Ductal Carcinoma In Situ (DCIS)

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Ductal Carcinoma In Situ (DCIS)

• JoAnne Zujewski, MD
• Head, Breast Cancer Therapeutics
• Clinical Investigations Branch
• Cancer Therapy Evaluation Program
• Division of Cancer Diagnostics and Treatment
• May 2011

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Questions

• How DCIS differs from Stage 1 breast cancer
• Types of DCIS that affect prognosis of
  DCIS/development of breast cancer
• Standard of Care surgery, radiation risks of
  under-treatment and overtreatment
• Can we improve diagnosis through MRI and sentinel
  lymph node biopsy?

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Pathobiologic Events Associated with DCIS
Burstein H et al. N Engl J Med 20043501430-1441
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DCIS Pathology
Cribiform, High grade
Comedo
Solid, Low grade
Rosens Breast Pathology, 1997
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DCIS actin Stain of Myoepithelium
Rosens Breast Pathology, 1997
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SEER Breast Carcinoma in situ5-year Survival
1992-1999
All lt 50 50
All 100.0 99.9 100.0
White 100.0 100.0 100.0
Black 100.0 99.5 100.0
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Survival DCIS RCT
NSABP B17 EORTC UKANZ CTG NSABPB24
N 813 1002 1694 1798
Mets 17 (2.1) 24 (2.4) 11 (0.6)
Breast Deaths 27 (3.3) 15 (1.5) 23 (1.4) 15 (0.8)
Years F/up 10.8 4.3 4.4 6.9
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Natural History

• 25 cases untreated with 16 yrs follow up
• 28 developed invasive cancer
• 11 fold increase in relative risk to controls
• Contralateral relative risk 2-3

Page et al Cancer 1985552698-708
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Role of Total Mastectomy
Year No. cases mortality
Ashikari 1971 182 0.9
Rosner 1980 182 2.0
Farrow 1970 181 2.0
Silverstein 1996 228 0
Bradley 1990 588 1.7
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Surgery

• Mastectomy has not been compared to BCT in
  randomized trials of DCIS
• Breast cancer deaths within 10 years after the
  diagnosis of DCIS occurs in 1-2 of all patients,
  irrespective of surgery type

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RATIONALE FOR RADIATION TREATMENT AFTER
LUMPECTOMY FOR DCIS

• All reported randomized trials show that
  radiation reduces the rate of local recurrence
  after lumpectomy by about half
• Patients who may avoid radiation therapy have
  not been reproducibly and reliably identified by
  any clinical trials. (1999 DCIS Consensus
  Conference Statement, Cancer, 2000)

Slide courtesy of L. Solin
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Oxford Overview of Randomized Trials of BCSRT
for DCIS
Presented NIH DCIS Conference, 2009 Darby, JNCI
Monograph, 2010
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ECOG STUDY E5194 (n 670)
Registration of small DCIS after wide excision
alone Negative margin width gt 3 mm Tamoxifen
optionalTwo arms (not randomized) Grade 1-2,
non-comedo, size lt 2.5 cm Grade 3, comedo, size
lt 1.0 cm
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ECOG E5194 EXCISION WITHOUT RADIATION (/-TAM)
High grade
Low or intermediate grade
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Year
Hughes, JCO, 2009
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LOCAL FAILURE ACCORDING TO PATHOLOGY
Lumpectomy plus radiation
Lumpectomy alone
Solin, JCO, 1996
Slide courtesy of L. Solin
Balleine, Clin Cancer Res, 2008
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DCIS NSABP B-24Role of Tamoxifen
Fisher, B, Lancet 3531993-2000, 1999
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DCIS NSABP B-24Median follow-up 7 years
placebo placebo tamoxifen tamoxifen P-value
All breast cancer 145 16 84 9.3
ipsilateral 100 11.1 72 7.7 0.02
Contra-lateral 45 4.9 25 2.3 0.01
survival 95 95
Fisher, B et al, Semin Oncol 28400-18, 2001
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NSABP B-24 Conclusions

• Tamoxifen decreases risk of breast cancer events
  by 40
• No difference in overall survival

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The Risk of Ipsilateral or Contralateral Breast
Tumor for Patients with DCIS Treated with
Excision Alone Excision and Radiotherapy
Excision, Radiotherapy, and Tamoxifen or
Excision, Radiotherapy, and Placebo
Burstein H et al. N Engl J Med 20043501430-1441
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DCIS Conclusions

• Local therapy
• Mastectomy
• Breast Conserving Surgery plus radiotherapy
• Consider omission if
• Short lifespan
• Sever co-morbidities
• Systemic therapy Tamoxifen
• Prevention intervention
• Consider individual risk/benefits

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What about lymph nodes?

• Axillary lymph node involvement is lt1 therefore
  axillary lymph node dissection is not recommended
• Sentinel lymph node biopsy?
• Not recommended due to low risk of disease unless
  performing a mastectomy (in the chance that
  invasive disease is found)
• Consider extensive high grade DCIS or palpable
  mass (increased chance of invasive disease being
  found)

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Potential Benefits

• SLNB at time of definitive surgery avoids 2nd
  operation in 2-21 of patients who have IDC at
  definitive surgery
• May identify subset of patients who would benefit
  from systemic therapy

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Risks of SLNB in DCIS

• Increase anxiety curable prognosis to one that
  is life-threatening
• SLNB risks
• infection, bleeding, seroma, paresthesias,
  anaphylaxis, lymphedema (3)
• Risks of full ALND in up to 13
• Risks of systemic chemotherapy ?
• Public health costs

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• Mammography is the current standard for detection
  of DCIS, MRI could help improve the ability to
  diagnose DCIS, especially in high-grade DCIS

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DCIS Calcifications Cannot be diagnosed as
non-invasive with cytology
Irregular clusters
Branching (comedo)
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MRI Contrast required..spatial resolution
improves morphologic assessment
Mass, heterogeneous and rim enhancement,
spiculated margins
DCIS consensus conference. C. Lehman
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DCIS diagnosed in high risk patient on screening
MRI with negative screening mammogram Fine
linear, branching NMLE in ductal distribution
DCIS consensus conference. C. Lehman
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ACR-ASS-CAP-SSO 2006 practice guideline

• The role of other image modalities, especially
  MRI, has yet to be established in DCIS.
• Berg found that MRI was more sensitive than
  mammography and sonography in detecting DCIS
  however, disease extent was overestimated in 50
  of involved breasts.
• The impact of MRI on clinical outcomes such as
  local recurrence in the preserved breast remains
  to be demonstrated.

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KEY QUESTIONS FOR THE MANAGEMENT OF DCIS
Courtesy of L. Solin 2010