Breast cancer Flashcards
Anatomy
Can be divided into two regions:
- Circular body
- Axillary tail - runs into axillary fossa
Can also be divided structurally:
- Mammary glands - consists of the functional apparatus of the breast in branched structure:
= Lactiferous ducts - one per lobe, exiting at the nipple
= Lobes - 15-20 per breast, each containing 20-40
= TDLUs: terminal duct lobular unit. Functional and histological unit of the breast. Made up of glandular tissue producing milk.
- Stroma: fibrous connective tissue, supports the structure of the breast and forms the suspensory ligaments of Cooper. Each lobule is demarcated by Cooper ligament.
Drainage system:
- Lobule
- Terminal duct
- Collecting duct
- Taking milk to the nipple
Where do most cancers and benign lesions occur
TDLU
Lobules and ducts layers
Lined by an epithelium consisting of two layers:
- Inner luminal epithelial cells
- Outer myoepthithelial cells
Where do most cancers occur
upper outer quadrant
Lymph node drainage
75% = axillary lymph nodes
20% = parasternal nodes
5% = posterior and intercostal nodes
What is the first lymph node to which the cancer cells are most likely to spread to?
The sentinel lymph node is the axillary lymph node due to its proximity to the breast = has implications with regards to staging and management
Epidemiology
General risk factors
- Increasing age
- Female: 99% of cases occur in females and is the biggest risk factor for developing breast cancer
- Previous history of breast cancer
- Family history
- Proliferative lesions: atypical hyperplasia
- Alcohol
- Smoking
- Post menopausal weight gain. Aromotase in fat cells helps convert testosterone into oestrogen
Genetic risk factors
BRCA1/BRCA2:
- tumour suppressor gene involved in DNA repair
Increased risk of breast and ovarian cancer
- MC cause of hereditary breast cancer
- Male breast cancer associated with BRCA2
Li-Fraumeni syndrome: autosomal dominant p53 mutation
- Breast, brain, adrenal, leukaemia/lymphoma, osteosarcoma
- Radiosensitive - will be treated often with chemotherapy
Peutz-Jeghers syndrome
- Benign intestinal hamartomas and malignancies involving GI tract, breast, pancreas, and GU tract
Klinefelter syndrome: 47 XXY
- Increased risk of breast cancer in men
Hormonal
Increased oestrogen exposure
- Endogenous
= Obesity
= Early menarche
= Late menopause
= Late pregnancy/ nulliparity
= Breastfeeding and multiparity are protective
- Exogenous oestrogen
= HRT
= Oral contraceptive use
Pathophysiology
- Complex series of genetic mutations and deranged cellular signalling leads to generation of malignant cells.
- Breast cancer can be linked to inherited genetic mutation such as BRCA-1
- Malignant cells metastasise though a 5 step process:
1. Invasion through basement membrane
2. Intravasation (entry into circulation)
3. Circulation
4. Extravasation
5. Colonisation
Most common mets are: Bone, brain, liver and lungs
Signs
Palpable mass
- Firm and non-tender
- Poorly defined
- Located in the upper outer quadrant most commonly
Nipple discharge
Nipple retraction
Skin changes: peau d’orange
- Tethering: mass fixes to surrounding structures, e.g. fascia, pectoral muscle, or Cooper ligaments
Evidence of metastasis:
- weight loss
- bony pain
- shortness of breath
Symptoms
Painless lump
- Breast
- Axilla
Skin changes
- Discolouration
- Erythema, swelling from oedema presenting as Peau d’orange are suggestive of inflammatory carcinoma
Nipple changes:
- Inversion
- Bloody discharge
- Eczema
2 week wait criteria
- 30+ and have an unexplained breast lump with or without pain
- 50+ and over with any of the following symptoms in one nipple only:
= Discharge
