Breast Cancer, DCIS

1. Ductal Carcinoma In Situ
(DCIS)
Dr. MohammedFathyBayomy
Lecturer of ClinicalOncology
ZagazigUniversity

2. Classification of breast CancerClassification of Breast Cancer

3. Incidence

4. Risk Factors

5. Pathology
TDLU

6. Pathology (Cont.,)
Pathogenesis

7. Pathology (Cont.,)
Pathogenesis (Cont.,)

8. Pathology (Cont.,)
Pathogenesis (Cont.,)

9. Pathology (Cont.,)
Pathogenesis (Cont.,)

10. Pathology (Cont.,)
Pathogenesis (Cont.,)

11. Pathology (Cont.,)
Pathogenesis (Cont.,)

12. Comedo Cribriform Solid
Micropapillary Papillary Invasive
Classification
Pathology (Cont.,)

13. Classification: Comedo Type
Pathology (Cont.,)

14. Classification: Cribriform Type
Pathology (Cont.,)

15. Classification: Cribriform Type (+microcalcification)
Pathology (Cont.,)

16. Classification: Micropapillary Type
Pathology (Cont.,)

17. Classification: Papillary Type
Pathology (Cont.,)

18. Classification: Solid Type
Pathology (Cont.,)

19. Clinical Picture
Pre-Screening: associated with Paget’s disease

20. Clinical Picture (Cont.,)
Post-Screening: abnormality in screening mammography

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

22. Investigations (Cont.,)
Diagnostic Mammography

23. Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

24. Intraductal
calcifications
Site of Calcification
Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

25. 

Distribution of Calcification
Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

26. Linear or form parallel tracks
Coarse or 'Popcorn-like'
Skin calcification
Milk of calcium
Morphology of Calcification
Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

27. Large Rod-like Round and punctate
Lucent-Centered Eggshell or Rim
Morphology of Calcification (Cont.,)
Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

28. DystrophicAmorphous
Coarse Heterogeneous
Fine Pleomorphic Fine Linear or Fine
Linear Branching
 
Morphology of Calcification (Cont.,)
Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

29. Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

30. Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

31. Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

32. Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

33. Fine Linear Calcifications – Segmental Distribution
Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

34. Fine Pleomorphic Calcifications - Linear Distribution
Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

35. Fine Pleomorphic Calcifications - Segmental Distribution
Investigations (Cont.,)
Diagnostic Mammography (Cont.,)

36. A- Right Craniocaudal Mammograms of 47 women with palpable mass.
B- Lateral spot magnification mammogram demonstrates segmental pleomorphic
calcifications corresponding to the palpable abnormality.
C- US image demonstrates a hypoechoic mass with microlobulated and angular margins and
calcifications.
Investigations (Cont.,)
Breast Ultrasound

37. Investigations (Cont.,)
Breast Ultrasound (Cont.,)

38. Investigations (Cont.,)
Breast Ultrasound (Cont.,)

39. Investigations (Cont.,)
Breast Ultrasound (Cont.,)

40. Investigations (Cont.,)
Breast Ultrasound (Cont.,)

41. Axial MR images obtained in a 52-year-old asymptomatic
woman.
(A) T1WIs Precontrast.
(B ;C), early postcontrast, and late postcontrast.
Magnetic Resonance Mammography
Investigations (Cont.,)
MRI

42. Investigations (Cont.,)
MRI (Cont.,)

43. Investigations (Cont.,)
MRI (Cont.,)

44. Time-signal intensity curve (TIC) = Kinetic curve
Plateau enhancement kinetic curve
Dynamic contrast-enhanced DCE-MRI
Investigations (Cont.,)
MRI (Cont.,)

45. MRI: Contrast
required…..spatia
l resolution
improves
morphologic
assessment
Mass, heterogenous and rim enhancement,
spiculated margins
Investigations (Cont.,)
MRI (Cont.,)

46. DCIS diagnosed in high risk patient on screening
MRI with negative screening mammogram
Fine linear, branching NMLE in ductal distribution
NMLE: Non-Mass Like Enhancement
Investigations (Cont.,)
MRI (Cont.,)

47. Investigations (Cont.,)
Tomosynthesis

48. Diagnosis
U/S guided core biopsy

49. Diagnosis (Cont.,)
Stereotactic guided core biopsy

50. Vaccum Assisted Biopsy (VAB)
Diagnosis (Cont.,)

51. Vaccum Assisted Biopsy (VAB) (Cont.,)
Diagnosis (Cont.,)

52. Wire localization & Excisional Biopsy
Diagnosis (Cont.,)

53. History and Physical exam.
Diagnostic bilateral mammography.
Pathology review.
Determination of tumor estrogen (ER) status
Genetic counseling: high risk for hereditary breast cancer.
Breast MRI: as indicated.
NCCN guideline for Work-up
Diagnosis (Cont.,)

