What is our finding?

Our recent study published in the British Journal of Cancer describes the relationships between body fatness at young ages and the risks of three major female cancers (breast, endometrial, and ovarian cancers) [1]. Breast, endometrial, and ovarian cancers are commonly diagnosed female cancers that share many common risk factors. In this study, we evaluated 37 prospective studies on BMI at young ages (including childhood, adolescence, and young adulthood) and estimated a 16% reduced breast cancer risk, a 40% increased endometrial cancer risk, and a 15% increased ovarian cancer risk associated with every 5-kg/m² increase in BMI (figure 1).

Given that childhood obesity may lead to adult obesity, a known risk factor for various noncommunicable diseases, our finding of inverse association between early-life BMI and breast cancer risk is intriguing. We observed that the inverse associations with breast cancer did not vary by menopausal status of women (premenopausal vs. postmenopausal), BMI assessment method (directly measured vs. self-reported), age of BMI (<18, at 18, >18 years), and geographic regions. After accounting for adult BMI, the inverse association with breast cancer did not change, whereas for endometrial cancer the positive association was substantially weakened. These findings support the long-term effect of early-life BMI on breast cancer risk through the pathways not mediated by adult BMI. On the other hand, for endometrial cancer, adult BMI may be more relevant.  

What does it tell us?

The inverse association specifically found with breast cancer but not with other cancers (e.g. ovarian and endometrial cancers) suggest that the differential mechanisms, such as breast tissue-specific effects, are likely to be involved. Although the exact mechanisms are unknown, there are potential pathways that may explain the associations. In our previous research, we observed several breast tissue-specific differences, such as overall breast density and spatial distribution of dense tissue on a mammogram [2], breast tissue composition [3], and breast tissue expression of cellular proliferation marker [4], between women who were obese and nonobese during their childhood. Early-life body fatness may influence breast cancer risk by contributing to lifelong setpoints of these intermediate markers.

What’s next?

Despite the reduced breast cancer risk associated with early-life body fatness, childhood obesity should not be promoted as a preventive strategy for breast cancer as it is also associated with increased risks of various other cancer sites including endometrial and ovarian cancers. Further studies are needed to investigate the potential mechanisms through which early-life body fatness influences female cancer risks and to identify ways to mitigate the excess breast cancer risk in lean girls.

References

1. Byun D, Hong S, Ryu S, Nam Y, Jang H, Cho Y, Keum N, Oh H. Early-life body mass index and risks of breast, endometrial, and ovarian cancers: a dose-response meta-analysis of prospective studies. Br J Cancer. 2021 Nov 12.
2. Oh H, Rice MS, Warner ET, Bertrand KA, Fowler EE, Eliassen AH., et al. Early-life and adult anthropometrics in relation to mammographic image intensity variation in the Nurses’ Health Studies. Cancer Epidemiol Biomarkers Prev.2020;29:343–51.
3. Oh H, Yaghjyan L, Austin-Datta RJ, Heng YJ, Baker GM, Sirinukunwattana K, et al. Early-life and adult adiposity, adult height, and benign breast tissue composition. Cancer Epidemiol Biomarkers Prev. 2021;30:608–615.
4. Oh H, Eliassen AH, Beck AH, Rosner B, Schnitt SJ, Collins LC, et al. Breast cancer risk factors in relation to estrogen receptor, progesterone receptor, insulin-like growth factor-1 receptor, and Ki67 expression in normal breast tissue. NPJ Breast Cancer. 2017;3:1–8.