Ductal Lavage and Ductoscopy: What Can We Learn From the Ductal Lining?
The Cleveland Clinic Foundation
It has long been known that breast cancer and its precursors arise from the ductal lining.
Access to this lining has been limited but recently technological advances have made it possible to both
visualize the ductal lining and sample cells from this lining.
The advantages for this approach include new ways to think about breast cancer risk assessment, early
breast cancer diagnosis and therapeutic modalities including directly treating lesions and following
cytologic changes to assess response to therapy. Many of these possibilities are hypothetical so today I
will focus on two procedures that are currently being used to approach the ductal lining. In our
laboratory we first started collecting cells during ductoscopy for cytologic analysis. I will discuss
our findings and experience with ductoscopy first and end with a discussion of the less invasive
procedure, ductal lavage as a tool for risk assessment
- Ductoscopy: Introduction
- Japanese extensive experience with ductoscopy, many were limited by optics, catheter characteristics
- Acueity Ductoscope (Larkspur, CA} 0.9mm rigid fiberoptic scope with a 200um working channel, excellent visualization of the duct lining, able to lavage area of interest and collect cells.
Ductoscopy: Patient Group - Spontaneous Nipple Discharge Group
- Standard approach has been: ductography, nipple discharge cytology, surgery
- 35-48% of women have intraductal papillomas
- Ductoscopy – ease of cannulation secondary to dilated ducts, visualization of lesion – guide surgery, limited excision, assist pathologist
- Lavage performed at the time of surgery to correlate cytologic and Histologic findings
Spontaneous Nipple Discharge
- 91 ductal lavage specimens from 89 patients
- 14-80 years, mean 54.5 years
- Ductograms – filling defects in 34 (38%) of patients
- Ductoscopy – visualized papillomas in 51/89 patients
- Twelve specimens were acellular
- Cellular specimens were evaluated for cytologic characteristics
Spontaneous Nipple Discharge: Cytologic and Histologic Findings
- Papillomas – moderate to marked nuclear atypia – 15 specimens
- Large epithelial clusters with papillary architecture with more abundant opaque cytoplasm – characteristic
- Single cells weren't predictive of pathology
- Intraductal papilloma – 59 (67%)
- Fibrocystic changes, duct hyperplasia, duct ectasia 23 (26%)
- DCIS – 2, Invasive carcinoma –1, atypical papilloma/LCIS – 1
- SND – cytology of papillomas could be a pitfall for a diagnosis of marked atypia or malignant in lavage specimen
- Ductoscopy was useful in visualizing and localizing pathology allowing for a more limited resection at times.
- Ductal Lavage : Role in Risk Assessment
- Effective options for preventing breast cancer have focused attention on risk assessment
- NSABP P-1 study showed overall 49% reduction in breast cancer for women on tamoxifen, prophylatic mastectomy – 90% reduction
- Tamoxifen reduced risk 86% in women with atypical ductal hyperplasis
- Risks of tamoxifen, pulmonary emboli, endometrial cancer, stoke in older women
- Port, et al found that high risk women reluctant to take Tamoxifen when counseled regarding risk and benefits
Atypical ductal cells: Can they be used to select patient group most appropriate for Tamoxifen therapy
- Nipple Aspirate Fluid (NAF) – 2,343 women followed for average of 12.7 years after NAF analyzed cytologically, 4.9x increased risk in women with atypical cells, 18x risk with family history
- Random FNA: Fabian et al, random FNA, analyzed cytologically followed for median of 45 months, 5.02x risk
- ADH/Biopsy: Dupont and Page, follow up 10-17 years, 4.3-5.3 x risk and 11-22x risk with family history
Ductal Lavage vs NAF
- Dooley, et al, 507 high risk women (elevated Gail Risk >1.7%), NAF and DL performed if fluid yielding ducts are present
- DL – increased cellular yields, increased atypical diagnoses, method to allow collect of ductal cells to assess for cytologic atypia and risk
- Only indicated for use in high risk patients
|Cytologic Diagnoses|| Dooley Paper|
|Insufficient cellular Material for Diagnosis (ICMD)|
(less than 10 epithelial cells)
|Mild Atypia|| 17%|
|Moderate atypia|| 6%|
Issues to consider include:
- Patient management – approach to patient with atypical cells
- Negative Predictive value- undefined
- Reproducibility of cytologic diagnosis
- Pitfalls in diagnosis – papillomas
- Role of molecular cytopathology for further defining risk and early detection-Evron, et al – Lancet 2001 methylation specific PCR in ductal lavage cells
- Shen KW, Wu J, Lu JS, et al: Fiberoptic ductoscopy for patients with nipple discharge. Cancer 2000;
- Dietz JF, Kim JA, Malycky JL, et al: Feasibility and technical considerations of mammary ductoscopy
in human mastectomy specimens. The Breast J 2000;6:161-165.
- Okazaki A, Hirata K, Okazaki M, et al. Nipple discharge disorders: current diagnostic management
and the role of fiberoptic ductoscopy. Eur Radiol 1999; 583-590.
- Sauter ER, et al: Nipple Aspirate fluid: a promising non-invasive method to identify cellular
markers of breast cancer risk. Brit J Canc 1997;76:494-501.
- Fabian CJ, Kimler BF, Zalles CM, et al: Short-term breast cancer prediction by random peri-areolar
fine-needle aspiration cytology and the Gail risk model. J Natl Cancer Inst 2000 92:1217-1277.
- Dupont and Page, "Risk Factors for breast cancer in women with proliferative breast disease. NEJM
- Wrensch, et al, Breast Cancer incidence in women with abnormal cytology in nipple aspirates of breast
fluid. Am J Epidemiol 135:130-141 1992.
- Fisher et al, Tamoxifen for prevention of breast cancer: report of the national surgical adjuvant
breast and bowel project P-1 study. J Natl Cancer Inst 90:1371-1388 1998.
- Hartman et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of
breast cancer NEJM 340:77-84 1999
- Dupont el al; Breast cancer risk associated with proliferative breast disease and atypical
hyperplasia. Cancer 71:1258-1265 1993
- Dooley et al: Ductal lavage for detection of cellular atypia in women at high risk for breast cancer
J Natl Cancer Inst 93: 1624-1632 2001
- Port et al. Patient reluctance toward tamoxifen use for breast cancer primary prevention. Annals of
surgical Oncology 8(7): 580-585.
- O'Shaughnessy, et al. Ductal lavage and the clinical management of women at high risk for breast
carcinoma. Cancer 94: 292-298 2002.
- Morrow M, Vogel V, et al, Evaluation and management of the woman with an abnormal ductal lavage. J
Am Coll Surg 194(5); 648-656. May 2002.
- Evron E, Dooley WS, Umbricht CB, et al. Detection of breast cancer cells in ductal lavage fluid by
methylation specific PCR. Lancet 2001; 357:1335-1336.