Which imaging best detects breast cancer?David
Department of Surgery Mayo Clinic College of Medicine Rochester, MN
Department Editor —
Mayo Clinic College of Medicine, Mayo Graduate School of Medicine, Rochester, MN
Mammography, MRI, ultrasound and PET: Friends or foes?
The care and treatment of American patients undergoes daily change. Nowhere is this more evident than in the management of breast cancer. While options for evaluation (imaging, tumor markers, genetic testing, biopsy techniques, and histopathologic analysis) increase, the onus remains on physicians to use our armamentarium efficiently and cost-effectively. How would you manage this month’s dilemma?
Screening mammography in a 42-year-old premenopausal woman detected dense breast tissue and a 7-mm spiculated nodule in the upper-outer quadrant of her right breast (FIGURE 1).
MRI showed three lesions in the right breast and two in the left breast.
Her family history included a paternal aunt with breast cancer at age 56.
An ultrasound-guided biopsy showed invasive ductal carcinoma, grade 2 (of 3) with extensive ductal carcinoma in situ.
She was referred to the Mayo Clinic for definitive management.
ANSWER THIS MONTH’S DILEMMA
The patient appeared fit and healthy. Physical examination revealed no palpable breast or axillary abnormalities.
Though far from a perfect screening tool, mammography has reduced breast cancer mortality.
She had obtained bilateral magnetic resonance imaging (MRI) of the breast before our consultation. The MRI revealed three lesions in the right breast: a 9-mm rapidly enhancing nodule at the 10 o’clock position that corresponded to the lesion seen on the mammogram; a 3-mm nodule at 12 o’clock; and a 9-mm mass in the retroareolar region (FIGURE 2).
The MRI also revealed two 3-mm enhancing nodules in the central portion of the left breast: posterior to the nipple and at 12 o’clock (FIGURE 3).
Given the MRI evidence of bilateral multiple indeterminate nodules, we reevaluated both breasts with ultrasound. Biopsies at 10, 11 and 12 o’clock positions of the right breast revealed invasive, Nottingham grade 2 (of 3) ductal carcinoma and ductal carcinoma in situ (DCIS). We did not obtain biopsies of the left breast because ultrasound results were negative for malignancy.
After detailed discussions with multiple caregivers (medical oncologist, radiation oncologist, internist, nurse practitioner, and a general surgeon), the patient opted for bilateral skin-sparing mastectomies and right-sided axillary sentinel lymph node biopsy.
Surgery confirms diagnosis
While the left mastectomy specimen was free of malignancy, we identified three separate foci of grade 2 invasive ductal carcinoma in her right breast. The largest tumor measured 0.8×0.7×0.7-cm. Although DCIS was evident, all surgical margins were free of tumor.
NSABP B-38 STUDY
The B-38S study1 is a phase III adjuvant trial comparing these three chemotherapy regimens in women with node-positive breast cancer:
Dose-dense (DD) doxorubicin/cyclophosphamide followed by DD paclitaxel (DD AC→P).
DD AC followed by DD paclitaxel plus gemcitabine (DD AC→PG).
The right-sided sentinel node biopsy was positive, and 2 of 20 right axillary lymph nodes were found to harbor estrogen- and progesterone-receptor positive cancer at greater than 10%. The HER2/neu marker was negative.
The patient received six cycles of chemotherapy in the NSABP B-38 study (BOX).1 She has faired well in follow-up with her local oncologist.
Problematic screening tools
Diagnostic mammography is recommended for any woman 35 or older who has a breast mass.2 Although mammography is the primary study for identifying clinically occult breast cancer, its limits in sensitivity and specificity have led physicians to use other imaging modalities.
Results from eight randomized controlled breast cancer screening trials using mammography with or without clinical breast examination demonstrated a protective effect in women age 50 and older.3 Although far from a perfect screening tool, mammography has resulted in a 20%–30% reduction in breast cancer-related mortality.4
Is MRI necessary?
Physicians now use MRI more frequently than before because it can assess and delineate soft breast tissue. While MRI increases the number of abnormalities detected by 27%–36% over mammography,5,6 it remains inferior to excisional biopsy for in situ cancers and cancers greater than 3 mm.
In patients with clinically suspicious or mammographically identifiable breast lesions, MRI was 88% sensitive but only 67% specific. It had a positive predictive value for malignancy at 72% (mammography 53%).7
High-risk patients have a strong family history of breast cancer and/or known gene mutations. Current research indicates these indications for MRI in high-risk patients (BOX).8
Strong family history of breast cancer. A study of 649 women with strong family histories of breast cancer analyzed the use of both mammography and MRI over 2 to 7 years.
The study found 35 cancers: 19 by MRI alone, 6 by mammography alone, 8 with both modalities, and 2 interval cases. MRI sensitivity was significantly higher (77%) than mammography (40%, p=0.01). Using both modalities, the sensitivity was 94%. Specificity was 93% for mammography, 81% for MRI, and 77% with both modalities.9
Genetic mutations. A prospective study investigated the use of MRI, ultrasound, mammography, and clinical breast examination for surveillance in 236 women with BRCA-1 and -2 mutations.
