*Results Reflect Estimates of Relative Risk (95% Confidence Interval)
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Appendix Table 1: Summary of Associations between Reproductive Factors and Tumor Subtypes for Cohort, Case-control Studies, and Case- case Studies Case-control and Cohort Studies Author, year Study design P Tumor Subtypes Results* o p u l a t i o n Warner, 2013 Prospective cohort 3 ER+/PR]; ER-/PR- Premenopausal women diagnosed <40 years of age [30] 7 Age at menarche 14+ vs. 12: [ER+/PR+] 0.50 (0.28- 4 0.90); [ER-/PR-] 0.70 (0.33-1.49) i n Age at first birth 30+ vs. 25-29: [ER+/PR+] 1.15 (0.65- c 2.03); [ER-/PR-] 0.77 (0.37-2.59) i Parity 2 children vs. nulliparous: [ER+/PR+] 0.97 (0.59- d 1.60); [ER-/PR-] 1.79 (0.92-3.50) e n Breastfeeding ever vs. never or less than 1 month: t [ER+/PR+] 0.79 (0.43-1.44); [ER-/PR-] 0.79 (0.38-1.64) c Parity and breastfeeding, 2+ children and never a breastfed [ER+/PR+] 1.19 (0.58-2.43); [ER-/PR-] 2.35 s (0.93-5.97) e s Parity and breastfeeding 2+ children and ever breastfed: o [ER+/PR+] 0.81 (0.50-1.32); [ER-/PR-] 1.30 (0.34-2.66) f p r Premenopausal women diagnosed 40+ years of age e Age at menarche 14+ vs. <12 years: [ER+/PR+] 0.95 m (0.80-1.13); [ER-/PR-] 1.06 (0.77-1.47) e Age at first birth 30+ years vs. 25-29 years: [ER+/PR+] n 1.15 (0.97-1.36); [ER-/PR-] 0.77 (0.37-2.59) o p Age at first birth < 25 years vs. 25-29 years: [ER+/PR+] a 0.83 (0.73-0.96) u Parity 3+ children vs. nulliparous: [ER+/PR+] 0.76 s (0.63-0.91); [ER-/PR-] 1.12 (0.75-1.68) a l Breastfeeding ever vs. never or less than 1 month: b [ER+/PR+] 0.81 (0.66-0.99); [ER-/PR-] 0.72 (0.32-1.61) r Parity and breastfeeding, 2+ children and never e breastfed vs nulliparous: [ER+/PR+] 1.07 (0.89-1.29); a [ER-/PR-] 1.17 (0.65-2.10) s t Parity and breastfeeding 2+ children and ever breastfed c vs. nulliparous: [ER+/PR+] 0.81 (0.70-0.94); [ER-/PR-] a 1.10 (0.45-2.29) n c e r d i a g n o s e d b e f o r e a g e 4 0 a n d 2 5 3 3 i n c i d e n t c a s e s o f p r e m e n o p a u s a l b r e a s t c a n c e r d i a g n o s e d a t a g e 4 0 o r o l d e r f r o m
N u r s e s ’ H e a lt h S t u d y C o h o r t Warner, 2013 Prospective cohort 1 ER+ only Analysis among all women, pre- and postmenopausal [16] 4 0 Parity parous vs. nulliparous: races combined 0.54 (0.4- , 0.73); black women 0.54 (0.18-1.58), white women 0.55 9 (0.40-0.76) 1 Age at first live birth, continuous variable, races 4 combined 1.04 (1.03-1.05); black women 1.04 (1.01-1.06); w white women 1.04 (1.03-1.06) o m Lactation > 6 months vs. never: races combined 1.02 e (0.88-1.2); black women 1.29 (0.91-1.83); white women n 0.92 (0.77-1.10) f Analysis among premenopausal women r o Parity parous vs. nulliparous: races combined 0.64 m (0.44-0.94); black women 0.86 (0.20-3.78), white women 0.58 (0.38-0.87) t h Age at first live birth, continuous variable: races e combined 1.04 (1.02-1.06); black women 1.01 (0.64-1.59); B white women 0.92 (0.73-1.14) l Lactation > 6 months vs. never: races combined 0.90 a (0.74-1.09); black women 0.98 (0.62-1.55); white women c 0.89 (0.71-1.11) k W o m e n ’ s H e a lt h S t u d y a g e d 2 1 - 6 9 a n d N u r s e s ’ H e a lt h S t u d y , a g e d 2 5 - 4 2 : 1 5 0 6 i n c i d e n t i n v a s i v e c a s e s o f E R + b r e a s t c a n c e r Rosato, 2013 Case-control 1 ER+/PR+; ER-/PR; Parity >3 births vs. nulliparous [ER+/PR+] 0.7 (0.5-0.9); [17] 0 ER-/PR+; ER+/PR- [ER-/PR-]: 0.9 (0.5-1.6) 7 Age at menarche > 15 years vs. < 13 years: [ER+/PR+] 5 0.9 (0.7-1.2); [ER-/PR-] 0.7 (0.4-1.2) w o Age at first birth >30 years vs. <25 years : [ER+/PR+] m 1.5 (1.1-2.1); [ER-/PR-]: 1.3 (0.8-2.2) e Menopausal status post vs. pre/perimenopausal: n [ER+/PR+] 0.6 (0.4-0.9); [ER-/PR-] 0.9 (0.5-1.6) w it Age at menopause age >=50 years vs. <50 years: h [ER+/PR+] : 1.3 (1.0-1.6); [ER-/PR-] 1.0 (0.6-1.6) i hormone replacement therapy ever vs. never: n [ER+/PR+] 1.4 (0.9-1.6); [ER-/PR-] 1.5 (0.8-2.8) c i d e n t b r e a s t c a n c e r, 1 4 7 7 h o s p it a l c o n t r o l s Li, 2013 Population based case-control study 2 ER+; HER2+; Age at menarche > 14 years vs. < 12 years: [ER+] 0.8 [15] 0 HER2+/ER-; (0.6-1.1); [TNBC] 0.7 (0.5-1.2); [HER2] 0.5 (0.2-1.4) - TNBC Parity parous vs. nulliparous: [ER+] 0.7 (0.5-0.8); 4 [TNBC] 0.7 (0.5-1.0); [HER2] 1.1 (0.6-2.2) 4 Number of live births: >3 vs. 1: [ER+] 0.7 (0.5-0.9); y [TNBC] 0.7 (0.4-1.2); [HER2] 0.6 (0.2-1.4) e Age at first birth: >35 years vs. <20 years: [ER+] 0.7 a (.5-1.1); [TNBC] 0.4 (0.2-0.8); [HER2] 0.4 (.1-1.5) r Interval between menarche and age at first live birth: o >20 years vs. <10 years: [ER+] 0.9 (.6-1.2); [TNBC] 0.5 l (0.3-0.9); [HER2] 0.5 (0.2-1.4) d Breastfeeding >12 months vs. never: [ER+] 1.0 (0.6- w 1.5); [TNBC] 0.5 (0.3-0.9); [HER2] 1.1 (0.3-3.6) o m e n 1 0 2 1 c a s e s ( 7 8 1 E R + , 1 8 0 T N B C , 6 0 H E R 2 + ) a n d 9 4 1 c o n t r o l s Chung, 2013 Case-control S ER+ or PR+ 1940s [31] e (HR+); ER-/PR- Menarche age per year: [HR+] 0.90 (0.85-0.96); [HR-] o (HR-) (0.95 (0.88-1.04) u Ever pregnant: [HR+] 0.30 (0.11-0.82); [HR-] 2.83 l (0.57-14.13) B Age at first full term pregnancy per year: [HR+] 1.02 r (0.98-1.05); [HR-] 0.98 (0.95-1.03) e Breastfeeding duration per month: [HR+] 1.0 (1.0-1.01); a [HR-] 1.01 (1.0-1.01) s Never breastfeeding: [HR+] 1.15 (0.79-1.67); [HR-] t 1.01 (1.0-1.01) C Duration of estrogen exposure before first pregnancy per a year (interval between menarche and age at first birth for n parous women and age at diagnosis for nulliparous women: c [HR+] 1.04 (1.01-1.06); [HR-] 0.99 (0.96-1.03) e 1950s r Menarche age per year: [HR+] 0.92 (0.88-0.97); [HR-] s (0.90 (0.84-0.96) t Ever pregnant: [HR+] 0.25 (0.18-0.52); [HR-] 1.12 u (0.36-3.56) d Age at first full term pregnancy per year: [HR+] 1.04 y (1.02-1.07); [HR-] 0.98 (0.94-1.02) , Breastfeeding duration per month: [HR+] 1.0 (0.99-1.0); i [HR-] 1.0 (0.99-1.01) n Never breastfeeding: [HR+] 1.17 (0.92-1.50); [HR-] c 0.66 (0.45-0.97) l Estrogen exposure before first pregnancy per year: u [HR+] 1.05 (1.03-1.08); [HR-] 1.01 (0.98-1.04) d 1960s e Menarche age per year: [HR+] 0.90 (0.84-0.96); [HR-] d 0.91 (0.83-1.0) 3 Ever pregnant: [HR+] 0.30 (0.12-0.71); [HR-] 1.08 , (0.30-3.89) 3 Age at first full term pregnancy per year: [HR+] 1.04 3 (1.01-1.07); [HR-] 1.01 (0.97-1.05) 2 w Breastfeeding duration per month: [HR+] 0.99 (0.98- o 1.0); [HR-] 1.0 (0.98-1.02) m Never breastfeeding: [HR+] 1.20 (0.96-1.50); [HR-] e 1.51 (1.11-2.05) n Estrogen exposure before first pregnancy per year: w [HR+] 1.05 (1.02-1.08); [HR-] 1.03 (1.0-1.07) it h b r e a s t c a n c e r a n d 3 6 2 0 c o n t r o l s ( g r o u p e d b y b i r t h y e a r : 1 9 4 0 s , 5 0 s , 6 0 s ) Ritte, 2013 Prospective Cohort E ER+/PR+; ER-/PR- Older age at first birth > 35 years vs. < 19 years: [32] P [ER+/PR+] 1.46 (1.15-1.88); [ER-/PR-] 0.93 (0.53-1.65) I Age at menarche > 15 years vs. <13 years: [ER+/PR+] C 0.76 (0.68-0.85); [ER-/PR-] 0.85 (0.69-1.04) , Age at menopause > 55 years vs. < 48 years: [ER+/PR+] m 1.19 (0.97-1.47); [ER-/PR-] 1.06 (0.71-1.58) u Parity vs. nulliparous: [ER+/PR+] 0.86 (0.77-0.95); lt [ER-/PR-] 0.97 (0.80-1.19) i Parity >3 children vs. 1 child: [ER+/PR+] 0.77 (0.69- - 0.85); [ER-/PR-] 0.89 (0.72-1.09) c Time between menarche and age at first full-term birth e >10 years vs. <10 years: [ER+/PR+] 1.21(1.12-1.31); n [ER-/PR-] 1.14 0.98-1.32) t Time since last full term childbirth >20 years vs. <20 e years: [ER+/PR+] 0.87 (0.78-0.96); [ER-/PR-] 1.00 (0.82- r 1.22) E Ever breastfed vs. never [ER+/PR+] 0.99 (0.90-1.09); u [ER-/PR-]: 0.97 (0.81-1.16) r o Cumulative breastfeeding duration >18 months vs. <1 p month: [ER+/PR+] 1.09 (0.91-1.31); [ER-/PR-] 1.04 (0.73- 1.46) e Oral contraceptive use current vs. never: [ER+/PR+] a 1.20 (0.97-1.47); [ER-/PR-] 1.08 (0.73-1.59) n Oral contraceptive use past vs. never: [ER+/PR+] 1.00 s (0.93-1.08); [ER-/PR-] 1.11 (0.96-1.28) t u d y , 3 4 5 , 1 5 3 w o m e n a g e d 2 5 - 7 0 ; 9 4 5 6 b r e a s t c a n c e r c a s e s Ritte, 2012 Prospective cohort E ER+/PR+; Postmenopausal women with current hormone [37] P ER+/PR-; ER-/ replacement therapy use: [ER-/PR-] 1.3 (1.05-1.62); I PR+; ER- PR- [ER+/PR+] 1.74 (1.56-1.95) C Among women in lowest tertile of BMI, hormone , replacement therapy use ever vs. never: [ER-/PR-] 1.74 m (1.15-2.63); [ER+PR+] 2.32 (1.84-2.92) u lt i - c e n t e r E u r o p e a n s t u d y , 3 1 4 , 6 7 6 w o m e n a g e d 2 5 - 7 0 ; 9 5 3 0 b r e a s t c a n c e r c a s e s Tamimi, 2012 Prospective cohort 1 Luminal A; luminal Age at menarche: 14+ vs. <12: [Luminal A] 0.7 (0.5- [34] 2 B; HER2+; basal- 0.9); [Luminal B] 1.0 (0.6-1.6); [HER2+] 1.1 (0.5-2.3); 1 like; unclassified [Basal] 0.8 (0.5-1.3) , Parity 3+ vs. nulliparous: [Luminal A] 0.7 (0.5-1.0); 7 [Luminal B] 1.1 (0.5-2.6); [HER2+] 0.7 (0.2-2.3); [Basal] 0 1.1 (0.4-2.9) 0 Age at first birth per 1 year increase: [Luminal A] 1.018 U (1.007-1.030); [Luminal B] 0.994 (0.964-1.024); [HER2+] . 1.024 (0.991-1.059); [Basal] 1.002 (0.968-1.037) S Age at menopause per 1 year increase: [Luminal A] . 1.0038 (1.021-1.058); [Luminal B] 1.067 (1.024-1.111); n [HER2+] 1.075 (1.006-1.150); [Basal] 1.012 (0.972-1.053) u Past hormone replacement therapy use among r postmenopausal (vs. referent never use): [Luminal A] 0.9 s (0.8-1.1); [Luminal B] 1.2 (0.8-1.7); [HER2+] 1.3 (0.7-2.4); e [Basal] 0.8 (0.5-1.4) s Postmenopausal current estrogen only hormone a replacement therapy: [Luminal A] 1.4 (1.1-1.7); [Luminal g B] 2.0 (0.7-1.7); [HER2+] 1.1 (0.6-2.3); [Basal] 1.4 (0.8- e 2.3) d Postmenopausal current estrogen and progesterone 3 hormone replacement therapy: [Luminal A] 1.5 (1.2-2.0); 0 [Luminal B] 1.3 (0.8-2.4); [HER2+] 0.3 (0.0-2.2); [Basal] - 1.8 (1.1-3.4) 5 Lactation 4+ months vs. never: [Luminal A] 0.8 (0.7- 5 1.0); [Luminal B] 0.8 (0.6-1.1); [HER2+] 0.9 (0.6-1.5); ; [Basal] 0.6 (0.4-0.9) 2 0 2 2 i n v a s i v e b r e a s t c a n c e r c a s e s
