Mammographic Density and Breast Cancer Risk: Evaluation of a Novel Method of Measuring Breast Tissue Volumes

Norman Boyd; Lisa Martin; Anoma Gunasekara; Olga Melnichouk; Gord Maudsley; Chris Peressotti; Martin Yaffe; Salomon Minkin

doi:10.1158/1055-9965.EPI-09-0107

DOI: 10.1158/1055-9965.EPI-09-0107 Published June 2009

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Figure 1.
Flowchart of recruitment of cases and controls.
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Figure 2.
Observed distributions and correlations between volume and area breast measurements for case-control triplets (n = 813). R_s, a Spearman correlation coefficient.

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Table 1.

Selected characteristics of all subjects (n = 1,020) by case-control status

	Cases (n = 364)	Controls
		Matched by machine (n = 359)	P*	Not matched by machine (n = 297)	P*
Risk factors
Height (cm)	162.6 (6.9)	163.1 (6.6)	0.32	163.4 (6.2)	0.12
Weight (kg)	68.3 (14.4) n = 362	68.0 (14.6) n = 358	0.75	68.3 (14.7)	0.96
BMI (kg/m²)	25.8 (5.2) n = 362	25.6 (5.5) n = 358	0.50	25.6 (5.2)	0.47
Age at mammogram (y)	59.6 (11.0)	59.5 (11.0)	0.90	58.4 (11.1)	0.17
Age at menarche (y)	12.7 (1.4) n = 361	12.8 (1.5)	0.51	12.7 (1.4) n = 295	0.93
Parity (% parous)	70.9	76.0	0.12	69.7	0.74
Age at birth of 1st child (y)	26.3 (5.0) n = 258	26.6 (5.4) n = 274	0.53	26.6 (5.6) n = 206	0.54
No. of live births	1.7 (1.4)	1.8 (1.4)	0.20	1.6 (1.4)	0.76
Menopausal status (% postmenopausal)	68.0 (n = 363)	69.9	0.59	69.6 (n = 296)	0.67
Age at menopause (y)	49.4 (6.2) n = 211	47.7 (6.4) n = 220	0.01	48.1 (6.5) n = 178	0.05
HRT ever used (% yes)	45.1	45.5 (n = 358)	0.90	44.4	0.88
Years HRT used (y)	4.0 (6.9)	4.2 (7.5) n = 358	0.69	3.8 (7.0)	0.73
Breast cancer in 1st degree relatives (% yes)	21.6 (n = 361)	26.3 (n = 357)	0.14	23.0 (n = 296)	0.68
Imaging parameters
Breast thickness (cm)	5.4 (1.2)	5.4 (1.4)	0.92	5.4 (1.4)	0.57
KVP	26.8 (2.0)	26.7 (2.0)	0.62	26.8 (2.1)	0.81
MAS	155.3 (48.7)	156.0 (57.9)	0.85	144.9 (52.4)	0.01
Compression force (N)	104.7 (32.6)	103.9 (31.8)	0.74	101.3 (33.0)	0.20
Volume breast measurements
Percent dense volume (%)	11.3 (16.1)	9.9 (14.6)	0.23	7.7 (12.9)	0.001
Dense volume (cm³)	57.9 (76.6)	53.6 (86.5)	0.25	38.9 (60.4)	0.0001
Total volume (cm³)	725.2 (360.8)	761.6 (417.2)	0.44	752.7 (406.8)	0.58
Area breast measurements
Percent dense area (%)	33.3 (20.5)	30.3 (19.7)	0.07	30.1 (19.9)	0.05
Dense area (cm²)	40.8 (26.9)	38.4 (27.3)	0.21	36.3 (23.4)	0.04
Total area (cm²)	141.5 (61.0)	146.4 (64.2)	0.31	144.6 (63.4)	0.55

NOTE: Shown are mean (SD) and percentage for, respectively, continuous and categorical variables.
HRT, hormone replacement therapy; KVP, kilovoltage peak; MAS, milliampere seconds.
↵* Two-sided two-sample t test for continuous variables, and χ² test for categorical variables. Cubic root and square root transformations were applied to, respectively, volume and area breast measurements.

