Background parenchymal enhancement: behavior during neoadjuvant chemotherapy for breast cancer and relationship with a pathological complete response

Teixeira, Sandra Regina Campos; Camargo Júnior, Hélio Sebastião Amâncio de; Cabello, Cesar

doi:10.1590/0100-3984.2019.0057

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Original Article • Radiol Bras 53 (2) • Mar-Apr 2020 • https://doi.org/10.1590/0100-3984.2019.0057 copy

Background parenchymal enhancement: behavior during neoadjuvant chemotherapy for breast cancer and relationship with a pathological complete response

Realce de fundo do parênquima: comportamento durante quimioterapia neoadjuvante para câncer de mama e relação com resposta patológica completa

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

To evaluate background parenchymal enhancement (BPE) and its characteristics, as well as its behavior before and after neoadjuvant chemotherapy (NAC), in both breasts of patients with unilateral breast cancer.

Materials and Methods:

This was a retrospective, cross-sectional observational study involving a consecutive sample of women with invasive breast cancer who underwent breast magnetic resonance imaging (MRI) between July 2007 and July 2017, as well as undergoing dynamic contrast-enhanced MRI before and after NAC. In both breasts, we evaluated the BPE in accordance with the Breast Imaging Reporting and Data System. We applied logistic regression analysis, and values of p < 0.05 were considered significant.

Results:

We evaluated 150 women. The mean age was 45.2 years (range, 20-74 years). The variables correlating independently with a high pre-NAC BPE, in the affected and contralateral breasts, were being under 50 years of age (odds ratio [OR] = 6.55; 95% confidence interval [95% CI]: 2.32-18.46, for both breasts) and a post-NAC BPE reduction (OR = 17.75; 95% CI: 4.94-63.73 and OR = 18.47; 95% CI: 5.19-66.49, respectively).

Conclusion:

Patients with invasive unilateral breast cancer who have a high pre-NAC BPE in both breasts tend to be under 50 years of age and to show a post-NAC reduction in BPE.

Keywords:
Breast neoplasms/diagnostic imaging; Magnetic resonance imaging/methods; Antineoplastic agents/therapeutic use; Neoadjuvant treatment; Treatment outcome; Parenchymal tissue/diagnostic imaging

Characteristic	Affected breast^* * Bolding indicates significance.
Characteristic	Minimal/mild (%)	Moderate/marked (%)	Total (%)	P
Age at dagnos s (years)
<40	28 (31.1)	26 (43.3)	54 (36)
40-49	18 (20.0)	27 (45.0)	45 (30)
≥50	44 (48.9)	7 (11.7)	51 (34)	<0.001
Total	90 (100)	60 (100)	150 (100)
Menopausal status
Premenopausal	50 (55.6)	51 (85.0)	101(67.3)
Postmenopausal	40 (44.4)	9 (15.0)	49 (32.7)	<0.001
Total	90 (100)	60 (100)	150 (100)
Body mass index
18.5-24.9 kg/m2 (normal-weight)	34 (47.9)	26 (56.5)	60 (513)
25.0-29.9 kg/m2 (overweight)	26 (36.6)	14 (30.4)	40 (34.2)
≥30.0 kg/m² (Obese)	11 (15.5)	6 (13.0)	17 (14.5)	0.659
Total	71 (100)	46 (100)	117 (100)
Tumor grade^† † Nottingham grading system.
1	3 (3.4)	1 (1-6)	4 (2.7)
2	52 (60.2)	29 (47.5)	81 (555)
3	32 (36.4)	29 (50.8)	61 (418)	0.359
Total	87 (100)	59 (100)	146 (100)
HER2 status
Negative	65 (72.2)	40 (66.7)	105 (70.0)
Positive	25 (27.8)	20 (33.3)	45 (30.0)	0.467
Total	90 (100)	60 (100)	150 (100)
Estrogen receptor status
Negative	40 (44.4)	27 (45.0)	67 (44.7)
Positive	50 (55.6)	33 (55.0)	83 (55.3)	0.947
Total	90 (100)	60 (100)	150 (100)
Progesterone receptor status
Negative	56 (62.2)	32 (53.3)	88 (58.7)
Positive	34 (37.8)	28 (46.7)	62 (41.3)	0.279
Total	90 (100)	60 (100)	150 (100)
Ki67 status
Negative	27 (30.3)	21 (35.0)	48 (32.2)
Positive	62 (69.7)	39 (65.0)	101 (67.8)	0.550
Total	89 (100)	60 (100)	149 (100)
Tumor subtype
Luminal A	14 (15.6)	12 (20.0)	26 (17.3)
Luminal B	24 (26.7)	11 (18.3)	35 (23.3)
HER2	12 (13.3)	9 (15.0)	21 (14.0)
Luminal B HE32	13 (14.4)	11 (18.3)	24 (16.0)	0.772
Tripie-negative	27 (30.0)	17 (28.3)	44 (29.4)
Total	90 (100)	60 (100)	150 (100)
Fibroglandular tissue (on MRI)
Almost entirely fat	0	1 (1-7)	1 (0.7)
Scattered fibroglanoular tissue	67 (74.4)	30 (50.0)	97 (64.7)
Heterogeneous fibroglandular tissue	22 (24.4)	25 (41.7)	47 (31.3)	0.004
Extreme fibroglandular tissue	1 (1.1)	4 (6.7)	5 (3.3)
Total	90 (100)	60 (100)	150 (100)
Breast density (on mammography)
Almost entirely fat	3 (4.1)	0	3 (2.4)
Scattered areas of fibroglanduar density	41 (56.2)	23 (45.1)	64 (51.6)
Heterogeneously dense	28 (38.3)	23 (45.1)	51 (41.1)	0.051
Extremer/ dense	1 (14)	5 (9.8)	6 (4.8)
Total	73 (100)	51 (100)	124 (100)
Post-NAC change in BPE^‡ ‡ After NAC, the BPE became symmetric in all cases and was marked in none.
Ncre or increase	49 (54.4)	3 (5.0)	52 (34.7)
Reduction	41 (45.6)	57 (95.0)	98 (65.3)	<0.001
Total	90 (100)	60 (100)	150 (100)

