Hereditary Breast Cancer

Publication Date: April 3, 2020
Last Updated: March 27, 2023

Management

Recommendation 1.1

Germline BRCA status should not preclude a patient with newly diagnosed breast cancer otherwise eligible for breast conserving therapy (BCT) from receiving BCT. ( CB , Ins , H , M )
3336

Recommendation 1.2

Surgical management of the index malignancy (BCT vs. ipsilateral therapeutic and contralateral risk-reducing mastectomy) in BRCA1/2 mutation carriers should be discussed considering the increased risk of contralateral breast cancer and possible increased risk of an ipsilateral new primary breast cancer compared to non-carriers. ( CB , Ins , B , M )
3336

Recommendation 1.3

The following factors should be considered for assessing risk of contralateral breast cancer (CBC) and role of risk-reducing mastectomy in BRCA1/2 mutation carriers: age of diagnosis (the strongest predictor of future contralateral breast cancer; family history of breast cancer, overall prognosis from this or other cancers (e.g., ovarian), ability of patient to undergo appropriate breast surveillance (MRI), comorbidities, and life expectancy. ( CB , Ins , H , W )
3336

Recommendation 1.4

BRCA1/2 mutation carriers who do not have bilateral mastectomy should undergo high-risk breast screening of remaining breast tissue with annual mammogram and MRI. ( CB , Ins , H , W )
3336

Recommendation 2.1

For women with newly diagnosed breast cancer who have a mutation in a moderate-penetrance breast cancer susceptibility gene, mutation status alone should not determine local therapy decisions for the index tumor or contralateral risk-reducing mastectomy. ( CB , Ins , H , W )
3336

Recommendation 2.2

In breast cancer patients with a mutation in a moderate-penetrance breast cancer susceptibility gene, BCT should be offered to patients for whom BCT is an appropriate treatment option. ( CB , Ins , H , W )
Note: There is a lack of data regarding ipsilateral breast cancer events after BCT among patients with moderate-risk mutations.
3336

Recommendation 2.3

The evidence regarding contralateral breast cancer risk is limited for mutations in moderate-penetrance breast cancer genes, aside from some data for CHEK2 1100delC. ( CB , Ins , H , W )
Note: Information about the specific gene and what is known about the risk of contralateral breast cancer should be discussed in the context of shared decision-making.
3336

Recommendation 2.4

Patients with mutations in moderate-penetrance genes who do not have bilateral mastectomy should undergo high-risk breast screening of remaining breast tissue with annual mammogram and MRI. ( CB , Ins , H , W )
3336

Recommendation 3.1

For women with newly diagnosed breast cancer undergoing mastectomy who have a deleterious mutation in BRCA 1 or 2, nipple-sparing mastectomy is a reasonable oncologic approach to consider in appropriately selected patients. ( CB , Ins , H , M )
3336

Recommendation 3.2

For women with newly diagnosed breast cancer undergoing mastectomy who have a deleterious mutation in moderate-penetrance genes, nipple-sparing mastectomy is a reasonable oncologic approach to consider in appropriately selected patients. ( CB , Ins , H , W )
3336

Recommendation 4.1

For women with breast cancer who have a BRCA1/2 mutation and who have been treated or are being treated with unilateral mastectomy, contralateral risk-reducing mastectomy (CRRM) should be offered. CRRM is associated with a decreased risk of contralateral breast cancer; there is insufficient evidence for improved survival. ( CB , Ins , H , M )
Note: The following factors should be considered for assessing risk of CBC and role of risk-reducing mastectomy: age of diagnosis (the strongest predictor of future contralateral breast cancer), family history of breast cancer, overall prognosis from this or other cancers (e.g., ovarian), ability of patient to undergo appropriate breast surveillance (MRI), comorbidities, and life expectancy.
3336

Recommendation 4.2

For women with breast cancer who have a mutation in a moderate-penetrance breast cancer predisposition gene and who have been treated or are being treated with unilateral mastectomy, the decision regarding CRRM should not be based predominantly on the mutation status. ( CB , Ins , H , W )
Note: Additional factors that predict CBC such as age at diagnosis and family history should be considered, as they are in all cases. The impact of CRRM on decreasing risk of CBC is dependent on the risk of CBC for each individual gene. Data regarding the risk of CBC due to moderate-penetrance genes are limited.
3336

