2005 sabcs review: surgery, radiation, and prevention laura esserman m.d.,m.b.a. director, ucsf...
Post on 28-Jan-2016
220 Views
Preview:
TRANSCRIPT
2005 SABCS Review: Surgery, Radiation, and Prevention
Laura Esserman M.D.,M.B.A.
Director, UCSF Carol Franc Buck Breast Care Center
Professor of Surgery and Radiology
Abstracts
• Surgical Practice Patterns (12)
• Surgical Techniques (406)
• Local Recurrence (29, 7,8)
• Sentinel Nodes (20,21)
• Prevention (36)
Surgical Practice Patterns (12)
• Surgical biopsy as a diagnostic tool adversely affects outcomes of breast cancer care – National Comprehensive Cancer Centers Network
Edge et. al.• 6282 women, 8 centers, 1997-2002
– Outcomes• Re-excision, total trips to the OR, elapsed time to complete
surgical care• Re-excision rate associated with initial biopsy (83% higher)• Re-excision affects time to complete surgery
– Mean time to complete surgery 30 vs. 48 days – Includes initial biopsy
Total Skin Sparing Mastectomy
• Nipple and areola complex dermis can be preserved (63 cases)
• Different techniques analyzed• Lateral incision most reliable• Expect skin sloughing, but dermis will regenerate• MRI used to avoid tumor present under nipple
– Pathology sectioning identified 2 cases with DCIS (microscopic) in excised nipple tissue
• Cosmetic results excellent• Technically challenging
SS/FG
TSS/RTSS/MTSS/I
TSS/N
Figure 2: Types of incisions used
BA
C D E
Figure 3: Total skin-sparing mastectomy pathology specimen
A C
B
R L
Figure 4: Post-operative successes
A B
CD
Local Recurrence
Biology predicts local recurrence
tumor biology
age, breast density
Gene Differences Predict Local Recurrence
• Confirms that biology drives both local and distant recurrence
• Suggests, however, that some features drive local recurrence alone and not distant recurrence
Association Between the 21-Gene Association Between the 21-Gene Recurrence Score Assay (RS) Recurrence Score Assay (RS)
and Risk of Loco-Regional Failure and Risk of Loco-Regional Failure in Node-Negative, ER-Positive Breast Cancer:in Node-Negative, ER-Positive Breast Cancer: Results from NSABP B-14 and NSABP B-20Results from NSABP B-14 and NSABP B-20
Eleftherios Mamounas,Eleftherios Mamounas,1,31,3 Gong Tang, Gong Tang,11 John Bryant, John Bryant,11 Soonmyung Paik, Soonmyung Paik,11 Steven Shak, Steven Shak,22 Joseph Costantino,Joseph Costantino,11 Drew Watson, Drew Watson,22 D. Lawrence Wickerham, D. Lawrence Wickerham,11 and Norman Wolmark and Norman Wolmark11
11NSABP Operations and Biostatistical Center, Pittsburgh, PANSABP Operations and Biostatistical Center, Pittsburgh, PA22Genomic Health Inc, Redwood City, CAGenomic Health Inc, Redwood City, CA
33Aultman Health Foundation, Canton, OHAultman Health Foundation, Canton, OH
Background Background
• The 21-Gene Recurrence The 21-Gene Recurrence
Score (Oncotype DX) is an Score (Oncotype DX) is an
RT-PCR based gene RT-PCR based gene
expression profiling assay expression profiling assay
that includes 16 cancer that includes 16 cancer
genes and 5 reference genes and 5 reference
genes.genes.
PROLIFERATIONPROLIFERATIONKi-67Ki-67
STK15STK15SurvivinSurvivin
Cyclin B1Cyclin B1MYBL2MYBL2
ESTROGENESTROGENERERPRPR
Bcl2Bcl2SCUBE2SCUBE2
INVASIONINVASIONStromelysin 3Stromelysin 3Cathepsin L2Cathepsin L2
HER2HER2GRB7GRB7HER2HER2
BAG1BAG1GSTM1GSTM1
REFERENCE GENESREFERENCE GENESBeta-actin, GAPDH, RPLPOBeta-actin, GAPDH, RPLPOGUS, TFRCGUS, TFRC
CD68CD68
Background (cont.) Background (cont.)
