Ductal Lavage

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Ductal Lavage

• Rama Suresh M.D.
• Hematology-Oncology Fellow
• Washington University School of Medicine

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Malignant Transformation
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Prevention of Breast Cancer

• NSABP P-1 study (JNCI 1998)
• Prophylactic mastectomy study (NEJM 1999)

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Gail risk

• age
• age at menarche
• age at first live birth
• number of first-degree relatives with breast
  cancer
• number of previous breast biopsies (whether
  positive or negative)
• any biopsy with atypical hyperplasia

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Limitations of Gail risk

• Population based risk
• Not evaluated for routine screening or case
  finding
• Not accurate in women younger than 40
• Not useful in assessing immediate risk

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Ductal anatomy

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Procedure

• FDA approved
• Only in women at high Gail Risk
• Detects atypical cells, DCIS when there is no
  palpable or imageable lesion
• Minimally invasive, office based

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Ductal Lavage Step 1
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Ductal Lavage Step 2
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Ductal Lavage Step 3
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Ductal Lavage Step 4
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Lavage fluid processing

• Similar to FNA, nipple discharge and NAF samples.
• Millipore filtration - Cytospin - Thin prep -Pap
  staining.
• Contain epithelial cells, foam cells and
  hematogenous cells. (rare Myoepithelial cells).

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Cytology
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Morbidity

• Pain
• Engorgement
• Ecchymosis
• Infection (rare)

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Atypical ductal cells

• NAF Wrensch et al. Am J Epi 1992.
• 2343 patients over 12.7 yrs.
• RR of 2.5 5 at 12.5 yrs.
• FH RR 18
• Random peri-areolar FNA Fabian et al. JNCI 2000.
  
• 480 patients over 45 months. RR 5.
• Cancer incidence (at 3 years) 15 vs 4
• RR of atypia atypical ductal hyperplasia
  (Dupont et al NEJM 1985 Cancer 1993, Page et
  al. Cancer 1985).

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Ductal lavage vs NAF

• Dooley et al (JNCI 2001)
• 507 high risk women with
• Gail risk more than 1.7,
• previous breast cancer
• BRCA 1 or 2 mutation carrier.
• Neg mammogram and physical exam within 12 months
  .

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DL vs NAF
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Ductal lavage vs random FNA

• Prevalence of atypical cells by DL (23)Dooley
  (JNCI 2001) is equivalent to that detected by
  random FNA (21) (Fabian et al. JNCI 2000).
• Less invasive and morbid (pain, bleeding and
  bruising)
• Localization to an individual duct.

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Morrow JACS 5/02
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Limitations of mammography

• Not all cancers can be seen
• Differences in the appearance of the normal
  breast
• Cannot distinguish malignant from benign tumors
• Younger women have more dense breast tissue
• Breast implants
• Powder or salve on the breasts
• Breast surgery

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Methylation specific PCR

• Genes have a lower expression in breast cancer
  than healthy tissue
• Genes are silenced by hypermethylation of
  promoter sequences (Evron et al. Cancer Res 2001,
  S.M. Sirchia et al. Oncogene 19 (2000) )
• Cyclin D2, RAR-b and Twist genes are
  hypermethylated in more than 30 of breast cancer
  tissue but unmethylated in healthy tissue.
• Noninvasive detection of small number of cancer
  cells.(J.G. Herman et al. PNAS 1996)

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MSP (E. Evron et al. Lancet 2001)

• 37 women with biopsy proven cancer
• Both ROBE and DL
• DNA from both ductal fluid cells and surgical
  samples tested with MSP

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(No Transcript)
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Cost of trials

• Phase III trials NSABP P2 (STAR)
• 22,000 participants and 200 million.

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Prevention

• ER tissue agents
• SERMs, SERD, isoflavones, aromatase
  inhibitors/inactivators, GNRH agonists.
• Retinoids, rexinoids and deltanoids

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Prevention

• ER/- agents
• Polyamine synthesis inhibitors
• Tyrosine kinase inhibitors
• Anti- EGFR antibodies
• COX 2 inhibitors
• Demethylating agents
• Histone deacetylase inhibitors
• Metaloprotease inhibitors
• Angiogenesis inhibitors
• Monoterpenes

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Ductal Lavage

• Best used in clinical trials of cancer detection
  and prevention.
• Assessing high- risk women
• Counseling for Tamoxifen