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Kyoung Eun, Lee MD. Ph.D
Hematology-Oncology
Ewha Womans University Hospital, Seoul, KOREA
Determining the optimal adjuvant chemotherapy for low or intermediate risk of breast cancer
- Who should receive adjuvant chemotherapy?
Disclosure
• There are no conflicts of interest and nothing to disclose
Milestones in the adjuvant chemotherapy
• Alkylating agents given after surgery decrease recurrence rate
• Adjuvant polychemotherapy “CMF” substantially reduces risk of recurrence and improves survival
• Anthracyclines and taxanes integrated into adjuvant chemotherapy regimens produce additional survival gains
• NIH consensus panel recommend chemotherapy to the majority of women with localized BC regardless of LN, menopause, HR status
Is adjuvant chemotherapy fit for all patients?
Not all BC with similar clinical features have the same biologic behavior
• Possibility of “overtreating” subsets who have truly localized disease CURED by surgery
• Possibility of “undertreating” subsets whose cancer is NOT SENSITIVE to the delivered drug
Walgren et al. J Clin Oncol 23:7342-7349
Outlines
• How to identify the risk in early stage breast cancer (ESBC) patient?
• Risk of recurrence for node(-) breast cancer patients
• Multi-gene assays
• How to choose the optimal chemotherapy regimen? • To use or not to use the Anthracyclines?
• To optimize the adjuvant therapy with Taxanes?
Outlines
• How to identify the risk in ESBC patients ? • Risk of recurrence for node(-) breast cancer patients
• Multi-gene assays
• How to choose the optimal chemotherapy regimen? • To use or not to use the Anthracyclines?
• To optimize the adjuvant therapy with Taxanes?
Biomarkers in ESBC?
• For women with early-stage breast cancer, with known ER, PR, HER2 status, are there additional biomarkers?
• Q: Who can be spared therapy? A: Prognostic markers needed
• Q: Which therapy will work best ? A: Predictive markers needed
Gyorffy et a. Breast Cancer Research (2015) 17:11
Who is low or intermediate risk group?
Clinicopathologic Features
Molecular Subtype
Genomic Assays
• Age
• TNM
• ER/PgR/HER2
• Grade
• Ki67
• uPA/PAI-1
• Luminal A
• Luminal B
• HER2 +
• Basal-like
• Claudin-low
• Oncotype DX®
• Mammaprint®
• PAM50®
• EndoPredict®
• Mammastrat
• BCI
• IHC4
Clinical Scoring System
• Nottingham Prognostic Index(NPI)
• Size, node, grade
• The PREDICT score • Age, mode of
detection, size, grade, node, HR, HER2, Ki-67
• Adjuvant! Online
Benefit from Chemotherapy: Adjuvant! Online
• Estimates: • Risk of cancer-related mortality or relapse without therapy
• Risk reduction with therapy
• Risk of side effects from
therapy
• Limitations • Prognostic factors are not all
inclusive
• HER2 status not included
• Small tumors not well characterized
Available at: http://www.adjuvantonline.com
Disease factor Patient factor LN
HER2
T stage
Grade
ER/PR
LVI
Age
Menopausal status
Medical comorbidities
Which characteristics are considered when making a decision regarding adjuvant systemic therapies?
LN(-) & T>5mm
1. Grade 3
2. Triple negative
3. LVI positive
4. OncotypeDX RS (estimated distant
relapse risk at 10 years ≥ 15%)
5.HER2+
Candidate for chemotherapy
May not benefit from chemotherapy
LN(-) & T ≤5mm
& No high risk feature
With high risk feature
What risk stratification tools may be used in determining the utility of certain systemic therapies in patients with ESBC?