• The RS has been shown The RS has been shown to quantify risk of to quantify risk of distant distant recurrencerecurrence in in node-node-negative, ER-positive, negative, ER-positive, tamoxifen-treated breast tamoxifen-treated breast cancer patients cancer patients and has and has been validated in two been validated in two independent data sets independent data sets (Paik et al., 2005, Habel et al., 2004)(Paik et al., 2005, Habel et al., 2004)
0 2 4 6 8 10 12 14 16
Years
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
DR
FS
Low R isk (R S < 18) Intermediate R isk (R S 18 - 30) H igh R isk (RS 31)
NSABP B-14 NSABP B-14 Validation StudyValidation Study
Paik S, et al: N Engl J Med, 2005Paik S, et al: N Engl J Med, 2005
Statistical Considerations (cont.)Statistical Considerations (cont.)
• RS categoriesRS categories were defined as in were defined as in previous studies on distant recurrence:previous studies on distant recurrence:
–Low RS: Low RS: < 18< 18
– Intermediate RS: Intermediate RS: 18-3018-30
–High RS: High RS: >> 31 31
NSABP NSABP Node-Negative, ER-Positive Node-Negative, ER-Positive
TrialsTrialsB-14: B-14: PlaceboPlacebo
vs.vs.TamoxifenTamoxifen
B-20:B-20: TamoxifenTamoxifen
vs.vs.MFT MFT vs.vs.
CMFTCMFT
B-14 B-14 Registry:Registry:
TamoxifenTamoxifen
SurgerySurgery
TypeType
B-14B-14
PlaceboPlacebo
(n=355)(n=355)
B-14B-14
TAMTAM
(n=668)(n=668)
B-20B-20
TAMTAM
(n=227)(n=227)
B-20B-20
TAM+ChemoTAM+Chemo
(n=424)(n=424)
LumpectomyLumpectomy 32%32% 42%42% 48%48% 39%39%
MastectomyMastectomy 68%68% 58%58% 52%52% 61%61%
Patient CharacteristicsPatient CharacteristicsSurgery TypeSurgery Type
• All lumpectomy patients received breast XRTAll lumpectomy patients received breast XRT• Post-mastectomy chest wall XRT was not allowedPost-mastectomy chest wall XRT was not allowed• Regional nodal XRT was not allowed irrespective of Regional nodal XRT was not allowed irrespective of
surgical proceduresurgical procedure
ResultsResults
• Based on the Based on the Ten-year K-M Estimate of LRF Ten-year K-M Estimate of LRF RateRate According to RS Category According to RS Category – Tamoxifen-Treated Pts from B-14 and B-20 Tamoxifen-Treated Pts from B-14 and B-20
(n=895)(n=895)
– Placebo-Treated Pts from B-14 Placebo-Treated Pts from B-14 (n=355)(n=355)
– Chemotherapy + Tamoxifen-Treated Pts from B-Chemotherapy + Tamoxifen-Treated Pts from B-20 20 (n=424)(n=424)
Tamoxifen-Treated Patients (B-14/B-20, n=895)Tamoxifen-Treated Patients (B-14/B-20, n=895)
10-Year LRF Rates 10-Year LRF Rates According to RS CategoryAccording to RS Category
00 22 44 66 88 1010
00101
0202
0303
0404
0
Time in YearsTime in Years
4.34.3
7.27.2
15.815.8
P<0.0001P<0.0001
Rat
e o
f L
RF
%R
ate
of
LR
F %
RS < 18RS < 18
RS RS >>3131RS 18-30RS 18-30
Placebo-Treated Patients (B-14, n=355)Placebo-Treated Patients (B-14, n=355)
10-Year LRF Rates 10-Year LRF Rates According to RS CategoryAccording to RS Category
