Reproductive Cancers Flashcards
What is a tumour?
Excessive, uncontrolled proliferation of cells as a result of an irreversible genetic change
How would you classify tumours?
Benign - tumours stay localised at their site of origin
Malignant - able to invade and move = cancer (the features of which are less differentiation, large pleopmorphic nuclei and fast growth).
What is primary tumours?
They arise at the site from cells normally present
What are secondary tumours?
Metastatic cancer (where it’s moved)
What are the steps of cancer cell development?
Mutation
Hyperplasia
Dysplasia
In situ cancer (confined to a local area)
Invasive cancer
What causes cancer to develop?
- A mutation causes proliferation of cells and a mutation inactivates DNA repair gene
- Loss of tumour suppressor gene function and gain of oncogene function
Steps towards breast cancer?
Normal breast epithelium
Atypical breast hyperplasia
Ductal carcinoma in situ (genetic alterations happen here)
Invasive ductul carcinoma
Metastatic disease
What are some genetic aberrations?
Duplication
inversion
Deletion
Insertion
Translocation
What is some epigenetic things? E.g their shape/structure etc
DNA Methylation packed into Histone code and nucleosomes
What are oncogenes?
Mutations in certain genes promote uncontrolled cell division.
What are the normal versions of oncogenes called
Proto-oncogenes
What are mutated oncogenes called?
Oncogenes
What type of mutations will turn a proto-oncogene into an oncogene?
Activating mutations and you only need one of these
What does activating a proto-oncogene mutation do?
Allows cells to bypass the need for extracellular growth signals
What does the oncogene mutations do to the proteins?
can make it hyperactive or be in an abnormal quantity, at the wrong time or in the wrong cell type.
What are tumour supressor genes?
P53 which pauses the cell cycle to help with DNA repair.
What type of mutational effect does mutants of P53 have?
Dominant negative
What things drive cancer?
Proliferation,
Angiogenesis,
Apoptosis turns of
Tissue invasion
Inflammatory supressors.
How does cancer mestasis?
A mutation in a cell grows into a primary tumour which vascularises. This then detaches and a cell intravasation occurs. This goes through blood until it extravasation, invades more cells and causes secondary tumours which also vascularise.
What are the different routes of invasion?
Local invasion
Lymphatic spread
Blood spread
Transcoelomic
Why isn’t mestatic cancer curable?
There is lots of different mutated genes (they need to be treated in different ways)
Survival and incidence of breast cancer?
Incidence is increasing as screening is better
Survival is increasing as screening is better and treatment is better
What are some risk factors to breast cancers?
Age (over 50)
Positive family history
Earlier menarche (less than 12)
Later menopause
Older first pregnancy
OC use
HRT
Endogenous estrogen exposure
Increased breast density
Radiation exposure
Obesity
Alcohol
What is BRCA?
Tumour supressor genes which commonly mutate in breast cancer (either BRCA1 or 2)
Symptoms of breast cancer?
New lump of thickening in breast or axilla
Altered shape, size or feel of breast, pain.
Skin changes - puckering, dimpling, skin oedema, rash, redness, feels different
Nipple changes - tethering/inversion, discharge, eczema- like changes in paget disease
Rarely widespread inflammtion, redness, pain in inflammatory cancer can stimulate infection
How do they diagnose breast cancer?
If you go to the doctors with a lump they send you to the breast clinic who do an exam, history, imaging (an ultrasound in younger people), pathology (biopsy)
What are the different grades of cancer and what does that mean?
Grade 1 - a well-differentiated tumour
Grade 2 - a moderately differentiated tumour
Grade 3 - poorly differentiated
Immunohistochemistry - breast cancer
What is the allred score?
They check for ER, PR, and HER2
If you see ER - the breast cancer uses oestrogen to fule it.
Can breast cancers signal to surrounding fat cells to secrete the oestrogen it needs to grow?
Yes
How does oestrogen cause breast cancer?
Oestrogen binds to ER which dimerizes and bind to the genome at promotor regions (ERE) this drives growth of the cell
What are some endocrine treatment of breast cancer
Selective Estrogen Receptor Modulators (SERMS) - tamoxifen
Aromatase Inhibitors (AI) - letrozole and anastrozole and Exemestane
What is HER2 positive breast cancer?
HER2 gene is amplified but the protein is normal although there is now lots of them which will turn on cell cycle through down stream signalling.
How do you test for HER2?
Immunohistochemistry (you wouold do antibodies or FISH)
What is the treatment for HER2 breast cancer?
