Guideline for Risk-Reducing Mastectomy
A guideline supporting the clinical procedure of risk-reducing mastectomy for women at increased risk of breast cancer based on genetic testing or personal/family history to assist clinicians and enhance patient experience and outcomes.
Appropriate management of women at high genetic risk of breast cancer can reduce the incidence of the disease. Unaffected women who carry a heritable mutation in a breast cancer predisposition gene such as BRCA1 (the BReast CAncer one gene), BRCA2 (the BReast CAncer two gene), TP53 (tumour protein p53) or PTEN (phosphatase and tensin homolog protein) are at high risk of breast cancer. Women with a mutation who have already had a diagnosis of breast cancer are at an increased risk of contralateral breast cancer. The relative risk of breast cancer for these women compared to those without a gene mutation is high (lifetime risk up to 80%) but is higher at an earlier age (less than 50 years), tapering off in later years. Women at a high genetic risk may consider careful screening, risk-reducing medication or risk-reducing surgery.
Genes and mutation
Specific inherited mutations in BRCA1 and BRCA2 increase the risk of female breast, ovarian, fallopian tube and primary peritoneal cancers, and account for about 5% of all breast cancers and at least 10% of ovarian cancers. BRCA1 and BRCA2 are normal genes that function to repair DNA damage and control cell growth and proliferation. Approximately 1 in 800 people carry a heritable mutation in BRCA1 or BRCA2 (although this rises to 1 in 50 in those of Ashkenazi Jewish background). Individuals with a BRCA1/2 gene mutation often have a strong family history of breast/ovarian cancer but this is not always the case. A BRCA1 or BRCA2 mutation can be inherited from the mother or father. Each child of a parent who carries a mutation in one of these genes has a 50% chance of inheriting that mutation.
Genetic testing is offered through family cancer clinics for those with a family history that indicates a possible inherited gene mutation. There are guidelines to assist in the selection of families that may benefit from testing (see eviQ: an internationally recognised online resource that provides evidence-based cancer treatment information to help health professionals identify the best course of cancer treatment and care for their patient's needs). The testing process usually starts by taking blood from a family member affected by breast or ovarian cancer. This is known as a mutation search. This test determines whether a gene mutation that causes the increased risk of cancer for the family can be identified. If a gene mutation is found, further predictive genetic testing may then be offered to other adult family members.
Genetic testing for heritable breast cancer susceptibility gene mutations (usually BRCA1 and BRCA2, but occasionally other genes) is also sometimes offered shortly after a breast cancer diagnosis and is now being used to inform women’s treatment choices. This generally applies to women who are younger and have either a strong family history of breast and/or ovarian cancer or who have a specific pathology (e.g. triple negative breast cancer - a subtype of breast cancer that is receptor negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2) - at 40 years or younger).
The aim of genetic testing is to identify women who are at high genetic risk. While some of these women are affected by cancer, the majority are unaffected.
High risk patients (affected or unaffected by breast cancer)
The high risk patient group includes:
- those with a heritable mutation in a breast cancer predisposition gene (such as BRCA1, BRCA2, TP53 or PTEN)
- those with a strong family history of breast and/or ovarian cancer (see Category 3 Cancer Australia Familial Aspects of Breast and Ovarian Cancer1)
- those with lobular carcinoma in situ (LCIS) plus a family history of breast cancer. Women with LCIS have an increased risk of developing invasive breast cancer in either breast.
Breast cancer risk reduction
Although intensified screening (using breast magnetic resonance imaging (MRI) in younger women) is offered to women with a high risk of breast cancer, screening does not prevent the disease. Medications such as the selective oestogen receptor modulators tamoxifen and raloxifene, aromatase inhibitors and exemestane reduce the risk of breast cancer, but their exact role in the management of gene mutation carriers is uncertain. Premenopausal risk-reducing salpingo-oophorectomy reduces the risk of breast cancer in women at high genetic risk and this is always advised in women with a proven BRCA1/2 mutation.
The most effective method of breast cancer risk reduction is risk-reducing mastectomy.
Risk-reducing mastectomy should be considered in all women aged under 50 at high genetic risk, whether or not they have a previous history of breast/ovarian cancer. However, counselling should consider the woman’s personal preference, age, general health, life expectancy, plans for further family or breastfeeding and other relevant factors. The benefit of risk-reducing surgery is greater in women under 50.
Breast reconstruction should be offered to all women having risk-reducing mastectomy.
Risk-reducing surgery is not considered an appropriate cancer prevention option for women who do not have a breast cancer-associated gene mutation or who do not have a high risk family history.
Young women with early breast cancer who are identified to have a gene mutation around the time of diagnosis (or who have strong family history) are considered to be at higher risk of developing cancer in the other breast and may choose therapeutic mastectomy (rather than conservation) with risk-reducing contralateral mastectomy as the first line of treatment.
Breast reconstruction following a mastectomy for breast cancer or for those at high risk of breast cancer is considered a medical procedure, not cosmetic surgery. Reconstruction following mastectomy can be offered at the time of mastectomy (immediate) or at a later date (delayed). It can be managed through:
- implant-based reconstruction
- tissue-based reconstruction
- a combination of the implant with tissue-based reconstruction (e.g. implant + latissimus dorsi flap).
Waiting list recommendations
The following points relate to the recommended categorisation of risk reducing mastectomy surgery:
- Bilateral risk-reducing mastectomy, with or without reconstruction: category three (dependent on patient need, diagnosis and urgency of care required)
- Unilateral risk-reducing mastectomy, with or without reconstruction for those who have previously had breast cancer surgery but who have an increased risk of contralateral breast cancer: category three (dependent on patient need, diagnosis and urgency of care required)
- Therapeutic mastectomy with risk-reducing contralateral mastectomy: category one (this should be same category as cancer surgery).
- Biotechnology Australia. 2007. Genetics in Family Medicine: The Australian Handbook for General Practitioners.