Overview of Breast Cancer. Donna Graham Medical Oncology SpR

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1 Overview of Breast Cancer Donna Graham Medical Oncology SpR

2 Learning Points Epidemiology Risk Factors Diagnosis Prognostic Markers Stage 0 III disease Stage IV disease Surveillance

3 Incidence in Ireland ( )

4 Mortality in Ireland Females with cancer ( )

5 Female years of life lost (1996 v 2006) cancer site PYLL Average YLL % of all years of life lost all sites % 100% oesophagus % 3% stomach % 3% colorectal % 9% pancreas % 5% lung % 16% breast % 21% ovary % 8% lymphoma % 4% leukaemia % 3%

6 Estimated incidence and mortality in Europe (2008)

7 Effect of Age Median Age at Diagnosis 59 Median Age at Death 72

8 Racial differences Black Americans Lower incidence breast ca Higher mortality Rate of triple negative breast cancer in younger black females >2x higher than in older black females

9 Risk Factor Gender (female vs male) 100 BRCA1 or 2 mutation 6 14 Family History of Breast ca First degree relative Second degree relative Age ( 50 vs <50) 6.5 Benign breast disease Atypical Hyperplasia Hyperplasia Nulliparity 2.0 Relative Risk Age at 1 st live birth (>30 vs <20yrs) Age at menopause (>55 vs <55) Age at menarche (<12 vs >14yrs) HRT Exposure to ionising radiation 1.4 Alcohol consumption (12g or 30ml/day vs none) Increased BMI Premenopausal Postmenopausal

10 Diagnosis Suspicious abnormality Physical Exam Screening Mammogram Ultrasound

11 Biopsy Incisional Core biopsy Palpation Image Guided Excisional Stereotactic Ultrasound guided Operative removal of entire lesion

12 Biopsy Findings Histological Type Histological Grade Lymphovascular Invasion Immunohistochemistry ER/PR+ HER2+

13 HER2 Activation Pohlmann P R et al. Clin Cancer Res 2009;15: by American Association for Cancer Research

14

15

16

17 Prognostic Determinants of Local Therapy Tumour Size and Extent Extensive intraductal component Lymphatic invasion Multiple tumour foci or microcalcifications Age BRCA1 or 2 mutations

18

19 Earlier stage = Better survival % 5-year survival I IIA IIB IIIA IIIB IV Survival Stage

20 Prognostic Determinants of Adjuvant Therapy Lymph Node Involvement Tumour Size Histologic Type Histologic Grade or Differentiation Lymphatic Invasion Markers of Proliferative Capacity Hormone Receptors Her2 Prognostic Indices

21 Gene expression patterns in breast tissue from 42 women Intrinsic classification Basal-like Mainly triple negative Luminal-A Luminal-B Her-2 positive ER+ low grade ER+, may express low levels of hormone receptors and often high grade High expression of ERBB2 gene and associated genes

22 Correspondence between Molecular Class and Clinicopathological Features of Breast Cancer Sotiriou C, Pusztai L. N Engl J Med 2009;360:

23 Kaplan Meier analysis of disease outcome in two patient cohorts Time to develop distant mets Overall survival Sørlie T et al. PNAS 2003;100: by National Academy of Sciences

24 Breast Cancer Treatment Considerations Breast Cancer Local Systemic Radiotherapy Surgery Hormone Therapy Chemotherapy Biological Therapy Breast Axilla

25 Breast Cancer Treatment Considerations Breast Cancer Local Systemic Radiotherapy Surgery Hormone Therapy Chemotherapy Biological Therapy Breast Axilla

26 Stage I or II Disease Clinical Stage I or II Invasive Breast Cancer Lumpectomy + Mastectomy SLN Bx AND Total + SLN Bx Modified Radical Neoadjuvant Chemotherapy (SLN Bx before, surgery after)

27 Clinical Stage III Disease Clinical Stage III Invasive Breast Cancer Neoadjuvant Chemotherapy Mastectomy Radiation Therapy

28 Mastectomy Total Mastectomy With or without reconstruction With or without sentinel lymph node biopsy Remove only the breast Modified Radical Mastectomy With or without reconstruction Remove the breast and axillary lymph nodes

29 Breast Conservation Therapy Lumpectomy + Radiation Therapy Remove the bulk of the tumor surgically and to use moderate doses of radiation therapy to eradicate any residual cancer Goal Preserve cosmetic outcome Provide survival equivalent to mastectomy Provide low rate of local recurrence

30 BCT vs Mastectomy Since 1970, 7 prospective randomized studies demonstrate equivalent outcome regardless of surgical choice for patients with Stage I or II disease