• Oncotype DX score
• For HR+, N0 or N1mic or ITC, and HER2(-)
• Adjuvant! Online • www.adjuvantonline.com
Gene Expression Profiles
• To gain additional prognostic and/or predictive information
• To predict the benefit of adjuvant chemotherapy
• IB evidence level from retrospective analyses of data from prospective trials
21-gene recurrence score Oncotype DXTM
• HR(+), HER2(-), Node(-) breast cancer
• RT-PCR assay, 21 genes, paraffin-embedded tissue
• In NSABP B-14 • Predict the risk of distant relapse after 18 years for patients with Node(-) BC
• In NSABP B-20 • RS correlates with benefit from chemotherapy in ER(+) tumors
• In TransATAC • For Node(+) & (-) group, independent predictor of distance recurrence
• Ongoing prospective trial • Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who
Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)
Paik et al. N Engl J Med 2004;351:2817-26
Validated as quantifying the likelihood of distant recurrence in tamoxifen-treated, node(-), ER(+) breast cancer
Category RS 10y risk (%)
Low RS<18 6.8
Intermediate 18≤ RS <31 14.3
High RS ≥ 31 30.5
21-gene recurrence score Oncotype DXTM
Paik et al. N Engl J Med 2004;351:2817-26
Largest Benefits of Tamoxifen Observed in Low and Intermediate Risk Groups (NSABP B-14)
Largest Benefits of Chemotherapy Observed in High Risk Groups (NSABP B-20)
Trial Assigning IndividuaLized Options for Treatment The TAILORx : 21-gene prospective trial
OncotypeDX
RS ≤ 10
Hormone Rx
RS > 25
Chemotherapy
+ Hormone Rx
RS 11-25 : Randomize
Hormone Rx vs.
Chemotherapy + Hormone Rx
Node-negative, ER-positive Breast Cancer
15.9% 67.3% 16.9%
2006-2010 N=10,253
OncotypeDX
RS ≤ 10
Hormone Rx
RS > 25
Chemotherapy
+ Hormone Rx
RS 11-25 : Randomize
Hormone Rx vs.
Chemotherapy + Hormone Rx
Node-negative, ER-positive Breast Cancer
Trial Assigning IndividuaLized Options for Treatment The TAILORx : 21-gene prospective trial
OncotypeDX
RS ≤ 10
Hormone Rx
RS > 25
Chemotherapy
+ Hormone Rx
RS 11-25 : Randomize
Hormone Rx vs.
Chemotherapy + Hormone Rx
Node-negative, ER-positive Breast Cancer
Trial Assigning IndividuaLized Options for Treatment The TAILORx : 21-gene prospective trial
OncotypeDX
RS ≤ 10
Hormone Rx
RS > 25
Chemotherapy
+ Hormone Rx
RS 11-25 : Randomize
Hormone Rx vs.
Chemotherapy + Hormone Rx
Node-negative, ER-positive Breast Cancer
Invasive DFS 99.3% Freedom from recurrence at 5y 98.7% OS 98.0%
Sparano et al. N Engl J Med 2015;373:2005-14
Trial Assigning IndividuaLized Options for Treatment The TAILORx : 21-gene prospective trial
Dowsett et al. J Clin Oncol 28:1829-1834
21-gene recurrence score “How about in node-positive patients?”
• For prediction of risk
• Post-menopausal
• TransATAC
In Node + patients, withholding the chemotherapy is NOT recommended now
Node negative
RxPONDER trial
Node positive
70-gene signature Mammaprint®
• FDA-approved for prognostication of patients with stage I, II node(-) BC with tumors <5cm
• Requires fresh or frozen samples (tumor cell content > 30%)
• Strong prognostic power
• Predicts the benefits of adding chemotherapy to endocrine therapy in the poor prognosis group, N=541
Knauer M et al. Breast Cancer Res Treat (2010) 120:655–661
Low risk group High risk group
70-gene signature Good vs. poor outcome model
van‘t Veer et al. Nature. 2002; van de Vijver et al. NEJM. 2002
MFS OS
PAM50 Risk of Recurrence Score PAM50-ROR
• 50-gene predictor developed using microarray and qRT-PCR from 189 untreated patients
• Evaluated the utility of the “intrinsic” subtypes (luminal A, luminal B, HER2+, basal-like and normal-like) to predict risk of relapse in 2 cohorts
• The intrinsic subtypes showed prognostic significance in multivariate analysis
• Intrinsic subtype model also predict benefit from neoadjuvant chemotherapy
Martin Filipits et al. Clin Cancer Res 2014;20:1298-1305
12-gene risk score EndoPredict(EP)
• HR(+), HER2(-) patients with endocrine therapy
• RT-PCR, FFPE tissue (98.6% successful)
• Validated in 2 large randomized phase III trials to predict early and late distant recurrence
• ABCSG-6 (N=378) • ABCSG-8 (N=1,324)
• More powerful if combined with clinical factors (size, LN) • EPclin
