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Manchester score: Predicting germline BRCA mutation in individual affected by cancer
Step 1: Assign score for current (index) patient
Gender
Female
Male
Is there a personal history of more than one BRCA associated primary cancer? Relevant cancers are: breast (including DCIS but not LCIS), ovarian, pancreatic or prostate cancer.

Only select YES if each was a new primary. i.e. not a recurrence or secondary.
No
Yes
Number of relevant primary cancers:

Breast cancer aged < 30 years +11 points
Breast cancer aged 30-39 years +8 points
Breast cancer aged 40-49 years +6 points
Breast cancer aged 50-59 years +4 points
Breast cancer aged ≥ 60 years +2 points
Epithelial ovarian Do not count borderline, germ-cell or mucinous histologies. cancer aged < 60 years +13 points
Epithelial ovarian Do not count borderline, germ-cell or mucinous histologies. cancer aged ≥ 60 years +10 points
Pancreatic cancer +1 points

Lobular histology -2 points
DCIS -2 points
Invasive ductal carcinoma 0 points

Grade 1 -2 points
Grade 2 0 points
Grade 3 +2 points

ER positive, HER2 positive -7 points
ER negative, HER2 positive -5 points
ER positive, HER2 negative -1 points
PR positive, ER negative, HER2 negative +1 points
Triple negative +4 points

High grade serous histology +2 points
Not high grade serous histology 0 points

Breast cancer aged < 60 years +13 points
Breast cancer aged ≥ 60 years +10 points
Prostate cancer aged < 60 years +2 points
Prostate cancer aged ≥ 60 years +1 points
Pancreatic cancer +1 points

Lobular histology -2 points
DCIS -2 points
Invasive ductal carcinoma 0 points

Grade 1 -2 points
Grade 2 0 points
Grade 3 +2 points

ER positive, HER2 positive -7 points
ER negative, HER2 positive -5 points
ER positive, HER2 negative -1 points
PR positive, ER negative, HER2 negative +1 points
Triple negative +4 points
Select patients cancer history: For breast cancer include invasive ductal or lobular carcinoma and DCIS. Do not include LCIS.
Breast cancer aged < 30 years +11 points
Breast cancer aged 30-39 years +8 points
Breast cancer aged 40-49 years +6 points
Breast cancer aged 50-59 years +4 points
Breast cancer aged ≥ 60 years +2 points
Epithelial ovarian Do not count borderline, germ-cell or mucinous histologies. cancer aged < 60 years +13 points
Epithelial ovarian Do not count borderline, germ-cell or mucinous histologies. cancer aged ≥ 60 years +10 points
Pancreatic cancer +1 points
No personal history of cancers listed above 0 points
Select patients cancer history: For breast cancer include invasive ductal or lobular carcinoma and DCIS. Do not include LCIS.
Breast cancer aged < 60 years +13 points
Breast cancer aged ≥ 60 years +10 points
Prostate cancer aged < 60 years +2 points
Prostate cancer aged ≥ 60 years +1 points
Pancreatic cancer +1 points
No personal history of cancers listed above 0 points
Adjust score for breast cancer histology
Invasive ductal carcinoma 0 points
DCIS only -2 points
Lobular -2 points

Grade 3 +2 points
Grade 2 0 points
Grade 1 -2 points

ER positive, HER2 positive -7 points
ER negative, HER2 positive -5 points
ER positive, HER2 negative -1 points
PR positive, ER negative, HER2 negative +1 points
Triple negative +4 points

High grade serous histology?
Yes +2 points
No 0 points
Does this patient lack knowledge of family history (e.g. adopted)?
Yes +4 points
No 0 points
Step 2: Assign score for family history
Does this patient have a family history of BRCA associated cancer? i.e. Breast, ovarian, prostate or pancreas cancer.

Affected family members can be on the maternal or paternal lineage, but will be scored seperately below. The lineage with the highest score will be used in final calculation.

