overview of Ductal carcinoma in situ

1. DR.BHAVIN VADODARIYA
DNB Surgical Oncology 1st year Resident,
Apollo CBCC Cancer Care,
Ahmedabad
Date-23/09/2017

2.  Introduction
 Pathology
 Radiology
 Treatment
 Surgery- BCS,MRM
 Radiotherapy
 Hormone Therapy
 Risk Factors
 Management of Recurrence
 Conclusion

3.  DCIS (ductal carcinoma in situ), also referred to as
non-invasive or intra-ductal cancer, is defined as a
neoplastic proliferation of epithelial cells confined to the
ductal system and is characterized by subtle to marked
cytological atypia as well as an inherent (but not
necessarily obligate) tendency to progress to IBC
(invasive breast cancer).

4.  DCIS is typically non-palpable, asymptomatic and
discovered incidentally as suspicious (pleomorphic,
grouped, linear or segmental) microcalcifications on
routine mammographic screening or adjacent to other
lesions in the breast .

5. Ductal Carcinoma In Situ
(Stage 0 Breast Cancer)

9. ductal cells
ductal carcinoma In situ
(DCIS)
Invasive ductal carcinoma

10. Burstein H et al. N Engl J Med 2004;350:1430-1441
Pathobiologic Events Associated with DCIS

11.  DCIS had been considered rare (2–3%) in the pre-
mammographic era but now respectively represents a
high proportion (20–25%) of newly diagnosed breast
cancers with age-incidence rates ranging from 0.6 to
1.3 per 1000 screening examinations in women aged
40–49 and 70–84 years, respectively
 Page et al Cancer 1985;55:2698-708
 Burstein H et al. N Engl J Med 2004;350:1430-1441

12.  Older age,
 Benign breast disease,
 A family history of breast cancer in first-degree
relatives, reproductive factors (such as nulliparity and
older age at the time of the first full-term pregnancy),
 Late age of menopause,
 Long-term use of postmenopausal hormone-
replacement therapy

13.  Genetic factors, such as germline mutations in one of
two breast cancer susceptibility genes, BRCA1 and
BRCA2, increase the likelihood of developing DCIS .
Demographic data predict that 5% of women withDCIS
carry a germline mutation in both genes
 Burstein H et al. N Engl J Med 2004;350:1430-1441

14.  Although DCIS is non-lethal, the evidence that DCIS is a
true precursor of IBC is indirect but convincing.
 IBC is rarely seen without adjacent DCIS.
 Women diagnosed with DCIS carry a 10 times higher risk of
developing ipsilateral invasive breast cancer if left untreated;
 Burstein H et al. N Engl J Med 2004;350:1430-1441

15.  DCIS and IBC from the same patient share similar
genetic features and molecular abnormalities;
microscopic examinations show the ruptured BM (basal
membrane) allowing the invasive cancer to merge with
an intraductal component ; and the risk factors for both
DCIS and IBC are similar

16.  Between 14 and 50% of DCIS lesions are estimated to
progress to invasive lesions if left untreated .
 To date, neither the histopathological classification nor
the conventional biomarkers can accurately predict
whether DCIS lesions can invade the surrounding
tissue and consequently progress to metastatic disease
 Erbas, B., Provenzano, E., Armes, J. and Gertig, D. (2006) The
natural history of ductal carcinoma in situ of the breast: a review.
Breast Cancer Res. Treat. 97, 135–144
.

18.  LG (low grade)-DCIS.
 HG (highgrade) non-comedo
 HG comedo-carcinoma (grouped as HGDCIS).
LG-DCIS and HG-DCIS are rarely found
together, and LG-DCIS rarely progresses to HG-DCIS

19.  It is characterized by monotonous cell proliferation;
 nuclear size approximates that of a normal ductal cell
with a variety of architectural patterns, including
cribriform, micropapillary, solid and papillary growth.
 Cells are well-polarized, and mitotic figures are rare.
 Punctate necrosis may be found, but large foci
of necrosis are uncommon and should not be more
than focal in LG-DCIS.
 Small laminated microcalcifications are a common
finding

21.  It shows large and pleomorphic, hyperchromatic nuclei
that sometimes exhibit prominent nucleoli.
 The nuclear size is variable, and mitotic cells may be
numerous.
 Cells may show a loss of polarity, and nuclei show up to
3-fold variations in size.
 Necrosis with cellular debris is a common finding in
small and large foci.

