Tyrer-Cuzick IBCIS risk assessment questions
In addition to LCIS, I have atypical hyperplasia. I'm 58. I took Tyrer-Cuzick test and reviewed the results with a breast surgeon. I was expecting lifetime breast cancer risk of 20% - 40%, which is what most research and cancer organizations typically state.
My genetic testing shows no BRCA genes; no previous cancers; no relatives with breast cancer (paternal grandmother died of ovarian cancer at 84); not overweight at all; started periods at 15 (rather late), menopause at 48 (rather early); no HRT.. Those factors should not elevate my risk a lot. No kids, which does elevate risk. Heterogeneously dense breasts which do elevate my risk. I inputted that I have atypical hyperplasia and LCIS. I think I am fairly average with my inputs for someone with LCIS.
It came back with 10-year risk of 30% and lifetime risk of 60% if I live to 85. The 60% lifetime is "Angelina Jolie, lop 'em off" stuff. Nothing in the general literature about LCIS says lifetime odds are against you. On the contrary, almost everything says "Most women with LCIS will never get cancer." That means under 50% to me. Nothing I have ever read or heard previously indicated a lifetime risk of over 50%.
The surgeon overseeing this process confirmed my inputs and this output. I did not screw up and put in something wrong.
So I do some research on the Tyrer-Cuzick IBIS (International Breast Cancer Intervention Study) model. The results and conclusion are shown in the next lines in bold.
My questions: HAVE ANY OF YOU HAD A SURPRISINGLY HIGH LIFETIME RISK %S FROM THE TYRER-CUZICK MODEL? ARE THE TYRER-CUZICK RESULTS TO BE RELIED UPON OR ARE THEY INACCURATE FOR THOSE WITH LCIS?
RESULTS:
Over a median follow-up of 14.6 years, 64 (19%) of the 331 women developed invasive breast cancer. In the first 10 years after biopsy, 31 women developed invasive breast cancer whereas the Tyrer-Cuzick model predicted 58.9. The observed-to-predicted ratio was 0.53 (95% CI, 0.37 to 0.75). The concordance statistic was 0.540, revealing that the Tyrer-Cuzick model did not accurately distinguish, on an individual level, between women who developed invasive breast cancer and those who did not.
CONCLUSION:
The Tyrer-Cuzick model significantly overestimated risk of breast cancer for women with atypia, and individual risk estimates showed poor concordance between predicted risk and invasive breast cancer development. Thus, we cannot recommend the use of the Tyrer-Cuzick model to predict 10-year breast cancer risk in women with atypical hyperplasia.
(Other studies I have seen have cited this shortcoming as applying to LCIS as well.)
Below is the study and authors:
J Clin Oncol. 2010 Aug 1; 28(22): 3591–3596.
Published online 2010 Jul 6. doi: 10.1200/JCO.2010.28.0784
PMCID: PMC2917314
PMID: 20606088
Evaluation of the Tyrer-Cuzick (International Breast Cancer Intervention Study) Model for Breast Cancer Risk Prediction in Women With Atypical Hyperplasia
Judy C. Boughey, Lynn C. Hartmann, Stephanie S. Anderson, Amy C. Degnim, Robert A. Vierkant, Carol A. Reynolds, Marlene H. Frost, and V. Shane Pankratz
Comments
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I think we all know that none of the risk assessment tools are accurate, but they are useful in giving you a general idea of the seriousness of the condition.
I ran the Tyrer-Cuzick test and came back with 72 to 78 percent lifetime risk. Yep, that is up there in Angelina Jolie territory. Even if the model is only half right, it is telling me there is a serious risk. I have some breast and ovarian cancer in my family and extremely dense breasts which I think was the reason for the high risk result.
Some literature says that a diagnosis of LCIS “seldom” leads to invasive cancer which sounds to me like it should be a less than 10 percent correlation. Other literature says that “most” do not go on to get invasive cancer which sounds to me like it is less than 30 percent. I am concerned that the websites making these statements do not take the LCIS condition seriously enough.
