Ductal Lavage for Breast Cancer Risk Assessment

Lisa A. Newman, MD, MPH, FACS, Cassann Blake, MD

Disclosures

Cancer Control. 2002;9(6) 

In This Article

Ductal Lavage as a Risk Assessment Tool

In the multicenter study reported by Dooley et al,[5] 84% of participants had fluid-yielding ducts that were amenable to lavage, and 82% of these fluid-yielding ducts were successfully cannulated. Of the patients who were successfully lavaged, 23% were found to have atypia (17% mild and 6% marked atypia), 54% had benign cytology, and <1% had frankly malignant cells identified. Of the lavaged participants, 22% had an inadequate specimen, compared with a 73% inadequacy rate for the nipple aspirate specimens. Furthermore, ductal lavage was more likely to yield a diagnosis of atypia compared to nipple aspirates. The subset of patients found to have atypia is particularly important because this category of elevated risk may be associated with increased benefits from chemoprevention.

The presence of atypical hyperplasia in breast tissue is an established risk factor for future breast cancer development.[2,3,6,7,8,9,10,11,12,13,14,15,16,17] The prevalence of atypical hyperplasia in the breasts of an unselected patient population is not fully defined, but it is probably less than 15% and is likely to vary according to method of ascertainment. An autopsy series from Australia reported by Bhathal et al[18] detected atypical hyperplasia in 12.6% of breasts examined histopathologically in 207 forensic postmortem examinations. Lee et al[19] and Wrensch et al[2,3] identified atypia in nipple aspirates in 2% to 3.4% of mammographically screened women and in 0.7% of unselected volunteers from the west coast of the United States.

One model for breast tumorigenesis features the evolution of breast ductal cells from normal to hyper-plastic, followed by the development of atypical hyperplasia. Further accumulation of genetic abnormalities as ductal cells proceed through the cell cycle leads to the development of carcinoma in situ and ultimately invasive cancer.[20] However, the pathogenesis of breast cancer may be heterogeneous. Not every case of breast atypical hyperplasia is committed to progressing through the complete sequence resulting in invasive cancer; some invasive phenotypes may develop without passing through the full spectrum of premalignant phases; and the chronology for these carcinogenic stages may vary.[20] Nonetheless, several studies have demonstrated that a diagnosis of atypical hyperplasia is associated with a relative risk for breast cancer that ranges from 3 to 5 over the following 5 years ( Table ). This risk may double if the patient also has a family history of breast cancer,[11,12] it appears to be unaffected by history of estrogen replacement therapy,[7] and it may begin to decline back to the baseline general population risk after 5 to 10 years if no intervening risk-related events occur.[21] Ma and Boyd[22] conducted a meta-analysis of 18 studies involving the strength of the association between atypical hyperplasia and subsequent breast cancer reported between 1960 and 1992. This pooled analysis resulted in a total sample size of over 180,000 patients, and the summary odds ratio for atypical hyperplasia as a breast cancer risk factor was 3.67 (95% confidence interval, 3.16-4.26). The authors rigorously applied the Bradford Hill criteria (eg, temporal relationship, strength of association/dose-response correlation, and biologic plausibility) for assessing the validity of a risk factor,[23] and they conclude that these guidelines "indicated strongly that atypical hyperplasia is a risk factor for breast cancer."

Seminal to discussions regarding the potential value of ductal lavage as a risk assessment tool is the fact that mode of detecting atypia appears to be irrelevant to the strength of the observed association between its presence and likelihood of future breast cancer development. Similar relative risks for breast cancer have been reported following atypical cells detected on open surgical biopsy specimens,[7,8,9,10,11,12,13] fine-needle aspirates,[6] and nipple aspirate material.[2,3] It has been assumed that atypical cells identified from ductal lavage fluid confer the same degree of increased breast cancer risk in the affected woman. It should be noted, however, that there have not yet been any long-term studies reported regarding outcome of women under-going ductal lavage. Therefore, the relative risk for atypical hyperplasia detected in this setting has not yet been conclusively documented, although the presumption of a similar measure of effect seems reasonable. Furthermore, breast cytopathology has evolved into a specialized field, and any medical institution that is developing a ductal lavage program should ensure the availability of a skilled, experienced cytopathologist.

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