Current Considerations in the Management of Patients with Hormonally Sensitive

Early-stage Breast Cancer

Harold J. Burstein, MD, PhDDana-Farber Cancer Institute

Harvard Medical SchoolBoston, MA

Clinical UpdatesHormonally Sensitive, Early-Stage Breast Cancer

Overview

• Case 1: Optimizing Therapy in Postmenopausal Women

– ER+, PR+, HER2 negative stage I breast cancer

• Case 2: Optimizing Therapy in Premenopausal Women

– Which patients with ER+ tumors should receive adjuvant chemotherapy?

Case 1

• Postmenopausal Women

– T = 0.8 cm

– ER+

– PR+

– HER2 negative

– Stage I breast cancer

• What issues should be considered to optimize endocrine therapy for postmenopausal women?

Key Issues in Adjuvant Endocrine Therapy for Postmenopausal Women

• When to start an AI

• When to stop an AI

• Whether and how to use tamoxifen– Tumor features (ER, PR, HER2)

– Clinical factors (patient preference, comorbidities)

– Pharmacogenomic factors

– Concurrent medication factors

• Minimizing side effects, esp. bones

• Late sequelae – good or bad – of AI therapy

Importance of Endocrine Therapy

• 2/3 of breast cancers are ER/PR+

• 3/4 of post-menopausal women have ER/PR+ tumors

• Overall little toxicity from endocrine treatment

• Significant benefit from optimizing use of endocrine agents in the post-menopausal population

Adjuvant Endocrine Agents: Tamoxifen

• Useful regardless of menopausal status

• In postmenopausal women:

– Reduces recurrence by 37 – 54%

– Reduces death by 11 – 33%

• Long-term side effects characterized

• Carryover effect documented

• Utility in sequence with AIs in post-menopausal women

Early Breast Cancer Trialists, Lancet 2005.

Adjuvant Endocrine Agents: Aromatase Inhibitors

• Inhibit peripheral conversion of androgens to estrogens by the aromatase enzyme

• 3 agents: anastrazole, letrozole, exemestane

• Utility of adjuvant AIs established through 3 trial designs– Upfront comparison with tamoxifen

• ATAC, BIG 1-98

– Sequential therapy after 2-3 years tamoxifen

• IES, ARNO/ABCSG, ITA

– Extended therapy after 5 years tamoxifen

• MA.17

Adjuvant Trials AIs in Postmenopausal Women

AI x 5 years

Tamoxifen x 5 years

AI x 5 years

Tamoxifen x 5 years

Tamoxifen x 5 years

Placebo x 5 years

Tamoxifen AI

Upfront vs Tamoxifen

Sequential vs Tamoxifen

Extended Rx, AI vs Placebo

5 years of AI is Established

• ATAC: 100 month follow-up

• Lower recurrence rate after 5 years, suggests carry-over effect

• No new toxicity signals

• No OS benefits

Forbes et al, Lancet 2008

ATAC: 100 Month Follow-up

Forbes et al, Lancet 2008

Coates, A. S. et al. J Clin Oncol; 25:486-492 2007

DFS

OS

Big 1-98: 5-year Analysis

Coates et al, J Clin Oncol 2007;25:486-92

Coombes, et al. Lancet 2007;369:559

IES Update 2007

ARNO 95 / ABCSG 8 / ITA Pooled Outcomes

Jonat, et al. Lancet Oncology 2006;7:991

Goss, P. E. et al. J. Natl. Cancer Inst. 2005 97:1262-1271; doi:10.1093/jnci/dji250

DFS OS

MA.17

ASCO Guidelines

“The Panel believes that optimal adjuvant hormonal

therapy for a postmenopausal woman with receptor-

positive breast cancer includes an aromatase inhibitor

as initial therapy or after treatment with tamoxifen.

Women with breast cancer and their physicians must

weigh the risks and benefits of all therapeutic options.”

Winer, et al JCO 2004

The Debate What is the Optimal Approach to the Use

of an AI in the Adjuvant Setting?