22.  Architecturally, HG-DCIS is variable but is more
frequently solid, although a single layer of highly
atypical cells is sufficient to diagnose HG-DCIS.
 Amorphous calcifications associated with necrotic foci
are common

24.  It is a special type of HG-DCIS.
 CC-DCIS is diagnosed from particular findings at
the clinical, gross and microscopic levels with clinical
implications.
 CC-DCIS is the only DCIS that is grossly observable;
therefore, it was over-represented in the breast cancers
identified in the pre-mammographic era.
 The term comedo refers to a yellowish creamy necrotic
material oozed from the ducts that resemble
comedones.

25.  Histologically, this subtype is characterized by enlarged
ducts filled with necrotic debris surrounded by zero to a
few layers of highly atypical epithelial cells and
numerous mitotic figures.
 Necrosis usually spans more than 90% of the duct
cross section.
 The abundant necrotic material calcifies and appears
as large linear branching calcifications on the
mammogram

28.  Useful for recognition and description but grade is more
clinically useful
 Cribriform
 Micropapillary
 Solid (mosaic, microacinar)
 Comedo

29.  CIS lesions containing a comedo or cribriform element
are more likely to have microscopic spread and
involvement of lobules and DCIS lesions containing a
papillary element are likely to be multicentric, whether
the pattern are predominant in the tumor or not.

32.  Multifocality is defined as separate foci of DCIS within
the same ductal system.
 Multicentricity is generally defined as DCIS in a
quadrant other than the quadrant in which the original
DCIS (index quadrant) was diagnosed.
 There must be normal breast tissue separating the 2
foci.

33.  The studies of Holland and associates and Noguchi
and coworkers suggest that a great deal of multifocality
may be artifactual, resulting from looking at a 3-
dimensional arborizing entity in 2 dimensions on a
glass slide.
 It would be analogous to saying that the branches of a
tree were not connected if the branches were cut at
one plane, placed separately on a slide, and viewed in
cross-section.
 Multifocality may be due to small gaps of DCIS or skip
areas within ducts,

34.  Two thirds of patients with low-to intermediate-grade
ductal carcinoma in situ have multifocal disease,
characterized by discontinuous intraductal growth, with
gaps of up to 1 cm between tumor foci.
 In contrast, high-grade lesions tend to be continuous,
with most having no gaps greater than 5 mm.

35.  Currently, when DCIS is diagnosed by core needle
biopsy, it should be followed by surgical resection
because of a 30% risk of underestimating an invasive
carcinoma adjacent to the biopsied area.
 When DCIS is diagnosed on surgical specimens, some
variables are important to the clinical decision-making
process and should be cited by the pathologist.

36.  Open surgical biopsy should only be used if the lesion
cannot be biopsied using minimally invasivetechniques.
 Whenever needle localization excision is performed,
whether for diagnosis or treatment, intraoperative
specimen radiography and correlation with the
preoperative mammogram should be performed.
 Margins should be inked or dyed and specimens
should be serially sectioned at 3- to 4-mm intervals.
 The tissue sections should be arranged and processed
in sequence.

37.  DCIS size,
 Status of surgical margins
 The distance to DCIS
 The presence of one or more foci,
 Type and extension of necrosis,
 DCIS grade
 Hormone receptor status

38.  Commonly used markers in DCIS include
 the ER (oestrogen receptor)
 PR (progesterone receptor).
 Less commonly used markers include
 the epidermal growth factor receptor family member 2
[ERBB2]
 HER2 (human epidermal growth factor
receptor) or HER2/neu],
 the androgen receptor and Tp53.

39.  It is a transmembrane protein with a tyrosine kinase
cytoplasmic domain.
 It is involved in proliferative and antiapoptotic triggering
signals as well as activation pathways such as MAPK
(mitogen-activated protein
kinase),PI3K(phosphoinositide 3-kinase)/Akt (protein
kinase B) and mTOR (mammalian target of rapamycin).
 Thus, ERBB2 plays an important role in tumour
development and progression.

