Invasive Breast Cancer

Transcription

1 Invasive Breast Cancer Eileen Rakovitch MD MSc FRCPC Sunnybrook Health Sciences Centre Medical Director, Louise Temerty Breast Cancer Centre LC Campbell Chair in Breast Cancer Research Associate Professor, Department of Radiation Oncology University of Toronto

2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.

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4 Breast Cancer in Canada 25,500 women diagnosed 5,100 died of Breast Cancer #1 cancer in women In Ontario 9,900 women diagnosed 1,950 women died of Breast Cancer

5 Epidemiology: Statistics

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8 Prognostic factors in Breast Cancer Clinical stage Tumor stage Size / local extension / inflammatory Nodal involvement Distant metastases

9 Breast Cancer Survival Stage I disease 95% Stage II disease 70%-85% Stage III disease 50%-52% Stage IV disease 17% National Cancer Institute of Canada/ Fisher et al. J Natl Cancer Inst Monographs *American Joint Committee on Cancer. Handbook for Staging of Cancer 1993.

10 Early Breast Cancer Treatment Schema SURGERY Adjuvant Chemotherapy Adjuvant Radiation Adjuvant Endocrine

11 Locally Advanced Breast Cancer Treatment Schema Neo-Adjuvant Chemotherapy SURGERY Adjuvant Radiation Adjuvant Endocrine

12 Seminal trials in breast cancer

13 Is a mastectomy necessary?

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15 Radical Mastectomy vs. Total Mastectomy

16 Mastectomy vs. Lumpectomy + Radiation

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18 Is Axillary Node Dissection necessary? Axillary vein thrombosis major nerve injury thoracodorsal long thoracic lymphedema shoulder dysfunction seroma formation

19 Sentinel Node Biopsy

20 Node negative NSABP B32

21 NSABP B32 Overall Survival Disease-free Survival

22 ACOSOG Z011 Node positive 891 patients Lumpectomy 1-2 SLN+ T 5 cm ALND no ALND Giuliano AE, JAMA 305:569, 2011

23 ACOSOG Z011 OMIT Axillary Dissection for 1-2 Node positive Node positive ALND 891 patients Lumpectomy 1-2 SLN+ T 5 cm no ALND Giuliano AE, JAMA 305:569, 2011

24 Assessing Sentinel Nodes Number of nodes involved Number of nodes removed Volume of disease Micro metastases (<2mm) Macro metastases (>2mm) Extra nodal extension

25 Summary Mastectomy and Breast-Conserving Surgery equivalent survival Axillary Nodal Dissection can be safely omitted node negative patients 1-2 positive nodes

26 Case No year-old female patient R breast lump Mammogram Ultrasound Ultrasound guided biopsy Invasive ductal carcinoma

27 Case No year-old female patient R breast lumpectomy and node dissection Pathology Invasive Ductal Carcinoma 2.5 cm size Tumour Grade II/III No lymphovascular invasion Margins clear (3mm) Lymph nodes 2/3 nodes involved ER 95% PR 90% Her2 positive

28 The Impact of Systemic Therapy

29 Prognostic factors in Breast Cancer Clinical stage Tumor stage Size / local extension / inflammatory Nodal involvement Distant metastases Grade Lymphovascular invasion Receptor status Hormone (ER/PR) Her2neu Gene expression profile

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31 Early Breast Cancer Trialists Group: Oxford Overview Impact of Chemotherapy on Recurrence

32 Early Breast Cancer Trialists Group: Oxford Overview Impact of Chemotherapy on Survival

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35 Anti-estrogen therapy: Mechanism of Action Smith et al. N Engl J Med 2004.

