Background
Methods
Study population and risk factor data
Pathology, immunohistochemical data, and molecular subtypes
Statistical analysis
Results
Descriptive analysis of sociodemographic and reproductive characteristics
Hospitals | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Overall (n=838) | AKU (n=350, 42%) | Kijabe (n=105, 13%) | Nyeri (n=110, 13%) | St Mary’s (n=122, 15%) | Others (n=151, 18%) | ||||||||
N | % | N | % | N | % | N | % | N | % | N | % | P* | |
Demographic | |||||||||||||
Age at diagnosis/year | |||||||||||||
20–29 | 32 | 3.8 | 17 | 4.9 | 2 | 1.9 | 2 | 1.9 | 5 | 4.1 | 6 | 4.0 | 0.11 |
30–39 | 177 | 21.2 | 64 | 18.3 | 23 | 21.9 | 22 | 20.4 | 34 | 28.1 | 34 | 22.5 | |
40–49 | 242 | 29.0 | 100 | 28.7 | 37 | 35.2 | 34 | 31.5 | 35 | 28.9 | 36 | 23.8 | |
50–59 | 211 | 25.3 | 105 | 30.1 | 26 | 24.8 | 23 | 21.3 | 19 | 15.7 | 38 | 25.2 | |
≥ 60 | 172 | 20.6 | 63 | 18.1 | 17 | 16.2 | 27 | 25.0 | 28 | 23.1 | 37 | 24.5 | |
Mean (SD) | 49.2 (12.8) | 49.0 (11.2) | 48.4 (11.3) | 50.5 (13.5) | 48.7 (15.1) | 49.7 (12.9) | |||||||
Median (IQR) | 48 (39, 57) | 49 (40, 56) | 47 (41, 57) | 49 (41, 60) | 45 (37, 58) | 49 (39, 59) | |||||||
Missing | 4 | 1 | 0 | 2 | 1 | 0 | |||||||
BMI/ kg/m2 | |||||||||||||
Normal (< 25.0) | 210 | 31.3 | 67 | 21.3 | 35 | 40.2 | 25 | 39.7 | 36 | 40.4 | 47 | 40.2 | < 0.0001 |
Overweight (25.0–29.9) | 264 | 39.3 | 126 | 40.0 | 33 | 37.9 | 28 | 44.4 | 37 | 41.6 | 40 | 34.2 | |
Obese (≥ 30.0) | 197 | 29.4 | 122 | 38.7 | 19 | 21.8 | 10 | 15.9 | 16 | 18.0 | 30 | 25.6 | |
Missing | 167 | 35 | 18 | 47 | 33 | 34 | |||||||
Family history of breast cancer in first-degree female relatives | |||||||||||||
No | 773 | 92.2 | 314 | 89.7 | 100 | 95.2 | 99 | 90.0 | 119 | 97.5 | 141 | 93.4 | 0.036 |
Yes | 65 | 7.8 | 36 | 10.3 | 5 | 4.8 | 11 | 10.0 | 3 | 2.5 | 10 | 6.6 | |
Occupation | |||||||||||||
Farmer | 253 | 30.3 | 47 | 13.4 | 43 | 41.0 | 82 | 74.5 | 39 | 32.5 | 42 | 27.8 | < 0.0001 |
Employed worker | 195 | 23.3 | 138 | 39.4 | 16 | 15.2 | 5 | 4.5 | 10 | 8.3 | 26 | 17.2 | |
Trader | 155 | 18.5 | 66 | 18.9 | 24 | 22.9 | 2 | 1.8 | 35 | 29.2 | 28 | 18.5 | |
Housewife | 156 | 18.7 | 68 | 19.4 | 19 | 18.1 | 8 | 7.3 | 27 | 22.5 | 34 | 22.5 | |
Casual worker | 32 | 3.8 | 11 | 3.1 | 3 | 2.9 | 4 | 3.6 | 8 | 6.7 | 6 | 4.0 | |
Other | 45 | 5.4 | 20 | 5.7 | 0 | 0.0 | 9 | 8.2 | 1 | 0.8 | 15 | 9.9 | |
Missing | 2 | 0 | 0 | 0 | 2 | 0 | |||||||
Highest education level | |||||||||||||
None | 257 | 30.7 | 54 | 15.4 | 41 | 39.0 | 44 | 40.0 | 57 | 46.7 | 61 | 40.4 | < 0.0001 |
Primary | 163 | 19.5 | 40 | 11.4 | 22 | 21.0 | 29 | 26.4 | 36 | 29.5 | 36 | 23.8 | |
Secondary | 209 | 24.9 | 99 | 28.3 | 24 | 22.9 | 31 | 28.2 | 21 | 17.2 | 34 | 22.5 | |
Tertiary | 209 | 24.9 | 157 | 44.9 | 18 | 17.1 | 6 | 5.5 | 8 | 6.6 | 20 | 13.2 | |
Place of residence | |||||||||||||
Rural | 511 | 61.0 | 173 | 49.4 | 79 | 75.2 | 99 | 90.0 | 65 | 53.3 | 95 | 62.9 | < 0.0001 |
Urban | 327 | 39.0 | 177 | 50.6 | 26 | 24.8 | 11 | 10.0 | 57 | 46.7 | 56 | 37.1 | |
Exposure to smoking† | |||||||||||||
Never exposed | 477 | 56.9 | 248 | 70.9 | 63 | 60.0 | 39 | 35.5 | 63 | 51.6 | 64 | 42.4 | < 0.0001 |