• In a LN(+) chemotherapy (FEC vs FEC-P) cohort • Validated as prognostic; however not predictive for chemotherapy
Filipits et al. Clin Cancer Res; 17(18); 6012–20
12-gene risk score EndoPredict(EP)
Filipits et al. Clin Cancer Res; 17(18); 6012–20
Multigene assays MammaPrint OncotypeDX Prosigna
Material Fresh frozen, FFPE
FFPE FFPE
Platform DNA microarray qRT-PCR nCounter
No. of genes 70 21 50+5
Target patients Stage I-II ER(+) stage I-II Stage I-III
Regulatory FDA NCCN/ASCO FDA
Categorize Good/poor prognosis
Recurrence Score: 3 risk groups (Low/Int/High)
Prosigna Score: 3 risk
groups(Low/Int/High)
Cost $4,200 $4,175 $2,080
Ongoing Trials
• OncotypeDx • TAILORx : prospective ER+, node negative disease to shrink the “intermediate”
category to RS 11-25
• RxPONDER : prospective ER+, node positive disease with RS <25, randomized to endocrine alone vs. endocrine + chemotherapy
• Mammaprint • MINDACT : prospective N0-1 disease to compare clinical vs. genomic risk
prediction for adjuvant chemotherapy decision
• I-SPY2 : neoadjuvant for locally advanced BC(tumor >3cm)
• Prosigna • RxPONDER secondary endpoint : head to head comparison of OncotypeDX and
PAM50
Gene Expression Profile (GEP) Testing and Chemotherapy Administration
Hassett MJ, et al. J Clin Oncol. 30:2218-2226.
Prospective registry data of 7,375 patients outlining the routine care provided to women diagnosed from 2006 to 2008 with HR-positive BC at 17 comprehensive and community-based cancer centers
Personalized treatment of ESBC
Present
• Most of our medical practice is based on standards of care
• Evidence based medicine is best for the average populations, NOT for specific individuals
• Some currently available genomic platforms
• But which platform is better?
Future • Next generation genomic sequencing
Outlines
• How to identify the risk in early stage breast cancer patients ? • Multi-gene assays
• Personalized treatment
• Risk of recurrence and chemotherapy benefit for node-negative breast cancer patients
• How to choose the optimal chemotherapy regimen? • To use or not to use the Anthracyclines?
• To optimize the adjuvant therapy with Taxanes?
Anthracyclines
• Introduced in the 1960s and has been the backbone for the last 40 years
• Problems • Cardiac toxicity & secondary hematologic malignancy (AML/MDS)
• But in low/intermediate risk of recurrence patients • Reasonable to substitute for well-established non-anthracycline
regimens
Introduction of anthracyclines AC(x4) vs. CMF(x6) : NSABP B-15
• 1984-1988
• N=2,194, Node (+)
• AC(x4) vs. CMF(x6) vs. AC(x4)+ivCMF(X3)
• AC(x4) was equal to CMF(x6) in patients with LN(+) BC
Fisher et al. J Clin Oncol 1990;8:1483-1496
Introduction of anthracyclines CEF120(x6) vs. CMF(x6) : MA.5
• 1989-1993
• N=710, Node (+)
• CEF120(x6) • Cyclophosphamide 75mg/m2
D1-14
• Epirubicin 60mg/m2 D1,8
• 5-FU 500mg/m2 D1,8
• CMF(x6) • Cyclophosphamide 100
mg/m2 D1-14
• MTX 40 mg/m2 D1,8
• 5-FU 600 mg/m2
Levine et al. J Clin Oncol 2005;23:5166-5170
10y RFS 52% vs. 45% HR 1.31, p=0.007
10y OS 62% vs. 58% HR1.18, P=0.085
CEF120(x6) was superior to classic CMF(x6) in patients with LN(+) BC
Introduction of anthracyclines CAF(x6) vs. CMF(x6) : SWOG/INT0102
• 1989-1993
• N=2,690
• Node(-), high S-phase
• CAF120(x6) ±tam • Cyclophosphamide 100 mg/m2
D1-14
• Doxorubicin 30mg/m2 D1,8
• 5-FU 500mg/m2 D1,8
• CMF(x6) ±tam • Cyclophosphamide 100 mg/m2
D1-14
• MTX 40 mg/m2 D1,8
• 5-FU 600 mg/m2
Hutchins et al. J Clin Oncol 2005;23:8313-8321
No DFS improvement with CAF compared with CMF CAF had slight OS benefit compared with CMF
10y eDFS 77% vs. 75% HR 1.09
10y eOS 85% vs. 82% HR1.19, P=0.03 (if one-sided test)
Introduction of anthracyclines ivCAF(x6) vs. ivCMF(x6) : GEICAM8701
• N=985, T1-3, N0-2
• Node (-, 42%)
• FAC(x6) • 5-FU 500mg/m2 D1 (iv)
• Doxorubicin 50mg/m2 D1 (iv)
• Cyclophosphamide 500 mg/m2 D1(iv)
• CMF(x6) • Cyclophosphamide 600
mg/m2 D1 (iv)
• MTX 60 mg/m2 D1 (iv)
• 5-FU 600 mg/m2 D1 (iv)
Martin et al. Annals of Oncology 2003;14: 833–842
5y DFS 75% vs. 67% P=0.046
5y OS, NR P=0.0378
FAC(x6) was superior to CMF(x6), especially in patients with LN(-) BC
FAC favor
Which adjuvant chemotherapy?
