If this is genetic why didn't it show up sooner?

EbonyEyes

I have three areas of cancer in my right breast. The surgeon called two of them "precancerous". Whatever they're called I still need a mastectomy. I asked him if that meant the cancer is spreading and he said no, there is no sign of spreading. He said when cancer develops like that it is usually a genetic thing. So, two questions:

I am 63. I thought genetic types of cancer show up at earlier ages.

If it is genetic how come it never showed up in my family before? I am the first one on either side to ever have breast cancer.

Jelson

the way I interpret what you quote your surgeon saying was that spreading/metastasing cancer is usually a genetic thing. your surgeon told you that yours was "precancerous" so his remark did not apply to your tumors. I am not even sure that spreading cancer is a genetic thing - on BCO we usually quote 15% for the cases of BC which are genetic in origin - however that might apply to only the genetic markers which have been identified. Your surgeon might, however, been referring to the broader idea of genetics in cancer which is that many times it is the result of random genetic mutations/damage which leads to other changes in our cells and on and on....which is not the meaning of genetics related to disease passed from one generation to another . In any event, I think you are correct that it is commonly believed that those breast cancers which we know currently to be passed through families via genes usually manifest themselves in earlier in life than 63 and that depending on the specific genetic mutation, one might expect to have some cancer history in the family - which again depending on the specific mutation might not necessarily be breast cancer.

614

Dear Ebony Eyes:

You need to have genetic testing to find out whether you have any mutations and testing may give you peace of mind.  There is no way to know if cancer is genetic unless you agree to genetic testing.  No doctor can accurately predict this information without testing.

Good luck.

inks

I think what your surgeon meant was that multifocal cancer is often BRCA positive. And it is not entirely true that genetic cancers turn up at a younger age. My grandmother is BRCA1+ but she got breast cancer in her early 70s. Your cancer may not be genetic but if it is - BRCA mutation can advance undetected through male lines. Let us know how it turns out.

Ddw79

kind of in the same boat Ebonyeyes.

I am 63 with negative BRCA 1 testing. I have ADH found on surgical biopsy last March. Is this what your surgeon means by precancerous ? I was told only that I am now high risk and a mx was actually discouraged so wondering why that was recommended in your case .

I recently did more genetic testing through Color Genomics. I'm still waiting on the results of this saliva test. I think it's important to get all information possible before I make major decisions like PMX

vlnrph

There is more to consider than BRCA 1/2 in terms of hereditary cancers. While those "classic" cases have now been studied for two decades, the other mutations which contribute to tumor formation have been found to correlate less significantly with age. A landmark paper was recently published which noted this phenomenon.

A certified genetic counselor is the correct person to see next. They can suggest the proper testing to be done and are trained to explain the results and provide referrals for follow-up therapies should a defect be identified.

BarredOwl

Hi EbonyEyes:

My short answer is that if either of the breast surgeons you have consulted suspected a genetic predisposition, they would have recommended that you seek genetic counseling. (This was my experience.)

Jelson has picked up on the possibility he was referring to the biology of cancer development and metastasis, which is driven by the accumulation of genetic changes or mutations, by which normal cells become cancerous, evade normal controls on cell replication, acquire the ability escape their location, and evade immune surveillance.

From other threads, your pathology report indicated that you have two areas of DCIS, and a small 3 mm area of IDC all in the same breast.

DCIS arises from the cells that line the ducts by a process of mutation. DCIS can be loosely considered a pre-cancer, because it is non-invasive. This means that the DCIS cells are still confined within the ducts. Current dogma is that DCIS is confined in the ducts and incapable of metastasis. However, the problem is that DCIS cells might acquire additional mutations over time and thereby become invasive. So surgery is being recommended.

IDC also arises from the cells that line the ducts, but it has acquired more changes and become "invasive". So it can break through the wall of the duct, and form a tumor. A very small IDC is probably a pretty new one, and is quite likely to be local only. Invasive cells can have/acquire additional mutations and abilities, such as the ability to metastasize. So surgery is being recommended.

Multi-centric disease (more than one spot) may sometimes be a contraindication for breast-conserving treatment (lumpectomy). Given the geometric location of the DCIS and IDC within the breast, if removal of all of it would probably lead to a poor cosmetic result, then mastectomy is recommended.