36 % Recurrence-free Tamoxifen: Improvement in Disease-Free Survival Recurrence as First Event Node -ve Tamoxifen (~5 y) Placebo Tamoxifen (~5 y) Placebo Node -ve: 14.9% SD 1.4: 2P< Node +ve: 15.2% SD 2.5: 2P< Node +ve Years Reprinted from The Lancet, vol 351, Early Breast Cancer Trialists Collaborative Group, 1451, 1998, with permission from Elsevier Science Absolute Recurrence Reduction Survival benefit: 6% Node neg 11% node pos

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38 Tamoxifen vs. Aromatase Inhibitors Toxicity Slight reduction in recurrence risk with AI Tamoxifen Endometrial cancer Venous thrombosis Hot flashes Vaginal dryness/bleeding Aromatase Inhibitors Hot Flashes Arthralgias / Myalgias Osteopenia/Osteoporosis May have a beneficial effect on endometrial pathology No increased risk of DVTs

39 Different Strategies Tamoxifen x 5 years Aromatase inhibitor x 5 years Tamoxifen x 2-3 years AI x 2-3 yr Tamoxifen x 5 years followed by an AI for 5 years Winer et al. JCO 2005.

40 Epidermal Growth Factors Regulate cell differentiation, proliferation, and survival Consists of a family of four receptors HER1 HER2 HER3 HER4 Act through tyrosine kinase pathway (TKP)

41 Human Epidermal Growth Factor Receptor (HER2) positive Disease ~ 25% of breast cancers

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43 Trastuzumab Mechanism of Action Inhibition of tumor cell proliferation (cytostatic) Potentiation (sensitization) of chemotherapy (cytotoxic) Promotes Anti-angiogenesis (cytotoxic) Facilitation /recruitment of immune cells

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45 Adjuvant Trastuzumab trials HERA Observation NSABP B-31 4 x AC 4 x paclitaxel 175 mg/m 2 2 HER2+ (IHC or FISH) Accepted CT: AC, EC, FAC, FEC, ET, AT, CMF HER2+ 1 year Trastuzumab (IHC or FISH) 2 years Trastuzumab 1 year Trastuzumab NCCTG N x AC 12 x paclitaxel 90 mg/m 2 BCIRG 006 AC T 4 x AC 4 x docetaxel 60/600 mg/m mg/m 2 HER2+ (IHC or FISH) 1 year Trastuzumab HER2+ (FISH) N=3222 AC TH TCH 1 year Trastuzumab 6 x docetaxel and platinum salts 75 mg/m 2 75 mg/m 2 or AUC 6 1 year Trastuzumab

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47 Main Side Effect is Cardiac Toxicity Risk of NYHA III/IV CHF up to 4% Need to monitor EF while on Treatment patients receive this every three weeks for one year with close cardiac follow up Data for 2 years vs. 1 year is pending

48 Systemic therapy improves breast cancer survival

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50 Molecular Expression Assay Prosigna (Nanostring) Oncotype DX Recurrence Score Prognostic and Predictive Low Risk no chemo Intermediate risk? High Risk chemo

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52 Summary Node negative ER+PR+her2- Molecular assay Her2+ chemotherapy + herceptin triple negative chemotherapy Node positive Most will receive chemotherapy Integration of molecular subtype to determine Benefit of chemotherapy Choose regimen

53 Early, invasive breast cancer

54 Whole Breast Radiation Reduces Local Recurrence Risk Node negative Node positive EBCTCG, Lancet 366: , 2005

55 Whole breast radiation: Effect on mortality 7.1% 5.1% Node negative Node positive EBCTCG, Lancet 366: , 2005

56 Breast Radiotherapy weeks of treatment Acute and delayed skin toxicities

57 Accelerated Partial Breast Irradiation Treat smaller volume Higher dose per fraction Shorter treatment time

58 Accelerated Partial Breast Irradiation Brachytherapy LDR / HDR (NSABP B 39) Mammosite (NSABP B 39) Permanent breast seed implant Intraoperative Radiotherapy Photons (TARGIT) Electrons (ELIOT) External Beam

