Karolinska Institutet , Stockholm , Sweden HORMONE-RELATED FACTORS AND BREAST CANCER-STUDIES OF RISK AND PROGNOSIS Lena

The main purpose of this thesis was to explore the influences of risk factors for breast cancer on breast cancer characteristics and survival. We evaluated the associations between number and timing of births and breast cancerspecific survival using data from the Swedish Cancer Register, the Swedish Cause of Death Register, and the Multi-Generation Register. We identified more than 27,000 women born in Sweden and diagnosed with breast cancer in 1958-1997. We found a successively worse prognosis for women with a shorter delay between last birth and breast cancer diagnosis. Compared to women with their last birth more than 10 years before diagnosis, the risk of breast cancer death was increased by 72% for those with breast cancer diagnosis in the first year after last birth, and 39% for those diagnosed in the 3 year after last birth. Women with a first birth before 20 years had a slightly worse prognosis than parous women with their first birth between 20-24 years. These findings suggest that a recent birth and possibly an early first birth influence tumor biology. For the three following studies we used a Swedish population-based case-control study including more than 3,000 women aged 50-74 diagnosed with breast cancer in 1993-1995, and more than 3,000 age-frequency matched controls. The study holds information from questionnaires, patient records, and the Swedish Cause of Death Register. We assessed the influence of menopausal hormone therapy, anthropometric factors, reproductive factors, recent smoking, recent alcohol intake, family history of breast cancer, and previous benign breast disease on the risk of ductal, lobular, or tubular breast cancer. Menopausal estrogen-progestin therapy was associated with increased risks for all subtypes, but the estimates for lobular and tubular cancer were stronger compared to ductal cancer. Menopausal estrogen alone therapy was similarly associated with ductal and lobular breast cancer. Recent alcohol intake was significantly associated with tubular cancer, and seemed non-significantly related to lobular but not ductal breast cancer. Increasing age at first birth was borderline significantly more strongly related to lobular compared to ductal breast cancer. Other reproductive factors, anthropometric factors, and smoking seemed similarly related to ductal and lobular breast cancer. The same risk factors were also evaluated by joint estrogen (ER) and progesterone receptor (PR) status of the tumors. We found menopausal estrogen-progestin therapy to increase the risk for all receptor groups except the ER-PRgroup. The risks were borderline significantly stronger for ER+PR+ tumors compared to ER-PRtumors. Menopausal estrogen alone therapy was similarly associated with all receptor-defined groups. A high age at first birth seemed to increase the risk only for the ER+ groups, and substantial adult weight gain was associated only with the PR+ tumor groups. Most other risk factors seemed similarly associated with all receptor-defined tumor groups. Current, but not past, compared to never use of menopausal hormone therapy was associated with tumors of low grade, low S-phase fraction, and improved breast cancer specific survival. The associations were stronger with longer duration, and breast cancer survival seemed more favorable with estrogen-progestin than estrogen alone therapy. The improved survival among current users of menopausal hormone therapy was only partly explained by differences in available tumor characteristics and mammography surveillance.