Recommendation 5.1

For breast cancer patients with a deleterious germline BRCA1/2 mutation interested in a contralateral risk-reducing mastectomy, physicians should discuss the option of nipple-sparing mastectomy as a reasonable oncologic option. ( CB , Ins , B , M )
3336

Recommendation 5.2

For breast cancer patients with a mutation in a moderate-penetrance gene who are interested in a contralateral risk-reducing mastectomy, physicians should discuss the option of nipple sparing mastectomy as a reasonable oncologic option. ( CB , Ins , H , W )
3336

Recommendation 6.1

For women with breast cancer who are treated with BCT or with mastectomy for whom post-mastectomy radiotherapy is considered, radiation therapy should not be withheld due to mutation status, except for mutations in TP53 (see Recommendation 6.3). ( CB , Ins , B , M )
Note: There is no evidence of a significant increase in toxicity or contralateral breast cancers (CBC) related to radiation exposure among patients with a mutation in a BRCA1/2 or a moderate-penetrance gene.
3336

Recommendation 6.2

For women with breast cancer who are carriers of an ATM mutation, radiation therapy should be offered when clinically indicated. Data regarding rates of toxicity between ATM mutation carriers and non-carriers are limited and inconsistent. Potential absolute risks appear to be small. However, more research is needed. ( CB , Ins , H , W )
Note: Discussion with ATM carriers interested in BCT is encouraged.
3336

Recommendation 6.3

For women with breast cancer who are carriers of a germline TP53 mutation, radiotherapy of the intact breast is contraindicated. Mastectomy is the recommended therapeutic option. Postmastectomy radiation therapy should only be considered in patients with significant risk of locoregional recurrence. ( CB , Ins , H , W )
3336

Recommendation 7

When offering chemotherapy for germline BRCA mutation carriers with metastatic breast cancer, platinum chemotherapy is preferred to taxane therapy for patients who have not previously received platinum. There are no data to address platinum efficacy in other germline mutation carriers. ( CB , Ins , H , M )
3336

Recommendation 8

For germline BRCA mutation carriers with breast cancer treated with (neo)adjuvant therapy, data do not support the routine addition of platinum to anthracycline and taxane-based chemotherapy. While single-agent platinum has demonstrated activity in the neoadjuvant setting, there are no data yet comparing it to standard chemotherapy. There are no data to address platinum efficacy in other germline mutation carriers. ( EB , Ins , H , M )
3336

Recommendation 9.1

For BRCA1/2 mutation carriers with metastatic HER2-negative breast cancer, olaparib or talazoparib should be offered as an alternative to chemotherapy in the 1st-3rd line setting. For BRCA1/2 mutation carriers with metastatic HER2-negative breast cancer, there are no data directly comparing efficacy of PARP inhibitor to platinum chemotherapy. ( EB , Ins , B , S )
3336

Recommendation 9.2

For breast cancer patients with mutations in moderate-penetrance genes, there are currently no robust data to support the use of PARP inhibitors. (IC, U, M, Ins)
3336

Recommendation 10

For germline BRCA mutation carriers, there is insufficient data at this time to recommend a PARP inhibitor for patients with non-metastatic breast cancer. ( EB , Ins , H , M )
3336

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

Management of Hereditary Breast Cancer

Authoring Organizations

Publication Month/Year

April 3, 2020

Last Updated Month/Year

April 13, 2023

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Target Patient Population

Women with hereditary breast cancer with germline mutations, advanced or early stage

Target Provider Population

Medical oncologists, radiation oncologists, surgical oncologists, oncology nurses, patients/caregivers

Inclusion Criteria

Female, Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Operating and recovery room, Outpatient, Radiology services

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Assessment and screening, Management

Diseases/Conditions (MeSH)

D061325 - Hereditary Breast and Ovarian Cancer Syndrome

Keywords

breast cancer, Hereditary Breast Cancer, Hereditary Cancer, PARP Inhibitors, germline mutations, Breast Cancer

