Exactly what I was thinking, BarredOwl. The available panels are unlikely to include these newly discovered genetic variants yet. But it is true that occasional re-testing with the latest panel may be recommended, since the companies that do these panels do update and expand their tests (this per my genetics specialist). As the BCO article indicates, though people have probably heard a lot about BRCA, there are other important genes to check as well. Also, I was told that the popular and relatively inexpensive genetic test that people do on their own is not as thorough as the one, such as Ambry, that your genetics specialist can order. Even for a particular gene, a more thorough test will look at more loci.

(P.S. The mods posted the same headline about the study in three other places here.)

Hi ShetlandPony and Traveltext:

Sadly, I did not and still do not have the energy to post in the multiplicity of threads.

To clarify, I am not recommending that multigene panel testing be pursued, but only that patients may wish to seek expert professional advice about it. (Still, the current commercially available multigene panels in use would NOT cover all of these ~70 "new loci".)

I agree that variants of unknown significance ("VUS") raise special issues and challenges ("a can of worms"). And indeed, per NCCN guidelines, "There is an increased likelihood of finding variants of unknown significance when testing for mutations in multiple genes." Patients may find the uncertainty of a VUS disturbing and confusing.

Another significant concern is that per NCCN guidelines:

"Multi-gene testing can include "intermediate" penetrant (moderate-risk) genes.[a] For many of these genes, there are limited data on the degree of cancer risk and there are no clear guidelines on risk management for carriers of mutations. Not all genes included on available multi-gene tests are necessarily clinically actionable."

Because of these and other considerations, instead of "ask your doctor" as suggested in the feature, I recommended that "you may wish to discuss the question of additional multigene panel testing with a Genetic Counselor". It would have been more comprehensive to say "Genetic Counselor, medical geneticist, or other health professional with expertise and experience in cancer genetics." Unfortunately, most "doctors" do not have much medical genetics training or familial risk assessment, and may not be the best situated person to fully advise patients regarding the pros, cons, and limitations of multigene panel testing or actionability of test results. In addition, in some cases, selection of an appropriately comprehensive panel may also entail medical genetic expertise.

Because it is not known whether a VUS either does or does not confer increased risk, one of several possible scenarios is that it does not confer any added risk, but that the person might carry a pathogenic mutation in another cancer predisposition gene. Therefore, I guess in addition to those who tested negative BRCA1 and BRCA2, those whose testing did not identify any known pathogenic BRCA mutation, but instead identified a VUS in BRCA1 or BRCA2 may also wish to consult with such a professional, including whether there is any new information regarding their particular VUS, and whether further multigene panel testing may be recommended and is right for them (or not).

You mentioned, "But, now these 72 new genes are out there I see chances of my variation being discovered as meaning something as remote." I do not necessarily see this recent work as impacting the likelihood of reclassification of your specific BRCA1 VUS, given that BRCA1 is a high penetrance gene and included in many on-going research efforts. The NCCN guidelines suggest that those with a VUS, "Consider a referral to research studies that aim to define the functional impact of variants[,] such as variant reclassification programs through clinical labs or registries."

My layperson understanding (which should be confirmed with a professional) is that ordinarily a VUS will not lead to testing of family members for clinical purposes under NCCN guidelines. However, family history is relevant, and should it be of interest in due course, the diagnosis of male breast cancer in a close relative is one criterion for referral to a cancer genetics professional for genetic under NCCN guidelines. (Your local guidelines may be similar.) Apart from consideration of whether any genetic testing is recommended or not, such a consultation may also include a discussion regarding the timing of initiation and recommended frequency of routine screenings (e.g., mammography) based on family history and individualized risk assessment, which may be of independent value.

BarredOwl

Depending on what genes these variants are associated with, the genes might potentially one day provide drug targets for treatment. At this time, the first paper re "65 new breast cancer risk loci" indicates that the significance of the work relates to genetic susceptibility to breast cancer:

"These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention."

"The identified SNPs [single-nucleotide polymorphisms] will be incorporated into risk prediction models, which can be used to improve the identification of women that are at high or low risk of breast cancer: for example, using a polygenic risk score based on the variants that have been identified to date, women in the highest 1% of the distribution have a 3.5-fold greater risk of breast cancer than the population average. Such risk prediction can inform targeted early detection and prevention."

The second paper per the title is about the "[i]dentification of ten variants associated with risk of estrogen-receptor-negative breast cancer." The significance is explained as being:

"These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.

BarredOwl

This is interesting:

Breast cancer doesn't discriminate by gender

OCTOBER 19, 2017 BY KARLA JAMES

October is National Breast Cancer Awareness month and statistics show that one in eight women in the U.S. will develop it over the course of her lifetime. Breast cancer doesn't discriminate by gender. Dr. Edibaldo Silva is a cancer surgery professor at the University of Nebraska Medical Center and says out of every 100 women, one man will develop breast cancer in their lifetime. He says many men are the primary carrier of the BRCA gene mutation that increases the risk of certain kinds of cancer.

Dr. Silva says a man may carry the gene but never develop breast or other forms of cancer in their lifetime. However, they can pass that mutation along to their children, both male and female, who have a 50% chance of then carrying that gene mutation.

Dr. Silva says he receives many calls from physicians saying they have a male patient diagnosed with breast cancer. He says, "My next question is always does he have prostate cancer. Almost all of the time the answer will be in the affirmative because the prostate cancer is carried by the same gene but often times expressed at a younger age than the breast cancer itself."

Dr. Silva says there is a reason that fewer males that carry the BRCA gene develop breast cancer than women. He says, "You need estrogen and the bad gene in a person with estrogen that is developed by the female ovary is what ultimately results in breast cancer in the female. Although the male can have the gene the frequency which they go on to develop breast cancer is a fraction of that in women. Women who carry the gene may have as high as 88% chance of developing breast cancer at a young age. In men, even though the gene may be present, in the absence of estrogen the risk of developing breast cancer is about 11%.

Dr. Silva says since men do not receive mammograms they typically first notice there is a problem when a mass develops. The treatment for male breast cancer is identical to that of women depending on the stage. That may include a mastectomy, chemotherapy and radiation.

Source: https://nebraskaradionetwork.com/2017/10/19/breast...

Traveltext, I wasn't really commenting on sputum vs. blood, but on how detailed the test is compared to other tests. I'll give you an example of what I mean, though this particular example comes from a tissue biopsy vs. a liquid (blood) biopsy and addresses a somatic mutation, not germline, i.e. just in the tumor vs. in me. But it still illustrates my point. Foundation One found a CDH1 mutation (a characteristic of ILC) but my liquid biopsy did not. I called the company to ask how that could be. The answer was that their test does check for some CDH1 mutations, but does not look at the particular exon on which mine is located. So the F1 test was more complete or detailed.

As far as germline testing, Ambry found a variant in me that is related to several kinds of cancer. Whether breast cancer is one of them is under question right now. BUT, it alerted a family member to get tested. The variant was present, and now this person knows to get earlier and more screening for the indicated cancers. In particular, more frequent colonoscopies that could actually prevent colon cancer by allowing for removal of precancerous polyps. So in our case the genetic testing provided useful information.

I agree with BarredOwl that asking your genetics specialist is much better than asking your doctor.