Background parenchymal enhancement in breast MRI before and after neoadjuvant chemotherapy: correlation with tumour response

Eur Radiol (2016) 26:1590–1596

ByDR. Naglaa Mahmoud

KCCC

Objectives

To correlate the decrease in background parenchymal enhancement (BPE) and tumour response measured with MRI in breast cancer patients treated with neoadjuvant chemotherapy (NAC).

Introduction

Contrast enhancement of fibroglandular tissue on magnetic resonance imaging (MRI) of the female breast is referred to as background parenchymal enhancement (BPE).

The amount of BPE is classified as minimal, mild, moderate or marked according to the BI-RADS® lexicon.

Although there are similarities in the classifications, it was shown that BPE does not correlate with the mammographic breast density.

In contrast-enhanced breast MRI, BPE is known to be influenced by the hormonal status of the patient.

BPE itself influences the accuracy of the radiologist’s tumour size estimation, with inaccurate estimation of the tumour size found in patients with moderate and marked BPE.

The influence of breast cancer treatment on the degree of BPE has been previously investigated.

In addition to surgical therapy, radiation, chemotherapy and antihormonal medications are well established in the treatment of breast cancer.

It was previously shown that whole breast radiation after breast conserving therapy was associated with a decrease of BPE in the irradiated breast.

A reduction of BPE in the contralateral breast was also observed.

However, many of the patients were treated not with radiotherapy alone but with additional chemotherapy or antihormonal medication.

Hence, the reduction of BPE may have been caused by any of these therapies or by their combination.

A quantitatively measured reduction of BPE by neoadjuvant chemotherapy (NAC) in the contralateral breast has already been shown.

An almost complete suppression of BPE due to Taxane containing NAC was observed in another study.

A reduction of BPE due to antihormonal medication has also been shown.

A reduction of BPE due to aromatase inhibitor therapy was observed in approximately one-third of the patients treated.

The decrease in BPE following Tamoxifen treatment was observed in the first 90 days of the treatment but did not significantly decrease any further thereafter.

Additionally, this effect was partly reversible because BPE increased again after the switch from Tamoxifen to an aromatase inhibitor, which caused a smaller reduction of BPE.

In the present study, none of the patients received any treatment other than chemotherapy before surgery.

Thus, the aim of this study was to analyse the effects of NAC alone on BPE, as classified according to the BI-RADS® 2013 categories, andto analyse the relationship between the change in BPE and tumour response.

Materials and methods

All patients who presented with biopsy-proven breast cancer during a time period of 24 months were analysed to identify those who received NAC.

73 patients with 80 breast cancers treated with NAC were retrospectively reviewed.

The inclusion criteria were that the patient received at least 6 cycles of chemotherapy and that MRI data were available from both before and after NAC.

The mean patient age at the time of the breast cancer diagnosis was 48.5±9.9 years (26.8–71.2 years).

The pre- or postmenopausal status of the patients was noted, as were the tumour characteristics, such as the cancer type (invasive ductal, invasive lobular or other carcinomas), hormone receptor status (oestrogen (ER), progesterone (PR), human epidermal growth factor receptor 2 (HER2) and nodal status.

Because all of the patients had biopsy proven breast cancer, MRI was performed regardless of the menstrual cycle to avoid a delay in treatment.

Breast magnetic resonance imaging (MRI) technique

MRI of the breast was performed using a 1.5 T MRI imager (Philips Achieva, Hamburg, Germany) with a dedicated 7channel breast coil.

After a T2w STIR sequence in the transverse plane (repetition time, 3,200 ms; echo time, 50 ms; inversion time, 160 ms; matrix, 512×512 pixels; field of view, 360 mm; slice thickness, 3.5 mm), T1w gradient echo sequences (repetition time, 7.5 ms; echo time, 3.7 ms; matrix, 512×512 pixels; field of view, 400 mm; flip angle, 20°; slice thickness, 1.5 mm) were acquired before and after intravenous (IV) injection of 0.16 mmol/kg body weight of gadolinium contrast medium (Gadobutrol, Gadovist®, Bayer HealthCare AG, Berlin, Germany).

Eight measurements were performed:

One before and seven after contrast agent injection.

Subtraction images were produced using the images obtained approximately 150 s after injection and at the start of the injection (0 s).

Maximum intensity projections (MIP) were obtained in the transverse, coronal and sagittal planes.

