Robert Blum Medical Oncologist Bendigo Health Care Group 1:8 if - PowerPoint PPT Presentation

Robert Blum Medical Oncologist Bendigo Health Care Group

 1:8 if live to age of 85  1: 25 will die from breast cancer  Increasing incidence (5303 in 1982  14181 in 2010)  Overall survival: 75% at 5 – years  Very early stage breast cancer, survival rate > 90%  Most recurrence occur in the first couple of years  Less common after 5 years

 Increasing Age  Birth to age 39 – 0.49 (1 in 203 women)  ● Age 40 to 59 – 3.76 (1 in 27 women)  ● Age 60 to 69 – 3.53 (1 in 28 women)  ● Age 70 and older – 6.58 (1 in 15 women)  ● Birth to death – 12.29 (1 in 8 women)

 FRA BOC- website Cancer Australia  Mother with breast cancer > 60 risk <1.5  Mother with breast cancer <40 risk 1.5-3 times  Mother with breast cancer < 40 and sister with breast cancer 50-60 >3.0 times  Known BRCA 1 65% for breast and 60% for ovarian  Known BRCA2 45% for breast and 16.5% for ovarian

 Based on some large cohort studies  Women’s Health Initiative  16608 women between 50-79  Conjugated HRT versus none  Increased risk of breast cancer 2.5%  8 excess per 10,000  Median treatment 8.5 years  Also the Million Women Study : combined RR 2.0 (1.88-2.12) vs oestrogen alone 1.3 ( 1.21-1.4)

Older age at first child birth  Nulliparity  Radiation Age 11- 14 approximately 20% risk  Biopsy proven benign proliferative disease with atypia  Early puberty  Late menopause 

 BMI: >25mg/m2 20-40% higher risk  Smoking : ND  Drinking (7% per standard drink per day)  Fat: ND  Red Meat: ND  Vitamin D replacement: ND  Lack of Exercise: ND 25% reduction in breast cancer incidence ? Oestrogen production, IGF, Insulin levels ?

 Current recommendations are 50-74 years of age  May continue beyond if likely to live 10 years  Reduces breast cancer mortality by approximately 20%

“ for every 10 000 UK women aged 50 years invited to screening for the next 20 years, 43 deaths from breast cancer would be prevented and 129 cases of breast cancer, invasive and non- invasive, would be overdiagnosed; that is one breast cancer death prevented for about every three overdiagnosed cases identifi ed and treated. Of the roughly 307 000 women aged 50 – 52 years who are invited to begin screening every year, just over 1% would have anoverdiagnosed cancer in the next 20 years

 BRCA1 or BRCA2 mutation carriers  ● Untested women who have a first-degree relative with a BRCA1 or BRCA2 mutation  ● Lifetime risk of breast cancer of 20 to 25 percent or more, defined by models that are largely dependent on family history (eg, BRCAPRO and others) (see "Risk prediction models for breast cancer screening")  ● Received radiation treatment to the chest between ages 10 and 30  ● Genetic mutation in the TP53 (Li-Fraumeni syndrome) or PTEN genes (Cowden syndrome)

 Screen detected  Mass in the breast  Mass in the axilla  Painful breast  Nipple discharge  Breast changes  Redness

 Mastitis in a non lactating women is rare  Red Flag  Both mammogram and US may be normal.  Proceed to biopsy

History  Physical Examination  Mammogram  Ultrasound of breasts and regional lymph nodes  ? MRI of breasts (optional)  Biopsy  CT Chest/Abdomen/Pelvis, as clinical indicated  Bone scan, as clinical indicated  Baseline blood tests 

 Tumour size  Grade  Hormonal status  Her-2/neu status  Nodal status  Lymphovascular invasion  Neurovascular invasion

 Base on genetic analysis of the breast cancer  Luminal A: ER+, PR+ Ki 67> 15% Her 2-  Luminal B: Low PR, Ki 67 > 15% Her 2+/-  Her 2 over expressed: Her 2+ ER-PR-  Triple negative: ER-, PR-, Her 2-

Lumpectomy   Small tumour  Agree to have post-op adjuvant radiotherapy Mastectomy   Had previous radiotherapy  Diffused or widespread disease  Tumour > 5cm  Existing connective tissue disease involving skin, ie: Lupus  Positive BRCA 1 or 2 Sentinel node biopsy   Clinically negative axillary involvement Axillary dissection   Patient with existing axillary disease, or positive sentinel node

 Adjuvant therapies:  Chemotherapy  Radiotherapy  Hormonal therapy:

Blocks oestrogen receptor  Reduced risk of recurrence by 47%  Reduced risk of death by 22%  Used in both pre-menopausal and post-menopausal women  Treatment for 5 years  Side-effects: menopausal symptoms, DVT, increased risk of  endometrial carcinoma Not to be used in conjunction with chemotherapy or  radiotherapy

 Anastrazole, Letrozole, Exemestane  Inhibit peripheral production of oestrogen  Only useful in post-menopausal women  ATAC study: suggests that in adjuvant setting, AI may be more effective than Tamoxifen  Side-effects: post-menopausal symptoms, arthralgia, accelerate osteopenia.

 Soft study: tamoxifen vs tamoxifen and ovarian suppression vs Aromasin and ovarian suppression in pre menopausal women  3066 women  5 year DFS 78% vs 82.5% vs 85.7%

 Randomized study of 3400 women in each arm  5 vs 10 years of tamoxifen  30% reduction in breast cancer mortality  937 deaths vs 722 deaths (217 women)  PEs 41 vs 21  Endometrial cancer 17 vs 11  IHD 127 vs 163

 Other options:  Taxanes:  Taxol  Taxotere  Nab-particle Paclitaxol  As single agent  Response rate about 30%  May be given weekly or 3 weekly  Require pre-medication with steroid, H1 and H2 antagonists due to high risk of anaphylactic reaction.

 For patients who have lumpectomy  DFS and OS comparable with mastectomy in women with node-negative early stage breast cancer  Recurrence rate reduced from 20% at 5-year to 2%  High risk cancers:  Mastectomy on tumour > 5cm  > 3 nodes involvement  NCIC-CTG MA.20:  Reduce locoregional recurrences: HR 0.59, P = 0.02  Increased DFS: HR 0.68, P = 0.003  Trend towards improved OS: HR 0.76, P = 0.07

 Reduce the risk of metastatic breast cancer  Greater impact on pre-menopausal women  Greater impact on biologically aggressive disease  Can be used to down stage disease

 NSABP B-31 and NCCTG N9831  Reduction in risk of recurrence: 48%, HR 0.52, P < 0.001  Reduction in risk of death: 39%, HR 0.61, P = 0.001

Pertuzumab + Trastuzumab (HER2 doble blockage)

 Pertuzumab is a monoclonal antibody that binds the extracellular domain of HER2 and prevents it from binding to itself or to other members of the EGFR family  Pertuzumab in combination with traztuzumab and docetaxel increases median survival to 56.6 months vs 40.8 for the group assigned traztuzumab and docetaxel alone

Trastuzumab Emtansine – Kadcyla Active trastuzumab/laptinib resistant metastatic disease

 T-MD1 vs Lapatinib and Xeloda  DFS 9.6 months vs 6.4 months  OS 30.9 months vs 25.1 months  Better tolerated

 Breast cancer has varying presentation  Think malignancy when considering mastitis in non lactating women  Breast cancer is not one disease  Treatments are being increasingly individualized

Any Questions?