Ultrasonography: an aid in molecular subtyping of breast carcinoma

Thakur, Shruti; Thakur, Charu Smita; Thakur, Vijay; Rana, Nidhi; Jhobta, Anupam; Kapila, Sumala

doi:10.15557/JoU.2025.0003

Figures & Tables

A 45-year-old female with invasive ductal carcinoma and luminal type A molecular subtype of breast cancer. Ultrasound image A. gray scale shows an irregular hypoechoic lesion, taller than wider, having spiculated margins, thick echogenic rim, and posterior acoustic shadowing, B. color Doppler shows minimal peripheral vascularity

A 55-year-old female with invasive lobular carcinoma and luminal type B HER2-positive molecular subtype of breast cancer. Ultrasound image A. gray scale shows an irregular hypoechoic lesion, taller than wider, having spiculated and microlobulated margins, and posterior acoustic shadowing B. color Doppler shows internal vascularity

A 45-year-old female with invasive ductal carcinoma and HER2/neu-enriched type molecular subtype of breast cancer. Ultrasound image A. gray scale shows a heterogeneously hypoechoic mass with multiple echogenic foci of calcification B. color Doppler shows internal vascularity

A 48-year-old female with invasive ductal carcinoma and triple-negative molecular subtype of breast cancer. Ultrasound image A. gray scale shows a well-circumscribed hypoechoic mass with macrolobulations and posterior acoustic enhancement B. color Doppler shows internal vascularity

Association of vascularity with estrogen, progesterone and HER2/neu receptor

Vascularity	Absent	Present	Total	p value
ER-negative (n = 16)	6 (35.29%)	10 (29.41%)	16 (31.37%)	0.67^†
ER-positive (n = 35)	11 (64.71%)	24 (70.59%)	35 (68.63%)
Total	17 (100%)	34 (100%)	51 (100%)
PR-negative (n = 23)	7 (41.18%)	16 (47.06%)	23 (45.10%)	0.691^†
PR-positive (n = 28)	10 (58.82%)	18 (52.94%)	28 (54.90%)
Total	17 (100%)	34 (100%)	51 (100%)
HER2/neu-negative (n = 33)	11 (64.71%)	22 (64.71%)	33(64.71%)	1^†
HER2/neu-positive (n = 18)	6 (35.29%)	12 (35.29%)	18 (35.29%)
Total	17 (100%)	34 (100%)	51 (100%)

Association of vascularity and its type with molecular subtype

Vascularity	HER2/neu-enriched type (n = 9)	Luminal type A (n = 17)	Luminal type B HER2-ve (n = 6)	Luminal type B HER2+ve (n = 9)	Triple-negative type (n = 10)	Total	p
Absent	4 (23.53%)	6 (35.29%)	2 (11.76%)	2 (11.76%)	3 (17.65%)	17 (100%)	0.823^*
Present	5 (14.71%)	11 (32.35%)	4 (11.76%)	7 (20.59%)	7 (20.59%)	34 (100%)
Total	9 (17.65%)	17 (33.33%)	6 (11.76%)	9 (17.65%)	10 (19.61%)	51 (100%)
Type of vascularity	HER2/neu-enriched type (n = 5)	Luminal type A (n = 11)	Luminal type B HER2-ve (n = 4)	Luminal type B (n = 7)	Triple-negative type (n = 7)	Total	p
Internal vascularity	4 (16.67%)	7 (29.16%)	3 (12.5%)	6 (25%)	4 (16.67%)	24 (100%)	0.312^*
Vessels in rim	1 (10%)	4 (40%)	1 (10%)	1 (10%)	3 (30%)	10 (100%)
Total	5 (14.71%)	11 (32.35%)	4 (11.76%)	7 (20.59%)	7 (20.59%)	34 (100%)

Distribution of pathological types, receptor status, and molecular subtypes of breast cancer

Type of tumor	Frequency	Percentage
Invasive ductal carcinoma	48	94.12%
Invasive lobular carcinoma	2	3.92%
Mucinous carcinoma	1	1.96%
Total	51	100.00%
Receptor status	Frequency	Percentage
Estrogen receptor	35	68.63%
Progesterone receptor	28	54.90%
HER2/neu receptor	18	35.29%
Molecular subtype	Frequency	Percentage
HER2/neu-enriched type	9	17.65%
Luminal type A	17	33.33%
Luminal type B (HER−ve)	6	11.76%
Luminal type B (HER+ve)	9	17.65%
Triple-negative type	10	19.61%
Total	51	100.00%

Association of ultrasonographic features with molecular subtypes of breast cancer