Exposed | 361 | 43.1 | 102 | 29.1 | 42 | 40.0 | 71 | 64.5 | 59 | 48.4 | 87 | 57.6 | |
Alcohol use | |||||||||||||
No | 760 | 90.7 | 304 | 86.9 | 98 | 93.3 | 109 | 99.1 | 115 | 94.3 | 134 | 88.7 | 0.0009 |
Yes | 78 | 9.3 | 46 | 13.1 | 7 | 6.7 | 1 | 0.9 | 7 | 5.7 | 17 | 11.3 | |
Ethnicity | |||||||||||||
Bantu | 656 | 78.3 | 266 | 76.0 | 92 | 87.6 | 109 | 99.1 | 106 | 86.9 | 83 | 55.0 | < 0.0001 |
Nilote | 141 | 16.8 | 65 | 18.6 | 5 | 4.8 | 0 | 0.0 | 10 | 8.2 | 61 | 40.4 | |
Cushite/Mixed | 41 | 4.9 | 19 | 5.4 | 8 | 7.6 | 1 | 0.9 | 6 | 4.9 | 7 | 4.6 | |
Reproductive | |||||||||||||
Age at menarche/year | |||||||||||||
9–12 | 68 | 8.5 | 30 | 8.6 | 10 | 11.1 | 7 | 6.9 | 7 | 5.8 | 14 | 10.0 | 0.40 |
13–14 | 340 | 42.4 | 150 | 42.9 | 31 | 34.4 | 39 | 38.2 | 61 | 50.8 | 59 | 42.1 | |
15–20 | 394 | 49.1 | 170 | 48.6 | 49 | 54.4 | 56 | 54.9 | 52 | 43.3 | 67 | 47.9 | |
Missing | 36 | 0 | 15 | 8 | 2 | 11 | |||||||
Age at first pregnancy/year | |||||||||||||
Nulliparous‡ | 37 | 4.5 | 23 | 6.6 | 4 | 3.9 | 2 | 1.9 | 2 | 1.8 | 6 | 4.0 | < 0.0001 |
< 20 | 216 | 26.3 | 62 | 17.7 | 29 | 28.4 | 34 | 31.8 | 38 | 34.2 | 53 | 35.3 | |
20–24 | 361 | 44.0 | 142 | 40.6 | 41 | 40.2 | 54 | 50.5 | 52 | 46.8 | 72 | 48.0 | |
25–29 | 150 | 18.3 | 90 | 25.7 | 21 | 20.6 | 14 | 13.1 | 14 | 12.6 | 11 | 7.3 | |
≥ 30 | 56 | 6.8 | 33 | 9.4 | 7 | 6.9 | 3 | 2.8 | 5 | 4.5 | 8 | 5.3 | |
Missing | 18 | 0 | 3 | 3 | 11 | 1 | |||||||
Number of children | |||||||||||||
Nulliparous‡ | 44 | 5.3 | 26 | 7.4 | 6 | 5.7 | 2 | 1.8 | 2 | 1.6 | 8 | 5.3 | 0.0001 |
1 or 2 | 226 | 27.0 | 110 | 31.4 | 25 | 23.8 | 25 | 22.7 | 34 | 27.9 | 32 | 21.2 | |
3 or 4 | 307 | 36.6 | 135 | 38.6 | 43 | 41.0 | 47 | 42.7 | 34 | 27.9 | 48 | 31.8 | |
≥ 5 | 261 | 31.2 | 79 | 22.6 | 31 | 29.5 | 36 | 32.7 | 52 | 42.6 | 63 | 41.7 | |
Cumulative breastfeeding duration/month | |||||||||||||
Nulliparous‡ | 37 | 4.6 | 23 | 6.6 | 4 | 4.0 | 2 | 1.9 | 2 | 1.7 | 6 | 4.2 | 0.013a |
Never breastfed | 7 | 0.9 | 3 | 0.9 | 2 | 2.0 | 0 | 0.0 | 0 | 0.0 | 2 | 1.4 | |
Q1: 1−< 39 | 191 | 23.5 | 82 | 23.7 | 27 | 27.0 | 23 | 21.3 | 32 | 27.8 | 27 | 18.9 | |
Q2: 39–< 62 | 192 | 23.6 | 100 | 28.9 | 28 | 28.0 | 24 | 22.2 | 16 | 13.9 | 24 | 16.8 | |
Q3: 62–< 96 | 182 | 22.4 | 80 | 23.1 | 17 | 17.0 | 28 | 25.9 | 24 | 20.9 | 33 | 23.1 | |
Q4: ≥ 96 | 203 | 25.0 | 58 | 16.8 | 22 | 22.0 | 31 | 28.7 | 41 | 35.7 | 51 | 35.7 | |
Missing | 26 | 4 | 5 | 2 | 7 | 8 | |||||||
Averaged breastfeeding duration per child/month | |||||||||||||
Nulliparous‡ | 37 | 4.6 | 23 | 6.6 | 4 | 4.0 | 2 | 1.9 | 2 | 1.7 | 6 | 4.2 | 0.0036a |
Never breastfed | 7 | 0.9 | 3 | 0.9 | 2 | 2.0 | 0 | 0.0 | 0 | 0.0 | 2 | 1.4 | |
< 12 | 120 | 14.8 | 53 | 15.3 | 23 | 23.0 | 8 | 7.4 | 18 | 15.7 | 18 | 12.6 | |
12–23 | 407 | 50.1 | 153 | 44.2 | 46 | 46.0 | 71 | 65.7 | 64 | 55.7 | 73 | 51.0 | |
≥ 24 | 241 | 29.7 | 114 | 32.9 | 25 | 25.0 | 27 | 25.0 | 31 | 27.0 | 44 | 30.8 | |
Missing | 26 | 4 | 5 | 2 | 7 | 8 | |||||||
Number of children and cumulative breastfeeding duration | |||||||||||||
