cancer risk. What I've seen is there's been a Dutch study that examined variations in alcohol dehydrogenase gene. It's called the ADA gene and it encodes for alcohol dehydrogenase, which is the enzyme responsible for metabolism of alcohol. There were no associations that were found in the variance of this gene that could modify the risk between alcohol and breast cancer. Similarly, there's a Danish study looking at CYP191a, it's a Cytochrome P450 family member, and it is called aromatase and it's an enzyme that is also known as estrogen synthase, which means it's responsible for the synthesis of estrogen. They have seen that variants of that enzyme also do not modulate the risk, which is good news in a way. Among women with BRCA1 and BRCA2 mutations that are known generally to elevate the risk of breast cancer, there is no studies that show that alcohol consumption is modifying that risk either. So far the evidence is not very strong in the space. That's really interesting because I think people think of breast cancer, and they think of genetic risks right away and that alcohol doesn't modify or that having a particular genetic factors doesn't modify the association between alcohol and breast cancers is interesting, or that we don't maybe know everything, yet. Yes. It slightly that we do not fully know everything because of the way and there are so many caveats in these studies because depending upon how they looked at the trajectory of drinking patterns or the woman's history of drinking because as we have heard from other panelists that drinking at a very young age, which is in the teens when the menstruation starts and the breast tissue is really vulnerable, that's when the influence is much higher. They has been very recent 2021 study I was looking at from Spain. They've done some trajectory modeling and have seen that the early consumption during early adolescence has the greater risk. More to learn, sounds like. Another aspect of the risk relationship I'd like to touch on before talking a little bit about awareness is that breast cancer, as you know isn't a homogenous disease , there's all subtypes. Does drinking alcohol increase the risk of any particular breast cancer some type, or is it the same for all of them? Very good question, and the short answer is it does. But the jury is still out as the data is inconsistent. To talk about breast cancer subtypes and which ones are more so some. Women are more susceptible to have one versus the other, it's useful to know, as you said, that breast cancer is not a single beast. It is a very heterogeneous disease. It is essentially a grab bag of many different kinds of breast cancers and for therapeutic decision-making in the clinic, it is characterized by three biomarkers. Let's just think of them as tags or labels present on a breast cancer cell. They are ER, which is the estrogen receptor, PR, progesterone receptor, and HER2, which is the human epidermal growth factor receptor 2. We have a fourth hidden category which lacks all these three tags. That is what is the triple-negative breast cancer. It is known by what it lacks rather than what it has. When you don't have these three tags, that's the triple-negative breast cancer and as we know, that's the most aggressive and no targeted therapies. Chemotherapy is the mean mainstay and that's the one which is also disproportionately affects black woman at a younger age. There are some studies that are clearly pointing that alcohol consumption increases the risk of hormone positive cancers which ERP are positive compared to those which are not, compared to the ER negative disease. For example, the epic study, which was a study in 360,000 women from Europe across, they recruited woman across 10 European countries and it reported increased risk of ER positive cancer compared to ER negative. This finding was also confirmed in the 2018 Meta Analysis Report from WCRF and EICR, the American Institute of Cancer research collaboration. They also found this similar finding that ER positive risk was higher, but the risk was more pronounced in their study in postmenopausal woman. Then there's another really interesting study coming out of the AMBER Consortium, which is a consortium of African American women and there they found that the risk for triple-negative was higher, in that study. In the context of alcohol. Alcohol consumption, yes. Alcohol consumption increase the risk of triple-negative disease in that AMBER study. But we have the Million Women Study from UK as well as another study which is a pooled analysis of 20 cohorts, which also has more than a Million Women. They did not find any association with subtype. That's how it feels like the data is inconsistent, but I again feel like there's so many variations and the confounding variables and what was considered and what was not depending upon that study design. There's a suggestion that is associated with hormone positive in triple-negative, but we're not entirely sure. That's very right. Thank you. Clearly, there's a lot that we know, there's still some stuff we need to figure out, but it's really clear that alcohol increases the risk of breast cancer. What do we know about the awareness of this? Clearly we know about it, but the general public. I'd like to move now to about awareness of this. Dr. Reynolds, I I'd like to hear what you think about, what the state of public awareness is of the link between alcohol use and breast cancer. Well, I think it's pretty interesting that this is something that's been evaluated in the scientific literature for quite a number of years. There's a very long history of evidence of increased risk, and yet it's something that few women who really seemed to be aware of. There are a number of surveys that have been conducted, there was a US national survey of young women recorded a few years back that found that 25 percent of women, which is actually more than I might have expected, reported awareness of