Does breast density measured through population-based screening independently increase breast cancer risk in Asian females?

Figures & data

Table 1 Baseline characteristics of breast density and selected risk factors of breast cancer of 1,561 pairs of breast cancer cases and matched controls

Characteristics	Incident breast cancer cases	Matched controls	P-value
Age, mean (standard deviation), years	53.0 (8.7)	53.0 (8.7)	0.97
Age at menarche, n (%)
≤13 years	163 (10.4)	470 (7.8)	<0.001
14–16 years	871 (55.8)	3258 (54.3)
≥17 years	454 (29.1)	2113 (35.2)
Missing	73 (4.7)	161 (2.7)
Number of live births, n (%)
0	106 (6.8)	271 (4.5)	<0.001
1	208 (13.3)	581 (9.7)
≥2	1208 (77.4)	5065 (84.4)
Missing	39 (2.5)	85 (1.4)
Breast feeding, n (%)
0	247 (15.8)	715 (11.9)	<0.001
<12 months	410 (26.3)	1777 (29.6)
≥12 months	876 (56.1)	3433 (57.2)
Missing	28 (1.8)	77 (1.3)
Age at menopause, n (%)
Premenopausal	369 (23.6)	1613 (26.9)	0.187
<45 years	76 (4.9)	336 (5.6)
45–54 years	868 (55.6)	3316 (55.3)
≥55 years	109 (7.0)	408 (6.8)
Missing	139 (8.9)	329 (5.5)
Hormone replacement therapy, n (%)
Never	667 (58.2)	2935 (68.5)	0.215
Ever	169 (14.7)	660 (15.4)
Missing	311 (27.1)	688 (16.1)
Oral contraceptive use, n (%)
Never	866 (55.5)	4061 (67.7)	0.053
<12 months	92 (5.9)	519 (8.6)
≥12 months	70 (4.5)	258 (4.3)
Missing	533 (34.1)	1164 (19.4)
Body mass index, n (%)
<23 kg/m^2	496 (31.8)	1951 (32.5)	0.476
23 to <25 kg/m^2	292 (18.7)	1225 (20.4)
≥25 kg/m^2	360 (23.1)	1357 (22.6)
Missing	413 (26.5)	1469 (24.5)
Past history of benign breast disease, n (%)
No	884 (56.6)	4962 (82.7)	<0.001
Yes	498 (31.9)	526 (8.8)
I do not know	179 (11.5)	514 (8.5)
Breast density, n (%)
Almost entirely fat	122 (7.8)	1001 (16.7)	<0.001
Scattered fibroglandular  densities	352 (22.6)	1564 (26.1)
Heterogeneously dense	667 (42.7)	2258 (37.6)
Extremely dense	420 (26.9)	1179 (19.6)

Table 2 Breast density as risk factor of breast cancer according to the age groupa

Results	All results			40–49 years of age			50–59 years of age			60–69 years of age			70+ years of age
Density	Case/control	OR	95% CI	Case/ control	OR	95% CI	Case/ control	OR	95% CI	Case/ control	OR	95% CI	Case/ control	OR	95% CI
Almost entirely fat	122/1001	1.0		4/85	1.0		27/314	1.0		60/407	1.0		31/195	1.0
Scattered fibroglandular densities	352/1564	2.4	1.8–3.1	56/349	4.4	1.5–13.2	143/692	2.8	1.7–4.6	113/421	2.0	1.3–2.9	40/102	2.2	1.1–4.2
Heterogeneously dense	667/2258	3.8	2.9–4.9	286/1126	7.0	2.4–20.3	265/847	4.8	2.9–7.7	96/237	2.7	1.7–4.4	20/48	2.5	1.1–6.0
Extremely dense	420/1179	5.0	3.7–6.7	277/839	9.4	3.2–27.4	128/309	6.0	3.5-10.1	15/29	5.1	2.1–12.2	0/2	–	–
P-trend			<0.001			<0.001			<0.001			<0.001			<0.001

Note:

a ORs are adjusted for age, age at menarche, number of live births, breast feeding, menopausal status/age at menopause, hormone replacement therapy use, oral contraceptive use, body mass index, past benign breast disease, and calculated by conditional logistic regression.