Margin	HER2/neu-enriched Odds ratio type [CI] (p)	Luminal type A Odds ratio [CI] (p)	Luminal type B Odds ratio HER2-ve [CI] (p)	Luminal type B Odds ratio HER2+ve [CI] (p)	Triple-negative type Odds ratio [CI] (p)
Circumscribed margins	0.64 [0.081–3.365] (0.60)	0.64 [0.151–2.436] (0.51)	1.22 [0.142–7.791] (0.82)	0.25 [0.01–1.83] (0.21)	*5.12^ [ 1.16–24.85] (0.03)**
Posterior features	0.82 [0.147–6.761] (0.80)	2.274 [ 0.453–17.45] (0.35)	1.24 [0.147–32.88] (0.84)	0.21 [0.041–1.14] (0.07)	2.5 [0.337–61.82] (0.44)
Enhancement	2.72 [ 0.597–13.18] (0.19)	0.278 [0.055–1.099] (0.06)	0.335 [0.013–2.683] (0.36)	¥	*29.42^ [4.117–725.4] (<0.001)**
Shadowing	0.17 [0.007–1.21] (0.08)	*3.85^ [1.12–13.98] (0.02)**	1.79 [0.278–11.53] (0.52)	2.45 [0.539–11.78] (0.24	¥
Mixed	1.608 [0.055–17.2] (0.69)	2.099 [0.202–21.8] (0.50)	2.72 [0.089–31.27] (0.46)	¥	¥
Vascularity	0.567 [0.123–2.727] (0.46)	0.8791 [0.253–3.181] (0.83)	1 [0.158–8.562] (0.97)	1.92 [0.37–14.98] (0.47)	1.20 [0.270–6.519] (0.83)
Internal vascularity	1.77 [0.189–49.21] (0.68)	0.62 [0.127–3.22] (0.56)	1.27 [0.118–37.42] (0.89)	2.91 [0.354–76.72] (0.37)	0.47 [0.0783–3.131] (0.42)
Vessels in rim	0.56 [0.02–5.272] (0.68)	1.59 [0.31–7.838] (0.56)	0.78 [0.026–8.417] (0.89)	0.34 [0.013–2.818] (0.37)	2.09 [0.319–12–76] (0.42)

Distribution of ultrasound findings of breast mass in the study subjects

Ultrasound findings	Frequency (n = 51)	Percentage
Size
Large (≥2 cm)	37	72.55%
Small (<2 cm)	14	27.45%
Shape
Irregular	39	76.47%
Oval	11	21.57%
Round	1	1.96%
Margin
Circumscribed	15	29.41%
Non-circumscribed	36	70.59%
Echo pattern
Heterogenous	16	31.37%
Hyperechoic	5	9.80%
Hypoechoic	30	58.82%
Posterior acoustic features
No posterior features	10	19.61%
Enhancing	18	35.29%
Shadowing	19	37.25%
Mixed	4	7.84%
Calcifications
Absent	28	54.90%
Present	23	45.10%
Vascularity
Absent	17	33.33%
Internal vascularity	24	47.06%
Vessels in rim	10	19.61%

Association of margins and posterior acoustic features with estrogen and progesterone receptors

Variables	ER-negative (n = 16)	ER-positive (n = 35)	Total	p value	PR-negative (n = 23)	PR-positive (n = 28)	Total	p value
Margin
Circumscribed	7 (46.67%)	8 (53.33%)	15 (100%)	0.129^†	8 (53.33%)	7 (46.67%)	15 (100%)	0.446^†
Non-circumscribed	9 (25%)	27 (75%)	36 (100%)		15 (41.67%)	21 (58.33%)	36 (100%)
Total	16 (31.37%)	35 (68.62%)	51 (100%)		23 (45.10%)	28 (54.90%)	51 (100%)
Posterior acoustic features
No posterior features	3 (30%)	7 (70%)	10 (100%)	<0.0001^*	5 (50%)	5 (50%)	10 (100%)	<0.0001^*
Enhancing	12 (66.67%)	6 (33.33%)	18 (100%)		15 (83.33%)	3 (16.67%)	18 (100%)
Shadowing	0 (0%)	19 (100%)	19 (100%)		1 (5.26%)	18 (94.74%)	19 (100%)
Mixed	1 (25%)	3 (75%)	4 (100%)		2 (50%)	2 (50%)	4 (100%)
Total	16 (31.37%)	35 (68.62%)	51 (100%)		23 (45.10%)	28 (54.90%)	51 (100%)

Association of margin and posterior acoustic features with HER2/neu receptor

Margin	HER2/neu-negative (n = 33)	HER2/neu-positive (n = 18)	Total	p value
Circumscribed	12 (80%)	3 (20%)	15 (100%)	0.202^*
Non-circumscribed	21 (58.33%)	15 (41.67%)	36 (100%)
Total	33 (64.71%)	18 (35.29%)	51 (100%)
Posterior features
No posterior features	4 (40%)	6 (60%)	10 (100%)	0.37^*
Enhancing	13 (72.22%)	5 (27.78%)	18 (100%)
Shadowing	13 (68.42%)	6 (31.58%)	19 (100%)
Mixed	3 (75%)	1 (25%)	4 (100%)
Total	33 (64.71%)	18 (35.29%)	51 (100%)