alcohol is a risk factor for breast cancer. This contrasts with 88 percent being aware of family history as a risk factor. This is because it's the most common cancer in women. I think there's some public awareness about some risk factors for the disease. Similar to this study There was a British survey from the same time period that recorded 18 percent awareness for link between alcohol and breast cancer, with an only slightly higher reported awareness of 30 percent in a region of the country that had an ongoing media campaign about the risk relationship. This suggested by the authors that population awareness can be somewhat influenced by social marketing and yet it's interesting that the increase in awareness isn't as much as you might have expected. There's actually an extensive literature on this with pretty much the same conclusions about limited awareness over time and from several countries. There was an interesting pre and post survey from a Danish mass media campaign 2017 and 2018, that recorded not only increased awareness, but also some increased support for minimum unit pricing, a ban on alcohol advertising, and mandatory nutrition labeling. From another point of view, there's a very recent study from Southern California as part of the UC, Athena cohort study that reported that even among women with knowledge, this is a risk factor, the women in their study who were more affluent and older, which is the subgroup generally at higher risk of breast cancer, expressed unwillingness to modify behavior and to reduce intake. There's an adage that knowledge is power. But in this case, there may be opportunities for population in public policy intervention it appears that are very complicated. I think we still have much to learn. I have to say the very recent work of you and your group on the Drink Less for Your Breast campaign may offer some additional insights. You may want to come in on that as well. Yes. The study showing that awareness is so low, particularly among young women, I think you were referring to the [inaudible] paper or study that showed that 25 percent of women knew about the risks, what that means is 75 percent don't. These if I recall was among women between the ages of 15 and 44. This is fine age for. Our very study and actually the other interesting factor in that is that the current drinkers in that study were less likely to believe it to be a risk factor. Yes. That was a huge motivator for the Drink Less for Your Breasts social media campaign which is ongoing. You can find us on Instagram. The goal really solely was to raise awareness. It's not about lowering consumption. We just want to get the message out there because general awareness is indeed so low. Great. Thank you, Peggy. I would like to move a little bit to the, I want to say pink elephant, but I think we all know it's there , the alcohol industry. What role the alcohol industry has played in our general awareness the link between alcohol use for breast cancer. Dr. Eck, could you comment on that? Thank you very much. I appreciate being here. It's great to be in the company of such wonderfully informed folks and to be able to talk about this stuff so openly. It's really complicated association as you've seen here. Probably from what you as the audience know in your background, there's been some mixed messaging. The heart health was already brought up. The lowest risk being at zero level of consumption. We've been able to talk about this very easily here for the last half an hour or so amongst ourselves. But there is this question about why is that message not being translated onto the general population? Why is it not catching on? Why is it not more popular that we know about this? Especially since we know that almost 50 percent of cancer risk is attributable to modifiable behaviors. When I first went to the National Cancer Institute, that was one of the most important things that I learned literally on day 1 is that there is a lot of things that we have control over in our cancer risk. Because a lot of times you can feel helpless, you can feel out of control. You could feel like this is something that's been put upon. However, these are things that we actually have control over in our own lives to some degree. Alcohol is the third largest risk. That is something that definitely should be a larger part of a message across the country within our clinician, neighborhoods, community neighborhoods and yet it's not. You asked me specifically about the industry and you also brought the word pink into it. I'll lead off right here. There's a term called pink washing and it's a play on the term whitewashing. It was first used by breast cancer action probably about 20 years ago. It was an organization focused on social environmental justice in the fight against breast cancer. This is really used as a critique on companies that are using the pink ribbon. Whether it's here, whether it's on their marketing materials, whether it's on the product yourself, they're using that pink ribbon on their product to market the product. But it is a product that is actually associated with cancer. Something that causes cancer, it's associated with cancer. When we see this, you probably had a number of examples pop into your mind. We just had breast cancer awareness month in October. Oftentimes you will see bottles of alcohol or liquor, beer, wine, and they are either pink, they're pink in color. The labels may be pink, the ribbon may be prominent. Or maybe a combination of all those types of things. Sometimes there's a suggestion that if you buy this product, there may be money donated towards some charity or it just maybe we're doing this for a sense of awareness and there may be no money donated to charity. Sometimes that is not necessarily clear, so that's part of the problem. The alcohol industry has done a number of things. There's three main tactics that have been looked at in the research. There's a number of folks