Islam, 2012 Population based case-control J All luminal (ER+); Age at menarche <12 years vs. > 15 years: [Luminal] [36] a ER-/PR-/HER2+; 1.67 (1.22-2.29); [HER2] 0.63 (0.31-1.28); [TNBC] 2.04 p TNBC (0.95-4.35) a Parity >3 vs. 0: [Luminal] 0.91 (0.66-1.27); [HER2+] n 1.15 (0.49-2.71); [TNBC] 0.67 (0.25-1.82) e Age at first live birth >30 years vs. <25 years: [Luminal] s 1.23 (0.86-1.74); [HER2+] 0.99 (0.66-1.32); [TNBC] 0.67 e (0.27-1.47) s Breastfeeding >6 months vs. never: [Luminal] 1.02 t (0.77-1.35); [HER2+] 1.09 (0.60-1.98); [TNBC] 0.91(0.48- u 1.73) d Age at menopause >50 years vs. <50 years: [Luminal] y 0.79 (0.58-1.08); [HER2+] 1.18 (0.60-1.98); [TNBC] 1.17 o (0.60-2.26) f 7 0 6 w o m e n a g e d 2 0 - 7 9 w it h b r e a s t c a n c e r a n d 1 4 1 2 a g e a n d m e n o p a u s a l s t a t u s m a t c h e d c o n t r o l s Bao, 2011 Population based case-control S ER+/PR+; Age at menarche >17 years vs. < 13 years: [ER+/PR+] [21] h ER+/PR-; ER-/ 0.66, (0.63-.82); [ER-/PR-] 0.62 (0.46-0.83) a /PR+; ER- /PR- Years of menstruation > 35 years vs. < 27 years: n [ER+/PR+] 1.66 (1.3-2.1); [ER-/PR-] 1.38 (1.01-2.11) g Parity never vs. ever: [ER+/PR+] 1.4 (1.03-1.9); [ER-PR-] h 0.9 (0.57-1.4) a Parity > 3 vs. 1: [ER+/PR+] 0.8 (0.58-1.12); [ER-/PR-] i 0.61 (0.40-0.95) B Parity among postmenopausal women >2 vs. 1 child: r [ER+/PR+] 0.69 (0.52-.91); [ER-/PR-] 1.12 (0.79-1.58) e Parity among premenopausal women >2 vs. 1 child a [ER+/PR+] 0.70 (0.49-0.99); [ER-/PR-] 0.60 (0.37-0.96) s Breastfeeding among parous premenopausal at diagnosis t >18 months vs. never: [ER+/PR+] 1.02 (0.56-1.84); C [ER-/PR-] 1.11 (0.48-2.49) a Breastfeeding among parous, postmenopausal at diagnosis n >18 months vs. never: [ER+/PR+] 0.66 (0.44-0.99); c [ER-/PR-] 0.48 (0.30-0.77) e Age at first live birth >29 years vs. < 24 years: [ER+/PR+] r 1.24 (1-1.54); [ER-/PR-] 0.98 (0.74-1.28) S Duration of breastfeeding, months >18 vs. never: t [ER+/PR+] 0.71 (.53-.95); [ER-/PR-] 0.76 (0.52-1.11) u Hormone replacement therapy ever vs. never: [ER+/PR-] d 2.25 (1.4-3.6); [ER+/PR+] 1.05 (0.74-1.5); [ER-/PR-] 1.24 y (0.81-1.91); [ER-/PR+] 0.51 (0.19-1.41) : 2 6 7 6 w o m e n w it h b r e a s t c a n c e r a g e d 2 0 - 7 9 a n d 3 4 7 4 c o n t r o l s Phipps, 2011 Prospective cohort R ER+; HER2 Parity: Nulliparous vs. parous: [ER+] 1.31 (1.23-1.39); [18] e overexpressing [ER-/PR-/HER2+] 1.15 (0.84-1.58); [TNBC] 1.07 (0.87- g (HER2+/ER-); 1.33) i TNBC Age at first birth: 30+ years vs. < 30 years: [ER+] 1.37 s (1.28-1.47); [ER-/PR-/HER2+] 1.83 (1.31-2.56); TNBC t 1.18 (0.93-1.51) r i e s o f 7 4 3 , 6 2 3 w o m e n , 1 0 , 8 9 6 w o m e n d i a g n o s e d w it h b r e a s t c a n c e r, a g e d 4 0 - 8 4 Phipps, 2011 Prospective cohort W ER+; TNBC Age at menarche >14 years vs. < 12 years: [ER+] 0.89 [35] o (0.79-1.0); [TNBC] 0.96 (0.67-1.39) m Age at menopause: ≥55 years vs. 45-54 years: [ER+] e 1.13 (1.00-1.27); [TNBC] 1.02 (0.68-1.52) n Parity nulliparous vs. >1: [TNBC] 0.61(0.37-0.97); ’ [ER+] 1.35 (1.2-1.52) s Parity >3 vs. 1 child: [TNBC]: 1.46 (0.82-2.63); [ER+] H 0.88 (0.74-1.04) e Age at first birth: >30 years vs. <20 years: [ER+] 1.36 a (1.10-1.67); [TNBC] 1.05 (0.53-2.06) lt Duration of breastfeeding > 12 months vs. never: [ER+] h 0.98 (0.85-1.13); [TNBC] 0.81 (0.53-1.26) I Lifetime oral contraceptive use > 10 years vs. never n [ER+] 0.8 (0.68-0.94); [TNBC] 1.11 (0.72-1.79) it Age at first oral contraceptive use < 20 vs. never used: i [ER+] 1.08 (0.67-1.72); [TNBC] 0.62 (0.15-2.69) a ti v e : 1 5 5 , 7 2 3 w o m e n a g e d 5 0 - 7 9 ; 3 0 7 T N B C s a n d 2 6 1 0 H R + b r e a s t c a n c e r c a s e s Gaudet, 2011 Case-control 8 Luminal A; Age at menarche: per 2 year increase: [Luminal A] 0.87 [20] 9 Luminal B; (0.75-1.01); [Luminal B] 0.60 (0.42-0.85); [HER2+] 0.82 0 HER2+; TNBC (0.63-1.07); [TNBC] 0.98 (0.81-1.18) b Parity nulliparous vs. parous: [Luminal A] 3.02 (1.47- r 6.23); [Luminal B] 4.11 (0.80-21.07); [HER2+] 2.21 (0.60- e 8.16); [TNBC] 1.08 (.41-2.81) a Age at first birth per 5 years: [Luminal A] 1.16 (1.01- s 1.33); [Luminal B] 1.31 (0.95-1.80); [HER2+] 1.19 (0.93- t 1.53); [TNBC] 1.08 (0.90-1.31) c Breastfeeding, per 6 months: [Luminal A] 0.94 (0.86- a 1.02); [Luminal B] 0.70 (0.48-1.01); [HER2+] 0.85 (0.70- n 1.04); [TNBC] 0.76 (0.64-0.90) c e r p a ti e n t s ; < 5 6 y e a r s o f a g e i d e n ti f i e d t h r o u g h S E E R r e g i s t r i e s , a n d 3 , 4 3 2 m a t c h e d c o n t r o l s Palmer, 2011 Prospective Cohort 5 ER+/PR+; Parity number of births 3+ vs. 0: [ER+/PR+] 0.53 (0.39- [19] 9 ER+/PR-; ER-/ PR- 0.73); [ER-/PR-] 1.48 (0.98-1.84) , Higher parity 2+ births vs. nulliparous among women 0 who ever lactated: [ ER-/PR-] 1.16 (1.09-2.23); [ER+/PR+] 0 0.73 (0.54-0.97) 0 Age at first birth: >30 years vs. <20 years: [ER+/PR+] A 1.34 (0.93-1.94); [ER-/PR-] 1.47 (0.94-2.29) f Years since last birth <10 vs. >15: [ER+/PR+] 1.69 r (1.08-2.63); [ER-/PR-] 1.61 (0.97-2.68) i Parity in older women (>45) > 3 vs. 0 births: c [ER+/PR+] 0.47 (0.33-0.66) [ER-/PR-] 1.39 (0.86-2.25) a Parity in younger women (<45) > 3 births vs. n nulliparous: [ER+/PR+] 0.76 (0.36-1.59); [ER-/PR-] 1.89 A (1.00-3.59) m Lactation among parous women yes vs. no: [ER+/PR+] e 1.13 (0.91-1.42); [ER-/PR-] 0.78 (0.6-1.03) r Age at first birth and older women (>45) > 30 years vs. i < 20 years: [ER+/PR+] 1.75 (0.85-3.61); [ER-/PR-] 1.16 c (0.65-2.07) a n Age at first birth and younger women (<45y) > 30 years w vs. <20 years: [ER-/PR-] 2.24 (0.76-3.86); [ER+/PR+] 1.75 o (0.85-3.61) m Years since last birth and younger women (<45y) <10 e years vs. > 15 years: [ER-/PR-] 2.18 (1.08-4.41); n [ER+/PR+]1.61 (0.88-2.95) ; Years since last birth and older women (>45y) <10 years vs. > 15 years: [ER-/PR-] 0.66 (0.16-2.79); [ER+/PR+]1.51 a (0.71-3.23) g Women with 2+ births, last greater than 10 years ago: e [ER-/PR-] 1.66 (1.13- 2.44) d Parity and years since last birth with nulliparous women 2 as referent, women with 2+ births, last less than 10 years 1 ago: [ER+/PR+] 1.24 (0.79- 1.94); [ER-/PR-] 2.05 (1.29- - 3.26) 6 9 , 9 2 2 c a s e s o f b r e a s t c a n c e r w it h h o r m o n e r e c e p t o r s t a t u s Yang, 2011 Pooled case-case of 12 population 3 ER+; [PR+; Case-control comparisons [33] based studies and case-control 5 ER+/PR+; Nulliparous vs parous, TNBC 0.94 (0.75-1.10); ER+ comparison , ER+/HER2+; 1.30 (1.21-1.40); ER- 1.01 (0.90-1.13) 5 HER2+ Age at first birth per 5 year increase: TNBC 0.95(0.86- 6 PR+/HER2+; 1.05); ER+ 1.12 (1.08-1.15); ER- 0.99 (0.94-1.03) 8 ER+/PR-; Age at menarche < 12 years vs > 15 years: ER+ 1.16 b ER-/PR+; ER-/ (1.06-1.15); ER- 1.11 (0.99-1.24) r PR-; TNBC e a s t c a n c e r p a ti e n t f r o m
3 4 s t u d i e s , a g e r a n g e 1 8 - 1 0 0 , p a r ti c i p a ti n g i n B r e a s t C a n c e r A s s o c i a ti o n C o n s o r ti u m Ma, 2010 Population based case-control 3 Luminal A; Parity >4 births vs. 0: [Luminal A] 0.55 (0.38-0.79); [23] 5 Luminal B; [Luminal B] 0.55 (0.26-1.20); [HER2+] 0.47 (0.19-1.15); - HER2+; TNBC [TNBC] 1.00 (0.60-1.67) 6 Age at first full term pregnancy > 30 years vs. < 19 4 years: [Luminal A] 1.03 (0.76-1.57); [Luminal B] 0.78 y (0.33-1.85); [HER2+] 0.91 (0.35-2.36); [TNBC] 1.32 (0.80- e 2.17) a Duration of Breastfeeding: > 24 months vs. never: r [Luminal A] 0.55 (0.34-0.88); [Luminal B] 0.91 (0.38- o 2.20); [HER2+] 1.31 (0.53-3.21]; [TNBC] 0.80 (0.47-1.36); l Oral contraceptive use ever vs. never: [Luminal A] d 0.93(0.74-1.17); [Luminal B] 1.23 (0.73-2.10); [HER2+] w 1.21 (0.69-2.11); [TNBC] 1.00 (0.72-1.39) o Young at first contraceptive use in older women (45-64 m years): <18 years vs. never: [Luminal A] 1.36 (0.75-2.48); e [TNBC] 2.87 (1.44-5.74) n Young at first contraceptive use in younger women (35- i 44 years) <18 years vs. never: [Luminal A] 0.82 (0.46- n 1.47); [TNBC] 0.70 (0.38-1.27) t Duration of breastfeeding in younger women (35-44 h years) >24 months vs. <1 month: [TNBC] 0.55 (0.24- e 1.28); [Luminal A] 0.35 (0.15-0.86) W Duration of breastfeeding in older women (45-64 years) o >24 months vs. <1 month: [TNBC] 0.82 (0.39-1.72); m [Luminal A] 0.69 (0.40-1.21) e Parity in older women (45-64 years) >4 births vs. 0: n [TNBC] 1.48 (0.68-3.21); [Luminal A] 0.56 (0.36-0.86) ’ Parity in younger women (35-44 years) >4 births vs. 0: s [TNBC] 0.76 (.35-1.67); [Luminal A] 0.56 (0.26-1.17) C o n t r a c e p ti v e a n d R e p r o d u c ti v e E x p e r i e n c e s s t u d y : 1 1 9 7 c a s e s a n d 2 0 1 5 c o n t r o l s Xing, 2010 Case-control 1 Luminal A; Age at menarche < 13 years vs. >13 years: [Luminal A] [22] 4 Luminal B; 2.35 (1.45-3.81); [Luminal B] 1.61 (0.70-3.71); [HER2+] 1 HER2+; TNBC 2.21 (0.90-5.45); [TNBC] 1.55 (0.79-3.05) 7 Parity 1 vs. nulliparous: [Luminal A] 0.35 (0.17-0.72); w [Luminal B] 0.17 (0.07-0.43); [HER2+] 0.20 (0.06-0.62); o [TNBC] 0.50 (0.18-1.4) m Parity > 3 vs. nulliparous: [Luminal A] 0.64 (0.74-3.62); e [Luminal B] 1.51 (0.55-4.12); [HER2+] 2.07 (0.59-7.33); n [TNBC] 3.02 (0.99-9.17) w Breastfeeding ever vs. never: [Luminal A] 0.44 (0.31- it 0.63); [Luminal B] 0.54 (0.31-0.95); [HER2+] 0.33 (0.18- h 0.61); [TNBC] 0.48 (0.30-0.77) b r e a s t c a n c e r f r o m
C h i n a a g e d 2 1 - 8 5 a n d 1 5 8 7 c o n t r o l s