Table 2.

Risk of breast cancer according to quintiles of percent and absolute density for all subjects (n = 1,020)

	Quintile of percent density									P*	Quintile of absolute density			P*
		1	2	3	4	5		1	2	P*	3	4	5	P*
	Percent dense volume (%)										Dense volume (cm³)
No. of cases	62	64	75	78	85		64	68	61	86	85
No. of controls	142	140	129	126	119		140	136	143	118	119
OR unadjusted (95% CI)	Reference	1.05 (0.7, 1.6)	1.33 (0.9, 2.0)	1.42 (0.9, 2.1)	1.64 (1.1, 2.5)	0.01	Reference	1.09 (0.7, 1.7)	0.93 (0.6, 1.4)	1.59 (1.1, 2.4)	1.56 (1.0, 2.3)	0.1
OR adjusted for risk factors^† (95% CI)	Reference	1.08 (0.7, 1.6)	1.39 (0.9, 2.1)	1.60 (1.0, 2.5)	1.98 (1.3, 3.1)	0.001	Reference	1.10 (0.7, 1.7)	0.98 (0.6, 1.5)	1.69 (1.1, 2.6)	1.68 (1.1, 2.6)	0.003
	Percent dense area (%)										Dense area (cm²)
No. of cases	70	60	76	76	82		71	62	69	78	84
No. of controls	134	144	128	128	122		133	142	135	126	120
OR unadjusted (95% CI)	Reference	0.80 (0.5, 1.2)	1.14 (0.8, 1.8)	1.14 (0.8, 1.7)	1.29 (0.9, 1.9)	0.06	Reference	0.82 (0.5, 1.2)	0.96 (0.6, 1.4)	1.16 (0.8, 1.7)	1.31 (0.9, 2.0)	0.05
OR adjusted for risk factors^† (95% CI)	Reference	0.92 (0.6, 1.4)	1.41 (0.9, 2.2)	1.49 (0.9, 2.3)	1.86 (1.1, 3.0)	0.003	Reference	0.90 (0.6, 1.4)	1.07 (0.7, 1.6)	1.29 (0.8, 2.0)	1.48 (1.0, 2.3)	0.02

NOTE: Shown are mean (SD) and percentage for, respectively, continuous and categorical variables.
↵* Unconditional logistic regression analysis. P value is from a test of linear trend with quintiles as an ordinary variable in the model.
↵† Age at mammogram (y), age at first birth (y), weight (kg), height (cm), menopausal status (premenopausal, postmenopausal), and parity (parous, nonparous).

Table 3.

Risk of breast cancer according to quintiles of percent and absolute density for case-control triplets (n = 813)

	Quintile of percent density									P*	Quintile of absolute density			P*
		1	2	3	4	5		1	2	P*	3	4	5	P*
	Percent dense volume (%)										Dense volume (cm³)
No. of cases	44	45	56	59	67		45	49	46	65	66
No. of controls	119	117	107	103	96		118	113	117	97	97
OR unadjusted (95% CI)	Reference	1.04 (0.6, 1.7)	1.42 (0.9, 2.3)	1.55 (1.0, 2.5)	1.89 (1.2, 3.0)	0.002	Reference	1.14 (0.7, 1.8)	1.03 (0.6, 1.7)	1.76 (1.1, 2.8)	1.78 (1.1, 2.8)	0.002
OR adjusted for risk factors^† (95% CI)	Reference	1.06 (0.6, 1.7)	1.48 (0.9, 2.4)	1.72 (1.0, 2.8)	2.21 (1.3, 3.7)	0.001	Reference	1.15 (0.7, 1.9)	1.04 (0.6, 1.7)	1.82 (1.1, 2.9)	1.86 (1.1, 3.0)	0.003
	Percent dense area (%)										Dense area (cm²)
No. of cases	41	45	68	56	61		40	46	55	67	63
No. of controls	122	117	95	106	102		123	116	108	95	100
OR unadjusted (95% CI)	Reference	1.14 (0.7, 1.9)	2.13 (1.3, 3.4)	1.57 (1.0, 2.5)	1.78 (1.1, 2.9)	0.01	Reference	1.22 (0.7, 2.0)	1.57 (1.0, 2.5)	2.17 (1.3, 3.5)	1.94 (1.2, 3.1)	0.0005
OR adjusted for risk factors^† (95% CI)	Reference	1.34 (0.8, 2.2)	2.60 (1.6, 4.3)	2.04 (1.2, 3.5)	2.40 (1.3, 4.3)	0.002	Reference	1.35 (0.8, 2.3)	1.74 (1.0, 2.9)	2.35 (1.4, 3.9)	2.11 (1.3, 3.5)	0.0005

