Epithelial Breast Cancer Flashcards
Describe the anatomy of a breast.
These consist mainly of adipose, connective and epithelial tissues. The layer of adipose tissue protects a large number of lobules, connected by ducts that lead towards the nipple. There has to be a more scientific word for nipple.
The breast also contains a large number of lymph nodes to protect against infection.
Describe the blood supply to the breast.
The internal mammary artery and vein branch off from the axillary artery and vein which run above the breast. The largely overlapping blood vessels have two primary branches running down either side with smaller offshoot vessels in the direction of the centre.
What is the role of the lymphatic system?
Lymph ducts drain interstitial fluid that carries white blood cells from the breast tissues into lymph nodes.
Lymph nodes filter harmful bacteria and play a key role in fighting off infection.
All major nodes are tested for metastatic growth if cancer is suspected.
How is the breast affected by the endocrine system?
The breast is extensively affected by various hormones.
Oestrogens and progesterone from the ovaries,
Prolactin and GH from the pituitary
and corticosteroid, progestone and oestrogen (converted from androgen in transit by aromatase) from the adrenal gland.
This is highly relevant to the cancers of the breast as they often become dependent upon such signalling, especially oestrogen signalling.
Describe the epidemiology of breast cancer.
Breast cancer is the most common lethal neoplasm in women, accounting for 25-30% of all female cancer; 1 out of 7 women will have BC over their lifetime
The incidence of male breast cancer is about 1 % of all breast cancer cases and causes 0.1% of male cancer deaths per year.
What are the non-hereditary risk factors specific for breast cancer?
- Family history of breast cancer
- Being age 55 or older
- Previous breast cancer
Personal Estrogen-Related Risks Increased risks: • Early menstruation (before 12yrs old) • Oral contraceptives • Child bearing (no children or 1st child after 30 yrs old) • Late menopause (after 55yrs old) • Long-term HRT (more than 5 years)
Decreased risks:
• Breastfeeding - 12+ months – decreased risk
What are the hereditary risk factors for breast cancer?
• 5-10% of breast cancer is caused by inherited
genetic mutations
• 25% of Familial Breast Cancer (FBC) occurs in
women younger than 30 years old
• 2-5% of BC is caused by inherited mutations
in BRCA 1 and BRCA 2 genes
How is the progression of breast cancer classified?
With the TNM staging system;
The Tumour Diameter increase
Lymph node involvement
Metastasis to distant tissues (primarily bone, liver, lungs and brain).
Other than that they are classed by the classical stage 1 (confined to original site, node negative), stage 2 (node positive), stage three (spread to superficial structures of chest wall) and stage four (advanced metastasis)
What non-cancerous conditions are often mistaken for breast cancer?
Fibrocystic changes: Lumpiness, thickening and swelling, often associated with a woman’s period
Cysts: Fluid-filled lumps can range from very tiny to about the size of an egg
Fibroadenomas: A solid, round, rubbery lump that moves under skin when touched, occurring mainly in young women
Infections: The breast will likely be red, warm, tender and lumpy
Microcalcifications: Tiny deposits of calcium can appear anywhere in a breast and often show up on a mammogram
Trauma: a blow to the breast or a bruise can cause a lump
What is mammography?
Use of a low-dose x-ray system to examine breasts
Digital mammography replaces x-ray film by solid-state detectors that convert x-rays into electrical signals. These signals are used to produce images that can be displayed on a computer screen (similar to digital cameras)
Mammography can show changes in the breast up to two years before a physician can feel them
What mammography screening habits are recommended?
Biannually or annually in 40-49 y/o
Annually in >50 y/o
15% relative risk reduction
What are the three biopsy techniques?
Fine needle aspiration (FNA) - Diagnostic and therapeutic (cystic lesions)
Stereotactic needle biopsy (SNB) - an ultrasoundguided and mammogram-directed needle aspiration biopsy of breast tissue
Excision biopsy - an excision of a breast lump through a small cut. Usually no other breast tissue or lymph nodes (glands) are removed
How is oestrogen signalling received by breast epithelial cells?
Oestrogen is recognised by one of the two of oestrogen receptor - membrane (mostly GPCRs) and soluble nuclear receptor: as a steroid hormone it able to diffuse through the plasma membrane into the cell.
The nuclear receptors directly interact with the transcription machinery to facilitate many functions, including stimulating proliferation.
Describe the Erb-B receptor family?
These have multiple names each, but are closely related RTKs.
EGFR, HER1, ErbB1 binds a variety of growth factor ligands mostly og the EGF family, and notably is the only one to bind EGF itself. It is capable of homodimerising and heterodimerising with Her2.
ErbB2, HER2, neu has no known ligand binding activity. It serves only to heterodimerise with activated ErbB receptors to stimulate the signal.
ErbB3, HER3 has ligand binding activity, binding HRG, but no RTK activity, so relies on heterodimerisation with HER2.
ErbB4, HER4 binds various ligands, mostly of the neuregulin family, and can transduce its own signal.
Which ErbB receptor is the most commonly mutated in breast cancer?
ErbB2/HER2/neu, despite its lack of ligand binding capacity it is amplified in 20-30% of breast cancer. This event occurs at early-stage of breast cancer development and is associated with increased disease recurrence and worse prognosis.
This receptor regulates signalling pathways which control cell growth, proliferation and survival. Overexpression also correlates with oestrogen receptor null mutation.
As such it is targeted by trastuzumab, which prevents dimerisation and so activation.