Abbreviations: CI, confidence interval; OR, odds ratio.

Figure 1 Breast density as risk factor of breast cancer according to menopausal status. Odds ratios are adjusted for age, age at menarche, number of live births, breast feeding, menopausal status/age at menopause, hormone replacement therapy use, oral contraceptive use, body mass index, past benign breast disease and calculated by logistic regression. In total, 139 cases and 329 controls whose menopausal status were missing were excluded from analysis.

Table 3 Breast density as risk factor of breast cancer according to screening results, assessment category, and time interval after non-recall screeninga

Density	Almost entirely fat		Scattered fibroglandular densities			Heterogeneously dense			Extremely dense			P-trend
Assessment categories	Case/ control	OR	Case/ control	OR	95% CI	Case/ control	OR	95% CI	Case/ control	OR	95% CI
Recallb	102/763	1.0	277/1162	2.2	1.7–3.0	462/1421	3.6	2.6–4.8	224/760	3.3	2.3–4.6	<0.001
Categories 4 and 5 (N=402 pairs)	60/351	1.0	114/423	2.0	1.3–2.9	153/462	2.6	1.7–4.0	75/316	1.8	1.1–3.1	0.030
Category 0 (N=663 pairs)	42/412	1.0	163/739	2.9	1.9–4.3	309/959	4.9	3.2–7.6	149/444	5.2	3.2–8.4	<0.001
P-heterogeneity				0.203			0.040			0.003
Non-recallc	20/238	1.0	75/402	3.0	1.6–5.5	205/837	5.2	2.8–9.8	196/419	12.1	6.3–23.3	<0.001
Diagnosis <1 year after screening (N=312 pairs)	14/158	1.0	42/245	3.3	1.5–7.1	121/529	5.4	2.5–11.9	135/267	16.7	7.3–38.5	<0.001
Diagnosis ≥1 year after screening (N=184 pairs)	6/80	1.0	33/157	3.6	1.2–11.1	84/308	7.6	2.4–24.2	61/152	12.1	3.7–39.6	<0.001
P-heterogeneity				0.900			0.631			0.663
P-heterogeneityd				0.371			0.301			0.001

Notes:

a ORs are adjusted for age, age at menarche, number of live births, breast feeding, menopausal status/age at menopause, hormone replacement therapy use, oral contraceptive use, body mass index, past benign breast disease and calculated by conditional logistic regression.

b Including BI-RADS categories 4 and 5 (suspicious for malignancy) and 0 (need additional imaging or prior examinations).

c Including BI-RADS categories 1 (negative) and 2 (benign).

d P-heterogeneity between recalled cases and non-recalled cases.

Abbreviations: BI-RADS, Breast Imaging Reporting and Data System; CI, confidence interval; OR, odds ratio.

Table S1 Breast density as risk factor of breast cancer according to results of screening, time interval after negative screening, type of breast cancer, and Surveillance, Epidemiology, and End Results stagea