Characteristic	Contralate-al breast^* * Bolding indicates significance.
Characteristic	Minimal/mild (%)	Moderate/martted (%)	Total (%)	P
Age at diagnosis (years)
<40	29 (31.2)	25 (43.9)	54 (36.0)
40-49	19 (20.4)	26 (45.6)	45 (30.0)
≥50	45 (48.4)	6 (10.5)	51 (34.0)	< 0.001
Total	93 (100)	57 (100)	150 (100)
Menopausal status
Premenopausal	53 (57.0)	48 (84.2)	101 (67.3)
Postmenopausal	40 (43.0)	9 (15.8)	49 (32.7)	< 0.001
Total	93 (100)	57 (100)	150 (100)
Body mass index
18.5–24.9 kg/m2 (normal-weight)	38 (48.7)	24 (55.8)	60 (51.3)
25.0-29.9 kg/m² (overweight)	26 (35.1)	14 (32.6)	40 (34.2)
≥30.0 kg/m² (ocese)	12 (18.2)	5 (11.6)	17 (14.5)	0.698
Total	74 (100)	43 (100)	117 (100)
Tumor grade^† † Nottingham grading system.
1	3 (3.3)	1 (1-6)	4 (2.7)
2	52 (58.9)	29 (49.2)	81 (55.5)
3	34 (37.8)	27 (49.2)	61 (41.8)	0.539
Total	69 (100)	57 (100)	146 (100)
HER2 status
Negative	68 (73.1)	37 (64.9)	105 (70.0)
Positive	25 (28.9)	20 (35.1)	45 (30.0)	0.287
Total	93 (100)	57 (100)	150 (100)
Estrogen receptor status
Negative	40 (42.1)	27 (45.8)	67 (44.7)
Positive	53 (57.9)	30 (54.3)	83 (55.3)	0.602
Total	93 (100)	57 (100)	150 (100)
Progesterone receptor status
Negative	57 (81.3)	31 (54.4)	88 (58.7)
Positive	38 (38.7)	26 (45.6)	62 (41.3)	0.405
Total	93 (100)	57 (100)	150 (100)
Ki67 status
Negative	29 (31.5)	19 (33.3)	48 (32.2)
Positive	63 (68.5)	38 (66.7)	101 (67.8)	0.818
Total	89 (100)	57 (100)	149 (100)
Tumor subtype
Luminal A	15 (16.1)	11 (19.3)	26 (17.3)
Luminal B	26 (28.0)	9 (15.8)	35 (23.3)
HER2	12 (12.9)	9 (15.8)	21 (14.0)
Luminal BHER2	13 (14.0)	11 (19.3)	24 (16.0)	0.511
Triple-negatve	27 (29.0)	17 (29.8)	44 (29.4)
Total	93 (100)	57 (100)	150 (100)
Fibroglandular tissue (on MRl)
Almost entirely fat	0	1 (1-8)	1 (0.7)
Scattered fibroglandular tissue	68 (73.1)	29 (50.9)	97 (64.7)
Heterogeneous fibroglandular tissue	24 (25.8)	23 (40.3)	47 (31.3)	0.008
Extreme fibroglandular tissue	1(1.1)	4 (7.0)	5 (3.3)
Total	93 (100)	57 (100)	150 (100)
Breast density (on mammography)
Almost entirely fat	3 (4.0)	0	3 (2.4)
Scattered areas of fibroglandular density	41 (54.7)	23 (46.9)	64 (51.6)
Heterogeneously dense	30 (40.0)	21 (42.9)	51 (41.1)	0.069
Extremely dense	1 (1-3)	5 (10.2)	6 (4.8)
Total	75 (100)	49 (100)	124 (100)
Post-NAC charge in BPE^‡ ‡ After NAC, the BPE became symmetric in all cases and was marked in none.
None or increase	52 (55.9)	3 (5.3)	55 (36.7)
Reduction	41 (44.1)	54 (94.7)	95 (63.3)	< 0.001
Total	93 (100)	57 (100)	150 (100)

