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Breast Magnetic Resonance Image Screening and Ductal Lavage in Women at High Genetic Risk of Breast Carcinoma

Posted on: Friday, 22 October 2004, 03:00 CDT

Objective:

To determine whether magnetic resonance imaging (MRI) and ductal lavage (DL) are more successful than mammography and clinical breast exam (CBE) at identifying earlier breast cancer and high-risk histologic lesions in women who are at increased genetic risk of developing breast cancer.

Introduction:

The only proven method of risk reduction in women who are at high- risk of developing breast cancer is bilateral prophylactic mastectomy and oophorectomy, although tamoxifen therapy may be a beneficial alternative. Current screening methods include mammography and clinical breast exam. In these women who are at extreme high-risk of developing breast cancer (50% incidence of invasive breast cancer by age of 50 years), a reliable screening protocol, especially in the < 50 age group would be valuable.

Methods:

Eligible patients were women identified as BRCA1 or BRCA2 mutations carriers or those with a > 10% 10 year risk of developing breast cancer, as estimated by the Claus model. Patients were accrued over a 19 month period from 2001-2003. At enrollment, patients were ≥ 25 years old or 5 years younger than the earliest age at which a relative was diagnosed.

Screening protocol:

* Biannual clinical breast exam.

* Annual mammogram.

* Breast MRI.

* Ductal lavage.

Results:

Patient characteristics:

* Forty-one patients aged 27-72 years (median age 42.5 years) were screened.

* BRCA1/BRCA2 carriers accounted for 58.5% of the patients. The others were high-risk, based on family history.

* Prior malignancy: 29.3% with breast cancer and 7.3% with ovarian cancer.

* Risk reduction: 36.6% with prior risk reduction (26.8% prior bilateralsalpingo-oophorectomy (BSO) and 14.6% receiving prior tamoxifen).

Imaging results:

* Abnormal MRI in 25 patients -15 patients with normal initial MRIs are still on follow-up with no biopsy; of the 25 abnormal MRIs, 11 were biopsied.

Ductal lavage results:

* Thirty patients had successful DL. Seven patients (8 ducts) had mild atypia, three had insufficient material for diagnosis (IMCD) and 20 were benign. Five out of eight atypical specimens came from non-fluid-yielding ducts. Of the atypical specimens, 42.9% came from women who were BRCA carriers. One of the patients with atypia had a normal mammogram and MRI.

Biopsy results:

* Abnormal MRI (n=11):

* DCIS (1).

* Radial scar/atypia (3).

* Benign (7).

* Palpable mass (n=11):

* Benign.

* Abnormal mammogram (n=11):

* ALH.

Conclusions:

In a high-risk population, breast MRI detected DCIS and high- risk lesions that were missed by mammography, and DL detected cytologic atypia. There was a trend toward a lower incidence of atypical and high-risk lesions in patients who had previous risk reduction. A larger screening trial to evaluate the efficacy of MRI and DL for early detection of breast cancer in a high-risk group, and whether that early diagnosis will affect morbidity and mortality, is needed.

Selected references:

Kuhl CK, Schmutzler RK, Leutner CC, Kempe A, et al. Breast MR imaging screening in 192 women proved or suspected to be carriers of a breast cancer susceptibility gene: preliminary results. Radiology 2000;215:267-79

Tilanus-Linthorst MM, Obdeijn IM, Bartels KC, de Koning HJ, et al. First experiences in screening women at high risk for breast cancer with MR imaging. Breast Cancer Res Treat 2000;63:53-60

Warner E, Plewes DB, Shumak RS, Catzavelos GC, et al. Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer. J Clin Oncol 2001:19:3524-31

Commentary:

This is a report of a pilot study for screening a heterogeneous population of women who are at high genetic risk of breast cancer. The clinician is challenged to provide surveillance in this population for whom there is no defined screening strategy.

The real value of a screening program for the high-risk patient is to determine if and at what point intervention should occur. These women develop breast cancer at a younger age than an average risk population and live with the constant fear that they may not have intervened early enough to prevent death from breast cancer. Screening mammography in this young population is not sensitive and carries with it the cumulative risk of exposure to radiation with repeated mammograms. Giving a woman an effective screening program during her child-bearing years helps her decide on the timing of intervention with tamoxifen, BSO or prophylactic mastectomy, all of which impact on fertility or lactation. This screening protocol may provide that tool and may also prove useful in women who have already had a diagnosis of breast cancer and have not yet decided on intervention with a risk-reducing strategy.

Future screening may entail using nipple aspirate fluid or ductal lavage supernatant to detect biologic markers associated with neoplastic change. This technique allows for analysis of acellular fluid and preserves intact cells for cytologic evaluation. As suggested by the authors, a larger trial will need to be performed to address the issues of the low specificity and high sensitivity of MRI, the cost incurred by this intensive screening protocol, the appropriate screening interval and the impact on morbidity and mortality.

Hartman AR, Daniel BL, Kurian AW, Mills MA, Nowels KW, Dirbas FM, Kingham KE, Chun NM, Herfkens RJ, Ford JM, Plevritis SK. Cancer 2004;100:479-89

Further reading:

Hollingsworth AB, Singletary SE, Morrow M, Francescatti DS, et al. Current comprehensive assessment and management of women at increased risk for breast cancer. Am J Surg 2004;187:349-62

Isaacs C, Cavalli LR, Cohen Y, Pennanen M, et al. Detection of LOH and mitochondrial DNA alterations in ductal lavage and nipple aspirate fluids from high-risk patients. Breast Cancer Res Treat 2004;84:99-105

Commentary by: Shawna C. Willey, MD, FACS, Lombardi Comprehensive Cancer Center Georgetown University, Washington, DC

Copyright CRC Press Jun 2004

Source: Women's Oncology Review

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