Association of margin and posterior acoustic features with molecular subtype

Margin	HER2/neu-enriched type (n = 9)	Luminal type A (n = 17)	Luminal type B HER2-ve (n = 6)	Luminal type B HER2+ve (n = 9)	Triple-negative type (n = 10)	Total	p
Circumscribed	2 (13.33%)	4 (26.66%)	2 (13.33%)	1 (6.67%)	6 (40%)	15 (100%)	0.138^*
Non-circumscribed	7 (19.44%)	13 (36.11%)	4 (11.11%)	8 (22.22%)	4 (11.11%)	36 (100%)
Total	9 (17.65%)	17 (33.33%)	6 (11.76%)	9 (17.65%)	10 (19.61%)	51 (100%)
Posterior features	HER2/neu-enriched type (n = 9)	Luminal type A (n = 17)	Luminal type B HER2-ve (n = 6)	Luminal type B HER2+ve (n = 9)	Triple-negative type (n = 10)	Total	p
No posterior features	2 (20%)	2 (20%)	1 (10%)	4 (40%)	1 (10%)	10 (100%)	<0.0001^*
Enhancing	5 (27.78%)	3 (16.67%)	1 (10%)	0 (0%)	9 (50%)	18 (100%)
Shadowing	1 (5.26%)	10 (52.63%)	3 (15.79%)	5 (26.32%)	0 (0%)	19 (100%)
Mixed	1 (25%)	2 (50%)	1 (25%)	0 (0%)	0 (0%)	4 (100%)
Total	9 (17.65%)	17 (33.33%)	6 (11.76%)	9 (17.65%)	10 (19.61%)	51 (100%)

Association of type of vascularity with estrogen, progesterone and HER2/neu receptor

Type of vascularity	Internal vascularity	Vessels in rim	Total	p value
ER-negative (n = 10)	7 (29.17%)	3 (30%)	10 (29.41%)	1^†
ER-positive (n = 24)	17 (70.83%)	7 (70%)	24 (70.59%)
Total	24 (100%)	10 (100%)	34 (100%)
PR-negative (n = 16)	12 (50%)	4 (40%)	16 (47.06%)	0.715^†
PR-positive (n = 18)	12(50%)	6(60%)	18 (52.94%)
Total	24 (100%)	10 (100%)	34 (100%)
HER2/neu-negative (n = 22)	13 (54.17%)	9 (90%)	22 (64.71%)	0.061^†
HER2/neu-positive (n = 12)	11 (45.83%)	1 (10%)	12 (35.29%)
Total	24 (100%)	10 (100%)	34 (100%)

Association of ultrasonographic features with hormone receptor and HER2/neu status

Imaging feature (n = 51)	Outcome characteristic	Odds ratio (OR)	Confidence interval (CI)	p value
Circumscribed margins	Estrogen receptor	0.38	0.1–1.4	0.129
	Progesterone receptor	0.625	0.18–2.1	0.45
	HER2/neu receptor	0.356	0.07–1.43	0.15
Posterior features	Estrogen receptor	0.92	0.17–4.15	0.94
	Progesterone receptor	1.272	0.298–5.428	0.741
	HER2 neu receptor	0.28	0.06–1.218	0.09
Enhancement	Estrogen receptor	0.074	0.016–0.298	<0.001
	Progesterone receptor	0.068	0.013–0.280	<0.001
	HER2/neu receptor	0.59	0.157–2.073	0.43
Shadowing	Estrogen receptor	¥
	Progesterone receptor	36.58	5.527–866.1	<0.001
	HER2 neu receptor	0.77	0.218–2.598	0.69
Mixed	Estrogen receptor	1.356	0.133–38.17	0.857
	Progesterone receptor	0.81	0.078–8.343	0.850
	HER2/neu receptor	0.59	0.021–6.022	0.72
Vascularity (n = 34)	Estrogen receptor	1.30	0.356–4.588	0.68
	Progesterone receptor	0.79	0.232–2.611	0.705
	HER2/neu receptor	1	0.291–3.592	0.75
Internal vascularity	Estrogen receptor	5.65	1.656–21.12	0.003
	Progesterone receptor	1	0.315–3.17	0,77
	HER2/neu receptor	0.72	0.224–2.282	0.56
Vessels in rim	Estrogen receptor	4.949	0.746–40.82	0.07
	Progesterone receptor	2.158	0.348–4.71	0.37
	HER2/neu receptor	0.019	0.0005–0.234	<0.001

Ultrasonography: an aid in molecular subtyping of breast carcinoma

Figures & Tables

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Association of vascularity with estrogen, progesterone and HER2/neu receptor

Association of vascularity and its type with molecular subtype

Distribution of pathological types, receptor status, and molecular subtypes of breast cancer

Association of ultrasonographic features with molecular subtypes of breast cancer

Distribution of ultrasound findings of breast mass in the study subjects

Association of margins and posterior acoustic features with estrogen and progesterone receptors

Association of margin and posterior acoustic features with HER2/neu receptor

Association of margin and posterior acoustic features with molecular subtype

Association of type of vascularity with estrogen, progesterone and HER2/neu receptor

Association of ultrasonographic features with hormone receptor and HER2/neu status

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