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WEEK 23:
Breast cancer development:
| Question | Answer |
|---|---|
| major blood supply sources | internal mammary and lateral thoracic artery |
| most lymph from breast drains where | axillary lymph nodes in the axilla |
| some lymphatic channels travel where | through rectus sheath and reach subperitoneal and subhepatic plexus which is clinically important because it means cancer can spread into abdomen/ liver region via these lymphs |
| what does it mean lymphatics are contralateral | lymph channels can travel and cross over to adjacent breast |
| milk line (mammary ridge) develops where | along trunk from axilla to groin in 5 week old fetus and then regresses to definitive site of adult nipple |
| when does the milk line (mammary ridge) develop | 5 week old fetus |
| remnants of ridge buds become | 15-20 solid epithelial column which canalises before birth to form lactiferous ducts |
| how are lactiferous ducts made | remnants of ridge buds become 15-20 solid epithelial column which canalises before birth |
| epithelial system becomes surrounded by what and becomes what | Epithelial system becomes surrounded by mesenchyme, which develops into connective tissue and fat |
| 6th week of gestation | remnant of mammary ridge proliferate to primary mammary bud |
| 7th week of gestation | bud grow downward a solid diverticulum into underlying dermis |
| 10th week of gestation | primary bud branches yielding secondary buds |
| 12th week of gestation | bud develops into mammary lobules |
| 20th weeks of gestation | canalisation of these buds with formation of lactiferous ducts |
| nipple appearance at birth and shortly after birth | at birth, rapidly arranged mammary lobes draining lactiferous ducts to ampullae empty to nipple and nipple appears like small pit in centre of thickened areola whereas after birth nipples becomes everted and areolar gets more pigmentation |
| stage I of tanner stages of breast development | no glandular tissues- areolar follows the skin contours of he chest |
| stage II of tanner stages of breast development | breast bud forms, with small area of surrounding glandular tissue (areola tissue begins to widen) |
| stage III of tanner stages of breast development | breast begins to become more elevated, and extends beyond border of areola which continues to widen by remains in contour with surrounding breast |
| stage IV of tanner stages of breast development | increased breast sizing and elevation; areola and papilla form secondary mound projecting from the contour of the surrounding breast |
| stage V of tanner stages of breast development | Breast reaches final adult size; areola returns to contour of the surrounding breast, with a projecting central papilla |
| terminal duct lobular units (TDLU) | basic structure units of breast and is the site of origin of most breast diseases including cancer |
| terminal duct lobular units (TDLU) composed of | small segment of terminal duct and a cluster of ductules/acini which are the effective secondary units and are surrounded by specialised connective tissue |
| effective secondary units of breast | cluster of ductules/ acini |
| site of origin of most breast diseases including cancer | terminal duct lobular units (TDLU) |
| breast duct consists of (3) | basement membrane, myoepithelial/ basal cell, and luminal epithelial cell |
| breast cancer is what type of cancer | heterogenous cancer |
| different histological types of breast cancer (5) | ductal, lobular, tubular, medullary, and metaplastic |
| different molecular markers for breast cancer | ER/PR/HER2 and luminal A/B, HER2 Enriched, and basal like |
| different grades of breast cancer (3) | grade 1,2,3 |
| breast cancer position can either be (2) | in situ or invasive |
| oestrogen during menstrual phase | oestradiol production increases by 8-10 fold |
| oestrogen in post menopause patients | oestrogen primarily synthesised by peripheral conversion of androstendione and testosterone and androgens produced by post menopausal ovaries and adrenal glands |
| aromatase | catalyses rate limiting and final step of oestrogen biosynthesis (aromisation of androgen to oestrogen) |
| oestrogen effect | causes breast ducts to grow |
| oestrogen peaks when in the cycle | mid cycle |
| progesterone peaks when in the cycle | later in cycle |
| progesterone effect | stimulates growth of breast lobules and alveoli (milk glands), with differentiative and proliferative roles in adult breast |
| how many cases of cancer are ER+ | 70% |
