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Clinical Reviews

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

Abnormal mammogram, self-palpated lesion, bloody nipple discharge, and inflammation of the breast

October 2006 · Vol. 18, No. 10


This week's quiz:
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What’s the most common cause of death in women 40 to 44 years of age?

Answer: Breast cancer.1

What population has the highest death toll from breast cancer?

Answer: Women age 40 and older. Approximately 95% of new breast cancer cases and 97% of breast cancer deaths occur in women 40 and older.2

Why are many women in their 40s under-screened?

Answer: Because clinicians sometimes under-appreciate their risk.

Of course, the majority of breast cancer cases and deaths involve postmenopausal women. But this doesn’t mean younger women don’t warrant heightened scrutiny. This article presents 4 cases that focus on breast disease in women 40 to 49 years of age and the optimal workup for patients with suspicious findings. It includes recommendations on:

Digital mammography may aid in evaluation of dense breast tissue

Although early breast cancer may be more difficult to identify on mammography in premenopausal women because of their denser breast tissue, there are good data on the benefits of screening mammography for women in the 40- to 49-year-old age group,3,4 as well as for women age 50 and older.5 In addition, digital mammography is often helpful in women with radiographically dense breasts.

Screening vs diagnostic mammography

Women who have no complaints and no abnormal physical findings on self- or clinical examination typically undergo screening mammography. In typical cases, 2 views of each breast are obtained, and the radiologist often postpones reading the images until the end of the day, when they are scrutinized in batches.

In contrast, diagnostic mammography is performed when a possible problem arises, and several additional “coned-down” views may be needed. The radiologist interprets the study while the patient is still in the radiology office.

It is essential that gynecologists indicate on the mammography referral form whether they are requesting a diagnostic or screening mammogram. If it is a diagnostic mammogram, the reason and precise location of any suspicious areas need to be clearly communicated to the radiologist. In either case, the patient should be reminded to provide any previous images the radiologist does not already have.

I obtain routine annual screening mammography for my average-risk patients from age 40 onward, since more than 50,000 American women under age 50 are diagnosed with breast cancer each year.

CASE 1 Abnormal mammogram

S.H. is a healthy 43-year-old who had vaginal deliveries at ages 25 and 28 and has always used barrier contraception. She has no family history of cancer or high-risk factors for breast cancer. Her breast and pelvic examinations at the time of her routine gynecologic visit are normal. She has undergone annual mammography since she was 40 years old, but recently moved from another state and did not bring her mammograms with her.

She is sent for a screening mammogram, and 2 radiographic views of each breast are obtained. Upon review, the images are classified as Breast Imaging Reporting and Data Systems (BI-RADS) category 0, indicating that mammographic assessment is incomplete. The radiologist wants additional images of an area in the upper outer quadrant of the right breast, and wants to compare this study with the patient’s old films if they are available. S.H. returns the next day for the additional imaging, and the radiologist identifies an 8-mm area of suspicious calcifications in the right breast, reclassifying the mammogram as BI-RADS category 4.

The radiologist recommends a stereotactic biopsy, but S.H. wants your advice on whether to comply or proceed immediately to open biopsy.

What do you tell her?

Barely invasive biopsy

Stereotactic needle biopsy offers precise positioning in 3 dimensions without the lag time and scarring associated with open biopsies.In the case above, stereotactic biopsy is a good option, since it can usually be scheduled rapidly, does not require an operating room or anesthesia, is less expensive than open biopsy, and involves less scarring.6 If a patient’s lesion is clearly benign on stereotactic biopsy, she may be spared an open biopsy. If it is malignant, she can immediately begin to make treatment decisions.

Breast imaging categories

BI-RADS categories have standardized the reporting of mammograms and include the following7:


S.H. schedules a stereotactic biopsy for the following day in the radiologist’s office. Tissue diagnosis reveals an invasive ductal carcinoma, and the patient elects to undergo lumpectomy and radiation therapy.

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.

CASE 3 Bloody nipple discharge

M.W. is a 48-year-old nulliparous woman who has noticed blood in her bra in the area of the right nipple several times during the past month. Her last mammogram, which was normal, was 1 year ago. Her history lacks any relevant problems other than the nipple discharge itself. Her menstrual periods are regular; the last one was 2 weeks earlier. Many years ago, she underwent a tubal ligation. She does not take any medications.

How should she be evaluated?

Nipple discharge is a common phenomenon, more so among women with benign problems (approximately 10%–15%) than in women with malignancies (approximately 3%).10

When taking a history from a woman with nipple discharge, ask about the color of the discharge; whether it is bilateral; whether it is spontaneous; and its frequency and duration.

Physical exam: Focus on 3 questions

During a routine, thorough examination of the breasts and axillae, focus on the following issues:

Although cytology of the discharge can be performed at this time, the yield may be low.

As with a mass, the cause of the discharge must be determined even if cytology is benign.


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