out of Australia who've looked at this. One of them is just denial or emission, if I don't talk about it, it doesn't exist, so let's focus on other things. Number 2 is distortion, we may mention there's some risk, but when we were really digging into this earlier about what is the level of risk? How does it work? What's the dose relationship? We're just going to pass all over that and we're not going to really talk about the specifics, so maybe mitigating that risk that's actually out there. The other thing is distraction and this is a really big one and this is probably the easiest one to do where we say, "Hey, there are so many things that cause cancer, alcohol really is just this really teeny tiny part of it that you don't even need to worry about." When you have those three things that are stack together and industry is very good at doing this and we have this documented in research, you can go out there and look at and find it yourself. Those things are really harmful to the messaging because not only would we have some mixed messaging already and the information we're getting is very complicated to understand it's relationship, but then we have this mixed messaging coming out of the industry itself, which is huge and everywhere with its advertising and its marketing. This could lead to some confusion in the general population. Thank you. What do you think then awareness about this link might mean for alcohol policies? One is that we know can help reduce the consumption overall, increasing taxes or reducing availability. What do you know about how general awareness impact support for those policies? Dr. Reynolds gave us a great introduction to some of that already, looking at some of the work again out of Australia and the UK. Most recently when I was at National Cancer Institute, I was working with a team there and there's a paper just now in press coming out showing that those who have a greater awareness of the link between alcohol and cancer have a greater support for alcohol policies in general. The ones that we looked at in NCI were related to nutrition labels on the alcohol bottles themselves, so that was one that you would think would be very easy to do, but isn't necessarily something that has gained a lot of traction. Are these policies directly related to a reduction in either cancer risk for cancer mortality? That's a very difficult question because we need long term studies to see that because cancer is a very long process. However, some of the initial studies that we have coming out, one of them coming out of Boston University shows that the more stringent your alcohol related policies are, there is an association with lower risk of cancer and they see a 10 percent increase in their stringency of those policies leads to reduction also in risk and mortality. These are some of the initial studies that are coming out again, these are associations, cross cutting they're not longitudinal, but we do have those things that are in the work and getting started on that will show us these associations and if they play out in the long term. Now, that being said, what we do know is, what do stronger alcohol policies do in general? Those reduce the consumption in the overall population, which reduces our risks to any number of things, whether acute processes like drink driving or longer term processes like cancer, so it reduces our risk in the population overall. If it plays out in these other ways that it has, we should see that there would be an association in the long term with reduction in cancer risk. For that study that you mentioned looking at stringency of policies and I forget if you said cancer risk or mortality, but was that for all cancers or was for that breast cancer in particular? To that question, yes, with every sub type that they looked at, it was associated with a lower association in mortality. Fair enough. I think this might be an interesting point for our audience also. We're talking very specifically about the link between alcohol use and breast cancer, but alcohol is closely associated with a total of seven cancers. Thank you so much Raime. Let's move on a little bit with the bit of time that we have left to talk about what we know about alcohol's impact in the presence of breast cancer. Because now we've been talking about alcohol leading up to it. I've been talking about the primary prevention side, let's talk a little bit about what we know about, what happens in the context of a breast cancer diagnosis? Can you tell us what we know about alcohol use either before or after a breast cancer diagnosis and its association with the risk of either recurrence or mortality from breast cancer? Yeah. Very interesting question to area of active investigation at the moment. Yeah. As we know that the most research of alcohol and breast cancer has focused on the risk of incidence and it is not yet very clear how over men's drinking history or the trajectory of drinking, if you will, during her lifetime, impacts her course of disease after a diagnosis. There's just a few studies in this space and the data, again, is not really consistent. But there are some studies that are compelling and one of them is the latest study, which is life after cancer epidemiology study, and it looked at a cohort of about 2,000 women that are recruited from the Kaiser Permanente Northern California Registry that uploaded that consumption of about more than three or four drinks per week increases the risk of breast cancer reoccurrence by 30 percent as well increases the risk of breast cancer mortality by 50 percent. This risk was even more pronounced in postmenopausal and obese women. There's another very compelling study from out of the Fred Hutchinson Cancer Center and that primarily focuses on a cohort of 17,000 women with hormone-positive, that's the ER positive disease. From that 17,000 cohort of ER positive women, the selected or maybe the eligibility criteria was able to put together