Breast Cancer

Question 1

Risk factors

Answer 1

1 in 8 women
Increasing incidence and decreasing mortality

Female gender
Age
Older age at first birth
Oestrogen
EtOH
Family history

Question 2

Genetics

Answer 2

5-10% of breast cancer is gene related

Family history:

• Multiple relative and breast and ovarian cancers
• Early age of onset
• > 1 primary cancer
• Rare malignancies
• Ovarian cancer <70yrs

BRCA1 and BRCA2, MSH2, MLH1, PTEN, p53, ATM

Question 3

BRCA 1

Answer 3

DNA repair gene
AD

Breast cancer 60%
Ovarian cancer 40%
Pancreatic cancer 5-10%

Question 4

BRCA 2

Answer 4

DNA repair gene
AD

Breast cancer 60%
Male breast cancer 5-10%
Ovarian cancer 20%
Prostate cancer 40%
Pancreatic cancer 10-15%

Question 5

p53

Answer 5

Li-Fraumeni syndrome

> 90% risk of breast cancer
Rare cancers - sarcomas and osteosarcoma, brain, adrenal, leukaemia, colon

Question 6

PTEN

Answer 6

Cowden syndrome

Breast cancer 25-50%
Thyroid, endometrial and GU cancers

Question 7

Management of women with high risk genes

Answer 7

Prophylactic surgery

• Mastectomy
• BSO

Yrly Mammogram or MRI from 40yrs
Tamoxifen or raloxifene
Anastrozole

Question 8

Diagnosis

Answer 8

triple testing:

• Clinical exam
• Imaging
• Biopsy

Question 9

Poor prognostic factors

Answer 9

Positive axillary lymph nodes!!!

Increasing size
Higher grade
Negative hormones
Positive HER2
Younger age
Lymphovascular invasion

Question 10

Treatment of early stage breast cancer

Answer 10

LWE or mastectomy and sentinel node biopsy

If sentinel node positive –> axillary dissection

Adjuvant Radiotherapy if LWE or large primary with mastectomy

Adjuvant chemotherapy if high risk cancer

Adjuvant endocrine therapy for 5yrs +

Question 11

Adjuvant chemotherapy

Answer 11

Anthracycline and taxane based
Doxyrubicine and paclitaxel

Anthracyclines = cardiac toxicity and secondary leukaemias

Question 12

SERMs

Answer 12

Selective oestrogen receptor modulators
= Tamoxifen

Premenopausal women with hormone receptor positive cancer

Antagonist on oestrogen receptor on breast tissue
Agonist on bone, uterus and liver –> increases BMD

Risk of VTE and uterine cancer

Question 13

Aromatase inhibitors

Answer 13

Block DHEA
= Anastrozole, letrozole, exemestane

Post menopausal women
Slightly more effective than tamoxifen

Decreases BMD
Arthralgias common

Question 14

HER2 positive cancers

Answer 14

HER2+ = chemotherapy and trastuzumab for all cancers

Trastuzumab = monoclonal Ab against HER2 receptor

12 months of therapy

Causes reversible cardiomyopathy

Question 15

Treatment for locally advanced disease

Answer 15

Neoadjuvant chemotherapy to downstage

• -> surgery
• -> chemoradiotherapy
• -> endocrine therapy

Question 16

Treatment of Metastatic disease

Answer 16

Endocrine therapy if hormone positive

Chemotherapy

Question 17

Use of mTOR inhibitors

Answer 17

Overcomes endocrine resistance

Combine with exemestane

Question 18

Metastatic HER2 positive cancers

Answer 18

Trastuzumab +pertuzumab + chemotherapy

CNS mets = lapatinib

Question 19

Metastatic BRCA cancers

Answer 19

PARP inhibitors

Prevents repair of single stranded DNA breaks –> apoptosis

Olaparib
Veliparib

Question 20

Is chemotherapy safe during pregnancy?

Answer 20

Anthracycline (doxorubicin) and taxane based chemo safe in 2nd & 3rd trimesters

Question 21

Side effect of trastuzumab?

Answer 21

Reversible cardiomyopathy

Question 22

Treatment for trastuzumab induced cardiomyopathy?

Answer 22

Withhold if LVEF <45%
Give ACE-I for cardiac failure

Can resume treatment if LVEF normalises

Question 23

Greatest risk of infertily after chemotherapy?

Answer 23

Age>40yrs