harold j. burstein, md, phd dana-farber cancer institute harvard medical school boston, ma
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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
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