Germline Testing in Patients with Breast Cancer

Publication Date: January 3, 2024
Last Updated: January 4, 2024

Treatment

Recommendation 1.1

All patients newly diagnosed with breast cancer with stage I–III or de novo stage IV/metastatic disease who are 65 years of age or younger at diagnosis should be offered BRCA1/2 testing. (CB, , , )
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Recommendation 1.2

All patients newly diagnosed with breast cancer with stage I–III or de novo stage IV/metastatic disease who are older than age 65 should be offered BRCA1/2 testing if:
  • they are candidates for poly (ADP-ribose) polymerase (PARP) inhibitor therapy for early-stage or metastatic disease,
  • they have triple-negative breast cancer,
  • their personal or family history suggests the possibility of a pathogenic variant,
  • they were assigned male sex at birth,
  • they are of Ashkenazi Jewish ancestry or are members of a population with an increased prevalence of founder mutations.
(CB, , , )
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Recommendation 1.3

Patients undergoing BRCA1/2 testing should also be offered testing for other cancer predisposition genes as suggested by their personal or family history. Consultation with a provider experienced in clinical cancer genetics can help guide this decision-making and should be made available to patients when possible. (CB, , , )
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Recommendation 2.1

All patients with recurrent breast cancer (local or metastatic) who are candidates for PARP inhibitor therapy should be offered BRCA1/2 testing regardless of family history. (CB, , , )
Qualifying statement: Small single-arm studies show that oral PARP inhibitor therapy demonstrates high response rates in women with metastatic breast cancer and germline pathogenic variants in PALB2.
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Recommendation 2.2

BRCA1/2 testing should be offered to patients with a second primary cancer either in the contralateral or ipsilateral breast. (CB, , , )
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Recommendation 3.1

All patients with a personal history of breast cancer diagnosed at or before age 65 years who are without active disease should be offered BRCA1/2 testing if the result will inform personal risk management or family risk assessment. (CB, , , )
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Recommendation 3.2

All patients with a personal history of breast cancer diagnosed over age 65 with no active disease, who meet one of the following criteria, should be offered BRCA1/2 testing if the result will inform personal risk management or family risk assessment:
  • their personal or family history suggests the possibility of a pathogenic variant,
  • they were assigned male sex at birth,
  • they had triple-negative breast cancer,
  • they are of Ashkenazi Jewish ancestry or are members of a population with an increased prevalence of founder mutations.
(CB, , , )
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Recommendation 4.1

Testing for high penetrance genes beyond BRCA1/2, including PALB2, TP53, PTEN, STK11, and CDH1, could inform medical therapy, influence surgical decision making, refine estimates of risks of second primary cancer, and inform family risk assessment, and thus should be offered to appropriate patients. (CB, , , )
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Recommendation 4.2

Testing for moderate penetrance breast cancer genes currently offers no benefits for treatment of the index breast cancer but may inform risks of second primary cancer or family risk assessment, and thus may be offered to appropriate patients who are undergoing BRCA1/2 testing. (CB, , , )
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Recommendation 4.3

If a multi-gene panel is ordered, the specific panel chosen should take into account the patient’s personal and family history. Consultation with a provider experienced in clinical cancer genetics can be helpful in selecting a specific multi-gene panel or interpreting its results and should be made available to patients when possible. (CB, , , )
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Recommendation 5.1

Patients undergoing genetic testing should be given sufficient information before testing to provide informed consent. (CB, , , )
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Recommendation 5.2

Patients with pathogenic variants should be provided with individualized post-test genetic counseling and offered referral to a provider experienced in clinical cancer genetics. (CB, , , )
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Recommendation 5.3

Variants of uncertain significance should not alter management. Patients should be made aware that variants of uncertain significance may be reclassified as being pathogenic, and they should understand that periodic follow up is necessary. Consultation with a provider experienced in clinical cancer genetics can be helpful and should be made available to patients when possible. (CB, , , )
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Recommendation 5.4

Patients without a pathogenic variant on genetic testing may still benefit from counseling, if there is a significant family history of cancer, and referral to a provider experienced in clinical cancer genetics is recommended. (CB, , , )
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Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Germline Testing in Patients with Breast Cancer

Authoring Organizations

American Society of Clinical Oncology

Society of Surgical Oncology

Publication Month/Year

January 3, 2024

Last Updated Month/Year

September 30, 2024

Document Type

Guideline

Country of Publication

US

Document Objectives

To develop recommendations for germline mutation testing for patients with breast cancer.

Target Patient Population

Patients with breast cancer

Target Provider Population

Oncologists, surgeons, medical geneticists, and genetic counselors.

PICO Questions

  1. Which patients with breast cancer should have germline genetic testing for pathogenic variants in cancer susceptibility genes?

  2. Should clinicians offer BRCA1/2 testing to all patients with newly diagnosed breast cancer?

  3. Should all people with recurrent disease, local or metastatic, or with second breast primary, be offered BRCA1/2 testing?

  4. Should people with a personal history of breast cancer (and no active disease) be offered BRCA1/2 testing?

  5. What is the value of testing patients with a diagnosis of breast cancer for breast cancer predisposition genes other than BRCA1/2?

  6. How should patients with breast cancer considering genetic testing be counseled?

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Outpatient

Intended Users

Genetics, nurse, nurse practitioner, physician, physician assistant

Scope

Counseling, Treatment

Diseases/Conditions (MeSH)

D001943 - Breast Neoplasms, D005817 - Genetic Counseling, D006580 - Genetic Carrier Screening, D005816 - Genetic Complementation Test, D005819 - Genetic Markers, D020022 - Genetic Predisposition to Disease

Keywords

breast cancer, Germline Testing, BRCA1, BRCA2, BRCA 1/2 testing

Source Citation

Bedrosian I, et al. Germline Testing in Patients with Breast Cancer: ASCO-SSO Guideline. J Clin Oncol. 2024 Jan 04. doi: 10.1200/JCO.23.02225

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
102
Literature Search Start Date
September 19, 2012
Literature Search End Date
January 11, 2023