Genetic predisposition to breast cancer (from inherited gene mutations) is not that common:

Inherited changes in certain genes, such as BRCA1, BRCA2, or certain other genes, increase the risk of breast cancer (and sometimes other cancers as well). These changes are estimated to account for about 10 percent of all breast cancers:

http://www.cancer.gov/types/breast/risk-fact-sheet

Age at diagnosis:

A diagnosis at age 63 is probably quite close to the average age of diagnosis. In my personal opinion as a layperson, your age is not suggestive of any particular genetic syndrome, and is largely uninformative.

The prevalence of breast cancer in BRCA1/2 carriers is strongly age dependent. Thus, a diagnosis before age 50 would be one factor that may suggest the possibility of a BRCA mutation. As stated above, some BRCA carriers luck out and never get breast cancer, and some get it after age 50. This is because the mutation by itself does not cause cancer; it undermines DNA repair, predisposing a carrier to mutations (which cause cancer). Thus, a later age at diagnosis does not mean you do not have a BRCA mutation, but it is not suggestive that you have one either.

To make things more confusing, other breast-cancer associated genes might behave differently from BRCA1/2. As noted by vinrph, one recent study did not observe a similar age effect with other breast cancer-associated gene mutations. This suggests that age at diagnosis may be not a reliable indicator of possible mutation in these other genes. So a later age at diagnosis may not be inconsistent with the presence of one of these other gene mutations.

http://oncology.jamanetwork.com/article.aspx?artic...

Factors suggestive of BRCA1/2 mutation:

Regarding genetic testing, to my knowledge as a layperson, "multi-centric" disease (more than one spot of DCIS and/or IDC in the same breast) is not considered to be a strong flag for a genetic mutation.

In contrast, bilateral breast cancer is a factor (breast cancer in both breasts). The Some of the family history factors that are associated with an increased likelihood of having a harmful mutation in BRCA1 or BRCA2, include:

• Breast cancer diagnosed before age 50 years
• Cancer in both breasts in the same woman
• Both breast and ovarian cancers in either the same woman or the same family
• Multiple family members with breast cancer
• Two or more primary types of BRCA1- or BRCA2-related cancers in a single family member
• Cases of male breast cancer
• Ashkenazi Jewish ethnicity

The source of the above list and more info on BRCA1/2 can be found here:

http://www.cancer.gov/about-cancer/causes-preventi...

[Edited to add: Please see thread below for additional information about additional factors that are used in patients diagnosed with breast cancer.]

Note that the factors associated with increased chances of having a mutation in other genes are different, and may include different kinds of cancers or other medical problems.

Genetic Counseling, BRCA Testing or Multigene Panel Testing:

While genetic mutations are sometimes found in people who do not meet the established criteria for testing for BRCA or other genes, testing everyone is not feasible yet. Therefore, medical professionals use these kinds of factors to determine who should be referred for genetic counseling. A patient who is diagnosed with breast cancer at age 63, with unilateral disease, and no family history of breast cancer would probably not automatically be referred to a genetic counselor, provided that no other suspicious factors, or personal or family history of other cancers or syndromes are present.

Do you have any of the other factors above? Any personal or family history of ovarian, peritoneal or fallopian tube cancer? Any personal or family history of any other types of cancers (e.g., colon, pancreatic, etcetera)? These could change the picture.

You can ask to be referred to a genetic counselor. A counselor will have the most up-to-date information about the various breast cancer-associated genes and the cancers/syndromes associated with these genes, will review your personal and family history, and make a recommendation about testing based on current criteria. They can also explain the possible outcomes of any genetic testing, its benefits, and its downsides.

Because genetic mutations are sometimes found in people who do not meet the established criteria for testing for BRCA or other genes, some patients who do not meet the criteria still suspect a genetic problem. They wish to find out if any of the known pre-disposing genes may have contributed to their breast cancer, and they seek genetic testing anyway. You may need to confirm whether the insurer or other payor will cover such self-directed testing (maybe not). A genetic counselor is in my view essential to understanding the results of such tests, the options for enhanced screening or risk reducing actions, if any.

Hope that helps.

BarredOwl

vlnrph

Great explanation BarredOwl! Thanks for including the link to the article I referenced. I suspect that you are either in education or health information: am I right?

One factor my insurance company employs to determine payment for genetic testing is the presence of more than one tumor at diagnoses. Since mine were of different pathologies (lobular and ductal, or what is now being called "no special type") it made me curious to find out how often that occurs. Not real common as it turns out.