Of the 22 cancers discovered (16 invasive, 6 DCIS), 17 were detected by MRI alone, 8 by mammography alone, 7 by ultrasound alone, and 2 by clinical breast exam. The sensitivity (MRI 77%, mammography 36%, ultrasound 33%, and clinical breast exam 9%) and specificity (MRI 95%, mammography 99%, ultrasound 96%, clinical breast exam 99%) were based on biopsy findings.10
Expense vs detection rate
MRI is a more sensitive tool for detecting breast cancer than mammography, ultrasound, or clinical breast exam alone,10 but its specificity remains troublesome.
Studies point out a clinically relevant rationale for using MRI in high-risk patients.
Should we order hundreds of $1500 tests to find 30% more “abnormalities”, most of which will be benign?
Both of the aforementioned studies9,10 point out a clinically relevant rationale for using MRI in high-risk patients who are younger, have dense breast tissue, and who have tumors with faster growth rates.
High false-positive rate
Screening mammography, MRI and clinical breast examination were prospectively compared in a cohort of 390 women within a 90-day period.11 Imaging examinations recommended 38 biopsies; 27 were actually performed revealing 4 cancers (MRI detected all 4; mammography found one). Biopsies were recommended in 9% of all MRI studies versus 2% with mammography.
Given the approximately 5% rate of the false-positivity with MRI (leading to benign biopsies),11 is catching a 3-mm cancer via MRI a year before mammography finds the now 5-mm lesion crucial to patient survival? We don’t know.
Breast ultrasound is a preferable imaging method for evaluation of a clinically symptomatic palpable lump over mammography alone, especially with women who have dense breast tissue, are under age 50, and are at higher risk.
While ultrasound detects mammographically occult cancers about 20% of the time, studies have shown it is not a good screening tool (sensitivity 95%, specificity 69%).12
Similarly, recent studies have not yet found positron emission tomograpy (PET) superior to more traditional imaging modalities in detecting primary breast cancer.13 Although PET is advantageous for research, its use for the diagnosis and management of breast cancer is limited.
WHEN TO USE MRI IN BREAST CANCER
Two important applications authors recently suggested for MRI in breast cancer are for screening or evaluating patients with silicone/saline breast implants, and when evaluation using ultrasound and mammography alone is difficult.8 The latter includes patients with:
A history of previous breast-conserving surgery.
Known cancer in whom contralateral disease needs to be ruled out.
Axillary metastasis but an unknown primary.
Very dense breast tissue.
Extensive breast scarring.
Breast ultrasound is preferable over mammography for clinically symptomatic palpable lumps.
We evaluated the lesions seen on MRI in our patient with ultrasound-guided biopsies in the right breast, confirming cancer. We did not find any worrisome lesions in the left breast using ultrasound.
The outcome of the biopsies allowed us to offer our patient a choice of treatments, and she was able to make an informed decision. Bilateral mastectomies confirmed our diagnosis.
Each and every patient is different. While we can’t be a different doctor for each of our patients, we can “morph” into our own best version for each life we touch: holding the hand of the great-grandma, cussing right along with the ornery farmer who is losing his wife to cancer, listening for an hour to the CEO who needs to vent, or tickling the toddler with otitis media.
This “physician transformation” and “adaptation to the patient” is most important when dealing with the patient who has breast cancer. This patient opted for bilateral mastectomy, another might desire breast conservation therapy, and still another may forego either option.
Surgeons need to use the best evidence available and help our patients make a decision that is best for them. Seems like you did that for this woman. Kudos to you!
- Protocol B-38. NSABP Clinical Trials Overview.
Available at: http://www.nsabp.pitt.edu/B-38.asp. Accessed July 11, 2006.
Evaluation of palpable breast masses.
Am Fam Physician. 2005;71:1731–1738.
Report of the International Workshop on Screening for Breast Cancer.
J Natl Cancer Inst. 1993;85:1644–1656.
The effectiveness of breast cancer screening by mammography in younger women.
Online J Curr Clin Trials.
1993 Feb 25;Doc No 32.
Accuracy of MR imaging in the work-up of suspicious breast lesions: a diagnostic meta-analysis.
Acad Radiol. 1999;6:387–397.
Value of MR imaging in clinical evaluation of breast lesions.
Acta Radiol. 2002;43:275–281.
- National Institutes of Health. Multi-institutional cooperative agreements for clinical evaluation of magnetic resonance imaging in breast cancer.
National Institutes of Health 2005 [cited 2004 Nov 16]; Available from: URL: http://grants.nih.gov/grants/guide/rfa-files/RFA-CA-96-012.html.
Magnetic resonance imaging in breast cancer: one step forward, two steps back?
, et al.
Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS).
, et al.
Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination.
, et al.
Screening women at high risk for breast cancer with mammography and magnetic resonance imaging.
Role of grey scale ultrasound in benign and malignant breast lesions.
J Coll Physicians Surg Pak. 2005;15:193–195.
Imaging in breast cancer: single-photon computed tomography and positron-emission tomography.
Breast Cancer Res. 2005;7:153–162.