Source Citation

DOI: 10.1200/JCO.20.00299 Journal of Clinical Oncology

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
58
Literature Search Start Date
January 1, 1999
Literature Search End Date
September 26, 2019
Description of External Review Process
The ASCO/ASTRO/SSO Writing Panel included medical oncology, surgical oncology, radiation oncology, patient representative, and 2 methodologists. ASCO's Clinical Practice Guideline Oversight Committee, ASTRO's Clinical Practice Guideline Committee, and SSO's Breast Cancer Disease Site Work Group concurrently conducted external review prior to respective Society endorsement determination.
Description of Public Comment Process
ASCO Guidelines are available for open comment for a 2 week period. Guideline recommendations available for open comment are posted on asco.org/open‐comment‐guidelines. Prospective reviewers must contact ASCO to request to review the draft guideline recommendations and are required to sign a non‐disclosure and confidentiality agreement before receiving the draft guideline recommendations. Reviewers must identify themselves by name and affiliation; anonymous comments will not be accepted. Guidelines staff review and summarize comments and bring relevant comments to the Expert Panel Co‐ chairs, and to the entire panel if necessary. Any changes made from the open comment process will be reviewed by the entire panel prior to CPGC approval. Comments are advisory only and ASCO is not bound to make any changes based on feedback from open comment. ASCO does not respond to reviewers or post responses to comments; however, major edits to the draft will be reflected in the open comment discussion.
Specialties Involved
Family Medicine, Internal Medicine General, Medical Genetics And Genomics, Oncology, Medical Oncology, Surgical Oncology, Radiation Oncology, Oncology, Oncology, Oncology
Description of Systematic Review
The Protocol specifies the purpose of the guideline product, target patient population, clinical outcomes of interest, key features of the systematic literature review, and a proposed timeline for completion. ASCO staff, the Expert Panel Co‐Chairs, and possibly other panel members selected by the Co‐Chairs (the Expert Panel Steering Committee), will typically draft the protocol for full panel review. A standard protocol worksheet is used for consistency. Once the Co‐Chairs have approved a first draft of the Protocol, the Protocol will be shared with the full Expert Panel. At the discretion of the Guidelines Director, the CPGC leadership and/or the CPGC Methodology Subcommittee may review the Protocol to make suggestions for revision intended to clarify aspects of the plan for developing the guideline. These suggestions are sent to the Expert Panel Co‐Chairs. Work on the systematic literature review can proceed upon the sign‐off of the Protocol by the Expert Panel.
List of Questions
This clinical practice guideline addresses 10 clinical questions: What is the appropriate surgical management of the index malignancy for women with newly diagnosed nonmetastatic breast cancer who have a BRCA1/2 mutation? What is the appropriate surgical management of the index malignancy for women with newly diagnosed nonmetastatic breast cancer who have a selected moderate-penetrance mutation? Among women with breast cancer who have a BRCA1/2 germline mutation or selected moderate-penetrance non-BRCA1/2 germline mutation who are undergoing therapeutic mastectomy, what is the role of nipple-sparing mastectomy? What is the role of contralateral prophylactic mastectomy for women with breast cancer who have a BRCA1/2 mutation or a selected moderate-penetrance gene mutation? Among women with breast cancer who have a BRCA1/2 germline mutation or selected moderate-penetrance mutation who are undergoing contralateral risk-reducing mastectomy (CRRM), what is the role of nipple-sparing mastectomy? What is the role of RT in women with breast cancer who have a BRCA1/2 germline mutation or selected moderate-penetrance non-BRCA1/2 germline mutation? What is the role of platinum chemotherapy in women who have a BRCA1/2 mutation or selected moderate-penetrance germline mutation and advanced breast cancer? What is the role of (neo)adjuvant platinum chemotherapy in women who have a BRCA1/2 mutation or selected moderate-penetrance germline mutation and breast cancer? What is the role of poly (ADP-ribose) polymerase (PARP) inhibitors in women who have a BRCA1/2 mutation or selected moderate-penetrance germline mutation and advanced breast cancer? What is the role of PARP inhibitors in women who have a BRCA1/2 mutation or selected moderate-penetrance mutation and nonmetastatic breast cancer?
Description of Study Criteria
The recommendations for the local therapy clinical questions were developed by using a systematic review of the literature and clinical experience. The literature review involved searches of PubMed for the period from January 1, 2010, through September 26, 2019 (surgery search), or January 1, 1999, through September 26, 2019 (RT search). The searches were broad and included a combination of treatment, genetic mutation, and breast cancer search terms (see Data Supplement [online only] 1 for more details of the literature search). Articles from the search were included if they reported data on outcomes of local therapy (therapeutic or prophylactic mastectomy, nipple-sparing mastectomy, RT) among women with newly diagnosed nonmetastatic or advanced breast cancer and a high- or moderate-penetrance germline mutation. Disease outcomes considered in the studies included in the literature were ipsilateral events, including true recurrences and new primary tumors, survival, cosmesis, contralateral breast cancer (CBC), and treatment toxicity/complications. An article was excluded from the local therapy literature review if (1) it was a narrative (v systematic) review of the literature, (2) it reported on a single case, (3) it reported on a study with a variant that was not pathogenic or likely pathogenic (eg, single-nucleotide polymorphisms or variant overexpression in the tumor), (4) it was a meeting abstract not subsequently published in peer-reviewed journal, or (5) it reported exclusively on a study of a group of women who received postmastectomy RT versus breast-conserving surgery (BCS) plus RT.
