my sister's diagnosis and genetic testing results?

TSeaboy

My sister was diagnosed with stage 4 breast cancer in July. She had genetic testing which came back negative. However, I have read a lot of stories about negative test results but families of a mom and multiple sisters getting breast cancer. I understand there are very many genes we know nothing about.

My question.. With a history of an immediate sister and a paternal great grandmother diagnosed with breast cancer and the negative test results - what's the best next step? Vigilant mammograms (scheduled already)/breast exams?

Just wondering "what would you do"s.

MTwoman

I would talk to my provider about the best monitoring protocol for you, given that there is no genetic mutation of significance that you know about, but that you have one close and one not-so-close relative with a history of bc. Now, if your great grandmother was in the typical age for bc when she was diagnosed, they may not count her, but it is always best to give all the information and let the medical professionals sort out what matters most. So, which relatives, what were their ages at diagnosis and what they were diagnosed with (as much info as you can get). Perhaps schedule a consultation apt with your provider for the discussion, as opposed to working it in during your annual.

Lula73

you can still be tested too. Just because your sister tested negative does not mean you will just like if she tested positive doesn't mean you will. The grandmother component would make me uneasy and I'd want as much reassurance as I can get

Outfield

Lula, a great-grandmother isn't an indication for genetic testing - insurance is not likely to pay for it.

TSeaboy, how old was your sister at diagnosis? I worry about my own sister because I was diagnosed young. If she lived near me, this is what I would do:

- Ask my own (your sister's) breast surgeon or oncologist. I love my breast surgeon - treating breast cancer is her life - and I would trust what she says. Since my sister is far away and in a tightly-protocol driven HMO, she doesn't have much choice

- Find out exactly what your sister was tested for. There are now panels looking at over 20 genes where variants can increase breast cancer risk. In 5 years, that number will probably be more

- Keep in touch with someone who is up-to-date on the testing, so you'll know when the panels have been updated to include new genes

- Be vigilant about self-exams. I know they aren't technically recommended anymore because they've never been proven to help, but it's not like there's an overwhelming amount of evidence against them either.

- If your breasts are dense, consider asking for imaging in addition to mammogram

There might be other things, but those are what pop to mind. I hope you never have to deal with cancer yourself, and I'm sorry your sister does.

Lula73

no a great grandmother won't get insurance to cover it but having a sister with BC does. The grandmother component is the part that would make me worry..

TSeaboy

Outfield: my sister is 39 and recently diagnosed. Stage 4, metaplastic, metastasized to the lymph nodes and liver by the time it was discovered.

My sister was tested for 19 panels.

Why does the grandmother cause more worries? The odds of genetics vs. coincidence?

Mandycat

my genetic testing was negative but there is a strong mother daughter pattern in my family going back to my great grandmother. The genetic tester said she felt strongly that there was a genetic component in my family but they just haven't identified all the genes that can cause this. My sister went to a high risk clinic and they advised her to take tam

Mandycat

they also advised every 6 month testing with MRI and mamm

Outfield

TSeaboy, unless your great-grandmother were also diagnosed very young, she's not a strong factor. An individual posting may feel concerned about that, but in the world of genetics testing it doesn't really add anything. She's not that close a relative, and, if the cancer were later in life, it's not nearly as strong a signal that there may be something going on that can be found in relatives. Most breast cancer is what's called "sporadic," meaning there doesn't seem to be a family pattern, and that's especially true for women who are diagnosed when they are older. The big concerns are male relatives with breast cancer, relatives who developed it very young, and first degree relatives (parents, siblings, children). If there's a first degree relative AND second degree relatives, then those second degree relatives up the concern, but a great-grandmother is third-degree relative and that by itself doesn't change your risk. Here's a link to a table on the CDC's website that lays it out:

https://www.cdc.gov/genomics/resources/diseases/breast_ovarian_cancer/risk_categories.htm

But that argument about your grandmother isn't really very important because your sister's cancer is the crux of the concern, and all by itself it's enough to warrant thinking about genetics. Until we're so old it doesn't matter, I'm going to pursue genetic testing for myself (I am the one who has had breast cancer) because I was young, had cancer in both breasts, and I have both a sister and a daughter. My daughter will start screening younger than standard recommendations, and I hope she'll be able to get MRI's as part of that screening. She's only 10, so the imaging world may be very different by the time she hits that age. If I were my sister (she is younger), I'd want to talk to a genetics counselor and I'd want an MRI. But insurance being insurance, unless you are independently wealthy, what you want isn't always what you can get.

