Breast Asymmetry and Predisposition to Breast Cancer

Diane Scutt; Gillian A Lancaster; John T Manning

Disclosures

Breast Cancer Res. 2006;8(2) 

In This Article

Abstract and Introduction

Introduction: It has been shown in our previous work that breast asymmetry is related to several of the known risk factors for breast cancer, and that patients with diagnosed breast cancer have more breast volume asymmetry, as measured from mammograms, than age-matched healthy women.
Methods: In the present study, we compared the breast asymmetry of women who were free of breast disease at time of mammography, but who had subsequently developed breast cancer, with that of age-matched healthy controls who had remained disease-free to time of the present study. The study group consisted of 252 asymptomatic women who had normal mammography, but went on to develop breast cancer. The control group were 252 age-matched healthy controls whose mammograms were also normal and who remained free of cancer during the study period. Breast volume was calculated from the cranio-caudal mammograms for each group, and the relationships between asymmetry, established risk factors and the presence or absence of breast cancer were explored.
Results: The group who went on to develop breast cancer had higher breast asymmetry than controls (absolute asymmetry odds ratio 1.50 per 100 ml, confidence interval (CI) 1.10, 2.04; relative asymmetry 1.09, CI 1.01, 1.18), increased incidence of family history of breast cancer, lower age at menarche, later menopause, later first pregnancies and a higher frequency of high risk breast parenchyma types. Conditional logistic regression analysis showed that breast asymmetry, height, family history of breast cancer, age at menarche, parenchyma type and menopausal status were significant independent predictors of breast cancer. When age at menopause was included in the model for the subgroup of post-menopausal women, absolute breast fluctuating asymmetry (FA) and relative breast FA remained significant effects.
Conclusion: Breast asymmetry was greater in healthy women who later developed breast cancer than in women who did not.

Humans, in common with most other vertebrates, show bilateral symmetry in paired morphological traits such as ear size, digit length and breast volume. Perfect symmetry may be disturbed by a number of intrinsic and extrinsic factors, including the secretion of hormones such as oestrogen.[1,2] The small, random deviations from perfect symmetry that result from such factors are termed fluctuating asymmetry (FA). 'Fluctuating' refers to a pattern of bilateral variation where variation on the right and left sides is both random and independent. It tends to be small (around 1% of trait size or less). These random departures from bilateral symmetry provide a surprisingly convenient measure of developmental precision: the more precisely each side develops the greater the symmetry. FA is a measure of developmental stability, and is one of many issues at the interface between biology and medicine that offer valuable information at the whole organism level. Such comprehensive information is a concept familiar to, and frequently used by, biologists, but is often overlooked in medicine.[3,4] Highly symmetrical human and non-human animals are preferred as mates in comparison to asymmetrical individuals.[5,6,7,8,9] If individuals that experience stress during ontogeny are less preferred as potential mates, then presumably mechanisms that reduce stressful developmental events would be favoured.[10]

FA in such traits as ear size and digit length is related to health measures including body mass index (BMI) in young women and men.[11] However, it is in sexually selected traits, such as breasts, that the highest values of FA may be found.[12,13,14] Sexually selected traits are more liable to be disrupted during development because they often show rapid growth rates, are generally elaborate in design and are highly susceptible to mutation that results from rapid cellular proliferation and the action of sex steroids.[15,16,17] Breasts develop rapidly just prior to and during puberty and the importance of estrogen in the development, growth and carcinogenesis of the mammary gland is well established.[18] The role of local estrogen production in breast cancer is now more apparent.[19,20,21,22] Symmetrical breast development may well be an indicator of an individual's ability to tolerate 'disruptive' hormonal variation whilst maintaining developmental stability. Møller and colleagues[23] found that large breasts had more FA than small breasts, breast FA was higher in nulliparous women, and that breast FA was a predictor of fecundity.

Breast cancer is the most common malignancy among women in Western society, with incidence rates continuing their upward trend, increasing by 70% cent since 1971, and by 15% in the 10 years to 2000 in England. It is the most common cause of cancer death in women.[24] There are large between-individual differences in size and asymmetry of breasts and this could be indicative of differences in developmental stability, and possibly disease predisposition.

Breast volume FA, as measured from mammograms, is related to several of the known risk factors for breast cancer,[1,2] and patients with diagnosed breast cancer have higher breast volume FA measured from mammography than age-matched healthy women.[25] It would be an important advance if additional variations in the normal mammogram, that is breast asymmetry, could be used to help predict the possibility of developing breast cancer, particularly in high risk individuals. The specific aim of the present study was to establish whether breast FA, as measured from mammograms, was greater in healthy women who later went on to develop breast cancer, compared to age-matched women who remained disease-free.

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