| PR is surrogate marker for what in breast cancer | PR is surrogate marker for ER activity in breast cancer (as expression of the PR gene is induced by estrogen-activated ER) |
| ER positive tumours can be (2) | PR+ or PR- |
| PR meaning | progesterone receptor |
| ER meaning | estrogen receptor |
| HER2 | membrane localised tyrosine kinase receptor encoded by erB2 gene |
| what happens when a mutation occurs in HER2 gene | causes EXCESS PRODUCTION of HER2 protein which signals cells to grow and divide rapidly |
| role of the mutated HER2 protein | signals cells to grow and divide rapidly |
| how many breast cancer cases are HER2 positive | 15-20% |
| prognosis of HER2 and breast cancer | poor prognosis |
| germline mutations | inherited from parents, occurs in every cells in body since birth and can be identified through genetic testing using blood samples eg BRCA1 and BRCA2 g |
| somatic mutations | not inherited from parents, occurs in some cells, identified by analysing tumour tissue directly and is due to aging/ exposure to sunlight/ smoking/ infections etc |
| difference in inheritance between germ line and somatic mutations | germ line is inherited from parents but somatic is not inherited from parents |
| difference in how germ line and somatic mutations occur in cells | germ line occurs in EVERY cell in body since birth but somatic mutations occur in only SOME cells |
| difference in how germ line and somatic mutations can be identified | germ line mutations can be identified through genetic testing using blood samples and somatic mutations can be identified by analysing tumour tissue directly |
| causes of somatic mutations | ageing, exposure to carcinogens, sunlight, smoking, and infections etc |
| example of germ line mutation | BRCA1 and BRCA2 |
| driver mutations | cause cells to become cancerous, are necessary for cells to show cancer like behaviour, give cells a growth and survival advantage over normal cells, and can occur in either proto-oncogenes or tumour suppressor genes |
| passenger mutations | irrelevant to tumour development, accumulate through DNA replication, provide no proliferative benefit, and can arise at any time in life history of any cell |
| BRCA1 causes how many cases of breast cancer | 55-72% |
| breast cancer stages (3) | early breast cancer, locally advanced, and advanced or metastatic |
| BRCA2 causes how many cases of breast cancer | 45-69% |
| early breast cancer (2) | is in situ or invasive |
| BRCA1 gene affects which chromosome | 17 |
| BRCA2 gene affects which chromosome | 13 |
| cancer initiation and progression | long and complex biological phenomenon caused by significant alterations in genome, proteome and chromatin or in any other cellular levels |
| driver mutations can lead to | structural and functional consequences and tumour heterogeneity and drug resistance rarely due to loss of ER expression but mainly due to ligand independent activate or ER |
| breast cancer treatment generally does what | target a gene or a protein with improved response with minimal side effects |
| what % of mutations in breast cancer are actionable | 10% |
| modifiable risk factors for breast cancer | obesity, alcohol, contraceptive pills, HRT (hormone replacement therapy), inactive, diet, and smoking |
| non modifiable risk factors for breast cancer | getting old, breast density, and genetic mutations |
| genetic and epigenetic factors | allow cells to escape normal mechanism that control their proliferation, survival, and migration |
| breast cancer initiation and progression do what to genes | activates proto-oncogenes and inactivate tumour suppressor genes |
| metastatic breast cancer | stage IV advanced cancer which has spread to other organs of the body occurring in 20-30% women with breast cancer where metastasis can develop many years later |
| metastatic cascade | primary tumour -> proliferation -> angiogenesis -> local invasion, detachment and intravasation -> embolisation and survival -> arrest and extravasation at target organs -> miceo-metastasis -> metastasis |
| breast cancer progression | normal breast duct -> intraductal hyperplasia -> dysplasia hyperplasia -> intraductal carcinoma -> invasive ductal carcinoma |
| angiogenesis meaning | forming new capillaries from pre-existing blood vessels |
| difference between intravasation and extravasation | intravasation involves cells entering the bloodstream, extravasation involves cells exiting the bloodstream to enter a new tissue |
Created by:
kablooey
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