👱‍♀️Early Breast Ca. 💝 Flashcards

Question

What are the indication of SLNB in EBC?

Answer 1

SLN: first LN or group of nodes draining the ca. **Indications:** - Clinically negative LN - Node clinical + ve → USG ± FNA or CNB - Negative → SLNB - Positive → ALND - Unifocal tumor of ≤3 cm - DCIS patient going for mastectomy (extensive high grade) **Contraindications of SLNB:** - Women with tumors >3 cm - Women with multicentric/multifocal tumours - Women with clinically positive nodes - Pregnant or breastfeeding women - Women with known allergies to radioisotopes or blue dye - Women with previously treated breast cancer or axillary surgery on the affected side * Sensitivity 90-95% , False negative rate 10% * Benefit: Lymphedema risk SLNB - 3% vs. ALND - 30%, with lower risk of nerve injury, shoulder dysfunction. *Similar 5 year DFS and OS vs ALND ( Z-0011 trial) * **Dual Technique with isotope and blue dye in performing SLNB is preferred**

Answer 2

Histopathological Types of Nodal Involvement: 1) **Isolated tumor cells (pN0 (i+))** - Small cluster ≤ 0.2mm or < 200 cells. **Considered node -ve**. No ALND required. 2) **Micro metastases** - >0.2 mm to 2mm. **Node +ve**. Significant but small impact on OS. ALND if ≥ 3 LN involved. 3)**Macro metastases** - > 2mm. **Node +ve**. ALND if ≥ 3 LN involved

Answer 3

- Comprises of removal of level I, II or III nodes relative to the pectoralis minor muscle. - **Typically 10 - 15 lymph nodes are retrieved.** - ALN receives 85% lymphatics from all quadrants, - Internal Mammary (no role of dissection, Adjuvant therapy adequate) receives 15% lymphatics, - Infraclavicular & Supraclavicular LN receives ± 1%. **Indications:** - Radiologically suspicious LN positive on FNA - **SLNB ≥ 3 positive LN in BCS (Z0011)** - Any SLNB + ve if patient has mastectomy – as they receive chest wall RT not WBRT. Therefore ↑ risk of LN recurrence. **Contraindications:** - **DCIS ( except for mastectomy or Extensive DCIS)** - Clinically Node negative EBC - No role in > 70 years with small ER +ve tumor receiving ET.

Answer 4

- **Level I:** Inferior and lateral to the pectoralis minor muscle - **Level II:** Posterior to the pectoralis minor and below the axillary vein - provides most benefit and achieve acceptable complication rate. - **Level III:** Medial to the pectoralis minor and against the chest wall (pN3 if +ve) - LN dissection if clinically palpable only.

Answer 5

**American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011)** study - **Clinically T1-2, N0** who underwent **BCS** and those with up to two positive SLNs identified by frozen section and **received WBRT (tangential) ± Adjuvant therapy post opt** were assigned to: - ALND or - No further axillary specific treatment - Result :No significant difference in DFS or OS (HR for OS=0.79 (95% CI 0.56 to 1.10), HR for disease free survival (DFS)=0.82 (95% CI 0.58 to 1.17), LR of 1.6% for SLND vs 3.1% for ALND (p=0.11)). - Study does not support routine ALND in limited nodal metastatic breast cancer - WBRT confer additional protection by RT exposure to axilla. **After Mapping of the Axilla: Radiotherapy or Surgery (AMAROS)** trial - **Clinically T1-2**, N0 who underwent **BCS or Mastectomy** and those with up to two positive SLNs identified by frozen section were assigned to: - ALND or - Axillary RT - Result: No significant difference in DFS or OS (HR for OS was 1.17 (95% CI 0.85 to 1.63) and DFS 1.18 (95% CI 0.93 to 1.51)). **- Axillary RT results in significantly less morbidity (lymphoedema, paresthesia, wound infection and seromas)**. **For patients with 3 or more positive sentinel nodes, ALND is generally considered the recommended approach, as this was not directly addressed by the AMAROS trial findings.**

Answer 6

- Therapy used after surgery to reduce rate of cancer recurrence. Includes chemotherapy, endocrine therapy, targeted therapy or RT. -**St. Gallen international consensus panel of expert’s guidelines**and recommendations for selection of adjuvant systemic therapy for breast cancer patients based on risk categories.

