Transcript Ductal Carcinoma In-Situ (DCIS)

Questions
 What are the histological differences between
atypical ductal hyperplasia (ADH), ductal
carcinoma in-situ (DCIS), atypical lobular
hyperplasia (ALH) and lobular carcinoma in-situ
(LCIS)? How do they each behave?
 What are the management options for DCIS and
what is the evidence?
 What surveillance is recommended for DCIS?
Benign Breast Disease
 Nonproliferative
 Proliferative without atypia
 Proliferative with atypia
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ADH
ALH
LCIS
 Considered “high risk” as they are associated with an
increase in the patient’s future risk of developing breast
cancer
 Not “premalignant”
Aytpical Hyperplasia (AH)
 Atypical Ductal Hyperplasia
(ADH)
 Characterised by proliferation of
uniform epithelial cells with
monomorphic round nuclei filling
part, but not all of the involved duct
 Shares some of the cytologic and
architectural features of low-grade
DCIS
 Atypical Lobular Hyperplasia
(ALH)
 Characterised by proliferation of
monomorphic, evenly spaced,
dyshesive cells filling part, but not all,
of the involved lobule
 Can also involve ducts
 Shares some cytologic and
architecural features of LCIS
ADH
 DCIS and invasive breast cancer is identified in 33-87%
of subsequent excision biopsies reported as ADH in
the core biopsy
Risk of Cancer After AH
 AH (especially multifocal lesions)
 Increased risk (RR 3.7-5.3) in ipsilateral and
contralateral breast (higher in ipsilateral)
 Conflicting data to suggest that the risk is higher
with ALH than ADH
 Relative risk increases when ADH occurs in
women with a family history of breast cancer in a
1st degree relative to 10 times that of the general
population with no family history
Lobular Neoplasia
 Spectrum of proliferative changes within the breast
lobule that includes both atypical lobular hyperplasia
(ALH) and LCIS
 Both associated with increased risk of invasive breast
cancer
 LCIS is non-invasive, multicentric proliferation of the
epithelial cells in the lobules and terminal ducts of the
breast
Histology
 LCIS diagnosed when all of the following occur:
 Cellular proliferation is characterised by round, cuboidal
or polyganal cells that are regularly arranged and evenly
spaced
 Cell nuclei are predominantly round, monotonous and
hyperchromatic
 Proliferation involves, distends and distorts at least half
the acini in the terminal duct-lobular unit and fills
involved lobular spaces, resulting in the absence of
central lumia
 ALH is diagnosed with a lesion fails to meet at
least one of the diagnostic criteria for LCIS in over
50% of acini within a lobular unit
LCIS
Cancer Risk
 ALH RR 3-4 (compared with general population)
 Greater risk in ipsilateral breast
 LCIS RR 7-9
 Appears to be as common in the contralateral breast as
in the ipsilateral breast
 Pleomorphic variant appears to have an aggressive
biologic profile
Management and Follow-Up
 Core Bx of ADH  excision biopsy due to
association with DCIS or invasive breast cancer
 No strong evidence about whether to perform
excision biopsy on women with LCIS or ALH on
core Bx
 Surveillance appears to be best the best
management option for women who have been
diagnosed with ADH, LCIS or ALH as the only
abnormality (annual clinical examination, annual
bilateral mammography for at least 15 years
following diagnosis)
Management and Follow-Up
 No role for CLE or mastectomy in the management of
ADH, LCIS or ALH
 Insufficient evidence to recommend the use of
tamoxifen for prevention of invasive breast cancer
following a diagnosis of ADH, LCIS or ALH (Australian
Guidelines)
DCIS
 Definition
 Abnormal proliferative condition of epithelial cells in
the mammary ducts
 Cells display cytological features of malignancy but
unlike invasive cancer, DCIS is confined within the ducts
 Why is it clinically significant?