The IBIS tool has been changed and updated since that study. It also seems to be the only one which takes the LCIS diagnosis into account in determining risk. I don’t know whether it is entirely accurate, but what I do know is that I had a significantly higher risk than I had previously thought based on the “seldom” and “most” comments.
I am willing to believe that my lifetime risk was somewhere between 40 to 80 percent. That is still too high for me. I chose PBMX and am happy with the decision. However I completely understand and respect other people who have chosen to deal with their condition in a different way. We all have to do what we feel comfortable with based on our own unique circumstances and shouldn’t let other people’s opinions stop us from doing what is best for ourselves.
I found this article which looks at the accuracy of the various models and the circumstances in which each model works best
https://academic.oup.com/jnci/article/102/10/680/2515894
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Thank you, Mammabear, for the response and link. May I ask how long after your LCIS diagnosis did you get the PBMX? The fact that you are happy with that decision makes me think it went well. Great!
The studies I have read that show what percent of those with LCIS get breast cancer after 5, 10, or more years after diagnosis with or without chemoprevention, etc. never reach beyond 50% getting cancer. Some go as high as 40%. So the data itself seemed to support the 20%-40% lifetime risk. Mayo currently shows 20% lifetime risk; this site, breastcancer.org, shows up to 40% lifetime risk in the info section; National Cancer Institute has 25% lifetime risk; In addition, all medical personnel I have consulted (2 surgeons, family doc, oncologist) all feel PBMX is definitely not warranted given the risks. One of the surgeons even confirmed that lifetime risk is 25% - 40%, before I did any personalized risk assessment.
BUT If the true lifetime risk for real-life women who do not have a lot of unusually high risk factors is really in the 60% to 70%+ range, then this disparity in information and advice is STAGGERING and can be life threatening.
Crucial decisions about our health and longevity need to be based on reliable evidence, which seems to be absent or at least grossly conflicting.
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Hi Lea
I had the PBMX about 2 months after the LCIS diagnosis. I spent that time researching everything I could possibly find, doing genetic testing (negative for BRCA), having very long discussions with my surgeon (who respected my decision but wanted to make sure I was fully informed) and seeing another surgeon for a second opinion. The second surgeon would not operate without me having a meeting with a psychologist. I didn’t see a psychologist as I was very clear with my decision, but I can see that it might help put everything into perspective.
I found talking to my immediate family very helpful (spouse and teenage children), but talking to extended family was not so useful. If they haven’t done the proper research they just do a quick google search and come up with the “seldom” line and it is exhausting trying to educate them that it might not be that straightforward. I only told a very few people about my surgery and I am very glad I kept it to myself as it makes it much easier to get back to normal when it is not being talked about (and I don’t have to constantly justify my decision).
The Bmx went really well. Of course it was difficult at first when I got out of hospital but after 3 weeks I started to feel more normal, and after 3 months was back to full strength. Of course there are things that will never be the same. The loss of sensation is something which I hadn’t really thought about before the mx, but it is probably the worst part. I also feel uncomfortable when I lie on my stomach. However there are some seriously good things. I had nipple sparing, direct to implant and went down in size from DD on one side and C on the other to C on both sides and I think they look much better than they previously did. I had previously had lots of biopsies which resulted in odd shaped breasts, so it is great to have an even pair. It is great not to have any breast pain or painful lumps for the week before my period, and the thought that I never again need to have a mammogram is liberating.