• Upfront AI x 5 years

– Proponents of an upfront AI cite early benefit and seek to minimize risk of early relapse, hoping this will lead to long-term benefit

• Tamoxifen x 2 years followed by AI x 3-5 years

– Proponents of cross-over approach seek to minimize risk of late recurrence by using two effective agents, hoping that short-term losses will be more than compensated by long-term gains

BIG 1-98: Design

2-Arm Option

Tamoxifen

Letrozole

Letrozole

Letrozole Tamoxifen

RANDOMIZE

0 2 5Years

A

B

C

D

Tamoxifen

Tamoxifen

Letrozole

A

B

4-Arm Option

SURGERY

Stratify

Institution

CT (Adjuvant/ Neoadjuvant)-Prior-None-Concurrent

N=1,828Enrolled

1998-2000

N=6,182Enrolled

1999-2003

N=8,010*

RANDOMIZE

*ITT: excludes 18 patients who withdrew consent and did not receive study treatment

N=911

N=917

N=1548

N=1540

N=1548

N=1546

Previous Analyses: Is 5 years Let superior to 5 years Tam as initial therapy?• Primary Core Analysis (PCA), Median follow-up 26 months• Monotherapy Arm Analysis, Median follow-up 51 months

RANDOMIZE

Summary of Previous Analyses

The PCA and monotherapy analyses showed that 5 years upfront letrozole is significantly superior to 5 years of upfront tamoxifen in terms of:

– Disease-free survival

– Time to distant recurrence

BIG 1-98 Collaborative Group, N Engl J Med 2005;353:2747-57Coates et al, J Clin Oncol 2007;25:486-92

*Let:Tam: breast cancer events, 321:363second (non breast) malignancy, 101:115deaths without prior cancer event, 87:87

Mouridsen HT, et al: SABCS 2008, Abstr. 13

BIG 1-98 Monotherapy UpdateMedian Follow-up 76 months

Mouridsen HT, et al: SABCS 2008, Abstr. 13

BIG 1-98 Sequential Treatment Disease-Free Survival

Sequential Treatment ComparisonsMedian Follow-up 71 months

Tam→Let vs. Let Let→Tam vs. Let

Mouridsen HT, et al: SABCS 2008, Abstr. 13

Breast Cancer EventsTamLet vs. Let

Overall By Nodal Status*

*42% of the population is node positive; 58% node negative

Mouridsen HT, et al: SABCS 2008, Abstr. 13

Breast Cancer EventsLetTam vs. Let

Overall By Nodal Status*

*42% of the population is node positive; 58% node negative

Mouridsen HT, et al: SABCS 2008, Abstr. 13

Conclusions

For postmenopausal women with endocrine-responsive breast cancer

• Updated results of BIG 1-98 suggest superior overall survival with letrozole compared with tamoxifen

• Adjuvant endocrine therapy should start with letrozole especially for patients at higher risk for early recurrence

• Patients commenced on letrozole can be switched after 2 years to tamoxifen, if required

• Safety is consistent with known safety profiles of each agent (data not shown)

• Improved therapeutic approaches beyond five years are required to control late relapses

Mouridsen HT, et al: SABCS 2008, Abstr. 13

Duration of Therapy

The Natural History of HR+ Breast Cancer is Very Long

• ER+ tumors demonstrate a relatively constant hazard of regression over time

• After TAM x 5 years, over half of all recurrences occur in years 6-15 (EBCTCG, Lancet 2005)

• MA-17: risk of recurrence was approx 2-3% each year on placebo arm (Ingle, SABCS 2005)

• With 5-8 years follow-up, none of the AI trials are truly mature

Saphner et al, JCO 1996

ATTom Results 2008

Gray et al, ASCO 2008

How Long Should AI Be Administered If Started After Tamoxifen?

• No direct evidence for more than 2-3 years of an AI after a 2-3 years of tamoxifen, BUT…

– In MA-17, a 5 year course of an AI is safe and data through 4 years of follow-up demonstrate ongoing effectiveness

– In IES, benefit of E over T appears to be largely while patients are on treatment

• Given these data, a 5 year course of AI treatment is reasonable when switching to AI after 2-3 years of tamoxifen

Ongoing Studies to Establish Optimal Duration of AI Therapy: MA.17R

Tamoxifen x 5y Letrozole x 5y

Tam x 2y

AI x 5y

AI x 5yPlacebo x 5y

Letrozole x 5y

Ongoing Studies to Establish Optimal Duration of AI Therapy

– NSABP B42

• Letrozole vs placebo; N = 3,800

– SALSA

• Anastrazole 2y vs 5y; N = 3,500

– SOLE

• 5y continuous vs intermittent letrozole

– Dutch

• Anastrazole 3y vs 6y, N = 1,800

– GIM4

• Letrozole 2y vs letrozole 5y; N = 4,000

> 10,000 pts will be studied

Can we identify which tumors and

which patients will benefit most from

the different strategies at our disposal?

