Role of mammogram and ultrasound imaging in predicting breast cancer subtypes in screening and symptomatic patients

doi:10.5306/wjco.v12.i9.808

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World Journal of Clinical Oncology

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Study

World J Clin Oncol. Sep 24, 2021; 12(9): 808-822
Published online Sep 24, 2021. doi: 10.5306/wjco.v12.i9.808

Table 1 Classification of imaging features based on American College of Radiology Breast Imaging Reporting and Data System Lexicon

Imaging feature	Classification
Mammogram
Appearance	Mass
	Asymmetry
	High risk microcalcifications¹
	Architectural distortion
Ultrasound
Margins	Spiculated
	Microlobulated
	Circumscribed
Posterior acoustic features	Shadowing
	Enhancement
	Mixed
	None
Size	Maximum dimension on ultrasound (in mm)
Echogenicity	Homogenous
	Heterogeneous
	Complex cystic
Adler’s index	Low (Grade I)
	Medium (Grade II)
	High (Grade III)

¹High risk microcalcifications refer to microcalcifications which show grouped, linear, or segmental distribution, or with a pleomorphic or branching morphology.

Table 2 Distribution of demographic and imaging parameters based on molecular subtype

	Total (n = 328)	DCIS (n = 53)	Luminal A (n = 139)	Luminal B (n = 38)	Her2 enriched (n = 50)	Triple negative (n = 48)
Mean age	61.1 ± 11.75	59.1 ± 11.67	61.8 ± 11.80	60.2 ± 12.23	62.0 ± 9.63	61.3 ± 12.60
Presentation
Clinic	237 (72%)	29 (55%)	98 (71%)	28 (74%)	36 (72%)	46 (96%)
Screening	91 (28%)	24 (45%)	41 (29%)	10 (26%)	14 (28%)	2 (4%)
Mass	200 (61%)	14 (26%)	91 (65%)	29 (76%)	29 (58%)	37 (77%)
Architectural distortion	17 (6%)	7 (13%)	10 (7%)	0 (0%)	0 (0%)	0 (0%)
Asymmetry	40 (12%)	6 (11%)	16 (12%)	3 (8%)	9 (18%)	6 (13%)
High-risk microcalcifications	105 (32%)	27 (51%)	33 (24%)	12 (32%)	24 (48%)	9 (19%)
Tumor size (on USG)
< 20	136 (41%)	22 (42%)	71 (51%)	20 (53%)	19 (38%)	4 (8%)
≥ 20	154 (47%)	9 (17%)	55 (40%)	17 (45%)	29 (58%)	44 (92%)
Margins (on USG)
Spiculated	100 (30%)	5 (9%)	63 (45%)	12 (32%)	8 (16%)	8 (17%)
Microlobulated	174 (60%)	23 (43%)	59 (42%)	25 (66%)	40 (80%)	29 (60%)
Circumscribed	16 (5%)	3 (6%)	4 (3%)	0 (0%)	0 (0%)	11 (23%)
Echogenicity (on USG)
Heterogeneous	144 (44%)	13 (25%)	58 (42%)	19 (50%)	28 (56%)	26 (54%)
Homogenous	146 (45%)	18 (34%)	68 (49%)	18 (47%)	20 (40%)	22 (46%)
Posterior acoustic features
Shadow	74 (23%)	5 (9%)	49 (35%)	10 (26%)	4 (8%)	6 (13%)
Enhancement	85 (26%)	5 (9%)	23 (17%)	8 (21%)	6 (32%)	33 (69%)
Mixed	36 (11%)	5 (9%)	15 (11%)	3 (8%)	9 (18%)	4 (8%)
None	95 (29%)	16 (30%)	39 (28%)	16 (42%)	19 (38%)	5 (10%)
Adler’s vascularity
High (Grade II & III)	81 (25%)	7 (13%)	22 (16%)	11 (29%)	21 (42%)	20 (42%)
Low (Grade I)	209 (64%)	24 (45%)	104 (75%)	26 (68%)	27 (54%)	28 (58%)
Axillary nodes
Present	56 (17%)	0 (0%)	25 (18%)	1 (3%)	14 (28%)	16 (33%)
Absent	234 (71%)	53 (100%)	101 (73%)	36 (95%)	34 (68%)	32 (67%)
Not visible on US	38 (14%)	22 (42%)	13 (9%)	1 (3%)	2 (1%)	0 (0%)

DCIS: Ductal carcinoma in situ; US: Ultrasound; USG: Ultrasonography.