54. Low GradeHigh Grade
Her2/neu ER
ER status
Diagnosis (Cont.,)

55. Van Nuys Prognostic Index
Prognosis

56. Grade and Necrosis
Prognosis

57. NCCN guideline for Treatment
PRIMARY TREATMENT
Lumpectomy+ Whole breast radiation therapy
With or without boost to tumor bed
Without lymph node surgery
Option 1
(category 1)
Option 2
(category 2A)
Total mastectomy + reconstruction (optional)
With or without sentinel node biopsy
Option 3
(category 2B)
Lumpectomy without radiation therapy
Without lymph node surgery

58. NCCN guideline for Treatment (Cont.,)
DCIS POSTSURGICAL TREATMENT
Risk reduction therapy for ipsilateral breast following
breast-conserving surgery:
Consider endocrine therapy for 5
years for:
Patients treated with breast-conserving
therapy (lumpectomy) and radiation
therapy (category 1), especially for those
with ER-positive DCIS.
Risk reduction therapy for contralateral breast:
Counseling regarding risk reduction
The benefit of endocrine therapy for ER-
negative DCIS is uncertain.
Patients treated with excision alone
(category 2A).
Endocrine therapy:
Premenopausal patients -->
Tamoxifen
Postmenopausal patients -->
Tamoxifen
or
Aromatase inhibitor
- Patients <60 years old or
- Concerns for thromboembolism

59. ESMO guideline for Treatment
SURGICAL TREATMENT
Breast Conservative Treatment (BCT)
1-
2-
Total Mastectomy
Circumferential margins <2 mm are considered less adequate
No DCIS on inked margins is a minimal requirement
Axillary
Node
Evaluation
SLNB: not required except
Mastectomy is required (incidental invasive cancer may
be subsequently identified in surgical specimen
Factors associated with increase risk of invasion:-
- Age: young.
- Associated density on mammogram.
- Mass: palpable.
- Microcalcifications: large extent
- Poorly differentiated DCIS.

60. ESMO guideline for Treatment (Cont.,)
POSTOPERATIVE RADIOTHERAPY
Post-BCS Whole
Breast RadioTherapy
(WBRT) • Decreases the risk of local recurrence.
• Survival equal to that after mastectomy.
Omitting Radiation
- Nuclear grade: low/ intermediate &
- Size: <10 mm &
- Surgical margins: adequate.
Boost to tumor bed
Post-Mastectomy
RadioTherapy (PMRT)
Not recommended
Considered for high risk DCIS
Optional for low risk DCIS
Recommended for majority

61. ESMO guideline for Treatment (Cont.,)
SYSTEMIC ADJUVANT THERAPY
Tamoxifen
• Decreases risk of both invasive & non-invasive
recurrences in ipsilateral breast.
• Reduces incidence of second primary (contralateral)
breast cancer.
• No effect on survival.
AIs
Post-BCT + ER-positive
Post-Mastectomy: considered
• Decrease the risk of contralateral breast cancer in
patients who are at a high risk of new breast tumours
Should not be used in routine care

62. Treatment

63. Treatment (Cont.,)

64. Treatment (Cont.,)

65. Treatment (Cont.,)

66. Treatment (Cont.,)

67. Surgical Treatment
Multiple suspicious calcifications in a large segmental area of the breast.
Multiple clusters - many with a linear branching arrangement - typical for DCIS. Because of the
large area with calcifications, a mastectomy was planned. A sentinel node procedure was also
performed because of the estimated size of the DCIS. Whenever a mastectomy is planned, an
SN-procedure is routinely included, because it cannot be performed afterwards.
Total Mastectomy

68. In this patient, there are two groups of suspicious calcifications which are about 5 cm apart.
First the larger group was biopsied. The idea was that if these calcifications were benign, then
the smaller cluster would probably also be benign. However, the larger group of calcifications
turned out to be DCIS grade 2. So a second biopsy was needed of the smaller group of
calcifications, and this also turned out to be DCIS grade 2. A mastectomy with a sentinel node
procedure was planned. The total area of DCIS was thought to be too large for breast conserving
treatment.
Surgical Treatment (Cont.,)
Total Mastectomy (Cont.,)