00 22 44 66 88 1010
00101
0202
0303
0404
0
Time in YearsTime in Years
10.810.8
20.020.0
18.418.4
P=0.022P=0.022
Rat
e o
f L
RF
%R
ate
of
LR
F %
RS < 18RS < 18
RS RS >>3131RS 18-30RS 18-30
10-Year LRF Rates10-Year LRF RatesAccording to RS CategoryAccording to RS Category
Chemo + Tamoxifen-Treated Patients (B-20, n=424)Chemo + Tamoxifen-Treated Patients (B-20, n=424)
00 22 44 66 88 1010
00101
0202
0303
0404
0
Time in YearsTime in Years
1.61.6
2.72.7
7.87.8
P=0.028P=0.028
Rat
e o
f L
RF
%R
ate
of
LR
F %
RS < 18RS < 18
RS RS >>3131RS 18-30RS 18-30
1.6 2.7
7.8
Chemo + TAM Chemo + TAM n=424n=424
P=0.028P=0.028
4.37.2
15.8
TAM TAM n=895n=895
P<0.0001P<0.0001
10.8
2018.4
Placebo Placebo n=355n=355
P=0.022P=0.022
00101
0202
0303
0404
0%%
10-Year LR Failure Rates 10-Year LR Failure Rates According to Treatment and RS CategoryAccording to Treatment and RS Category
RS < 18RS < 18
RS RS >>3131RS 18-30RS 18-30
VariableVariable P-valueP-value HRHR 95% CI for HR95% CI for HR
Age (Age (>> 50 vs. < 50) 50 vs. < 50) <0.0001<0.0001 0.380.38 (0.24, 0.61)(0.24, 0.61)
CTS ( >2 cm vs. CTS ( >2 cm vs. << 2 cm) 2 cm) 0.7870.787 1.071.07 (0.66, 1.72)(0.66, 1.72)
Mastectomy vs. Mastectomy vs. Lumpectomy +XRTLumpectomy +XRT 0.0420.042 0.620.62 (0.39, 0.98)(0.39, 0.98)
Grade (Mod vs. Good)Grade (Mod vs. Good) 0.6190.619 1.171.17 (0.63, 2.19)(0.63, 2.19)
Grade (Poor vs. Good)Grade (Poor vs. Good) 0.0020.002 2.582.58 (1.40, 4.74)(1.40, 4.74)
VariableVariable P-valueP-value HRHR 95% CI for HR95% CI for HR
Recurrence ScoreRecurrence Score <0.0001<0.0001 3.163.16 (2.00, 5.07)(2.00, 5.07)
Cox Proportional Hazard ModelsCox Proportional Hazard Models TAM-Treated Pts (n=895)TAM-Treated Pts (n=895)
VariableVariable P-valueP-value HRHR 95% CI for HR95% CI for HRRecurrence ScoreRecurrence Score 0.0050.005 2.162.16 (1.26, 3.68)(1.26, 3.68)
Age (Age (>> 50 vs. < 50) 50 vs. < 50) 0.00020.0002 0.400.40 (0.25, 0.65)(0.25, 0.65)
Mastectomy vs. Mastectomy vs. Lumpectomy + XRTLumpectomy + XRT 0.0470.047 0.620.62 (0.39, 0.99)(0.39, 0.99)
CTS ( >2 cm vs. CTS ( >2 cm vs. << 2 cm) 2 cm) 0.9330.933 0.980.98 (0.61, 1.59)(0.61, 1.59)
Grade (Mod vs. Well)Grade (Mod vs. Well) 0.9660.966 1.101.10 (0.54, 1.92)(0.54, 1.92)
Grade (Poor vs. Well)Grade (Poor vs. Well) 0.1050.105 1.761.76 (0.89, 3.48)(0.89, 3.48)
Multivariate Cox Proportional Hazard Multivariate Cox Proportional Hazard ModelsModels
TAM-Treated Pts (n=895)TAM-Treated Pts (n=895)
AgeAge RSRS LRF RateLRF Rate 95% CI95% CI P-valueP-value EventsEvents<50<50 < 18< 18 1.5%1.5% (0, 4.5%)(0, 4.5%) 0.0010.001 2/732/73
18 - 3018 - 30 7.6%7.6% (0, 17.6%)(0, 17.6%) 2/312/31≥ ≥ 3131 23.8%23.8% (9.4%, 38.1%)(9.4%, 38.1%) 9/499/49
≥ ≥ 5050 < 18< 18 2.6%2.6% (0.1%, 5%)(0.1%, 5%) 0.0050.005 6/1896/18918 - 3018 - 30 3.8%3.8% (0, 8.1%)(0, 8.1%) 3/823/82≥ ≥ 3131 12.8%12.8% (4.3%, 21.3%)(4.3%, 21.3%) 9/819/81
10-Year Loco-Regional Failure Rates 10-Year Loco-Regional Failure Rates TAM-Treated Pts with TAM-Treated Pts with MastectomyMastectomy (n=505) (n=505)