Answer 7

- Five years of adjuvant endocrine therapy is the standard of care in ER/PR + ve patients. **Current options:** - Tamoxifen alone for 5 years. - AI' s alone for 5 years (risk of fracture due to bone loss). - Tamoxifen for 5 years and AI's for 5 years (Improved DFS not OS. Hot flushes, arthralgia and arthritis were the most significant side effects). - **Tamoxifen up to 10 years (reduced the risk of recurrence, mortality. However, risk of endometrial Ca 3.1% vs 1.6% 5 years group).** - Tamoxifen followed by extended AI s for 10 years (No improved DFS). - 2011 EBCTCG metanalysis compare TMX 5 yrs VS no Tx - ↓ LR, ↓Ca mortality at 15 yrs.

Answer 8

- Selective inhibition or stimulation of Estrogen Receptor. - Ovary main source of estrogen in pre-menopausal. - Agonist for bone tissue (improve osteoporosis in postmenopausal) but is antagonistic on mammary and uterine tissue - Tamoxifen - 20 mg OD. - Raloxifene - 60 mg OD - Toremifene - 60 mg OD.

Answer 9

Block Estrogen receptors at both mammary and uterine tissue. - Fulvestrant - for metastatic Ca after previous treatment with SERM. **Side Effects:** - TMX ↑ risk endometrial Ca (1%), Raloxifene (less risk), **Fulvestrant (none)** - DVT - ↑ risk - Hot flashes (80%), Vaginal discharge, Menstrual irregularity, - Teratogenic - Premenopausal advice on contraception, Post treatment advised to wait 2 months before conception.

Answer 10

- In post-menopausal breast cancer patients (↓ LR, ↑ OS) - Inhibit action of enzyme aromatase which converts androgens → estrogens in **peripheral tissues** (fat, muscle, liver). Types: 🍊**Reversible non-steroidal inhibitors:** - Anastrozole (Arimidex) 1 mg OD - Letrozole (Femara) 2.5 mg OD 🍎**Irreversible steroidal inhibitors:** - Exemestane (Aromasin) 25 mg OD **Side effects:** - Bone: ↑ risk of osteoporosis. - AIMSS (AI associated musculoskeletal syndrome) - arthralgia, joint stiffness and bone pain (30%) - Treat with exercise, NSAID, change to TMX or another AI - CVS: ↑ risk of AMI, DLP - Sexual dysfunction: Vaginal symptoms, sexual dysfunction - Risk of reactivation of ovarian function

Answer 11

- **NICE recommends Bone mineral density using dual‑energy X‑ray absorptiometry (DEXA) scan** for all patients before starting AI and for those on AI periodically thereafter. - Osteopenia -Calcium 1.5g/day + Vit D 600 iu/day - Osteoporosis any 2 risk factors present: - Age >65 years old - T score < -1.5 on DEXA scan - Smoking (current and previous) - Family history of hip fracture - Personal history of fragility fracture above the age of 50 years old - Oral corticosteroids use of >6 months -Denosumab or Bisphosphonates (Alendronate 70mg/wk) + Calcium 1.5g/day + Vit D 600 iu/day. or - All breast cancer patients who are on AI should have bone densitometry done at baseline and periodically thereafter. - Bisphosphonates or denosumab should be started if T score is < -2.0 on dual‑energy X‑ray absorptiometry or patient has two or more risk factors of osteoporosis.

Answer 12

- Inhibition of estrogen production from ovaries especially premenopausal women. - Premenopausal with high risk early or advanced stage breast cancer of luminal types (ER ± PR + ve) - improved DFS and OS (SOFT and TEXT trials). **Type of Ovarian Treatment:** **1) Permanent ablation** – surgical oophorectomy (rapid onset) or ovarian irradiation (delayed onset menopause (6/52)). **2) Temporary suppression** - temporary amenorrhea by LHRH Agonist. - LHRH agonist → continuous stimulation → -ve feedback → pituitary blockade → ↓LH → ↓ estrogen. - Menopause by 21 days. - Poorer control vs. surgical excision. - Goserelin (Zoladex) - 3.6mg/28 days.

