High Risk - means what? How much time before you could have "c"

someone_in_nj

High Risk - means what? How much time before you could have "c"

someone_in_nj

can someone enlighten me with their experience please.

If you were told you are at high risk - did you get cancer? and how long after you were told?

DiveCat

In my case I was "high risk" due to family history, so my experience may differ from someone who is told they are "high risk" due to other factors, such as having LCIS or other atypical conditions, whose risk comes from mantle radiation, and so on.  My assessment came from a couple different genetic counselors, after genetic testing and based on my family history. My risk was estimated at a 40% lifetime risk.

I had a prophylactic mastectomy and pathology came back clean (no cancer, only other hormonal changes). But, I am 34 and a lifetime risk is exactly that, a lifetime risk and it is not 100%. I may have never got breast cancer, I may have got it at 70, or in my 40s like my relatives, or in 2 years. And, quite frankly, as a mastectomy does not remove all risk, I still may get breast cancer (however, my risk has now been reduced significantly and my risk is now estimated to be below average).

Being high risk is not a guarantee you will get cancer, and if you do get cancer there is no real way to determine "when" it would happen. It's a guesstimate at best (say for example you have a family history of early onset breast cancer, in one's 30's and 40's, you may be able to guesstimate that IF you did get cancer, you have a higher chance of also having early onset breast cancer, but again this is STILL not a guarantee you will get cancer, or that if you do you would get it at the same age as your relatives).

leaf

I think that the term 'high risk' is used loosely. Maybe they have to use this kind of terminology to get funded, I don't know.  I think the science of breast cancer prediction is in its infancy.

This paper looked at the Tyrer-Cuzick, the BRCAPRO, and the Claus   models.  It found each model found a different group of patients, and only 0.2%of the group tested as 'high risk' in all 3 models.

http://cebp.aacrjournals.org/content/22/1/146.long

This abstract referred to high-risk breast lesions, including flat epithelial atypia,
atypical ductal hyperplasia, lobular neoplasia, radial scar, papillary
lesions, and mucocelelike lesions, after diagnosis with core needle
biopsy. http://www.ncbi.nlm.nih.gov/pubmed/22268202

I have seen papers that classify ADH and ALH as 'high risk' lesions, and, although the numbers are very soft, I've seen numbers that roughly estimate these women has roughly a 15-25% lifetime risk.   With classic LCIS and a weak family history, I was given about a 30-40% lifetime risk.  With some deleterious single BRCA mutations, some women have up to about a 90% lifetime risk.  

I don't think that women in a 15-20% lifetime risk category  (especially when the 'average' lifetime risk of a woman in the US is about 13-14%) are in the same ballpark as a woman who has a 90% lifetime risk.

DiveCat

leaf, 

Where I am, 15-20% is more of a "above average/moderate" risk and they aren't recommended to get high risk screenings, preventative surgeries, and so on. High risk recommendations here start at 20-25%, but even then things like preventative surgeries at that 25% are more on a "case by case basis" rather than "recommended" as they might be for someone with an 80% lifetime risk. The higher risk of "87%" for breast cancer in BRCA+ women is actually based on the original studies which involved certain mutations, and certain families. Now they know that is not the case for all families/carriers (http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA):

Breast cancer: About 12 percent of women in the general population will develop breast cancer sometime during their lives (4). By contrast, according to the most recent estimates, 55 to 65 percent of women who inherit a harmful BRCA1 mutation and around 45 percent of women who inherit a harmful BRCA2 mutation will develop breast cancer by age 70 years (5, 6).

Ovarian cancer: About 1.4 percent of women in the general population will develop ovarian cancer sometime during their lives (4). By contrast, according to the most recent estimates, 39 percent of women who inherit a harmful BRCA1 mutation (5, 6) and 11 to 17 percent of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by age 70 years (5, 6).

It
is important to note that these estimated percentages of lifetime risk
are different from those available previously; the estimates have
changed as more information has become available, and they may change
again with additional research. No long-term general population studies have directly compared cancer risk in women who have and do not have a harmful BRCA1 or BRCA2 mutation.

It
is also important to note that other characteristics of a particular
woman can make her risk higher or lower than the average risks. These
characteristics include her family history of breast, ovarian, and, possibly, other cancers; the specific mutation(s) she has inherited; and other risk factors, such as her reproductive history. However, none of these other factors is as strong as the effect of carrying a harmful BRCA1 or BRCA2 mutation.