NOTE: Shown are mean (SD) and percentage for, respectively, continuous and categorical variables.
↵* Unconditional logistic regression analysis. P value is from a test of linear trend with quintiles as an ordinary variable in the model.
↵† Age at mammogram (y), age at first birth (y), weight (kg), height (cm), menopausal status (premenopausal, postmenopausal), and parity (parous, nonparous).

Table 4.

Risk of breast cancer according to continuous percent and absolute density for all subjects (n = 1,020)

		Regression coefficient	P	Regression coefficient	P
		Percent dense volume* (%)		Dense volume* (cm³)
Unadjusted	Separate predictors	0.1814	0.01	0.1197	0.005
Unadjusted		Both in the model	0.1427	0.11	0.1071	0.04
Adjusted for risk factors^†	Separate predictors	0.2549	0.001	0.1372	0.003
Adjusted for risk factors^†		Both in the model	0.1573	0.08	0.1106	0.03
		Percent dense area^‡ (%)		Dense area^‡ (cm²)
Unadjusted	Separate predictors	0.0703	0.03	0.0568	0.06
Unadjusted		Both in the model	0.0286	0.49	0.0160	0.65
Adjusted for risk factors^†	Separate predictors	0.1478	0.0005	0.0760	0.02
Adjusted for risk factors^†		Both in the model	0.1079	0.03	0.0382	0.30

NOTE: Unconditional logistic regression analysis.
↵* Cubic root transformed.
↵† Age at mammogram (y), age at first birth (y), weight (kg), height (cm), menopausal status (premenopausal, postmenopausal), and parity (parous, nonparous).
↵‡ Square root transformed.

Table 5.

Risk of breast cancer according to continuous percent and absolute density for all case-control triplets (n = 813)

		Regression coefficient	P	Regression coefficient	P
		Percent dense volume* (%)		Dense volume* (cm³)
Unadjusted	Separate predictors	0.2252	0.005	0.1597	0.001
Unadjusted		Both in the model	0.0873	0.41	0.0979	0.10
Adjusted for risk factors^†	Separate predictors	0.2797	0.003	0.1705	0.002
Adjusted for risk factors^†		Both in the model	0.1150	0.29	0.1062	0.09
		Percent dense area^‡ (%)		Dense area^‡ (cm²)
Unadjusted	Separate predictors	0.1262	0.001	0.1148	0.001
Unadjusted		Both in the model	0.0993	0.05	0.0759	0.07
Adjusted for risk factors^†	Separate predictors	0.2041	<0.0001	0.1227	0.001
Adjusted for risk factors^†		Both in the model	0.1742	0.002	0.0858	0.05

NOTE: Unconditional logistic regression analysis.
↵* Cubic root transformed.
↵† Age at mammogram (y), age at first birth (y), weight (kg), height (cm), menopausal status (premenopausal, postmenopausal), and parity (parous, nonparous).
↵‡ Square root transformed.