31 Radiation Therapy External beam Daily therapy for 6 weeks Side effects Skin changes Pulmonary toxicity Cardiotoxicity

32 Contraindications to breast conservation therapy Absolute 2 or more primary tumors in separate quadrants Diffuse malignant appearing calcifications History of previous irradiation to the breast region Pregnancy Persistent positive margins

33 Contraindications to breast conservation therapy Relative History of collagen vascular disease Multiple gross tumors in the same quadrant and indeterminate calcifications Large tumor in a small breast Breast size Winchester et al, Ca Cancer J Clin, 1998

34 Contraindications to breast conservation therapy The following should not prevent patients from being candidates for BCT: Presence of clinical or pathologic involvement of axillary lymph nodes Tumor location Family history

35 Therapy of Regional Nodes Axillary Node Dissection Sentinel Lymph Node Biopsy

36 Axillary Node Dissection Typically Levels I and II lymph nodes removed 15 20% incidence of lymphedema

37 Sentinel node biopsy The sentinel node is the first node to receive lymphatic drainage from a primary breast cancer and reflects the status of the entire nodal basin Identifies the node(s) most likely to contain cancer Lessens the morbidity of lymph node staging (3 4% incidence of lymphedema) More detailed pathologic analysis with H&E Axillary node dissection for those with positive sentinel nodes

38 Sentinal Lymph Node Biopsy

39 Breast Cancer Treatment Considerations Breast Cancer Local Systemic Radiotherapy Surgery Hormone Therapy Chemotherapy Biological Therapy Breast Axilla

40 Neoadjuvant chemotherapy Chemotherapy given before surgery Shrink the tumor In Vivo assessment of response to chemo No survival advantage or disadvantage

41 Adjuvant therapy The administration of chemotherapy or radiation therapy after primary surgery of breast cancer to kill or inhibit clinically occult micrometastases or residual disease

42 Adjuvant therapy recommendation Tumor size ER status Nodal Status Recommendation <1 cm +/ None required >1 cm + Tam +/ Chemo Chemo Any size + + Tam +/ Chemo + Chemo

43 Chemotherapy Commonly used regimens Adriamycin (doxorubicin) and cyclophosphamide +/ taxane (AC+/ T) Taxane and carboplatin (TC) Cyclophosphamide, methotrexate and fluorouracil (CMF) Fluorouracil, Epirubicin and Cyclophosphamide (FEC) +/ Trastuzumab (Herceptin)

44 SERM Selective estrogen receptor modulators Tamoxifen For those with ER (estrogen receptor) positive breast cancer Prescribed for 5 years Antiestrogenic and estrogenic effects Side effects Hot flashes Vaginal dryness, discharge Increased risk of endometrial cancer Increased risk of thromboembolic events Cataracts

45 Aromatase inhibitors Blocks aromatase enzyme peripherally For those with ER positive disease Less side effects than tamoxifen May be more effective for treatment and prevention Arimidex Femara Exemestane

46 Herceptin (trastuzumab) Monoclonal antibody that targets the Her2 gene Her2 is overexpressed in 25% of breast cancers Codes for a growth factor Increases the effectiveness of chemotherapy without added toxicity

47

48 Early Stage Disease

49

50 Treatment planning

51 ER/PR+ HER2+

52 HER2 +

53 Triple Negative

54 Metastatic Disease Metastaticbreastcancerisincurable Treatmentispalliative Endocrine treatment: best effect in ER / PgR+ Chemotherapy in HR or HR+ and resistant or fast progressive disease (liver / lung mets) Median OS once chemotherapy is indicated: months HER2+: different options

55 Likelihood of response to chemotherapy by previous lines of treatment %

56 Goals of Therapy in Metastatic Breast Cancer Individual Goals Extend survival Improve/maintain quality of life Outcomes Response rate Response duration TTP TTF OS Quality of life

57 ER/PR+ Hormone Therapy Chemotherapy Metastatic Breast Cancer Her2+ Biological Therapy Chemotherapy Triple Negative Chemotherapy

58 Chemotherapy Options Antimetabolite Therapy Single Agent Therapy Anthracycline Taxanes Combination Therapy Microtubule Inhibitors

59 Oncologist Radiotherapist Nursing staff Surgeon Patient Palliative Care team GP Physiotherapist and Occupational Therapist Social Worker Dietician

60 Summary Breast cancer is a common female cancer with significant health burden Stage of disease determines outcome Treatment is multidisciplinary with local and systemic considerations

KEY MESSAGES. Of the cases diagnosed in 2003, 33.6% were women between 40 and 49 years of age.

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