Nulliparous or ≤3 children and < 62 months | 354 | 43.60 | 179 | 51.7 | 44 | 44.0 | 43 | 39.8 | 44 | 38.3 | 44 | 30.8 | < 0.0001 |
≤ 3 children and ≥ 62 months | 79 | 9.73 | 43 | 12.4 | 5 | 5.0 | 10 | 9.3 | 8 | 7.0 | 13 | 9.1 | |
≥ 4 children and < 62 months | 73 | 8.99 | 29 | 8.4 | 17 | 17.0 | 6 | 5.6 | 6 | 5.2 | 15 | 10.5 | |
≥ 4 children and ≥ 62 months | 306 | 37.69 | 95 | 27.5 | 34 | 34.0 | 49 | 45.4 | 57 | 49.6 | 71 | 49.7 | |
Missing | 26 | 4 | 5 | 2 | 7 | 8 | |||||||
Age at first pregnancy and number of children | |||||||||||||
Nulliparous | 44 | 5.36 | 26 | 7.4 | 6 | 5.8 | 2 | 1.9 | 2 | 1.8 | 8 | 5.3 | < 0.0001 |
Age 25+ years, 1–3 births | 154 | 18.76 | 98 | 28.0 | 16 | 15.5 | 13 | 12.1 | 13 | 11.7 | 14 | 9.3 | |
Age < 25 years, 1–3 births | 244 | 29.72 | 101 | 28.9 | 27 | 26.2 | 38 | 35.5 | 37 | 33.3 | 41 | 27.3 | |
Age 25+ years, 4+ births | 49 | 5.97 | 23 | 6.6 | 12 | 11.7 | 4 | 3.7 | 6 | 5.4 | 4 | 2.7 | |
Age < 25 years, 4+ births | 330 | 40.20 | 102 | 29.1 | 42 | 40.8 | 50 | 46.7 | 53 | 47.7 | 83 | 55.3 | |
Missing | 17 | 0 | 2 | 3 | 11 | 1 | |||||||
Menopausal status | |||||||||||||
Premenopausal | 438 | 52.4 | 183 | 52.3 | 64 | 61.0 | 50 | 45.5 | 67 | 55.4 | 74 | 49.3 | 0.18 |
Postmenopausal | 398 | 47.6 | 167 | 47.7 | 41 | 39.0 | 60 | 54.5 | 54 | 44.6 | 76 | 50.7 | |
Missing | 2 | 0 | 0 | 0 | 1 | 1 | |||||||
Age at menopause/yearb | |||||||||||||
< 50 | 191 | 57.4 | 91 | 55.8 | 18 | 62.1 | 28 | 59.6 | 20 | 71.4 | 34 | 51.5 | 0.45b |
≥ 50 | 142 | 42.6 | 72 | 44.2 | 11 | 37.9 | 19 | 40.4 | 8 | 28.6 | 32 | 48.5 | |
Missing | 65 | 4 | 12 | 13 | 26 | 10 | |||||||
Cumulative hormonal contraception exposure/month | |||||||||||||
< 48 | 216 | 45.9 | 88 | 46.3 | 25 | 44.6 | 26 | 40.0 | 27 | 34.6 | 50 | 61.0 | 0.014 |
48 | 255 | 54.1 | 102 | 53.7 | 31 | 55.4 | 39 | 60.0 | 51 | 65.4 | 32 | 39.0 | |
Missing | 367 | 160 | 49 | 45 | 44 | 69 |
Distributions of tumor subtypes and pathologic characteristics in the overall study population and by hospitals
Tumor characteristic | Overall (n=838) | Hospitals | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
AKU (n=350, 42%) | Kijabe (n=105, 13%) | Nyeri (n=110, 13%) | St Mary’s (n=122, 15%) | Others (n=151, 18%) | |||||||||
N | % | N | % | N | % | N | % | N | % | N | % | P* | |
Tumor subtypes | |||||||||||||
ER status | |||||||||||||
Negative | 256 | 30.6 | 101 | 28.9 | 25 | 23.8 | 45 | 40.9 | 32 | 26.2 | 53 | 35.1 | 0.029 |
Positive | 582 | 69.5 | 249 | 71.1 | 80 | 76.2 | 65 | 59.1 | 90 | 73.8 | 98 | 64.9 | |
PR status | |||||||||||||
Negative | 340 | 40.6 | 138 | 39.4 | 36 | 34.3 | 50 | 45.5 | 48 | 39.3 | 68 | 45.0 | 0.36 |
Positive | 498 | 59.4 | 212 | 60.6 | 69 | 65.7 | 60 | 54.5 | 74 | 60.7 | 83 | 55.0 | |
HER2 status | |||||||||||||
Negative | 596 | 72.6 | 246 | 71.3 | 75 | 72.1 | 81 | 76.4 | 91 | 74.6 | 103 | 71.5 | 0.84 |
Positive | 225 | 27.4 | 99 | 28.7 | 29 | 27.9 | 25 | 23.6 | 31 | 25.4 | 41 | 28.5 | |
Missing | 17 | 5 | 1 | 4 | 0 | 7 | |||||||
Tumor molecular subtype | |||||||||||||
Luminal Aa | 286 | 34.8 | 121 | 35.1 | 46 | 44.2 | 37 | 34.9 | 40 | 32.8 | 42 | 29.2 | 0.080 |
Luminal B | 294 | 35.8 | 127 | 36.8 | 33 | 31.7 | 26 | 24.5 | 52 | 42.6 | 56 | 38.9 | |