CMF#6
Observation
Benefit
AC#4
CEF120#6
MA.5 N(+)
NSABP B-15 N(+)
CAF120#6
SWOG/INT0102 N(-) high 100%
FAC#6
GEICAM8701 N(-) 42%
Introduction of anthracyclines CMF vs. Anthracyclines: Meta-analysis
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Lancet 2012; 379: 432–44
Introduction of anthracyclines AC(x4) vs. AC(x6) : CALGB 40101
• 2002-2008
• Node(-) :94%
HER2(-), 84%
• AC(x4) vs. AC(x6) vs. T(X4) vs. T(x6)
• 4 cycles vs. 6 cycles • 4y RFS 90.9% vs. 91.8%
• HR for RFS 1.03(95% CI, 0.84 to 1.28; P =0..77)
Shulman et al. J Clin Oncol 2012;30:4071-4076
EBC, N0~3
N=3,171
AC4 (N=1,142)
AC6 (N=789)
P4 (N=1,151)
P6 (N=789)
RFS OS
Which adjuvant chemotherapy?
CMF#6
Observation
AC#4
Benefit
CEF120#6
MA.5 N(+)
NSABP B-15 N(+)
CAF120#6
SWOG/INT0102 N(-) high 100%
FAC#6
GEICAM8701 N(-) 42%
AC#6
CALGB 40101 N(-) 94%
Introduction of anthracyclines Between anthracyclins : Meta-analysis
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Lancet 2012; 379: 432–44
Recurrence
Breast cancer mortality
Cumulative dosage of doxorubicin 360mg/m2 240mg/m2
53% Node + 61% Node +
Adjuvant taxanes?
Adjuvant taxanes in Node(+) disease Meta-analysis
DFS HR 0.83
OS HR 0.85
De Laurentiis et al. J Clin Oncol 2008;26:44-53
How about in Node(-) disease?
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Lancet 2012; 379: 432–44
Docetaxel adjuvant chemotherapy Meta-analysis
Jacquin et al. Breast Cancer Res Treat (2012) 134:903–913
DFS
Introduction of Taxanes AC(x4) vs. TC(x4) : USO 9735
• 1997-1999
• N=1,016, stage I-III
• Tumor size ≥1.0 cm and smaller than 7.0 cm
• About 50% node(-)
• AC(x4) vs. TC(x4)
Primary Objective : DFS
Secondary Objective :
OS, Safety
Jones et al. J Clin Oncol 2006;24:5381-5387, Jones et al. J Clin Oncol 2009;27:1177-1183.
Stage I, II, or III
71% ER
48% LN negative
R
Tamoxifen was given to all ER+ patients
Median follow up: 5.5 ys
4 x TC q3w
Docetaxel (75 mg/m2)
Cyclophosphamide (600 mg/m2)
4 x AC q3w
Doxorubicin (60 mg/m2)
Cyclophosphamide (600 mg/m2)
A → T
TC (n=506) AC (n=510)
Median Age, ys (range) 52 (27-77) 51(27-77)
Stage (%) I II III Unknown
104 (20) 373 (74) 27 (5) 2 (1)
112 (22) 364 (71) 34 (7) 0 (0)
HR status (%) ER /PR(+/+,-/+,+/-) ER-/PR- Unknown
367 (72) 136 (27)
2 (1)
352 (69) 157 (31) 1 (<1)
Positive nodes (%) 0 1-3 ≥ 4
239 (47) 209 (41) 58 (12)
248 (49) 212 (42) 50 (9)
Introduction of Taxanes AC(x4) vs. TC(x4) : USO 9735
A → T
DFS OS
6% 5%
Introduction of Taxanes AC(x4) vs. TC(x4) : USO 9735
Jones et al. J Clin Oncol 2006;24:5381-5387, Jones et al. J Clin Oncol 2009;27:1177-1183.