In addition, I find the age threshold of 50 to be somewhat arbitrary. Undergoing menopause later than average gives certain cancers more time to become established due to hormonal stimulation. It usually takes a couple years or more for a tumor to grow enough to be detected which means they probably started in your forties when you're diagnosed in your early fifties.

Original poster should keep in mind that, as inks points out, mutations can be passed through men. If your ancestors had small families with mostly boys, hereditary breast & ovarian disease could be hidden for generations. Plus, in the not too distant past, people died of causes never revealed to them. Relatives may have thought the big c to be shameful so kept it hushed up and not spoken about directly. Often female conditions were described as stomach or abdominal problems instead of using more accurate terms.

inks

According to this small study 42.9% of women with BRCA2 mutation had multifocal disease but ....However when further work was carried out adjusting for other variables in MLR, although multifocality was associated with a positive odds ratio of 1.87 for BRCA2 mutations it was not statistically significant (p=0.084).

downloads a PDF

inks

This study used multifocality in the patient as basis for genetic testing

"If the pedigree displayed at least one of the criteria for further counseling (e.g., (1) breast cancer in the patient or a relative <40 years of age, (2) patient had two or more relatives with breast cancer, (3) multifocal, multicentric, or bilateral breast cancer in the patient or a relative with the first breast cancer diagnosed <50 years of age, (4) ovarian cancer in the patient or a relative, or (5) a male relative with breast cancer), the patient was referred to the Department of Medical Genetics for genetic counseling and a BRCA test "

http://www.nature.com/gim/journal/v9/n11/full/gim2...

So I respectfully disagree that multifocal disease is not a predictor of BRCA mutation. But that's just my opinion and I am not a doctor I just happen to have multifocal disease and have tried to find an explanation to my own multifocal disease.

Edited to add that my own genetic counselor used my multifocal disease as a reason for genetic testing, my cancer came from a male line and therefore not enough close relatives with BC.

inks

Barred owl the criterea for basis of genetic testing that you refer and link to at http://www.cancer.gov/about-cancer/causes-preventi... is for women who do not have cancer

"Because harmful BRCA1 and BRCA2 gene mutations are relatively rare in the general population, most experts agree that mutation testing of individuals who do not have cancer should be performed only when the person's individual or family history suggests the possible presence of a harmful mutation in BRCA1 or BRCA2."

BarredOwl

Hi Inks and vinprh:

Thank you very much for your additional information, correction with citation, and clarifications.

Vinprh: I completely agree that age 50 is a bit arbitrary, for the reasons you note. My own personal experience is completely in accord. I commented on that in another thread:

"Younger age at diagnosis (before age 50) can be suspicious. (The age 50 risk is reflected in some screening guidelines that commence at age 50.) However, such hard lines can be a bit arbitrary. For example, I was diagnosed at age 52, but was premenopausal at the time, so that increased the suspicion in my case. Some limits on family history are that they are snap shots in time, and sometimes people are not aware of the health status of some relatives (particularly of prior generations)."

I also agree that some family histories can be less informative than others as you note. There also are limits on family history because they are snap shots in time. My own family history would have appeared sporadic, up until the moment that two members in successive generations were simultaneously diagnosed with BRCA-related cancers. (I was BRCA negative (2013, Myriad), but have not had any other testing.) NCI PDQ states:

"The accuracy and completeness of family histories must be taken into account when they are used to assess risk. A reported family history may be erroneous, or a person may be unaware of relatives affected with cancer. In addition, small family sizes and premature deaths may limit the information obtained from a family history. Breast or ovarian cancer on the paternal side of the family usually involves more distant relatives than does breast or ovarian cancer on the maternal side, so information may be more difficult to obtain. . . Additional limitations of relying on family histories include adoption; families with a small number of women; limited access to family history information; and incidental removal of the uterus, ovaries, and/or fallopian tubes for noncancer indications. Family histories will evolve, therefore it is important to update family histories from both parents over time. (Refer to the Accuracy of the family historysection in the PDQ summary on Cancer Genetics Risk Assessment and Counseling for more information.)"

Inks: Thank you very much for correcting my error about multifocal, multi-centric disease and for the citation. I edited my post above in light of your comments. Your point about the focus of the link I provided in my earlier post is well-taken, although there is some overlap in criteria. The "Cancer Genetics Risk Assessment and Counseling" link found at the end of the quote in this current post has a broader focus (not just BRCA), encompasses personal history, and indeed it lists "multifocal" disease.