Answer 13

- In pre-menopausal women, medical (GRHA) or surgical (oophorectomy) induced menopause with addition of tamoxifen confer better OS benefits after 8 years vs tamoxifen alone (93.3% vs 91.5%) - **Medical/surgical menopause + AI vs tamoxifen showed similar OS but better distant metastasis freedom at 8 years with AI (91.8% vs 89.7%)**

Answer 14

- Reduced recurrence rate by 50% depending on stage of disease

Answer 15

Has small but significant benefits on 10 years mortality (tamoxifen) and distant recurrence (AI) but associated with higher incidence of endocrine therapy complications. • Decision for endocrine therapy beyond 5 years can be considered in high risk patient and should be individualized

Answer 16

- **Post-mastectomy** - ≥1 lymph node positive - lymph node negative in T3 or T4 - positive margin not amenable for surgery - Intermediate or high risk patients according to St Gallen international consensus - Timing of starting: **4 to 6 weeks post operation** ( maximum 3 months) - **no benefit after 3 months!**

Answer 17

-**Chemotherapy regime AC or TC regime** usually use in **Luminal A** to where risk of toxicity is more important -**TAC or AC-T mainly reserved for Luminal B, TNBC or pN2-3**. TAC associated with more toxicities

Answer 18

1. **IHC for Ki67 proliferative index** (>10% is high risk) – No standardize value for Ki67 2. **Multi-gene assays** (Endopredict, MammaPrint, Oncotype DX, Prosigna) 3. **Protein based ELISA** for urokinase plasminogen activator (uPA)/PAI 4. Clinical **PREDICT** algorithm (NHS-UK) 5. **St. Gallen recommendation (Malaysia CPG 3rd edition)** – Low, Intermediate and High risk

Answer 19

- **Antracyclines** based ( Doxorubicin, Epirubicin) - **Taxane** based (Paclitaxel, Docetaxel) - **Combination Anthracycline & Taxane** ( AC - T , FEC -T ) - Non anthracycline , non Taxane based **(CMF)**

Answer 20

- **Inhibit DNA/RNA synthesis & topoisomerase II**, O2 free radicals damage DNA. - **Complications** - **Cardiotoxicity** (heart failure, cardiomyopathy), Febrile neutropenia - **🚨Pre starting chemo requirements - ECHO** - Daunorubicin, Doxorubicin, Epirubicin - Regime - **FEC (Fluorouracil, Epirubicin, Cyclophosphamide)**

Answer 21

- **Disruption of microtubule function** → inhibit cell division (frozen mitosis) - **Complications** - Febrile neutropenia, Myalgia, Peripheral neuropathy, Mouth sore, **Alopecia** - **Paclitaxel, Docetaxel** - TC – Docetaxel D1 IV, Cyclophosphamide D1 IV – every 21 days x 4 cycle

Answer 22

- **AC –T:** -**Doxorubicin (A)** D1 IV, **Cyclophosphamide (C)** D1 IV – every (21 (HER2 +ve) or 14 days) X 4 cycle - **Paclitaxel (T)** D1 IV then (weekly X 12 weeks **(if HER2 +ve, with anti HER2 agents)** or 2 weeks 4 cycle). - **FEC -T**: FEC 3 cycle follow by Docetaxel 3 cycle. - Taxane-based adjuvant chemotherapy recommended especially in node + ve. - **Taxane-anthracycline regimen reduced incidence of leukemia, venous thrombosis, severe cardiac toxicity compared with anthracycline based**. - Higher incidence of neurotoxicity and non-recurrent death. **🚨HER2 agents only given together at Taxane (T) regime, not together with Antracycline (AC) ( in view of cardiotoxicity for Antracycline and HER2 agent)**