Table 3 Binomial univariate and multivariate logistic regressions (ER/PR positive vs negative)

ER/PR positive vs negative		Univariate			Multivariate (AUC = 0.792)
		P	OR	CI	P	OR	CI
Posterior acoustic features¹	Enhancement	^d	0.46	(0.193 1.050)	^d	0.45	(0.174 1.143)
	Shadowing	^b	4.26	(1.617 11.633)	Not significant
Margins²	Spiculated	^a	4.16	(2.268 7.975)	^a	0.41	(1.085 4.606)
Margins²	Circumscribed	^a	0.15	(0.023 0.594)	Not significant
Size	Small < 20 mm	^c	4.51	(2.499 7.443)	^a	2.74	(1.475 5.204)

¹Mixed posterior acoustic features were set as the baseline with OR = 1.

²Microlobulated ultrasound margins were set as the baseline with OR = 1.

^aSignificant at the 0.001 level.

^bSignificant at the 0.01 level.

^cSignificant at the 0.05 level.

^dSignificant at the 0.10 level.

Area under the receiver operating characteristic curve for multivariate regression on posterior acoustic features, ultrasound margins, MM high-risk microcalcifications, and size (large or small).

Table 4 Binomial univariate and multivariate logistic regressions (Triple-negative breast cancer vs Non-triple-negative breast cancer)

TNBC vs Non-TNBC		Univariate			Multivariate (AUC = 0.853)
		P	OR	CI	P	OR	CI
Posterior acoustic features¹	Enhancement	^b	5.08	(1.808 18.201)	^a	4.77	(1.556 18.291)
Margins²	Spiculated	^a	0.43	(0.179 0.951)	Not significant
Margins²	Circumscribed	^c	11.00	(3.712 37.166)	^b	8.24	(2.151 38.923)
Size	Large > 20 mm	^c	13.2	(5.152 44.845)	^c	10.5	(3.792 38.436)
Axillary node metastasis	Yes	^b	2.52	(1.247 4.988)	Not significant
Adler’s Index	High	^a	2.12	(1.104 4.020)	Not significant
^aScreening	Yes	^d	0.003	(0.000 0.222)	^d	0.004	(0.000 0.452)
^aInteraction term	Screen × unit size	^d	1.17	(1.003 1.505)	^d	1.16	(1.001 1.430)

¹Mixed posterior acoustic features were set as the baseline with OR = 1.

²Microlobulated ultrasound margins were set as the baseline with OR = 1.

^aSignificant at the 0.001 level.

^bSignificant at the 0.01 level.

^cSignificant at the 0.05 level.

^dSignificant at the 0.10 level.

Area under the receiver operating characteristic curve for multivariate regression on posterior acoustic features, ultrasound margins, and size (large or small). AUC: Area under the receiver operating characteristic curve; TNBC: Triple-negative breast cancer.

Table 5 Binomial univariate and multivariate logistic regressions (HER2+ vs Non HER2+)

HER2+ vs Non HER2+		Univariate			Multivariate (AUC = 0.747)
HER2+ vs Non HER2+		P	OR	CI	P	OR	CI
Margins¹	Microlobulated	^c	3.92	(1.830 9.410)	^b	3.26	(1.469 8.026)
Margins¹	Circumscribed	Not significant			Not significant
High-risk microcalcifications	Present	^c	3.51	(1.804 6.821)	^c	3.38	(1.685 6.816)
Adler’s Index	High	^a	2.32	(1.203 4.437)	^a	1.99	(0.999 4.010)

¹Spiculated ultrasound margins were set as the baseline with OR = 1.

^aSignificant at the 0.001 level.

^bSignificant at the 0.01 level.

^cSignificant at the 0.05 level.

^dSignificant at the 0.10 level.

Area under the receiver operating characteristic curve for multivariate regression on ultrasound (US) margins, MM high-risk microcalcifications, and US Adler index (low or intermediate/high). AUC: Area under the receiver operating characteristic curve.

Table 6 Binomial univariate and multivariate logistic regressions (Ductal carcinoma in situ vs Invasive cancers)

DCIS vs Invasive cancers		Univariate			Multivariate (AUC = 0.719)
		P	OR	CI	P	OR	CI
Posterior acoustic features¹	None	^a	3.24	(1.204 10.292)	^a	3.45	(1.255 11.118)
High-risk microcalcifications	Present	^b	2.80	(1.516 5.208)	Not significant
Architectural distortions	Yes	^b	5.34	(1.546 16.709)	Not significant
Size	Small < 20 mm	^a	2.59	(1.420 7.361)	^a	2.72	(1.172 6.182)

¹Posterior acoustic enhancement was set as the baseline with OR = 1.

^aSignificant at the 0.001 level.

^bSignificant at the 0.01 level.

^cSignificant at the 0.05 level.

^dSignificant at the 0.10 level.

