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WEEK 23:
Breast cancer treatment:
| Question | Answer |
|---|---|
| when can surgery be used to remove entire tumour | if cancer localised |
| neoadjuvant therapy | used to shrink tumour size before surgery |
| adjuvant therapy | after surgery |
| adjuvant therapy is based on | type of cancer, stage, grade, biology, and patient health |
| surgery treatment consists of (2) | breast conserving surgery (excision of tumour with surrounding normal breast tissue) and mastectomy (remove whole breast) |
| sentinel lymph node biopsy/ targeted axillary disesstion/ axillary lymph node dissection involves | removing lymph nodes so it can not spread to other organs |
| when is mastectomy offered | large tumour more than one area affected large areas of DCIS are pregnant and you can’t have radiotherapy have had radiotherapy to the chest wall before male breast cancer very high risk of developing breast cancer due to family history |
| mastectomy | low risk of cancer recurrence, no radiotherapy, and no subsequent mammograms |
| breast conserving surgery | aims to keep most of breast tissue so is less of a change to body and has a recovery time of 2-3 weeks |
| when should adjuvant chemotherapy/ radiotherapy be started | as soon as clinically possible and certainly within 31 days of completion of surgery |
| who should have radiotherapy | patients with early invasive breast cancer who have had breast conserving surgery with clear margins |
| adjuvant chest wall radiotherapy should be given to which patients | patients with early invasive breast cancer who have had a mastectomy and are at a high risk of local recurrence |
| side effects of radiotherapy | irritation and darkening of skin on breast leading to sore red weepy skin, extreme fatigue, and lymphoedema (excess fluid build up in arm caused by blockage of axillary lymph nodes) |
| docetaxel (taxane) mechanism | tubulin binding drugs (microtubule stabilisers) which prevent normal spindle function during mitosis so chromosomes cant attach properly to spindle and cell cannot complete division and undergoes cell death (mitotic catastrophe) |
| standard adjuvant chemotherapy regime | FEC x 6 cycles, AC x 4 cycles, and FEC–T x 6 cycles |
| FEC x 6 cycles | Fluorouracil 600mg/m2 Epirubicin 75mg/m2 Cyclophosphamide 600mg/m2 |
| AC x 4 cycles | Doxorubicin 60mg/m2 Cyclophosphamide6 00mg/m |
| FEC–T x 6 cycles | Fluorouracil 500mg/m2 Epirubicin 100mg/m2 Cyclophosphamide 500mg/m2 x 3 cycles Followed by Docetaxel 100mg/m2 x 3 cycles |
| neoadjuvant chemotherapy increasingly being use to treat | early breast cancer (HER2+, TNBC) |
| advantages of neoadjuvant chemotherapy (NACT) | reducing the extent of breast and axillary surgery and providing an in vivo assessment of tumour sensitivity to treatment |
| chemotherapy side effects | infections loss of appetite feeling sick being sick tiredness hair loss sore mouth |
| women with ER+ tumours will benefit from | AT LEAST 5 years of anti-oestrogen therapy SO all patients with ER+ disease should receive endocrine therapy |
| endocrine therapy includes (2) | a)Anti-oestrogens Tamoxifen (Nolvadex®) Fulvestrant b) Oestrogen deprivation Aromatase inhibitors (androgen to oestrogens) |
| tamoxifen function | blocks oestrogen as a selective estrogen-receptor modulator (SERM) to treat breast cancers in pre and peri (right before) menopausal women with use of 5 years increasing overall survival in women |
| tamoxifen mechanism | bind to ER and lead to conformational change in domain |
| difference between tamoxifen and E2 | both bind to ER but tamoxifen leads to persistent but less efficient transcription of most oestrogen dependent genes |
| aromatase inhibitors | prevents peripheral conversion of androgens into oestrogens in post menopausal women |
| what should be given as a first line therapy in postmenopausal women with ER+ invasive breast cancer who are at medium or high risk of disease recurrence | aromatase inhibitor |