So back to the statistics... I have read and re-read the statistics and studies. I try to follow the research methodologies to see if I can explain why there seems to be such a discrepancy. What I have come up with is that I think the 1 percent risk per year is too low. The 29 year longitudinal study didn’t actually follow women for 29 years (most women were followed up for much shorter period). It came up with 2 percent risk per year, but that included the women on chemoprevention so the risk for surveillance only must be significantly higher. They also “censored” women who subsequently chose BMX (no idea what that means). They also excluded women who had a LCIS diagnosis, but then relatively quickly went on to get “something worse”. However in the real world that is actually something that could have happened to me, so I would want to know about it! Even your study on the accuracy of the IBIS showed inaccurate results based on the 10 year anniversary, but was much more accurate when you looked at the 14.6 year figures. The studies also only count diagnosed cancer, so it is possible that many of the “cancer free” statistics could actually have invasive cancer lurking but just undiagnosed.
What we want to know is what is the risk for us, and the 5 and 10 year statistics aren’t that relevant. I would like to know my lifetime risk, and I have every intention that my lifetime will be until I am at least 90 years old, so a 10 year risk is only telling a small part of the story. However,the studies seem to show that we have time to make a proper decision. It rarely immediately moves to invasive, so we can take time to make a well thought through decision which we will (hopefully) never regret.
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This is a study about the modified Gail model, which automatically excludes LCIS women. The modified Gail model is widely used in the general population. But if they have this much uncertainty in predicting which individual women will get breast cancer in the general population, just think how much knowledge they have about a condition as unusual as LCIS...
https://academic.oup.com/jnci/article/98/23/1673/2...
So I learned that the risk of breast cancer in a population of people is MUCH easier/more accurate to predict than the risk of breast cancer in an individual woman.
At one point I got almost 90% lifetime risk from this Hall's calculator http://halls.md/breast/risk.htm
and my risk estimate from a tertiary hospital that is NCI-approved said I had 'between a 10% and ?70%' (I can't remember the 2nd figure, but it was something like that) 'lifetime risk. If I had to guess it would be closer to 10% than' 70% (or whatever the upper number was.) 'If I want a more accurate figure then you'll have to go to the literature.'
NOTE: that a 10% lifetime risk is LESS than the risk of the 'average' woman in the USA, which is about 1 in 8, or about 12%. But why quibble when the modified Gail model gives incorrect predictions for individuals about 40% of the time?
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Mine came up at 80%, but the geneticist says it is probably closer to 20-25
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I do know the Gail model excludes those with LCIS. 10% - 70% where 10% is below the average population raises questions about that model. Gail is incorrect 40% of the time? Really? Then it is not a model, just a guessing game. I think the algorithms that throw ads onto my computer screen when I am online do a better job than 40%. Thanks for sharing that, Leaf!
80% but really 20-25%? How utterly useless for your decision-making, MelissaDallas. But I can think of a very useful purpose for these models. HIgh #s help with insurance coverage of MRIs.Thanks for the thoughtful followup Mammabear. I agree that the 10 year longevity is nowhere near as relevant to me as lifetime. If I were much older, then maybe 10 years would be more meaningful. In that 29-year study you mention, I believe none of the double mastectomies got cancer.
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I just realized after the fact that I probably should include a link to this Tyrer-Cuzick IBCIS risk assessment model that is being discussed. This is version 8, the most recent version that I know of.
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Lea, I get 26.5 lifetime on that one WITH an ovarian cancer history, though the type I had is not a cancer syndrome type. Pretty close to what I was told. About twice average risk
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Thanks for reporting that Melissa. All the post-menopausal hypothetical women I entered with no risks other than LCIS, meaning very favorable made-up inputs, were over 40% lifetime risk, most in the upper 50%s to 60%s. If I put them on a strict diet so that they weighed 125 lbs or less, I could get the lifetime risk to go down, though.
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I put in age 56, 5'3", 220 pounds,first period at age 10, no live births,menopausal, no HRT ever, positive history of ovarian cancer at 49, tested history negative of BRCA, breast biopsy positive fo LCIS
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So Lea,
i don't understand ypur results, because I have many inputunfavorable factors, such as obesity and positive history of ovarian cancer.
