Guideline: Breast surgeons recommend genetic testing for all breast cancer patients

IN-DEPTH 

Background:

An estimated 266,000 new cases of invasive breast cancer and an estimated 40,000 related deaths occur annually in the U.S. About ten percent of these patients will have a mutation in a breast cancer gene.

Identification of women and men with increased risk of breast cancer due to a gene mutation offers the possibility of preventive action. For individuals without cancer this can include increased surveillance, risk-reducing surgery or chemoprevention.

• Enhanced screening is recommended for patients with mutations in ATM, CDH1, CHEK2, NBN, NF1, PALB2 and STK11.
• For BARD1, MSH2, MLH1, MSH6, PMS2, EPCAM, BRIP1, RAD51C and RAD51D some data suggests an elevated lifetime risk of breast cancer and may not warrant different breast cancer risk management. However, preventive issues may need to be considered regarding increased risk of other cancers (ovarian cancer for several mutations or colorectal cancer for people with mutations in Lynch syndrome genes PMS2 and MSH6).

For individuals with breast cancer, knowledge of having a mutation can alter treatment options or follow-up plans. Patients with risk-increasing mutations can make more educated decisions about surgical removal of their contralateral (healthy) breast to lower the risk of breast cancer and removal of their ovaries and Fallopian tubes to reduce both breast and ovarian cancer risk. PARP inhibitors were recently approved for treating metastatic breast cancer patients with BRCA mutations. Studies are underway to determine their usefulness as treatment for early-stage breast cancer.

• Radiation is not recommended for individuals with TP53 mutations because of the increased risk of radiation-induced cancers.

Identification of a mutation in one person also indicates that other family members may have similar heightened risk; they may also want to speak to a genetic counselor who can explain whether they should also consider testing and possibly preventive options.

Despite efforts to identify individuals who may have a mutation in a breast cancer gene, many mutation carriers remain untested and undetected. In studies of genetic testing in unselected cases, 50% of people with a mutation would be missed by NCCN guidelines. In some cases, this is due to small family size (i.e., lack of other cancers in the family) or lack of knowledge of a family’s medical history. The American Society of Breast Surgeons met to create a consensus guideline for evaluating patients for genetic testing. 

Consensus statement recommendations with details

1. Breast surgeons, genetic counselors and other medical professionals who are knowledgeable in genetic testing can provide patient education, counseling, and recommendations regarding genetic testing.

• Referral to a genetic counselor or genetics professional may be useful for patients who have a medical history or test results that are complex.
   
  • Pre-test counseling improves risk perception accuracy and follow through for testing. Pre-test counseling should include discussion of the types of results that are possible and that testing may not yield clear actionable results. Studies show pre-test counseling reduces distress, improves risk understanding and follow through with testing.
     
  • Post-test counseling is important regardless of the actual result including inconclusive results. NCCN guidelines indicated post-test counseling is current best practice. This allows patients to ask questions and understand the implications and limitations of their results.

[FORCE recommends genetic counseling before and after genetic testing for patients to be appropriately prepared to understand their results and impact of those results. It is important to note that not all health care professionals have had advanced training in genetics. Visit the FORCE website for information on how to find an expert in cancer genetics.]

• There is no consensus about which genes should be tested.
  • Testing should include BRCA1, BRCA2 and PALB2 with other genes as appropriate for the clinical scenario and family history. These include but are not limited to Li-Fraumeni syndrome genes (TP53), Cowden syndrome gene (PTEN), diffuse gastric cancer syndrome gene (CDH1), Peutz-Jagher syndrome gene (STK11).
     
  • Although the ASBS guidelines suggest that evidence is insufficient to warrant changes in breast cancer risk management, there is a growing recognition that mutations in some Lynch syndrome genes (namely MSH6 and PMS2) increase breast cancer risk. See XRAYS review of Lynch syndrome genes and breast cancer here (https://www.facingourrisk.org/XRAY/lynch-syndrome-breast-cancer). Genetic testing for mutations in these Lynch syndrome genes may also be warranted.
     
  • There is no consensus about risk and clinical management of mutations in some genes.

2. Genetic testing should be made available to all patients who have a personal history of breast cancer.

• Identification of a mutation may impact treatment recommendations and systemic therapy.
• Family members may be offered genetic testing and tailored risk reduction strategies.

3. Patients who previously had genetic testing may benefit from updated testing.

• Every patient who has already had genetic testing and with a negative result should be re-evaluated and should also consider having updated testing.
   
• Patients who were tested for mutations in BRCA1 and BRCA2 and for whom no mutation was identified and have no known BRCA1 or BRCA2 mutation in the family should be considered for additional testing, particularly in PALB2 or other potentially relevant genes or certain types of mutations (large genomic rearrangements) in BRCA1 or BRCA2 (that were not previously tested).

4. Genetic testing should be made available to patients who do not have a history of breast cancer, but who meet NCCN guidelines.

• Whenever possible, individuals without breast cancer should be informed that first testing a relative who has cancer may be more informative.
   
• When it is not feasible to test the affected relative first, then the person without cancer should be considered for testing if they are interested, with careful pre-test counseling to explain the limited value of "uninformative negative" results.
   
• It is reasonable to order a multi-gene panel:
  • If the family history is incomplete (i.e., a case of adoption or uncertainty of the type of cancer affecting family members)
  • If the family history includes other cancers

[See FORCE's webpage on Genetic testing for hereditary Cancer for a summary of NCCN guidelines.

5. Variants of uncertain significance are DNA sequences that are NOT clinically actionable (medical care should be managed as it would be without this result).

• The effect of a variant of uncertain significance (VUS) is unknown. Patient care should be based on the individual’s risk factors and not influenced by a VUS result.

[See FORCE’s page on VUS for more information.}

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Limitations:

These guidelines reflect the opinion of the American Society of Breast Surgeons given the current state of knowledge about the genes that increase breast cancer risk. Other professional organizations have not adopted these guidelines as of yet. As new information is available about additional genes or mutations in known genes, recommendations about testing and which results are actionable are expected to change.

Conclusions:

The American Society of Breast Surgeons released a consensus statement recommending that genetic testing should be made available to all patients with a personal history of breast cancer. Genetic counseling before and after genetic testing is recommended. Every patient who has previously had genetic testing with a result of no pathogenic variant identified should be re-evaluated and updated testing considered. Genetic testing should be made available to patients who do not have a history of breast cancer but who meet NCCN guidelines.

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Posted 3/25/19