HER2-enriched | 88 | 10.7 | 37 | 10.7 | 11 | 10.6 | 14 | 13.2 | 12 | 9.8 | 14 | 9.7 | |
Triple negative | 153 | 18.6 | 60 | 17.4 | 14 | 13.5 | 29 | 27.4 | 18 | 14.8 | 32 | 22.2 | |
Missing | 17 | 5 | 1 | 4 | 0 | 7 | |||||||
Luminal Aa | 286 | 36.9 | 121 | 36.7 | 46 | 48.9 | 37 | 37.4 | 40 | 33.9 | 42 | 31.1 | 0.094 |
Luminal B - HER2- | 157 | 20.2 | 65 | 19.7 | 15 | 16.0 | 15 | 15.2 | 33 | 28.0 | 29 | 21.5 | |
Luminal B - HER2+ | 137 | 17.7 | 62 | 18.8 | 18 | 19.1 | 11 | 11.1 | 19 | 16.1 | 27 | 20.0 | |
HER2-enriched | 88 | 11.3 | 37 | 11.2 | 11 | 11.7 | 14 | 14.1 | 12 | 10.2 | 14 | 10.4 | |
Core-basal like | 57 | 7.3 | 24 | 7.3 | 2 | 2.1 | 13 | 13.1 | 7 | 5.9 | 11 | 8.1 | |
Five negative | 51 | 6.6 | 20 | 6.4 | 2 | 2.1 | 9 | 9.1 | 7 | 5.9 | 12 | 8.9 | |
Missing | 62b | 20 | 11 | 11 | 4 | 16 | |||||||
Tumor pathology | |||||||||||||
Surgery | |||||||||||||
Core biopsy only | 435 | 51.9 | 157 | 44.9 | 26 | 24.8 | 46 | 41.8 | 73 | 59.8 | 133 | 88.1 | < 0.0001 |
Lumpectomy or mastectomy | 403 | 48.1 | 193 | 55.1 | 79 | 75.2 | 64 | 58.2 | 49 | 40.2 | 18 | 11.9 | |
Tumor size (cm) | |||||||||||||
< 2 | 41 | 7.6 | 29 | 13.1 | 8 | 8.1 | 2 | 2.3 | 1 | 1.9 | 1 | 1.3 | < 0.0001 |
2–< 5 | 287 | 53.5 | 134 | 60.4 | 53 | 53.5 | 39 | 44.8 | 26 | 50.0 | 35 | 45.5 | |
≥ 5 | 209 | 38.9 | 59 | 26.6 | 38 | 38.4 | 46 | 52.9 | 25 | 48.1 | 41 | 53.3 | |
Missingc | 301 | 128 | 6 | 23 | 70 | 74 | |||||||
Tumor overall grade | |||||||||||||
Grade 1 (low) | 35 | 5.0 | 20 | 7.3 | 4 | 4.4 | 6 | 5.7 | 2 | 1.7 | 3 | 2.8 | 0.17 |
Grade 2 (intermediate) | 319 | 45.9 | 130 | 47.3 | 34 | 37.8 | 44 | 41.5 | 59 | 50.9 | 52 | 48.2 | |
Grade 3 (high) | 341 | 49.1 | 125 | 45.5 | 52 | 57.8 | 56 | 52.8 | 55 | 47.4 | 53 | 49.1 | |
Missing/not applicable | 143 | 75 | 15 | 4 | 6 | 43 | |||||||
Lymphovascular invasion | |||||||||||||
No | 326 | 38.9 | 139 | 39.7 | 30 | 28.6 | 34 | 30.9 | 47 | 38.5 | 76 | 50.3 | 0.0029 |
Yes | 512 | 61.1 | 211 | 60.3 | 75 | 71.4 | 76 | 69.1 | 75 | 61.5 | 75 | 49.7 | |
Among cases with lumpectomy or mastectomy (n=403): | |||||||||||||
Tumor stage | |||||||||||||
Stage 0, i | 30 | 8.2 | 21 | 12.1 | 2 | 2.6 | 6 | 10.3 | 1 | 2.4 | 0 | 0.0 | 0.0040 |
Stage ii | 154 | 42.3 | 85 | 49.1 | 30 | 39.5 | 20 | 34.5 | 12 | 29.3 | 7 | 43.8 | |
Stage iii, iv | 180 | 49.5 | 67 | 38.7 | 44 | 57.9 | 32 | 55.2 | 28 | 68.3 | 9 | 56.3 | |
Missing | 39 | 20 | 3 | 6 | 8 | 2 | |||||||
Lymph nodes with metastasis | |||||||||||||
No | 162 | 40.2 | 89 | 46.1 | 23 | 29.1 | 22 | 34.4 | 20 | 40.8 | 8 | 44.4 | 0.96 |
Yes | 241 | 59.8 | 104 | 53.9 | 56 | 70.9 | 42 | 65.6 | 29 | 59.2 | 10 | 55.6 | |
Extranodal extension | |||||||||||||
No | 244 | 60.6 | 132 | 68.4 | 39 | 49.4 | 35 | 54.7 | 26 | 53.1 | 12 | 66.7 | 0.022 |
Yes | 159 | 39.5 | 61 | 31.6 | 40 | 50.6 | 29 | 45.3 | 23 | 46.9 | 6 | 33.3 |
Associations between breast cancer risk factors and tumor subtypes ER, PR, and HER2