59 HDR brachytherapy

60 Mammosite

61 TARGIT-A Photons Electrons

62 External beam partial breast irradiation

63 Partial breast irradiation Patient selection important Age > 50 years Tumor < 3 cm Risk of higher rates of Local recurrence Risk of higher toxicity Target volume is important

64 Regional Nodal Irradiation In Node Positive Breast Cancer After lumpectomy After mastectomy

65 Local recurrence: effects of RT

66 Breast cancer mortality: effects of RT

67 Regional Nodal Irradiation For Node Positive Breast Cancer Increased DFS at 5 years Reduced Locoregional Recurrence Reduced Distant Recurrence Trend towards improved overall survival Increase radiation pneumonitis and lymphedema

68 Locally Advanced Breast Cancer

69 Neglected Indolent tumors Rapidly growing tumors Inoperable tumors Inflammatory Breast Cancer

70 Neoadjuvant Adjuvant Chemotherapy Surgery Surgery Chemotherapy Radiation

71 Is less more? The de-escalation of breast cancer therapy Remember, Crookshank, less is more. Which brings us to your salary.

72 Trials de-escalation therapy Node negative LUMINA Node positive Omission of RT in Luminal A, 1-3+ nodes Post-neoadjuvant chemotherapy Omitting Axillary nodal dissection (Alliance) Omitting Radiation Therapy (NRG B51)

73 Follow-Up

74 Role of Family Physician FPs remain the primary care givers for most of these patients FPs may provide follow-up as Sole provider of care In conjunction with the cancer centre Ontario Study Randomized breast cancer follow-up to Cancer centres Family physicians No difference

75 Why Follow Patients? Psychosocial support and counseling Detect recurrent and metastatic disease Surveillance for other other malignancies Monitor toxicities related to current or previous treatment

76 Canadian Steering Committee on Clinical Practice Guidelines (Canadian Task Force) History and physical Guidelines Every 3-6 months first 3 yrs after primary therapy Then q 6 months for 2 yrs Then annually Annual mammogram Encourage monthly BSE Educate re: recurrence symptoms Canadian Steering Committee on Clinical Practice Guidelines. CMAJ American Society of Clinical Oncology. JCO 1998.

77 Guidelines No Role for Routine CBC, renal function tests, liver function tests, albumin, protein, calcium Chest X-ray Bone scan Liver ultrasound CT Tumour markers: CEA, CA 15-3 Canadian Steering Committee on Clinical Practice Guidelines. CMAJ American Society of Clinical Oncology. JCO 1998.

78 For Patients On Endocrine Therapies No need for routine blood work Bone mineral density (BMD) Of particular importance for patients on aromatase inhibitors Recommend baseline, then annually Ophthalmologic evaluation Symptom driven If previous history annual exam No role for routine U/S, Doppler, etc.

79 Cardiac toxicity Common Health Issues Prior anthracyclines, Herceptin Risk factors Acute (during administration) Arrhythmias, pericarditis-myocarditis Early (days to months post-treatment) CHF, with peak at 3 months after last dose Late (years post-treatment) CHF may develop up to yrs after last anthracycline dose Cumulative dose strongest risk factor Age Prior irradiation Concomitant administration of other agents Previous history of cardiac disease

80 Osteoporosis Early menopause Chemotherapy effect Endocrine therapy (AI) Health Issues Early menopause Menopausal symptoms Psychological effects Osteoporosis Secondary cancers New breast cancer (1%/year) Second malignancies (smokers)

81 Other Concerns Lymphedema Referrals to supportive care services Family members Screening for breast cancer Screening for other cancers Genetic assessment

82 When Should FPs Refer Patients to Cancer Centre? Cancer related New breast lump or local lymphadenopathy New primary breast cancer Cancer recurrence Concerning distant symptoms Secondary cancers Treatment related New endocrine treatment for follow-up population Toxicities Patient driven

83 When to refer back? Oncologist?New lump?new node?distant yrs hormone therapy?pt driven Surgeon Medical Radiation Family physicians Follow-Up

84 Thank you