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I think the reason I had been coming up with such high risk is because of the combination of extremely dense breasts and LCIS. All the other factors (age, weight, family history) don’t seem to make very much difference, even the LCIS on its own still had the risk below 40 percent. It was when I added in the dense breasts that the risk skyrocketed past 70 percent.
The National Breast Cancer Foundation website which seems to equate the risk from having dense breasts as being somewhat equivalent risk to having BRCA mutations. This is something that I hadn’t really comprehended before
I wonder how many people with LCIS also have dense breasts? If so, it could explain the high risk numbers coming up on IBIS.
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By George, I think you have hit on something Mammabear. Damn dense breasts.
This would make sense.
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By George, I think you have hit on something Mammabear. Damn dense breasts.
This would make sense.
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I'm going to try tomorro because I think the test was loading weird or acting weird when I used it today.
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I did the risk calculator too, with LCIS, ALH, heterogeneously dense breasts, significant family history (mother, aunt and grandmother), no kids, early surgical menopause and estrogen replacement therapy and it came up with a 63.9% lifetime risk. Too darn high for my liking
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I did 12 scenarios of different women, 11 of the scenarios have been diagnosed with LCIS, all using version 8 of IBIS. The lifetime risk of bc was over 50% for 10 of the 12 scenarios, and 2 were upper 40s%. Very few of these scenarios had any other high risk factors. Case 8 had no LCIS but some other high risk factors. Case 12 had very dense breasts as an added risk factor.
If this highly praised model is indeed fairly accurate, then all the breast cancer sites (including this one) that cite the 20% to 40% lifetime risk are way understating the risks. Because this IBIS model was faulted in a study for overstating hyperplasia, none of my scenarios included hyperplasia.
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I am 42 years old, dense breast, LCIS (diagnosed 2/2018), menarche 17, still menstuating, 4 kids. My risk was 67%! I havent even been geneticly tested yet! I almost fainted!
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I am 42 years old, dense breast, LCIS (diagnosed 2/2018), menarche 17, still menstuating, 4 kids. My risk was 67%! I havent even been geneticly tested yet! I almost fainted!
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Lea
What do you make of the fact that all the risk factors considered in the Tyrer-Cuzick assessment were the very same risk factors that were thought to NOT influence cancer risk in the 2015 29 year longitudinal test on LCIS. In that review, it was concluded that family history, age at diagnosis, breast density, menopausal status, and presence of atypical hyperplasia, among others, were not considered risk factors. Only tumor volume (number of slides with LCIS to total number of slides) was significantly greater in women whose disease progressed. What am I missing ????
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What good questions, Barbara1120. I wish there were some experts and researchers who would delve into these types of questions and issues and then publish their results for all to see. Instead, it's ladies with LCIS and a spreadsheet but no medical background.
Family history: Looks like family history is excluded from this Tyrer-Cuzick IBIS model when LCIS is present because my risk did not change between no family history and entering 7 female family members with no breast cancer. I just did a profile of a woman with LCIS with no family history entered. Then I gave her 5 of her closest female family members with breast cancer. No difference in bc risk.
Result: IBIS is consistent with the 29-year longitudinal study; family history was not a factor in determining breast cancer risk when LCIS is present.
Age at diagnosis: While we enter the age for the IBIS model, it is not age at diagnosis, but current age. So age at diagnosis is not part of this model.
Result: IBIS is consistent with the 29-year longitudinal study; age at diagnosis is not a factor in determining breast cancer risk when LCIS is present.
Breast density: This seems to be a huge factor in this IBIS model, resulting in 30 or more percentage point swings, depending on the level of density, all other variables being constant. When I used the lowest of the 4 BiRads breast density ratings, which is "fatty," the lifetime risk %s for women with LCIS did fall under 40% for most of the trials I ran. But only about 10% of women have the lowest density rating of "fatty" breasts.
