The influence of familial and hereditary factors on the prognosis of breast cancer

Background: Family history is a well recognized risk factor for breast cancer, but its impact in terms of breast cancer survival is uncertain. The recent identification of breast cancer predisposing genes has provided new clinical insights in this field. Design: English literature identified through Medline between 1976 and February 1999 was reviewed including search terms: breast cancer, survival, prognosis, family history, genetics, BRCA1, BRCA2, and related articles. Results: Publications were divided into three categories. Family history-based studies: eighteen articles were reviewed. Four studies showed a statistically significant better survival in patients with a family history of breast cancer, and two studies demonstrated a significantly worse prognosis in this context. The remaining articles showed no significant difference. Linkage studies: Two studies based on linkage to BRCA1 found that overall survival was better in linked families. A third one concluded to a worse outcome in BRCA2-linked tumors. Mutation-based studies: 10 studies looking at the association between germ-line mutations in BRCA1/BRCA2 and clinical outcomes were reviewed. Eight articles reported no significant difference in outcome, whereas two studies showed a worse outcome in patients with mutations. Conclusions: Conflicting data exist as to whether the prognosis of familial or hereditary breast cancer differs from that of sporadic cases. Some of the discrepancies may be explained by methodological differences or biases. However, no studies showed a survival advantage for BRCA1 mutation carriers. This seems to indicate that BRCA1-related breast cancer is not associated with a survival advantage, and that in fact, certain BRCA1 germline mutations confer a worse prognosis. However, to adequately answer this question, more efficient molecular tools to identify all the genetic changes responsible for breast cancer predisposition, and large cohort studies to evaluate their clinical consequences, are needed.