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Appendix D Summary Table on Estimates of Population Attributable Risk 387

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388 BREAST CANCER AND THE ENVIRONMENT TABLE D-1 Summary of Estimates of Population Attributable Risk for Risk Factors for Breast Cancer Source Study Location and Type Study Population Characteristics United States Madigan et al. U.S. NHANES I Epidemiologic Follow-up (1995) Study (NHEFS) (1971–1987) Cohort Women, ages 25–74 at initial examination 7,508 in analytic cohort 193 breast cancer cases Rockhill et al. U.S. Carolina Breast Cancer Study (1998) (1993–1996) Unmatched case–control with randomized Women, ages 20–74 (white women for recruitment PAR analysis) 513 cases 445 controls Tseng et al. U.S. NHANES III (1988–1994) (1999) Survey data for risk factor No age restrictions prevalence U.S. women Adjusted RR from meta-analysis Incidence rates from SEER data (1990–1994)

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389 APPENDIX D Population Attributable Risk in Percentb Risk Factors and Impact on Relative Risk Estimatesa (95% CI, where available) Absolute Risk Estimates for U.S. History of breast cancer in 1st All factors: 41 (1.6–80.0) NHEFS age adjusted degree relative = 2.6 Family history: 9 (3.0–15.2) baseline incidence Income in upper two thirds of Higher income: 19 (-4.3–42.1) per 100,000 U.S. population = 1.7 Later age at first birth or (standardized Age at first birth > than 29 nulliparity: 30 (5.6–53.3) to 1970 U.S. yrs = 1.9 population) Nulliparity = 1.8 Estimates for NHEFS All factors: 47 (16.7–76.7) History of breast Family history: 8 (2.3–13.9) cancer in 1st degree Higher income: 23 (5.4–39.9) relative = 470 Later age at first birth or Income in upper nulliparity: 30 (8.9–51.4) two thirds of U.S. population = 259 Age at first birth > than 29 = 260 Nulliparity = 259 Early menarche (< age 12 = All: 25 (6–48) Not reported 1.24; age 12–13 = 1.08) With menarche at < age 14 and first birth at ≥ age 20, Later age of first full-term pregnancy (≥ age 20) 1.08 or nulliparity to 1.53, depending on age group All: 15 (~5–20) Breast cancer in mother or With menarche at < age 12 and first birth at ≥ age 30, sister = 1.36 History of benign breast or nulliparity biopsy = 1.06 Alcohol consumption Alcohol consumption: 2 Not reported None = 1.0 (~1.2–2.9) Light (0.1–6.4 g/day) = 1.0 Moderate (6.5–25.9 g/day) = 1.1 Heavy (≥ 26 g/day) = 1.3 continued

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390 BREAST CANCER AND THE ENVIRONMENT TABLE D-1 Continued Source Study Location and Type Study Population Characteristics Clarke et al. U.S. California Health Interview Survey, 2001 (2006) Survey data for risk factor White, non-Hispanic women, ages prevalence 40–79 Published literature for Analysis for counties and hypothetical RRs populations Incidence from California 3,781,621 women Cancer Registry 13,019 breast cancer cases (1998–2002) Sprague et al. U.S. Collaborative Breast Cancer Study— (2008) Wisconsin, Massachusetts, New Unmatched case–control Hampshire (1996–2000) Cases from cancer Women, ages 20–69 (95% white, registries; population- non-Hispanic) based controls 3,499 cases 4,213 controls

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391 APPENDIX D Population Attributable Risk in Percentb Risk Factors and Impact on Relative Risk Estimatesa (95% CI, where available) Absolute Risk Alcohol (2+ drinks/day on 10+ Alcohol: 3.5 Alcohol: 450 cases/yr days/mo) = 1.4 HT (E+P): 4.4 HT (E+P): 567 cases/yr HT (E+P) = 1.26 Physical inactivity: 7.5 Physical inactivity: Physical inactivity (no 1,422 cases/yr vigorous/moderate activity in past month) = 1.3 Not modifiable Not modifiable 57.3 Not reported Age at menarche (< age 15 (47.5–65.4) yrs) = 1.20–1.37 Age at menarche: 18.8 Age at menopause (≥ age 45 (7.9–29.0) yrs) = 1.22–1.40 Age at menopause: 13.7 Age at first full-term (6.6–19.6) pregnancy (< age 20 yrs, Age at first full-term parous women only) = pregnancy: 5.2 (–3.2–13.9) 1.02–1.42 Parity: 13.3 (6.9–19.8) Parity (< 4 births) = 1.13–1.35 1st degree family history: 8.5 1st degree family history = (6.5–10.5) 1.66 History of benign breast History of benign breast disease: 9.7 (7.3–12.0) disease = 1.53 Height at age 25: 11.0 Height at age 25 (≥ 1.6 m) = (3.5–18.5) 1.11–1.27 Modifiable 40.7 (23.0–55.1) Modifiable Alcohol: 6.1 (2.1–10.3), Alcohol (≥ 1 drink/wk) = HT, current use: 4.6 1.12–1.43 (–3.5–11.9) HT, current use (E, E+P, or Physical activity: 15.7 other) = 0.96–1.31 (–6.5–33.7) Physical inactivity (≤ 5 hrs/ Weight gain: 21.3 (13.1–29.3) wk) = 1.17–1.26 Weight gain (since age 18, > 5 kg) = 1.27–1.57 continued