Ma, 2010 Prospective cohort C ER+; ER-; Parous vs. nulliparous: [ER+] 0.87 (0.78-0.97); [ER-] [24] a ER+/PR+; ER-/PR- 0.99 (0.74-1.31); [ER+/PR+] 0.81 (0.71-0.91); [ER-/PR-] li 1.04 (0.77-1.41) f Number of full pregnancies: >4 vs. 1: [ER+] 0.76 (0.65- o 0.89); [ER-] 0.90 (0.61-1.34); [ER+/PR+] 0.71 (0.59-0.85); r [ER-/PR-] 0.9 (0.59 to 1.37) n Age at first pregnancy: > 35 years vs. < 21 years: [ER+] i 1.37 (1.02-1.83); [ER-] 1.21 (0.52-2.81); [ER+/PR+] 1.36 a (0.98-1.89); [ER-/PR-] 1.07 (0.44-2.60) T Breastfeeding > 24 months vs. never: [ER+] 1.02 (0.83- e 1.25); [ER-] 1.00 (0.61-1.66); [ER+/PR+] 1.00 (0.80-1.27); a [ER-/PR-] 1.06 (0.64-1.78) c h e r s S t u d y ; 1 3 3 , 4 7 9 w o m e n ; 2 , 8 2 8 w it h b r e a s t c a n c e r a g e d 3 5 - 6 4 y e a r s Dolle, 2009 2 pooled population based case- 8 Non-TNBC; Age at menarche 15+ years vs. 8-12 years: [TNBC] 0.4 [41] control studies 9 TNBC; ER-; ER+; (0.2-1.0); [non-TNBC] 0.8 (0.6-1.2) 7 HER2-; HER2+; Number of live births 4+ vs. 0: [non-TNBC] 0.5 (0.3- b ER-/HER2+; 1.0); [TNBC] 0.6 (0.2-1.9) r ER-/HER2-; Age at first birth: 30+ vs. none: [TNBC] 1.2 (0.5-3.0); e ER+/HER2+; [non-TNBC] 1.0 (0.6-1.8) a ER+/HER2- Lactation 12+ months vs. never: [non-TNBC] 1.0 (0.7- s 1.8); [TNBC] 1.0 (0.6-1.7) t Duration of Oral contraceptive use 6+ years vs. 1-3 c years: [TNBC] 2.9 (1.6-5.3); [non-TNBC] 1.1 (0.8-1.5) a Duration of OC use 6+ years vs. 1-3 years: n [ER-] 2.2 (1.4-3.4); [ER+] 0.9 (0.6-1.3); [HER2-] 1.4 (1.0- c 2.0); [HER2+] 1.2 (0.8-1.8); [ER-/HER2-] 2.5 (1.5-4.2); e [ER+/HER2-] 0.9 (0.6-1.3); [ER-/HER2+] 1.7 (0.8-3.4); r [ER+/HER2+] 1.0 (0.6-1.7) c a s e s a g e d 2 0 - 4 5 y e a r s ; 8 9 7 c a s e s a n d 1 5 6 9 a g e - m a t c h e d c o n t r o l s Trivers, 2009 Case-case and case-control W ER+ or Case-control comparisons [25] o PR+/HER2-; Age at menarche <12 years vs. 12+ years: m ER+or [ER/PR+/HER2+] 0.93 (0.50-1.73); [TNBC] 1.60 (1.17- e PR+/HER2+; 2.19); [HER2+] 1.63 (0.92-2.88); [ER/PR+/HER2-] 1.09 n HER2+; TNBC (0.84-1.42) d Age at first birth <18 years vs. nulliparous: i [ER/PR+/HER2+] 0.32 (0.09-1.13); [TNBC] 0.67 (0.39- a 1.17); [HER2+] 2.53 (0.81-7.94); [ER/PR+/HER2-] 0.23 g (0.12-0.44) n Parity >4 births vs. nulliparous: [ER/PR+/HER2+] 0.53 o (0.20-1.41); [TNBC] 0.62 (0.36-1.07); [HER2+] 0.90 (0.25- s 3.23); [ER/PR+/HER2-] 0.28 (0.17-0.46) e Recency of birth <5 years vs. nulliparous: d [ER/PR+/HER2+] 0.62 (0.24- 1.61); [TNBC] 1.04 (0.62- w 1.74); [HER2+] 2.53 (0.81-7.94) [ER/PR+/HER2-] 0.46 it (0.27-0.79) h Breastfeeding 12+ months vs. never: : b [ER/PR+/HER2+] 0.12 (0.03-0.56) [TNBC] 0.53 (0.32- r 0.85); [HER2+] 0.37 (0.13- 1.08); [ER/PR+/HER2-] 0.68 e (0.48- 0.96) a s t c a n c e r a g e d 2 0 - 5 4 a n d 9 1 3 c o n t r o l s Setiawan, 2009 Prospective cohort 8 ER+/PR+, Age at menarche > 15 years vs. <12 years : [ER+/PR+] [26] 4 ER+/PR-, 0.82 (0.69-0.97); [ER+/PR-] 0.74 (0.49-1.11); [ER-/PR-] , ER-/PR+, ER-/PR- 1,15 (0.88-1.57) 4 Age at menarche for women who underwent menopause 2 after age 55 vs. < 45: [ER+/PR+] 1.52 (1.17-1.98) 7 Age at first birth > 30 years vs. < 21 years: [ER+/PR+] w 1.52 (1.22-1.90); [ER+/PR-] 1.68 (1.01-2.80); [ER-/PR-] o 1.32 (0.87-1.99) m Parity > 4 births vs. 1 birth: [ER+/PR+] 0.73 (0.60- e 0.88); [ER+/PR-] 0.98 (0.62-1.54); [ER-/PR-] 1.07 (0.76- n 1.51) i Hormone replacement therapy use among n postmenopausal women, current use of estrogen/progestin t therapy: [ER+/PR+] 2.28 (1.97-2.64); [ER-/PR-] 1.11 h (0.82-1.51) e M u lt i e t h n i c C o h o r t S t u d y a g e d 4 5 - 7 5 ; 2 5 4 3 b r e a s t c a n c e r c a s e s Li, 2008 Population based case-control W ER+ or PR+ Premenopausal white women [27] o grouped together: Age at menarche > 16years vs. <12years: [HR+] 0.8 m HR+; ER-/PR- (0.6-1.2); [ER-/PR-] 1.0 (0.6-1.6) e Age at first term birth > 30 years vs. <19 years: [HR+] n 1.4 (1.0-2.0); [ER-/PR-] 1.0 (0.6-1.6) ’ Nulliparous vs. parous: [HR+] 2.0 (1.4-2.8); [ER-/PR-] s 1.0 (0.6-1.5) C Interval between age at menarche and age at first full A term birth, > 16 years vs. < 5 years: [HR+] 1.7 (1.1-2.8); R [ER-/PR-] 1.2(0.6-2.1) E Interval between age at menarche and age at first full term birth, nulliparous vs. <5 years: [HR+] 2.5 (1.5-4.1); S [ER-/PR-] 1.1 (0.6-1.9) t u Premenopausal black women d Age at menarche > 16 years vs. <12 years: [HR+] 0.8 y (0.5-1.3); [ER-/PR-] 1.1 (0.6-1.8) , Age at first term birth > 30 years vs. <19 years: [HR+] 4 1.0 (0.6-1.6); [ER-/PR-] 0.7 (0.4-1.2) 0 Nulliparous vs. parous: [HR+] 1.2 (0.8-1.7); [ER-/PR-] 1 0.8 (0.5-1.2) 3 Interval between age at menarche and age at first full w term birth, > 16 years vs. < 5 years: [HR+] 0.9 (0.6-1.4); o [ER-/PR-] 0.8(0.5-1.4) m Interval between age at menarche and age at first full e term birth, nulliparous vs. <5 years: [HR+] 1.0 (0.7-1.6); n [ER-/PR-] 0.9 (0.5-1.5) w it Postmenopausal women h Age at menarche > 15 years vs. <12 years: [HR+] 0.9 b (0.7-1.1); [ER-/PR-] 0.9 (0.6-1.4) r Age at first term birth > 30 years vs. <19 years: [HR+] e 1.4 (1.0-1.9); [ER-/PR-] 1.2 (0.8-2.0) a s Interval between age at menarche and age at first full t term