Breast cancer and exposure to tobacco smoke during potential windows of susceptibility

Supplemental Materials

Alexandra J. White1, Aimee A. D’Aloisio1,2, Hazel B. Nichols3, Lisa A. DeRoo1,4, Dale P. Sandler1

Author Affiliations: 1 Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA; 2Social & Scientific Systems, Inc., Durham, NC, USA; 3Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA;4 Department of Global Public Health & Primary Care, University of Bergen, Bergen, Norway.

Supplemental Table I. Cigarette smoking history and invasive breast cancer with the referent group as non-smokers limited to those without ETS exposure, NIEHS Sister Study.

Cigarette smoking status / Person-years (178,702) / Invasive breast cancer (N=1,035) / Age Adjusted
HR (95% CI)1 / Fully adjusted HR (95% CI)2 / Fully adjusted plus alcohol
HR (95% CI)3
Cigarette smoking status
Never smoked / 36,047 / 177 / 1 / 1 / 1
Ever smoked / 142,655 / 858 / 1.10 (0.93, 1.3) / 1.11 (0.94, 1.31) / 0.98 (0.80, 1.19)
Past smoker / 116,535 / 721 / 1.11 (0.93, 1.31) / 1.11 (0.93, 1.31) / 0.97 (0.80, 1.18)
Current Smokers / 26,120 / 137 / 1.07 (0.86, 1.34) / 1.13 (0.90, 1.42) / 1.01 (0.78, 1.31)
Age started smoking
Never smoked / 36,047 / 177 / 1 / 1 / 1
<15 years / 17,971 / 99 / 1.08 (0.84, 1.38) / 1.10 (0.86, 1.42) / 0.93 (0.70, 1.23)
15-19 years / 91,471 / 572 / 1.14 (0.96, 1.36) / 1.16 (0.97, 1.38) / 1.02 (0.83, 1.25)
20+ years / 33,192 / 187 / 0.98 (0.80, 1.21) / 0.97 (0.79, 1.20) / 0.88 (0.70, 1.12)
Total pack-years
Never smoked / 36,047 / 177 / 1 / 1 / 1
<10 pack-years / 71,233 / 391 / 1.03 (0.86, 1.24) / 1.04 (0.87, 1.25) / 0.91 (0.74, 1.12)
10-19 pack-years / 29,545 / 185 / 1.17 (0.95, 1.44) / 1.18 (0.95, 1.46) / 1.04 (0.82, 1.32)
20-29 pack-years / 19,183 / 123 / 1.16 (0.92, 1.47) / 1.19 (0.94, 1.51) / 1.08 (0.82, 1.40)
30+ pack-years / 20,910 / 146 / 1.17 (0.93, 1.46) / 1.22 (0.96, 1.54) / 1.04 (0.8, 1.36)
Total years smoked cigarettes
Never smoked / 36,047 / 177 / 1 / 1 / 1
<10 years / 45,446 / 255 / 1.07 (0.88, 1.30) / 1.08 (0.89, 1.31) / 0.94 (0.75, 1.17)
10-19 years / 39,139 / 231 / 1.1 (0.91, 1.35) / 1.09 (0.89, 1.33) / 0.96 (0.77, 1.20)
20-29 years / 30,351 / 185 / 1.11 (0.90, 1.37) / 1.14 (0.92, 1.42) / 1.03 (0.81, 1.31)
30+ years / 26,996 / 183 / 1.13 (0.92, 1.4) / 1.20 (0.96, 1.50) / 1.06 (0.83, 1.37)
Past smokers, total years
Never smoked / 36,047 / 177 / 1 / 1 / 1
<10 / 44,472 / 251 / 1.08 (0.89, 1.31) / 1.09 (0.9, 1.33) / 0.95 (0.76, 1.18)
10 to 19 / 36,021 / 224 / 1.15 (0.94, 1.41) / 1.14 (0.93, 1.4) / 1.00 (0.79, 1.25)
20 to 29 / 22,819 / 149 / 1.14 (0.91, 1.43) / 1.16 (0.92, 1.46) / 1.03 (0.80, 1.34)
30+ / 13,149 / 96 / 1.15 (0.89, 1.49) / 1.21 (0.92, 1.58) / 1.04 (0.76, 1.4)
Past smokers, time since smoking
Never smoked / 36,047 / 177 / 1 / 1 / 1
<10 years / 18,026 / 109 / 1.21 (0.95, 1.54) / 1.25 (0.98, 1.6) / 1.09 (0.83, 1.44)
10 to 24 years / 47,002 / 284 / 1.14 (0.94, 1.38) / 1.14 (0.93, 1.38) / 0.98 (0.78, 1.22)
25+ years / 51,455 / 328 / 1.07 (0.88, 1.3) / 1.08 (0.89, 1.31) / 0.95 (0.77, 1.19)
Current smokers, usual cigarettes/day
Never smoked / 36,047 / 177 / 1 / 1 / 1
<10 cig/day / 8,088 / 46 / 1.18 (0.85, 1.63) / 1.19 (0.85, 1.68) / 1.04 (0.70, 1.53)
10-19 cigs/day / 8,536 / 40 / 0.97 (0.69, 1.37) / 1.03 (0.71, 1.47) / 0.99 (0.67, 1.48)
20+ cigs/day / 9,463 / 51 / 1.08 (0.79, 1.47) / 1.13 (0.81, 1.59) / 1.11 (0.76, 1.62)
Current smokers, total pack-years
Never smoked / 36,047 / 177 / 1 / 1 / 1
<20 pack-years / 11,304 / 48 / 0.96 (0.69, 1.32) / 0.99 (0.71, 1.39) / 0.80 (0.54, 1.19)
20+ pack-years / 13,834 / 82 / 1.13 (0.86, 1.47) / 1.16 (0.86, 1.55) / 1.14 (0.82, 1.59)
Current smokers, total years
Never smoked / 36,047 / 177 / 1 / 1 / 1
<30 years / 11,623 / 47 / 0.96 (0.69, 1.34) / 1.01 (0.72, 1.43) / 0.92 (0.63, 1.35)
30+ years / 13,847 / 87 / 1.15 (0.88, 1.50) / 1.21 (0.91, 1.62) / 1.15 (0.82, 1.61)
1 adjusted for age
2 adjusted for age, race, education, age at menarche, age at first birth, parity, use of hormonal birth control, use of postmenopausal hormones, age at menopause and menopausal status and BMI
3 adjusted for covariates in model 2 plus alcohol.