40.  Studies have shown that 50–60% of ERBB2/HER2
amplification/overexpression in DCIS is associated with
poorly differentiated lesions and the high-grade
comedo subtype [26].
 However, ERBB2/HER2 expression/amplification
status is not currently considered in the decision-
making process for DCIS.
 DiGiovanna, M. P., Chu, P., Davison, T. L., Howe, C. L., Carter, D.,
Claus, E. B and Stern, D. F. (2002) Active signaling by HER-2/neu
in a subpopulation of HER-2/neu-overexpressing ductal carcinoma
in situ: clinicopathological correlates. Cancer Res. 62, 6667–6673

41.  Mammogram shows calcifications in 90 % of cases.
 In 75%, microcalcifications are the only radiologic
finding; in 15%, calcifications coexist with a soft tissue
abnormality
 In 10%, DCIS manifests as a mass or architectural
distortion on mammography
(Eur J Radiol 2005;54:55)

42.  Fine linear and fine linear branching morphologic
features are usually associated with high grade DCIS,
while amorphous calcifications are more common in
low grade DCIS (Acta Radiol 2011;52:481)
 Despite these findings, there are significant overlaps
between the mammographic appearance of these
lesions, and it has been shown that fine pleomorphic
calcifications are the most common appearance for
both high grade and non high grade lesions
(Radiographics 2013;33:1569, Acta Radiol
2011;52:481)

43.  A hypoechoic mass with non-circumscribed margins, parallel
orientation, and normal acoustic transmission is the most common
US finding in DCIS.
 In the setting of calcified DCIS, US is helpful in evaluating for a
possible invasive component and in guiding biopsy.
 Noncalcified DCIS may be identified in the evaluation of a
mammographic mass or asymmetry, in symptomatic patients, at
high-risk screening US, or in the evaluation of disease extent.
 30% of patients with non calcified DCIS have false negative
imaging (J Ultrasound Med 2009;28:903)

44.  MRI may be a useful adjunct to detect non calcified
DCIS (Breast J 2005;11:382)
 MR imaging can allow improved presurgical planning
as well as depict contralateral, multifocal, and
multicentric disease.

45. Irregular
clusters
Branching (comedo)

47. DCIS diagnosed in high risk patient on screening MRI
with negative screening mammogram
Fine linear, branching NMLE in ductal distribution

49.  Preoperative magnification views to establish extent of
ipsilateral disease
 Contralateral-breast imaging to rule out concurrent
bilateral disease
 Radiography to confirm excision of microcalcifications
 Postexcision breast imaging to confirm removal of
suspicious-appearing areas
 Annual surveillance to screen for recurrence and
contralateral cancer

50.  Exclusion of invasive breast cancer
 Characterization of nuclear grade, size and extent of
tumor, presence or absence of comedonecrosis, and
tumor architecture
 Assessment, including measurement, of surgical
margins
 Determination of estrogen-receptor status in patients
considering tamoxifen therapy after breast-conserving
surgery

51.  Assessment for possible breast-conserving surgery on
the basis of the extent of ductal carcinoma in situ or
associated calcifications, suitability for subsequent
radiotherapy, anticipated cosmetic result, and the
patient’s preference.
 Excisional biopsy, with careful orientation of the
specimen, to remove ductal carcinoma in situ with
negative margins at least 1 mm in width

52.  Reexcision as necessary to obtain negative margins
 Simple mastectomy, with or without reconstruction, if
the patient is not a candidate for breast-conserving
surgery or if the patient prefers mastectomy

55.  Breast conservation surgery (BCS) may consist of
quadrantectomy, wide excision, lumpectomy (local
excision).
 A primary goal of BCS for DCIS is to achieve the best
possible cosmetic outcome along with negative margins
 microscopic complete excision is essential for optimal
local control in breast-conserving therapy for DCIS.

57.  The NCCN Panel accepts the definition of a negative
margin as "No ink on the tumor," from the 2016
SSO/ASTRO/ASCO Consensus Guidelines on
Margins.
 For pure DCIS, margins of at least 2 mm are
associated with a reduced risk of ipsilateral breast
tumor recurrence (IBTR) relative to narrower negative
margin widths in patients receiving WBRT.