 Historically data suggests that 20-30% of untreated
DCIS progresses to invasive cancer
 No reliable predictors for probability to progression to
invasive carcinoma
 Risk may be greater when DCIS displays features such
as comedo necrosis or high nuclear grade
 Natural history is largely unknown
Histology
 5 architectural subtypes:
comedocarcinoma, solid,
cribiform, papillary and
micropapillary
 Majority show a mixture of
patterns
 Malignant polyclonal
population of cells limited
to ducts and lobules by the
basement membrane
Paget’s Disease
 DCIS arising within the
ductal system that extends
up the lactiferous ducts and
into the skin of the nipple
without crossing the
basement membrane
Diagnosis
 Most commonly detected as mammographic
caclification
 BI-RADS Classification
0. Incomplete
1. Negative
2. Benign
3. Probably benign
4. Suspicious
5. Highly suggestive of malignancy
6. Known biopsy-proven malignant
General Principles of Management
 Small, mammographically detected lesions should be treated
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with complete local excision
If disease is extensive, total mastectomy may be a more reliable
treatment
RCTs demonstrate a reduction in DCIS recurrence and invasive
breast cancer if radiotherapy is performed after CLE
ALND is not indicated
Chemotherapy has never been investigated
Tamoxifen in the adjuvant setting reduces risk of DCIS
recurrence and invasive breast cancer
MDT
•Surgery (breast and axilla)
•Radiotherapy
•Chemoprophylaxis
Surgery
 Aim is to ensure complete excision with best possible
cosmetic result
 Pre-operative localisation is essential for a
mammographically detected impalpable lesion
 Optimal margins
 No reliable definition
 Must be completely excised
 “Clear margins” (no DCIS at section edge) provides acceptable
local control when combined with radiotherapy
 <1mm considered inadequate
Surgery
 Axillary Dissection
 No place for ALND
 What about SLNB?
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High suspicion for invasive cancer
 Large size
 Aggressive histologic features
 Palpable mass
Surgery that will compromise ability to perform SLNB in the
future
Surgery
 Mastectomy
 Widespread contiguous or multi-focal DCIS
 Widespread microcalcification in the presence of proven
DCIS
 Recurrence of DCIS following initial treatmen when
either of the above indiciations is present
 Woman’s choice
 Other relevant risk factors for breast cancer
Radiotherapy
 Lower recurrence rate demonstrated (4 RCTs) when
DCIS is treated with complete local excision (CLE) and
adjuvant radiotherapy compared with CLE alone
regardless of grade and pathological subgroup
 Insufficient statistical power to detect small
differences in survival
 2009 Meta Analysis of RTx compared to no further
treatment following excision showed RTx resulting in
reduction in risk of all ipsilateral breast events (HR
0.49; 95% CI 0.41-0.58)
Risk of Recurrence
 Relatively low for DCIS with good prognostic pathological
features
 Clear margins
 Low-grade
 No necrosis
 Small extent (<10mm)
 High grade DCIS with necrosis, close margins and larger
size should have radiotherapy
Systemic Treatment
 Chemotherapy
 Never investigated or used in treatment with DCIS
Systemic Treatment
 Tamoxifen
 Must have ER + disease
 In women who have breast conservation treatment, postoperative
tamoxifen is more effective than placebo in reducing the risk of
invasive breast cancer (NSABP B-17 and B-24) (8.5 vs 10%
 Meta-analysis (2009): Tamoxifen reduces recurrence risk of
ipsilateral breast (HR 0.75, 95%CI 0.60-.092), trend to reduction in
risk of invasive carcinoma (HR 0.79, 95%CI 0.60-1.01), lower risk for
contralateral carcinoma (HR 0.57, 95%CI 0.39-0.83)
 No apparent survival benefit
 Risks: endometrial cancer, VTE
Systemic Treatment
 NCCN 2013 Guidelines
 Consider tamoxifen for 5 years:
 Patients treated with breast conservation, especially if ER +
 Patients treated with surgery alone and ER +
 Australian Guidelines 2003
 Further research required, tamoxifen may reduce risk of
subsequent local invasive breast cancer in women who
have had breast conservation treatment
 No data for aromatase inhibitors
 Limited data for HER2-directed therapy
The Evidence
Local Recurrence Rates (%)
Trial
No. of
Patients
Follow
up (yr)
CLE
CLE +
XRT
NSABP B- 818
17
12
30.8
14.9
<0.00000
5
EORTC
10853
1010
4.25
16
9
<0.005
UK ANZ
1707
5
20
8
SweDCIS
1067
5
7
22
NSABP B- 1807
24
7
9
CLE +
XRT +
Tam
6
p value
<0.0001
<0.0001
6
0.04
Post Treatment Surveillance
 Overall survival for women >67 is similar to those
without breast cancer
 Women >67 are more likely to die of cardiovascular
disease than breast cancer
 Australian Guidelines
 No evidence defining optimum follow-up protocol
 Consensus recommendation is for annual review with
examination and mammography indefinitely
Post Treatment Surveillance
 NCCN Guidelines
 Interval history and physical examination every 6-12
months for 5 years then anually
 Mammogram annually and 6-12 months post radiation
therapy if breast conserved
 Breast awareness
 If treated with tamoxifen
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Annual gynae assessment
Opthalmology exam
Manage symptoms as per guidelines