Area under the receiver operating characteristic curve for multivariate regression on posterior acoustic features, MM high-risk microcalcifications, architectural distortions, and size (large or small). AUC: Area under the receiver operating characteristic curve; DCIS: Ductal carcinoma in situ.

Table 7 Multinomial univariate logistic regressions: Impact of imaging features on relative odds of molecular subtypes

			Luminal A baseline			Luminal B baseline			DCIS baseline			HER2 enriched baseline			TNBC baseline
			P value	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI	P value	OR	95%CI
Posterior acoustic features	Shadowing	Luminal A vs							^d	3.27	(0.832 12.83)	^b	7.35	(1.979 27.300)
		Luminal B vs										^a	7.50	(1.307 43.030)
		DCIS vs	^d	0.31	(0.078 1.202)
		HER2+ vs	^b	0.14	(0.037 0.505)	^a	0.13	(0.023 0.765)
		TNBC vs
	Enhancement	Luminal A vs													^b	0.19	(0.055 0.633)
		Luminal B vs
		DCIS vs													^a	0.12	(0.024 0.610)
		HER2+ vs													^a	0.22	(0.058 0.807)
		TNBC vs	^b	5.38	(1.581 18.310)				^a	8.25	(1.638 41.55)	^a	4.64	(1.239 17.38)
Margins (on US)	Spiculated	Luminal A vs				^a	2.45	(1.130 5.31)	^b	5.41	(1.931 15.14)	^c	5.88	(2.544 13.58)	^c	4.26	(1.805 10.056)
		Luminal B vs	^a	0.41	(0.188 0.885)							^d	2.40	(0.861 6.690)
		DCIS vs	^b	0.19	(0.066 0.518)
		HER2+ vs	^c	0.17	(0.074 0.393)	^d	0.42	(0.150 1.16)
		TNBC vs	^c	0.24	(0.099 0.554)
	Circumscribed	Luminal A vs													^b	0.09	(0.019 0.445)
		Luminal B vs
		DCIS vs
		HER2+ vs
		TNBC vs	^b	10.8	(2.246 52.043)
Size	Large	Luminal A vs										^a	0.51	(0.258 0.999)	^c	0.07	(0.024 0.208)
		Luminal B vs													^c	0.08	(0.023 0.259)
		DCIS vs													^c	0.04	(0.010 0.134)
		HER2+ vs	^a	1.97	(1.001 3.878)										^c	0.14	(0.043 0.450)
		TNBC vs	^c	14.20	(4.811 41.915)	^c	12.94	(3.856 43.427)	^c	26.89	(7.445 97.114)	^c	7.21	(2.224 23.354)
High-risk Microcals	Present	Luminal A vs							^c	0.30	(0.154 0.583)	^b	0.34	(0.171 0.665)
		Luminal B vs							^d	0.44	(0.186 1.061)
		DCIS vs	^c	3.34	(1.715 6.488)	^d	2.25	(0.942 5.37)							^b	4.50	(1.606 9.96)
		HER2+ vs	^b	2.97	(1.504 5.844)										^b	4.00	(1.824 11.10)
		TNBC vs							^b	0.22	(0.090 0.548)		0.25	(0.100 0.623)
Adler	High	Luminal A vs										^c	0.27	(0.131 0.566)	^b	0.30	(0.142 0.618)
		Luminal B vs
		DCIS vs										^d	0.38	(0.136 1.037)	^d	0.41	(0.147 1.131)
		HER2+ vs	^c	3.68	(1.767 7.650)				^d	2.67	(0.965 7.37)
		TNBC vs	^b	3.38	(1.618 7.045)				^d	2.45	(0.884 6.78)
Axillary node adenopathy	Yes	Luminal A vs				^a	3.08	(1.063 61.96)							^a	0.44	(0.209 0.919)
		Luminal B vs	^a	0.12	(0.224 0.470)							^a	0.07	(0.009 0.556)	^b	0.05	(0.007 0.430)
		DCIS vs
		HER2+ vs				^a	14.40	(1.798 115.17)
		TNBC vs	^a	2.28	(1.088 4.778)	^b	18.50	(2.323 147.34)

^aSignificant at the 0.001 level.

^bSignificant at the 0.01 level.

^cSignificant at the 0.05 level.

^dSignificant at the 0.10 level.

Only statistically significant results are shown. Bold results show higher relative odds. DCIS: Ductal carcinoma in situ; TNBC: Triple-negative breast cancer; US: Ultrasound.

Citation: Ian TWM, Tan EY, Chotai N. Role of mammogram and ultrasound imaging in predicting breast cancer subtypes in screening and symptomatic patients. World J Clin Oncol 2021; 12(9): 808-822
URL: https://www.wjgnet.com/2218-4333/full/v12/i9/808.htm
DOI: https://dx.doi.org/10.5306/wjco.v12.i9.808