69. Surgical Treatment (Cont.,)
SLNB

70. Post-Lumpectomy Radiotherapy

71. Post-Lumpectomy Radiotherapy (Cont.,)

72. Post-Lumpectomy Radiotherapy (Cont.,)

73. Post-Lumpectomy Radiotherapy (Cont.,)

74. Post-Lumpectomy Radiotherapy (Cont.,)

75. Registration of
- Small DCIS after wide excision alone (without RT)
- Negative margin width > 3 mm
- Tamoxifen optional
N= 670
Two groups (not randomized)
Grade 1-2, non-comedo, size < 2.5 cm
Grade 3, comedo, size < 1.0 cm
ECOG E5194
Low/intermediate grade High grade
Tumor size (median) 6 mm 5 mm
Negative margin width
>5mm 69.2% 82.9%
>10mm 48.5% 53.3%
Study Design

76. ECOG E5194 (Cont.,)
Results at 5 years follow-up

77. Year
0 2 4 6 8
0.00.050.15
Ipsilateral (43 events/ 572 cases)
Contralateral (18 events/ 572 cases)
6%
4%
15%
Low or intermediate grade
High grade
ECOG E5194 (Cont.,)
Results at 5 years follow-up (Cont.,)

78. RTOG 9804
Study Design
Whole Breast Radiotherapy After Lumpectomy in Good-Risk DCIS
Primary endpoint: ipsilateral breast local failure
Secondary endpoints: contralateral breast failure, DFS, OS
Women with good-risk*
DCIS undergoing
lumpectomy with
≥ 3-mm margins
(N = 636)
Radiotherapy (no boost)
50 Gy at 2 Gy/fraction x 25,
50.4 Gy at 1.8 Gy/fraction x 28, or
42.5 Gy at 2.65 Gy/fraction x 16
(n = 287)†
Observation
(n = 298)†
Stratified by age (< vs > 50 yrs), tumor size (≤ vs > 1 cm),
margin width (3-9 mm vs > 1 cm or negative)
*Good risk defined as: no symptoms (mammographic or incidental finding), only low to intermediate
grade, ≤ 2 cm, margin width ≥ 3 mm.
†51 women ineligible or withdrew consent after enrollment; 585 patients evaluable for efficacy and safety.

79. RTOG 9804 (Cont.,)
Results
Breast Failure
62% of patients received tamoxifen on both arms
Recurrence in the same quadrant of ipsilateral breast
Observation: 10 patients + 2 patients in both same and other quadrant
Invasive histology: 33%
Noninvasive histology: 67%
Radiotherapy: None
No difference in OS (HR: 1.35; 95% CI: 0.67-2.71; P = .40)
CasesofFailure
inBreast(n)
2 (0.7%)
15 (5%)
RT (n = 287) Observation (n = 298)
20
15
10
5
0
Ipsilateral
Contralateral
11 (3.7%)
8 (2.8%)

80. NSABP B-17
Study Design
A Protocol to Evaluate Natural History and Treatment of Patients with Noninvasive
Intraductal Adenocarcinoma.
The primary objective of this
study is to determine
whether lumpectomy and
postoperative breast
irradiation is more effective
than lumpectomy alone in
controlling the subsequent
occurrence of ipsilateral
invasive and/or noninvasive
cancers in patients with
noninvasive intraductal
carcinoma.

81. NSABP B-17 (Cont.,)
Results at 5 years of follow-up

82. NSABP B-17 (Cont.,)
Results at 5 years of follow-up (Cont.,)

83. NSABP B-17 (Cont.,)
Results at 5 years of follow-up (Cont.,)

84. NSABP B-17 (Cont.,)
Results at 8 years of follow-up

85. NSABP B-17 (Cont.,)
Results at 8 years of follow-up (Cont.,)

86. NSABP B-17 (Cont.,)
Results at 12 years of follow-up

87. NSABP B-17 (Cont.,)
Results at 12 years of follow-up (Cont.,)

88. EORTC 10853
Study Design

89. EORTC 10853 (Cont.,)
Results at 20 years follow-up

90. EORTC 10853 (Cont.,)
Results: subgroup analysis (forest plot)

91. SweDCIS
Study Design

92. SweDCIS (Cont.,)
Results at 20 years follow-up

93. Adjuvant Tamoxifen Therapy

94. NSABP B-24
Study Design
A Clinical Trial to Evaluate the Worth of Tamoxifen in Conjunction with Lumpectomy and
Breast Irradiation for the Treatment of Noninvasive Intraductal Carcinoma (DCIS) of the
Breast
The specific aim for this protocol is
to determine, for patients with
noninvasive intraductal cancer
(DCIS), whether lumpectomy and
postoperative breast irradiation plus
prolonged tamoxifen therapy is
more effective than lumpectomy
and breast irradiation without
tamoxifen in preventing the
subsequent occurrence of ipsilateral
and contralateral breast cancers

