In 1995, Lamartiniere et al.1,2 proposed that the isoflavone genistein when consumed early in life reduces risk of developing breast cancer later in life. Over the past nearly 30 years, both animal3 and epidemiologic evidence4-7 has accumulated in support of this proposal. Nevertheless, the hypothesis that consuming isoflavone-rich soy during childhood and/or adolescence reduces breast cancer risk remains speculative. However, new research from Chile not only supports a protective role for early isoflavone intake, but provides a way to more definitely explore this hypothesis.8
In that same year that Lamartiniere et al.1,2 proposed their hypothesis, Colditz and Frazier9 recommended shifting breast cancer prevention earlier in life because in their analytical model, the years before the birth of the woman’s first child were identified as the most crucial in establishing future risk of breast cancer. The importance of early life events is supported by the observation that women having their first child when aged under 18 years have only about one-third the breast cancer risk of those whose first birth is delayed until the age of 35 years or more.10
Guzman et al.11 suggested that the elevated levels of estrogen and progesterone that occur during full term pregnancy likely induce protection from mammary cancer. This suggestion may be applicable to genistein since genistein interacts with estrogen receptors;12 however, the precise mechanism(s) by which early pregnancy reduces breast cancer risk has yet to be determined.13
The epidemiologic evidence consistently supports the notion that “early soy intake” reduces breast cancer risk.4-7 However, all four relevant studies have used a retrospective design. That is, women with and without breast cancer are interviewed to determine their soy intake during the teenage years. Childhood eating habits track into adulthood and this type of retrospective study is routinely used, but it is obviously difficult to recall with precision dietary habits decades earlier.
The Chilean study by Lesser et al.8 is the first to use a prospective design to examine the “early soy intake” hypothesis. However, instead of breast cancer incidence, breast tissue density was the primary outcome. Breast tissue density is an accepted marker of breast cancer risk.14 Markers need to be used rather than cancer, because the duration of a prospective study that focused on the latter would need to be at least 50 years.
The study by Lesser et al.8 involved 329 girls with dietary data (multiple 24-hour recalls) from puberty until two years after menarche onset. Breast composition was measured by dual energy x-ray absorptiometry (DXA) at two years after menarche. An inverse association was found between consumption of isoflavones and absolute fibroglandular volume (AFGV). Breast tissue density reflects the relative amount of glandular and fibrous tissue (fibroglandular tissue) that each woman has in her breasts compared with the amount of fatty tissue. Dense breasts have relatively high amounts of glandular tissue and fibrous connective tissue and relatively low amounts of fatty breast tissue.
Breast tissue density is commonly assessed by mammography. However, because of the radiation exposure, using mammography to assess density in healthy girls is not ethical. In the Chilean study, breast composition was determined by DXA, which represents a low-radiation option to measure breast density,15
One limitation of the study by Lesser et al.8 is that because it was conducted in Chile, isoflavone intake was low. In fact, mean isoflavone intake was only 0.7 mg/day, and even in the 4th intake quartile, the mean was only 2.6 mg/day. There is ample reason to question whether such a low intake can exert a biological effect.16
To further examine this outcome, this type of study needs to be conducted in a high-soy-consuming population such as an Asian country like Japan. However, extrapolating the results from one ethnic group and culture to a much different ethnic group and culture is fraught with difficulties, especially in this case because Asians may metabolize isoflavones differently than non-Asians.17 Therefore, an argument can be made that a better choice would be to conduct a study involving Seventh-day Adventist (SDA) girls since research has already shown there is a wide range of soy intake among this population.18
Prospectively assessing the relationship between isoflavone intake during childhood and/or adolescence and breast composition in SDA girls may represent the best approach for more definitely exploring the early soy intake hypothesis.
- Lamartiniere CA, Moore J, Holland M, Barnes S. Neonatal genistein chemoprevents mammary cancer. Proc Soc Exp Biol Med 1995;208:120-3.
- Lamartiniere CA, Moore JB, Brown NM, Thompson R, Hardin MJ, Barnes S. Genistein suppresses mammary cancer in rats. Carcinogenesis 1995;16:2833-40.
- Peng JH, Zhu JD, Mi MT, Li FJ, Cai L, Dong JZ, Zhang HX, Zhao Y, Xue RL. Prepubertal genistein exposure affects erbB2/Akt signal and reduces rat mammary tumorigenesis. Eur J Cancer Prev 2010;19:110-9.
- Shu XO, Jin F, Dai Q, Wen W, Potter JD, Kushi LH, Ruan Z, Gao YT, Zheng W. Soyfood intake during adolescence and subsequent risk of breast cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 2001;10:483-8.
- Wu AH, Yu MC, Tseng CC, Stanczyk FZ, Pike MC. Dietary patterns and breast cancer risk in Asian American women. Am J Clin Nutr 2009;89:1145-54.
- Korde LA, Wu AH, Fears T, Nomura AM, West DW, Kolonel LN, Pike MC, Hoover RN, Ziegler RG. Childhood soy intake and breast cancer risk in Asian American women. Cancer Epidemiol Biomarkers Prev 2009;18:1050-9.
- Baglia ML, Zheng W, Li H, Yang G, Gao J, Gao YT, Shu XO. The association of soy food consumption with the risk of subtype of breast cancers defined by hormone receptor and HER2 status. Int J Cancer 2016;139:742-8.
- Lesser C, Mericq V, Reyes M, Garmendia ML, Shepherd JA, Michels KB, Corvalan C, Pereira A. Habitual phytoestrogen intake is associated with breast composition in girls at 2 years after menarche onset. Cancer Epidemiol Biomarkers Prev 2022.
- Colditz GA, Frazier AL. Models of breast cancer show that risk is set by events of early life: prevention efforts must shift focus. Cancer Epidemiol Biomarkers Prev 1995;4:567-71.
- MacMahon B, Cole P, Lin TM, Lowe CR, Mirra AP, Ravnihar B, Salber EJ, Valaoras VG, Yuasa S. Age at first birth and breast cancer risk. Bull World Health Organ 1970;43:209-21.
- Guzman RC, Yang J, Rajkumar L, Thordarson G, Chen X, Nandi S. Hormonal prevention of breast cancer: mimicking the protective effect of pregnancy. Proc Natl Acad Sci U S A 1999;96:2520-5.
- Oseni T, Patel R, Pyle J, Jordan VC. Selective estrogen receptor modulators and phytoestrogens. Planta Med 2008;74:1656-65.
- Meier-Abt F, Bentires-Alj M. How pregnancy at early age protects against breast cancer. Trends Mol Med 2014;20:143-53.
- Yaghjyan L, Colditz GA, Collins LC, Schnitt SJ, Rosner B, Vachon C, Tamimi RM. Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to tumor characteristics. J Natl Cancer Inst 2011;103:1179-89.
- Maskarinec G, Morimoto Y, Daida Y, Laidevant A, Malkov S, Shepherd JA, Novotny R. Comparison of breast density measured by dual energy X-ray absorptiometry with mammographic density among adult women in Hawaii. Cancer Epidemiol 2011;35:188-93.
- Messina M. Western soy intake is too low to produce health effects. Am J Clin Nutr 2004;80:528-9.
- Setchell KD, Clerici C. Equol: history, chemistry, and formation. J Nutr 2010;140:1355S-62S.
- Segovia-Siapco G, Pribis P, Messina M, Oda K, Sabate J. Is soy intake related to age at onset of menarche? A cross-sectional study among adolescents with a wide range of soy food consumption. Nutrition journal 2014;13:54.
This blog is sponsored by SNI Global and U.S. Soy.