Information of hormonal receptors, including estrogen receptor (ER) and progesterone receptor (PR), is essential in management of breast cancer patients. In a recent study by Chen et al., it was found that ER positive and negative breast cancers demonstrated different imaging features on MRI [1]. However, since the status of PR was consistent with that of ER in most patients (ER+/PR+ or ER−/PR−) in that study, the impact of PR was not analyzed. Previous studies have shown that lack of PR expression was associated with aggressive tumors [2, 3]. In this work the association between PR status and MR imaging features was investigated. In a retrospective review of our breast MRI database from 2001 to 2007, 25 patients with ER+/PR− invasive breast cancer were found, including 21 invasive ductal cancers and 4 invasive lobular cancers. A group of 29 consecutive patients with ER+/PR+ invasive ductal cancer was taken from the previously published study [1] for comparison. The age range was 34−70 years old (mean 53) for the ER+/PR+ patients, and 34−81 years old (mean 59) for the ER+/PR− patients (P = 0.05). The MRI features between these 2 groups were compared. This study was approved by the institutional review board (IRB) and was HIPPA-compliant. All patients gave informed consent.
The MRI study was performed using a 1.5 T MR scanner with a standard bilateral breast coil. The imaging protocol consisted of high-resolution pre-contrast imaging and bilateral axial dynamic contrast-enhanced imaging. For the dynamic imaging acquisition, a 3D SPGR (RFFAST) pulse sequence was prescribed. The sequence was repeated 16 times, four pre-contrast, and 12 post-contrast sets. The subtraction images at 1-min after contrast injection from 32 slices were generated, then used to form the maximum intensity projection (MIP). Tumor size was measured as the longest tumor dimension on the MIP. The enhancement kinetics was analyzed from manually-drawn region of interest on each subtraction imaging slice at 1-min post injection containing the lesion. The enhancement time course was calculated by subtracting the mean pre-contrast signal intensity from each of the subsequent 12 post-contrast signal intensities. The tumor morphology and kinetic enhancement features were analyzed based on ACR Breast Imaging Reporting and Data System (BI-RADS) MRI lexicon [4]. The axillary lymph node status was evaluated on pre-contrast sagittal view images.
Most of the patients in both groups, including all ER+/PR+ cancers (29/29) and 21 of 25 ER+/PR− cancers presented as mass type lesion (P < 0.05). Four ER+/PR− breast cancers presented as non-mass type lesions, including 3 regional enhancements and one linear enhancement. The mean tumor size was significantly bigger in the ER+/PR− cancers than the ER+/PR+ cancers (2.4 ± 1.3 cm vs. 1.7 ± 1.0 cm, P < 0.05). For lesions multiplicity, 5 ER+/PR− patients (5/25, 20%) and 8 ER+/PR+ patients (8/29, 27.5%) showed multiple lesions (P=0.54). Axillary lymph nodes were detected by MRI in 9 ER+/PR− patients (9/25, 36%) and in 6 ER+/PR+ patients (6/29, 21%, P= 0.23). Regarding kinetic enhancement curve, malignant type enhancement occurred in 33 of 36 measured ER+/PR− lesions (29 washout and 4 plateau), and in 31 of 34 measured ER+/PR+ lesions (27 washout and 4 plateau). Three lesions in both groups showed the benign type continuous enhancement curve (P= 1). Table 1 summarized the imaging findings.
Table 1.
MR Imaging Features of ER+/PR+ and ER+/PR− Patients
| ER+/PR+ | ER+/PR− | P value | |
|---|---|---|---|
| MR imaging features | |||
| Tumor size | 1.69 ± 1.00 cm | 2.35 ± 1.25 cm | < 0.05 |
| Lesion multiplicity | 8/29 (28%) | 5/25 (20%) | 0.54 |
| Mass-type lesion | 29/29 (100%) | 21/25 (86%) | < 0.05 |
| Non-mass type lesion | 0/29 (0%) | 4/25 (16%) | < 0.05 |
| Axillary L.N. | 6/29 (21%) | 9/25 (31%) | 0.23 |
| Malignant enhancement kinetics | 31/34 (91%) | 33/36 (92%) | 1 |
**Significant difference between ER+/PR+ and ER+/PR− patients was found for tumor size and non-mass type lesion
PR status can provide strong prognostic information on the risk of recurrence in endocrine-treated breast cancer patients [5]. ER+/PR− breast cancers are less sensitive to tamoxifen than are ER+/PR+ tumors [6-8]. In post-menopausal women, the ER+/PR− group had a worse disease free survival and overall survival compared to ER+/PR+ group [8]. It has been shown that the PR status is a better prognostic predictor than the ER status [9]. Correlation of PR with imaging features is rarely studied. In a few studies of PET uptake with prognostic factors of breast cancer, controversial results were found regarding impact of PR on maximal standardized uptake value [10-12]. In this study we found that ER+/PR− cancer has larger tumor size compared to ER+/PR+ cancer, and it is more likely to present non-mass type lesions. The finding is consistent with that of Arpino G et al. [2]. Another study by Ponzone R et al. also showed that PR negative tumors were characterized by larger size and higher tumor grade [3].
