Clinical stage of breast cancer by parity, age at birth, and time since birth: a progressive effect of pregnancy hormones?

Breast cancer diagnosed during pregnancy or 1 to 2 years after birth often occurs at a late stage. Little is known about tumor characteristics in the high-risk period shortly after a childbirth. We here explore whether stage of disease differs according to timing of births. Results are based on 22,351 Norwegian breast cancer patients of parity 0 to 5, ages 20 to 74 years. The proportion of stage II to IV tumors was considerably higher among parous than nulliparous women at age <30 years (52.7% versus 36.8%, P=0.009), but similar or lower in other age groups (P(interaction)=0.029). In general, the largest proportion of stage II to IV tumors was found among women diagnosed during pregnancy or <2 years after birth. However, among women with late-age births (first or second birth >or=30 years, third birth >or=35 years), as well as women with an early second birth (<25 years), the proportion with advanced disease was rather similar or even higher among those diagnosed 2 to 6 years after birth (49.3-56.0%). The association between clinical stage and time since birth reached statistical significance among women with a late first or second birth and among all triparous women (P <or= 0.032). The subgroups with a high proportion of advanced disease 2 to 6 years after birth corresponded quite well to those previously found to have the most pronounced transient increase in risk after birth. Thus, pregnancy hormones may have a progressive effect on breast cancer tumors in addition to a possible promoting effect. A potential effect of prolactin is discussed.