Ductal Lavage and Detection of Abnormal Cytology in Women at High Risk for Breast Cancer
William Dooley, Umberto Veronesi, Richard Elledge, Joyce O’Shaughnessy, Susan Love, Britt Marie Ljung and the Ductal Lavage Investigators

Breast cancer originates in the milk ducts. Ductal fluid cytology is routinely used clinically to evaluate spontaneous nipple discharge. Cytology from nipple aspirate fluid (NAF) has also been used in the research setting. Wrensch and Petrakis, et al., have reported on 2,300 women followed for 12.7 years with cytology on NAF. Women with cellular atypia had a 4.9-fold increase in the relative risk of developing breast cancer. The increase in relative risk was 18-fold in women with cellular atypia and a positive family history. Fabian, et al., reported a 5.0-fold increase in relative risk in a high-risk cohort of women with hyperplasia with atypical cells obtained by random fine needle aspiration. Similar increases in risk are conferred by atypical ductal hyperplasia (ADH) in studies by Dupont and Page.

• To determine the safety and feasibility of ductal lavage using a microcatheter in women at high risk for breast cancer.
  
  
• To determine the relative sensitivity of nipple aspiration and ductal lavage.

Subjects underwent nipple aspiration followed by ductal lavage of all fluid-yielding ducts. Women who did not have NAF did not undergo ductal lavage.

ASPIRATION		CANNULATION OF DUCT
1.	Gentle suction is applied to the nipple to elicit fluid.	2.	Microcatheter is inserted into duct.
INFUSION		MASSAGE OF BREAST
3.	10-20 mL of saline is slowly introducedinto the milk duct in 2 - 4 mL increments to lavage the duct and collect epithelial cells.	4.	The breast is massaged to bring fluid forward.

• NAF obtained in 84% of subjects
  
  
• Average of 1.5 NAF-yielding ducts/breast
  
  
• 417 subjects had samples sent for NAF cytology n 383 subjects had samples sent from 591 ducts for ductal lavage cytology
  
  
• 92% of subjects had at least one attempted duct successfully cannulated n There were no procedure-related serious adverse events
  
  
• Two local infections were treated with oral antibiotics
  
  
• Median subject rating of procedure discomfort was 24 with 0 representing no pain and 100 severe pain

DUCTAL LAVAGE SAMPLE			Ductal lavage obtained, on average, 40,000 epithelial cells per duct. 78% of samples were adequate for diagnosis. In comparison, NAF samples had ~1,800 epithelial cells per breast and only 27% were adequate.

BENIGN		MILDLY ATYPICAL
SUSPICIOUS (MARKEDLY ATYPICAL)		MALIGNANT

Occult DCIS detected in 4/11 surgical workups:

• 2 cases of fibrocystic changes

Issues

• Over-reading of cytology?
  
  
• Incomplete surgical resection?
  
  
• Incomplete histopathology?

Case Study: Subject CW

• 29 y.o. with previous cancer/mastectomy in R breast; underwent ductal lavage in L breast
  
  
• Suspected malignant cells in one duct in L breast
  
  
• Negative mammogram and ductogram after lavage
  
  
• Lymphazurin infused down suspicious duct and exploration/resection of "blue" ducts performed

Suspicious for Malignancy	Extensive DCIS, intermediate grade, 6.0 cm (greatest dimension)

• 62 y.o. woman, Gail 2.9 with 4 negative mammograms prior to lavage
  
  
• First lavage 8/99: malignant cells in a single duct in one breast

  Negative mammogram and ductogram (high mag) after lavage

• Second lavage 10/99: Suspicious duct cannulated; malignant cytology confirmed
  
  
• Third lavage and surgery 11/99: Suspicious duct cannulated; lymphazurin injected down duct and "blue" ductal system resected

Pathology Results:

• High grade DCIS with focal comedo necrosis
  
  
• 1.8 cm in estimated size involving large lactiferous ducts extending to 2 mm from inked margins

CYTOLOGY	PATHOLOGY

• Ductal lavage is a safe, well-tolerated and minimally invasive procedure for collecting breast ductal epithelial cells for the determination and differentiation of normal, premalignant and malignant cells.
  
  
• Ductal lavage collects ductal epithelial cells far more efficiently than nipple aspiration and is more sensitive than nipple aspiration for detecting cellular abnormalities in the breast.
  
  
• Ductal lavage may be a useful adjunct to mammography and other currently available imaging modalities for the early detection of intraductal breast pathology.

Ductal Lavage Investigators:

• W. Dooley, Johns Hopkins
• U. Veronesi, Istituto Europeo di Oncologia
• R. Elledge, Baylor/Houston
• J. O'Shaughnessy, Baylor/Dallas
• H. Kuerer, MD Anderson
• S. Khan, SUNY Ð Syracuse
• D. Hung, Pro¥Duct Health
• R. Phillips, Atlanta
• P. Ganz, UCLA
• D. Euhus, U. Texas, SW
• L. Esserman, UCSF
• B. Haffty, Yale
• M. Kelley, Vanderbilt
• M. Anderson, King/Drew
• P. Schmit, UCLA/Olive View
• R. Clark, Santa Barbara
• B. Anderson, U. Washington
• S. Troyan, Beth Israel Deaconess
• R. Arias, USC

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