Results of adjusted associations between risk factors and ER status are shown inTable 3. Compared to ER-positive patients, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = 1.11, 3.72, Ptrend = 0.021, comparing ≥ 5 to ≤ 2 children). ER-negative patients were also more likely to have longer cumulative breastfeeding duration (OR = 2.38, 95% CI = 1.33, 4.24; comparing ≥ 62 to < 39 months); however, these positive associations became insignificant after adjusting for a number of children. In fact, analyzing parity and breastfeeding variables together showed that the association was driven by parity (Table 3). In addition, the average duration of breastfeeding per child did not vary significantly by ER. Overall, we observed similar associations for PR to those for ER (Supplementary Table 2). BMI, either overall or by menopausal status, did not significantly vary by ER or PR status. When stratified by HER2 status, we found that, compared to HER2-negative patients, HER2-positive patients were less likely to be obese (OR = 0.58, 95% CI = 0.34, 0.97, Ptrend = 0.038), especially among postmenopausal women (OR = 0.26, 95% CI = 0.10, 0.62, Ptrend = 0.0026) (Supplementary Table 2). Similar results were observed when we restricted to early-stage patients (OR = 0.76, 95% CI = 0.59, 0.98, Ptrend = 0.038) suggesting that the association was unlikely to be due to the reverse causation.Table 3.Associations between breast cancer risk factors and ER status in Kenyan breast cancer patients (N=838)
ER+ N=582 ER- N=256 ER- vs. ER+ N % N % OR (95% CI)† P† Age at diagnosis/year 20–39 155 26.8 54 21.1 1.00 (Ref) 40–49 166 28.7 76 29.7 1.38 (0.82, 2.32) 0.23 50–59 138 23.9 73 28.5 1.20 (0.51, 2.83) 0.68 ≥ 60 119 20.6 53 20.7 0.84 (0.30, 2.35) 0.74 Trend‡ 0.995 (0.72, 1.39) 0.98 BMI/ kg/m2 Normal (< 25.0) 136 29.8 74 34.6 1.00 (Ref) Overweight (25.0–29.9) 185 40.5 79 36.9 0.77 (0.49, 1.21) 0.26 Obese (≥ 30.0) 136 29.8 61 28.5 0.84 (0.51, 1.38) 0.49 Trend‡ 0.92 (0.71, 1.18) 0.49 Premenopausal: BMIa Normal (< 25.0) 89 34.6 41 39.8 1.00 (Ref) Overweight (25.0–29.9) 102 39.7 30 29.1 0.58 (0.31, 1.10) 0.09 Obese (≥ 30.0) 66 25.7 32 31.1 0.91 (0.46, 1.77) 0.77 Trend‡ 0.93 (0.66, 1.31) 0.69 Postmenopausal: BMIa Normal (< 25.0) 47 23.6 33 29.7 1.00 (Ref) Overweight (25.0–29.9) 83 41.7 49 44.1 1.07 (0.55, 2.08) 0.85 Obese (≥ 30.0) 69 34.7 29 26.1 0.77 (0.37, 1.61) 0.49 Trend‡ 0.87 (0.61, 1.26) 0.47 Age at menarche/year ≤ 13 (9–13) 141 25.4 57 23.2 1.00 (Ref) 14 139 25.0 71 28.9 1.57 (0.94, 2.61) 0.083 ≥ 15 (15–20) 276 49.6 118 48.0 1.29 (0.81, 2.04) 0.28 Trend‡ 1.10 (0.88, 1.37) 0.41 Age at first pregnancy/year < 20 130 22.9 86 34.1 1.00 (Ref) 20–24 253 44.5 108 42.9 0.71 (0.44, 1.15) 0.16 25–29 115 20.2 35 13.9 0.58 (0.30, 1.11) 0.10 Nulliparousb or age ≥30 70 12.3 23 9.1 1.14 (0.48, 2.70) 0.76 Trend‡ 0.92 (0.71, 1.20) 0.54 Parity Nulliparousb 37 6.4 7 2.7 0.36 (0.10, 1.32) 0.12 Parous 545 93.6 249 97.3 1.00 (Ref) Number of children 1–2 171 31.4 55 22.1 1.00 (Ref) 3–4 217 39.8 90 36.1 1.43 (0.86, 2.36) 0.16 ≥ 5 157 28.8 104 41.8 2.03 (1.11, 3.72) 0.021 Trend‡ 1.43 (1.05, 1.93) 0.021 Cumulative breastfeeding duration/monthc Q1: 1–< 39 152 28.8 39 16.2 1.00 (Ref) Q2: 39–< 62 127 24.1 65 27.0 2.38 (1.33, 4.24) 0.0033 Q3: 62–< 96 124 23.5 