95. NSABP B-24 (Cont.,)
Results at 7 years follow-up

96. NSABP B-24 (Cont.,)
Results at 7 years follow-up (Cont.,)

97. NSABP B-24 (Cont.,)
Results at 12 years follow-up
0.69 31%
PHR
0.02
Reduce risk by
0.83 0.33
43%0.0030.57
17%

98. NSABP B-24 (Cont.,)
Results at 12 years follow-up (Cont.,)

99. CALGB 9343
Study Design

100. CALGB 9343 (Cont.,)
Results at 10 years follow-up

101. UKCCR (UK/ANZ)
Study Design

102. UKCCR (UK/ANZ) (Cont.,)
Result at 4.4 years follow-up

103. UKCCR (UK/ANZ) (Cont.,)
Result at 15 years follow-up

104. UKCCR (UK/ANZ) (Cont.,)
Result at 15 years follow-up (Cont.,)

105. UKCCR (UK/ANZ) (Cont.,)
Result at 15 years follow-up (Cont.,)

106. UKCCR (UK/ANZ) (Cont.,)
Result at 15 years follow-up (Cont.,)

107. UKCCR (UK/ANZ) (Cont.,)
Result at 15 years follow-up (Cont.,)

108. 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.
NSABP B-17 and B-24 Combined analysis

109. Adjuvant Anastrozole Therapy

110. NSABP B-35
Study Design
A Clinical Trial Comparing Anastrozole with Tamoxifen in Postmenopausal Patients with
Ductal Carcinoma In Situ (DCIS) Undergoing Lumpectomy with Radiation Therapy
The primary aim of this Phase III
trial is to compare the value of 1
mg/day of anastrozole to 20
mg/day of tamoxifen, each given
for 5 years, in preventing the
subsequent occurrence of breast
cancer (local, regional and distant
recurrences, and contralateral
breast cancer) following
lumpectomy with radiation
therapy in postmenopausal
women with ductal carcinoma in
situ (DCIS).

111. NSABP B-35 (Cont.,)
Results at 9 years follow-up

112. NSABP B-35 (Cont.,)
Results at 9 years follow-up (Cont.,)

113. NSABP B-35 (Cont.,)
Results at 9 years follow-up (Cont.,)

114. IBIS-II DCIS
Study Design
Anastrozole versus tamoxifen for the prevention of loco-regional and contralateral recurrence
in postmenopausal women with Ductal Carcinoma In-Situ

115. IBIS-II DCIS
Results at 10 years follow-up

116. IBIS-II DCIS
Results at 10 years follow-up (Cont.,)

117. NSABP B-43
Study Design
A Phase III Clinical Trial Comparing Trastuzumab Given Concurrently with Radiation
Therapy and Radiation Therapy Alone for Women with HER2-Positive Ductal Carcinoma
In Situ Resected by Lumpectomy
* Patients with ER-positive and/or PgR-
positive DCIS should receive a minimum
of 5 years of hormonal therapy.
Primary aim to determine the
value of trastuzumab given during
radiation therapy (RT) compared
to RT alone in preventing the
subsequent occurrence of
ipsilateral breast cancer
recurrence, ipsilateral skin cancer
recurrence, or ipsilateral DCIS
(IIBCR-SCR-DCIS) in women with
HER2-positive DCIS resected by
lumpectomy.

118. NSABP B-43 (Cont.,)
Study Design (Cont.,)

119. Oncotype Breast DX DCIS score
Do I need Radiotherapy?

120. Oncotype DX Breast DCIS score (Cont.,)

121. Oncotype DX Breast DCIS score (Cont.,)

122. Oncotype DX Breast DCIS score (Cont.,)

123. Local Transdermal Endocrine Therapy

124. COMET
Study Design
Comparison of Standard of Care Versus Active surveillance + Medical Endocrine Therapy
for Low risk DCIS.

125. LORIS
Study Design
Comparison of Surgery versus Active surveillance in Low risk DCIS.

126. LORD
Study Design
Comparison of Standard of Care Versus Active surveillance in Low risk DCIS.

127. EORTC 22085‐10083
Study Design

128. BONBIS
Study Design

129. ECOG‐ACRIN E4112
Study Design
Genetic Profiling of DCIS