Clinical Review

4 Cases that Test Your Skills: Workup for premenopausal breast complaints

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CASE 2 Self-palpated lesion

L.J., 45, has no personal or family history of cancer and no high-risk factors, and she has undergone annual mammograms since the age of 40. Her last mammogram, which was negative, was 3 months ago.

Today L.J. reports that she felt a 1-cm lesion in the upper outer quadrant of her left breast during monthly breast self-examination. Although she is somewhat reassured by the normal mammogram 3 months earlier, she had been instructed by her gynecologist to call if she ever had any abnormal findings on breast self-examination.

Her gynecologist performs a thorough history and physical examination of the breasts and lymph nodes, confirming the presence of the lesion but no other abnormalities.

What is the next step?

Self-examination and imaging don’t always agree

It is vital that a diagnosis be made whenever a mass is present in the breast—even if the mammogram is normal—since 10% to 15% of women with breast cancer have normal mammograms.1

In this case, the first step is to review the prior mammogram. If no abnormality is found on the mammogram, the patient should undergo further imaging to ascertain whether the lesion appears benign or suspicious for malignancy.

However, even if all radiologic studies are normal, definitive diagnosis is crucial when a mass is present.

MRI may be useful when other imaging is inconclusive

In 2004, the American College of Radiology (ACR) published guidelines for breast MRI,8 which advise against using the modality for breast cancer screening in the general population of asymptomatic women because of the likelihood of false positives. However, MRI is recommended by the ACR in a wide range of situations, including those in which other imaging such as mammography or ultrasound has been inconclusive.

I encourage self-examination

Because 75% of women diagnosed with breast cancer lack major high-risk factors, all women should be screened, and I believe self-examination should be encouraged. Although data from randomized controlled trials of breast self-examination do not confirm a reduction in overall breast cancer mortality with the practice, it may lead to earlier detection in some women.9


While L.J. is in the office, the gynecologist telephones the radiologist and asks her to review the mammogram. The radiologist does so, comparing the latest films with prior mammograms, and calls back to report the absence of abnormal findings.

The patient is then sent for ultrasound of the breast, which does not reveal a cyst but does show some suspicious changes. After a breast MRI is consistent with malignancy, the lesion is biopsied and diagnosed as invasive lobular carcinoma.


Mammography isn’t perfect. Neither is magnetic resonance imaging (MRI). But both can be revealing in the right patients. MRI studies suggest it is better at imaging soft tissues and can detect lesions not visible on mammogram in 27% to 37% of patients.12,13

The downside: cost. Because MRI is 10 to 15 times more costly than mammography, it is usually limited to patients with suspicious findings or high risk.

Higher predictive value, biopsy still needed

Bluemke DA, Catsonis CA, Chen MH, et al. Magnetic resonance imaging of the breast prior to biopsy. JAMA. 2004;292:2735–2742.

A prospective multicenter study by the International Breast MR Consortium involved 821 women referred for breast biopsy at 14 university hospitals in North America and Europe. All women had BI-RADS category 4 or 5 mammographic evaluation and breast MRI prior to the biopsy, with imaging interpreted at each site without knowledge of the biopsy results.

Findings: MRI correctly identified cancer in 356 of 404 cancer cases, for a sensitivity of 88.1% (95% confidence interval [CI] 84.6–91.1). It also correctly ruled out cancer in 281 of 417 cases with benign findings, for a specificity of 67.7% (95% CI 62.7–71.9). The positive predictive value of MRI for 356 of 492 patients was 72.4% (95% CI 68.2–76.3), compared with 52.8% for mammography in 367 of 695 patients (95% CI 49.0–56.6).

Conclusion: Despite the higher predictive value of MRI, tissue sampling is still needed when suspicious findings are detected.

Annual MRI and mammography for women at high risk

Leach MO, Boggis CR, Dixon AK, 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. Lancet. 2005;365:1769–1778.

This prospective, multicenter study compared mammography with contrast-enhanced MRI in 649 women aged 35 to 49 who had a strong family history of breast cancer or a high probability of BRCA1, BRCA2, or TP53 mutation. The women had annual screening with both modalities for 2 to 7 years.

Findings: Thirtyfive cancers were diagnosed—19 by contrast-enhanced MRI only, 6 by mammography only, and 8 by both, with 2 “interval” cases. Sensitivity for contrast-enhanced MRI was significantly higher than for mammography (77% vs 40%; 95% CI 60–90 vs 24–58); when both modalities were used, it was 94% (95% CI 81–99). The contrast in sensitivity between the 2 modalities was particularly sharp in women with BRCA1 mutations: 92% for MRI vs 23% for mammography (P=.004). However, specificity was higher for mammography (93% vs 81%; 95% CI 92–95 vs 80–83); when both mammography and MRI were used, specificity was 77% (95% CI 75–79).

Leach et al noted a high proportion of grade 3 cancers in this study, but the tumors were small and most women were node-negative.

Conclusion: Annual screening with both contrast-enhanced MRI and mammography would detect most cancers in high-risk women.

MRI is more cost-effective in women with BRCA1/2 mutations

Plevritis SK, Kurian AW, Sigal BM, et al. Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA. 2006;295:2374–2384.

Using a computer model to simulate the life histories of individual BRCA1 and BRCA2 mutation carriers, Plevritis et al compared mammography and breast MRI for cancer screening, using published data to estimate the accuracy of the 2 modalities. Breast cancer survival was based on the Surveillance, Epidemiology, and End Results (SEER) database, whereas utilization rates and intervention costs were based on published data and Medicare payments for 2005.

Findings: For each quality-adjusted life-year (QALY) gained, the cost of annual MRI in addition to annual mammography ranged from less than $45,000 to more than $700,000, depending on the patient’s age and specific BRCA mutation. Compared with mammography alone, the cost of MRI for each QALY gained in women aged 35 to 54 years was $55,420 for BRCA1 mutation carriers, $130,695 for BRCA2 mutation carriers, and $98,454 for BRCA2 mutation carriers with mammographically dense breasts.

Conclusion: Breast MRI screening is more cost-effective in women with BRCA1 mutations. The cost-effectiveness of adding it to mammography also varies greatly by age.

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