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

Background: Family history is a well recognized risk factor for breast canc er, but its impact in terms of breast cancer survival is uncertain. The rec ent identification of breast cancer predisposing genes has provided new cli nical insights in this field. Design: English literature identified through Medline between 1976 and Febr uary 1999 was reviewed including search terms: breast cancer, survival, pro gnosis, family history, genetics, BRCA1, BRCA2, and related articles. Results: Publications were divided into three categories. Family history-ba sed studies: eighteen articles were reviewed. Four studies showed a statist ically significant better survival in patients with a family history of bre ast cancer, and two studies demonstrated a significantly worse prognosis in this context. The remaining articles showed no significant difference. Lin kage studies: Two studies based on linkage to BRCA1 found that overall surv ival was better in linked families. A third one concluded to a worse outcom e in BRCA2-linked tumors. Mutation-based studies: 10 studies looking at the association between germ-line mutations in BRCA1/BRCA2 and clinical outcom es were reviewed. Eight articles reported no significant difference in outc ome, 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 t he 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 mutati ons confer a worse prognosis. However, to adequately answer this question, more efficient molecular tools to identify all the genetic changes responsi ble for breast cancer predisposition, and large cohort studies to evaluate their clinical consequences, are needed.