58.  For patients treated with excision alone (without
radiation), regardless of margin width, the risk of IBTR
is substantially higher than treatment with excision and
whole breast radiation therapy (even in predefned low-
risk patients).
 The optimal margin width for treatment with excision
alone is unknown, but should be at least 2 mm.
 Some evidence suggests lower rates of IBTR with
margin widths wider than 2 mm.

59.  Repeatedly positive margins
 Multicentric disease ( >2 quadrants)
 Diffuse malignant calcifications on mammogram
 Prior RT to breast
 Pregnancy
 History of scleroderma
 Large tumor in small breast: cosmetically undesirable

60.  Specimen mammography
 Post excision mammography
 Frozen section analysis
 Complete histopathological assessment of specimen
*Standard for the Management of Ductal Carcinoma In Situ of the BreastCA
Cancer J Clin 2002;52:256-276

61.  ADVANTAGES:
 Allows surgeons to asses the adequacy of excision
 Reduce the no of reexcisions required to achieve margin –
ve resections
 less tissue excised : better cosmesis
 Reduces frequency of missed lesions: hard copy
confirmation reduces litigations

62.  DISADVANTAGES:
 Prolongs surgical procedure
 Increases cost
 False + & false - results
 Limited ability to predict margin status due to
magnification & compression views
 Discordance between SM & pathological & post
excision mammography results

63.  Done post excision & pre radiotherapy
 obtained to document complete removal of
calcifications.
 can be performed as soon as the patient can tolerate
compression however, a large seroma may obscure
small residual calcifications.

64.  Magnification views taken( may show calcifications not
evident on nonmagnified views)
 It is used as a complementary means of assessing the
completeness of excision.
 If reexcision is performed for residual calcifications,
specimen radiography and a post-excision
mammogram should again be obtained to reassess the
tumorectomy site.

65.  *Frozen sections should be avoided if possible especially
on lesions, which measure <1cm. in diameter
 Advantages:
 Indicated when information is necessary for immediate
therapeutic decisions
 reduction in the rate of reexcision
 Disadvantages
 Methodological difficulties
 Ductal carcinoma in situ is more difficult to identify in FSA
 small foci of microinvasion may be lost or rendered
uninterpretable by freezing artifact.
* Association of Directors of Anatomic and Surgical Pathology. Immediate
management of mammographically detected breast lesions. Am J Surg Pathol
1993;17:850-851

66.  Following should be included in the pathology report
 Nuclear grade,
 Presence/absence of necrosis
 Architectural pattern(s)
 Size/extent
 Distance to excision margins/margin status
 Calcification in the Tumour (or DCIS): Yes/ No
 Estrogen Receptor Status: PR Status/Her-2 neu
Status

67.  Patient age
 Symptomatic presentation
 Lesion size
 Multifocality
 Histopathologic subtype
 Nuclear/cytologic grade
 Central necrosis
 Margin status

68.  Mastectomy is a highly effective treatment for DCIS
 Loco regional control rate of 96% to 100%
 Cancer-specific mortality rates of ≤4%.
 No randomized study has compared mastectomy with
BCS for DCIS.

70.  If BCS is contraindicated
 Repeatedly positive margins after BCS
 Patient desire. minimize the chance of ipsilateral
recurrence or for other reasons
 Recurrent disease

71.  Axillary lymph node involvement is <1% 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)

72.  Neither axillary-node dissection nor sentinel-lymph-
node mapping routinely indicated.
 Consideration of sentinel axillary lymph node
evaluation in women undergoing mastectomy for
ducted carcinoma in situ or in women at higher risk for
occult invasive disease
 Patient with a clinically palpable mass or
 Area of ductal carcinoma in situ over 4 cm
 those undergoing mastectomy

73.  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
Burstein H et al. N Engl J Med
2004;350:1430-1441

74.  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)

75.  Breast irradiation reduces the risk of subsequent invasive or
noninvasive carcinoma in the treated breast
 Four prospective randomized studies of excision only versus
excision plus breast irradiation for DCIS have been performed
 all have shown that the rate of local recurrence was reduced with
the addition of radiation
 NSABP B-17 trial
 EORTC 10853 trial
 United Kingdom, Australia, and New Zealand (UK/ANZ)
DCIS
 Swedish Breast Cancer Group SweDCIS study