birth, > 16 years vs. < 5 years: [HR+] 1.7 (1.2-2.3); c [ER-/PR-] 1.1(0.7-1.7) a Interval between age at menarche and age at first full n term birth, nulliparous vs. <5 y: [HR+] 2.0 (1.5-2.7); c [ER-/PR-] 0.5 (0.3-0.8) e r a g e d 2 5 - 6 4 a n d 4 0 6 9 c o n t r o l s Millikan, 2008 Case-case and population based case- 1 Luminal A; luminal Case-control comparing Luminal A and Basal vs. controls [38] control 8 B HER2+; basal; Age at menarche < 13 years vs. > 13 years: [Luminal A] 0 unclassified; TNBC 1.1 (0.9-1.3); [Basal] 1.4 (1.1-1.9) 3 (included basal and Parity >3 vs. nulliparous: [Luminal A] 0.7 (0.5-0.9); c unclassified) [Basal] 1.9 (1.1-3.3) a Age at first full term pregnancy < 26 vs. nulliparous: s [Luminal A] 0.7 (0.5-0.9); [Basal] 1.9 (1.2-3.2) e Breastfeeding ever vs. never: [Luminal A] 0.9 (0.7-1.0); s [Basal] 0.7 (0.5-1.0) a Number of children breastfed >2 vs. 0: [Luminal A] 1.0 n (0.8-1.2); [Basal] 0.6 (0.4-0.9) d Average breastfeeding per child > 4 months vs. never: 1 [Luminal A] 0.9 (0.8-1.1); [Basal] 0.6 (0.4-0.9) 5 Parity > 3 births and ever breastfed vs. nulliparous: 6 [Luminal A]: 0.7 (0.5-0.9); [Basal] 1.3 (0.7-2.3) 4 Parity >3 births and never breastfed vs. nulliparous: m [Luminal A] 0.7 (0.5-0.9); [Basal] 1.9 (1.0-2.8) a Parity >3 births and age at first birth < 26 years: t [Luminal A] 0.7 (0.5-0.9); [Basal] 1.6 (1-2.8) c h e d c o n t r o l s ; a g e d 2 0 - 7 4 y e a r s Phipps, 2008 Pooled analysis of two population 5 Luminal (A and B Age at menarche <13 years vs. >13 years: [Luminal] 1.0 [40] based case-control studies 5 grouped together); (0.9-1.2); [HER2+] 2.7 (1.4-5.5); [TBNC] 1.1 (0.7-1.7) - HER2+; TNBC Breastfeeding: >6 months vs. never: [Luminal] 0.8 (0.6- 7 1.0); [TNBC] 0.5 (0.3-0.9); [HER2+] 1.5 (0.7-3.3) 9 Age at menopause: >55 years vs. <45 years: [Luminal] y 1.6 (1.2-2.2); [HER2+] 2.9 (0.8-10.7); [TNBC] 1.2 (0.5- e 3.0) a r o l d w o m e n i d e n ti f i e d t h r o u g h C a n c e r S u r v e il l a n c e S y s t e m o f W e s t e r n W a s h i n g t o n S t a t e : 1 1 4 0 c a s e s a n d 1 4 7 6 c o n t r o l s Lord, 2008 Population based case-control 1 ER+/PR+; ER-/PR- Parity >1 vs. nulliparous when age at first < 25 years: [39] , [ER+/PR+] 0.59 (0.42-0.82); [ER-/PR] 1.62 (0.84-3.11) 4 Parity > 1 vs. nulliparous when age at first >25 years: 5 [ER+/PR+] 1.05 (0.73-1.51); [ER-/PR-] 2.07 (1.03-4.16) 7 Parity > 4 births vs. 1 birth and age at first birth < 25 w years: [ER+/PR+] 0.51 (0.33-0.80); [ER-/PR-] 1.10 (0.55- o 2.19) m Parity > 4 births vs. 1 birth and age at first birth > 25 e years: [ER+/PR+] 1.63 (0.73-3.63); [ER-/PR-] 2.76 (0.94- n 8.07) w Parity > 4 births and ever vs. never breastfed: it [ER+/PR+] 0.58 (0.34-0.99); [ER-/PR-] 0.89 (0.41-1.95) h Age at first live birth < 25 years, ever vs. never b breastfed: r [ER+/PR+] 0.91 (0.71-1.15); [ER-/PR-] 0.82 (0.6-1.14) e Age at first live birth > 30 years, ever vs. never a breastfed: [ER+/PR+] 0.89 (0.44-2.92); [ER-/PR-] 1.10 s (0.41-2.92) t c a n c e r a g e d 5 5 - 6 4 , a n d 1 , 4 5 5 c o n t r o l s w h o p a r ti c i p a t e d i n t h e W o m e n ’ s C A R E
s t u d y Yang, 2007 Case-control 8 Luminal A; Age at menarche per 2 year increase: [Luminal A] 0.90 [28] 0 Luminal B; (0.95-1.08); [Luminal B] 0.98 (0.75-1.28); [HER2+] 1.14 4 HER2+; basal; (0.86-1.50); [Basal] 0.78 (0.68-0.89); [unclassified] 0.92 b unclassified (0.72-1.18) r Parity > 2 births: [Luminal A] 0.42 (0.21-0.84); e [Luminal B] 0.56 (0.07-4.56); [HER2+] 1.15 (0.17-7.63); a [Basal] 1.80 (0.37-8.85); [unclassified] 0.71 (0.09-5.71) s Age at first full term birth per 5 year increase: [Luminal t A] 1.08 (0.95-1.23); [Luminal B] 1.04 (0.70-1.55); c [HER2+] 0.87 (0.60-1.05); [Basal] 0.95 (0.71-1.27); a [unclassified] 1.06 (0.71-1.58) n Age at menopause per 5 year increase: [Luminal A] 1.13 c (1.01-1.28); [Luminal B] 1.10 (0.78-1.57); [HER2+] 1.09 e (0.81-1.46); [Basal] 1.02 (0.82-1.28); [unclassified] 1.46 r (0.99-2.15) p a ti e n t s a n d 2 5 0 2 p o p u l a ti o n m a t c h e d c o n t r o l s p a r ti c i p a ti n g i n a P o li s h B r e a s t C a n c e r S t u d y ; A g e d 2 0 - 7 4 Ma, 2006 Meta-analysis of 2 cohort studies, 6 C ER+/PR+; ER-/PR- Parity in case-control studies highest vs. nulliparous [29] population based case-control studies, o [ER+/PR+] 0.67 (0.55-0.82); [ER-/PR-] 0.98 (0.92-1.04) and 2 hospital based case-control h Parity in cohort studies > 4 vs. nulliparous: [ER+PR+] studies o 0.74 (0.61-0.89); [ER-PR-] 1.17 (0.80-1.7) r Parity in cohort studies per birth: [ER+/PR+] 0.93 (0.8- t 1.08); [ER-/PR-]: 1.11 (0.95-1.29) s Breastfeeding ever vs. never: [ER+/PR+] 0.95 (0.87- t 1.05); [ER-/PR-] 0.91 (0.83-1.08) u Age at menarche oldest vs. youngest category: d [ER+/PR+] 0.72 (0.64-0.80); [ER-/PR-] 0.84 (0.75-0.94) i Age at first birth, summary for both case-control and e cohort studies, oldest age vs. youngest age categorical s value: [ER+/PR+] 1.27 (1.05-1.60); [ER-/PR-] 1.01 (0.85- i 1.20) n c l u d e d 2 1 9 2 w o m e n w it h b r e a s t c a n c e r ; c a s e - c o n t r o l s t u d i e s i n c l u d e d 9 7 3 9 w o m e n w it h b r e a s t c a n c e r a n d 3 3 , 6 6 5 c o n t r o l s ; A g e r a n g e 2 0 - 8 0