Heterogeneity of ER+ Breast Cancer

Tumors

• HER2 status

• PR status

• Grade

• Luminal A vs B, or other genetic signature

• …and more

Patients

• Variability in drug metabolism

– CYP2D6

• Risk of toxicity

• …and more

And the lists will grow much longer in the years ahead

Risk of Distant Recurrence Using Oncotype DX (21-Gene RS) in Patients Treated with

Anastrozole or Tamoxifen: ATTAC Study

• Objective was to evaluate the prognostic ability of 21-gene RS assay in patients treated in ATAC study

• RS score was predictive of risk of recurrence in postmenopausal patients with ER+ with either node negative or node positive disease being treated with either tamoxifen or anastrozole

Rate of Distant Recurrence at 9 Years

Population N Low RS Intermediate RS High RS

Lymph Node Negative 872 4% 10% 22%

• Tamoxifen 432 3% 10% 30%

• Anastrozole 440 4% 11% 12%

Lymph Node Positive 306 16% 27% 46%

• Tamoxifen 152 14% 28% 42%

• Anastrozole 154 17% 25% 50%

Dowsett et al. SABCS 2008, Abstract 53

CYP2D6 and Tamoxifen Pharmacogenetics

CYP2D6 and Tamoxifen Metabolism

Goetz, M. P. et al. J Clin Oncol; 23:9312-9318 2005

CYP2D6 and Tamoxifen Metabolism CYP2D6 Polymorphism

Jin, JNCI 2005

Jin, JNCI 2005

Concomitant Drug Use and CYP2D6

Clinical Evidence Tamoxifen Pharmacogenetics and Clinical Outcomes

Goetz, et al JCO 2005

DFS OS

Clinical EvidenceTamoxifen Pharmacogenetics and Clinical Outcomes

Goetz, et al JCO 2005

AI Toxicities

• Arthralgias

• Sexual Dysfunction

• Osteoporosis

TEAM TrialJones, S. E. et al. J Clin Oncol; 25:4765-4771 2007

AI Toxicities

Trial Timing Comparison HRQOL Endocrine Symptom

ATAC Post surg A vs. T No effect Vag dryness, sexual dysfunction

TEAM Post surg E vs. T NA Vag dryness, bone/muscle aches

IES >2-3 Tam yrs E vs. T No effect ---

MA.17 > 5 yrs Tam L vs. Pl No effect Vasomotor symptoms, bodily pain, sexual dysfunction

AI Trials SummaryAI Trials Summary

From Whalen, 2006

Vaginal Estrogens for Genitourinary Symptoms Related to AI Therapy

• Common complaint in postmenopausal women; aggravated by estrogen deprivation of AI

• Topical / intravaginal estrogens may alleviate sx

• Are they safe?

• Kendall, SABCS 2005: E2 levels in women receiving concurrent AI treatment and Vagifem 25 g PV BIW

Estradiol Levels

AI BL Day 14 Day 28LET < 3 220 40LET < 3 232 31LET 3.5 77 16ANA < 3 46 2.4

AI Arthralgia Syndrome

Common complaint

• Symmetric

• Hands, feet, pelvis/hip, arms

• Pathognomonic criteria:

– “I aged overnight.” “I feel like an old lady.”

– Squeezing hands/joints gesture

• Etiology unclear

ATAC Arthralgia Incidence over Time

Sestak, et al. Lancet Oncology 2008

Diagnosis: AI-associated Joint SymptomsPts referred to rheumatology at Michigan and Hopkins

Diagnosis Number of patients (%)

Bursitis 8 (21.1%)

  Trochanteric 6 (15.8%)

Carpal tunnel syndrome 8 (21.1%)

Osteoarthritis 11 (28.9%)

  Knee 3 (7.9%)

  Hand 2 (5.3%)

Tendonitis 14 (36.8%)

  Rotator cuff/shoulder 8 (21.2%)

  Wrist 3 (7.9%)

  Elbow 2 (5.3%)

Patellofemoral syndrome 7 (18.4%)

AI Arthralgia Syndrome

Practical Suggestions

1. Alert patients to this side effect

2. Reassure patients that this is not associated with destructive arthritis and that most cases are mild and abate over time

