Background
Methods
Patient group
At least one of the following criteria has to be met: | |
1. Personal history of breast cancer diagnosed < age 45 years | |
2. Personal history of breast cancer diagnosed < age 50 years and at least one case of breast cancer at any age in close blood relative | |
3. Personal history of triple negative breast cancer diagnosed < age 60 years | |
4. Personal history of breast cancer diagnosed at any age and at least two cases of breast cancer diagnosed at any age or at least one close blood relative with breast cancer diagnosed ≤50 years or at least one blood relative with ovarian carcinoma or a close male blood relative with breast cancer | |
5. Personal history of ovarian cancer | |
6. Personal history of male breast cancer |
Nr. | Probands age at diagnosis (years) | Primary cancer site | Morphological subtype | Breast cancersubtype | Tumor grade | Family history |
---|---|---|---|---|---|---|
1 | 54 | Breast | Ductal | Luminal | missing | Mother and maternal aunt – breast cancer age 60; daughter - polycytemia vera age15, brother – melanoma age 60 |
2 | 40 | Breast | Ductal | Triple-negative* | G3 | Mother - Breast and ovarian cancer age 40 |
3 | 33 and 38 | Left Breast/ Right Breast | Ductal/ Ductal | Triple-negative/ Luminal | G3/G3 | Paternal grandmother - unknown primary gynecological cancer age 50 |
4 | 63 | Breast and Ovaries | Ductal | Triple-negative | G2 | Mother with breast cancer age 55; sister - ovarian cancer age 59 |
5 | 37 | Ovaries | NA | NA | NA | Mother - breast cancer age 64 |
6 | 58 | Breast | Lobular | Luminal | G2 | Mother and maternal aunt – breast cancer age > 60 |
7 | 43 | Breast | Ductal | Triple-negative | G3 | No |
8 | 42 | Breast | Ductal/Medullary | Triple-negative | G2 | Mother - breast cancer age 60 |
9 | 50 | Breast | Ductal | Triple-negative | G3 | Mother - breast cancer age 52 |
10 | 35 | Breast | Ductal | Triple-negative | G3 | Mother - breast cancer age 46 |
11 | 52 | Breast | Ductal | Luminal B HER2 positive | G2 | Mother and maternal aunt – breast cancer age > 50 |
12 | 41 | Breast | Ductal | HER2 positive | G3 | No |
13 | 53 | Breast | Ductal | Triple-negative | missing | No |
14 | 36 | Breast | Ductal | Luminal | missing | No |
15 | 53 | Breast | Ductal | Luminal | missing | Mother and maternal grandmother – breast cancer age > 60 years |
16 | 40 | Breast | Ductal | Luminal B HER2 positive | missing | No |
DNA testing
Statistical analysis
Results
Nr. | Mutation | Clinical significance of mutation | NCCN inclusion criteria | Manchester score [13] | Swedish Breast cancer group criteria for screening of mutation in BRCA1 and BRCA2 |
---|---|---|---|---|---|
1 | RAD50c.980G > A | VUS | NCCN4 | 17 | One case of male breast cancer |
2 | BRCA1c.5075-?_5152 +?del | PAT | NCCN2 | 29 | One case of triple-negative breast cancer ≤age 40 |
3 | BRCA1c.1-?_c.134 +?del | PAT | NCCN3 | 20 | One case of breast cancer ≤age 35 |
4 | BRCA2c.6998dupT | PAT | NCCN4 | 19 | Breast cancer and ovarian cancer in one individual. |
5 | BRCA1c.5117G > A | PAT | NCCN5 | 15 | Do not match |
6 | RAD50c.251 T > A | VUS | NCCN4 | ||
MRE11Ac.1715G > A | VUS | 6 | NA | ||
7 | BRCA1c.1961delA | PAT | NCCN3 | 14 | Do not match |
8 | BRCA2c.280C > T | VUS | NCCN4 | 14 | Do not match |
9 | BRCA1c.5117G > A | PAT | NCCN4 | 16 | Do not match |
10 | BRCA1c.4996_4997dupTA | PAT | NCCN4 | 20 | One case of triple-negative breast cancer ≤age 40 |
11 | Negative | Negative | NCCN4 | 2 | Do not match |
12 | Negative | Negative | NCCN1 | 2 | Do not match |
13 | Negative | Negative | NCCN3 | 8 | Do not match |
14 | Negative | Negative | NCCN1 | 8 | Do not match |
15 | CDH1 c.808 T > G | VUS | NCCN4 | 8 | Do not match |
16 | Negative | Negative | NCCN1 | 0 | Do not match |
Criteria | Sensitivity | Specificity | Accuracy |
---|---|---|---|
NCCN | 100% | 50% | 64% |
Manchester scoring system | 85.7% | 88.9% | 87.5% |
Swedish Breast cancer group | 57.1% | 88.9% | 75% |