| types of endocrine therapy (2) | tamoxifen and aromatase inhibitors |
| side effects of tamoxifen | Hot flushes and sweats oedema Nausea Fatigue Vaginal changes Skin rash |
| side effects of aromatase inhibitors | osteoporosis and its complications |
| exemestane (aromasin) | steroidal aromatase inhibitor which is irreversible and can only be overcome by the synthesis of new enzyme |
| mechanism of exemestane (aromasin) | blocks conversion of testosterone into ER and androstenedione into E1. Inhibition of aromatase occurs through competitive binding of aromatase to the heme group of cytochrome P450 decreasing oestrogen biosynthesis in peripheral tissues |
| example of steroidal aromatase inhibitor | exemestane (aromasin) |
| example of non steroidal aromatase inhibitors (2) | Anastrozole (Arimidex) and Letrozole (Femara) |
| function on non steroidal aromatase inhibitors eg Anastrozole (Arimidex) and Letrozole (Femara) | competitive aromatase inhibitors with reversible action (bind reversibly to aromatase by competing with endogenous ligands for active site of aromatase) forming a non covalent bond to haem iron atom in active site |
| difference between non steroidal and steroidal aromatase inhibitors | SA are irreversible (forms covalent bond) and NSA are reversible (forms non covalent bond) |
| HER 2 targeted therapies | Trastuzumab (Herceptin MAB, Pertuzumab (Perjeta, Omnitarg) MAB, Ado-trastuzumab emtansine (T-DM1, Kadcyla) MAB + covalently linked to the cytotoxic agent DM1, and HER2 tyrosine kinase inhibitors Lapatinib Neratinib |
| example of trastuzumab | herceptin - MAB which binds to domain IV of HER2 to disrupt ligand independent signalling |
| example of pertuzumabs | perjeta and omnitarg - MAB |
| example of ado-trastuzumab emtansine | T-DM1, Kadcyla - MAB covalently linked to cytotoxic agent DM1 |
| examples of HER2 tyrosine kinase inhibitors (tinib) | lapatinib and neratinib |
| how does trastuzumab work | trastuzumab Fc region can bind to Fcy receptor III present on surface of effect cells from immune system and trigger tumour cell death via antibody dependent cell mediated cytotoxicity (ADCC) |
| how does pertuzumab work | binds to an epitope present on domain II of HER2 inhibiting dimerisation (two small parts together make one big - dimer) and can also induce ADCC |
| how does trastuzumab work | binds to HER2 and is internalised and undergoes lysosomal degradation resulting in release of DM1 which binds to tubulin resulting suppression of microtubule dynamic instability and prevent of microtubule polymerisation |
| describe resistance to HER2 targeted therapies | Primary and acquired resistance to HER2-targeted therapies is often seen. |
| how does transtuzumab resistance | binding site for trastuzumab is gone so it cant actually bind BUT intracellular kinase domain is still active so the receptor can still send growth signals and driver cancer growth |
| CD4/ CDK6 inhibitors use | clinical use in combination with endocrine therapy in patients with metastatic HR+ and HER2- breast cancer |
| CD4/ CDK6 inhibitors examples (3)- clib | palbociclib, ribociclib and abemaciclib |
| what is used to treat PD-L1-positive, triple-negative, advanced breast cancer (2) | pembrolizumab or atezolizumab |
| what does HER2+ mean | cancer cells have high amounts of HER2 receptors on their surface (are overexpressed) so signalling for growth is increased |
| what does HER2- mean | tumour does not overexpress HER2 so HER2 is either absent or present at normal low levels |
| what does ER+ mean | tumour has oestrogen receptors (cancer respond to oestrogen so this stimulates tumour growth) |
| what does ER- mean | tumour lacks oestrogen receptors so oestrogen is not driving cancer and hormone therapy will not work |
| ER+ responds to | tamoxifen and aromatase inhibitors (endocrine therapy) |
| HER2+ tumour respond to | trastuzumab pertuzumab lapatinib |
Created by:
kablooey
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