3. Encourage weight reduction and regular exercise

4. For more severely affected patients, suggest AI withdrawal to gauge relationship to treatment

5. Options: tamoxifen, other AIs, none

Fracture Rates in Adjuvant AI Trials

Aromatase

Inhibitor

Tamoxifen /

Placebo% Increase Reference

ATAC 340 (11%) 237 (7.7%) 43% Howell et al 2005

BIG 1-98 228 (5.8%) 162 (4.1%) 41% Thurlimann et al 2005

IES 162 (7.0%) 111 (4.9%) 45% Coombes et al 2006

ABCSG/

ARNO34 (2.0%) 16 (1.0%) 113% Jakesz et al 2005

MA.17 137 (5.3%) 119 (4.6%) 15% Perez et al 2006

Influence of Different AI Strategies on BMD

Coleman et al Lancet Oncology 2007

0 1 2 3 4 5 6 7 Years

43210-1-2-3-4-5-6-7-8

x

x

% changeIn BMD from baseline

x

x xAnastrazole (ATAC)

Tamoxifen (ATAC) Tamoxifen (IES)

Exemestane (IES) x xLetrozole (MA-17)

Placebo (MA-17)

x

ATAC IES MA-17

x

ATAC: Annual Bone Fracture Rates

ATAC Trialists, Lancet Oncology 2008;9:45

Bone Health Guidelines

• Consider bone health when choosing adjuvant endocrine therapies

• Check BMD at baseline when initiating AI therapy

• Recheck BMD at 1-2 years

• Initiate therapy for osteporosis / osteopenia according to standard guidelines derived from normal postmenopausal patient experience

• Interventions that “work” in general population with osteopenia / osteoporosis also work in breast cancer survivors

Case 2

• Premenopausal Women, 35 years old– T = 1.5 cm

– ER+

– PR+

– HER2 negative

– Grade 2

– LVI+

• Which patients with ER+ tumors should receive adjuvant chemotherapy?

Q: Which patients with ER+ breast cancer should receive chemotherapy?

A: Those patients… • where tumor is not eradicated by surgery, or radiation, or

adjuvant endocrine therapy, and

• where tumor is sensitive to chemotherapy, and

• where the patient is not likely to suffer gravely from other medical conditions before breast cancer recurrence, and

• where the realistic benefits outweigh the risks of chemotherapy.

Case 2 Optimizing Therapy in Premenopausal Women

The Dilemma Just exactly who are those patients?

Current Recommendations for Chemotherapy for ER+ Breast Cancer

NIH Consensus Conference 2000• LN+

• LN – if T > 1 cm

NCCN 2006• LN+

• LN – if T > 1cm

• Consider for LN – if 0.6 to 1.0 cm

St. Gallen 2005 (endocrine responsive)• LN + (>4 LN if HER2 negative, any if HER2+)

• Consider for LN – if: T > 2 cm, or grade 2-3, or LVI+, or HER2+, or age < 35 years

Why Not Just GiveChemotherapy to Everyone?

• Early Breast Cancer Trialists’ Group overview suggests benefit for chemotherapy irrespective of ER status, tamoxifen treatment, nodal status, or age

• Landmark trials show benefit of chemotherapy for women with breast cancer compared to tamoxifen alone– Postmenopausal node positive (SWOG 8814)

– Pre/postmenopausal node negative (NSABP B-20)

• 2nd / 3rd generation trials of optimal chemotherapy show gains in outcome for ER+ and ER- tumors

Why Not Just GiveChemotherapy to Everyone?

1. Chemotherapy-induced amenorrhea

2. Treatment regimens not contemporary

e.g. chemotherapy without endocrine therapy

3. ER status

positive vs negative vs low/poor vs missing

4. Patient age

5. Absolute vs. relative benefit

The studies have major limitations

that affect their application to patients in 2000

Why Not Just GiveChemotherapy to Everyone?

The studies have major limitations that affect

their application to patients in 2006

1. Evolving taxonomy of breast cancer

Biological subsets of breast cancer defined by pathological markers or gene expression arrays

2. Quantitative levels of ER / PR

3. Introduction of HEr testing and anti-HER2 therapy

4. Neoadjuvant chemotherapy studies demonstrate lower chance of pCR in ER+ in patients

5. Lack of molecular predictors for chemotherapy benefit

All Breast Cancer

ER+65-75%

HER2+15-20%

Basaloid15%

Clinical Breast Cancer Subsets

Adjuvant Treatment for a 2 x 2 Marker Model of Breast Cancer

ER + ER --

HER2+Trastuzumab Chemo

Endocrine

Trastuzumab Chemo

HER2 - Endocrine

± ChemoChemo

Candidate Gene SelectionFrom ~40,000 genes

*Sources include: 1) Sotiriou et al., Breast Cancer Res Treat 4:R3, 20022) Scherf et al., Nat Genetics 24:236-44, 20003) Lamendola et al., Cancer Res 63:2200-5, 20034) Chang et al., Lancet 362:362-9, 20035) Staunton et al., Proc Natl Acad Sci U S A 98:10787-92, 2001