A → T
All grade
0%
20%
40%
60%
80%
100%TC (docetaxel /…
G3,4
0%
20%
40%
60%
80%
100%
▼ 3 fatal events (CHF, MDS, MF) were found in AC arm
Introduction of taxanes AC vs. Paclitaxel : CALGB 40101
• 2002-2008
• Node(-) :94%
HER2(-), 84%
Shulman et al. J Clin Oncol 2012;30:4071-4076, Shulman et al. J Clin Oncol 2014;32:2311-2317
EBC, N0~3
N=3,171
AC4 (N=1,142)
AC6 (N=789)
P4 (N=1,151)
P6 (N=789)
Taxane without A might be an option in low-risk EBC
AC4: superior to T4 or T6
• But small : Δ3% and Δ1%
AC: Higher hematologic toxicity and..
Cause of Death AC
(n = 1,931)
T
(n = 1,940)
Breast cancer 60 87
TRM 9 0
AML/MDS 7 0
Cardiotoxicity 2 0
Other 47 63
Total 116 150
A → T
Which adjuvant chemotherapy?
CMF#6
Observation
AC#4
Benefit
CEF120#6
MA.5 N(+)
NSABP B-15 N(+)
CAF120#6
SWOG/INT0102 N(-) high 100%
FAC#6
GEICAM8701 N(-) 42%
AC#6
CALGB 40101 N(-) 94%
TC#4
USO9735 N(-) 48%
T#4/6
CALGB 40101 N(-) 94%
Introduction of Taxanes FAC(x6) vs. TAC(x6): GEICAM 9805
• 1999-2003
• N=1,060
• Node(-), high risk • Tumor size >2 cm,
• ER/PR -/-,
• Hstologic grade 2 or 3
• Age <35 ys
• Primary end point • DFS
• Key secondary end points
• OS
Martin et al. N Engl J Med 2010;363:2200-10
EBC, R0 resected
N0, high risk
TAC#6
+ Prophyl Antibiotics+G-CSF*
FAC#6
1:1
*amended d/t high incidence of Neutropenic Fever
A + T
• DFS :
• ER+/HER2+: 0.73 (95% CI, 0.12–4.36); P=0.73 ER-/HER2+: 0.73 (95% CI, 0.12–4.35); P=0.72
• ER+/HER2-: 0.48 (95% CI, 0.25–0.90); P=0.02 ER-/HER2-: 0.59 (95% CI, 0.32–1.07); P=0.08
• Higher toxicity related with TAC (G3,4 neutropenia 50.8% vs. 39.5%, p<0.001 & G3,4 neuropathy 8.6% vs. 1.7%, p<0.001)
DFS: HR=0.68 (0.49-0.93); p=0.01 OS: HR=0.76 (0.45-1.26); p=0.29
95.2%
93.5% 87.8%
81.8%
Δ6% Δ2%
Introduction of Taxanes FAC(x6) vs. TAC(x6): GEICAM 9805
Martin et al. N Engl J Med 2010;363:2200-10
A + T
EBC, R0 resected T1-3, N0, high risk*
(N=1,925)
FAC#4wP#8
FAC#6
1:1
Martin et al. 2013 J Clin Oncol 31:2593-2599
Introduction of Taxanes FAC(x6) vs. FAC(x4)-wP: GEICAM/2003-02
• High risk, Node(-)
• High risk • Tumor size >2 cm
• ER/PR -/-
• HG 2 or 3
• Age <35 ys
• FAC vs. FAC followed by weekly paclitaxel
• Primary end point :DFS
• Secondary end point :OS
A + T
DFS: HR=0.73 (0.54-0.99); p=0.04 OS: HR=0.76 (0.45-1.26); p=0.29
97.4%
95.8% 93%
90.3%
Δ2.7% Δ1.6%
Martin et al. 2013 J Clin Oncol 31:2593-2599
Introduction of Taxanes FAC(x6) vs. FAC(x4)-wP: GEICAM/2003-02
Median F/U 63.3months Similar efficacy across characteristics More neuropathy with FAC-wP (5.5 v.0%)
A + T
Which adjuvant chemotherapy?
