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)