76. NSABP B-17
(Fisher et al.
1998c,
2001b)
first randomized trial which confirmed the effectiveness
of RT in decreasing local recurrence after lumpectomy
with negative resection margins in DCIS

77. • 813 pts. stratified by age (≤49 years vs. >49 years), DCIS versus
DCIS plus LCIS, method of detection, and whether an axillary
dissection was performed.
• Mean follow-up time was 90 months (range, 67 to 130).
• Of the patients enrolled, 83% had nonpalpable tumors
813 patients

78. The updated analysis with 15-year follow-up showed a decreased
cumulative incidence of both invasive and non-invasive ipsilateral
breast recurrences from 35% to 19.8% with the addition of radiation
therapy.
The incidence of invasive ipsilateral breast recurrence was also
decreased from 19.4 to 8.9% with the addition of radiation therapy to
lumpectomy.
Increased LR with: +margins, moderate/marked comedonecrosis ,and
microcalcifications>1 cm

80. Burstein H et al. N Engl J Med
2004;350:1430-1441

81. EORTC 10853
(Julien et al. 2000;
Bijker et al. 2006)
PATIENTS AND METHODS:
 Between March 1986 and July 1996, 1,010 women were randomly
assigned to no further treatment (503 patients) or to RT(507 patients)
after LE
 analysis performed in August 2005, at median duration of follow-up: 10.5
years
 The median age of the women was 53 years;
 71% of them were mammographically detected.
 Extent of free margins was not specified other than that DCIS should not
be present at microscopic examination of margins.
 irradiation dose was 50 Gy in 25 fractions to the whole breast. No boost
was advised .Tamoxifen not recommended.
 primary end points were both invasive and DCIS LR in the treated
breast.
 Secondary end points included metastasis, death, and contralateral
breast Cancer

82. RESULTS:
 The 10-year LR-free rate was 74% in the group treated with LE alone
compared with 85% in the women treated by LE plus RT
 The risk of DCIS and invasive LR was reduced by 48% (P = .0011) and 42% (P
= .0065) respectively.
 Both groups had similar low risks of metastases and death.
 The effect of RT was homogeneous across all assessed risk factors.

83. At multivariate analysis,
factors significantly
associated with an
increased LR risk were
young age
symptomatic detection
intermediately or poorly
differentiated DCIS
cribriform or solid
growth pattern
doubtful margins
treatment by LE alone

84. 2x2 factorial designed randomised controlled trial.
Aim: to compare excision alone versus excision plus tamoxifen versus
excision plus radiotherapy versus excision plus radiotherapy and tamoxifen
in completely excised DCIS
 complete surgical excision was confirmed by specimen radiography and
histology
 tamoxifen was prescribed as 20 mg per day
 radiotherapy was delivered through whole-breast tangential fields to a total dose
of 50 Gy. Boost was not recommended
Between May, 1990, and August, 1998, 1701 patients recruited from
screening programmes were randomised to 4 arms
Arm 1: excision alone
Arm 2 : excision plus tamoxifen
Arm 3: excision plus radiotherapy
Arm 4:excision plus radiotherapy and tamoxifen
UKANZ(2003)

85. primary endpoint: incidence of ipsilateral invasive disease
Results
median follow-up 53 months:
rates of all breast events were 8, 18, 22, and 6%, respectively.
When analysing those randomized to RT vs. no RT,
 RT reduced LF (invasive or noninvasive) in ipsilateral breast from 14
to 6% but there was no effect on the occurrence of contralateral
disease.
 Ipsilateral invasive disease was not reduced by tamoxifen but
recurrence of overall ductal carcinoma in situ (i/l & c/l )was
decreased (hazard ratio 0.68 [0.49-0.96]; p=0.03).
Conclusion: Radiotherapy can be recommended for patients with
ductal carcinoma in situ treated by complete local excision; however,
there is little evidence for the use of tamoxifen in these women

