DCIS Update DL Wickerham MD Deputy Chairman NRG Oncology Oct 5, 2015.
-
Upload
bertina-robertson -
Category
Documents
-
view
216 -
download
0
Transcript of DCIS Update DL Wickerham MD Deputy Chairman NRG Oncology Oct 5, 2015.
DCIS Update
DL Wickerham MDDeputy Chairman
NRG OncologyOct 5, 2015
National Surgical Adjuvant
Breast and Bowel Project
231,840 New Cases 40,290 Deaths
4% Melanoma of skin
6% Thyroid
29% Breast13% Lung and bronchus
3% Kidney & renal pelvis
8% Colon and rectum
3% Leukemia
7% Uterus
3% Pancreas
4% Non-Hodgkin lymphoma
20% All other sites
2015 American Cancer SocietyCancer Incidence
2% Brain
26% Lung and bronchus
15% Breast7% Pancreas
9% Colon and rectum
5% Ovary
4% Uterus
3% Non-Hodgkin lymphoma
4% Leukemia
3% Liver & intrahepatic bile duct
22% All other sites
2015, American Cancer Society, Inc., SEER; Siegel RL, et al. CA Cancer J Clin. 2015 http://onlinelibrary.wiley.com/enhanced/doi/10.3322/caac.21254/
Topic Outline
• What is DCIS?
• Treatment Options
• Future Research Directions
• Questions & Answers
What is DCIS?
• Ductal Carcinoma In-situ
• Cancer?
• Pre - cancer?
• Risk factor for cancer?
Breast Carcinogenesis
Normal epitheliumNormal
epithelium
Invasivebreastcancer
Invasivebreastcancer
Atypicalhyperplasia
Atypicalhyperplasia
Proliferativedisease
without atypia
Proliferativedisease
without atypiaDCISDCIS
Normal Duct
In Situ Cancer
Invasive Cancer
Atypical Hyperplasia
For training purposes only, not for use in detailing 2/1/08
Breast Cancer Pathologic Staging
Stage I Stage II
Stage III Stage IV
STAGE 0 THE DEFINITIONCells that look like cancer but have not invaded surrounding tissue are called ductal carcinoma in situ (cancer confined to the duct). The lesions may be tiny as pinpoints and may pop up throughout the breast.
THE OPTIONSPatients whose lesions are tightly focused can be treated with lumpectomy and XRT. Some surgeons think surgery alone may be sufficient in certain cases.
DCIS with Micro-
calcificationTIME, Feb. 18, 2002
Treatment Options
• Surgery
• Radiation
• Adjuvant therapy (hormonal)
Surgery
Radical Mastectomy
Lumpectomy
Clinical Tumor Size < 4.0 cm
NSABP B-06
Stratification• Clinical Nodal Status• Clinical Tumor Size
TotalMastectomy+ Ax. Diss.