Cancer Literature

Microarray

Data*

Gen

omic

Dat

abas

e

s

384 cancer-related genes*

Molecu

lar

Biology

PROLIFERATIONKi-67

STK15Survivin

Cyclin B1MYBL2

ESTROGENERPR

Bcl2SCUBE2

INVASIONStromolysin 3Cathepsin L2

HER2GRB7HER2

BAG1

GSTM1

REFERENCEBeta-actin

GAPDHRPLPO

GUSTFRC

CD68

16 Cancer and 5 Reference Genes

Best RT-PCR performance and most robust predictions

Single Gene Analysis in ER+, Tam+ Patients from Multiple Studies

The Recurrence Score (RS)• The recurrence score unscaled is defined as:

RSu= 0.47 x HER2 Group Threshold Score– 0.34 x ER Group Score

+ 1.04 x Proliferation Group Threshold Score

+ 0.10 x Invasion Group Score

+ 0.05 x CD68 – 0.08 x GSTM1 – 0.07 x BAG1

• Then the RSu is rescaled to be between 0 and 100: RS=(Rsu-6.7) x 20 and

If RS<0, then RS=0;

If RS>100, then RS=100.

• Classification into three groups:Low risk group: if RS<18;

Intermediate risk group: if 18≤RS<31;

High risk group: if RS≥31.

• Objective– Validate Recurrence Score as predictor of distant recurrence in N-, ER+,

Tamoxifen-treated patients

• Design– Pre-specified 21 gene assay, algorithm, endpoints, analysis plan– Blinded laboratory analysis of three 10 micron tumor block sections

Genomic Health-NSABP B-14 Prospective Clinical Validation Study

Randomized

Registered

Placebo--Not Eligible

Tamoxifen--Eligible

Tamoxifen--Eligible

B-14

0 2 4 6 8 10 12 14 16

Years

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

DR

FS

B14-ResultsDRFS - All 668 Patients

10 year DRFS = 85%

Oncotype DX™ Validation Study B-14

Rates of Distant Recurrence at 10 Years by RS Risk Category

Paik et al. NEJM 2004;351:2817

All Pts

Low Risk (RS <18)

Int Risk (RS 18-30)

High Risk (RS ≥31)

Oncotype DX™ NSABP B-14: RS Subgroups by Patient Age

Age >60

Age 50–60

Age 40–50

Age <40

40% 60% 80% 100%% Distant Recurrence-free at 10 Years

All patients (N = 668)

59161033

135662940

301175

6264

173814844

All PtsLow Risk (RS<18)Int Risk (RS 18-31)High Risk (RS≥31)

Oncotype DX™ NSABP B-14: RS Subgroups by Tumor Grade

20% 40% 60% 80% 100%% Distant Recurrence-free at 10 Years

All Patients

224166

4117

296139

8077

148332887

N = 668

Well

Moderate

Poor

Recurrence Score and HER2 Status

HER2 Status

RS Result FISH + FISH -

Low 0 334

Intermediate 5 142

High 50 129

0%

5%

10%

15%

20%

25%

30%

35%

40%

0 5 10 15 20 25 30 35 40 45 50

Recurrence Score

Dis

tan

t R

ecu

rren

ce a

t 10

Yea

rs

Low Risk Group High Risk Group Intermediate Risk Group

Recurrence Score as a Continuous Predictor

95% CI

0%

5%

10%

15%

20%

25%

30%

35%

40%

0 5 10 15 20 25 30 35 40 45 50

Recurrence Score

Dis

tan

t R

ecu

rren

ce a

t 10

Yea

rs

Low Risk Group High Risk Group Intermediate Risk Group

Recurrence Score as a Continuous Predictor

My RS is 30, What is the chance of recurrence within 10 yrs?

My RS is 30, What is the chance of recurrence within 10 yrs?