•XRT overview suggests that there is a 1% decrease in mortality for every 5% difference in local recurrence
•biology and density may contribute to decisions about XRT even after mastectomy
AgeAge RSRS LRF RateLRF Rate 95% CI95% CI P-P-valuevalue EventsEvents
<50<50 < 18< 18 12.5%12.5% (4.4%, 20.7%)(4.4%, 20.7%) 0.0570.057 10/7210/7218 - 3018 - 30 27.7%27.7% (8.8%, 46.6%)(8.8%, 46.6%) 7/237/23≥ ≥ 3131 26.5%26.5% (12.2%, 40.8%)(12.2%, 40.8%) 12/4512/45
≥ ≥ 5050 < 18< 18 3.6%3.6% (0.1%, 7.1%)(0.1%, 7.1%) 0.6630.663 6/1396/13918 - 3018 - 30 3.7%3.7% (0, 8.7%)(0, 8.7%) 4/584/58≥ ≥ 3131 4.8%4.8% (0, 11.2%)(0, 11.2%) 3/533/53
10-Year Loco-Regional Failure Rates 10-Year Loco-Regional Failure Rates TAM-Treated Pts with TAM-Treated Pts with Lumpectomy/XRTLumpectomy/XRT (n=390) (n=390)
Lower rates of recurrence in postmenopausal women suggest that partial breast radiation is likely to be most effective in that group
Biology
• Biology, as measured by recurrence score, or grade, and age, predicts local recurrence.– Women<50 with mastectomy had high local recurrence if
RS high– Women>50 with mastectomy had low local recurrence
rates– Women <50 with lumpectomy had higher local recurrence
if RS >18
• Supports recurring observation of high LRF in young women, but refines it based on biology of tumor
• Opportunity may be to look at the interaction of stroma and tumor to predict Local Recurrence
XRT benefits depend on age and tumor type
• Abstract 7: Radiotherapy in breast-conserving treatment for ductal carcinoma in situ (DCIS): 10 year results of EORTC randomized trial 10853 Bijker et al– 1010 women randomized to XRT vs not, 50Gy (5wks)
• Tumors <5cm• Detection:Clinical (30%) or Mammographic (71%)• Median F/U 10.2
– LR 75% vs. 85% , no RT vs. RT• DCIS and invasive cancer equally reduced• No difference in metastatic disease, OS
– Highest Risk for LR with Breast Conservation• Women < 40 HR =1.95• Positive margins HR= 1.82• Clinical Detection HR=1.53• Grade 3,2 vs. 1 HR=1.77, 1.3• Solid, cribriform vs. micropapillary, clinging HR=2.21, 2.28• Lumpectomy alone vs. RT HR=1.74
XRT benefits depend on age and tumor type
• Abstract 8: Breast Conservation without radiotherapy in low risk breast cancer patients- results of 2 prospective clinical trials of the Austrian Breast and Colorectal Cancer Study Group involving 1,518 postmenopausal patients with endocrine responsive breast cancer Grant et al
– XRT in ER+ postmenopausal women: OS not different, 11 fold decrease in LR, but absolute difference in 3% range
– Local Recurrence Rate 5.2 vs. O.4 with XRT vs. not (all patients)
– Randomized Trial (ABCSG-8): Median FU 121 months• Overall survival: No difference• Overall LR 1.71% (No RT 0.24 vs. RT 3.19%)
DCIS
RT does not affect OS
Biology may predict LR and impact of RT
Option of using RT for LR failure
Think about Prevention first?
