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
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…
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%
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