Lumpectomy+ Ax. Diss
Lumpectomy+ Ax. Diss
+ XRT
B-06 Cumulative Incidence of IBTR
0
10
20
30
40
50
60
70
0 2 4 6 8 10 12 14 16 18 20Year
L 570 pts., 220 IBTR’sL+XRT 567 pts., 78 IBTR’s
P < 0.00139
14
%
Mammography =Breast x-ray
Breast XRT
No Further Therapy
Stratification
• Age• Method of Detection
• Pathologic Characteristics
• Axillary Dissection
NSABP B-17
DCIS Treated by Lumpectomy
B-17
• No difference in survival(86% vs. 85% at 14 years)
Radiation
B-17 Cumulative Incidence ofIpsilateral Breast Cancer
RR=0.43P<.0001
N # Events 12 Yr CIL 403 131 32%L+XRT 410 65 15%
B-17 Ipsilateral Invasive Breast Cancer
N # Events 12 Yr CIL 403 72 18%L+XRT 410 32 7%
RR=0.39P<.0001
Adjuvant Therapy (hormonal)
Chemical Structure of Tamoxifen
Chemical Structure of Tamoxifen
(CH3) 2 N (CH2) 2 O
C2 H5
Tamoxifen
DCIS patients afterlumpectomy +XRT
Stratification• Age ( 49, 50)
NSABP B-24
Placebo
B-24 Cumulative Incidence of All BC
N # Events 9 Yr CIPlacebo 899 183 21%Tam 899 126 13%
RR=0.66P=.0003
Sites of 1st Events by HR Status and Treatment
Frequency (Percentage)
All Breast CancerEvents
IBT
Regional/Distant
Contralateral
68 (24%)
42 (15%)
4 (1%)
22 (8%)
40 (14%)
27 (9%)
0 (0%)
13 (4%)
HR Positive
PlaceboN=282
TamN=292
B-24
• Increased frequency of endometrial cancer (11 vs. 4)
• No difference in survival(92% vs. 94% at 10 years)
ExemestaneO
CH2
O
Nonsteroidal
Steroidal
Chemical Structures
Anastrozole
N
N
NC CN
NN
LetrozoleN
N
N
CH3
CN
CH3
CN
CH3CH3
Postmenopausal Women withER or PR Positive DCIS, Treated with
Lumpectomy + XRT
AnastrozoleTamoxifen
NSABP DCIS Trial B-35
0 12 24 36 48 60 72 84 96 108 1200
20
40
60
80
100
Time Since Randomization (months)
B-35: Overall SurvivalS
urv
ivin
g %
At Risk by Year # of %Treatment 0 6 10 Events 10 yrs HR P-value
Tamoxifen 1543 1388 368 88 92.1
Anastrozole 1540 1390 396 98 92.5 1.110.48
92.1%
92.5%
NRG Oncology ASCO 2015
0 12 24 36 48 60 72 84 96 108 1200
20
40
60
80
100
Time Since Randomization (months)
B-35: BCFI by Age GroupE
ven
t-F
ree
%
Treatment N Events HR P-value
Tamoxifen 722 58
Anastrozole 725 31 0.52
0.003
0 12 24 36 48 60 72 84 96 108 1200
20
40
60
80
100
Ev
ent-
Fre
e %
Treatment N Events HR P-value
Tamoxifen 816 56
Anastrozole 814 53 0.95 0.77
≥ 60 years< 60 years
88.2%
94.9%
90.2%
92.2%
NRG Oncology ASCO 2015
B-35: Other Secondary Endpoints
Number of EventsHazard Ratio(HR)
P-value
Tamoxifen(N=1,538)
n (%)
Anastrozole(N=1,539)
n (%)
Ipsilateral Recurrence
53 (3.4) 43 (2.8) 0.80 0.27
Invasive 21 (1.4) 14 (0.9) 0.65 0.22 DCIS 32 (2.0) 29 (1.9) 0.89 0.66Contralateral Breast Cancer
55 (3.5) 37 (2.4) 0.67 0.06
Invasive 36 (2.3) 20 (1.3) 0.55 0.03 DCIS 19 (1.2) 17 (1.1) 0.89 0.72
NRG Oncology ASCO 2015
Future Directions
• Over diagnosis Mis-diagnosis
• Molecular evaluation
• The “switch”
• HER2+ and ER–
≠
Herceptin Mechanism
NSABP B-43 Schema
* Patients with ER+ and/or PgR+ DCIS should receive a minimum of 5 years of hormonal therapy
STRATIFICATION· Menopausal Status (premenopausal; postmenopausal)· Plan for Hormonal Therapy (yes; no)· Nuclear Grade (low or intermediate; high)
RANDOMIZATION
Group 1*
Radiation Therapy
Group 2*
Radiation Therapy+
Trastuzumab x 2 doses
Dose 1: 8 mg/kg IVDose 2: 6 mg/kg IV
given 3 weeks after Dose 1
DCIS Resected by Lumpectomy Determined to be HER2-Positive by Central Testing