Invasive Cancer
Should biology be the guide for choosing RT, targeted RT, or
nothing?
Sentinel Nodes
Issues Addressed
• NSABP B-32– If you find a sentinel node that is positive, what is the
likelihood of finding other positive nodes?• Depends on how many sentinel nodes are positive• Depends on the total number of nodes removed
• Moffit South Florida Cohort Study– If you find microscopic tumor in a node, IHC+ or H&E+
(<2mm) what does it signify?• That you have a 12-15% risk of macroscopic tumor in other
lymph nodes• Impact on survival determined by the presence of true H&E
positive disease
J Cox, M.D., A Riker, M.D., L White, B.S., D Hasson, B.S., N Allred, D Ramos, M J Cox, M.D., A Riker, M.D., L White, B.S., D Hasson, B.S., N Allred, D Ramos, M Myers, E Dupont, M.D., J King, B.S., A Cantor, Ph.D., V Vrcel, M.D., N Diaz, Myers, E Dupont, M.D., J King, B.S., A Cantor, Ph.D., V Vrcel, M.D., N Diaz,
M.D., N Draper, M.D., C Schuetz, M.D., andM.D., N Draper, M.D., C Schuetz, M.D., and S Khera, M.D.S Khera, M.D.
Significance of Sentinel Lymph Node Micrometastasis on Significance of Sentinel Lymph Node Micrometastasis on Survival for Patients With Invasive Breast CancerSurvival for Patients With Invasive Breast Cancer
Charles E. Cox, M.D.
Abstract 216781 patients
N1+n=3047
• N0(i+):N0(i+): 15/11615/116 12.9%12.9%• N1mi :N1mi : 17/111 17/111 15.3%15.3%
______________________________________________________________• Total:Total: 32/22732/227 14.1%14.1%
Non=2762N?
n=227
Results: T-Stage Comparison
P = 0.008
Overall Survival Comparison by T Stage For N0(i-) Patients
Results
• T1-T3 N1mi patients F/U T1-T3 N1mi patients F/U >> 5yrs had significantly worse OS 5yrs had significantly worse OS (p=0.005) and DSF (p=0.016) than T1-T3 N0(i-) pts.(p=0.005) and DSF (p=0.016) than T1-T3 N0(i-) pts.
• T1 N1mi patients show a significantly worse OS than T1 T1 N1mi patients show a significantly worse OS than T1 N0(i-) pts. (p = 0.04) at 2yrs of F/UN0(i-) pts. (p = 0.04) at 2yrs of F/U
THESE DIFFERENCES DISAPPEARED WHEN THESE DIFFERENCES DISAPPEARED WHEN MACROSCOPIC CASES ARE REASSIGNEDMACROSCOPIC CASES ARE REASSIGNED
• T2 N1mi patients OS is not significantly worse than T2 N0(i-) T2 N1mi patients OS is not significantly worse than T2 N0(i-) pts. (p = 0.14) ( T size and F/U may be factors)pts. (p = 0.14) ( T size and F/U may be factors)
Practice Changing
N0 (i+)N1 mi ALND
N1
N0
SLN
(-) no ALND
(+)ALND
Thomas B Julian MD, Stewart Anderson PhD, Ann Brown ScD, Harry Bear MD, David Krag MD, Seth Harlow MD, Taka Ashikaga PhD, Donald Weaver MD, Barbara Miller RN MSN, Lynne Jalovec MD, Thomas Frazier MD, Richard
Dirk,Noyes MD, Andre Robidoux MD, Hugh Scarth MD, Denise Mammolito MD, David McCready MD, Eleftherios P Mamounas MD, Joseph Costantino DrPH, John
Bryant PhD, and Norman Wolmark MD
NSABP Operations and Biostatistical Centers, Pittsburgh PA Department of Surgery University of Vermont, Burlington VT San Antonio Breast Cancer Symposium December 9, 2005
Continued Technical Results of NSABP B-32: Does a Positive Sentinel Node Biopsy Always
Require an Axillary Dissection?