The "average risk" covers the risk for ALL women in the population, so it is skewed by those who are high risk, and those who are very low risk. The individual "base risk" for most women is actually a lot lower than the average, like 3-4%.

I think a lot of the differences between the three models in assessments is also greatly explained by the factors they consider. Using the Claus model for example, many women who come from families with male breast cancer, or ovarian cancer, or more than 2 relatives, would potentially be assessed as lower risk they they might really be (from the study you linked):

The BRCAPRO model requires a family pedigree as the only input, including age of the individual, ages of relatives, age of
onset for particular cancers, and ethnic heritage. This model is designed to predict who is a BRCA-1 or BRCA-2 gene mutation carrier and who is at the risk of developing breast and ovarian cancer. The BRCAPRO model is based on a Mendelian
approach that assumes an autosomal dominant pattern of inheritance.

In contrast, the Tyrer-Cuzick model
includes family history and a number of other inputs: the individual's
age, family history
of breast and ovarian cancer, age at menarche,
parity, age at first childbirth, age at menopause, use of hormone
replacement
therapy (HRT), Ashkenazi Jewish heritage, history
of breast biopsy and atypical hyperplasia, lobular carcinoma in situ (LCIS), height, and body mass index. The model is a statistical model based on the Mayo Clinic Benign Breast Disease cohort,
which is made up of 9,376 women, age 18 to 85 years, who had an open breast biopsy between 1967 and 1991.

Finally, the Claus model includes the
number of first- and second-degree relatives with breast cancer and the
age of cancer
onset. The Claus model was developed from the
cancer and steroid hormone (CASH) population-based, case–control study
involving
4,730 patients with histologically documented
breast cancer and 4,688 matched controls. This model is based on the
premise
that breast cancer risk is transmitted as an
autosomal-dominant trait and bases the statistical calculation on the
genetic
relationships between the affected relatives and
the woman in question.

In terms of outcomes, the lifetime risk of breast cancer estimated by the Tyrer-Cuzick and Claus models includes the risk
of both invasive breast cancer and ductal carcinoma in situ (DCIS), where BRCAPRO predicts only the risk of invasive breast cancer.

.....

The widely
used version of the Claus model uses family history
of only female breast cancer in up to 2 relatives. While a modification
of the Claus model includes ovarian cancer, we did
not use that model and instead used the model put forth in the ACS
guidelines
and used by the ACRIN 6666 clinical trial

I was assessed with both BRCAPRO and Tyrer-Cuzick and my results were quite comparable between them with the Tyrer-Cuzick being a bit higher. The Tyrer-Cuzick allows a lot more detailed input and I saw how those factors like parity affected the results and of course if it considers risk of non-invasive cancer that may also explain the higher result. My counselors also referred to Dr. Narod's studies of BRCA-negative families with multiple cases of breast cancer, which found around 40% risk for non-affected relatives. In my own family it is likely there are polygenic factors at play (and I have had other testing for research purposes which supports this likelihood...but there are no clinical guidelines in that case at this point and they just refer to family history).

All that being said, I agree prediction is in its infancy. I just did not feel comfortable waiting for it to grow up!

edwards750

Neither my sister and I had the genetic test. We both got BC. Our mother had BC in her late 60s. She died 10 years ago but not from BC. My ONC said 70% of BC cases were not from high risk. 1 in 8 women will get BC. Genetics notwithstanding, we just got an unlucky draw. So try not to worry before if has even happened, save that for when or if it does. I will say that if I knew I was carrying the gene I might have had a MX before I was DX 

Diane 

DiveCat

90% of breast cancer cases are sporadic, leaving about 10% to be hereditary.

Only about 25% of hereditary breast cancer is due to a BRCA-mutation. If you come from a family with high rates of breast and/or ovarian cancer and none of those affected members are BRCA+, you may still be at high risk for hereditary breast cancer. BRCA-mutations do NOT explain all hereditary risk. There are other potential mutations, or maybe yet to he discovered mutations/genes. This is why it is very important to talk to a genetic counsellor or other genetics expert. I have seen way too many oncologists, OB/GYNs, family doctors either grossly overestimate OR underestimate risk. Having two primary relatives (like a mother and sister) with breast cancer is one of those factors that can "flag" cancer as hereditary, be it due to a BRCA mutation or otherwise. 

