Breast Cancer Research in the Nurses' Health Studies: Exposures Across the Life Course

Abstract

Objectives: To review the contribution of the Nurses' Heath Study (NHS) and the NHS II in identifying risk and protective factors for breast cancer incidence and survival.

Methods: We conducted a narrative review of NHS and NHS II articles on breast cancer incidence and survival published from 1976 to 2016, with a focus on exogenous and endogenous hormones; lifestyle factors, including diet, physical activity, and aspirin use; intermediate markers of risk; and genetic factors.

Results: With the investigation of individual risk factors, as well as their incorporation into risk prediction models, the NHS has contributed to the identification of ways in which women may reduce breast cancer risk, including limiting alcohol consumption, reducing the duration of postmenopausal estrogen-plus-progestin use, avoiding weight gain, and increasing vegetable consumption. In addition, the NHS has helped elucidate the roles of several biomarkers and contributed to the identification of risk alleles.

Conclusions: The NHS has contributed to our understanding of lifestyle, hormonal, and genetic risk factors for breast cancer, highlighting the importance of exposures across the life course, and has helped identify lifestyle changes that may reduce risk and improve survival after a diagnosis of breast cancer.

FIGURE 1—

Relative Risks for the Associations Between Selected Risk Factors and Risk of Breast Cancer: The Nurses’ Health Study, United States Note. E = estrogen; E+P = estrogen plus progestin; MET = metabolic equivalent. Whiskers indicate 95% confidence intervals. The relative risks presented are from studies with different time frames. For exact dates, see source articles. Source. Sisti et al., Rosner et al., Eliassen et al., and Chen et al. ^a12 grams of alcohol per day is equivalent to approximately 1 drink per day. ^b9 MET-hours per week is equivalent to 3 hours of walking at an average pace per week.

FIGURE 2—

Relative Risks for Circulating Biomarkers and Risk of Breast Cancer, by Years Between Blood Collection and Diagnosis: The Nurses’ Health Study (NHS) and NHS II, United States Note. Estradiol categories are ≤ 4, > 4 to 6, > 6 to 9, and > 9 pg/mL; testosterone categories are ≤ 14, > 14 to 19, > 19 to 26.9, and > 26.9 ng/dL; prolactin categories are ≤ 8.1, > 8.1 to 11.0, > 11.0 to 15.7, and > 15.7 ng/ml; total carotenoids categories are < 729, 729 to < 917, 917 to < 1124, 1124 to < 1379, and ≥ 1379 μg/dL. The relative risks presented are from studies with different time frames. For exact dates, see source articles. Source. Zhang et al., Tworoger et al., and Eliassen et al.

FIGURE 3—

Relative Risks for the Associations Between Physical Activity and Aspirin Use After Diagnosis and Risk of Breast Cancer Death: The Nurses’ Health Study, United States Note. MET = metabolic equivalent. The relative risks presented are from studies with different time frames. For exact dates, see source articles. Source. Holmes et al. ^a9 MET-hours per week is equivalent to 3 hours of walking at an average pace per week.