Dr. Newman has written a comprehensive
and judicious review
on the highly topical subject
of ductal lavage, and is to be
congratulated. We would like to give
particular emphasis to several of the
issues she raises.
How Well Does Ductal Lavage
While most authorities have been careful to define ductal lavage as a tool for risk assessment and not for cancer detection, ductal lavage continues to be promoted anecdotally as "the Pap smear of the breast" by patients and physicians alike. We recently performed ductal lavage immediately prior to mastectomy in 28 consecutive women with proven breast cancers. Among 30 ducts successfully lavaged, the cytologic findings were benign in 43%, mildly atypical in 30%, markedly atypical in 13%, and malignant in none. More disturbing, among patients in whom the lavaged ducts were also mapped with blue dye, 79% of ducts were in proximity to the known cancer. These findings are comparable to those of Love et al, Khan et al, and King et al, who found malignant cytology on ductal lavage in only 3% to 20% of patients with proven cancers. These results raise concern not only that ductal lavage fails to detect cancer, but that patients might be falsely reassured by the finding of a normal or mildly atypical ductal lavage (even in the presence of other suspicious findings). The promotion of the ductal lavage technology is of particular concern in a medicolegal environment, where the most frequent malpractice lawsuit is an alleged failure to diagnose breast cancer. While we as physicians can state that ductal lavage is only a "tool to identify increased risk," the patient with an atypical ductal lavage who presents with a breast cancer 1 to 2 years later might easily feel otherwise, claiming that an "abnormal test" was not acted upon at the time. Can Ductal Lavage Detect Duct Epithelial Atypia?
As Dr. Newman states, the case for ductal lavage is based on the hypothesis that cytologic atypia in nipple duct washings indicates an increased breast cancer risk comparable to that conveyed by atypia in nipple aspirates,[ 5,6] atypia from blind fourquadrant fine-needle aspiration, or a histologic diagnosis of atypical ductal hyperplasia. This hypothesis, while reasonable, remains untested and must await the results of long-term follow-up in patients with atypical ductal lavage (such as those described by Dooley et al). Although the ductal lavage device has been approved as safe by the US Food and Drug Administration (FDA), this does not mean (as one might assume) that the FDA has also approved ductal lavage cytology as a diagnostic test; it has not. Even if we accept that ductal lavage is a test only for the detection of duct epithelial atypia, how does ductal lavage measure up by the standards used to evaluate any other diagnostic test?
- Sensitivity: For patients with duct epithelial atypia, how likely is ductal lavage to detect it? We don't know, and therefore risk providing false reassurance on the basis of a normal ductal lavage.
- Specificity: For patients without duct epithelial atypia, how likely is ductal lavage also to be normal? We don't know, and therefore risk incorrectly advising normal-risk patients of increased risk based on an atypical ductal lavage. While the diagnostic criteria for atypia in a fineneedle aspiration sample have been defined based on experience gathered by many investigators, cytologic atypia in ductal lavage samples has not yet been the subject of such intense evaluation, and experience is still too limited to draw any definitive conclusions. For example, mammary foam cells in a ductal lavage sample can mimic ductal epithelial cells and be misinterpreted as atypical in a ductal lavage sample.
- Positive predictive value: For patients with atypia on ductal lavage, how likely is the patient to really have duct epithelial atypia? We don't know, and therefore risk overdiagnosis based on a false-positive ductal lavage (for the reasons noted above).
- Negative predictive value: For patients with a negative ductal lavage, how likely is the patient not to have duct epithelial atypia? We don't know, and therefore risk missing ductal atypia based on a false-negative ductal lavage. Until we have studies that systematically correlate the results of ductal lavage with the underlying breast histopathology or prospectively evaluate and follow patients undergoing ductal lavage, we lack the most basic information that we would require of any other diagnostic test in medicine. The current enthusiasm over ductal lavage has even resulted in a detailed algorithm for the management of an abnormal result. In the absence of supportive data, such reports give ductal lavage the appearance of a legitimacy that it has not yet earned.
As the assessment of breast cancer risk is always multivariate, how often does ductal lavage simply confirm what we already know? Individuals with a personal history of breast cancer, biopsy-proven atypical ductal hyperplasia, lobular carcinoma in situ, or deleterious mutations of BRCA1/2 (suspected or proven) are already at sufficient risk that ductal lavage would provide no additional information whatsoever. Would any of us be reassured by a normal ductal lavage in a patient with any of the above risk factors? Paradoxically, it is precisely this group of high-risk women who would be most attracted to ductal lavage in the false hope of an earlier cancer diagnosis. Is Ductal Lavage Cost-Effective?
Ductal lavage has been the subject of an intensive marketing campaign- both directly to the public and to physicians- by the manufacturer of the ductal lavage device. For physicians who complete training in the technique of ductal lavage, the manufacturer assists with the referral of interested patients (through a geographic directory), advises on billing, and offers assistance in seeking insurance reimbursement. While the commercial appeal of ductal lavage as a new, "high-tech," office-based, practicebuilding, and potentially lucrative procedure is clear, ductal lavage has not yet undergone scientific validation. Until then, it will remain an expensive test of unproven benefit. The Promise of Ductal Lavage
The single proven fact about ductal lavage is that it provides cytologic specimens that are greatly superior to those obtained from nipple aspiration.[ 8] Ductal lavage therefore has considerable promise as a source of cellular specimens and protein-laden fluid for research; here we would share the enthusiasm of those currently working in the field, and reviewed by Dr. Newman. In the clinical realm, we would urge restraint. Ductal lavage is not ready for prime time and should only be used in the context of a clinical trial.