For some of those who do not come from BRCA+ families but do have a strong family history (or just don't know as no one has been tested), being told "not to worry until or if it happens" can seem a little patronizing and dismissive. Especially as many of us have dealt with that in the medical community already because many non-genetics experts have little understanding of hereditary risk, or that it can exist without BRCA. And wait for what? Until I too get diagnosed with advanced cancer and face a future of metastatic disease like my loved ones?  My mother was originally told she was at lower than average risk (6%) by an oncologist, though her mother (who had two primaries) and two grandmothers both had breast cancer, all between 48-60. 2 of them died of it, one later died of colon cancer. My mum was diagnosed with Stage III ILC at 48, and now has metastatic breast cancer 8 years later. I will always wonder what the outcome may have been if she had been recommended for annual MRIs (her mammograms missed it) or been advised of her risk by a genetic counsellor and given options of Tamoxifen or surgery.  While no guarantee, it might have meant my mother would be in a very different position today. 

I don't mean to sound prickly, but the only way someone can know whether or not to be concerned about their own risk if they have a stronger family history is to talk to a genetics counsellor/expert. They may indeed still qualify for high risk screening (like MRI) and preventative measures (like chemo prevention or surgery), qualify for genetic testing (BRCA or other genetic testing) and so on. Or maybe they will be assessed as average or moderate risk, and really can just not "worry", and instead follow the recommendations for the average risk population. 

leaf

Hi DiveCat,

I think you know a lot more about hereditary breast cancer factors than I do, and corrected my numbers, but I think we basically agree.  Thank you for your additional info about the family history factor that I didn't know.

leaf

I, too, thought the Gail model was fine.  Of course, it automatically excludes anyone with DCIS, LCIS, or invasive breast cancer.

But, even for the 'average' woman in the USA, note the fine printl:

Although a woman's risk may be accurately estimated, these predictions do not allow
one to say precisely which woman will develop breast cancer. In fact, some women
who do not develop breast cancer have higher risk estimates than some women who
do develop breast cancer.

http://www.cancer.gov/bcrisktool/about-tool.aspx

Unfortunately, it does not give the magnitude of the uncertainty.

In this academic opinion paper,

...The resulting calculation produced a concordance statistic, whose value
could range from 0.50 (equivalent to
a coin toss) to 1.0 (perfect discrimination). The
concordance statistics for the Italian and Gail models were essentially
the same, approximately 0.59 (with 95% confidence
intervals that ranged from 0.54 to 0.63). In other words, for 59% of the
randomly selected pairs of women, the risk estimated
for the woman who was diagnosed with breast cancer was higher than the
risk estimated for the woman who was not.
Unfortunately, for 41% of the pairs of women, the woman with breast
cancer received
a lower risk estimate than her cancer-free
counterpart. Thus, for any given woman, the two models were better at
prediction
than a coin toss—but not by much...

http://jnci.oxfordjournals.org/content/98/23/1673....

(emphasis mine)

If their model is this poor for the 'average' woman, just think how much they know about the risk for a person with a personal history of DCIS, LCIS, or invasive breast cancer.   

I know there are the proverbial 'lies, damn lies and statistics', but these papers point out why I think the science of breast cancer is in its infancy.

DiveCat

Yeah, as leaf stated the Gail model is quite flawed....and is useless for many women (like those under 35, or who have a family history of male breast cancer, or small families with few first degree relatives, or those with mostly second/third degree relatives with breast cancer. In my opinion only including first degree relatives is a huge flaw that can underestimate risk.  It also does not consider age of onset. Another big flaw. It might be appropriate for those without family history, but not so much for those with. The modified Gail models do consider number of benign biopsies and whether ALH has been found.