86. Cusck J, Sestak I, Pinder SE, et al. Effect of tamoxifen and radiotherapy in women with locally excised
ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial Lancet Oncol 2011;12:21–29
median follow-up of 12.7 years.
addition of radiotherapy was demonstrated to reduce the risk of IBTR.
Of the 1,030 patients randomized between no radiotherapy versus
radiotherapy, ipsilateral IBTR was 19.4% versus 7.1%, respectively
(p <.0001).
The addition of tamoxifen offered no benefit toward overall ipsilateral
local control when administered in addition to radiotherapy;
however, tamoxifen did appear to reduce the ipsilateral recurrence rate
of DCIS (but not invasive carcinoma) in the absence of radiotherapy.
Long term results of United Kingdom, Australia,
and New Zealand (UK/ANZ) DCIS trial*

87. randomized trial
enrolled 1,067 patients from 1987 to 1999, with 1,046 of these patients
followed for a mean of 8 years.
Patients randomized between lumpectomy f/b RT & lumpectomy only
 Following a sector resection, microscopic clear resection was not
required, and 50 Gy in 25 fractions to the whole breast was delivered in
the majority of patients.
 A split course, 54 Gy in 2-Gy fractions, delivered in two treatment series
separated by a 2 week break was allowed.
 No boost dose was delivered.
 The in-breast failure risk reduction reported as 16% at 10 years (95%
confidence interval [CI] 10.3% to 21.6%) with a relative risk of 0.40 (95%
CI 0.30 to 0.54).
 Detailed analysis did not identify any patient or tumor characteristic
subgroups that did not benefit of postoperative radiotherapy.
Holmberg L, Garmo H, Granstrand B, et al. Absolute risk reductions for local recurrence after postoperative
radiotherapy after sector resection for ductal carcinoma in situ of the breast J Clin Oncol 2008;26:1247–125
SweDCIS trial (JCO2008)

88. Four randomized trials of BCS ±RT
(EORTC 2006; NSABP 1998; SweDCIS 2008; UKCCCR
2003).
3,925 patients.
Analysis confirmed a statistically significant benefit from the
addition of radiotherapy
on all ipsilateral breast events (hazards ratio (HR) 0.49;
95% CI 0.41 to 0.59, P < 0.00001)
ipsilateral DCIS recurrence (HR 0.64; 95% CI 0.41 to 1.01,
P = 0.05).
All the subgroups analysed benefited from addition of RT
No significant long-term toxicity from radiotherapy was
found.
(Goodwin et al.
2009).

89. Early Breast Cancer Trialists’ Collaborative Group, Correa C, McGale P, Taylor C, et al. Overview of the randomized
trials of radiotherapy in dictal carcinoma in situ of the breast. J Natl Cancer Inst Mongr 2010;(41):162–167.
 meta-analysis of the four randomized trials
 total of 3,729 women eligible for analysis
 RT reduced the absolute 10-year risk of any ipsilateral breast event
(recurrent DCIS or invasive disease) by 15.2% (standard error [SE]
1.6%, 12.9% vs. 28.1%, 2 p <.00001).
 approximately reduces the risk of IBTR by 50%.
 Subgroup analyses demonstrated that the absolute benefits of
radiotherapy are greater in women at increased risk for tumor
recurrence, such as with involved surgical margins. younger women,
tumors that have high-grade or comedonecrotic
 little impact of RT on contralateral or distant events

90.  Indication: after breast-conserving surgery
 Not Indicated :for post mastectomy & nodal irradiation
 Benefit of addition of RT to BCS more in
 Young women
 +margin
 High grade & comedonecrosis
 Fields: tangential fields to the whole breast
 Dose: 45 to 50 Gy delivered in daily fractions of 180 to
200 cGy.
 Radiation Boost :to the tumor bed may be added
particularly for close surgical margins, although the
benefit of a boost not established.

93. Fisher, B, Lancet 353:1993-2000, 1999

94. placebo 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 28:400-18, 2001

95.  Tamoxifen decreases risk of breast cancer
events by 40%
 No difference in overall survival

97.  The use of tamoxifen in the treatment of DCIS treated with
BCS & RT is unclear due to conflicting results.
 The NSABP B-24 updated results showed that with a
median follow-up of 163 months, the addition of tamoxifen
translated into a significant 32% reduction in invasive IBTR
(9.0% vs. 6.6%, p = .025), a nonsignificant 16% reduction in
DCIS-IBTR (7.6% vs. 6.7%, p = .33), and a significant 32%
reduction in contralateral breast cancer (8.1% vs. 4.9%,
p = .023); however, no survival benefit was found

