‘Hormonal’ risk factors, ‘breast tissue age’ and the age-incidence of breast cancer

Abstract

For most cancer sites there is a linear log-log relationship between incidence and age. This relationship does not hold for breast cancer, and certain 'key' breast cancer risk factors suggest that breast tissue does not 'age' in step with calendar time. A quantitative description of 'breast tissue age' is suggested which brings the age-incidence curve of breast cancer into line with the common log-log cancers and explains quantitatively the known key risk factors. The model also explains the 'anomalous' finding that although early first birth is protective, late first birth carries a higher risk than nulliparity. US breast cancer rates are some four to six times the rates in Japan--the model suggests that the key risk factors, when considered jointly with weight, can explain about 85% of the difference.

Body mass index and post-menopausal breast cancer: an age-specific analysis

“…The present study not only confirms that overweight and obese women are at increased risk of post-menopausal breast cancer (Pike et al, 1983;Hsieh et al, 1990;Hunter and Willett, 1993;Stoll, 1994), but also indicates that such an association becomes stronger with advancing age.…”

“…This also has important implications for prevention as the incidence of breast cancer increases with age (Pike et al, 1983;Pike, 1987). Consequently, the absolute breast cancer excess risk related to being overweight is even larger at elderly age than indicated by the relative risk estimates.…”

“…This is attributed to elevated levels or availability of circulating oestrogens in obese post-menopausal women due to the conversion of androgens to oestrogens in peripheral adipose tissue and to lower levels of sex hormone-binding globulin (SHBG) in overweight women (Pike et al, 1983;Hunter and Willett, 1993;Stoll, 1994).…”

“…A direct trend in risk has been observed between postmenopausal breast cancer and measures of body mass index (BMI) (Pike et al, 1983;Hsieh et al, 1990;Hunter and Willett, 1993;Stoll, 1994), but little attention has been paid to measures of the duration-risk relationship or to any other time factor. It is conceivable, in fact, that the association increases with prolonged exposure to overweight-related high oestrogen levels, i.e.…”

Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms

“…Our study allowed for deeper analysis of the sources and mechanisms causing this heterogeneity. We used a biologically motivated model that was specified by cancer subtype (ductal and lobular), race, stage, grade, and hormone receptor status, thus extending existing breast carcinogenesis models [6,[15][16][17][18][19]. The results demonstrated that grade plays the primary role in breast cancer heterogeneity, with ER/ PR status ''strengthening'' the grade effect.…”