Hereditary Breast and Ovarian Cancer
The aetiology of breast and ovarian cancer is multifactorial and associated with genetic and non-genetic risk factors. Among the genetic risk factors, two genes are associated with the majority of HBOC families: BRCA1 and BRCA2. BRCA stands for BReast CAncer. A woman with a BRCA1 or BRCA2 pathogenic variant has a high lifetime risk of developing breast cancer up to 60-80%, whereas the risk for an average woman is about 13%. A woman with a BRCA1 pathogenic variant has up to 40% risk of developing ovarian cancer, usually of a high-grade serous type. A woman with a BRCA2 pathogenic variant has up to 20% risk, whereas the risk for an average woman is about 1-2%. Female carriers who have had breast cancer, have an increased risk for second primary breast cancer. Men with a BRCA2 pathogenic variant may also have an increased risk of breast cancer up to 8% and prostate cancer up to 12%, while men with a BRCA1 pathogenic carrier have similar risks to non-carriers.
BRCA1 or BRCA2 pathogenic variants are the most common ones identified in HBOC families. Other genes less commonly associated with an increased risk of developing breast cancer include PALB2, CHEK2, ATM, BARD1, RAD51C/D, PTEN and TP53.
Genes linked to ovarian cancer include RAD51C, RAD51D, BRIP1 and the Lynch syndrome genes (MSH2, MSH6, MLH1, PMS2).
There is also the possibility of increased genetic risk due to the combination of multiple low-risk genetic alterations (called polygenic risk), which constitutes the genetic architecture of a person. This polygenic combination is independent of other high risk genetic alterations and may modify their average risk.
The probability of transmission of the altered gene copy from the affected parent to the offspring is 50%, regardless of the gender.
The surveillance depends on the level of the risk which varies on which gene is involved and the family history of cancer.
Breast surveillance should begin at age 25-30 and include clinical examinations, breast MRI and also mammograms at a later time.
Besides screening, preventive surgical removal of both breasts can reduce the risk of breast cancer by more than 90%. Only about 3% of breast cancers associated with BRCA1/2 pathogenic variants are diagnosed before age 30, so surgery could be deferred to over the age of 30 for most women.
Screening for ovarian cancer is not recommended. Preventive surgical removal of the ovaries and fallopian tubes can reduce the risk of ovarian cancer by approximately 90%. Preventive surgery is therefore advised starting from the age of 35-40 (BRCA1) or 40-45 (BRCA2) years. Alternatively, the fallopian tubes may be removed up to 5 years prior to removal of the ovaries (TUBA WISP II study).
More information regarding HBOC can be found on:
GeneReviews® - BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer
Orphanet: Hereditary breast and/or ovarian cancer syndrome
https://www.genomicseducation.hee.nhs.uk/resources/genetic-conditions-factsheets/item/80-hereditary-breast-and-ovarian-cancer/
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Clinical practice guidelines |
ERN GENTURIS care pathway |
ERN GENTURIS patient journey |
ERN GENTURIS publications |
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Endorsed guidelines for Hereditary breast and ovarian cancer syndrome |
Care pathway - Hereditary breast and ovarian cancer syndrome (HBOC) |
Patient journey - Hereditary breast and ovarian cancer syndrome (HBOC) |
Thematic Group 3: Hereditary breast and ovarian cancer syndrome |
ERN GENTURIS webinars - Thematic group 3: Hereditary breast and ovarian cancer syndrome (HBOC)
ERN GENTURIS webinars - General
A list of healthcare providers with expertise in Thematic Group 3: Hereditary breast and ovarian cancer syndrome can be found here.
A non-exhaustive list of patient associations for genetic tumour risk syndromes in EU member states can be found here.