March 3, 2016

New NCCN Guidelines For Hereditary Breast And Ovarian Cancer

By UCSFcounselor2

The National Comprehensive Cancer Network (NCCN) released it's newest version of guidelines for hereditary breast and ovarian cancer titled: Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 1.2016. You maybe asking, what NCCN guidelines address? According to the NCCN website, "These guidelines are the recognized standard for clinical policy in cancer care and are the most thorough and most frequently updated clinical practice guidelines available in any area of medicine." In other words, they are guidelines used by clinicians and providers to help steer their decisions in determining who should have genetic counseling and testing for hereditary cancer and what screening/prevention is best based on a person's genetic status.


 

Multi-gene Panel Testing for Hereditary Breast and Ovarian Cancer

The most recent Genetic/Familial High-Risk Assessment: Breast and Ovarian NCCN guidelines has a new section on multi-gene genetic testing. Multi-gene panel testing is when someone undergoes genetic testing for more than one or two genes. Mutations in different genes can cause the same type of cancer. These genes can be looked at either one at a time, or a number of genes at the same time. By testing a number of genes all at once, it may be possible to find the cause of cancer in a family more quickly.

Multi-gene panel testing can test a person for 5-50 (possibly more) genes in one test. Below are NCCN's most recent overview and recommendations for multi-gene testing:

  • The recent  introduction of multi-gene testing for hereditary forms of cancer  has rapidly altered  the clinical approach to testing at-risk patients and their  families. Based on next-generation sequencing technology, these tests  simultaneously analyze a set of genes that are associated with  a specific family cancer  phenotype or multiple phenotypes.
  • Patients who have a personal or family history suggestive of a single inherited cancer  syndrome are most  appropriately managed by genetic testing for that specific syndrome. When more than one gene can explain an inherited cancer  syndrome, than multi-gene testing, may be more efficient and/or  cost-effective.
  • There is also a role for multi-gene testing in individuals who have tested  negative (indeterminate) for a single syndrome, but whose  personal or family history remains strongly suggestive of an inherited susceptibility.
  • As commercially available tests  differ in the specific genes analyzed  (as well as classification of variants and many other  factors), choosing the specific laboratory and test panel is important.
  • Multi-gene testing can include “intermediate” penetrant (moderate-risk) genes. 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. As is the case with  high-risk genes, it is possible that the risks associated with moderate-risk genes may not be entirely due to that gene alone, but may be influenced by gene/gene  or gene/environment interactions. Therefore, it maybe difficult to use a known mutation alone to assign risk  for relatives. In many cases the information from testing for moderate penetrance genes does not change risk management compared to that based on family history alone.
  • There is an increased likelihood of finding variants of unknown significance when testing for mutations in multiple genes.
  • It is for these and other reasons that multi-gene testing are ideally offered in the context of professional genetic expertise for pre- and post- test counseling.

BREAST AND OVARIAN MANAGEMENT BASED ON GENETIC TEST RESULTS

With multi-gene panel testing more and more people are testing positive for genetic mutations in the BRCA1 and BRCA2 as well as many other hereditary cancer genes. There are a number of new genes that are now recognized to cause hereditary breast and ovarian cancers. Some of these genes we still don't know enough about to provide accurate screening recommendations. Other genes we know quite a bit of information about and that information will help women make decisions about breast and ovarian cancer risk. NCCN has put together a table of genes associated with hereditary breast and/or ovarian cancers and recommendations for breast and ovarian cancer screening including risk-reducing surgery.

BREAST AND OVARIAN MANAGEMENT  BASED ON GENETIC TEST RESULTS

Recommend MRIc

(>20% risk  of breast  cancerd)

Recommend RRSO* Discuss Option of RRM**
Intervention Warranted based on gene and/or  risk  level ATM BRCA1

BRCA2

CDH1

CHEK2

PALB2

PTEN STK11

TP53

BRCA1

BRCA2

Lynch syndromee

BRCA1

BRCA2

CDH1

PTEN TP53

Insufficient evidence for intervention BARD1

BRIP1

BARD1

BRIP1

PALB2

RAD51C RAD51D

ATM BARD1

CHEK2

PALB2

STK11

*RRSO: Risk Reducing Salpingo- Oopherectomy (surgery to remove a woman's ovaries and fallopian tubes to prevent her from getting ovarian and fallopian tube cancer)

**RRM: Risk Reducing Mastectomy (surgery to remove a woman's breast tissue to prevent her from getting breast cancer)

 

To review these updated guidelines click here v1.2016 Breast and Ovarian Cancer NCCN Guidelines 

Tags: News

I have a very strong family history of breast cancer (sister at 39, 2 maternal aunts, maternal grandmother, 3 maternal great aunts — which makes all women in that generation) and a Chek2 1100delC mutation. The genetic counselor puts my risk at 44%. I have been going to a high risk breast clinic for several years and doing yearly mammograms and MRIs. This year (after just having received the news on the Chek2 gene) the breast surgeon and oncologist both recommended that I seriously consider a PBM. That seems to contradict the NCCN guidelines. Can you help clear this up please?

COMMENT

@PeggyGoetzConradMS can you answer my question? Any guidance here? Thanks

COMMENT

@kcheyney you bring up a good question and I understand why you might be questioning your oncologist’s and breast surgeon’s recommendations. The NCCN recommendations are based only on a person’s genetic status and does not take into account a person’s family history. We know that mutations in the CHECK2 gene increases a woman’s life time risk for breast cancer but there are also other factors that can increase their risk even more. Those are typically other genes and environmental exposures that are shared with other family members. As you mentioned, you have a very strong family history of breast cancer and some of those breast cancers were diagnosed at very young ages. I would imagine that your oncologist and breast surgeon are recommending RRM based on both your genetic status and your strong family history of breast cancer. That is why the NCCN guidelines states that there is insufficient evidence and that you should manage a woman’s breast cancer risk based on her family history. I have add the NCCN table of screening recommendations that states the piece about breast cancer screening and RRM based on a woman’s family history.

One other important thing to bring up is your mutation, 1100delC. This is a well known and documented mutation in CHECK2. It is a European founder mutation and there has been a lot of research done on this mutation. We know that the risk for breast cancer with this mutation is somewhere around 44%. There are 100’s of other mutations in the CHECK2 gene that we know very little about. By this I mean that we don’t know exactly how new or rare mutations in CHEK2 impact the functionality of the gene and therefore we don’t know the lifetime risk for a woman to develop breast cancer. Some mutations in CHECK2 may only increase a woman’s life time risk of developing cancer by a little bit. Since your mutation is well known we have a good idea of the lifetime risk for breast cancer.

I hope this helps to answer your question. Please let me know if you have any other questions or further clarification!

COMMENT

Thank you so much. Just thought I’d check before I scheduled a RRM 🙂

COMMENT
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