Initial Evaluation Clinical Stage Pre-Treatment Evaluation Treatment and pathological stage Less than 4 positive lymph nodes Adjuvant Treatment ER Positive HER2 Negative (see page 2 & 3 ) HER2 Positive (see page 4) Primary Diagnosis: Mammography History and physical Fine needle aspiration Core biopsy Full blood count Chest X-Ray Biochemistry Operable by Conservation Surgery Operable by Mastectomy Surgery Candidate for Primary Medical Treatment 4 or more positive lymph nodes Bone Scan CT chest and abdomen Ultrasound liver If staging positive ER Negative PR Negative HER2 Negative (see page 5) Primary medical therapy (see page 6) Metastatic disease (see page 7) August 2008 Breast Cancer CMG Version 1.0 1
Pathological stage Adjuvant Treatment Low risk: G1 & <1cm Tamoxifen de Negative Pre-menopausal ER Positive HER2 Negative Medium risk: G1 > 1.1cm or G2 <2cm G2 Post-menopausal See page 3 High Risk: G2 >2cm or G3 G3 Pre-menopausal Post-menopausal Tamoxifen 5 years See page 3 G1 or G2 1-3 nodes Post-menopausal See page 3 de Positive >4 des 1 SEE PAGE 8 AC or Epi / CMF Pre-menopausal Tamoxifen 5 years TC if previous anthracyclines or cardiac issues August 2008 Breast Cancer CMG Version 1.0 2
Adjuvant Hormonal Therapy POSTMENOPAUSAL? ANY ONE OF: Menopausal Status - Definitions: Post Menopausal at time of diagnosis of breast cancer defined as: Amenorrhea > 2 Years and > 50 years If amenorrhea <2 years and/or < 55 years check LH/FSH/Oestrodiol before chemotherapy Grade 3 de +ve 1 ER poor 2 Her 2 +ve Path size 5cm (T3 & T4) Prev. neoadj AI with response Aromatase Inhibitor 3 5 years duration CHEMOTHERAPY INDUCED AMENORRHOEA DOES NOT EQUAL POSTMENOPAUSAL And ovarian function tests are unreliable post chemotherapy/hormonal therapy If pre-menopausal before chemotherapy with persisting chemo induced amenorrhoea following chemo then at the time of considering an AI : If < 50 years old exclude- unless ovarian ablation If 50-55 years use assessment of menopausal status pre chemotherapy ALL OF: Grade 1 AND de -ve 1 AND Size <2cm ALL THE REST i.e. Grade 2 node ve 1 Size<5cm Grade 1 node ve 1 Size 2-5cm Tamoxifen 5 years duration Extended adjuvant 3 (5yrs tam +3yearsAI) Or Switch 3 (2.5 yrs tam +2.5years AI) If > 55 years class as postmenopausal Ineligible for AI Consider tamoxifen 1micrometastases defined as 0.2-2mm = node positive, isolated tumour cells defined as <0.2mm = node negative 2ER poor defined as Allred 3-5 3Aromatase inhibitor as per current licenses. The choice of AI should be as per local Health Board policy and approvals August 2008 Breast Cancer CMG Version 1.0 3
Pathological stage Adjuvant Treatment Low risk: G1 & <1cm ER positive? systemic therapy de Negative Medium risk: G1 & < 3cm or G2 & <2cm ER positive? Pre-menopausal Post-menopausal Ovarian suppression + Tamoxifen Aromatase inhibitor a HER2 Positive Pre-menopausal Ovarian suppression + Tamoxifen ER positive Trastuzumab 2 1: SEE PAGE 8 AC or Epi/CMF if node negative FEC > D or TC if node positive de Positive Post-menopausal Aromatase inhibitor 3 2: See Trastuzumab guideline, page 6 3: Aromatase inhibitor as per current licence & Health Board policy ER negative August 2008 Breast Cancer CMG Version 1.0 4
Pathological stage Adjuvant Treatment de Negative Low risk: G1 & <2cm systemic therapy >70 years ER Negative PR Negative HER2 Negative <70 years de Positive 1 SEE PAGE 8 AC or Epi/CMF if node negative : FEC > D or TC if node positive August 2008 Breast Cancer CMG Version 1.0 5
Primary medical therapy Postmenopausal Either Letrozole 2.5mg od 4-6 months ER Positive Premenopausal Fit FEC100 X 3 Poor response Good response Docetaxel [See note A below ]100mg/m 2 x 3 FEC100 X 3 Un-Fit AC 4-6 Inoperable Large Inflammatory Surgery + 3 field radiotherapy Tamoxifen 5 yrs + OS if HER2 pos ER/PR positive Premenopausal Postmenopausal further tx ER/PR negative ER Negative A: Pre-operative Docetaxel subject to non-formulary process, unless remains inflammatory/ inoperable. Requires primary prophylaxis with G-CSF. B: Trastuzumab subject to nonformulary process if initially inflammatory tumour. HER 2 Positive > Add 1 year Trastuzumab [see note B] ER/PR positive Complete 5 yrs letrozole ER/PR negative further tx August 2008 Breast Cancer CMG Version 1.0 6