Answer 23

**CMF:** -**Cyclophosphamide** PO D1-14 -**Methotrexate** D1 & D8 IV -**Fluorouracil** D1 & D8 IV x 6 cycle every 28days

Answer 24

- Improved OS and DFS in early and locally advanced HER2-positive breast cancer. - Trastuzumab recommended for HER2 + ve receiving adjuvant chemotherapy – for 1 year (recommended) or 6 months (with less cardiotoxicity and fewer severe adverse events) at discretion of admitting surgeon (PERSEPHONE trial - Addition of Pertuzumab as dual HER2 blockade may be considered in high risk patients – improved DFS (Aphinity trial). - **PERJETA® (pertuzumab) is a prescription medicine approved for use in combination with Herceptin® (trastuzumab) and chemotherapy** - SC trastuzumab is an alternative to IV trastuzumab in both neoadjuvant and adjuvant setting in patients with HER2-positive, clinical stage I-III breast cancer. - Timing for HER2: - Surgery only : Start 6 weeks post op - Chemotherapy : Start after chemo - Radiotherapy : Can start together or after completion - HER 2 & chemo : Given post chemotherapy. Together with HER 2 * **CLEOPATRA TRIAL (for mBC):** CLEOPATRA trial to examine the effect of adding a second HER2 monoclonal antibody or placebo to docetaxel plus trastuzumab as initial treatment for HER2-positive metastatic breast cancer ( different from Aphinity Trial !!) Result: In patients with HER2-positive metastatic breast cancer, the addition of pertuzumab to trastuzumab and docetaxel, as compared with the addition of placebo, significantly improved the median overall survival to 56.5 months

Answer 25

Reduces risk of local recurrence in the affected breast by half and risk of death by a sixth and eradicate any tumor deposits remaining. **Indications**: - Post BCS all patients with clear margin - Post Mastectomy - ≥ 1 + ve LN or - Positive margin not amenable for surgery - Considered in LN - ve, T3 or T4 breast cancer. **Contraindications**: - Connective Tissue Disease (especially scleroderma) - Previous RT (RT can only be given once) - Pregnancy

Answer 26

Divided into: 🍎**-Local RT : (post BCS and Post Mastectomy):** **Post BCS:** 1) Whole breast radiation therapy ( WBRT) / Whole breast irradiation (WBI) 2) RT Boost 3) Accelerated partial breast irradiation (APBI) 4) Intraoperative radiation therapy (IORT): Single fraction, showing non inferior result as compared to EBRT , TARGIT (A, B and E) trial A: not suitable for high risk patients ( age<45, grade, size) **Post mastectomy:** 1) Chest wall RT - Targeting ipsilateral chest wall, mastectomy scar, drain sites ( when indicated ) 🍎**-Regional/Locoregional RT** - RT to supraclavicular LN - Axillary bed RT not given post ALND, high risk of lymphedema 40% vs 3% with supraclavicular RT

Answer 27

- Patient on adjuvant CT : RT post chemo - Patient on ET: RT first or combined - Patient on Herceptin : RT combined

Answer 28

**Local:** - Lymphedema and Breast Edema - Skin Complications (Subcutaneous fibrosis and telangiectasias, Increased breast stiffness) - Brachial Plexopathy - Contralateral Breast Cancer and Irradiation -Post irradiation Angiosarcoma of the Breast **Systemic:** - Pulmonary Sequelae (Pneumonitis, Apical pulmonary fibrosis) - Cardiac Sequelae (Pericarditis) - Second Malignancies (lung and esophagus as well as leukemia and sarcoma)

Answer 29

1. Hereditary breast cancers or genetic high risk 2. dense breast tissue 3. Lobular histology 4. suspected multi centric disease 5. occult disease (cT0 N+/M+ disease)

Answer 30

BRCA1 AND BRCA2 - Breast CA susceptibility gene a/w 80% of hereditary breast CA but accounts for only 5% of all breast CA - Autosomal Dominant inheritance - BRAC 1 mutation17 – lifetime risk (by age 70) of 57% for breast CA & 40% for ovarian CA - BRCA 2 mutation – lifetime risk (by age 70) of 49% for breast CA & 18% for ovarian CA **BRCA1 mutations are more commonly linked to TNBC, while BRCA2 mutations are often associated with luminal B** **Criteria for referral for genetic counselling:** **a) Family History** ≥ 2 relatives with breast cancer, one under 50 ≥ 3 relatives with breast cancer, any age Previously identified BRAC 1 / 2 mutation in the family Pancreatic cancer with breast and/or ovarian in same side of family Ashkenazi Jewish ancestry **b) Personal History** Breast cancer dx at age 50 or younger Ovarian cancer Male breast cancer Triple negative breast cancer * Besides breast CA, BRCA1 gene mutation ↑risk of ovarian, fallopian tube and prostate cancers **PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). - Olaparib: In December, 2014, the EMA and US FDA approved olaparib as monotherapy (at 400 mg taken twice per day) for patients with germline BRCA mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.**