Data analysis

All images from the 73 included patients were reviewed by two radiologists (BW and HP) who, respectively, had 8 and 3 years of experience reading breast MR images.

The readers were aware that the patients had undergone NAC because of breast cancer and reviewed the data sets consecutively to determine the changes in BPE after NAC.

BPE was categorised into 4 BPE categories (BEC) that ranged from 1 to 4, which indicated minimal, mild, moderate and marked enhancement, respectively.

The readers were blinded to the other reader's results.

The tumour response to NAC was classified according to RECIST 1.1 criteria (complete remission (CR), partial response (PR), stable disease (SD) or progressive disease(PD).

The average (mean) baseline BPE before therapy and the change in BPE after therapy in the cases with a CR, PR, SD and PD were calculated and compared to investigate whether the baseline BPE or the change in BPE could predict the tumour response in patients undergoing NAC.

Results

1-Tumour characteristics and response to therapy

Histopathological analysis showed that invasive ductal carcinoma was present in 89 % (71/80) of the patients, invasive lobular carcinoma in 10 % (8/80) and invasive apocrine carcinoma in 1 % (n=1).

The receptor analysis showed that 13 of 80 carcinomas were triple-negative.

1-Tumour characteristics and response to therapy

Histopathological tumour response of the 80 tumours was a CR in 15 cases (19 %), PR in 44 cases (57 %), SD in 10 cases (13 %) and PD in 8 cases (10 %).

The morphological response was CR in 17 cases (21 %), PR in 44 cases (55 %), SD in 10 cases (13 %) and PD in 9 cases (11 %).

2-Background parenchymal enhancement categories (BEC)

There was no change in BPE in 27 cases according to reader 1 and in 25 cases according to reader 2.

A decrease in BPE was found in 53 cases according to reader 1 and in 55 cases according to reader 2, and neither reader noted an increase in BPE in any case.

BPE was significantly higher in premenopausal patients.

The change in BPE also differed significantly between the groups.

Premenopausal women had a significantly greater change, which indicated a higher reduction in BEC, than did the non-premenopausal women, with a mean reduction of 1.05 in premenopausal compared with 0.50 in non premenopausal women.

3- Correlation analysis

BPE was analysed before and after NAC according to the tumour response to investigate whether the baseline BPE or the change in BPE could predict the tumour response to NAC.

On average, BPE decreased by 0.87 BEC in all patients.

The correlation analysis showed a significant correlation between the decrease in BEC and the tumour response, which showed a stronger reduction of BPE in cases with a better tumour response.

Based on the tumour response, the average decrease in BEC was 1.3±0.099 categories for cases with CR, 0.83±0.080 in cases with PR, 0.85±0.083 in cases with SD and 0.40±0.056 in cases with PD.

The decrease in BEC was significantly higher in the cases with CR than in those with PD.

The mean differences in BEC after NAC subclassified based on the tumour responses is shown.

According to reader 1, the average decrease in BEC was 0.54 BEC in patients with PD, but according to reader 2, it was 0.27 BEC.

Discussion

In this study, authors analysed a cohort of cancer patients with a mean age of 48.5 years old, the majority of the patients presented with minimal or mild BPE, which is in agreement with the values given in the literature.

These results emphasise the fact that in contrast to X-ray mammography, MRI has a high assessability in most patients.

The results show that this also holds true even if the examination is not carried out between days 7 and 14 of the menstrual cycle because the menstrual cycle is neglected in patients with proven breast cancer.

There was a significant difference in BPE in premenopausal women compared with non-premenopausal women.

The change in BPE also differed between the groups, with a significantly higher decrease in premenopausal women than in peri or postmenopausal women.

In this study, the baseline BPE before NAC did not predict the tumour response.

In the present study, the decrease in BEC after the completion of NAC was significantly higher in the cases showing a complete remission compared with progressive disease, and there was a slight but significant correlation between the tumour response and the change in BEC.

This observation may indicate that the degree of the change in BPE can be considered a predictor of the tumour response, especially in cases where the exact tumour size and extension are difficult to measure.

ConclusionThe degree of decrease in BPE on contrast-enhanced MRI in patients undergoing NAC may be a predictor of the tumour response.

The initial amount of BPE does not serve to predict the tumour response.

Further studies are needed to investigate the impact of BPE measurements on the disease-free survival and overall survival.

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