Density Assessment categories	Almost entirely fat	Scattered fibroglandular densities	Heterogeneously dense	Extremely dense	P-trend
	OR	OR (95% CI)	OR (95% CI)	OR (95% CI)
Invasive breast cancer
All (N=1,332 pairs)	1.0	2.2 (1.7–2.9)	2.3 (2.6–4.5)	4.6 (3.3–6.2)	<0.001
Recallb(N=933 pairs)	1.0	2.0 (1.5–2.7)	3.1 (2.3–4.2)	2.8 (1.9–4.0)	<0.001
Categories 4 and 5 (N=375 pairs)	1.0	1.8 (1.2–2.7)	2.3 (1.5–3.6)	1.7 (1.0–2.9)	0.058
Category 0 (N=558 pairs)	1.0	2.6 (1.7–4.0)	4.2 (2.7–6.6)	4.3 (2.6–7.1)	<0.001
Non-recallc(N=399 pairs)	1.0	3.3 (2.8–12.1)	5.8 (2.8–12.1)	15.5 (7.3–33.2)	<0.001
Diagnosis <1 year after screening (N=253 pairs)	1.0	3.5 (1.4–8.8)	6.8 (2.7–16.9)	25.0 (9.4–66.3)	<0.001
		4.5 (1.2–16.8)	8.0 (2.1–31.0)	13.5 (3.3–54.7)
Diagnosis ≥1 year after screening (N=146 pairs)	1.0				0.001
Localized breast cancer
All (N=733)	1.0	2.1 (1.5–3.1)	3.1 (2.1–4.4)	5.7 (3.8–8.7)	<0.001
Recallb(N=500 pairs)	1.0	1.9 (1.3–2.9)	2.7 (1.8–4.1)	3.1 (1.9–5.0)	<0.001
Categories 4 and 5 (N=186 pairs)	1.0	1.5 (0.9–2.7)	2.1 (1.1–3.9)	1.5 (0.7–3.2)	0.102
Category 0 (N=314 pairs)	1.0	2.7 (1.5–4.8)	3.8 (2.1–7.0)	5.7 (2.9–11.4)	<0.001
Non-recallc(N=233 pairs)	1.0	3.5 (1.3–9.4)	6.5 (2.3–18.3)	28.5 (9.6–84.3)	<0.001
		4.1 (1.1–14.9)	10.4 (2.6–40.9)	42.6 (10.3–175.6)
Diagnosis <1 year after screening (N=156 pairs)	1.0				<0.001
		4.5 (0.6–33.5)	5.2 (0.7–37.8)	32.5 (3.8–280.7)
Diagnosis ≥1 year after screening (N=77 pairs)	1.0				<0.001
Regional/distantd breast cancer
All (N=479)	1.0	2.1 (1.3–3.4)	3.8 (2.3–7.1)	3.5 (2.0–5.9)	<0.001
Recallb(N=348 pairs)	1.0	2.0 (1.8–3.3)	3.4 (2.0–5.8)	2.9 (1.6–5.3)	<0.001
Categories 4 and 5 (N=151 pairs)	1.0	1.9 (0.9–3.8)	2.1 (1.0–4.5)	1.6 (0.6–4.0)	0.125
Category 0 (N=197 pairs)	1.0	2.7 (1.0–4.9)	5.6 (2.5–12.8)	4.4 (1.8–10.6)	<0.001
Non-recallc(N=131 pairs)	1.0	3.1 (0.9–10.5)	5.7 (1.7–18.8)	6.0 (1.7–21.4)	0.001
		3.0 (0.6–14.9)	3.3 (0.8–14.9)	7.9 (1.5–43.1)
Diagnosis <1 year after screening (N=75 pairs)	1.0				0.002
		13.7 (0.9–200.2)	89.6 (4.9–999.9)	24.4 (1.5–389.9)
Diagnosis ≥1 year after screening (N=56 pairs)	1.0				0.100
Ductal carcinoma in situ
All (N=229 pairs)	1.0	4.9 (2.1–11.9)	11.2 (4.5–28.1)	13.9 (5.3–36.8)	<0.001
Recallb(N=132 pairs)	1.0	9.4 (2.6–34.26)	28.3 (7.1–112.8)	33.2 (7.6–144.7)	<0.001
Non-recallc(N=97 pairs)	1.0	2.1 (0.6–7.9)	4.1 (1.1–15.8)	6.0 (1.5–24.8)	0.001

Notes:

a ORs are adjusted for age, age at menarche, number of live births, breast feeding, menopausal status/age at menopause, hormone replacement therapy use, oral contraceptive use, body mass index, past benign breast disease and calculated by conditional logistic regression.

b Including BI-RADS categories 4 and 5 (suspicious for malignancy) and 0 (need additional imaging or prior examinations).

c Including BI-RADS categories 1 (negative) and 2 (benign).

d Only 40 were distant breast cancer cases.

Abbreviations: BI-RADS, Breast Imaging Reporting and Data System; CI, confidence interval; OR, odds ratio.