Table 3.

Breast cancer risk factor associations by histologic subtype within relevant strata of age at start of follow-up and HT use

TOTALDuctal casesLobular casesMixed cases
n (%)*Person-years (%)n (%)*HR (95% CI)n (%)*HR (95% CI)n (%)*HR (95% CI)
Family history of breast cancer (first degree female relatives)
Overall
    No2,709,038 (86)5,136,569 (88)10,830 (81)1.0 (Reference)1,150 (80)1.0 (Reference)1,170 (81)1.0 (Reference)
    Yes434,781 (14)729,282 (12)2,539 (19)1.55 (1.48-1.62)294 (20)1.63 (1.43-1.86)279 (19)1.52 (1.33-1.74)
    Missing187,925456,7091,449158152
Age 40-49 y
    No1,058,329 (88)2,039,322 (89)2,744 (82)1.0 (Reference)238 (78)1.0 (Reference)302 (81)1.0 (Reference)
    Yes150,074 (12)244,264 (11)621 (18)1.80 (1.65-1.97)66 (22)2.06 (1.56-2.72)71 (19)1.78 (1.36-2.32)
    Missing67,084163,0843192538
Age 50-69 y
    No1,322,073 (86)2,389,958 (87)5,841 (82)1.0 (Reference)613 (80)1.0 (Reference)618 (80)1.0 (Reference)
    Yes218,679 (14)355,422 (13)1,323 (18)1.50 (1.41-1.59)153 (20)1.61 (1.34-1.93)151 (20)1.53 (1.28-1.84)
    Missing90,005206,9917877582
Age 70-84
    No328,636 (83)707,289 (85)2,245 (79)1.0 (Reference)299 (80)1.0 (Reference)250 (81)1.0 (Reference)
    Yes66,028 (17)129,596 (15)595 (21)1.42 (1.29-1.56)75 (20)1.38 (1.06-1.79)57 (19)1.23 (0.91-1.66)
    Missing30,83686,6343435832
Breast density (BI-RADS) §
Overall
    1205,527 (9)396,096 (8)511 (5)0.59 (0.52-0.67)43 (4)0.48 (0.31-0.74)40 (4)0.41 (0.26-0.66)
    21,073,985 (45)2,114,668 (45)4,536 (43)1.0 (Reference)467 (41)1.0 (Reference)442 (39)1.0 (Reference)
    3921,472 (39)1,808,306 (39)4,625 (44)1.35 (1.27-1.44)534 (47)1.56 (1.29-1.89)551 (49)1.56 (1.30-1.89)
    4173,158 (7)341,732 (7)837 (8)1.62 (1.45-1.81)95 (8)1.62 (1.15-2.26)94 (8)1.76 (1.27-2.42)
    Missing957,6021,673,6174,309463474
Age 40-64 y
    1140,467 (8)260,805 (7)235 (4)0.50 (0.42-0.61)18 (3)0.47 (0.24-0.89)20 (3)0.41 (0.22-0.77)
    2795,852 (43)1,537,220 (42)2,667 (40)1.0 (Reference)239 (34)1.0 (Reference)275 (36)1.0 (Reference)
    3767,001 (41)1,492,912 (41)3,363 (50)1.41 (1.31-1.53)367 (52)1.83 (1.44-2.33)384 (50)1.53 (1.22-1.92)
    4157,284 (8)308,960 (9)731 (11)1.79 (1.58-2.03)79 (11)1.80 (1.22-2.66)82 (11)1.83 (1.28-2.61)
    Missing756,1611,295,5612,934266310
Age 65-84 y
    165,060 (13)135,291 (13)276 (8)0.69 (0.57-0.83)25 (6)0.47 (0.26-0.85)20 (5)0.41 (0.20-0.86)
    2278,133 (54)577,448 (54)1,869 (53)1.0 (Reference)228 (52)1.0 (Reference)167 (46)1.0 (Reference)
    3154,471 (30)315,393 (30)1,262 (36)1.24 (1.10-1.39)167 (38)1.19 (0.87-1.64)167 (46)1.65 (1.18-2.29)
    415,874 (3)32,771 (3)106 (3)0.97 (0.71-1.33)16 (4)1.35 (0.65-2.80)12 (3)1.25 (0.54-2.89)
    Missing201,441378,0561,375197164
BMI at start of follow-up (kg/m2)
Age 40-49 y