IBIS/Tyrer-Cuzick, BRCAPRO are better models for those with family history. You can download a copy of the IBIS calculator but again discuss your own risk with an expert.

http://www.ems-trials.org/riskevaluator/

WolfsLady

I agree that only including 1st degree relatives is a huge flaw.  In my case breast cancer risk runs higher on my dad's side than my mom's.  At least 2 of his sisters and his father were dx'd between the ages of 48 and 54.  My sisters are all younger than I am and of the 3 cousins I had that were older I only know the medical history of 1.  A 2nd one possibly had some sort of cancer but her mom is secretive and they are semi-estranged and they live so far away that no one in my family has seen her since she was about 4 years old.  My secretive aunt and another of my dad's sisters had hysterectomies in their late 20's or early 30's for what they were told was cancer but once again no one seems to know what kind.  One was his sister who died in her 60's of unknown causes.  She was mentally ill.  Her daughter, my 3rd older cousin died in an auto accident in her 20's.  My dad had bladder cancer about 5 years ago but unlike his sisters and his father he was older.  Thankfully they caught it early.  My doctor told me that since 2 of them possibly had their ovaries removed that it could have lowered their cancer risk because they wouldn't produce estrogen.  At least one of my Aunts was estrogen positive. 

 At any rate by leaving out family history they discount that 4 of my father's 5 sisters had a "female" cancer.  Plus his father.   And lower my risk because my younger sisters, who are 3 and 8 years younger than I, haven't had cancer.   On my mom's side so far her mother and her were both blessed to have been spared breast cancer.  Although my grandmother had many other health issues and she also had a hysterectomy pretty young, but I don't believe it was cancer related.  But both of my mom's grandmother's had breast cancer in their 50's.  One of her mom's sister's was dx'd in her 50's.  I don't believe her mom's other sister ever had it, but one of her daughter's was dx'd at 52 and her other daughter has just hit that age.  Hers was estrogen positive too. I'm hoping that the double generation skip (My mom is 70) means that if there was gene there it skipped our line.  But I know that I can't count on that.  

I know that my risk was raised some because I didn't have my only child until I was over 40.  I worry because I took fertility meds for about 6 years trying to have him.   I also wonder if having busy breasts raises my risk at all.  But my mom says she had 2 extensional biopsies of benign masses so I guess her's were busy too.  (Her doctor back then recommended removing anything that grew because her grandmother's and aunt had breast cancer.)  But she doesn't seem to know what they were.  I'm guessing fibroadnomas since she was pretty young when she had it done.  Early 30's at the latest.  And that is what 2 of my masses are.  I can't believe how lax she is that she doesn't even know.  I just feel better knowing exactly what I had and rather the risk is very low or if I need to vigilant.  

lintrollerderby

Wolfslady said: "I'm hoping that the double generation skip (My mom is 70) means that if there was gene there it skipped our line. But I know that I can't count on that."

I'm very sorry about your family history. I did want to clarify that as far as BRCA is concerned, there is no ability for it to skip generations. You either inherit a mutation or you don't. Mutation carriers sometimes never develop breast or other related cancers, so it can appear that a mutation skips, but it does not. Certainly, for other lesser-known genetic breast cancer mutations, if there are polygenic factors that contribute to the development of the disease, a possibility could exist for a mutation to skip. With BRCA genes, a person inherits one copy of BRCA1 from the mother and one copy of BRCA1 from the father. (The same is true for the BRCA2 genes). If either of those genes is mutated, the person carries a BRCA mutation and has an increased risk of cancer because the gene is mutated and can not properly protect the person from DNA damage. It is thought that cancer appears in a mutation carrier when their wild-type or "good copy" of the BRCA gene that was inherited from the other parent is damaged and stops functioning. This means that the mutated copy has to do the work of DNA damage repair and since it's mutated and doesn't function properly, it can't do its job very well. If the person doesn't lose their "good copy", then they don't have to rely on the mutated one. This is thought to explain why some BRCA mutation carriers do not develop cancer. When the mutation carrier has a child, that child inherits a copy of each BRCA gene from both parents. If the parent who is a BRCA mutation carrier passes on the "good copy" that they received from the parent without a mutation, then the child will not inherit the parent's BRCA mutation, and as a result, will not be able to pass it on to their children. 

Hope this helps.

Lilith08

This--what exactly all the risk factors really mean, if anything--is what I'm struggling with right now. I'm new here and haven't seen mention of numbers in any of the discussion threads I've looked at so far.

About 5 weeks ago I had my 4th and 5th excisional biopsies--left side included ALH and papilloma. The ALH bumped my lifetime risk factor up from about 28% to 44%. My surgeon said this is "very high" and recommended that I consult with an oncologist about starting Tamoxifen. While my mother did have DCIS (19 years ago and doing well), my family history is not strong. The risks are mostly related to my "busy breasts" (first time I've heard this term!) and no pregnancies.