Description of Search Strategy
Upon approval of the Protocol, a systematic review of the medical literature is conducted. ASCO staff use the information entered into the Protocol, including the clinical questions, inclusion/exclusion criteria for qualified studies, search terms/phrases, and range of study dates, to perform the systematic review. Literature searches of selected databases, including The Cochrane Library and Medline (via PubMed) are performed. Working with the Expert Panel, ASCO staff complete screening of the abstracts and full text articles to determine eligibility for inclusion in the systematic review of the evidence. Unpublished data from meeting abstracts are not generally used as part of normal ASCO guideline development (“Meeting Data”). However, abstract data from reputable scientific meetings and congresses may be included on a case‐by‐case basis after review by the CPGC leadership. Expert Panels should present a rationale to support integration of abstract data into a guideline. The CPGC leadership will consider the following inclusion criteria for the unpublished scientific meeting data: 1) whether the data were independently peer reviewed in connection with a reputable scientific meeting or congress; 2) the potential clinical impact of the unpublished data; 3) the methodological quality and validity of the associated study; 3) the potential harms of not including the data; and 4) the availability of other published data to inform the guideline recommendations.
Description of Study Selection
Literature search results were reviewed and deemed appropriate for full text review by two ASCO staff reviewers in consultation with the Expert Panel Co-Chairs. Data were extracted by two staff reviewers and subsequently checked for accuracy through an audit of the data by another ASCO staff member. Disagreements were resolved through discussion and consultation with the Co-Chairs if necessary. Evidence tables are provided in the manuscript and/or in Data Supplement.
Description of Evidence Analysis Methods
ASCO guideline recommendations are crafted, in part, using the GuideLines Into DEcision Support (GLIDES) methodology. ASCO adopted a five‐step approach to carry out quality appraisal, strength of evidence ratings and strength of recommendations ratings. The ASCO approach was primarily adapted from those developed by the AHRQ,, USPSTF, and GRADE, however with the validation of the GRADE methodology, the sole use of GRADE is being evaluated by the Clinical Practice Guidelines Committee.
Description of Evidence Grading
High: High confidence that the available evidence reflects the true magnitude and direction of the net effect (i.e., balance of benefits v harms) and that further research is very unlikely to change either the magnitude or direction of this net effect. Intermediate: Moderate confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research is unlikely to alter the direction of the net effect; however, it might alter the magnitude of the net effect. Low: Low confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research may change either the magnitude and/or direction this net effect. Insufficient: Evidence is insufficient to discern the true magnitude and direction of the net effect. Further research may better inform the topic. The use of the consensus opinion of experts is reasonable to inform outcomes related to the topic.
Description of Recommendation Grading
ASCO uses a formal consensus methodology based on the modified Delphi technique in clinically important areas where there is limited evidence or a lack of high‐quality evidence to inform clinical guidance recommendations. Evidence Based: There was sufficient evidence from published studies to inform a recommendation to guide clinical practice. Formal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. Therefore, the Expert Panel used a formal consensus process to reach this recommendation, which is considered the best current guidance for practice. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). The results of the formal consensus process are summarized in the guideline and reported in the Data Supplement (see the Supporting Documents" field). Informal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. The recommendation is considered the best current guidance for practice, based on informal consensus of the Expert Panel. The Panel agreed that a formal consensus process was not necessary for reasons described in the literature review and discussion. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). No recommendation: There is insufficient evidence, confidence, or agreement to provide a recommendation to guide clinical practice at this time. The Panel deemed the available evidence as insufficient and concluded it was unlikely that a formal consensus process would achieve the level of agreement needed for a recommendation.
Description of Funding Source
ASCO provides funding for Guideline Development.
Company/Author Disclosures
ASCO Conflict of Interest Policy complies with the CMSS Code for Interactions with Companies. ASCO requires disclosure by individuals involved in drafting, reviewing, and approving guideline recommendations.
Percentage of Authors Reporting COI
100