According to the ACR BI-RADS MRI lexicon [4], non-mass type lesion indicates that enhancement occurs in an area of the fibroglandular tissue without space-occupying effect. It represents a breast lesion with infiltrative process. In malignant cancer, the infiltrative process might be regarded as an aggressive tumor behavior. However, interpretation of this data should be cautious since there were 4 patients of lobular cancer included in the ER+/PR− cohort and 2 of them showed non-mass type enhancement. If these 4 patients were excluded, the difference is not significant (2/21 vs. 0/29, P= 0.17). Other imaging features, including multiple lesions, kinetic enhancement curve, and axillary lymph nodes metastasis, were not significantly different.
In conclusion, in this study we compared the MR imaging features between ER+/PR+ and ER+/PR− cancers, and found that PR negative cancer had significantly bigger tumor size and more non-mass type lesions. Our study provides imaging evidence that PR in invasive breast cancer does impact imaging features and PR negative invasive breast cancer is more aggressive, consistent with findings of several previous studies showing that missing PR in ER positive breast cancer is more aggressive than its counterpart of ER+/PR+ cancer.
Acknowledgements
This study was supported in part by NIH/NCI R01 CA90437, CA121568 and California Breast Cancer Research Program # 9WB-0020.
REFERENCES
- 1.Chen JH, Baek HM, Nalcioglu O, Su MY. Estrogen Receptor and Breast MR Imaging Features: A Correlation Study. JMRI. doi: 10.1002/jmri.21330. in press. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Arpino G, Weiss H, Lee AV, et al. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J Natl Cancer Inst. 2005 Sep 7;97(17):1254–61. doi: 10.1093/jnci/dji249. [DOI] [PubMed] [Google Scholar]
- 3.Ponzone R, Montemurro F, Maggiorotto F, et al. Clinical outcome of adjuvant endocrine treatment according to PR and HER-2 status in early breast cancer. Ann Oncol. 2006 Nov;17(11):1631–6. doi: 10.1093/annonc/mdl296. [DOI] [PubMed] [Google Scholar]
- 4.American College of Radiology . Breast imaging reporting and data system atlas (BI-RADS atlas) American College of Radiology; Reston, VA: 2003. [Google Scholar]
- 5.Bardou VJ, Arpino G, Elledge RM, Osborne CK, Clark GM. Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol. 2003 May 15;21(10):1973–9. doi: 10.1200/JCO.2003.09.099. [DOI] [PubMed] [Google Scholar]
- 6.Lamy PJ, Pujol P, Thezenas S, et al. Progesterone receptor quantification as a strong prognostic determinant in postmenopausal breast cancer women under tamoxifen therapy. Nov. 2002;76(1):65–71. doi: 10.1023/a:1020228620173. [DOI] [PubMed] [Google Scholar]
- 7.Stendahl M, Rydén L, Nordenskjöld B, Jönsson PE, Landberg G, Jirström K. High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients. Clin Cancer Res. 2006 Aug 1;12(15):4614–8. doi: 10.1158/1078-0432.CCR-06-0248. [DOI] [PubMed] [Google Scholar]
- 8.Yu KD, Liu GY, Di GH, et al. Progesterone receptor status provides predictive value for adjuvant endocrine therapy in older estrogen receptor-positive breast cancer patients. Breast. 2007 Jun;16(3):307–15. doi: 10.1016/j.breast.2006.12.011. [DOI] [PubMed] [Google Scholar]
- 9.Gelbfish GA, Davidson AL, Kopel S, et al. Relationship of estrogen and progesterone receptors to prognosis in breast cancer. Ann Surg. 1988 Jan;207(1):75–9. doi: 10.1097/00000658-198801000-00015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Ikenaga N, Otomo N, Toyofuku A, et al. Standardized uptake values for breast carcinomas assessed by fluorodeoxyglucose-positron emission tomography correlate with prognostic factors. Am Surg. 2007 Nov;73(11):1151–7. [PubMed] [Google Scholar]
- 11.Mavi A, Cermik TF, Urhan M, et al. The effects of estrogen, progesterone, and C-erbB-2 receptor states on 18F-FDG uptake of primary breast cancer lesions. J Nucl Med. 2007 Aug;48(8):1266–72. doi: 10.2967/jnumed.106.037440. [DOI] [PubMed] [Google Scholar]
- 12.Buck A, Schirrmeister H, Kühn T, et al. FDG uptake in breast cancer: correlation with biological and clinical prognostic parameters. Eur J Nucl Med Mol Imaging. 2002 Oct;29(10):1317–23. doi: 10.1007/s00259-002-0880-8. [DOI] [PubMed] [Google Scholar]