Breast cancer hypothesis: a single cause for the majority of cases

Abstract

Study objective-The main cause of breast cancer remains unknown. Numerous causal factors or predisposing conditions have been proposed, but account for only a small percentage of the total disease. The current search for multiple causes is unavailing. This report explores whether any single aetiological agent may be responsible for the majority of cases, and attempts to define its properties. Methods-Examination of all relevant epidemiological and biological evidence. Main results-Genetic inheritance is not the main cause of breast cancer because most cases are sporadic, there is a low prevalence of family history, and genetically similar women have diVering rates after migration. Environmental exposure, such as pollution by industrialisation, is not a major cause, as deduced from a spectrum of epidemiological data. The possibility of infection as cause is not persuasive as there is no direct biological evidence and no epidemiological support. Oestrogen status is closely related to breast cancer risk, but there are numerous inconsistencies and paradoxes. It is suggested that oestrogens are not the proximate agent but are promoters acting in concert with the causal agent. Dietary factors, and especially fat, are associated with the aetiology of breast cancer as shown by intervention and ecological correlation studies, but the evidence from case-control and cohort studies is inconsistent and contradictory. Conclusions-The hypothesis that best fits the epidemiological data is that dietary fat is not itself the causal agent, but produces depletion of an essential factor that is normally protective against the development of breast cancer. Many of the observed inconsistencies in the epidemiology are explainable if deficiency of this agent is permissive for breast cancer to develop. Some properties of the putative agent are outlined, and research investigations proposed. (J Epidemiol Community Health 2000;54:851-858) The main cause of breast cancer remains unexplained by the known epidemiology.

Hormone replacement therapy: pathobiological aspects of hormone-sensitive cancers in women relevant to epidemiological studies on HRT: a mini-review

“…Chlebowski (2003) 1.24 1.01-1.54 migration into other social or lifestyle environments. Nonetheless, some studies of high risk families have demonstrated an impact on the occurrence of breast cancer and an interaction with hormone use at least in first degree relatives (Wiseman, 2000). Moreover, it has been suggested that the population-attributable risk of factors such as education, family history as well as individual reproductive and hormonal factors may explain up to 50% of the breast cancer riskeven if external hormone use is not considered (Henderson and Bernstein, 1996).…”

“…The exact pathogenetic mechanisms of breast cancer initiation and/or promotion are still poorly understood (Olsson et al, 1996;Adami et al, 1998;Hofseth et al, 1999;Li et al, 2000;Wiseman, 2000;Brekelmans, 2003). Therefore, no firm causal conclusions can be established from the associations found between risk factors, including hormone use, and breast cancer.…”

Common soil of smoking-associated and hormone-related cancers: estrogen deficiency

“…Dynamics of breast cancer initiation and promotion is still poorly understood [13,[94][95][96][97]. Thus, firm causal conclusions cannot be established from the associations between hormone treatment and breast cancer found on inhomogeneous female populations.…”

Pregnancy postponement and childlessness leads to chronic hypervascularity of the breasts and cancer risk

“…Whereas numerous Classical Risk Factors are statistically linked to breast cancer, in fact they account for only a small proportion of the total disease. Here we deal with a factor, hypervascularity, which may be on the final common path to cancer (Wiseman, 2000). It has screening potential (Simpson et al, 1995).…”