98.  In contrast to the findings of the NSABP B-24 trial, the
UK/ANZ DCIS trial found that tamoxifen had no effect in
reducing local recurrence rate when combined with
whole-breast radiation therapy
 Because DCIS is a precursor to invasive breast cancer,
tamoxifen is used as target for preventive measures
 Additional studies are being conducted evaluating the
role of aromatase inhibitors and Her2Neu targeted
treatment in DCIS

100.  Scoring system using histopathologic features in an attempt
to stratify patients according to local failure risk after
excision plus or minus whole-breast irradiation.
 There are 3 variables. Each variable is assigned a score of
1 to 3, and the sum total defined the Van Nuys Prognostic
Index.
 This scheme is drawn from the retrospective analysis of a
patient cohort in which there exist several
methodologic shortcomings, and it has not been
independently validated.

102.  333 patients with pure DCIS treated with breast preservation were studied with
detection of local recurrence as the end point.
 195 treated by excision only and 138 by excision plus radiation therapy
Score # 1 # 2 # 3
Path Other Comedo High
Grade
Size <15mm 16-40mm >40mm
Margins >10mm 1-9mm < 1mm

103. Conclusions:
Score 3 – 4 : Lumpectomy alone (local control is 100% vs
97%)
Score 5 – 7: Lumpectomy + Radiation (local control from
68%- 85%)
Score 8-9: Mastectomy
Cancer 1996 Jun 1;77(11):2267-74
RESULTS:
no statistical difference in 8 year LRFS in patients with VNPI scores of 3 or 4,
regardless of whether or not radiation therapy was used (100% vs. 97%; P =
not significant).
Patients with VNPI scores of 5, 6, or 7 received a statistically significant 17%
LRFS benefit when treated with radiation therapy (85% vs. 68%; P = 0.017).
Patients with scores of 8 or 9, showed the greatest relative benefit from
radiation therapy, however had recurrence rates in excess of 60% at 8
years regardless of irradiation, and should be considered for mastectomy.

104.  Retrospective review of 706 patients status post-BCT with or
without RT scored based on four parameters:
1. tumor size (≤1.5, 1.6–4.0, >4.1 cm)
2. Pathology (non high-grade without necrosis, nonhigh-grade with
necrosis, high grade)
3. margins (≥1, 0.1–0.9, <0.1 cm)
4. age (>60, 40–60, <40 years)
 For low-risk (score 4, 5, 6), no significant difference in 12-year
local RFS (>90–95%) with or without RT.
 For intermediate-risk (score 7, 8, 9), addition of RT provided 12–
15% 12-year local RFS benefit.
 For high-risk (score 10, 11, 12), mastectomy recommended due to
high 5-year LR (~50%) with or without RT.

105. Updated Van Nuys Prognostic
Index
Parameter 1 Point 2 Points 3 Points
Size <15mm 16-40mm >40mm
Grade I/II
non high-
grade without
necrosis,
I/II Necrosis
nonhigh-grade
with necrosis,
III
high grade
Margin 10mm 1-9mm <1mm
Age >60 40-60 <40
4,5, 6 = Lumpectomy Alone
7, 8, 9 = Lumpectomy +
Radiation
10, 11, 12 = Mastectomy
2003 Update PMID 14682107 -- "An argument against routine use of radiotherapy for ductal carcinoma
in situ." (Silverstein MJ, Oncology (Williston Park). 2003 Nov;17(11):1511-33; discussion 1533-4, 1539,
1542 passim.)

106.  Attempts to validate the VNPI scoring system have
yielded mixed results in various retrospective studies
 MacAusland et al. 2007;
 Di Saverio et al. 2008;
 Gilleard et al. 2008
 Altintas et al. 2011;
 Lee et al. 2013;).

