The breast ducts can be examined and evaluated for the presence of fluid or hyperplasia via fiberoptic ductoscopy, providing direct visual examination by means of a small endoscope. 

Fiberoptic ductoscopy as well as analysis of breast ductal fluid cytology have been proposed as diagnostic and risk assessment tools in individuals at high risk of breast cancer with or without mammographic abnormalities, as well as those with a high risk of breast cancer who are considering initiating tamoxifen chemoprevention.

Investigational and Not Medically Necessary:

Cytologic analysis of breast ductal fluid, acquired invasively or non invasively, is considered investigational and not medically necessary as a diagnostic or risk assessment tool for those considered at high risk for breast cancer, as well as for general population screening.

Breast fiberoptic ductoscopy is considered investigational and not medically necessary for the detection, diagnosis or treatment of breast cancer.

The published data on breast aspirate cellular material consists primarily of the results of a multi-center clinical trial in which the diagnostic yield of ductal lavage was compared to that of nipple aspiration in 507 women considered at high risk of breast cancer and who did not have mammographic abnormalities. High risk was defined as those who would meet the criteria established for the randomized trial of chemoprevention; including anyone with a Gail score of greater than 1.7 or BRCA mutation positive. Fifty seven percent (57%) of the participants had a prior history of breast cancer. All participants first underwent nipple aspiration, followed by ductal lavage. Nipple aspiration produced adequate samples for analysis in 27% of women, compared to ductal lavage, which produced adequate samples in 78%. A total of 24% of ductal lavage samples revealed atypical cells, compared to 6% of fine needle aspiration samples (Dooley, 2001). Treatment decisions and outcomes based on these findings have not been reported.

Other studies have found inconsistencies with cytological analysis. Visvanathan and colleagues (2007) found that the use of ductal lavage is limited by the technical challenges of duct cannulation, inconsistent nipple aspirate fluid production, a high rate of inadequate cellular material for diagnosis and a fair cytologic reproducibility.

Supportive data for using results of ductal lavage as a risk assessment tool are based on studies that have shown that atypical hyperplasia is associated with an increased risk of cancer (Degnim, 2007; Fabian, 2000), which if identified accurately, can be significantly reduced with tamoxifen therapy. The major unanswered clinical question is whether the natural history of atypical hyperplasia identified in mammographically normal women (i.e. in the ductal lavage clinical study) confers the same degree of risk of atypical hyperplasia associated with mammographic abnormalities (i.e. in the tamoxifen cancer chemoprevention trial), and whether the two populations of participants respond similarly to tamoxifen. Additionally, since the sensitivity of ductal lavage is unknown, a negative test (i.e. absence of atypical hyperplasia) is not informative for the individual and should not contribute to decision-making about whether to initiate tamoxifen therapy.

In a study designed to determine which histological lesions produce cellular atypia in lavage specimens and whether ductoscopy adds useful information for the evaluation of high-risk individuals with atypical lavage cytology, Cyr and colleagues (2011),  prospectively studied 102  women who were 35 years or greater at high risk for developing breast cancer. All underwent ductal lavage. Women found to have atypia underwent ductoscopy-directed duct excision (group 1). Women without atypia were observed (group 2). The median follow up was 80 (range 5-90) months. Data included participant demographics, risk assessment, cytologic and histologic findings, and outcomes. Descriptive statistics were utilized for data summary and were compared using Fisher's exact test. Overall, 27 (26%) had atypical lavage cytology (group 1), and 75 (74%) had benign cytology (group 2). Subsequent duct excision in group 1 revealed benign histology in 11 (44%), papillomas in 9 (36%), atypical hyperplasia (AH) in 4 (16%), and ductal carcinoma in situ (DCIS) in 1 (4%). At follow-up, three participants developed breast cancer, including one group 1 participant and two group 2 participants. There were no differences between groups 1 and 2 according to their demographics, Gail scores, or risk for subsequent breast cancer (p greater than 0.05). The authors concluded that although 20% of high-risk women with ductal lavage atypia have AH or malignancy on subsequent excision, the majority do not. Atypia identified by ductal lavage is not associated with a higher risk of developing subsequent breast cancer, even in this high-risk population.

