Individual with any of the following:

1. Living affected individual (proband) with:

a)Breast cancer < 30 years, OR

b)Breast cancer < 40 years if high-grade and HER-2 negative, OR

c)Bilateral breast cancer, both < 50 years, OR

d)Triple negative breast cancer < 60 years, OR

e)Breast and serous ovarian cancer (any age), OR

f)High-grade serous ovarian cancer < 70 years, OR

g)Breast cancer < 45 years and a FDR with breast cancer < 45 years, OR

h)Pathology-adjusted Manchester score 15+ or BOADICEA score >10%

2. Living unaffected individual with:

a)FDR affected by breast or serous ovarian cancer, AND

b)Pathology-adjusted Manchester score ≥20 or BOADICEA score ≥20% (for the FDR), AND

c)No living affected individual is available for genetic testing, AND

d)No deceased affected individual with tumour material available for testing

3. Deceased affected individual with breast or ovarian cancer with:

a)A stored DNA, blood or tissue sample available for DNA extraction, AND

b)Pathology-adjusted Manchester score 15+ or BOADICEA score 10%, AND

c)No living affected individual is available for genetic testing

4. Offer testing for 3 common Ashkenazi Jewish founder BRCA1 and BRCA2 gene mutations in individuals with:

a) Ashkenazi Jewish ancestry, AND

b)Personal history of breast or ovarian cancer, OR

c)Relative (FDR, SDR or TDR) with breast or ovarian cancer

-FDR = First degree relative; SDR = Secord degree relative; TDR = Third degree relative.

-Relative = FDR or SDR only, except when calculating a Manchester score. Females through an intervening male shift up one degree of relationship.

-The proband's cancer and majority of reported cancers in the family should have been confirmed.

-Testing should principally be targeted at those where a molecular diagnosis will guide management or alter advice.

Pathology-adjusted Manchester Scoring System

Cancer, age at diagnosis / BRCA1 / BRCA2
FBC,<30 / 6 / 5
FBC, 30–39 / 4 / 4
FBC, 40–49 / 3 / 3
FBC, 50–59 / 2 / 2
FBC,>59 / 1 / 1
MBC,<60 / 5 / 8
MBC,>59 / 5 / 5
Ovarian cancer,<60 / 8 / 5
Ovarian cancer,>59 / 5 / 5
Pancreatic cancer / 0 / 1
Prostate cancer,<60 / 0 / 2
Prostate cancer,>59 / 0 / 1
Breast cancer path adjustment in index case
Grade 3 / 2 / 0
Grade 1 / −2 / 0
ER positive / −1 / 0
ER negative / 1 / 0
Triple negative / 4 / 0
HER2+ / −6 / 0
Ductal carcinoma in situ / −2 / 0
Lobular / −2 / 0
Ovarian cancer adjustment – any case in family*
Mucinous germ cell or borderline tumours / No score, that is, score as 0 / No score, that is, score as 0
Highgrade serous<60 / +2 / 0
Adopted no known status in blood relatives / +2 / +2

*As long as not related to index case through more than one unaffected woman aged>60years.

FBC,female breast cancer; MBC, male breast cancer.

EvansDG,HarknessEF,PlaskocinskaI, et al. Pathology update to the Manchester Scoring System based on testing in over 4000 families. Journal of Medical Genetics2017;54:674-681.

12.03.2018 AM and LS Review date: March 20201