Case-Case Studies Author, year Population Tumor Subtypes Results Martinez, 2013 1041 women of Mexican descent Luminal A; HER2+; Luminal A as comparison [48] from Ella Binational Breast Cancer TNBC study living in Mexico and the US, Age at menarche per 5 years: [HER2+] 0.93 (0.58-1.50); age >18 years of age [TNBC] 1.64 (0.95-2.82) Parity > 3 children vs. 1-2 children: [HER2+] 0.87 (0.61-1.24); [TNBC] 1.68 (1.10–2.55) Age at first full-term pregnancy > 25 years vs. < 21 years : [HER2+] 0.99 (0.68-1.46); [TNBC] 0.61 (0.39-0.95) Time since last full-term pregnancy <10 years vs. >10 years: [HER2+] 1.83 (0.96-3.48); [TNBC] 0.76 (0.38–1.52) Lifetime duration of breastfeeding >12 months vs. never: [HER2] 0.97 (0.63-1.50); [TNBC] 2.14 (1.24–3.68) Breastfeeding duration per birth > 5 months vs. never: [HER2] 1.03 (0.67-1.59); [TNBC] 2.07 (1.20-3.58) Time from menarche to first pregnancy per 10 years: [HER2+] 0.99 (.85-1.14); [TNBC] 0.78 (0.65-0.93) Duration of menstruation accounting for pregnancy per 5 years: [HER2+] 1.09 (0.95-1.24); [TNBC] 0.79 (0.69- 0.91) Duration of menstruation accounting for pregnancy and breastfeeding, per 5 years: [HER2+] 1.04( 0.92-1.18); [TNBC] 0.82 (0.72-0.93) Age at menopause per 5 years: [HER2+] 1.07 (0.90- 1.27); [TNBC] 0.8 (0.67-1.01) Hormone replacement therapy ever vs. never [HER2+]: 1.09 (0.69-1.72); [TNBC] 0.99 (0.56-1.77) HCT ever vs. never: [HER2+] 0.91 (0.66-1.26); [TNBC] 0.70 (0.49-1.01) Turkoz, 2012 1884 women with invasive breast Luminal A; Luminal B; Each subtype compared to all other subtypes combined [49] cancer in Turkey; HER2+; TNBC Age at menarche < 12 years vs. > 12 years: [Luminal A vs. others] 1.09 (0.88-1.36); [Luminal B vs. others] 0.97 (0.71-1.34); [HER2+ vs. others]: 60.85 (0.57-1.25); [TNBC vs. others] 0.99 (0.72-1.36) Age at first pregnancy: ≥30 years vs. <30 years: [Luminal A vs. others] 1.14(1.08-1.30); [Luminal B vs. others]: 1.56 (1.08-2.3); [HER2+] 0.96(0.55-1.69); [TNBC] 0.71(0.41-1.22) Nulliparous vs. age at first full term pregnancy < 30 years: [Luminal A vs. others]: 1.48 (1.03-2.13); [Luminal B vs. others] 1.59(1.01-2.46); [HER2+ vs. others] 0.67 (0.39- 1.15); [TNBC vs. others] 0.72 (0.46-1.12) Parity ≥2 vs. nulliparous: [Luminal A vs. others] 0.59 (0.38-0.71); [Luminal B vs. others] 0.66 (0.45-0.97); [HER2+ vs. others] 1.46 (0.85-2.50); [TNBC vs. others] 1.37 (0.87-2.15) Breastfeeding Yes vs. no: [Luminal A vs. others] 0.71 (0.56-0.98); [Luminal B vs. others] 0.69 (0.48-0.96); [HER2+ vs. others] 1.34 (0.81-2.21); [TNBC vs. others] 1.26 (0.83-1.92) Hormone replacement therapy use ≥5 years vs. never: [Luminal A vs. others] 1.73 (0.92-3.26); [Luminal B vs. others] 1.47 (1.14-2.55); [HER2+ vs. others] 2.02 (0.92- 4.41); [TNBC vs. others] 0.3 (0.07-1.25) Oral contraceptive use >5 years vs. never: [Luminal A vs. others] 1.33 (0.79-2.33); [Luminal B vs. others]: 0.83 (0.37-1.84); [HER2+ vs. others] 0.66 (0.23-1.84); [TNBC vs. others] 1.41 (0.72-2.74) Cruz, 2013 627 premenopausal breast cancer HR+; HER2-; HER2+; Interval between last birth and diagnosis <10 years vs. >10 [51] cases: 414 Mexican-American TNBC years: [HER2+ vs. ER+/PR+/ HER2-] 1.68 (1.12-2.52) women from the U.S. and women living in Mexico; 213 premenopausal breast cancer cases from a population- based study in Spain Pilewskie, 2012 289 women with breast cancer 25-54 HR -; HER2-; TNBC Time from last pregnancy >5-10 years vs. nulliparous: [60] years of age; 175 parous cases [HR-]: 2.9 (1.3-6.9); [HER2 negative] 0.6 (0.2-1.5); compared with 114 nulliparous cases [TNBC] 1.2(0.4-3.6) Diagnosed when pregnant vs. nulliparous: [TNBC] 9.6 (1.9-49.3); [HR-] 5.8 (1.2-29.0); [HER2-] 0.6 (0.2-1.8) Diagnosed within 6 months of lactating vs nulliparous: [HR-] 6.6 (1.5-28.6); [TNBC] 2.7 (0.6-13.1); [HER2-] 0.5(0.1-2.4) Diagnosed during or within 6 months of pregnancy, or while lactating vs. nulliparous: [TNBC] 4.8 (1.5-15.5); [HR-] 6.0 (1.9-18.9); [HER 2-] 0.5 (0.1-1.7) Diagnosed with breast cancer 0-2 years from pregnancy but excluding lactating at diagnosis vs. nulliparous: [TNBC] 2.9 (1.1-8.2); [HR-] 2.4 (0.9-6.4); [HER2-] 0.6 (0.2-1.8) Redondo, 2012 510 breast cancer patients in Spain, Luminal A; Luminal B; TNBC compared to luminal A [50] aged HER2+; TNBC Age at first full-term pregnancy >28 years vs. <22 years: 28-84 [TNBC] 1.38 (0.48-3.39) Age at menarche >15 years vs. <13 years: [TNBC] 0.65 (0.21-1.68) Age at menopause >50 years vs. < 50 years: [TNBC] 1.28 (0.63-2.61) Lifetime duration of Breastfeeding: ≥7 vs. 0 months: [TNBC] 