Benefit
CMF#6
Observation
AC#4
CEF120#6
MA.5 N(+)
NSABP B-15 N(+)
CAF120#6
SWOG/INT0102 N(-) high 100%
FAC#6
GEICAM8701 N(-) 42%
AC#6
CALGB 40101 N(-) 94%
TC#4
USO9735 N(-) 48%
T#4/6
CALGB 40101 N(-) 94%
TAC#6
GEICAM 9805 N(-) high 100%
FAC#4-wP
GEICAM/2003-02 N(-) high 100%
Introduction of Taxanes AC(x4) vs. AT(x4): ECOG 2197
• 1997-1999
• N=2,882, N1-3 or
Node(-) & >1cm
• AC(x4) • Doxorubicin 60mg/m2 D1
• Cyclophosphamide 600mg/m2, D1
• AT(x4) • Doxorubicin 60mg/m2 D1
• Docetaxel 60mg/m2 D1
Goldstein et al. J Clin Oncol 2008;26:4092-4099
(No G-CSF primary prophylaxis) Higher G3 neutropenia (54% vs. 38%; p<0.05) Higher neutropenia associated with fever or infection (26% v 10%; P <0 .05)
No difference in DFS
A + T
Which adjuvant chemotherapy?
AT#4
ECOG 2197 N(-) 66%
CMF#6
Observation
AC#4
Benefit
CEF120#6
MA.5 N(+)
NSABP B-15 N(+)
CAF120#6
SWOG/INT0102 N(-) high 100%
FAC#6
GEICAM8701 N(-) 42%
AC#6
CALGB 40101 N(-) 94%
TC#4
USO9735 N(-) 48%
T#4/6
CALGB 40101 N(-) 94%
TAC#6
GEICAM 9805 N(-) high 100%
FAC#4-wP
GEICAM/2003-02 N(-) high 100%
Introduction of Taxanes What taxanes? : E1199
• Node(+) or High risk Node(-):12% (T2,3 N0)
• 12 years follow up was reported
• P1 was associated with improved survival
P3 P1 D3 D1
Sparano et al. N Engl J Med 2008;358:1663-71
A + T
5.3 y follow up 12.1 y follow up
No difference of DFS, OS Between P1 and D3
No benefit of OS in HR(+), HER2(-) pts
Sparano et al. N Engl J Med 2008;358:1663-71
Which adjuvant chemotherapy?
Benefit
CMF#6
Observation
AC#4
CEF120#6
MA.5 N(+)
NSABP B-15 N(+)
CAF120#6
SWOG/INT0102 N(-) high 100%
FAC#6
GEICAM8701 N(-) 42%
AC#6
CALGB 40101 N(-) 94%
TC#4
USO9735 N(-) 48%
T#4/6
CALGB 40101 N(-) 94%
TAC#6
GEICAM 9805 N(-) high 100%
AT#4
ECOG 2197 N(-) 66%
FAC#4-wP
GEICAM/2003-02 N(-) high 100%
AC#4-wP
E1199
AC#4-3wD
E1199 AC#4-3wP
E1199 N(-) 12%
Adjuvant therapy regimens NCCN guideline: HER2(-)
Preferred regimens • dd AC-paclitaxel q2w
• dd AC-paclitaxel q1w
• TC
Others • Dose-dense AC
• AC q 3w
• CMF
• AC-3wD
• AC-wP
• EC
• FEC/CEF-wP
• FAC-wP
• TAC
Adjuvant therapy regimens NCCN guideline: HER2(-) for N(-) ESBC ?
Preferred regimens • dd AC-paclitaxel q2w
• dd AC-paclitaxel q1w
• TC
Others • Dose-dense AC
• AC q 3w
• CMF
• AC-3wD
• AC-wP
• EC
• FEC/CEF-wP
• FAC-wP
• TAC
Take Home Message
• How to identify the risk in ESBC ?
• How to choose the optimal chemotherapy regimen?
Use tumor and patient risk factors LN, HER2, T-stage, Grade, HR, LVI, Age, Menopause, Co-morbidities
Use multigene assay Low risk patients are in low risk!
Larger dose A showed benefit, but lager toxicities Additional T to A showed benefit, but larger toxicities T instead of A might be a option in this low risk group
Thank you for your attention