Birth Weight as a Risk Factor for Breast Cancer
ABSTRACT & COMMENTARY
Synopsis: A woman’s own birth weight is a risk factor for her development of breast cancer.
Source: Michels KB, et al. Lancet 1996;348:1542-1546.
It has been proposed by several investigators that the risk of developing breast cancer may be determined to some extent before birth. Numerous studies have provided information to support this hypothesis. However, many of these studies were small, and not all identified a positive correlation between birth weight and the later development of breast cancer.
It is known that, before birth, the glandular tissue in the human breast remains in a somewhat undifferentiated state. It is possible that these immature cells could be influenced by the hormonal milieu present during pregnancy. The fact that hormonal changes later in life, such as age of menarche and age at first full-term live birth, are associated with changes in the risk of breast cancer also supports this hypothesis.
The women participating in the Nurses’ Health Study (NHS) and its offspring, the Nurses’ Health Study II (NHS II), comprise the population from which the cases and controls were drawn. The women in these studies have been extensively studied and followed for many outcomes, and the strengths and weaknesses of studies that use these cohorts are well-known.
Permission to contact their mothers was obtained from women with incident cases of breast cancer who were in the study as well as matched controls. As usual for these groups, most women complied with this request. Appropriate exclusions of mothers were madethose who had died, those with Alzheimer’s disease or other mental problems that were incapacitating, inability to read the questionnaire, and a small number of refusals.
Only women with invasive breast cancer were used as cases for this study. Five hundred eighty-two breast cancer cases and 1569 matched controls comprised the study cohorts. Information was solicited concerning the daughter’s birth weight, history of prematurity, the mother’s use of tobacco products during pregnancy, and the family history of breast cancer. Mother’s recall of birth weight was compared to the daughter’s recall of her own birth weight.
A strong association between a female’s own birth weight and her later development of breast cancer was identified. Specifically, those females who weighed more than 4000 g at birth were approximately twice as likely to develop breast cancer compared to those who weighed under 2500 g. The risk steadily increased as birth weight increased.
The authors were not able to demonstrate a significant decrease in breast cancer among women born prematurely. However, the information collected by Michels et al concerning this variable was rudimentary and likely inaccurate.
When the increased risk of breast cancer among higher birth weight women was adjusted for known adult breast cancer risks, the association remained. The increased risk was significant only for those cases who developed breast cancer before 45 years of age.
In the discussion of this paper, the investigators attempt to explain why the association they report is biologically sound. They consider that the increased levels of estrogen in utero "may prime the mammary tissue for excessive responses at puberty or during early adult life." However, they do admit that their study "does not necessarily implicate pregnancy estrogens, although a role for these hormones seems highly likely." The authors also address the potential weaknesses of their study.
COMMENT BY KENNETH L. NOLLER, MD
This is a well-designed and well-executed study from the prestigious Harvard School of Public Health. The epidemiologists involved in the study are experts in the area that they have chosen to study. Their study material seems appropriate, as do their analyses. Thus, their conclusion that the development of breast cancer is related to birth weight is likely true, though the cause for this increase is not at all certain. The authors believe it is the intrauterine hormonal milieu, but other explanations might be operative.
It is interesting how our concept of cancer has changed over time. When I first started my education in medicine, it was largely assumed that cancer was something that just happened, most likely by chance. This was followed closely by the revelation that smoking "caused" lung cancer and was associated with many other tumors. We now have a long list of environmental factors that increase our risk of developing neoplasia.
We also have learned that certain lifestyles are more likely to be associated with the development of cancer at a later time than others. For example, high-fat diets increase one’s risk of colorectal cancer, while high fiber-content diets decrease the risk.
Only recently has there been more focus on ourfor lack of a better wordpredetermined risk of developing cancer. It now appears that all of us carry around certain flaws in our DNA that make us more susceptible to various types of cancer. Eventually, we will probably each be provided with a printout of our own unique DNA and will know which of several cancers we are more likely to develop during our lifetimes. Hopefully, these will be cancers for which modified behaviors can lower the ultimate risk. To some extent, we have been led to believe that we maintain a bit of control over our chance of developing cancer if we but lead a flawless life.
Unfortunately, this article suggests that we are in less control than we might believe. Perhaps the months we spend in the womb irreparably alter our risk of cancer. (Hopefully, other authors will find that some intrauterine factors decrease our risk of various cancers.) For now, it appears that those women who were born underweight may be only half as likely to develop breast cancer as their more rotund nursery mates.
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