Answer 31

Ultrasound18 (Stavros Study) - Usually 1st investigation in young patients (<35 years old) or pregnant, lactating patients; - **Not the gold standard for screening** - Sensitivity = 98.4%, Negative Predictive Value = 99.5% 􏰁 permits imaging rather than biopsy for benign lesions on u/s - **Uses:** 🍎Differentiates both palpable and mammographic lesions as either cystic or solid 🍎Subsequent characterization and classification of solid nodules (see below) 🍎Guide procedures e.g. Biopsy, drainage of abscess, aspiration of cyst 🍎Evaluation of a palpable mass with a negative mammogram 🍎Evaluation in mammographically-difficult areas e.g. chest wall, axilla - **Pitfalls:** ⏳Operator dependent, non-standardised techniques, poor resolution, ⏳Unable to detect most micro calcifications - **Features of malignancy [BITCH]** 🔥Borders = spiculation, microlobulation, angular margins 🔥Internal Calcification 🔥Taller than wide (fir-tree appearance; invasion of fascia) - in AP view 🔥Central Vascularity / Compressibility (malignant lesions displace breast tissue w/o change in height) 🔥Hypoechoic nodule / Posterior acoustic shadowing 🔥Cortical thickness > 0.3mm = more suspicious with loss of fatty hilum - **Benign Features:** ❄️Smooth Margins, well circumscribed ❄️Thin Echogenic Capsule ❄️Ellipsoid Shape (wider than deep) ❄️Macrolobulations ❄️Hyperechogenicity

Answer 32

**Mammography** - Most sensitive of the proven breast imaging modalities - Usually performed in asymptomatic older women (>40YO) [breast tissue in younger women is denser; more difficult to pick up abnormalities], but >35YO in symptomatic women - Normally, 2 views are done: **craniocaudal (CC)** 🏹Right /Left 🏹70% tumours in lateral quadrant (upper) **mediolateral oblique (MLO)** 👨‍🔧Captures the tail 👨‍🔧Right /Left 👨‍🔧80% tumours in oblique milky way - **Additional specialised views: magnification and coned compression**; done on request to help magnify areas of abnormality to further characterize any lesion. - Look at the axilla on the MLO view for any enlarged lymph nodes - Comment about hyperdense mass with irregular margin or not, microcalcification ( only can see with magnification) - **Malignant Mammographic Findings:** 🔥New or spiculated masses 🔥Clustered micro-calcifications in linear or branching array 🔥Architecture Distortion - **Benign Mammographic Findings:** ❄️Radial Scar ❄️Fat Necrosis – characteristic oil cyst ❄️Milk of Calcium – characteristic microcalcifications appear discoid on CC view and sickle shaped on MLO view **Abnormal features:** **(a) Microcalcifications (<0.5mm in size):** 🥡If calcifications >0.5mm 􏰁 macrocalcifications; >5/mm2 􏰁 cluster 🥡Sole feature of 33% of cancers detected on mammography 🥡Causes: **DCIS** (microcals in a straight line), invasive cancer, fibrocystic disease (microcals scattered), papilloma **(b) Spiculated mass or stellate lesion with poor outline or comet sign:** 🥢95% of spiculated masses on mammography are due to malignancy 🥢Stellate lesion is a localised distortion of the breast parenchyma without perceptible mass lesion – high chance of it being malignant 🥢Causes: Invasive cancer, radial scar (benign), fat necrosis, abscess, etc. **(c) Architectural distortion (of the contour), tent sign , nipple changes** **(d) Neo-density or asymmetric density (look for bilateral synchronous ca; satellite lesion)** - Look for Multicentricity ( will decide the types of operation!) Comment - details and view - hyperdense / margin - surrounding microcalcification ( clustered or not) - skin thickened or not

Answer 33

**HER2 known case human epidermal growth factor receptor 2:** 🍊proto-oncogene located at the long arm of human **chromosome 17** ( 17q12) 🍊is overexpressed in 25-30% of breast cancers through gene amplification and trannscriptional up regulation 🍊can be diagnosed with : **FISH, Silver in situ hybridization (SISH)** 🍊HER2 over expression is a marker of poorer prognosis and associated with poor endocrine response 🍊predictive marker of good response to antracyclinen chemotherapy 🍊can be targeted with humanised monoclonal antibody to the extracellular domain of the HER2 protein.

👱‍♀️Early Breast Ca. 💝 Flashcards

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