Affected relatives should only be counted if there is no more than one intervening female unaffected by cancer. Cancers through intervening unaffected male relatives should be included without restriction.
Yes
No
Number of BRCA associated cancers in maternal lineage: A relative with a history of more than 1 primary cancer should be counted twice here. Affected females should be included if there is no more than one intervening female unaffected by cancer. Cancers through intervening unaffected male relatives should be included.

Female breast cancer aged < 30 years +11 points
Female breast cancer aged 30-39 years +8 points
Female breast cancer aged 40-49 years +6 points
Female breast cancer aged 50-59 years +4 points
Female breast cancer aged ≥ 60 years +2 points
Male breast cancer aged < 60 years +13 points
Male breast cancer aged ≥ 60 years +10 points
Epithelial ovarian Do not count borderline, germ-cell or mucinous histologies. cancer aged < 60 years +13 points
Epithelial ovarian Do not count borderline, germ-cell or mucinous histologies. cancer aged ≥ 60 years +10 points
Pancreatic cancer +1 points
Prostate cancer < 60 years +2 points
Prostate cancer aged ≥ 60 years +1 points

High grade serous histology +2 points
Not high grade serous histology 0 points
Number of BRCA associated cancers in paternal lineage: A relative with a history of more than 1 primary cancer should be counted twice here. Affected females should be included if there is no more than one intervening female unaffected by cancer. Cancers through intervening unaffected male relatives should be included.

Female breast cancer aged < 30 years +11 points
Female breast cancer aged 30-39 years +8 points
Female breast cancer aged 40-49 years +6 points
Female breast cancer aged 50-59 years +4 points
Female breast cancer aged ≥ 60 years +2 points
Male breast cancer aged < 60 years +13 points
Male breast cancer aged ≥ 60 years +10 points
Epithelial ovarian Do not count borderline, germ-cell or mucinous histologies. cancer aged < 60 years +13 points
Epithelial ovarian Do not count borderline, germ-cell or mucinous histologies. cancer aged ≥ 60 years +10 points
Pancreatic cancer +1 points
Prostate cancer < 60 years +2 points
Prostate cancer aged ≥ 60 years +1 points

High grade serous histology +2 points
Not high grade serous histology 0 points
Patient score:
Total Manchester score:

Manchester score: Predicting germline BRCA mutation in individual affected by cancer

Interpretation:
The Manchester Scoring System (MSS) is a model system for predicting the chance of finding a pathogenic germline BRCA1 or BRCA2 mutation in an individual affected by cancer.
  • In a UK based population, a score of 15 or higher corresponds to a ≥ 10% chance of a pathogenic BRCA1/2 mutation.
  • A score of 20 corresponds to 20% chance of a pathogenic mutation.
  • Typically, germline genetic testing is performed when the ≥ 10% threshold has been reached.
  • The score was first published in 2004 as a simple to use model and originally scored the BRCA1 and 2 genes separately. The latest version of the Manchester Score provides a combined score for both genes reflecting that in practice both genes are now tested together.
  • The score was updated in 2009 and 2017 to incorporate pathological variables which have resulted in improved sensitivity in detecting pathogenic BRCA1/2 mutations.
  • The score is not suitable in the Jewish population as they were excluded in the studies which developed the tool as they were the only significant founder population in Manchester.
References:
1. Evans DGR, Eccles DM, Rahman N, et al. A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO. J Med Genet. 2004;41(6):474-480. doi:10.1136/jmg.2003.017996
2. Evans DG, Harkness EF, Plaskocinska I, et al. Pathology update to the Manchester Scoring System based on testing in over 4000 families. J Med Genet. 2017;54(10):674-681. doi:10.1136/jmedgenet-2017-104584
3. Evans DGR, Lalloo F, Cramer A, et al. Addition of pathology and biomarker information significantly improves the performance of the Manchester scoring system for BRCA1 and BRCA2 testing. J Med Genet. 2009;46(12):811-817. doi:10.1136/jmg.2009.067850