No AxillaryDissection
Clinically Negative Axillary Nodes
NSABP B-32 NSABP B-32
GROUP 1Sentinel Node Resection*
Followed ByAxillary Dissection
Axillary Dissection
Path. Neg.Sentinel Node
GROUP 2Sentinel Node
Resection *
Randomization
Stratification• Age• Clinical Tumor Size• Type of Surgery
Path. Pos.Sentinel Node
NSABP B-32Sentinel Node
Identification/Evaluation
• Combined technique of isotope, dye, and palpation for identification
• Sectioned at 2-3 mm intervals
• 5m sections for H&E stains
NSABP B-32
• SN identification rate: 97.1%
• SN positive rate: 26%
• False negative rate: 9.8%
• Average SNs: 3.0
• SLNs were the only positive node in 61.4%
of node positive patients
Question
Can factors be identified which predict for positive non-sentinel axillary nodes (PNSN) in AND specimen following a
positive SN biopsy?
Study Design
• 5,611 patients randomized with 2,807 in the SNR/AND Group 1 and 2,804 in the SNR Group 2
• 1,361 patients had a positive SN and AND in both Groups combined
• 1,355 of these patients underwent multivariate analysis
Univariate AnalysisFactors Associated with Positive NSN
Variable CategoryNumber of
Positive SN Patients
% Positive NSN
P-value
Study
Group
SNR with AND
(G1)
691 35.5
0.02SNR only AND
(G2)670 41.9
Number of SN
Examined
1 – 3 929 41.4 0.002
4 or more 432 32.6
Univariate AnalysisFactors Associated with Positive NSN
Variable CategoryNumber of
Patients% Positive
NSNP-value
Number of Positive
SN
1 859 28.2
<0.0001†2 306 49.3
3 122 61.5
4 or more 74 78.4
Number of
Hot Spots
0 96 63.5<0.0001‡
1 or more 1265 36.8
† p-value for test of trend ‡ p-value for test of heterogeneity
Univariate AnalysisFactors Associated with Positive NSN
Variable CategoryNumber
of Patients
% Positive NSN
PositiveP-value
Clinical
Tumor Size
≤ 1 cm 295 32.2
<0.0001†1.1 – 2 cm 631 34.4
> 2 cm 435 49.2
Location of Primary Tumor§
UOQ 539 43.00.007 ‡All other 816 35.5
§ Six values are unknown † p-value for test of trend ‡ p-value for test of heterogeneity
Univariate Factors not Significant Predictors for Positive NSN
• Age
• Type of biopsy
• Histologic grade
• ER/PR status
Multivariate Analysis
VariableOdds Ratio
95% CI P-value
Study Group (SNR+AND†, SNR) 1.32 (1.04 – 1.68) 0.023
Number of SN examined § 0.74‡ (0.68 – 0.80) < 0.0001
Number of SN positive § 2.53‡ (2.16 – 2.96) < 0.0001
Location (UOQ†, All others) 0.75 (0.59 – 0.96) 0.022
Clinical Tumor Size § 1.21‡ (1.10 – 1.34) 0.0002
Number of Hot spots § 0.54‡ (0.37 – 0.80) 0.0020
Logistic model of proportion of patients who are NSN Positive
† Baseline for comparison
§ Modeled as continuous variable‡ Odds ratio for increase of one unit
*Removed is the Number of NSN
Predicted Probability of a Patient with Positive NSN as a Function of Clinical Tumor Size and the Number of Sentinel
Nodes Removed with One Positive Sentinel Node
1 SN
3 SN
5 SN
7 SN
9 SN
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
Clinical Tumor Size (cm)
Pro
bab
ilit
y o
f P
osi
tive
NS
N
UOQ1 PSN1 Hot Spot
Predicted Probability of a Patient with Positive NSN as a Function of Tumor Size and the Number of Positive
Sentinel Nodes with 5 Sentinel Nodes Removed
Clinical Tumor Size (cm)
0 1 2 3 4 5
SN 1+
SN 2+
SN 3+
SN 4+SN 5+
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Pro
bab
ility
of
Po
siti
ve
NS
N
UOQ1 Hot Spot5 SN Removed
Conclusions
No subset of patients could be identified that had a sufficiently low probability for PNSN to allow for omission of AND unless the number of sentinel nodes removed approached that of an axillary dissection.
