A 40 year old woman has the following family and personal history: her mother died of breast cancer at age 64, she smokes one pack/day, she drinks five or more cups of coffee/day, she has no children, and she takes bih control pills. Which of the following is the most significant risk factor for breast cancer in this patient?

Positive family history is definitively the most significant risk factor of developing breast cancer among the ones mentioned in the list. About 5% to 10% of cases are attributable to inheritance of autosomal dominant genes. Most hereditary cases of breast cancer are due to two genes, BRCA1 and BRCA2, which are tumor suppressor genes probably involved in DNA repair. There are additional rare "susceptibility" genes, namely those causing Li-Fraumeni syndrome (mutations of p53), Cowden syndrome (mutations of a gene on chromosome 10), and ataxia-telangiectasia (mutations of ATM gene). Note, however, that 80% to 90% of women with breast cancer do not have a positive family history. The role of exogenous estrogens, including those administered with bih control pills or postmenopausal replacement therapy, is still debated. If there is any associated risk for breast cancer, this is minimal. There is no convincing evidence linking caffeine consumption or cigarette smoking to breast cancer. Ref: Hunt K.K., Newman L.A., Copeland E.M., Bland K.I. (2010). Chapter 17. The Breast. In F.C. Brunicardi, D.K. Andersen, T.R. Billiar, D.L. Dunn, J.G. Hunter, J.B. Matthews, R.E. Pollock (Eds), Schwaz's Principles of Surgery, 9e.