Alcohol Consumption Between Menarche and Pregnancy and Breast Cancer Risk: Factors in Risk Accumulation   


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In a study recently published in the Journal of the National Cancer Institute and summarized in this issue of The ASCO Post, we found a relationship between alcohol intake between menarche and first pregnancy and risk for breast cancer. Placing this study in context can help us interpret the data and the implications for prevention of breast cancer. When in life will we gain the most benefit from prevention programs? How much should we change lifestyle, for how long, and at what age? And when we have known carcinogens, such as alcohol, are there other components of lifestyle (for example, diet or physical activity) that can counter their adverse effects?

Known Carcinogens

Alcohol is a known breast cancer carcinogen. The International Agency for Research on Cancer (IARC), which reviews scientific evidence against defined criteria, lists alcohol as a breast carcinogen.1 It is also well known to cause head and neck cancer, colorectal cancer, and liver cancer.

We also know that reproductive factors including menarche, first pregnancy, number and spacing of children, and age at menopause drive in large part a woman’s lifetime risk of breast cancer.2,3 Risk accumulates across the life course with the rate of increase in accumulated tissue damage highest from menarche to first pregnancy. With industrialization, we have seen age at menarche drop from an average of 17 or 18 in low-income agrarian societies, to around 12 in high-income countries.4,5 Parity has decreased (from 6 or 7 to an average of around 2), and age at first birth has increased with greater access to education and safe contraception for women.

With these changes, we have an increase in breast cancer incidence. Incidence has increased in industrialized countries over the past 100 years, and this increase in incidence rates is now seen in Asian countries as they pass through the economic and epidemiologic transition.6,7

Key Time Interval

Animal models of breast cell proliferation together with human data support a slower rate of risk accumulation after the first pregnancy. This evidence shows that the interval from menarche to first pregnancy is the time for most rapid accumulation in risk.8 With industrialization, this time interval has been extended, perhaps by more than 15 years. In the current study, we add alcohol to the underlying accumulation through the early reproductive years and observe that the adverse effect of alcohol in the breast cells during this interval is greatest when the interval is longer.

One challenge of studying adolescent exposures and breast cancer risk is that prospective studies are hindered by the extended time interval from menarche or adolescence to the years when breast cancer is diagnosed. To help overcome some of the elapsed time, we have used benign breast lesions as an intermediate marker of risk.9 Proliferative benign lesions double a woman’s risk for invasive breast cancer.10

From this study, it is also clear that higher alcohol intake in adolescence and early adult years drives an increase in risk for benign breast lesions that carry the highest risk of subsequent breast cancer.11 By using these proliferative benign lesions as an endpoint, we shorten the interval for follow-up and see that the risk associated with higher alcohol consumption is also present for these premalignant lesions. Together, these data show resoundingly that this time period from menarche to first full-term pregnancy is critical for breast cancer risk accumulation.

Other Risk Factors

From these data, one would therefore infer that we should explore other lifestyle factors in this time period that may increase or decrease risk. We, and others, have studied physical activity in this time period and show that it is also related to protection against breast cancer.12,13 Diet in this time period is less commonly studied, in part because following women from adolescence to adult years and actual breast cancer development takes so long. Concern that recall of diet is somewhat less accurate has limited the number of studies asking women in their 30s to recall past diet and then following them over time for development of breast lesions.14,15

We have overcome some of this difficulty with our study of daughters of women participating in the Nurses’ Health Study (NHS) II, in which we assessed diet in the teenage years and followed participants to their 20s and early 30s. It was found that higher vegetable protein and vegetable fat intake is related to lower risk of benign breast lesions confirmed by breast biopsy16. We also asked women in the first Nurses’ Health Study and the NHSII to recall their high school diet.17 We followed them forward from this recall and observed that those who reported higher fiber intake (regardless of source from fruit, vegetables, or grains) had significantly lower subsequent risk of proliferative benign breast lesions (those that carry the very highest risk of progression to breast cancer).18

Other components of diet have not been studied as thoroughly in relation to benign lesions, although milk intake has been found to be unrelated to risk,19 and a recent conference presentation showed that higher carotenoid intake was inversely related to risk. Studies of soy intake at the level achieved in the traditional Asian diet also show that childhood and adolescent intake are strongly inversely related to risk of breast cancer.20,21

Further Research

Clearly, more studies are warranted to build on these data and to show how alcohol increases risk, how diet may reduce risk, and how we can use markers of risk to better understand the pathways involved in risk increase and risk reduction. With such information, we will be better positioned to inform prevention strategies that can reduce breast cancer risk through improved diet, physical activity, and limitation of alcohol intake, together leading to a reduced burden of breast cancer in the United States and globally. ■

Dr. Colditz is Associate Director, Prevention and Control, Alvin J. Siteman Cancer Center, and Niess-Gain Professor, Washington University School of Medicine, St. Louis.