58 24.1 1.44 (0.74, 2.80) 0.28 Q4: ≥ 96 124 23.5 79 32.8 1.58 (0.76, 3.30) 0.22 Trend‡ 1.10 (0.87, 1.39) 0.43 Mean breastfeeding duration per child/month < 12 84 15.9 36 14.9 1.00 (Ref) 12–23 277 52.6 130 53.9 1.10 (0.62, 1.94) 0.74 ≥ 24 166 31.5 75 31.1 1.25 (0.68, 2.30) 0.48 Trend‡ 1.12 (0.83, 1.51) 0.45 Age at first pregnancy and number of children Age 25+ years, 1–3 births 117 22.0 37 15.0 1.00 (Ref) Age < 25 years, 1–3 births 173 32.6 71 28.9 1.20 (0.68, 2.12) 0.53 Age 25+ years, 4+ births 34 6.4 15 6.1 1.47 (0.60, 3.61) 0.40 Age < 25 years, 4+ births 207 39.0 123 50.0 1.69 (0.93, 3.05) 0.085 Trend‡ 1.19 (0.99, 1.43) 0.063 Number of children and cumulative breastfeeding duration Nulliparous or ≤ 3 children and < 62 months 265 47.0 89 35.9 1.00 (Ref) ≤ 3 children and ≥ 62 months 56 9.9 23 9.3 1.09 (0.56, 2.09) 0.81 ≥ 4 children and < 62 months 51 9.0 22 8.9 1.52 (0.74, 3.09) 0.25 ≥ 4 children and ≥ 62 months 192 34.0 114 46.0 1.44 (0.89, 2.34) 0.14 Trend‡ 1.14 (0.97, 1.33) 0.12 Menopausal statusa Premenopausal 317 54.6 121 47.5 1.00 (Ref) Postmenopausal 264 45.4 134 52.5 1.44 (0.74, 2.81) 0.28 Age at menopause/yeard < 50 117 21.8 74 31.5 1.00 (Ref) > 50 102 19.0 40 17.0 0.73 (0.40, 1.36) 0.32
Associations between breast cancer risk factors and molecular subtypes
Tumor subtypes | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Luminal A n=286 | Luminal B n=294 | Luminal B vs. Luminal A | HER2-enriched n=88 | HER2-enriched vs. Luminal A | Triple negative n=153 | Triple negative vs. Luminal A | ||||||||
N | % | N | % | OR (95% CI)† | P† | N | % | OR (95% CI)† | P† | N | % | OR (95% CI)† | P† | |
Age at diagnosis/year | ||||||||||||||
< 50 | 142 | 50.2 | 180 | 61.4 | 1.00 (Ref) | 44 | 50.0 | 1.00 (Ref) | 77 | 50.3 | 1.00 (Ref) | |||
≥ 50 | 141 | 49.8 | 113 | 38.6 | 0.87 (0.36, 2.06) | 0.74 | 44 | 50.0 | 1.84 (0.57, 5.92) | 0.30 | 76 | 49.7 | 0.52 (0.20, 1.40) | 0.20 |
BMI/ kg/m2 | ||||||||||||||
Normal (< 25.0) | 60 | 27.3 | 71 | 30.5 | 1.00 (Ref) | 29 | 41.4 | 1.00 (Ref) | 43 | 32.6 | 1.00 (Ref) | |||
Overweight (25.0–29.9) | 84 | 38.2 | 99 | 42.5 | 1.09 (0.66, 1.82) | 0.73 | 25 | 35.7 | 0.55 (0.28, 1.11) | 0.10 | 49 | 37.1 | 0.91 (0.49, 1.68) | 0.75 |
Obese (≥ 30.0) | 76 | 34.5 | 63 | 27.0 | 0.76 (0.43, 1.33) | 0.33 | 16 | 22.9 | 0.36 (0.16, 0.81) | 0.013 | 40 | 30.3 | 0.89 (0.46, 1.72) | 0.73 |
Trend‡ | 0.87 (0.66, 1.15) | 0.32 | 0.59 (0.39, 0.88) | 0.011 | 0.94 (0.68, 1.32) | 0.73 | ||||||||
Premenopausal: BMIa | ||||||||||||||
Normal (< 25.0) | 36 | 32.4 | 51 | 34.7 | 1.00 (Ref) | 16 | 45.7 | 1.00 (Ref) | 23 | 38.3 | 1.00 (Ref) | |||
Overweight (25.0–29.9) | 43 | 38.7 | 59 | 40.1 | 0.98 (0.51, 1.88) | 0.95 | 11 | 31.4 | 0.52 (0.19, 1.40) | 0.20 | 16 | 26.7 | 0.49 (0.20, 1.21) | 0.12 |
Obese (≥ 30.0) | 32 | 28.8 | 37 | 25.2 | 0.78 (0.37, 1.61) | 0.49 | 8 | 22.9 | 0.44 (0.14, 1.35) | 0.15 | 21 | 35.0 | 0.84 (0.34, 2.07) | 0.71 |
Trend‡ | 0.89 (0.62, 1.27) | 0.52 | 0.65 (0.37, 1.1) | 0.13 | 0.91 (0.57, 1.45) | 0.69 | ||||||||
Postmenopausal: BMIa | ||||||||||||||
Normal (< 25.0) | 24 | 22.0 | 20 | 23.5 | 1.00 (Ref) | 13 | 37.1 | 1.00 (Ref) | 20 | 27.8 | 1.00 (Ref) | |||