Result: IBIS is NOT consistent with the 29-year longitudinal study, which states breast density does not affect breast cancer risk when LCIS is present. In contrast, breast density is a heavily weighted factor in the calculation breast cancer risk in the IBIS model.
Menopausal status: Risk did not change when I changed only menopausal status. Comparing a woman at 61 who had not yet gone through menopause (???!!!) with a 61 year old who had gone through menopause at 47, produced the same breast cancer risk. So menopausal status is not part of this model.
Result: IBIS is consistent with the 29-year longitudinal study; age of menopause is not a factor in determining breast cancer risk when LCIS is present.
Presence of atypical hyperplasia: Lifetime risk did not change when hyperplasia was present along with LCIS. I have ALH and checked the box on my profile. No difference for me when I removed that check. No difference in other trials with or without the ALH box checked, when LCIS is present.
Result: IBIS is consistent with the 29-year longitudinal study; atypical hyperplasia is not a factor in determining breast cancer risk when LCIS is present.
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A little more on the breast density...
Only breast density changed in these 4 trials of a 48-year old with LCIS, using the Tyrer-Cuzick IBIS risk assessment.
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Lea,
Holy smokes! Your work on this is impressive - thank you for taking the time to perform this exercise. I was aware breast density was a risk factor, but was absolutely clueless as to how critical it appears to be in the whole mix of risk factors. Really appreciate your brining this to our attention.
Barbara
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But we srill know that the predictor tools are highly innaccurate because in reality the true numbers are closer to 20-30%
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Very interesting! Good questions and great work, Barbara1120 and Lea7777. My question my be a little off topic since it's not about the Tyrer-Cuzick tool, but it is about the findings of the study 29 Year longitudinal LCIS study Barbara mentioned. In regards to predicting LCIS progression to DCIS or invasive cancer, the only factor that was found to be relevant was the volume of disease (defined as the ratio of LCIS slides compared with the total number of slides taken). My question: did any of you find that data (the ratio indicating volume of disease) in your pathology report? I find the total number of slides in my report, but nothing indicating the number of LCIS slides. It seems like this is a number which should be reported by the pathologists due to the importance of its predictive value. Just curious what others found in this regard
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Digging a little deeper into this IBIS model I found this at http://www.ems-trials.org/riskevaluator/
Description of breast cancer risk program
The program assumes that there is a gene predisposing to breast cancer in addition to the BRCA1/2 genes. The woman's family history is used to calculate the likelihood of her carrying an adverse gene, which in turn affects her likelihood of developing breast cancer. The risks of developing breast cancer for the general population were taken from data on the first breast cancer diagnosis (ICD-10 code C50) in Thames Cancer Registry area (UK) between 2005-2009. The risk from family history (caused by the adverse genes) is modelled to fit the results in "Familial Breast and Ovarian Cancer: A Swedish Population-based Register Study, Anderson H et al., American Journal of Epidemiology 2000, 152: 1154-1163".
The risk from other classical factors including age at first child and benign disease are combined with familial risk. (my italics)
The latest version of the model (v8) incorporates mammographic density.Contact Details
Prof. Jack Cuzick
Centre for Cancer Prevention,
Wolfson Institute of Preventive Medicine,
Charterhouse Square,
London
EC1M 6BQemail: riskevaluator@ems-trials.org
This states familial risk is included, but it never made a difference for those with LCIS in the trials I did, even when 5 close female family members had breast cancer vs. no family history entered. When 7 close female family members with no cancer were entered the risk was no different than if no family history was entered. The 29-year longitudinal study stated family risk was not a factor.
This states benign disease is included, but it never made a difference in bc risk for those with LCIS in the trials I did, whether atypical hyperplasia was checked or not. The 29-year longitudinal study stated family risk was not a factor.
This states age at first child is included, but it never made a difference in bc risk for those with LCIS in the trials I did. I used different ages for first child, but all before age 30, some were childless.
