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?