Breast cancer Flashcards
Incidence of breast cancer
1 in 9 women will develop breast cancer during their lifetime
Risk factors for breast cancer x10
Gender Increasing age Nulliparity- late age at first baby Early menarche, late menopause Oral contraception/HRT Greater height/weight (obesity) Ionising radiation Carcinogen exposure Family hx Alcohol
Peak age for male breast cancer
71 years
Relationship of male breast cancer and gynaecomastia
No increased risk of MBC with gynaecomastia once treated by radiotherapy
Relationship of breast cancer risk to steroid hormones
Longer the duration that the breast epithelium is exposed to steroid hormones - especially in cyclical form - greater risk of malignancy
Risk factors for male breast cancer x4
Work in hot environment (testicular failure)
Males taking oestrogens (transsexuals and prostate carcinoma)
Undescended testis
Mumps >20 years
Genetics and male breast cancer
Almost all male breast cancer of genetic origin is due to BRCA2 mutations
Association of Klinefelters syndrome and breast cancer
Risk of breast cancer is similar to that in females
What is a new risk factor for breast cancer
Higher levels of serum gamma-glutamyl transferase (GGT) in premenopausal women
Serum GGT may be a marker of prior exposure to carcinogens
Protective factors against breast cancer x5
Pregnancy
Oophorectomy (before age of 50)
Lactation
Late menarche and early menopause
Relationship of oral contraception and breast cancer risk
Risk is increased when on oral contraception but decreases when you stop it
Relationship of smoking and breast cancer risk
Smoking has anti-oestrogenic effects therefore induction of earlier menopause, but does not protect against breast cancer - could be because of increase in more aggressive ER- lesions
Role of alcohol and breast cancer
Alcohol increases oestrogens
Relationship of diet and breast cancer
Significant relationship between national mortality rates from breast cancer and fat consumption
Risk of breast cancer and ovarian cancer with BRCA2
50-85% breast cancer
10-30% ovarian cancer
Where are breast cancers derived from?
The epithelial cells that are found within the terminal duct lobular unit - TDLU
Difference between non-invasive (DCIS) and invasive
non-invasive are within the basement membrane of the duct unit whereas invasive has dissemination of cancer cells outside of the basement membrane into adjacent normal tissue
What is the grade of a breast cancer?
It is a characteristic of the tumour which does not change with time - eg. a low grade well-differentiated DCIS evolves slowly into a well-differentiated grade 1 invasive cancer
High grade into high grade
What is the stage of a breast cancer?
Duration of breast cancer and may reflect delay
eg. DCIS stage can develop into a cancer
What do the majority of ER- positive cancers express?
Progesterone receptors therefore also have greatest probability of responding to hormone therapy
Other gene which is associated with increased risk of breast cancer
TP53 gene - also assocaited with other malignancies and Li Fraumeni syndrome (soft tissue/osteosarcoma - early onset breast cancer, glioma and childhood adrenal cancer)
Investigation of breast cancer
2 view mammography, whole breast ultrasound, image-guided core biopsy and if invasive cancer then axillary ultrasound with FNA or core biopsy of suspicious lymph nodes - sentinel node biopsy
What contributes to the grading of a cancer?
Degrees of glandular formation, nuclear pleomorphism and frequency of mitoses - Nottingham modification
What % of breast cancers express significant amounts of oestrogen receptor
75%
What % of breast cancers are HER2 (human epidermal growth factor receptors) positive
15-20%
Relationship of ER and HER2 positive cancers
Most ER positive cancers are HER2 negative
What are triple negative breast cancers
HER2, ER and PR negative - more common in BRCA1 carriers
1/2 respond well to chemotherapy, but some are chemo resistant
How can breast cancer present? x10
Breast lump Nipple discharge Inversion of the nipple Skin dimpling/deformity Mammographic abnormality Lump in axilla (secondary spread) Lymphoedema (secondary spread) Bone pain, weight loss (secondary spread) Paraneoplastic syndromes (secondary spread)
Grading of cancer diagnostically
1 - normal 2 - benign 3 - interderminate, probably benign 4 - suspicious of malignancy 5 - malignant
Extra classification of grading diagnostically
B5a - DCIS
B5b - Invasive
Features of pathological nipple discharge x4
Spontaneous
Unilateral
Blood stained
Single duct
Which breast cancers are treated with intention to cure?
All stages apart from stage 4 (distant mets)
Stage 1 breast cancer?
Small - T1 = less than 2cm
Treatment strategy for loco-regional invasive breast cancer
Surgery - breast conserving/wide excision + radiotherapy or mastectomy
Stage 3 breast cancer?
Locally advanced, T3 = larger than 5cm
Stage 4 breast cancer?
Distant mets - t4 any involvement of chest wall or skin
What are 2 relative contraindications to breast conserving surgery
Multifocal disease
Large operable cancer
When is breast reconstruction best?
Immediate - one procedure, better planning of incisions, can be modified and better cosmetic outcomes, also if delayed then post-radiotherapy chest wall makes surgery more difficult and probably causes more complications
Options for breast reconstruction x3
Implants (expandable = saline+silicone or solid = silicone)
Using own tissue, SC fat and muscle (lattismus dorsi and transvers rectus abdominus muscle)
Or combination of own tissue and implants
Treatment strategy for systemic invasive breast cancer
Chemotherapy
Endocrine treatment
Or targeted treatment
What are 2 absolute contraindications to breast conserving surgery
Diffuse disease or multicentric disease
What is Sentinel node biopsy?
First port of call for lymph from breast - can be identified with dye or isotope (technetium colloid)
In theory if sentinel is okay then axilla will be negative
Use of chemotherapy in breast cancer
Can be given as primary systemic therapy prior to surgery to downstage tumour - neoadjuvant chemotherapy - can enable breast conservation
Also adjuvant therapy following surgery
What are the benefits of axillary clearance?
Gives very important prognostic information - can also have a therapeutic effect as inadequate axillary treatment can lead to increased loco-regional relapse and increased breast cancer mortality
What is now routine chemotherapy?
Athracycline (…rubicin) containing regimes
FAC (5-fluorouracil , doxorubicin, cyclophosphamide)
FEC (5-fluorouracil, epirubicin and cyclophosphamide)
Options other than axillary clearance x3
Doing nothing
Axillary sampling (hit and miss)
Axillary irradiation - more morbidity and lack of prognostic information
Adjuvant treatment for HER2 positive cancers
Herceptin/Trastuzumab - monoclonal antibody that intereferes with the HER2 receptor
What is the standard chemotherapy for breast cancer?
CMF - 6 cycles
Cyclophosphamide, methotrexate and 5-fluorouracil
What is tamoxifen
Selective oestrogen receptor modulator
Another possible drug for ER- positive breast cancers?
Aromatase inhibitors - block synthesis of oestrogen - only if post-menopausal eg. anastrozole, letrozole
Signs of breast cancer on mammography
Branching or lineal microcalcifications (calcifications very indicative of malignant disease)
Spiculated lesions
Bloods in breast cancer suspicion
FBC, U&E, Ca2+ (can get hypercalcaemia), bone profile, LFTs, tumour marker (CA-15-3)
Node staging of breast cancer
N1 - mobile ipsilateral axillary node
N2 - fixed ipsilateral axillary node
N3 - ipsilateral internal mammary node
Other hormonal therapy for BC
Ovarian ablation with LNRH-analogues eg. goserelin
Selective oestrogen down-regulators eg. fulvestrant and progestins