95% CI

Chemotherapy Response and Oncotype DX NSABP Study B-20

Design:

Randomized

Tam + MF

Tam + CMF

Tam

Objective:

Determine the magnitude of the chemotherapy benefit as a function of 21 gene Recurrence Score assay

Paik, S. et al. J Clin Oncol; 24:3726-3734 2006

NSABP B-20Outcome by Recurrence Score

Overall

Int risk 18-30

Low risk < 18

High risk > 30

Paik, S. et al. J Clin Oncol; 24:3726-3734 2006

Linear fit of Distant Recurrence as a Continuous Function of RS for TAM and TAM + Chemo

0.00

0.25

0.50

0.75

1.00

Dis

ease

-fre

e su

rviv

al

0 2 4 6 8 10

Years since registration

Tamoxifen (n=55, 15 events)CAF-T (n=91, 26 events)

Stratified log-rank p = 0.97 at 10 years

Low risk (RS < 18)

Disease-Free Survival by Treatment

SWOG 8814Postmeno, ER+, LN+Tam ± CAF Albain, et al. SABCS 2007

0.0

00

.25

0.5

00

.75

1.0

0

Dis

ease

-fre

e su

rviv

al

0 2 4 6 8 10

Years since registration

Tamoxifen (n=47, 26 events)CAF-T (n=71, 28 events)

Stratified log-rank p = 0.033 at 10 years

High risk (RS ≥31)

Disease-Free Survival by Treatment

0.0

00

.25

0.5

00

.75

1.0

0

Dis

ease

-fre

e su

rviv

al

0 2 4 6 8 10

Years since registration

Tamoxifen (n=46, 22 events)CAF-T (n=57, 20 events)

Stratified log-rank p = 0.48 at 10 years

Intermediate risk (RS 18-30)

Disease-Free Survival by Treatment

Sparano, J. A. et al. J Clin Oncol; 26:721-728 2008

TAILORx

• Objective– Validate Recurrence Score as predictor of distant recurrence in

N-, ER+, Tamoxifen-treated patients

• Design

Genomic Health-NSABP B-14 Prospective Clinical Validation Study

•Pre-specified 21 gene assay, algorithm, endpoints, analysis plan•Blinded laboratory analysis of three 10 micron tumor block sections

B-14Tamoxifen--Eligible

Randomized

Registered

Placebo--Not Eligible

Tamoxifen--Eligible

Low Risk (RS<18)N

171142

0 2 4 6 8 14 16

Years

0.0

0.2

0.4

0.6

0.8

1.0

DR

FS

PlaceboTamoxifen

1210

Int Risk (RS 18-30)N8569

0 2 4 6 8 14 16

Years

0.0

0.2

0.4

0.6

0.8

1.0

DR

FS

PlaceboTamoxifen

1210

High Risk (RS≥31)N9979

0 2 4 6 8 14 16

Years

0.0

0.2

0.4

0.6

0.8

1.0

DR

FS

PlaceboTamoxifen

1210

Benefit from Tamoxifen in the NSABP B14by Oncotype DX Recurrence Score

How Many Genomic Assays Do We Need?

Fan C et al. N Engl J Med 2006;355:560-569

Multi-gene Arrays and Prediction of DFS inCohort of ER+ Breast Cancer

ASCO Tumor Marker PanelMultiparameter Gene Expression Analysis for Breast Cancer

• Oncotype DX™ can be used to determine prognosis in newly diagnosed patients with node-negative, estrogen-receptor positive breast cancer who will receive tamoxifen. Indications:

– To predict risk of recurrence in patients considering treatment with tamoxifen

– To identify patients who are predicted to obtain the most therapeutic benefit from adjuvant tamoxifen and may not require adjuvant chemotherapy

– Patients with high recurrence scores appear to achieve relatively more benefit from adjuvant chemotherapy (specifically CMF) than from tamoxifen

• Conclusions may not be generalizable to hormonal therapies other than tamoxifen, or to other chemotherapy regimens.

• Several other multi-parameter assays have been reported and a few are commercially available, including Mammaprint and the Rotterdam Signature. However, the Committee felt that the precise clinical utility and appropriate application for these other assays were insufficiently defined to recommend their use.

ASCO 2007; available at http://jco.ascopubs.org/cgi/content/full/25/33/5287

Case 2 Summary Optimizing Therapy in Premenopausal Women

• Traditional criteria for recommending chemotherapy in ER+ breast cancer relate to risk of recurrence, not chemotherapy sensitivity

– T, N stage

– Age

• Chemotherapy benefits vary from tumor to tumor, and thus patient to patient

• Genomic assays can inform the likelihood of sensitivity to chemotherapy

Concluding Remarks

Current Considerations in the Management of Patients with Hormonally Sensitive

Early-stage Breast Cancer

Clinical UpdatesHormonally Sensitive, Early-Stage Breast Cancer