Antonis C. Antoniou, Paul D.P. Pharoah, Steven A. Narod et al.|The American Journal of Human Genetics|2003
Cited by 3.7kOpen Access
University of Szczecin
ORCID: 0000-0002-4666-4481Publishes on BRCA gene mutations in cancer, Genetic factors in colorectal cancer, DNA Repair Mechanisms. 172 papers and 11.9k citations.
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Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920-1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program (http://www.srl.cam.ac.uk/genepi/boadicea/boadicea_home.html).
BACKGROUND: Ten patients with breast cancer and a breast cancer susceptibility gene 1 (BRCA1) mutation, who presented with stages I to III breast cancer between December 2006 and 2007, were treated with four cycles of neoadjuvant cisplatin, followed by mastectomy and conventional chemotherapy. METHODS: The excised breast tissue and lymph nodes were examined for the presence of residual disease. RESULTS: Pathologic complete response was observed in nine patients (90%). CONCLUSIONS: Platinum-based chemotherapy appears to be effective in a high proportion of patients with BRCA1-associated breast cancers. Clinical trials are now warranted to determine the optimum treatment for this subgroup of breast cancer patients.