Kathleen Cuningham Foundation Consortium for research into Familial Breast cancer
Current criteria - Amended February 2008
CATEGORY 1. Families in which no predisposition mutation has been identified. All of the following are required:
Important, please note: Multicase families fitting the criteria for category 1 should be submitted to kConFab with the usual pedigree information and the clinic’s Manchester or BrcaPro score(s), so that this information can be used to select families for recruitment.
CATEGORY 2. Families in which a BRCA1 or BRCA2 mutation has been identified (pathogenic, splice site or unclassified variant). kConFab will recruit all families in which there are at least two or more living potential female mutation carriers (affected and/or unaffected) amongst first and second degree relatives from the informative side of the family.
CATEGORY 3. Families with mutations in other breast cancer predisposition genes.
A small number of pedigrees submitted by the FCC have some features of other cancer syndromes that include breast cancer and are of interest to kConFab because they carry mutations in PTEN, TP53 or ATM. Families that carry pathogenic mutations in these genes and have two or more living carriers, or potential carriers are eligible for enrolment into kConFab. Families must carry a mutation to be enrolled into Category 3.
If the clinical features suggest a relevant cancer syndrome (eg LiFraumeni Syndrome) but no mutation has been identified, the family can only be enrolled if they fulfil the Category 1 criteria.
CATEGORY 4. High risk breast cancer families from which tumour is available but who do not fit other kConFab criteria.
Families that fit the National Breast Cancer Centre Category 111 guidelines but do not fit category 1, 2 or 3 above are of value to kConFab if a family member wishes to enrol in kConFab and consent for a portion of their tumour (breast and ovarian) to be collected from surgery and used for research.
Previous criteria - Amended February 2007 - this section for reference only. See above for current criteria
kConFab wants to recruit families that fit the specific criteria. The initial criteria were set in 1997 following review of >700 family pedigrees that were provided by Family Cancer Clinics in Australia and New Zealand. The criteria were revised in 2000 to include BRCA1/2 carriers who were having surgery but did not fulfil the kConFab criteria, and in 2003 to include male breast cancer as a high-risk feature, families with two cases of ovarian cancer but only one or fewer cases of breast cancer, and high-risk women who were having surgery (even if they are not known to carry BRCA1/2 mutations) who do not fulfil the other kConFab criteria. These criteria define kConFab’s requirements for the number of individuals affected by breast cancer in each family, and for the number of unaffected potential carriers of mutations in genes that predispose to breast cancer. Members of the families that fit these criteria are asked whether they wish to enter the kConFaB research study. Those agreeing to do so are asked to complete epidemiological and dietary questionnaires and to provide blood samples for genetic testing. With their permission, data collected from individual family members are entered into the KConFab database.
1. Families in which no predisposing mutation has been identified
All of the following are required:
1+. CATEGORY 1 FAMILIES WITH FOUR OR MORE LIVING AFFECTEDS WITH BREAST CANCER (not two or three such cases as previously collected under Category 1) AND THEY WILL BE REFERRED TO A CATEGORY 1+ (“ONE-PLUS”) FAMILIES
1B. Families in which no predisposing mutation has been identified
All of the following are required:
2. Families in which a BRCA1 or BRCA2 mutation has been identified
kConFab is interested in “mutation-positive” families where there are two or more carriers (or likely carriers amongst first and second degree relatives from the informative side of the family). Not all mutation-positive families will fit these criteria. A ‘mutation-carrier’ is defined for this purpose as the carrier of a pathogenic, splice site or unclassified variant in BRCA1 or BRCA2.
For inclusion in KConFab, mutation-positive families must fulfil at least one of the following criteria:
The criteria for families that have been shown to carry a predisposing mutation are summarised in the following table. Each column in the table shows the number of affected individuals, and the number of first- and second-degree female relatives of affecteds that are required for enrolment of a mutation-positive family in KconFab.
Criteria for Families in which a Predisposing Mutation has been Identified
|Affected individuals or proven female carriers||2||1||1||1||0||0||0||0||0|
|First-degree female relative of affected or proven female carrier||0||2||1||0||4||3||2||1||0|
|Second degree female relative of affected or proven female carrier||0||0||2||4||0||2||4||6||8|
3. Families with mutations in other breast cancer predisposing genes
A small number of pedigrees submitted by the FCCs have some features of other cancer syndromes that include breast cancer and are of interest to KConFab because they carry mutations in PTEN, TP53, or ATM. Families that carry pathogenic mutations in these genes, and have two or more alive carriers, or potential carriers (see above) are eligible for enrolment into kConFab. Families must carry a mutation to be enrolled under Category 3.
If the clinical features suggest a relevant cancer syndrome (eg Li Fraumeni Syndrome) but no mutation has been identified, the family can only be enrolled if they fulfil the criteria for Category 1 or 1B.
3B. Families with a clinically relevant p53 mutation
As of Sept 2006, kConFab will recruit families with clinically relevant p53 mutations, even if there is only one alive male or female carrier, affected or unaffected.
4. High-risk breast cancer families from which fresh tumour is available, but who do not fit other kConFab criteria
Families that fit the National Breast Cancer Centre Category III guidelines (http://www.nbcc.org.au), but do not fit the 1, 1A or 2 criteria above, are of value to kConFab (whether or not they are known to carry a BRCA1 or BRCA2 mutation) if a family member wishes to enrol in kConFab and consent for a portion of their tumour to be collected from surgery and used for research.
FROM FEBRUARY 2007 WE WILL COLLECT ALL FAMILIES THAT FIT THE NBCC CATEGORY III GUIDELINES, BUT DO NO FIT THE 1+, 3 OR 3B CRITERIA, IF A FAMILY MEMBER WISHES TO ENROL IN kConFab AND CONSENT FOR A PORTION OF THEIR TUMOUR (OF ANY TYPE) TO BE COLLECTED BY kConFab.
** NOTE: as previously we will recruit families through Category 4 if a woman is having surgery for a suspected tumour. As previously, we will also collect normal tissue that is prophylactically removed at the time of this surgery for a suspected tumour. However, we will no longer collect tissue from prophylactic surgeries if no tumour is suspected.
5. Families with two cases of ovarian cancer among first degree relatives which do not fit any of the other kConFab criteria.
From January 2003, kConFab will start to enrol families with two or three cases of ovarian cancer.
All of the following are required: