THE CHANGING PATIENT PATHWAY IN BREAST CANCER: FROM GP TO CURE

1. THE CHANGING PATIENT PATHWAY IN BREAST CANCER: FROM GP TO CURE MR TERENCE J. BOYLE Consultant Breast Surgeon BEACON HOSPITAL Clinical Lead - Beacon Breast Centre & ST JAMES’S HOSPITAL Clinical Lead - Breast Care Department

2. OUTLINE • Presentation/initial work-up • Triple Assessment • Subsequent investigation • Staging: Breast, axilla, systemic • Characterising the disease • Tumour GRADE, Disease STAGE • Biomarker Profile • Treatment strategies • Surgery, systemic therapies, radiotherapy • Follow-up/ongoing care issues • Psychological support (NB: Specialist Nurses) • Physiotherapy, chronic pain, ‘reconstruction’

3. RAPID DIAGNOSTICBREAST CLINIC (Beacon Breast Centre)- Rapid Access- TRIPLE ASSESSMENT • Discussion at weekly Breast Care Multi-Disciplinary Team Meeting (MDM - Treatment Planning) • ‘Results’ Clinic

4. GP Breast Referral Guideline Development GroupMeeting 7: 25/03/2019

5. CLINICAL ASSESSMENT PHYSICAL EXAMINATION • HISTORY • Details of breast symptomatology • Lump, nipple changes/discharge • skin changes, change in size/shape, duration • Past history of breast disease • Previous breast imaging • Family history of breast disease • Gynaecologic history • Factors increasing risk

6. RADIOLOGY

7. BREAST PATHOLOGY- INVASIVE DISEASE • HISTOLOGIC TYPE • DUCTAL vs LOBULAR • Paget’s disease of the nipple • Inflammatory breast cancer • TUMOUR CHARACTERISTICS • Tumour size • Tumour grade (I, II, III) • Hormone receptor status • (oestrogen / progesterone) • HER-2 protein status • Ki67 Proliferation Index • NB: Triple negative breast cancer • (ER neg, PR neg, HER-2 neg) • NB: Phyllodes tumour / cystosarcomaphyllodes

8. STAGING BREAST CANCER

9. Staging-TNM • T0: subclinical • T1: <2cm • T2: >2cm, <5cm • T3: >5cm • T4: chest wall or skin involvement

10. Staging-TNM • N0: no nodes • N1: ipsilateral axillary mobile nodes • N2: ipsilateral axillary fixed nodes • N3: Ipsilateral internal mammary nodes • M0: no distant metastases • M1: distant metastases

11. MANAGEMENT OFBREAST CANCER

12. MANAGEMENT OFBREAST CANCER • - Breast conservation vs mastectomy • Sentinel Lymph Node Biopsy vs Axillary Clearance • Downstage disease to reduce surgical complexity

13. The Sentinel Node

14. TUMOUR BIOLOGY • ‘LETHAL’ BREAST CANCER: • Triple Negative Breast Cancer (ER/PR Neg, HER-2 Neg) • HER-2 Pos Breast Cancer (NB: anti-HER-2 therapies) • ‘FAVOURABLE’ BREAST CANCER: • Hormone receptor positive, HER-2 Negative • Axillary node negative

15. SYSTEMIC STAGING OFBREAST CANCER SITES OF METASTATIC SPREAD • NODAL: • Ipsilateral / contralateral axilla • Neck: supraclavicular fossa / cervical chain • Internal mammary chain • Distant / systemic • SKELETAL: anywhere • VISCERAL: • Lungs, liver, brain

16. STAGING BREAST CANCER PRE-OPERATIVE SYSTEMIC STAGING INVESTIGATIONS • Baseline bloods: (FBC, coag, CRP, L/R/B profile, glucose, CA 153) • CXR (early disease) or • CT Thorax/Abdomen/Pelvis • Isotope bone scan • Other investigations as indicated (PET-CT, MRI)

17. TREATMENT STRATEGIESFOR BREAST CANCER • SURGICAL THERAPY • Primary vs Delayed • CHEMOTHERAPY • Adjuvant (post-operative) • Neo-adjuvant (primary / pre-operative) • Palliative • HORMONAL THERAPY • Disease must be ER / PR positive • IMMUNOTHERAPY • Disease must overexpress HER-2 • RADIOTHERAPY • NOVEL THERAPIES (Anti-angiogenics etc)

18. MANAGEMENT OFBREAST CANCER

19. Molecular profiling to determine ifpatientwill benefit from Chemotherapy? • Gene assay performed on paraffin-embedded archival breast cancer tissue • Predicts risk of recurrence at 10yrs • Data generated from retrospective analysis of archival tissue • Gene set has been validated across multiple validation sets using prospectively defined end points (NSABP B14 & Kaiser Permanente) • Final gene set: relapse-free interval correlations across three independent studies: testing 250 genes in 447 patients

20. ONCOTYPE DX:Prognosis & Risk of Recurrence 16 Cancer and 5 Reference Genes From 3 Studies PROLIFERATION Ki-67 STK15 Survivin Cyclin B1 MYBL2 ESTROGEN ER PR Bcl2 SCUBE2 GSTM1 BAG1 INVASION Stromelysin 3 Cathepsin L2 CD68 REFERENCE Beta-actin GAPDH RPLPO GUS TFRC HER2 GRB7 HER2 Paik et al. N Engl J Med. 2004;351:2817-2826.

21. ONCOTYPE DX:Recurrence Score

22. POPULATION-BASED RISKFOR BREAST CANCER

23. ModifiableRisk Factors Modifiable

24. Familial Breast Cancer Risk Assessment Guidelines LOW RISK MEDIUM RISK HIGH RISK HIGH RISK SIGNIFICANT FACTORS • TWO1st or 2nd degree relatives with breast cancer < 50 years( one must be 1st degree relative) • THREE 1st or 2nd degree relatives with breast cancer < 60 years (one must be 1st degree relative) • FOURRelatives with breast cancer at any age (one must be a 1st degree relative ) Ovarian Cancer • ONErelative with ovarian cancer at any age PLUS on the same side of the family there is: • ONE1st or 2nd degree relative with breast cancer before age 50 • ONEadditional relative with ovarian cancer at any age • TWO1st or 2nd degree relatives with breast cancer at average age of < 60 Bilateral Breast Cancer • ONE1st degree relative with cancer in both breasts before average age of 50 • ONE 1st or 2nd degree relative Male Breast Cancer ONEmale breast cancer at any age PLUS ON SAME SIDE OF FAMILY: • ONE1st or 2nd degree relative with breast cancer before 50 • TWO1st or 2nd degree relatives with breast cancer before average age of 60 • ONE 1st degree relative with breast cancer > 40 years • ONE 2nd degree relative at any age • ONE1st degree relative with breast cancer < 40 years • TWO1st or 2nd degree relatives with breast cancer at an average age of > 50 years • THREE1st or 2nd degree relatives with breast cancer at an average age of > 60 years • ONE1st degree relative with breast cancer < 40 years • TWO1st or 2nd degree relatives with breast cancer at an average age of > 50 years • THREE1st or 2nd degree relatives with breast cancer at an average age of > 60 years *Bilateral breast cancer *Male breast cancer *Ovarian cancer *Jewish ancestry *Sarcoma in a relative<45 *Glioma or childhood adrenal cortical carcinomas *Complicated patterns of multiple cancers at a young age Lifetime risk of breast cancer is less than 17% A less than 3% risk of developing breast cancer in the next 10 years for women aged 40-49 Lifetime risk of breast cancer is 17% or greater but less than 30% A 3-8% risk of developing breast cancer in the next 10 years for women aged 40-49 IMAGING REQUIRED • No imaging required • Follow up in primary care IMAGING REQUIRED IMAGING REQUIRED • Annual mammography for women aged between 40-49 years (imaging to commence at age of 5-10 years younger than youngest affected relative) • Women aged between ages 50-64 years, mammography to take place in National Breast Screening Programme. High Risk • Annual mammography for women aged >40 years (imaging to commence at age 5-10 years younger than youngest affected relative) +/- • Annual MRI breast for women aged between 30-49 for following criteria: *TP53, BRCA1 & BRCA2 mutation carriers (or with equivalent high risk) • Lifetime risk of breast cancer is 30% or greater Risk of faulty BRCA1, BRCA2 or TP53 gene is 20% or greater A greater than 8% risk of developing breast cancer for women aged 40-49

25. MULTIDISCIPLINARY MANAGEMENT OFWOMEN AT HIGH RISK FOR BREAST CANCER

26. Thank you!