Trastuzumab (herceptin) and Pertuzumab are monoclonal antibodies
What are stages in breast cancer diagnosis?
How spread the cancer is e.g. stage 1 and stage 4
What are breast cancer treatment options?
Surgery - cut lump out or remove breasts
Radiotherapy
Chemotherapy
Immunotherapy
Targeted therapy
Hormone therapy
Incidence of Cervical cancer
Most common malignancy in women worldwide and normally between 34 - 44 years old.
The PAP smear has reduced incidence and mortality
What is the aetiology of cervical cancer?
Persistant infection with HPV which is spread through skin to skin sexual contact
What can HPV form on the skin?
Warts
What is our main preventative treatment of cervical cancer?
The HPV vaccine
What is the normal pathophysiology of cervical cancer?
The two main oncoproteins involved in HPV are E6 and E7 and the tumour supressor p53 is inactivated by E6.
E7 competes with pRb protein releasing transcription factor E2F which pushes infections through the cell cycle
Risk factors for cervical cancer?
Age 45 - 49
HPV infection
Multiple Sexual Partners
Non-barrier contraception
Early onset of sexual activity (less than 18),
Immunosuppression - HIV and transplant patients
Smoking - reduces viral clearance
What is the presentation of cervical cancer?
Cervical Smear
Post-coital bleeding
Abnormal vaginal bleeding
Weight loss
Ureteric obstruction
Bowel disturbance
What are the investigations of cervical cancer?
- Vaginal and bi-manual examination
- HPV testing
- Colposcopy (irregular cervical surface, abnormal vessels)
- Punch biopsy or diagnostic loop biopsy
Depends on stage and age
How do you manage cervical cancer?
Surgery,
Radiotherapy
Chemotherapy
Immunotherapy
What is the pap smear - how is it done?
Method of cervical screening used to detect potentially precancerous and cancerous processes in the cervix
What are the cytology markers of cervical cancer?
Increased nuclear to cytoplasmic ration
Abnormally shaped/dense nuclei
Inflammation
Infection
Mitosis
What is colposcopy?
Magnified visualisation of the transformation zone after application of 5% acetic acid
Cervical Cancer
What would you do if the colposcopy was abnormal?
Do a punch biopsy
What is the histology of cervical cancer?
Cervical intra-epithelial neoplasia (CIN)
You can get CIN 1 - 3 and this tells you how it should be treated.
This is based on the CIN number
How do you manage cervical cancer?
Large loop excision of transformation zone (LLETZ)
CIN1 will spontaneously regress so conservative management and a LLETZ is persistant
CIN3 = LLETZ followed up at 6 months with cytology and HPV test
Is a LLETZ safe and can it be done under local?
Yes
What are complications of a LLETZ?
Heamorrhage, infection, cervical stenosis, cervical incompetence
What is the incidence of ovarian cancer?
Increased incidence with increasing age
Ovarian cancer - the silent killer?
Over 60% of advanced disease at initial presentation however many women have abdominal issues years before diagnosis
What is Epithelial ovarian cancer?
Common type of ovarian cnacer which is derived from serosal surface of ovary, arise from single layer of cells that cover the ovary or lines cysts. Increasing evidence of tubal origin in high grade perous tumours
What are the 2 types of ovarian cancer?
High grade serous - resembles fallopian tube mucosa or p53 mutations
Arise from ovarian surface epithelium and mullerian inclusion cysts - endometriod, clear cell, mucinous, low grade serous
How does ovarian cancer spread?
Direct extension (transcoelemic)
Exfoliation into the peritoneal cavity
Lymphatic invasion
Risk factors of ovarian cancer?
Smoking
Low parity
One child is protective
Oral contraceptives
Infertility (but independant on drugs)
Tubal ligation
Early menarche
Late menopause
Do we screen for ovarian cancer?
No as the two trials are showing no evidence to support screening (even in high risk women)
What is the presentation of ovarian cancer?
Symptoms are vague and non-specific
Altered bowel habit
Abdominal pain/bloating
Difficulty eating
Feeling full quick
Urinary/pelvic symptoms
Bowel obstruction
SOB
How do you investigate ovarian cancer?
Ultrasounds
Look into CA125 (glycoprotein elevated in malignancies, and benign things such as menstruation).
CT - used to determine initial treatment and response to treatment
Treatment for ovarian cancer?
Not usually curative
Surgery - major role, primary debulking surgery, delayed primary surgery
Chemotherapy - Neo-adjuvant, adjuvant
Radiotherapy
