genetics of breast cancer - university of leicester · pdf filegenetics of breast cancer ......

GENETICS OF BREAST CANCER

Dr. Joyce Solomons Clinical Genetics

Breast cancer diagnosis in UK, 2010

NUMBERS 1

(ONS, 2012)

Age specific Incidence Rates, females, UK, 2008-2010

NUMBERS 2

(ONS, 2012)

NUMBERS 3

(ONS, 2012)

All Breast Cancers Family History

High penetrance gene mutations BRCA1,BRCA2, TP53

Hereditary cancers account for only a small proportion of all cancer

Familial Breast Cancer: Collaborative reanalysis. The Lancet 358, 1389-1399 (2001)

Features suggestive of a dominantly inherited cancer susceptibility syndrome

• Several close (1st or 2nd) degree relatives with a common cancer

• Several close relatives with related cancers. e.g. breast + ovary

• An unusually early age of onset

• Bilateral tumours in paired organs

• Synchronous or successive (metachronous) tumours

• Tumours in more than one organ system in one individual e.g. Breast+ovary

• Specific histopathology or receptor status of tumours

• Younger age of onset • Implications for unaffected family members

• Increased risk of a second primary breast cancer

• Increased risk of developing other related

cancers (ovarian cancer 20-40%, prostate cancer:7-14%)

Breast cancer due to dominantly inherited cancer susceptibility syndrome (2)

Promoting genes PROTO-ONCOGENES/ ONCOGENES

Suppressing genes TUMOUR SUPPRESSOR GENES/ CARETAKER, GATE-KEEPER GENES

CELL GROWTH

CELL DEATH/ SENESCENCE

BIOLOGY OF CANCER

Many Mutations Lead to Cancer

Malignant Cells

Normal Cell

First Mutation

Second Mutation

Third Mutation

Fourth or Later

Mutation

BRCA1 Breast, Ovary, Prostate BRCA2

Breast, Ovary, Male breast, Pancreas, Melanoma, Stomach

TP53 (Li Fraumeni Syndrome) Breast, Brain, Sarcoma, Leukaemia, Adrenocortical

PTEN (Cowden Syndrome) Breast, Thyroid, Endometrial, Renal, Benign mucocutaneous, Lipomas, Fibromas

INHERITED BREAST CANCER ASSOCIATED SYNDROMES

LBK1 /STK11 (Peutz- Jeghers Syndrome) GI, Bowel, Pancreas, Breast, Uterus, Cervix, Ovary, Testis, Lung

NF1 (Neurofibromatosis type1) Breast, Endocrine, Optic glioma, CNS, MPNST, Neurofibromata

GP

Surgeon

Oncology

Breast only FH

Complex/Ovarian

? BRCA mutation carrier &/or requesting further surgery

? BRCA mutation carrier

Test

Cascade

Test

Reassure

Glenfield Offer Mamm

Genetics Offer Gene test

Advice

Recommend Mamm+/-OCS

HR

LR

Genetics

M&HR

Cascade

Glenfield

1. Patient request 2. Three breast cancers at any age/ one breast cancer less than 35 3. Ovarian cancer & family history of breast and/or ovarian cancer 4. Bowel cancer less than 50, especially if associated with polyps and/or

a family history of gastrointestinal, gynaecological, urological or dermatological tumours.

5. Three bowel cancers at any age 6. Retinoblastoma 7. Three or more separate primary tumours 8. Sarcoma with a family history of sarcoma, breast, brain or adreno-

cortical tumours. 9. Three cases of lymphoma, leukaemia, prostate, renal or stomach

cancer in biologically related individuals. 10. Known inherited gene mutation in family

UHL-Clinical Genetics Referral guidelines

0116 258 5736

Julian Barwell, Joyce Solomons, Vanita Jivanji, Catherine Hartigan, Demetra Georgiou, Penny Van Besouw

And Beckie Speak

THANK YOU!