0.25 (0.08-0.68) Parity any vs. nulliparous: [TNBC] 1.81 (0.67-6.32) Longer Breastfeeding (>7 months) and lower (parity < 2 births) combo: [TNBC] 0.09 (0.005-0.54) Longer Breastfeeding (>7 months) and greater parity 3+ births: [TNBC] 0.37 (0.08-1.65) Yang, 2011 Pooled case-case of 12 population ER+; [PR+; ER+/PR+; Age at menarche < 12 years vs. > 15 years: [ER- vs, [33] based studies and case-control ER+/HER2+; HER2+ ER+] 0.92 (0.85-1.01); [PR- vs. PR+] 0.88 (0.81-0.95); comparison PR+/HER2+; [ER+/PR- vs. ER+/PR+] 0.83 (0.74-0.93); [ER-/PR- vs. 35,568 breast cancer patient from 34 ER+/PR-; ER-/PR+; ER+/PR-]: 0.90 (0.81-0.99); [ER+ or PR+/HER2+ vs. ER+ studies, age range 18-100, ER-/ PR-; TNBC or PR+/HER2-] 1.01 (0.84-1.22) participating in Breast Cancer Parity Nulliparous vs. parous: [ER- vs. ER+] 0.82 (0.76- Association Consortium 0.89); [PR- vs. PR+] 0.91 (0.84-0.98); [ER-/PR- vs, ER+/PR+ ] 0.80 (0.73-0.88); [TNBC vs. [ER+ or PR+ /HER2-] 0.69 (0.59-0.81) Age at first full birth: <20y vs. >35y: [ER- vs. ER+]: 0.90 (0.87-0.93); [ER+/PR- vs. ER+/PR+]: 1.05 (1.01- 1.10); [ER-/PR- vs. ER+/PR+]: 0.91 (0.88-0.95); [TNBC vs. ER+ or PR+/HER2-]: 0.89 (0.83-0.95) Lara-Medina, 2074 Hispanic women with breast non TNBC; TNBC Diagnosed while postmenopausal: [TNBC vs. non- 2011 cancer, aged 19-96 treated at National TNBC] 0.72 (0.58-0.88) [46] Cancer Institute of Mexico Increased parity >2 births vs. <2: [TNBC vs. non- TNBC] 1.32 (1.03-1.69) Hormone contraceptive use: [TNBC vs. non-TNBC] 1.20 (1.003-1.54) Shinde, 2010 2473 hospital-based breast cancer ER+/HER2-; non- Breastfeeding duration per child >2 months vs. never: [61] cases TNBC; TNBC [TNBC vs. non-TNBC] 0.54 (0.40-0.77); [TNBC vs. Age categorized by three categorical ER+/HER2-] 0.56 (0.41-0.76)) variables: < 40, 40-59, >60 years Parity >3 vs. nulliparous: [TNBC vs. non-TNBC] 2.76 (1.86-4.08); [TNBC vs. ER+/HER2-] 2.97 (1.98-4.46) Trivers, 2009 Case-case and case-control study ER+ or PR+/HER2-; ER/PR+/HER2- as comparison [25] Women diagnosed with breast cancer ER+or PR+/HER2+; Age at menarche <12 years vs. 12+ years: [TNBC] 1.55 aged 20-54 and 913 controls HER2+; TNBC (1.08-2.23); [HER2+] 1.68 (0.92-3.08); [ER/PR+/HER2+] 0.8 (0.42-1.52) Age at first birth <18 years vs. nulliparous: [TNBC] 2.83 (1.30-6.14); [HER2+] 9.49 (2.64-34.11); [ER/PR+/HER2+] 1.3 (0.32-5.29) Parity >4 births vs. nulliparous: [TNBC] 2.4 (1.24-4.64); [HER2+] 2.89 (0.76-11.03); [ER/PR+/HER2+] 1.25 (0.45- 3.48) Recency of birth <5 years vs. nulliparous: [TNBC] 2.25 (1.16-4.36); [HER2+] 5.05 (1.43-17.86); [ER/PR+HER2+] 1.09 (0.38- 3.11) Breastfeeding 12+ months vs. never: [TNBC] 0.83 (0.48-1.43); [HER2+] 0.50 (0.17-1.51); [ER/PR+HER2+] . 019 (0.04-0.85) Kwan, 2009 2544 women with breast cancer aged Luminal A; Luminal B; Oral contraceptive use ever vs. never: [Luminal B vs. [62] 18-70 years HER2+; TNBC Luminal A] 0.73 (0.55-0.96) Parity > 3 vs. nulliparous [Luminal B vs. Luminal A] 1.03 (0.7-1.5) Age at first pregnancy: >26 vs nulliparous: [Luminal B vs. Luminal A] 1.04 (0.72-1.52); [HER2+ vs. Luminal A] 2.02 (1.07-3.80); [TNBC vs. Luminal A] 0.93 (0.63-1.38) Lifetime duration of Breastfeeding > 4 months vs. never: [Luminal B vs. Luminal A] 0.86 (0.65-1.14); [HER2+ v Luminal A] 0.86 (0.54-1.38); [TNBC vs. Luminal A] 0.78 (0.59-1.03) Parity among never breastfed: >3 births vs. nulliparous: [Luminal B vs. Luminal A] 1.01 (0.58-1.76); [TNBC vs. Luminal A] 1.68 (1.00-2.81); [HER2+ vs. Luminal A] 3.03 (1.27-7.23) Parity among > 4 months breastfed, >3 births vs. nulliparous: [Luminal B vs. Luminal A] 0.84 (0.54-1.32); [TNBC vs. Luminal A] 0.99 (0.63-1.55); [HER 2+ vs. Luminal A] 1.23 (0.57-2.66) Millikan, 2008 Case-case and population-based case Luminal A; luminal B Luminal A as comparison [38] control HER2+; basal; Age at menarche <13 years vs. >13 years: [HER2+] 1.0 1803 cases and 1564 matched unclassified; TNBC (0.7-1.5); [Basal] 1.3 (0.9-1.7); [Luminal B] 0.9 (0.7-1.4); controls; (included basal and [unclassified] 1.5 (1.0-2.1) aged 20-74 years unclassified) Parity >3 vs. nulliparous: [Basal] 1.7 (1.0-2.9); [HER2+] 1.0 (0.5-1.7); [Luminal B] 1.3 (0.7-2.3); [unclassified] 1.7 (1.0-3.0) Breastfeeding >4 months vs. never: [Basal] 0.7 (0.5- 1.1); [HER2+] 0.9 (0.6-1.5); [Luminal B] 1.0 (0.6-1.5); [unclassified] 1.1 (0.5-1.2) Oral contraceptive use ever vs. never: [Basal] 0.9 (0.6- 1.3); [HER2+] 1.1 (0.6-1.7); [Luminal B] 0.9 (0.6-1.5); [unclassified] 0.8 (0.5-1.3) Hormone replacement therapy use ever vs. never: [Basal] 0.8 (0.5-1.3); [HER2+] 1.2 (0.7-2.1); [Luminal B] 1.6 (0.9-2.8); [unclassified] 1.4 (0.8-2.4)
ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor; luminal A, ER+ and/or PR+, HER2-; luminal B, ER+ and/or PR+/ HER2+; HER2+, ER-/PR- and HER2+; TNBC, triple-negative breast cancer *Results reflect estimates of Relative Risk (95% confidence interval).