Clinical Update - Breast Cancer
MRI detected contralateral breast cancer among women with recently diagnosed unilateral breast cancer
Commentary by Dr James Anderson
The article
Lehman CD, Gatsonis C, Kuhl CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. New Engl J Med 2007;356:1295–303.
Reviewer
Dr James Anderson, Consultant Radiologist Royal Perth Hospital.
Summary
Abbreviations
Breast Imaging Reporting and Data System (Bi-RADS), Confidence Interval (CI), Ductal Carcinoma in Situ (DCIS), Magnetic Resonance Imaging (MRI).
Study design
This US study examined the effectiveness of MRI in detecting contralateral breast cancer, among women recently diagnosed with unilateral breast cancer, in comparison to mammography and clinical breast examination. Nine hundred and sixty nine patients, diagnosed with unilateral breast cancer within 60 days and with no abnormal clinical and mammographic results in the contralateral breast within 90 days, were included in the study. Participants underwent dynamic, contrast-enhanced MRI and cancer status was followed for one year. The primary outcome was the diagnostic yield of breast MRI, defined as the proportion of women diagnosed with contralateral breast cancer by MRI, who had recently been diagnosed with unilateral breast cancer and had a negative contralateral clinical and mammographic examination. Secondary outcomes include sensitivity, specificity, negative predictive value and positive predictive value of MRI and the associated positive biopsy rate. These outcomes were also examined in relation to breast density, menopausal status and the type of index cancer.
Findings
Within one year from the beginning of the study, 33 contralateral breast tumours were detected. Of these, 30 tumours (18 invasive and 12 DCIS) were detected following a positive MRI result. The three tumours for which MRI gave a false negative result were all DCIS.These tumours were found in the breasts of patients who had prophylactic mastectomies. The sizes of these DCIS lesions were 1mm, 3mm and 4 mm. MRI scanning resulted in biopsies in additional 91 women (9%) who did not have cancer.
Diagnostic performance of MRI:
- Diagnostic yield 3.1% (95% CI: 2.0, 4.2)
- Sensitivity 91% (95% CI: 76, 98)
- Specificity 88% (95% CI: 86, 90)
- Negative predictive value 99% (95% CI: 99, 100)
- Positive predictive value 21% (95% CI: 14, 27)
- False positive rate 75% of women having biopsies (91/121), 9% of all women scanned (91 of 969)
Neither breast density, menopausal status nor the type of index cancer were found to be associated with diagnostic yield, sensitivity or negative predictive value. The following variables were significantly higher among postmenopausal women compared to pre- or perimenopausal women: specificity (91% vs. 84%; p=0.002), positive predictive value (31% vs. 11%; p=0.006) and positive biopsy rate (35% vs. 14%; p=0.009).
Conclusion
The authors concluded that MRI can detect cancer in the contralateral breast that is missed by mammography and clinical examination at the time of initial breast-cancer diagnosis.
Commentary
In the Editorial which discusses this article, Smith1 draws attention to the increasing availability of breast MRI in the United States. The Editorial emphasizes the importance of detecting other breast cancers not only in the same breast (multicentric) but also in the contralateral breast (synchronous). Evidence for the use of MRI to detect both types of additional lesions is accumulating.
What does this article add to existing clinical evidence in this area?
It is well established that women with a unilateral breast cancer have an increased risk of having or developing subsequently a cancer in the contralateral breast in up to 10% of cases. This article,2 in a multi-centre trial (25 sites), confirms the published findings of an earlier single-centre trial,3 that MRI can increase the number of cancers detected in the contralateral breast when added to clinical and mammographic evaluation. The large amount of data resulting from this multi-centre study adds significantly to the evidence supporting the hypothesis that MRI can visualize cancers in breast tissue, not evident on clinical examination or by mammography.
How adequate was the methodology used in addressing the aim of the study?
The stated aim was to determine the additional number of cancers detected by MRI over and above those detected clinically and by mammogram in the contralateral breast. A standard MRI protocol was used which incorporated a high resolution technique (voxels smaller than 0.9mm). The American College of Radiology Breast Imaging Reporting and data system (Bi-RADS) was used for interpretation of the images. It would have been helpful for the reading of the article if in Table 2 footnote, the test positive and negative definitions necessary for the calculation of the 91% sensitivity and 88% specificity of MRI had been listed. Exact sensitivity and specificity estimation was not possible because 10% of the test subjects refused biopsy and the original test status was deduced by analysis of follow up imaging. The reasons why the women refused biopsy were not stated, but there was resistance to recommended biopsy in a significant number. There was a high biopsy rate, 121 of 969 women (12%), of whom only 30 were found to have cancer and 91 women therefore underwent a biopsy that proved negative. The paper did not indicate whether targeted conventional imaging (mammography and ultrasound) was used to confirm suspicious lesions seen on MRI and or to then use these traditional imaging modalities to biopsy breast lesions. The only comment in the article about biopsies was that it was a prerequisite for a person to be an investigator to have performed five MRI guided breast biopsies. Assuming that some of the sites had radiologists with more experience than others, it would have been helpful to know whether more experienced radiologists had different results from those less experienced.
What are the implications of this study for clinical practice in Australia?
Although MRI was found to detect contralateral cancers in over 3% of patients, the use of MRI on all women with recently diagnosed cancer would have significant human and equipment resource implications. The authors did suggest however, that for women who had recently been diagnosed with breast cancer and were contemplating bilateral mastectomy, MRI may be used instead to search for cancer in the contralateral breast. The validity of these women choosing this management option is supported by the high negative predictive value (99%) of a MRI yielding a negative result, reported in this publication. Additional equipment to perform biopsies under MRI control would be necessary for this indication.
In summary, this is an important article in which Lehman et al 2 were successfully able to complete a multi-centre study which showed that MRI imaging in this group of patients detected a significant number of cancers in the contralateral breast. However, detecting these cancers (30) required three times as many women (91) to have a biopsy that proved negative. Thus if MRI were to be offered to this group of women, they should be made aware of this data and the consequential relatively high negative biopsy rate. This publication provides yet more evidence for the benefit of MRI in women with recently diagnosed breast carcinoma and has potential implications for future resourcing of health services.
Acknowledgements
Dr Ashley Bennett radiology registrar Royal Perth Hospital.
References
1. Smith RA. The evolving role of MRI in the detection and evaluation of breast cancer. N Engl J Med 2007;356:1362–64
2. Lehman CD, Gatsonis C, Kuhl CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med 2007;356:1295–303
3. Liberman L, Morris EA, Kim CM, et al. MR imaging findings in the contralateral breast of women with recently diagnosed breast cancer. Am J Roentgenol 2003;180:333–41
Editor: Dr Karen Luxford, General Manager, National Breast Cancer Centre.
Editorial Committee: Mr John Collins - Surgeon,
Dr Sue-Anne McLachlan - Medical Oncologist,
Dr Sue Pendlebury - Radiation Oncologist,
A/Prof Martin Stockler - Medical Oncologist, Ms Jo Keyser - Specialist Breast Nurse, Dr Sally Meade - Breast Surgeon, Dr Warwick Lee - Radiologist, Dr Penny Schofield - Senior Research Fellow.
Disclaimer
Clinical Update - Breast Cancer is produced by the National Breast Cancer Centre (NBCC) and is intended to provide health professionals with timely expert commentary on new research in breast cancer. Commentaries included in Clinical Update - Breast Cancer do not replace recommendations included in NBCC clinical practice guidelines.
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