107.  Such studies have had uneven population distributions,
most patients having low to intermediate scores.
 Although patient age, tumor size, and tumor grade
were set at patient diagnosis, margin width may be
downgraded by re-excision or TM.
 Such efforts to salvage treatment have resulted in a
disproportionately low rate of patients with high VNPI
scores

108.  Van Nuys Prognostic Index :4-6
 DCIS size < 1.5 cm
 Negative margin > 1 cm
 Not high grade
 No comedo necrosis
 Age > 61
 ER + tumors
 To date, prospective data have failed to validate the elimination of
RT for women completing BCS for DCIS
 Few prospective trials have attempted to identify a subset of
patients with low-risk DCIS who may not benefit from the addition of
radiation therapy following a local excision
 Confirmatory results are yet not available because either the trials
stopped early due to poor accrual or high LR or their results are
awaited

109. Risk factors for local
recurrence

110.  Positive surgical margins,
 high nuclear grade and presence of comedo
necrosis

111.  Architectural growth pattern,
 Presence of necrosis,
 Young age of patient,
 Larger lesion size,
 Involved margins
 symptomatic detection

112. factors important to lower the risk of recurrence after
BCS in patients with DCIS (
 Extent of the lesion
 adequate margin of excision (safe margin)

113. Oncotype DX is genomic test that predicts chemotherapy
benefit and the likelihood of distant breast cancer recurrence
in DCIS patients treated with BCS
Oncotype dx analyzes the activity of 21 genes that can
influence how likely a cancer is to grow and respond to
treatment.
 Oncotype DX test is both a prognostic test and predictive
test
http://www.genomichealth.com/en-US/OncotypeDX.aspx

114. Oncotype DX test results assign a Recurrence Score — a
number between 0 and 100
Recurrence Score Any Recurrence Invasive Recurrence
Low Risk less than
18
12% 5%
Intermediate
Risk:18-31
25% 9%
High Risk: more
than 31
27% 19%

115.  CBE & baseline mammogram 6 to 12 months after
initial therapy and at least annually thereafter
 Ipsilateral tumor recurrences usually detected on
surveillance mammography, although one-quarter
may be detected on the basis of changes on physical
examination of the breast or chest wall.
 Distant breast cancer metastases in the absence of
regional recurrence are unusual.

117.  Local recurrences
 After excision only: local excision & RT
 After BCT+RT: treated with mastectomy.
 The clinical outcome of ipsilateral tumor recurrence is
governed by the nature of the recurrence.
 Patients with recurrent DCIS have an excellent
prognosis, with <1% risk of further recurrence after
salvage mastectomy.
 Patients with invasive recurrence after breast-
conserving surgery for DCIS have a prognosis similar
to those with early-stage breast cancer, with a 15% to
20% risk of metastatic recurrence at 8 years.

118.  DCIS represents a proliferation of malignant-appearing
cells in the breast that have not invaded beyond the
ductal basement membrane.
 It is a very late stage of premalignant evolution and is a
precursor for the development of IBC; however, it is
usually curable if detected and excised before it can
progress.
 Regardless of treatment, the long-term prognosis of
DCIS is excellent, with survival rates at 10 years
exceeding 95%.

119.  Therefore, the challenge in the treatment of DCIS is to
balance the risk for local recurrence (especially invasive
recurrence) without creating excessive unnecessary
morbidity.
 Today, DCIS is usually diagnosed by mammography and
core biopsy.

120.  Therapy involves complete surgical excision by either
BCT or mastectomy, depending on the area of disease
and size of the breast.
 BCT is usually a reasonable option, as long as all
microcalcifications are removed and clear margins of at
least 2–3 mm are obtained.

121.  Radiation therapy is generally recommended for
BCT in DCIS, and in fact, no subgroup of patients has
been shown not to benefit from its use.

122.  Adjuvant therapy with tamoxifen should be considered
in ER-positive DCIS, although conventional
chemotherapy has not been found to be particularly
effective.
 Neoadjuvant therapy and the use of trastuzumab for
DCIS are currently under investigation and may be
future treatment options for DCIS.

123.  Consideration of tamoxifen after breast-conserving
surgery and radiotherapy to reduce risk of ipsilateral
recurrence and contralateral disease, particularly in the
case of estrogen-receptor–positive ductal carcinoma in
situ.

124.  Omission of radiotherapy for a low-risk patient
treated with excision alone (appropriate clinical
and pathological criteria for selecting such patients
are not uniformly established; no supporting data
from prospective studies)
 Evaluation of novel systemic adjuvant treatments