Overweight (25.0–29.9) | 41 | 37.6 | 40 | 47.1 | 1.35 (0.57, 3.20) | 0.50 | 14 | 40.0 | 0.48 (0.17, 1.40) | 0.18 | 33 | 45.8 | 1.70 (0.68, 4.26) | 0.25 |
Obese (≥ 30.0) | 44 | 40.4 | 25 | 29.4 | 1.10 (0.43, 2.82) | 0.84 | 8 | 22.9 | 0.24 (0.07, 0.81) | 0.022 | 19 | 26.4 | 1.28 (0.48, 3.46) | 0.62 |
Trend‡ | 1.02 (0.64, 1.64) | 0.92 | 0.47 (0.26, 0.88) | 0.018 | 1.10 (0.68, 1.78) | 0.71 | ||||||||
Age at menarche/year | ||||||||||||||
≤ 13 (9–13) | 69 | 25.8 | 71 | 24.8 | 1.00 (Ref) | 23 | 26.4 | 1.00 (Ref) | 33 | 22.9 | 1.00 (Ref) | |||
14 | 68 | 25.4 | 69 | 24.1 | 1.28 (0.73, 2.25) | 0.39 | 26 | 29.9 | 1.65 (0.73, 3.74) | 0.23 | 37 | 25.7 | 1.43 (0.73, 2.81) | 0.30 |
≥ 15 (15–20) | 131 | 48.9 | 146 | 51.1 | 1.29 (0.79, 2.13) | 0.31 | 38 | 43.7 | 1.32 (0.64, 2.73) | 0.46 | 74 | 51.4 | 1.43 (0.78, 2.60) | 0.24 |
Trend‡ | 1.13 (0.88, 1.45) | 0.34 | 1.12 (0.78, 1.59) | 0.54 | 1.18 (0.88, 1.58) | 0.28 | ||||||||
Age at first pregnancy/year | ||||||||||||||
< 20 | 72 | 26.2 | 58 | 19.9 | 1.00 (Ref) | 31 | 35.6 | 1.00 (Ref) | 51 | 34.0 | 1.00 (Ref) | |||
20–24 | 121 | 44.0 | 133 | 45.5 | 1.51 (0.84, 2.70) | 0.17 | 30 | 34.5 | 0.64 (0.29, 1.37) | 0.25 | 69 | 46.0 | 0.81 (0.43, 1.51) | 0.51 |
25–29 | 51 | 18.5 | 62 | 21.2 | 1.76 (0.85, 3.65) | 0.13 | 16 | 18.4 | 0.92 (0.34, 2.51) | 0.87 | 19 | 12.7 | 0.67 (0.28, 1.60) | 0.37 |
Nulliparousb or ≥ 30 | 31 | 11.3 | 39 | 13.4 | 1.06 (0.40, 2.82) | 0.90 | 10 | 11.5 | 1.18 (0.31, 4.53) | 0.81 | 11 | 7.3 | 0.66 (0.20, 2.18) | 0.50 |
Trend‡ | 1.09 (0.82, 1.45) | 0.54 | 1.02 (0.67, 1.56) | 0.93 | 0.84 (0.59, 1.20) | 0.33 | ||||||||
Parity | ||||||||||||||
Nulliparousb | 14 | 4.9 | 20 | 6.8 | 1.09 (0.30, 3.88) | 0.90 | 4 | 4.5 | 0.56 (0.07, 4.77) | 0.60 | 3 | 2.0 | 0.67 (0.11, 4.12) | 0.66 |
Parous | 272 | 95.1 | 274 | 93.2 | 1.00 (Ref) | 84 | 95.5 | 1.00 (Ref) | 150 | 98.0 | 1.00 (Ref) | |||
Number of children | ||||||||||||||
1–2 | 73 | 26.8 | 101 | 36.9 | 1.00 (Ref) | 19 | 22.6 | 1.00 (Ref) | 31 | 20.7 | 1.00 (Ref) | |||
3–4 | 113 | 41.5 | 101 | 36.9 | 0.47 (0.28, 0.79) | 0.005 | 26 | 31.0 | 0.85 (0.37, 1.98) | 0.71 | 59 | 39.3 | 1.16 (0.59, 2.29) | 0.66 |
≥ 5 | 86 | 31.6 | 72 | 26.3 | 0.45 (0.23, 0.87) | 0.018 | 39 | 46.4 | 1.71 (0.65, 4.53) | 0.28 | 60 | 40.0 | 1.27 (0.56, 2.89) | 0.56 |
Trend‡ | 0.65 (0.47, 0.90) | 0.0099 | 1.34 (0.82, 2.20) | 0.24 | 1.11 (0.75, 1.66) | 0.60 | ||||||||
Cumulative breastfeeding duration/monthc | ||||||||||||||
Q1: 1–< 39 | 64 | 24.3 | 88 | 33.2 | 1.00 (Ref) | 15 | 18.3 | 1.00 (Ref) | 20 | 13.9 | 1.00 (Ref) | |||
Q2: 39–< 62 | 59 | 22.4 | 68 | 25.7 | 0.99 (0.54, 1.80) | 0.97 | 22 | 26.8 | 2.48 (0.97, 6.33) | 0.058 | 40 | 27.8 | 2.98 (1.33, 6.71) | 0.008 |
Q3: 62–< 96 | 71 | 27.0 | 53 | 20.0 | 0.66 (0.33, 1.30) | 0.23 | 14 | 17.1 | 0.80 (0.27, 2.39) | 0.69 | 40 | 27.8 | 1.80 (0.74, 4.38) | 0.20 |
Q4: ≥ 96 | 69 | 26.2 | 56 | 21.1 | 0.99 (0.44, 2.20) | 0.97 | 31 | 37.8 | 1.30 (0.40, 4.16) | 0.66 | 44 | 30.6 | 1.87 (0.69, 5.07) | 0.22 |
Trend‡ | 0.93 (0.71, 1.20) | 0.56 | 0.97 (0.67, 1.41) | 0.88 | 1.12 (0.82, 1.52) | 0.47 | ||||||||