BarredOwl

Hi TSeaboy:

In your situation, I would request a referral to Genetic Counselor.

It sounds like your sister received multi-gene panel testing using a test panel that included 19 different cancer predisposition genes. If a cancer predisposition gene has not yet been identified in your family, then her negative test result (while favorable for her) is considered an "uninformed negative." It is possible for her to have breast cancer and yet to test negative, while other members of your family (e.g., a parent) might carry a pathogenic mutation in a gene conferring a predisposition to certain cancers (including a mutation in one of the 19 genes she tested negative for). (A "true-negative" is based on an identified mutation in a family member coupled with a negative test result for that mutation, and per NCCN guidelines indicates that: "The person is not a carrier of a known cancer-predisposing gene that has been positively identified in another family member.")

The NCCN guidelines for "Breast and/or Ovarian Cancer Genetic Assessment" (Version 2.2017) contain a chart at the beginning entitled, "CRITERIA FOR FURTHER GENETIC RISK EVALUATION" (Chart BR/OV-1). The chart sets forth a long list of considerations which can lead one to: "Consider referral to cancer genetics professional" for genetic risk evaluation.

You clearly satisfy at least one of the criteria for such a referral given your sister's diagnosis at age 39 (a first-degree relative), for example this one:

"An individual with no personal history of cancer but with . . . First- or second-degree relative with breast cancer ≤45 y"

The guidelines specify: "First-degree relatives: parents, siblings, and children" and "second-degree relatives: grandparents, aunts, uncles, nieces, nephews, grandchildren, and half-siblings."

In connection with the criteria for referral to a cancer genetics professional for risk evaluation, under NCCN guidelines, certain cancers in third-degree relatives can be factors that contribute to consideration of such a referral. For example, note also this (rather poorly worded) criterion, citing to note (d):

An individual with no personal history of cancer but with

> A close relative with any of the following: [d,f]

. . . ≥2 individuals with breast cancer primaries on the same side of family with at least one diagnosed ≤50 y . . .

As explained in note (d), "Close blood relatives include first-, second-, and third-degree relatives."

The guidelines specify "third-degree relatives: great-grandparents, great-aunts, great-uncles, great-grandchildren, and first cousins."

The list of factors is extensive and may differ based on whether a person has a diagnosis or not and by type of diagnosis. Depending on your specific circumstances, it is possible that other criteria may apply. For those who would like to access Chart BR/OV-1 for review of the criteria with a referring physician, a copy of the guideline can be accessed here at no charge with free registration:

https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf

It is periodically updated, so as best practice, always access the latest version on the web. The above should be used to inform consultations with your medical providers and is not a substitute for case-specific medical advice.

Again, the above-quoted criteria go to whether referral for genetic risk evaluation may be warranted.

The NCCN guidelines also note that: "The criteria for further risk evaluation and [for] genetic testing are not identical." As part of a genetic risk evaluation, a personal medical and family history is taken, a genetic/familial risk assessment is performed, and a recommendation will be made regarding genetic testing. If recommended, the scope of such genetic testing, as well as the pros, cons, and limitations of such testing will be discussed. The patient may pursue or decline any recommended testing at their option.

Even if you do not pursue genetic testing, as part of the consultation, you may request an estimate of your lifetime risk of breast cancer that may further inform questions such as the timing of initiation of screening, mode(s), and frequency of screening.

BarredOwl