Evaluation for metastases Treatment of metastases Good response Other (eg Megestrol) Poor response >2 years ago Taxane and Traztuzumab (if HER2 Positive) See note A, page 9 Good response Alternative AI Poor response Previous Taxane <2 years ago Relapse Relapse Aromatase inhibitor Poor response Primary Diagnosis: Mammography History and physical Fine needle aspiration Core biopsy Full blood count Chest X-Ray Biochemistry Bone Scan CT chest and abdomen Ultrasound liver Metastatic Diagnosis ER positive ER negative Hormone treatment candidate Suitable for chemotherapy Palliative therapy Previous adjuvant treatment Fluorouracil/epirubicin/ cyclophosphamide or Epirubicin See note B, page 9 Relapse Taxane and Traztuzumab (if HER2 Positive) See note A, page 9 Bone Metastases Bisphosphonate with other treatment See note E, page 9 Capecitabine or Vinorelbine See note C, page 9 Consider 3th/4 th line therapies See note D, page 9 August 2008 Breast Cancer CMG Version 1.0 7 Relapse Relapse
Adjuvant/Primary Chemotherapy Regimens For full details please refer to relevant WoSCAN chemotherapy protocol Acceptable regimens for adjuvant/primary chemotherapy: AC : Doxorubicin (Adriamycin) 60mg/m 2 + Cyclophosphamide 600mg/m2 3 weekly x 4 cycles For women > 70 or low risk or patients needing chemotherapy but thought not able to tolerate more intensive regimen Epi >CMF: Epirubicin 100mg/m2 3 weekly x 4 cycles > CMF day 1+8 4 weekly x 4 cycles x 4 cycles Standard anthracycline based schedule FEC > D: Fluorouracil 500mg/m2 + Epirubicin 100mg/m2 + Cyclophosphamide 500mg/m2 x 3 cycles 3 weekly > Docetaxel 100mg/m2 x 3 cycles 3 weekly Taxane based chemotherapy preferred option [node positive, triple receptor negative or HER2 positive]. < 65 years, Performance status 0,1 TC: Docetaxel 75mg/m2 / cyclophosphamide 600mg/m2 3 weekly x 4 cycles For patients who need chemotherapy but not suitable for anthracycline due to cardiac history. Taxane based chemotherapy preferred [node positive, triple receptor negative or HER2 positive] but not fit enough for FEC > D or > 65 years of age. FEC 100: Fluorouracil 500mg/m2 + Epirubicin 100mg/m2 + Cyclophosphamide 500mg/m2 3 weekly x 6 cycles Pre-operative anthracycline based chemotherapy August 2008 Breast Cancer CMG Version 1.0 8
Metastatic Chemotherapy Regimens For full details please refer to relevant WoSCAN chemotherapy protocol The choice of metastatic therapies are dictated by the individual patient s previous therapy, general health, liver/renal/bone marrow function, response to previous treatments and sites of disease. Definitive recommendations can therefore not be made. A. Acceptable regimens : Paclitaxel 80mg/m 2 weekly; Paclitaxel 175mg/m 2 3 weekly; Docetaxel 100mg/m 2 3 weekly. Trastuzumab either 4mg/kg loading dose then 2mg/kg weekly or 8mg/kg loading followed by 6mg/kg 3 weekly. B Acceptable regimens: Epirubicin 30mg/m 2 weekly; Epirubicin 100mg/m 2 3 weekly; FEC 600/60/600mg/m 2 3 weekly. C Acceptable regimens: Capecitabine 1000mg/m 2 bd days 1-14, 3 weekly; Vinorelbine 25mg/m 2 IV or 60 mg/m 2 oral days 1+8, 3 weekly. D Phase 1 or 2 trials should be considered. Otherwise suitable options include: - Vinorelbine or Capecitabine if not previously received - Weekly Paclitaxel if responded to previous Docetaxel - Mitoxantrone - Low-dose oral Cyclophosphamide E Bisphosphonates as per WOS guidelines. August 2008 Breast Cancer CMG Version 1.0 9
Algorithm Conservation Offer <60 years or primary/neoadjuvant medical patient 50Gy in 25# with 10Gy in 4# boost Sentinel node de positive Further surgery or radiotherapy to axilla and SCF (4 field) >60 years 50GY in 25# boost de negative radiotherapy to axilla (2 field) 1-3 nodes positive plus one of: LVI Multifocality Grade 3 >10% risk of recurrence Offer Axillary Surgery Axillary Sample 3 nodes recovered (unknown axillary status de positive Further surgery or radiotherapy to axilla and SCF (4 field) to axilla and SCF (4 field) Mastectomy Any one of: T3 or T4 tumour Inadequate clearance (<0.5cm) Residual disease post-surgery Initially inoperable or locally advanced tumour with neoadjuvant systemic therapy 1-3 nodes positive with extra-capsular spread ne of these May still require radiotherapy depending on axillary status, if so: 45Gy in 20# or 50GY in 25# (if reconstruction) 1 or more or 20-40% risk or recurrence Offer 45Gy in 20# or 50Gy in 25# (if reconstruction) Axillary dissection >3 nodes recovered de negative Any one of: 4 nodes positive Extracapsular tumour spread Perinodal invasion Apical lymph node positive Initially inoperable/locally advanced treated with neoadjuvant systemic therapy radiotherapy to axilla (2 field) to medial SCF (3 field) August 2008 Breast Cancer CMG Version 1.0 10