I also included varying ages of first menstrual period from 11 to 17 for those with LCIS--no difference in bc risk; varying ages of menopause from 47 to 54 for those with LCIS--no difference in bc risk. This model does not specifically tout duration of menstruation as a classical factor that is incorporated. The 29-year longitudinal study stated age of menopause is not a factor.
A diagnosis of ovarian cancer at any age made no difference in bc risk for those with LCIS. This model does mention ovarian cancer from a Swedish study.
Using Hormone Replacement Therapy for more than* 6 years in the past with a projection of more than 6 years into the future made no difference in bc risk for those with LCIS. That would indicate you can pop those Premarin pills for a lifetime, ladies, with no impact on your bc risk. Really?
The conclusion that I, a layperson, draw is that LCIS and breast density trump all in the Tyrer-Cuzick IBIS model and other factors have no impact on breast cancer risk. The other inputs appear to be disabled in this program when LCIS is included.
These findings do not support the description of the model that states it incorporates specific classical factors. How can that be? Especially when women with LCIS have no other model to use of course we will think that these classical factors are being included for us when it states they are. How many people take their Saturday night doing dozens of input trials to determine which factors are used and which are not? That's asking too much of the user.
Either the IBIS description needs to be modified to indicate other classical factors are excluded or are immaterial for those with LCIS OR the model is not functioning correctly.
Either this is a valid model which helps inform important life decisions (and it is the only show in town because no other current model incorporates LCIS) or it is too inaccurate to rely upon. We are not using this model as a silly parlor game, nor are the professionals we consult from breast surgeons to genetic counselors, who have used this model with me. Are we supposed to just shrug and figure, "You get what you pay for"? Should we lump this in with other freebie surveys on the Internet? Our medical providers who use this obviously place trust in the inputs and outputs.
* Not to be the nit-picky grammar police, but in the HRT section of the program, it has an option of "more then 6 years" for two separate inputs. It should be "more than 6 years." While mixing up an e and an a does not invalidate a logarithm, it does show a lack of attention to detail and makes me wonder if such lack of attention to detail has permeated the whole damn thing.
We deserve accurate information and I am certain those working on this model wish it to be a useful tool and not a frivolous Internet survey game. Professor Cuzick, or whoever is on the other end of riskevaluator@ems-trials.org is getting an email from me.
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"My question: did any of you find that data (the ratio indicating volume of disease) in your pathology report?"
No, but I will ask.
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Nor did my pathology report provide any information on slides - neither total number nor the number that had LCIS. I looked again this morning and did not see either piece of information but I will asking for it this week.
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Personally, I think that at least a good part of the problem is that for us LCIS women, they need to compare a model's prediction to an actual population of LCIS women. Factors that change our LCIS risk profile may be different than those in other higher risk populations. We don't have a lot of studies that detail other potential risk factors LCIS women may have.
The LCIS picture may also be more complicated: if you go on to get invasive breast cancer where you had a spot of LCIS, you may have different pathology than if you get invasive breast cancer at a place that looked totally normal in the past.
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"The conclusion that I, a layperson, draw is that LCIS and breast density trump all in the Tyrer-Cuzick IBIS model and other factors have no impact on breast cancer risk. The other inputs appear to be disabled in this program when LCIS is included."
While it is disheartening to think that LCIS diagnosis + breast density = our fate and that other factors, except to some extent our size, play no role...if that is the reality, then that should be made clear to those of us with LCIS. The lack of other classical factors' effect on bc risk when LCIS is present, also makes me wonder if factors over which we do have more control like diet, alcohol intake and exercise make a much of a difference with this diagnosis. Of course indirectly, diet and exercise affect weight. And a healthy lifestyle generally decreases breast cancer.
But if 12+ years of hormone replacement therapy has NO EFFECT on breast cancer risk when LCIS is present, according to the IBIS model, I wonder how eating salads and drinking Brassica tea instead of martinis will change our outcomes? Or is this model not working as it should?
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