ORIGINAL ARTICLE

Distinction between hereditary and sporadic breast cancer on the basis of clinicopathological data

P van der Groep¹, A Bouter³, R van der Zanden³, I Siccama⁶, F H Menko⁴, J J P Gille⁴, C van Kalken⁷, E van der Wall², R H M Verheijen⁵, P J van Diest¹

¹ Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
² Division of Internal Medicine and Dermatology, University Medical Center Utrecht
³ Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands
⁴ Departments of Clinical Genetics and Human Genetics, VU University Medical Center
⁵ Departments of Obstetrics and Gynecology, VU University Medical Center
⁶ KiQ, Amsterdam
⁷ NDDO Research Foundation, Amsterdam

Correspondence to:
Dr P J van Diest
Department of Pathology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands; p.j.vandiest{at}azu.nl

Background: About 5% of all breast cancer cases are attributable to germline mutations in BRCA1 or BRCA2 genes. BRCA mutations in suspected carriers, however, may be missed, which hampers genetic counselling.

Materials and methods: Different clinicopathological features were compared between 22 breast cancers from carriers of proved BRCA1 mutations and 604 cancers from sporadic controls. In addition, 5 BRCA2-related breast cancers and 66 breast cancers of untested patients at intermediate risk and 19 breast cancers of untested patients at high risk of hereditary disease on the basis of family history were evaluated.

Results: A "probably sporadic" class (age 54 years and epidermal growth factor receptor (EGFR) negative; 68% of cases) with a 0% chance of BRCA1-related breast cancer containing 79% of the sporadic cases was yielded by using a decision tree with age, Ki67 and EGFR. A 75% chance of BRCA1-related breast cancer was shown by the "probably BRCA1-related" class (age <54 years and Ki67 25%; 8% of cases) with 82% of the BRCA1-related cases but only 1.4% of the sporadic cases. Most cases at intermediate or high risk of hereditary disease on the basis of family history could be classified with high probability as either probably BRCA1 related or probably sporadic.

Conclusion: Breast carcinomas can be classified with a high level of certainty as sporadic or related to BRCA1 germline mutations by using a decision tree with age, Ki67 and EGFR. This can be clinically useful in mutation analysis in families with a borderline risk of hereditary disease.

Abbreviations: EGFR, epidermal growth factor receptor, MAI, mitotic activity index

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