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

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, 

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!

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. 

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.

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.  

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?