Mean breastfeeding duration per child/month | ||||||||||||||
< 12 | 34 | 12.9 | 48 | 18.1 | 1.00 (Ref) | 11 | 13.4 | 1.00 (Ref) | 23 | 16.0 | 1.00 (Ref) | |||
12– 23 | 142 | 54.0 | 139 | 52.5 | 0.65 (0.35, 1.21) | 0.18 | 49 | 59.8 | 1.24 (0.47, 3.29) | 0.66 | 71 | 49.3 | 0.75 (0.36, 1.59) | 0.46 |
≥ 24 | 87 | 33.1 | 78 | 29.4 | 0.64 (0.32, 1.27) | 0.20 | 22 | 26.8 | 1.21 (0.42, 3.52) | 0.73 | 50 | 34.7 | 1.09 (0.49, 2.43) | 0.83 |
Trend‡ | 0.84 (0.60, 1.16) | 0.28 | 1.07 (0.66, 1.72) | 0.80 | 1.13 (0.76, 1.66) | 0.55 | ||||||||
Age at first pregnancy and Number of children | ||||||||||||||
Age 25+ years, 1–3 births | 54 | 20.7 | 64 | 23.5 | 1.00 (Ref) | 15 | 17.9 | 1.00 (Ref) | 20 | 13.6 | 1.00 (Ref) | |||
Age < 25 years, 1–3 births | 80 | 30.7 | 93 | 34.2 | 0.93 (0.52, 1.67) | 0.81 | 19 | 22.6 | 0.82 (0.31, 2.15) | 0.69 | 47 | 32.0 | 1.39 (0.65, 2.97) | 0.40 |
Age 25+ years, 4+ births | 15 | 5.7 | 18 | 6.6 | 0.77 (0.29, 2.05) | 0.60 | 8 | 9.5 | 2.10 (0.58, 7.54) | 0.26 | 7 | 4.8 | 1.12 (0.29, 4.27) | 0.87 |
Age < 25 years, 4+ births | 112 | 42.9 | 97 | 35.7 | 0.55 (0.29, 1.05) | 0.068 | 42 | 50.0 | 1.31 (0.51, 3.39) | 0.58 | 73 | 49.7 | 1.38 (0.62, 3.08) | 0.43 |
Trend‡ | 0.81 (0.66, 0.99) | 0.041 | 1.16 (0.86, 1.56) | 0.33 | 1.07 (0.84, 1.37) | 0.58 | ||||||||
Number of children and Cumulative breastfeeding duration | ||||||||||||||
Nulliparous or ≤ 3 children and < 62 months | 117 | 42.2 | 146 | 51.2 | 1.00 (Ref) | 31 | 36.0 | 1.00 (Ref) | 51 | 34.7 | 1.00 (Ref) | |||
≤ 3 children and ≥ 62 months | 30 | 10.8 | 25 | 8.8 | 0.61 (0.30, 1.22) | 0.16 | 6 | 7.0 | 0.41 (0.11, 1.56) | 0.19 | 17 | 11.6 | 1.19 (0.53, 2.66) | 0.68 |
≥ 4 children and < 62 months | 20 | 7.2 | 30 | 10.5 | 0.89 (0.38, 2.07) | 0.79 | 10 | 11.6 | 2.34 (0.78, 6.99) | 0.13 | 12 | 8.2 | 1.31 (0.49, 3.53) | 0.59 |
≥ 4 children and ≥ 62 months | 110 | 39.7 | 84 | 29.5 | 0.52 (0.30, 0.89) | 0.02 | 39 | 45.3 | 1.26 (0.57, 2.78) | 0.56 | 67 | 45.6 | 0.96 (0.50, 1.84) | 0.91 |
Trend‡ | 0.81 (0.68, 0.97) | 0.02 | 1.11 (0.85, 1.44) | 0.44 | 0.99 (0.80, 1.22) | 0.91 | ||||||||
Menopausal statusa | ||||||||||||||
Premenopausal | 144 | 50.3 | 174 | 59.4 | 1.00 (Ref) | 44 | 50.0 | 1.00 (Ref) | 68 | 44.7 | 1.00 (Ref) | |||
Postmenopausal | 142 | 49.7 | 119 | 40.6 | 0.69 (0.32, 1.48) | 0.33 | 44 | 50.0 | 0.69 (0.22, 2.10) | 0.51 | 84 | 55.3 | 1.82 (0.78, 4.28) | 0.17 |
Age at menopause/year | ||||||||||||||
Premenopausal | 144 | 50.3 | 174 | 59.4 | N/A | 44 | 50.0 | N/A | 68 | 44.7 | N/A | |||
< 50 years | 58 | 22.5 | 58 | 20.9 | 1.00 (Ref) | 28 | 33.7 | 1.00 (Ref) | 44 | 32.1 | 1.00 (Ref) | |||
> 50 years | 56 | 21.7 | 46 | 16.6 | 0.88 (0.45, 1.74) | 0.72 | 11 | 13.3 | 0.38 (0.15, 0.997) | 0.049 | 25 | 18.3 | 0.66 (0.31, 1.40) | 0.28 |
Discussion
The etiology of early-onset breast cancers is particularly lacking across populations given their rarity. Studying African populations where risk factors differ and where onset is almost a decade earlier could provide new insights on breast cancer etiology given the etiologic and molecular subtype heterogeneity in diverse populations.