Disclosure: Dr. Colditz reported no potential conflicts of interest.

References

1. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2007: Lyon France). Alcohol consumption and ethyl carbamate. Lyon, France; International Agency for Research on Cancer; Distributed by WHO Press; 2010.

2. Rosner B, Colditz GA, Willett WC: Reproductive risk factors in a prospective study of breast cancer: The Nurses’ Health Study. Am J Epidemiol 139:819-835, 1994.

3. Colditz G, Rosner B: Cumulative risk of breast cancer to age 70 years according to risk factor status: Data from the Nurses’ Health Study. Am J Epidemiol 152:950-964, 2000.

4. Cho GJ, Park HT, Shin JH, et al: Age at menarche in a Korean population: Secular trends and influencing factors. Eur J Pediatr 169:89-94, 2010.

5. Morris DH, Jones ME, Schoemaker MJ, et al: Secular trends in age at menarche in women in the UK born 1908-93: Results from the Breakthrough Generations Study. Paediatr Perinat Epidemiol 25:394-400, 2011.

6. Seow A, Duffy S, McGee M, et al: Breast cancer in Singapore: Trends in incidence 1968-1992. Int J Epidemiol 25:40-45, 1996.

7. Jung YS, Na KY, Kim KS, et al: Nation-wide Korean breast cancer data from 2008 using the breast cancer registration program. J Breast Cancer 14:229-236, 2011.

8. Pike MC, Krailo MD, Henderson BE, et al: “Hormonal” risk factors, “breast tissue age” and the age-incidence of breast cancer. Nature 303:767-770, 1983.

9. Berkey CS, Willett WC, Frazier AL, et al: Prospective study of adolescent alcohol consumption and risk of benign breast disease in young women. Pediatrics 125:e1081-e1087, 2010.

10. London SJ, Connolly JL, Schnitt SJ, et al: A prospective study of benign breast disease and the risk of breast cancer. JAMA 267:941-944, 1992.

11. Liu Y, Colditz G, Rosner B, et al: Alcohol intake between menarche and first pregnancy: A prospective study of breast cancer risk. J Natl Cancer Inst. August 28, 2013 (early release online).

12. Maruti SS, Willett WC, Feskanich D, et al: A prospective study of age-specific physical activity and premenopausal breast cancer. J Natl Cancer Inst 100:728-737, 2008.

13. Bernstein L: Exercise and breast cancer prevention. Curr Oncol Rep 11:490-496, 2009.

14. Maruti SS, Feskanich D, Colditz GA, et al: Adult recall of adolescent diet: reproducibility and comparison with maternal reporting. Am J Epidemiol 161:89-97, 2005.

15. Maruti SS, Feskanich D, Rockett HR, et al: Validation of adolescent diet recalled by adults. Epidemiology 17:226-229, 2006.

16. Berkey CS, Willett WC, Tamimi RM, et al: Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women. Breast Cancer Res Treat. September 17, 2013 (early release online).

17. Frazier AL, Willett WC, Colditz GA: Reproducibility of recall of adolescent diet: Nurses’ Health Study (United States). Cancer Causes Control 6:499-506, 1995.

18. Su X, Tamimi RM, Collins LC, et al: Intake of fiber and nuts during adolescence and incidence of proliferative benign breast disease. Cancer Causes Control 21:1033-1046, 2010.

19. Berkey CS, Willett WC, Tamimi RM, et al: Dairy intakes in older girls and risk of benign breast disease in young women. Cancer Epidemiol Biomarkers Prev 22:670-674, 2013.

20. Wu AH, Yu MC, Tseng CC, et al: Epidemiology of soy exposures and breast cancer risk. Br J Cancer 98:9-14, 2008.

21. Lee SA, Shu XO, Li H, et al: Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Women’s Health Study. Am J Clin Nutr 89:1920-1926, 2009.


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