So I'm trying to decide whether taking medication (Tamoxifen wouldn't work for me because of antidepressants, so my ONC prescribed Evista) is enough for me--it would lower my risk from 44% to 19%. Knowing that these numbers are all a bit of a guessing game at best, how do I decide if that 19% is worth it? After 20 years of breast issues, I'm about ready to opt for a PBM. But, of course, I worry that I'm overreacting. So, yes, what does "high risk" really mean, and is there a magical number at which it becomes too high to ignore?

leaf

'High risk' can mean just about anything.  I have classic LCIS, without a strong family history, and have seen LCIS referred to as everything from 'medium risk' to 'high risk' (in the same paper! - it must be committee-speak) to 'the highest risk non-cancerous lesion seen under the microscope'.  (Pathologically LCIS is more advanced than ALH, and all papers I've seen say LCIS has a higher risk than ALH.)

There aren't numbers because we don't know the numbers with any certainty (see my previous post about the modified Gail model)- particularly with ALH or LCIS (without a strong family history).

To be valid, they need to look at populations of people _with your risk factors_ to form a model. It is _not_ valid to just add your breast cancer risk factors together.  Why?  If you look at this breast cancer risk model

http://www.halls.md/index.php (which for me is currently down, and uses the modified Gail model and adds other risk factors to it) which adds together your risk factors (as does the modified Gail model).  The modified Gail model _has_ been compared to populations; this Hall's breast cancer risk model (that includes LCIS) has not.  Both models flatly say they should NOT be used to make medical decisions. 

This Hall's calculator could give me a lifetime risk (without the use of tamoxifen) of 88%, which is higher than any other estimate I've seen in any paper. (The highest I've seen is about 1% per year; since most ALH/LCIS women are diagnosed in their 40s or 50s (including me), this would be about 30 or 40%.  An NCI-certified center gave my lifetime risk as 'anything between 10% and 60%, but probably closer to 10% than 60% - if you want better information you need to look at papers.'  My oncologist said 40% (without tamoxifen) and my genetics counselor 30%.  I also have ALH, so would it make sense to add my risk for classic LCIS to my risk for ALH?  Probably not.

This paper, when combining ALH and ADH, found over 12 years that 143/698 'developed breast cancer', which is 20%.   In the abstract, they don't define what they mean, but I wouldn't be surprised if they include LCIS and DCIS in their definition of 'developed breast cancer'.  http://www.ncbi.nlm.nih.gov/pubmed/24480577  

In this paper, the ALH patients had an 'Estimated 10 year breast cancer risk of ...20.7 % with ALH',

http://www.ncbi.nlm.nih.gov/pubmed/23117858

So the 'breast cancer risk' of someone with ALH may be 'artificially' high if they count DCIS, or especially LCIS in their definition of 'having breast cancer'.  (If they diagnosed me with classic LCIS again, that wouldn't count as another diagnosis because I already have classic LCIS, but they might for you because you don't have known LCIS already.)

Note that the 'average' woman in the USA has a lifetime risk of breast cancer of 12.4%  http://www.cancer.gov/cancertopics/factsheet/dete...

The longest term study I have found for LCIS (which I realize you don't have) is this one. http://jco.ascopubs.org/content/23/24/5534.long which found a minimum of  7.1% risk of breast cancer after 10 years. http://jco.ascopubs.org/content/23/24/5534.long    This 7.1% number is, of course, lower than the 20% numbers in the other papers, plus LCIS is normally considered as higher risk than ALH.

All of this also ignores the uncertainty of breast cancer prediction in an individual (see my previous post.)

No one can guess for you.  No other person can decide how much anxiety breast screening has for you, how much your breasts mean to you, and how you view your alternatives.  You also need, of course, to look at the risks involved.  Breast surgery can have complications including chronic pain, infection, and cosmetic issues; antihormonals can have adverse effects such as the risk of clots and uterine cancer; watchful waiting has the risk of increased anxiety.  Its a risk vs benefit situation.

After my core biopsy in 2005, I had a breast excision in 2006. I started tamoxifen in 2006 and ended in 2011 (and was on sertraline).   I had 2 more breast biopsies in 2007, both nothing worse than what I had.  I have had no other breast issues since 2007.

This does not mean, of course, that you should choose tamoxifen.  The majority of classic LCIS women will never go on to get breast cancer.  The breast cancer risk for ALH is normally considered lower than for LCIS.