Variable	Category	Univariate analysis^* * Bolding indicates significance. (n = 150)			Stepwise multivariate analysis^* * Bolding indicates significance. (n = 137)
Variable	Category	P	OR^† † For moderate/marked pre-NAC BPE (n = 56) vs. minimal/mild pre-NAC BPE (n = 81).	95% CI	P	OR^‡ ‡ For moderate/marked pre-NAC BPE (n = 60) vs. minimal/mild pre-NAC BPE (n = 90).	95% CI
Age at dagnoss (years)	≥ 50 (ref.)	-	1.00	-	-	1.00	-
	<50	<0.001	7.24	2.97-17.64	<0.001	6.88	2.45-19.34
Body mass index	18.5-24.9 kgm² (normal-weight, ref.)	-	1.00	-	-	-	-
	25.0-29.9 kg/m² (overweight)	0.405	0.70	0.31-1.61	-	-	-
	≥30.0 kg/m2 (obese)	0.554	0.71	0.23-2.18	-	-	-
Menopausal status	Postmenopausal (ref.)	-	1.00	-	-	-	-
	Premenopausal	<0.001	4.53	1.99-10.31	-	-	-
Breast density	Fat/scattered fibroglandular density (ref.)	-	1.00	-	-	-	-
	Heterogeneously/extremely dense	0.097	1.85	0.90-3.81	-	-	-
Fibroglandular tissue	Fat/scattered fibroglandular tissue (ref.)	-	1.00	-	-	-	-
	Heterogeneous/extreme	0.005	2.73	1.36-5.45	-	-	-
Post-NAC change in BPE, affected breast	None or increase (ref.)	—	1.00	—	—	1.00	—
	Reduction	<0.001	22.70	6.62-77.88	<0.001	17.75	4.94-63.73
Post-NAC change in BPE, contralateral breast	None or increase (ref.)	-	1.00	-	-	-	-
	Reduction	<0.001	10.76	4.20-27.53	-	-	-
Tumor grade^§ § Nottingham grading system.	1 or 2 (ref.)	-	1.00	-	-	-	-
	3	0.138	1.68	0.85-3.25	-	-	-
Tumor subtype	Luminal B (ref.)	-	1.00	-	-	-	-
	Luminal A	0.243	1.87	0.65-5.35	-	-	-
	HER2+ or Luminal B HER2+	0.238	1.75	0.69-4.40	-	-	-
	Triple-negative	0.507	1.37	0.54-3.51	-	-	-
Estrogen receptor status	Negative (ref.)	-	1.00	-	-	-	-
	Positive	0.947	0.98	0.51-1.89	-	-	-
Progesterone receptor status	Negatve (ref.)	-	1.00	-	-	-	-
	Positive	0.280	144	0.74-2.80	-	-	-
HER2 status	Negative (ref.)	-	1.00	-	-	-	-
	Positive	0.468	1.30	0.64-2.64	-	-	-
Ki67 status	Negative (ref.)	—	1.00	—	—	-	—
	Positive	0.551	0.81	0.40-1.62	-	-	-
Clinical pre-NAC tumor size	Continuous variable	0.703	0.964	0.798-1.165	-	-	-
Ultrasound pre-NAC tumor size	Continuous variable	0.183	0.860	0.690-1.073	-	-	-
MRI pre-NAC tumor size	Continuous variable	0.598	0.9S8	0.816-1.124	-	-	-