These results support the need for AND with PSN by H&E for staging and treatment planning.
Analysis of the NSABP B-32 sentinel node negative patients by IHC may yet identify patient populations where AND can be avoided.
Estrogen Receptor-Negative (ER-) Breast Cancers
are Less Likely to Arise among Statin Users
Anjali Kumar MD, MPH, Veronica Shim MD,Christina Minami, Dan Moore PhD, Chris Benz MD,
and Laura Esserman MD, MBA
University of California San FranciscoKaiser Permanente Oakland Medical Center
HMG-CoA Reductase
Cholesterol
Acetyl-CoA
HMG-CoA
Mevalonate
GGP
FPP Ras pathway effects
Rho pathway effectsRho pathway effects
Statins
Mechanism
Statin Score CardPro
Kochhar 2005, RR=0.5
Boudreau 2004, RR=0.7
Mortimer 2003, RR=0.4
Cauley 2003, RR=0.3
Blais 2000, RR=0.7
Con
Bonovas 2005, RR=1.0
Eliassen 2005, RR=0.9
Friis 2005, RR=1.0
Beck 2003, RR=1.1
Coogan 2002, RR=1.5
Kaye 2002, RR=1.0
Lipophilic statins only or stratified data for statin typeLipophilic statins only or stratified data for statin type
Hypothesis
Lipophilic statin use reduces the likelihood of developing ER- breast cancer
Methods
• Retrospective cohort study• Kaiser Permanente
– Largest HMO in the Western U.S.– Estrogen receptor staining performed
centrally – Electronic pharmacy records available
• Individual chart review
– Atorvastatin, lovastatin and simvastatin are the only statins on formulary• All lipophilic
Population for Analysis
• All Breast cancer patients 2141– All Statin users (lipophilic) 387 (18%)
– Statin users >1 year
before diagnosis 303 (17%)
• Analysis – Statin use for > 1 year vs. no statin use or use
1 year
– Chi-square, logistic regression
Results
n=2141
None or 1 yr Statin Use
>1 yr Statin Use *
* P = 0.001
35 (2%)354 (17%)ER -
Results
Odds of developing ER-neg tumor
Statin use >1 year vs. use 1 year
Age-adjusted OR=0.64
95% CI = 0.44 – 0.93
(P=0.02)
Lower probability of ER – cancers seen across all age groups
20 40 60 80 100
age at diagnosis
Statin Use ≤1yr
Statin Use >1yr
0.35
0.30
0.25
0.20
0.15
0.10
Pro
bab
ilit
y o
f E
R-N
egat
ive
Tu
mo
r
Limitations
• Cannot assess risk reduction rates
• Limited information on factors which may influence estrogen receptor– Body mass index (BMI)– Alcohol use– Exercise– Family history
Conclusions
• ER negative cancers were less likely to develop among patients who used statins for >1 year
• Continue to explore the role of lipophilic statins in breast cancer prevention, particularly ER- cancers
Core Bx DCIS or Stage I
Fluvastatin 20 mg
Fluvastatin 80 mg
RRAANNDDOOMMIIZZEE
OR3-6 wks3-6 wks
BB BB
Pilot Biomarker Trial Schema
• UCSF, U of Chicago, Dana Farber Cancer Center, Memorial Sloan Kettering Cancer Center
BB = Biomarkers: tumor, blood, imaging (MRI)
top related