Adjuvan Chemotherapy in Breast Cancer

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Harvey Richards
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1 Adjuvan Chemotherapy in Breast Cancer Prof Dr Adnan Aydıner Istanbul University, Oncology Institute aa1

2 Slide 1 aa1 adnan aydiner;

3 15-Year Reductions in Recurrence and Disease-Specific Mortality Treatment Comparison EBCTCG. Lancet. 2005;365: Breast Cancer Log Rank Breast Cancer Recurrence, 2P Mortality, % Please % note when formatting: Log Rank 2P - Table Multiagent text minimum size is 14pt - Use chemotherapy Blue (R43 G133 vs B184) for table headers. If a table has a 2-row header (see below) use both none blue and gray. If there are bullets within a cell, they should be square, and in Black (see below table). Entry age < 50 yrs 12.3 < < Entry age yrs 4.1 < < Tamoxifen 5 yrs vs none, ER-positive women Ovarian ablation or suppression vs none 11.8 < <

4 Determination of Systemic Therapy Chemotherapy Size Grade Lymph node status Hormonal status Her-2 status Ki-67 status Gene signature (eg: Oncotype Dx) Hormonal therapy Does the tumor express estrogen (progesterone) receptors? Targeted therapy Does the tumor express the target? Example: her2 (+) tumors treated with trastuzumab

5 Relative vs. Absolute Risk Reduction Scenario #1: 40% Risk of recurrence 50% Relative risk reduction with intervention (RR=0.5) Scenario #2: 4% Risk of recurrence 50% Relative risk reduction with intervention (RR=0.5)

6 Risk Estimation Several techniques are now available for assessing prognosis and estimating benefit of some types of both chemotherapy and hormonal adjuvant therapy in patients with breast cancer Adjuvant! ( Guidelines Oncotype DX

7 Recurrence Risk: St Gallen St Gallen risk categories Features for patients with breast cancer Node negative and all of the following: Risk Low Tm 2 cm, grade 1, LVĐ (-), ER and PgR (+), HER2 (-), 35 yrs of age Intermedi ate Node negative and 1 of the following: Tm > 2 cm, grade 2-3, LVI (+), ER and PgR (-), HER2 gene over-expressed or amplified, < 35 yrs of age Node positive 1-3 nodes and ER and/or PgR (+) and HER2 (-) High Node positive 1-3 nodes involved, ER and PgR (-) or HER2 overexpressed/amplified Node positive 4 involved nodes Goldhirsch A, et al

8 Recurrence Risk: NCCN Factors used to stratify patients into risk groups Number of involved axillary lymph nodes Tumor size Unfavorable features: angiolymphatic invasion, nuclear or histologic grade or high Ki67.* Gene signature * These features were used to stratify N 0 T 1b cases NCCN. Available at:

9 Molecular Prognostic Assays Gene expression based tests for biomarkers of breast cancer Available to help identify patients who might benefit from adjuvant therapy Oncotype DX (21-gene recurrence score estimate) GeneSearch (Rotterdam signature; 76-gene microarray) MammaPrint (70-gene microarray) More in development None incorporated into Adjuvant! Lack of data on correlation with response to chemotherapy Paik S, et al. SABCS Abstract 16. Paik S, et al. N Engl J Med. 2004;351:

10 Thresholds for treatment modalities Treatment modality Endocrine therapy Anti-HER2 therapy Chemotherapy In HER2-positive disease (with anti- HER2 therapy) In triple-negative disease In ER-positive, HER2- negative disease (with endocrine therapy) Indication Any ER staining ASCO/CAP HER2 positive [>30% intense and complete staining (IHC) or FISH >2.2+] Trial evidence for trastuzumab is limited to use with or following chemotherapy b Most patients Variable according to risk Comments ER negative and PgR positive are probably artefactual May use clinical trial definitions Combined endocrine therapy + anti-her2 therapy without chemotherapy in strongly ERpositive, HER2-positive is logical but unproven No proven alternative; most at elevated risk Goldhirsch et al. Annals of Oncology 20: , 2009

11 Chemoendocrine therapy in patients with ER-positive, HER2-negative disease Clinicopathological features ER and PgR Histological grade Relative indications for chemoendocrine therapy Lower ER and PgR level Factors not useful for decision Grade 3 Grade 2 Grade 1 Proliferation High Intermediate Low Nodes PVI Node positive (four or more involved) Presence of extensive PVI Node positive (one to three involved) pt size >5 cm cm 2 cm Patient preference Multigene assays Use all available treatments Relative indications for endocrine therapy alone Higher ER and PgR level Node negative Absence of extensive PVI Avoid chemotherapyrelated side-effects Gene signature High score Intermediate score Low score Goldhirsch et al. Annals of Oncology 20: , 2009

12 Chemotherapy for Early Stage Breast Cancer Indications for chemotherapy Node positive disease High-risk node negative disease Hormone receptor negative Large tumors High grade tumors Young patients Multiple effective regimens involving combinations of two or more drugs Benefit of chemotherapy is greatest when risk of recurrence is highest

13 Adjuvan Treatment in 2010 Risk category Endocrine High responsive Endocrine Less responsive Endocrine Not responsive Low risk ET ET NA Nil Nil Intermediate risk ET CT ET CT ET (CT+ET) CT (CT+ET) High risk CT ET CT ET CT (CT+ET) (CT+ET)

14 Survival benefit with adjuvan Taxan: 4AC = 6CMF < 6FAC, 6CAF, 6 CEF or 6 FE(100)C 4AC < 4AC+4paclitaxel 4AC+4paclitaxel < Dose dense 4AC+4paclitaxel 6FAC < 6 TAC 6FE(100)C < 3FE(100)C + 3Taxoter 4AC < 4 TC

18 Chemotherapy - Summary Multiple effective drugs and regimens Improvements in survival from newer, better drugs and strategies Focus on: Improving chemotherapy regimens for those who need treatment Identifying patients who will benefit from chemotherapy

Multigene Testing in NCCN Breast Cancer Treatment Guidelines, v1.2011

Multigene Testing in NCCN Breast Cancer Treatment Guidelines, v1.2011 Robert W. Carlson, M.D. Professor of Medicine Stanford University Chair, NCCN Breast Cancer Treatment Guidelines Panel Selection of