= Retraction
= Other changes of concern
Considerations for 2 week wait
- Skin changes that suggest breast cancer
- 30+ with an unexplained lump in the axilla
A non-urgent referral
<30 with an unexplained breast lump with or without pain
Diagnosis
Triple Assessment:
- Clinical score 1-5 (history and examination)
- Imagining score 1-5
- Biopsy score 1-5
Imaging
= Mammography: varied appearance but include an irregular SPICULATED mass, clustered microcalcifications and linear branching calcification
= Ultrasound: adjunct to mammography esp in younger patients (< 40 years old) with denser breasts. Features include a hypoechoic irregular mass, architectural distortion, and calcification
Types of biopsy
Core biopsy
Fine needle aspiration
Staging
TNM Staging
T0 - No evidence primary
T1 < 2cm
T2 2-5cm
T3 > 5cm
T4 - Extends to chest wall or skin or inflammatory
N0 - No nodes
N1 - Mobile nodes
N2 - Fixed/matted nodes
N3 - Internal mammary nodes
M0 - No mets
M1 - Mets
Management
FIRST LINE: Surgical therapy:
- Breast-conserving: wide-local excision is indicated in localised smaller tumours
Mastectomy:
- Total mastectomy
- Skin-sparing
- Nipple-sparing
- Radical mastectomy
- Modified radical mastectomy
Axillary surgery:
- Sentinal lymph node biopsy: Px with no detectable axillary lymphadenopathy preoperativly = sentinel node identified (first node the breast cancer will metastasise to).
- Axillary lymph node dissection: Px with known axillary lymphadenopathy = multiple axillary lymph nodes are removed
Indications for breast conserving therapy
- Localised
- Small tumour size:breast ratio
Indications for mastectomy
- Multifocal
- Large tumour size:breast ratio
- Breast-conserving surgery tissue removed has positive margins
- Significant skin involvement
- BRCA genetics - with high incidence of reoccurance
- Previous lumpectomy + radiotherapy. Cannot irradiate the same place twice
- DCIS > 40mm
Adjuvent management to breast conserving surgery
Radiotherapy
- Indicated in those who have had breast-conserving surgery
- Considered in those who have had mastectomy if there are multiple lymph nodes positive, large tumours and/or positive margins.
Hormone therapy
- If tumour is invasive, systemic third line therapy indicated:
- Indicated if the patient is ER-positive and continued for 5-10 years
- Premenopausal: majority of oestrogen produced by ovaries
= Selective oestrogen receptor modulators: e.g. tamoxifen and toremifene
= Ovarian suppression: GnRH analogues like goserelin can also be used - Postmenopausal:
= Aromatase inhibitor (prevents peripheral oestrogen synthesis): ANASTROZOLE/ LETROZOLE
Biological therapy
Indicated if Human epidermal growth factor receptor 2 (HER2) positive
- Trastuzumab: also known as Herceptin, blocks HER2
- Chemo therapy given as adjuvant therapy
Chemotherapy
- Can be adjuvant or neoadjuvant:
= TAXANE + ANTHRACYCLINE
= taxane e.g.: paclitaxel, docetaxel
= ACT e.g: doxorubicin, cyclophosphamide - Chemotherapy should be considered in the following:
= Triple-negative disease
= Early-stage disease and high risk of recurrence e.g. triple-negative or HER2 positive
=Lymph node positive disease
= Advanced disease
Complications
Cancer-related
- Metastasis: bone, liver, lung, brain
- Malignant pleural effusion
- Recurrance
Treatment-related
- Surgery:
= cosmetic defect e.g. asymmetry
= seroma
= lymphoedema post-axillary node dissection
- Hormone and biologic therapy
= Tamoxifen: increased risk of endometrial cancer and VTE
= Herceptin: cardiotoxic/cardiac failure
= Aromatase inhibitor: osteoporosis - given bisphosphonates as adjuvant therapy
- Chemotherapy
= Neutropaenia
= Taxanes: peripheral neuropathy