In a retrospective review, Fisher and colleagues (2011) supported mammary ductoscopy because it allows direct visualization of the ductal system and a method for directed excision and pathologic diagnosis. The authors reviewed those who underwent ductoscopy by the same surgeon for pathologic nipple discharge at one  institution from 2006-2010. Data included imaging characteristics, indications, operative findings, and pathologic outcomes. Descriptive statistics were used for data summary. One hundred twenty one participants underwent ductoscopy and directed duct excision for pathologic nipple discharge, including 66 (55%) with bloody discharge. Breast imaging (mammography, ultrasound, and/or MRI) revealed the Breast Imaging Reporting and Data System (BIRADS) category I/II/III findings in 112 (93%), BIRADS category IV findings in 6 (5%), and was unknown in 3 (2%) participants. Final pathology revealed papillomas in 64 (53%) participants, duct ectasia and associated benign findings in 48 (40%) participants, DCIS in 7 (6%) participants, and atypical ductal hyperplasia in 2 (1%) participants. The authors acknowledged that majority of those with pathologic nipple discharge have benign nonproliferative findings or benign papillomas. Although in this study, atypia and malignancy were diagnosed in only 7% of those who underwent ductoscopy for pathologic nipple discharge, there were, however, no routine imaging findings indicative of these diagnoses preoperatively.

Fiber optic ductoscopy enables direct visual examination of the breast ducts using a small endoscope, advanced through an enlarged duct at the nipple. Its utility for the detection, diagnosis and treatment of breast cancer has not been demonstrated by randomized controlled studies. In addition, data is lacking as to whether ductoscopy-directed duct excision for those with pathologic nipple discharge can reduce the occurrence of ipsilateral breast cancer development.

The American Cancer Society (ACS) states: 

Ductal lavage is an experimental test developed for women who have no symptoms of breast cancer but are at very high risk for it. It is not a test to screen for or diagnose breast cancer, but it may help give a better picture of a woman's risk of developing it.

…Ductal lavage is not thought to be helpful for women who aren't at high risk for breast cancer. It is not clear whether it will ever be a useful tool. The test has not been shown to detect cancer early. It is much more useful as a test of cancer risk rather than as a screening test for cancer. More studies are needed to better define the usefulness of this test.

Nipple aspiration also looks for abnormal cells from the ducts, but is much simpler, because nothing is put into the breast. The device for nipple aspiration uses small cups that are placed on the woman's breasts. The device warms the breasts, gently compresses them, and applies light suction to bring nipple fluid to the surface of the breast. The nipple fluid is then collected and sent to a lab for testing. As with ductal lavage, the procedure may be useful as a test of cancer risk, but is not thought to be helpful as a screening test for cancer. The test has not been shown to detect cancer early (ASC, 2010).

The 2011 National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology™, Breast Cancer Screening and Diagnosis Guidelines stated that current evidence does not support the routine use of ductal lavage as a screening procedure.

The American Society of Breast Surgeons (ASBS) position states that:

Ductal lavage is a minimally-invasive method of collecting breast epithelial cells for cytological examination. Cytologic interpretation of fluid obtained by ductal lavage is not an approved screening tool for the detection of breast cancer. The American Society of Breast Surgeons cautions that ductal lavage should not replace standard cancer screening methods. Long-term studies are necessary to better define the risk assessment contribution of cytologic atypia detected via these and other methods. The American Society of Breast Surgeons encourages participation in such trials.

Breast cancer is the most common of female malignancies worldwide (excluding skin cancers) and the second leading cause of cancer death in women in the U.S. According to American Cancer Society predictions, nearly 212,000 new cases of breast cancer will be discovered in the United States this year, and more than 40,000 women will die of the disease. About 95% of breast cancers originate in the ducts, and abnormal cells found there are believed to be associated with a significant increased risk of breast cancer. Early detection based on established and effective screening programs, a high degree of awareness of the disease in the population, and aggressive multi-modality therapy have led to a decline in mortality from breast cancer in the developed world.

Since 95% of breast cancers originate in the breast ducts, analysis of epithelial cells found in ductal fluid has been studied as an early indicator of breast cancer. These cells, if atypical, might indicate the possibility of future breast cancer.

Breast ductal fluid can be obtained by ductal lavage or nipple aspiration via suction or random periareolar fine needle aspiration (RPFNA). Ductal lavage is an invasive procedure that obtains ductal fluid by the cannulation of the breast milk ducts via the nipple. Fluid is aspirated and analyzed. There are three devices approved by the FDA for ductal lavage: FirstCyte^® Aspirator, FirstCyte^® MicroCatheter, and FirstCyte^® MicroDilator (Cytyc Corp., Marlborough, Ma.) all of which are Class II devices. Another invasive technique for ductal aspiration is random periareolar fine needle aspiration (RPFNA). In this procedure, a fine gauge needle with suction capabilities is introduced into a duct in the nipple area. Gentle suction is applied for fluid acquisition.