    <25333,751 (53)562,453 (52)835 (55)1.0 (Reference)88 (60)1.0 (Reference)114 (59)1.0 (Reference)
    25-29166,357 (26)290,447 (27)366 (24)0.86 (0.76-0.98)30 (20)0.69 (0.45-1.06)44 (23)0.62 (0.42-0.92)
    30+130,414 (21)235,615 (22)309 (20)0.85 (0.74-0.98)29 (20)0.77 (0.50-1.21)35 (18)0.78 (0.53-1.14)
    Missing480,479899,3921,448107144
Age 50-84 y
    Not HT user at start
        <25212,402 (43)355,965 (42)942 (38)1.0 (Reference)104 (44)1.0 (Reference)102 (38)1.0 (Reference)
        25-29160,914 (32)274,512 (32)811 (33)1.08 (0.98-1.20)76 (32)0.96 (0.70-1.30)89 (33)1.12 (0.84-1.50)
        30+125,967 (25)221,986 (26)716 (29)1.22 (1.11-1.35)55 (23)0.94 (0.67-1.33)78 (29)1.21 (0.89-1.64)
        Missing429,211790,4142,393252228
    HT user at start
        <25157,442 (48)246,415 (47)787 (49)1.0 (Reference)105 (50)1.0 (Reference)105 (48)1.0 (Reference)
        25-29104,714 (32)169,000 (32)511 (32)0.94 (0.84-1.06)60 (29)0.86 (0.62-1.19)71 (33)0.97 (0.71-1.31)
        30+65,538 (20)111,546 (21)320 (20)0.94 (0.83-1.08)45 (21)0.97 (0.67-1.39)41 (19)0.91 (0.63-1.32)
        Missing243,357394,2581,291153128
Parity
    Nulliparous395,541 (18)692,804 (18)1,744 (19)1.0 (Reference)172 (16)1.0 (Reference)218 (20)1.0 (Reference)
    Parous1,802,553 (82)3,214,852 (82)7,250 (81)0.80 (0.76-0.84)878 (84)0.96 (0.81-1.15)867 (80)0.79 (0.68-0.93)
    Missing1,133,6502,431,0965,824552516
Age at first birth (parous women)
    <301,461,227 (83)2,627,722 (83)5,894 (83)1.0 (Reference)686 (79)1.0 (Reference)660 (78)1.0 (Reference)
    ≥30308,778 (17)526,043 (17)1,197 (17)1.24 (1.16-1.33)179 (21)1.72 (1.44-2.06)183 (22)1.74 (1.45-2.07)
    Missing32,54861,0871591324
Current HT use at start of follow-up
    No1,797,148 (72)3,201,220 (74)7,183 (69)1.0 (Reference)683 (64)1.0 (Reference)767 (67)1.0 (Reference)
    Yes
        No known hysterectomy455,417 (18)744,216 (17)2,223 (21)1.17 (1.11-1.23)265 (25)1.46 (1.25-1.70)287 (25)1.29 (1.11-1.50)
        Reported hysterectomy231,739 (9)383,729 (9)974 (9)0.98 (0.91-1.05)121 (11)1.26 (1.03-1.54)84 (7)0.74 (0.58-0.93)
    Missing383,762664,6221,732205191
  • *Multiple observations per woman possible in the total population but only one case observation per woman.

  • Adjusted for age at start of follow-up (5-y categories), white race, family history of breast cancer, and history of prior breast procedure (that is, surgery, aspirate, or nonaspirate biopsy).

  • Additionally adjusted for BMI and current HT use at the time of the most recent mammogram.

  • §BI-RADS scale: 1, almost entirely fat; 2, scattered fibroglandular densities; 3, heterogeneously dense; 4, extremely dense.

  • Time axis truncated at 5 y (maximum) after the first eligible mammogram during the study period due to violations of proportional hazards assumptions at later time points.