a cohort of about 500 women that had had contralateral breast cancer, which means there cancer in the other breast. What they found was alcohol consumption of seven or more drinks per week increases the risk of contralateral breast cancer by 90 percent. Of course, this risk was higher than the first breast cancer. The primary breast cancer was ER positive. Is all that? Yeah. But there are a few studies like there was a small study from the Moffitt Cancer Center which did not see any association with disease-free survival and in an adjuvant setting for alcohol consumption but the limitations of these studies are that they have only considered alcohol drinking during 12 month preceding the diagnosis. There are caveats like that as to when the drinking patterns were considered and also are you looking at post-diagnosis drinking and because you're not drinking, habits change and people just get scared and they think that if they stop now then everything is going to be written off. Those behavioral changes are also important to capture. Then many of these studies haven't taken into account subtype, which is very important. Another caveat that I feel is treatment information because treatments are also so and some are considering all-cause mortality, which is mortality from several non-breast cancer outcomes. There's a lot of players variables that have to be accounted for robust a clear answer. Yeah. Of course, there's a lot going on. You mentioned treatment. Do we know about how alcohol use may interact with treatment among women with breast cancer? Yes. Very good question but we have no information about that. I know and that's my area of interest and designing some studies in animals that are looking at treatments, efficacy is reduced if they are consuming alcohol so we're feeding alcohol to mice and trying to see if we have any answers there. Yeah, that's great. That seems so relevant because that leads me into my next question. What do we say to our breast cancer patients when they come in with a diagnosis and whether or not they're going to go into treatment? What do we tell them about drinking? At this time, and I think it's a really important point that a lot of these studies are limited by not looking at the life course of drinking. Because we know, like we talked about earlier, the window susceptibility and how that's often at a younger age and so that can carry forward with us. But what are we telling them when they are in clinic? From what I know among my teams and the clinicians, and the oncologist and the surgeons, there are no current guidelines about how we talk to patients about alcohol consumption, the norms, guideline so far. Another wow. I think that touches on the overall awareness and conversation. We're not really having conversations about this and all these areas that we could further drink less for your dress campaign, for your breast campaign to use. In the preparation for it, we did a survey assessing health literacy and how are young women got health information because we thought that that would inform how we do our campaign. I think it was over 50 percent reported that if they wanted to learn information about alcohol use and breast cancer, that they would go to their health care provider. This was from women all over California. I thought, oh my God providers have a real opportunity here to impart this information to their patients. It sounds like developing some guidelines, some resources for them on how to do that would be really vital. To end our time together in this really interesting conversation, I'd like for each of our panelists to say a one line take-home message for our audience to take away from this talk. So I'll start with Dr. Rasanayagam Thank you. Yeah, I always like to end with more of a positive note. I do think the more alcohol you drink, the higher risk of breast cancer. That also means the less you drink, you can lower your risk. Even though not drinking at all would be best, any reduction in alcohol consumption will decrease your risk of breast cancer. Try moderate as much as possible. Thank you. I will also point out that that is part of the premise of our drink less campaign. We're seeing drink less for your breast, not don't drink. Because we recognize two realities, one, women drink alcohol and it's part of our culture and two, the drinking less does meaningfully decrease your risk of breast cancer. Thank you. Dr. Reynolds. Well, maybe this isn't very original. But since this is one of only a very few established risk factors for breast cancer that is under individual control, and the message is pretty clear that for this, not to mention other health outcomes, less is better. Thank you. Dr. Aneja. Yes. So mine is similar. Boos bumps, breast cancer risk. It's like the BBB, boos bumps, breast cancer risk, and every drink matters. So less is better. Brilliant. Dr. Eck. I like going last because sometimes it's easier just to say ditto. All these things that before me, but the one thing I really focus on is that we do have some control here. You're not left feeling helpless. Both for as an individual, you have some control over this. Just knowing about it, I think can give you a little bit more control and then making a plan to do something about it if you think you might want to. But then also at the higher level, the community level, at the state level, at the population level, we do have these interventions then have a very broad reaching effect, not on other types of alcohol related harm, but very specifically can affect our risk of breast cancer. We're not left feeling helpless. We do have things that we can do now and more as the research progresses. Wonderful. Thank you so much for doing this with me all of you. I know, all of you professionally, so this was just a real treat for me to get to spend time with you. I hope that for the audience that this was useful and informative and drink less for your breasts. Thanks everyone.