The HALO™ Breast Pap Test (NeoMatrix, LLC, Irvine, CA) is an FDA approved noninvasive device that is positioned on the nipple and acquires ductal fluid by applying heat, cyclic compression and suction.  This device is discussed in one small study funded by the manufacturer and concludes that although the device can collect the duct fluid noninvasively, well designed randomized controlled studies are required to determine the utility of cytological analysis of breast ductal fluid (Proctor, 2007).

In general, this testing is problematic in that not all ducts produce fluid, or if fluid is found, the quantity may not be sufficient for testing. Furthermore, ducts producing fluid may not be the source of the atypical cells associated with early stages of cancer.  These inconsistencies need to be resolved before this testing is considered efficacious for early identification of breast cancer.

Fiberoptic ductoscopy has been developed for structural examination of the breast duct.  The procedure involves the enlargement of the duct at the nipple with small metal wires. A ductoscope, which is a small tube with a camera attached, is passed into the duct and advanced into the breast. Water may be injected through the scope into the duct to allow easier passage of the scope. Fluid may be collected through the scope and examined and/or a very thin wire probe may be passed up to several inches into the breast to sample any abnormalities that might be found.  Fiberoptic ductoscopy is currently being performed in research centers and studied in clinical trials for use in various clinical situations.  The ViaDuct™ Microendoscope (Acueity Inc., Palo Alto, CA), used for ductal endoscopy, received 510(k) clearance by the FDA in 2001.

Atypical: Irregular, not conformable.

BIRADS: The Breast Imaging Reporting and Data System is a tool used to categorize results of breast mammography, ultrasound and magnetic resonance imaging (MRI). It is divided into the following levels:
BIRADS 0: Assessment incomplete.  Additional imaging evaluation
BIRADS 1: Negative.  Routine follow-up for age
BIRADS 2: Benign finding. Routine follow-up for age
BIRADS 3: Probably benign. Short-term follow-up (usually in 6 months)
BIRADS 4: Suspicious abnormality. Tissue sampling
BIRADS 5:  Highly suspicious of malignancy. Tissue sampling

Cannula: A tube for insertion into a duct or cavity.

Duct: A duct is a passageway with well-defined walls, especially a tube for the passage of excretions or secretions.

Ductal: Relating to a duct.

Gail Model:  A computer program that uses personal and family history to estimate a woman's chance of developing breast cancer.

Orifice: An opening.

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time for service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary. 

Peer Reviewed Publications:

1. Adduci KM, Annis CE, DeVries S, et al. Fluorescence in situ hybridization of ductal lavage samples identifies malignant phenotypes from cytologically normal cells in women with breast cancer. Cancer. 2007; 111(3):185-191.
2. Arun B, Valero V, Logan C, et al. Comparison of ductal lavage and random periareolar fine needle aspiration as tissue acquisition methods in early breast cancer prevention trials. Clin Cancer Res. 2007. 15; 13(16):4943-4948.
3. Brogi E, Robson M, Panageas KS, et al. Ductal lavage in patients undergoing mastectomy for mammary carcinoma: a correlative study. Cancer. 2003; 98(10):2170-2176.
4. Bushnaq ZI, Ashfaq R, Leitch AM, Euhus D. Patient variables that predict atypical cytology by nipple duct lavage. Cancer. 2007; 109(7):1247-1254.
5. Carruthers CD, Chapleskie LA, Flynn MB, Frazier TG. The use of ductal lavage as a screening tool in women at high risk for developing breast carcinoma. Am J Surg. 2007; 194(4):463-466.
6. Cyr AE, Margenthaler JA, Conway J, Rastelli AL, et al. Correlation of Ductal Lavage Cytology with Ductoscopy-Directed Duct Excision Histology in Women at High Risk for Developing Breast Cancer: A Prospective, Single-Institution Trial. Ann Surg Oncol. 2011 Aug 17. [Epub ahead of print]
7. Danforth DN, Abati A, Filie A, et al. Combined breast ductal lavage and ductal endoscopy for the evaluation of the high-risk breast: A feasibility study. J Surg Oncol 2006; 94:555-564.
8. Dietz JR, Crowe JP, Grundfest S, et al. Directed duct excision by using mammary ductoscopy in patients with pathologic nipple discharge. Surgery. 2002; 132(4):582-588.
9. Dooley WC, Ljung BM, Veroneri U, et al.  Ductal Lavage for the detection of cellular atypical in women at high risk for breast cancer.  J Natl Cancer Inst. 2001; 93(21):1624-1632.
10. Dooley WC.  Routine operative breast endoscopy during lumpectomy. Ann Surg Oncol 2003; 10(1): 38-42.
11. Escobar PF, Crowe JP, Matsunaga T, Mokbel K. The clinical applications of mammary ductoscopy. Am J Surg. 2006; 191(2):211-215.
12. Fabian CJ, Kimler BF, Zalles CM, et al. Short-term breast cancer prediction by random periareolar fine-needle aspiration cytology and the Gail risk model. J Natl Cancer Inst. 2000; 92(15):1217-1227.
13. Fisher CS, Margenthaler JA. A Look into the Ductoscope: Its Role in Pathologic Nipple Discharge. Ann Surg Oncol. 2011 Aug 23. [Epub ahead of print]
14. Khan, SA, Wiley EL, Rodriguez N, et al. Ductal lavage findings in women with known breast cancer undergoing mastectomy. J. Natl Cancer Inst 2004; 96(20):1510-1517.
15. Locke I, Kote-Jarai Z, Bancroft E, et al. Loss of heterozygosity at the BRCA1 and BRCA2 loci detected in ductal lavage fluid from BRCA gene mutation carriers and controls. Cancer Epidemiol Biomarkers Prev. 2006; 15(7):1399-1402.
16. Louie LD, Crowe JP, Dawson AE, et al. Identification of breast cancer in patients with pathologic nipple discharge: does ductoscopy predict malignancy? Am J Surg. 2006; 192(4):530-533.
17. O'Shaughnessy JA, Ljung BM, Dooley WC, et al. Ductal lavage and the clinical management of women at high risk for breast carcinoma. Cancer. 2002; 94(2):292-298.
18. Shen KW, Wu J, Lu JS, et al. Fiberoptic ductoscopy for patients with nipple discharge. Cancer. 2000; 89(7): 1512-1519.
19. Shen KW, Wu J, Lu JS, et al. Fiberoptic ductoscopy for breast cancer patients with nipple discharge.  Surg Endosc. 2001; 15(11):1340-1345.
20. Visvanathan K, Santor D, Ali SZ, et al. The reliability of nipple aspirate and ductal lavage in women at increased risk for breast cancer--a potential tool for breast cancer risk assessment and biomarker evaluation. Cancer Epidemiol Biomarkers Prev.  2007; 16(5):950-955.
21. West KE, Wojcik EM, Dougherty TA, et al. Correlation of nipple aspiration and ductal lavage cytology with histopathologic findings for patients before scheduled breast biopsy examination. Am J Surg. 2006; 191(1):57-60.
22. Heinig J, Witteler R, Schmitz R, et al. Accuracy of classification of breast ultrasound findings based on criteria used for BI-RADS. Ultrasound Obstet Gynecol. 2008; 32(4):573-578.
23. Wrensch MR, Petrakis NL, Mike R, et al. Breast cancer risk in women with abnormal cytology in nipple aspirates or breast fluid.  J Natl Cancer Inst. 2001; 93(23):1791-1798.
24. Zalles CM, Kimler BF, Simonsen M et al. Comparison of cytomorphology in specimens obtained by random periareolar fine needle aspiration and ductal lavage from women at high risk for development of breast cancer. Br Cancer Res Treat 2006; 97:191-197.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Blue Cross Blue Shield Association. Use of Epithelial Cell Cytology in Breast Cancer Risk Assessment and High-Risk Patient Management. TEC Assessment, 2002; 17(1).
2. The American Society of Breast Surgeons (ASBS). Ductal Cell-Based Risk Assessment Statement. 2007. Available at: http://www.breastsurgeons.org/statements/PDF_Statements/Ductal_Cell.pdf . Accessed on September 22, 2011.
3. NCCN Clinical Practice Guidelines in Oncology™ (NCCN). © 2011 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org/index.asp. Accessed on September 22, 2011.
   • Breast Cancer Screening (V1. 2011). Revised November 19, 2010.

1. American Cancer Society (ACS). Other breast imaging tests. 2011. Available at:  http://www.cancer.org/Treatment/UnderstandingYourDiagnosis/ExamsandTestDescriptions/MammogramsandOtherBreastImagingProcedures/mammograms-and-other-breast-imaging-procedures-other-br-imaging-tests. Accessed on September 22, 2011.
2. National Cancer Institute (NCI). Breast Cancer Screening Modalities. Available at:  http://www.cancer.gov/cancertopics/pdq/screening/breast/healthprofessional/Page4#Section_256 . Accessed on September 22, 2011.

Ductal Lavage
Ductoscopy, Fiberoptic
FirstCyte® Aspirator
FirstCyte® MicroCatheter
FirstCyte® MicroDilator DucPrep™ Breast Aspirator 
HALO™

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.