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392 BREAST CANCER AND THE ENVIRONMENT TABLE D-1 Continued Source Study Location and Type Study Population Characteristics Europe and Canada Mezzetti et al. Italy Unmatched hospital cases (ages 23–74, (1998) median 55 yrs) and controls (ages Case–control 20–74, median 56 yrs) (1991–1994) 2,569 cases 2,588 controls Bakken et al. Norway Norwegian Women and Cancer study (2004) Cohort Postmenopausal women, ages 45–64, recruited in 1991–1992 or 1996–1997 Cases identified from national cancer registry 31,451 in cohort Neutel and Canada National Population Health Survey Morrison (2010) (1994–2006) Survey data for risk factor prevalence Canadian women ages 50–69 Published literature for RRs National age-adjusted cancer incidence rates

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393 APPENDIX D Population Attributable Risk in Percentb Risk Factors and Impact on Relative Risk Estimatesa (95% CI, where available) Absolute Risk Low levels of physical activity Aggregate: 19.2 (1.5–36.8) Not reported = 1.5 Physical activity: 11.6 Alcohol consumption (–0.1–23.3) (> 20 g/day) = 1.25 Alcohol: 10.7 (4.4–17.0) HT, ever used = 1.9 Current use of HT: 27 300 cases/yr HT, current use = 2.1 (HT formulations different from those in U.S.) Modifiable risk factors: Not reported 2000 All: 28.9 Alcohol (> 9 drinks/wk) = 1.4 Alcohol: 1.8 HT use = 1.4 HT use: 11.5 Obesity (BMI ≥ 30 kg/m(2)) Obesity: 7.6 = 1.4 Physical inactivity: 8.0 Physical inactivity = 1.15 Smoking: 3.8 Smoking, current = 1.25 2006 All: 23.6 Alcohol: 2.6 HT use: 5.2 Obesity: 8.8 Physical inactivity: 6.4 Smoking: 3.1 continued

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394 BREAST CANCER AND THE ENVIRONMENT TABLE D-1 Continued Source Study Location and Type Study Population Characteristics Barnes et al. Germany Mammary carcinoma Risk factor (2010) Investigation (MARIE) (2001–2005) Case–control Postmenopausal women, ages 50–74 3,074 cases 6,386 controls Friedenreich et Europe (15 countries) Eurobarometer, Wave 58.2 (2002) al. (2010) Survey data for risk factor Incidence (2008) prevalence Review of published literature for RR Incidence from estimates by IARC

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395 APPENDIX D Population Attributable Risk in Percentb Risk Factors and Impact on Relative Risk Estimatesa (95% CI, where available) Absolute Risk Not modifiable Not modifiable: 37.2 Not reported Age at menarche (< age 15 (27.1–47.2) yrs) = 1.11–1.16 Age at menarche: 7.7 Age at menopause (≥ age 45 (0.2–14.1) yrs) = 1.12–1.36 Age at menopause: 12.0 Parity (< 3 births) = 1.08–1.30 (3.9–20.2) 1st degree family history = Parity: 10.9 (1.3–18.8) 1.49 1st degree family history: 5.7 History of benign breast (4.1–7.5) disease = 1.24 History of benign breast disease: 7.9 (4.4–11.6) Modifiable Alcohol (≥ 1 g/day) = Modifiable: 26.3 (13.7–37.5) 0.93–0.93 Alcohol: –7.6 (-21.1–3.6) BMI (> 22.4 kg/m(2)) = BMI: 2.4 (-2.8–7.4) 0.93–1.06 HT: 19.4 (15.9–23.2) HT, current use (E, E+P, or Physical activity: 12.8 other) = 1.19–2.25 (5.5–20.8) Physical activity (< 76.5 MET hrs/wk of recreational activities since age 50 yrs) = 1.16–1.23 Physical activity = 0.75 Insufficiently active: 20 Insufficiently active: Sedentary: 10 83,353 cases/yr Sufficiently active (3,000 Sedentary: 42,837 MET-minutes in 7 days cases/yr or 1,500 MET-minutes of vigorous activity over 3 or more days) Not sedentary (≥ 600 MET- minutes over 7 days) continued