I am also just a layperson, and my comments should always be taken as such, including that I may be completely wrong. The area is complex and continuously evolving, which is why I am a proponent of seeking current advice from a professional genetic counselor when there is a suspicion.

Thanks again.

BarredOwl

vlnrph

I still think BarredOwl is either a professional educator or scientific writer but it's ok if she wants to stay anonymous: just keep providing us with information and food for thought! Inks is also a great contributor.

It does seem that menopausal status should be given more weight than age at diagnosis in determining suitability for genetic testing. Also, I find it curious that insurance company guidelines allow a sister to be checked for mutations due to my experience as well as our mother having hadcancer but I only have one first degree relative with a qualifying disease so my coverage was not automatic (the two different tumors ILC/IDC are what tipped the balance. I was still faced with a denial which I won upon appeal, appearing in person before a review committee)

Ddw79

Barredowl thanks so much for that comprehensive and elucidating piece of work. That was amazing

I myself do not exhibit BRCA 1 gene. All women in my family died of breast / ovarian cancer. I was one of first people in U.S. To be tested for this in study over 20 years ago. Now I have something that put me at high risk and I have done more genetic testing . Waiting for results from Color Genomics which only set me back $ 250 so very affordable. 19 mutations tested. Waiting a month already

BarredOwl

Hi Ddw79:

Inks and vlnrph provided some excellent comments, corrections and information. There is always more to learn.

It is very interesting that you are a part of the early history of genetic testing (a patient pioneer), as well as its continuing evolution.

BarredOwl

Ddw79

I was indeed a pioneer and boy have things changed. Initial BRCA 1 took almost two years to turn around. WTF I am back at it again even with negative result and working at it sadly again at the Dana Farber with same Dr. I thought it was over 😒.

614

Thanks for all of the wonderful information. 

In my case, I was diagnosed at age 49 and I was premenopausal.  I had not even had any perimenopausal symptoms and all at the time.  I was told that 50 is an arbitrary age but that is what the insurance companies go by. 

In my case, I was able to have the genetic tests because I had 2 family members with bc, I was diagnosed prior to age 50, and I am Ashkenazi Jewish.  I was told that 3 factors is what it takes to have the test mostly paid for by my insurance co. I still had a copay but it was only a few hundred dollars.  After reading this post, I found out that I actually had more risk factors.  I have a lot of other cancer in my family.  Also, I had 2 tumors and more than 1 kind of cancer.  (PILC, PLCIS - those would be counted as basically the same thing, I believe, but I also had Invasive Tubular Carcinoma.)  They did not count both tumors for me at the time that I was considering genetic testing because the larger of my tumors came back as being benign at the time of the biopsy.  It was actually malignant but that was not discovered until my pathology report came back from my double lumpectomy. 

My genetic counselor was fantastic.  She was so knowledgeable and helpful.  She spent a great deal of time with me.  She really helped me.

The only problem with my genetic testing is that my results came back with a genetic mutation that is unknown.  That makes it stressful for me.  They have absolutely no information on this particular mutation aside from the fact that it may be for the colon but they really have no idea.

Good luck to everyone here.

BarredOwl

Hi 614:

You might be interested in this article by Dr. Mary Claire King discussing a study of population-based screening in an Ashkenazi Jewish population in Israel.

http://jama.jamanetwork.com/article.aspx?articleid...

It also highlights the challenge of small, uninformative family histories and makes some interesting observations about the variability in practice in the assessment of family history citing a 2011 report:

"Population-based screening enables mutation carriers to be identified independent of physician referral or family involvement. This is important, because at present, there is marked variability in practice in following USPSTF guidelines. A recent survey revealed that only 19% of US primary care physicians accurately assessed family history for BRCA1/BRCA2 testing. In our study in Israel, only 35% of families with high incidence of breast or ovarian cancer had been previously referred for genetic counseling, despite common knowledge of the increased risk due to BRCA1 and BRCA2 in the Ashkenazi Jewish population and the availability of free testing and counseling in the Israeli health system. Population-based screening circumvents these barriers."

BarredOwl

614

Dear Barred Owl:

Thank you so much for the link and for the information.  You are a vast wealth of knowledge and you have a gift for research.  I admire that.  Thanks again for everything.

Sincerely,

614