Risk and prognosis of breast cancer among women at high risk of the disease

The overall objectives of this thesis were to increase our understanding of the risk and prognosis of breast cancer using the high risk groups of women with bilateral and familial breast cancer. Data from the Swedish Cancer Register, the Multi-Generation Register and the Cause of Death register was used in Paper I-III to identify women with bilateral cancer and study risk and prognosis of the disease. The incidence of synchronous breast cancer (< 3 months of first cancer) increased by age and by 40% during the 1970s, whilst the incidence of metachronous cancer (≥ 3months of first cancer) decreased by age and by about 30% since the early 1980s most likely due to increasing use of adjuvant therapy. In the first 20 years following a diagnosis of primary breast cancer, the incidence of metachronous cancer decreased from about 0.8% to 0.4%/yr in patients diagnosed with the first breast cancer before age 45 years, whilst the incidence remained stable at 0.5– 0.6%/yr among those who were older than 45 years at diagnosis. After 30 years of follow-up, the cumulative risk of metachronous bilateral breast cancer approached 15% regardless of age at first primary breast cancer. Women who developed bilateral cancer within 5 years and before age 50 were 3.9 times (95% CI 3.5-4.5) more likely to die from breast cancer than women with unilateral cancer. Women with a bilateral cancer diagnosed more than 10 years after the first cancer had a prognosis similar to that of a unilateral breast cancer. Adjuvant chemotherapy of primary cancer is a predictor of poor survival after diagnosis of early metachronous cancers. In paper III we compared the incidence patterns of familial and non-familial bilateral disease to the risk of breast cancer in twin sisters identified using the Twin Registers of Sweden, Finland and Denmark. We observed differences in risk of breast cancer that are up to 5 to 7-fold larger in absolute terms with an entirely different age pattern when comparing the risk of disease in the opposite breast and in twin sisters to the general female population. The risk of cancer in the non-affected twin and the opposite breast was not affected by age or time since first event. The relative risk of familial bilateral cancer was 52% higher (IRR 1.52, 95%CI; 1.42-1.63) and the relative risk in the dizygotic twin sister was 26% lower (IRR 0.74 95%CI; 0.61-0.90) compared to the risk of non-familial bilateral cancer. In paper IV we assessed if breast cancer prognosis is inherited using a linked data set from the Swedish Cancer Register and the MultiGeneration register. We identified 3,618 mother-daughter and sister pairs with breast cancer and classified 5-year breast cancer specific prognosis among proband (mother or oldest sister) into tertiles as poor, intermediary or good. After adjusting for potential confounders daughters and sisters of a proband with poor prognosis had a 60 percent higher 5-year breast cancer mortality compared a proband with good prognosis (relative risk 1.6; 95%CI 1.2-2.2; p for trend 0.002). In conclusion, the risk of familial disease is high and differs by age from the risk in the general population. The risk of bilateral breast cancer is high and prognosis is poor and both related to adjuvant therapy. Finally there is evidence that breast cancer prognosis is inherited.