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396 BREAST CANCER AND THE ENVIRONMENT TABLE D-1 Continued Source Study Location and Type Study Population Characteristics Petracci et al. Italy Absolute risks: Florence cancer registry (2011) (1989–1993) Model to predict absolute risk; tested with For model development: Case–control independent data subjects (1991–1994), ages 20–74 For validation: Florence-EPIC cohort (1998–2004), ages 35–64 NOTES: Variation across studies in estimated PAR values reflects differences in the prevalence of exposure, in overlap among multiple risk factors, in susceptibility to the risk factor, and in the degree of control for confounding. For these and other reasons, the PARs should be viewed as ballpark estimates based on current science and the assumption that measured associations for these factors are primarily causal. REFERENCES Bakken, K., E. Alsaker, A. E. Eggen, and E. Lund. 2004. Hormone replacement therapy and incidence of hormone-dependent cancers in the Norwegian Women and Cancer study. Int J Cancer 112(1):130–134. Barnes, B. B., K. Steindorf, R. Hein, D. Flesch-Janys, and J. Chang-Claude. 2010. Population attributable risk of invasive postmenopausal breast cancer and breast cancer subtypes for modifiable and non-modifiable risk factors. Cancer Epidemiol 35(4):345–352. Clarke, C., D. Purdie, and S. Glaser. 2006. Population attributable risk of breast cancer in white women associated with immediately modifiable risk factors. BMC Cancer 6(1):170. Friedenreich, C. M., H. K. Neilson, and B. M. Lynch. 2010. State of the epidemiological evidence on physical activity and cancer prevention. Eur J Cancer 46(14):2593–2604. Madigan, M. P., R. G. Ziegler, J. Benichou, C. Byrne, and R. N. Hoover. 1995. Proportion of breast cancer cases in the United States explained by well-established risk factors. J Natl Cancer Inst 87(22):1681–1685. Mezzetti, M., C. La Vecchia, A. Decarli, P. Boyle, R. Talamini, and S. Franceschi. 1998. Popu- lation attributable risk for breast cancer: Diet, nutrition, and physical exercise. J Natl Cancer Inst 90(5):389–394.

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397 APPENDIX D Population Attributable Risk in Percentb Risk Factors and Impact on Relative Risk Estimatesa (95% CI, where available) Absolute Risk Aggregate contribution of Entire population Absolute risk reduction elimination of risk factors from elimination of 10-yr period risk factors, reported (no alcohol consumption, Age 45: 20.5 (11.0–29.2) in percentage point physical activity of ≥ 2 hrs Age 55: 24.5 (14.7–34.2) change (95% CI) per week, and BMI at age ≥ Age 65: 24.5 (14.6–34.1) 50 yrs of < 25 kg/m2) Entire population 20-yr period Age 45: 20.9 (11.6–29.6) 10-yr period Age 55: 24.0 (14.4–33.7) Age 45: 0.6 (0.3–1.0) Age 65: 24.0 (14.3–33.6) Age 55: 0.8 (0.5–1.1) Age 65: 0.9 (0.5–1.3) 20-yr period Age 45: 1.4 (0.7–2.0) Age 55: 1.6 (0.9–2.3) Age 65: 1.6 (0.9–2.3) Abbreviations: BMI, body mass index; CI, confidence interval; E, estrogen-only hormone therapy; E+P, estrogen–progestin hormone therapy; EPIC, European Prospective Investigation into Cancer; HT, hormone therapy; IARC, International Agency for Research on Cancer; MET, metabolic equivalent; NHANES, National Health and Nutrition Examination Survey; PAR, population attributable risk; RR, relative risk. aIncludes relative risks or odds ratios, when reported; range of relative risks provided when multiple risk categories were used in the original report. bPopulation attributable risk is the fraction of all cases of breast cancer in the studied popu- lation in which the factor of interest appears to play a role. Neutel, C. I., and H. Morrison. 2010. Could recent decreases in breast cancer incidence really be due to lower HRT use? Trends in attributable risk for modifiable breast cancer risk factors in Canadian women. Can J Public Health 101(5):405–409. Petracci, E., A. Decarli, C. Schairer, R. M. Pfeiffer, D. Pee, G. Masala, D. Palli, M. H. Gail. 2011. Risk factor modification and projections of absolute breast cancer risk. J Natl Cancer Inst 103(13):1037–1048. Rockhill, B., C. R. Weinberg, and B. Newman. 1998. Population attributable fraction estima- tion for established breast cancer risk factors: Considering the issues of high prevalence and unmodifiability. Am J Epidemiol 147(9):826–833. Sprague, B. L., A. Trentham-Dietz, K. M. Egan, L. Titus-Ernstoff, J. M. Hampton, and P. A. Newcomb. 2008. Proportion of invasive breast cancer attributable to risk factors modifi - able after menopause. Am J Epidemiol 168(4):404–411. Tseng, M., C. R. Weinberg, D. M. Umbach, and M. P. Longnecker. 1999. Calculation of population attributable risk for alcohol and breast cancer (United States). Cancer Causes Control 10(2):119–123.

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