Supplemental Table II. Theassociation between lifetime alcohol average intake (drinks/year) and breast cancer risk stratified by smoking status, NIEHS Sister Study

Never Smoker / Former Smoker / Current Smoker
Lifetime alcohol average intake (drinks/year) 1 / Cases (N) / HR (95% CI)2 / Cases (N) / HR (95% CI)2 / Cases (N) / HR (95% CI)2
≤20.4 / 232 / 1 / 82 / 1 / 22 / 1
20.5-61.2 / 200 / 1.10 (0.91, 1.33) / 121 / 0.94 (0.71, 1.25) / 20 / 0.60 (0.33, 1.11)
61.3-143.8 / 195 / 1.24 (1.02, 1.51) / 168 / 1.10 (0.84, 1.44) / 27 / 0.80 (0.45, 1.42)
≥143.9 / 138 / 1.22 (0.98, 1.52) / 263 / 1.44 (1.11, 1.85) / 52 / 0.91 (0.55, 1.53)

1 multiplicative p for interaction = 0.9

2adjusted for age, race, education, age at menarche, age at first birth, parity, use of hormonal birth control,use of postmenopausal hormones, age at menopause and menopausal status and BMI

Supplemental Table III. Cigarette smoking status and breast cancer tumor characteristics, NIEHS Sister Study

Never Smoker / Former Smoker / Current Smoker
Tumor Characteristics1 / N / HR (95% CI)2 / N / HR (95% CI)2 / N / HR (95% CI)2
Staging
Stage 0 / 301 / 1 / 222 / 1.22 (0.99, 1.49) / 39 / 1.10 (0.76, 1.58)
Stage I / 599 / 1 / 462 / 1.02 (0.89, 1.17) / 75 / 0.91 (0.70, 1.18)
Stage II-IV / 315 / 1 / 207 / 0.94 (0.76, 1.15) / 38 / 0.91 (0.63, 1.32)
Estrogen receptor status (ER)
ER+ / 742 / 1 / 565 / 1.01 (0.89, 1.15) / 91 / 0.91 (0.71, 1.16)
ER- / 148 / 1 / 87 / 0.87 (0.64, 1.17) / 22 / 1.01 (0.61, 1.67)
Invasive histologic type
Ductal / 726 / 1 / 544 / 1.01 (0.88, 1.14) / 91 / 0.91 (0.71, 1.16)
Lobular / 96 / 1 / 60 / 0.83 (0.57, 1.20) / 14 / 1.06 (0.57, 2.00)
Menopausal Status at Diagnosis
Premenopausal / 243 / 1 / 112 / 0.98 (0.77, 1.26) / 27 / 0.78 (0.51, 1.21)
Postmenopausal / 735 / 1 / 605 / 0.99 (0.87, 1.13) / 109 / 1.15 (0.91, 1.44)
1 Estrogen receptor status, histologic type and menopausal status at diagnosis limited to invasive cases
2 adjusted for age, race, education, age at menarche, age at first birth, parity, use of hormonal birth control, alcohol intake, use of postmenopausal hormones, age at menopause and menopausal status and BMI

Supplemental Table IV. Environmental tobacco smoke (ETS) and breast cancer tumor characteristics, NIEHS Sister Study

No ETS / ETS
Tumor Characteristics1 / N / HR (95% CI)2 / N / HR (95% CI)2
Staging
Stage 0 / 59 / 1.00 (referent) / 239 / 1.17 (0.82, 1.66)
Stage I / 120 / 1.00 (referent) / 469 / 0.80 (0.64, 1.00)
Stage II-IV / 50 / 1.00 (referent) / 260 / 1.25 (0.88, 1.78)
Estrogen receptor status (ER)
ER+ / 144 / 1.00 (referent) / 586 / 0.87 (0.71, 1.07)
ER- / 25 / 1.00 (referent) / 121 / 1.21 (0.72, 2.02)
Invasive histologic type
Ductal / 135 / 1.00 (referent) / 581 / 0.89 (0.72, 1.1)
Lobular / 15 / 1.00 (referent) / 79 / 1.32 (0.69, 2.53)
Menopausal Status at Diagnosis
Premenopausal / 70 / 1.00 (referent) / 172 / 0.79 (0.58, 1.07)
Postmenopausal / 107 / 1.00 (referent) / 612 / 1.14 (0.89, 1.46)
1 Estrogen receptor status, histologic type and menopausal status at diagnosis limited to invasive cases
2 adjusted for age, race, education, age at menarche, age at first birth, parity, use of hormonal birth control, alcohol intake, use of postmenopausal hormones, age at menopause and menopausal status and BMI