A short overview of breast and ovarian cancers with a focus on the susceptibility genes (mainly BRCA) that predispose to them

1. Prepared by:
Rawa Muhsin

2. Basic Anatomy

3. Basic Classification
Non-Invasive Invasive

4. Breast Cancer Stages

5. Breast Cancer Metastasis

6. Symptoms of Breast Cancer
 Presence of a lump in the region
of the breast
 Change in breast shape or size
 Nipple discharge
 Nipple inversion and tenderness
lump

7. Symptoms of Ovarian Cancer
 Pain in the abdominopelvic regions or legs
 Swollen abdomen
 Tiredness
 Nausea, indigestion, constipation,
abdominal gas, diahrrea
 Less frequent symptoms are shortness of
breath, urgency to urinate and unusual
vaginal bleeding

8. Diagnosis
 Breast cancer can be diagnosed by:
CBE, mammography, ultrasound,
MRI, PET, biopsy, or blood tests (for
tumor markers)
 Ovarian cancer is diagnosed by:
Ultrasound, biopsy, blood tests (for
CA-125 antigens)
non-specific, only ~79% test positive
used to monitor ovarian cancer rather than for
diagnosis

9. Risk Factors
 Age – directly proportional
 Age at menarche – earlier age has
higher risk
 Personal history
 Multiparity, tubal ligation, ORC,
breastfeeding (for ovarian cancer)
 Family history

10. The Evil Genes
Susceptible
Gene
Associated
Syndrome
Mutation
frequency
Penetrance for
breast cancer
BRCA1 HBOC Rare Very high
BRCA2 HBOC Rare High
p53 Li-Fraumeni Very rare High
PTEN Cowden Very rare High
ATM Ataxia-telangiectasia
(heterozygotes)
Common Low to moderate
STK11 Peutz-Jeghers Very rare High
 Inherited mutations account for only 5-6% of all breast
cancer cases
 BRCA 1/2 mutations affect only about 0.1-0.8% of the
general population

11. BRCA 1/2 – Identity
BRCA = breast cancer, early onset
BRCA1 is located at 17q21
BRCA2 is located at 13q12.3

12. BRCA 1/2 – Normal Function
BRCA1
BRCA2
et al.

13. BRCA 1/2 – Mutated
BRCA1
BRCA2
et al.

14. Homologous Recombination
 In this pathway, the breaks are repaired
using the information on
 the intact sister chromatid (available in G2
after chromosome duplication), or on the
 homologous chromosome (in G1; that is,
before each chromosome has been
duplicated). This requires searching around
in the nucleus for the homolog
 same chromosome if there are duplicate
copies of the gene on the chromosome
oriented in opposite directions (head-to-
head or back-to-back).

15. BRCA 1/2 – Summary
 They encode proteins termed breast
cancer 1/2, susceptibility proteins
 They belong to a family of tumor
suppressors
 They repair double-stranded DNA breaks by
homologous recombination
 Inherited mutation represents the first hit of
Knudsen’s two-hit model
 If second allele develops a defect, stage is
set for cancer
 Hundreds of mutations have been
identified thus far

16. Genetic Testing
 Genetic testing for BRCA 1/2 for several
known rearrangments can cost over 3000$!
 The “founder effect” has an important role
in choosing rearrangments for screening:
Three mutations are common among the
Ashkenazi Jews
 Testing can be helpful for:
Reassurance of your genetic status and
informing close relatives
Considering medical management
Family planning: to have children or not to have
children?! Now that is the question…

17. Genetic Testing – Who should do
it?

18. Treatment
 Surveillance:
 Monthly BSE (breast self-examination)
 2-4 CBE (clinical breast examination) / year
 Annual mammography + MRI
 Ultrasound and CA-125 Antigen (for ovarian
cancer)
 Prophylactic Surgery:
 Mastectomy: lumpectomy, simple, or radical
– decreases breast cancer risk by 90%
 Oophorectomy: decreases ovarian cancer
risk by 96% and breast cancer risk by 50%

19. Mammographs
malignant mass puckers the
overlying skin as it invades
stellate invasive DC with
microcalcifications

20. Treatment - Mastectomy

21. Treatment - Chemoprevention
 If the cancerous cells
have estrogen
receptors (called ER+),
treatment with
estrogen antagonists
might reduce risk by
38%
 An official drug is
tamoxifen
 Drugs can be
administered IV, IP, or
orally A: Estrogen Receptor
B: Estrogen
C: Estrogen Helper Proteins

22. Treatment - Radiotherapy
 Mostly used after surgery to remove any
remaining tumor cells
 Can be used before surgery to make the
tumor shrink
 Side effects:
 skin reddening
 tiredness
 nausea

23. Future Treatment Possibility–
Synthetic Lethal Screening

24. Breast Cancer in Iraq

25. Breast Cancer Prevalence in Iraq

26. Thank you for your
attendance and listening.