Variable	Category	Univariate analysis^* * Bolding indicates significance. (n = 150)			Stepwise multivariate analysis^* * Bolding indicates significance. (n = 137)
Variable	Category	P	OR^† † For moderate/marked pre-NAC BPE (n = 56) vs. minimal/mild pre-NAC BPE (n = 81).	95% CI	P	OR^‡ ‡ For moderate/marked pre-NAC BPE (n = 60) vs. minimal/mild pre-NAC BPE (n = 90).	95% CI
Age at diagnosis (years)	≥ 50 (ref.)	—	1.00	—	—	1.00	—
	<50	<0.001	7.97	3.12-20.37	<0.001	6.55	2.32-18.46
Body mass index	18.5-24.9 kg/m2 (normal-weight, ref.)	-	1.00	-	-	-	-
	25.0-29.9 kg/m² (overweight)	0.614	0.81	0.35-1.85	-	-	-
	≥ 30.0 kg'm² (obese)	0.429	0.63	0.20-2.00	-	-	-
Menopausal status	Postmenopausal (ref.)	-	1.00	-	-	-	-
	Premenopausal	<0.001	4.03	1.77-9.16	-	-	-
Breast density	Fat/scattered fibroglandular density (ref.)	-	1.00	-	-	-	-
	Heterogeneously/extremely dense	0.201	1.60	0.78-3.31	-	-	-
Fibroglandular tissue	Fat/scattered fibroglandular tissue (ref.)	-	1.00	-	-	-	-
	Heterogeneous/extreme	0.011	2.45	1.22-4.90	-	-	-
Post-NAC change in BPE, affected breast	None or increase (ref.)	-	1.00	-	-	-	-
	Reduction	<0.001	20.04	585-68.66	-	-	-
Post-NAC change in BPE, contralateral breast	None or increase (ref.)	-	1.00	-	-	1.00	-
	Reduction	<0.001	22.83	6.66-78.30	<0.001	18.57	5.19-68.49
Tumor grade^§ § Nottingham grading system.	1 or 2 (ref.)	-	1.00	-	-	-	-
	3	0.274	1.46	0.74-2.85	-	-	-
Tumor subtype	Luminal B (ref.)	-	1.00	-	-	-	-
	Luminal A	0.176	2.12	0.72-628	-	-	-
	HER2+ or Luminal B HER2+	0.087	2.31	0.89-6.03	-	-	-
	Triple-negative	0.227	1.82	0.69-4.80	-	-	-
Estrogen receptor status	Negative (ref.)	-	1.00	-	-	-	-
	Positive	0.603	0.84	0.43-L63	-	-	-
Progesterone receptor status	Negative (ref.)	-	1.00	-	-	-	-
	Positive	0.405	1.33	0.68-2.59	-	-	-
HER2 status	Negative (ref.)	-	1.00	-	-	-	-
	Positive	0.288	1.47	0.72-3.00	-	-	-
Ki67 status	Negative (ref.)	-	1.00	-	-	-	-
	Positive	0.818	0.92	0.46-1.86	-	-	-
Clinical pre-NAC tumor size	Continuous variable	0.420	0.923	0.759-1.22	-	-	-
Ultrasound pre-NAC tumor size	Continuous variable	0.287	0.887	0.711-1.106	-	-	-
MRI pre-NAC tumor size	Continuous variable	0.267	0.911	0.773-1.074	—	—	—

variable	Category	P ^* * Bolding indicates significance.	OR^† † For achieving a pCR (n = 67) vs. not achieving a pCR (n = 79).	95% Cl
Symmetry of pre-NAC BPE	Asymmetric (reference)	-	1.00	-
	Symmetric	0.316	4.21	0.11-15L98
Level of pre-NAC BPE, affected breast	Minimal (reference)	-	1.00	-
	Mild	0.728	1.19	0.44-3.22
	Moderate	0.375	1.66	0.54-5.04
	Marked	0.829	0.87	0.24-3.13
Level of pre-NAC BPE, contralateral breast	Minimal (reference)	-	1.00	-
	Mild	0.811	1.13	0.42-3.04
	Moderate	0.302	1.80	0.59-5.53
	Marked	0.919	0.94	0.26-3.41
Post-NAC change in BPE, affected breast	None or increase (reference)	-	1.00	-
	Reduction	0.007	2.94	1.34 - 6.42
Post-NAC change in BPE, contralateral breast	None or increase (reference)	-	1.00	-
	Reduction	0.003	3.19	1.48-6.91

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[1] Correspondence: Dr. Sandra Regina Campos Teixeira. CDE - Diagnóstico por Imagem. Avenida Itapura, 933, Guanabara. Campinas, SP, Brazil, 13020-431. Email: santx@icloud.com.