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Breast > Epithelial Malignancy > Flashcards

Epithelial Malignancy Flashcards

1
Q

Tamoxifen- side effects

A

Estrogen agonist in uterus: chance for endometrial CA agonist in lipids and bones: preserves bone density and lowers cholesterol Hot flashes and vaginal dryness

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2
Q

Adjuvant hormonal therapy for pre-menopausal and post-menopausal patients?

A

Pre-menopausal: -Tamoxifen x 5-10 years Post-menopausal: -AI x 5 years (preferred) -Tamoxifen x 2-3 years –> AI x 2-3 years (total = 5 years adjuvant hormonal therapy) -Tamoxifen x 5-10 years (if AI contraindicated)

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3
Q

Risk factors for breast cancer

A

1) Age 2) Reproductive risk factors -related to number of lifetime menstrual cycles -early menarche (before 12) or late menopause (after 55) -first child after 30 -nulliparity 3) Familial -family history (first degree relative) 4) Genetic -BRCA -Li Fraumeni -Cowden -Muir-Torre -Hereditary diffuse gastric CA -Peutz-Jeghers syndrome 5) Benign breast disease -proliferative without atypia (RR 1.5-2) -atypical hyperplasias (RR 4)

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4
Q

Lifetime risk of developing contralateral breast cancer as BRCA carrier?

A

over 60%

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5
Q

Name the chromosomal abnormality associated with each syndrome: a) Li-Fraumeni b) Cowden c) Lynch d) Muir-Torre e) Hereditary Diffuse gastric cancer (HDGC) f) Peutz-Jeghers Syndrome

A

Li-Fraumeni: p-53 Cowden: PTEN Lynch- MMR genes Muir-Torre- attenuated form of Lynch (MLH-1, MSH-2, MSH-6) HDGC: CDH-1 Peutz-Jeghers: STK11

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6
Q

How do you manage the axilla in the neoadjuvant setting for: a) LN negative breast cancer at baseline, post NACT b) LN positive breast cancer at baseline, post NACT

A

a) SLNB -must have three sentinel nodes, if you cannot get that must go on to ALND b) controversial and in transition -can try SLNB but must get three nodes -AHS guidelines says ALND is standard of care (on written exam, better to say ALND)

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7
Q

Recommended surveillance for BRCA- carriers with intact breasts? (AHS Guidelines, 2011)

A

1) Mammography and MRI annually from age 25-30 years old to 65-69 years old 2) US can possibly replace MRI in patients who cannot have it (due to logistics or patient claustrophobia, etc) 3) clinical breast exam q6 months starting at age 25 34

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8
Q

Four molecular subtypes of breast cancer?

A

1) ER-positive (Luminal A/B) 2) Basal-like (Triple negative) 3) HER-2 positive 4) normal like

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9
Q

Indications for MRI in breast cancer screening?

A

Can use it in high risk women (alternate MRI with mammo): 1) known BRCA mutation 2) known first degree family member with BRCA 3) history of chest radiation (i.e. Hodgkin’s, mantle cell lymphoma) 4) genetic syndrome (Li Fraumeni, Cowden, etc)

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10
Q

indications for pre-op MRI?

A

Staging: 1) axillary adenocarcinoma with unknown primary 2) discordant clinical and mammographic/ultrasound findings 3) high risk for multifocal/multicentric disease, extent of disease unclear 4) evaluate response to neoadjuvant chemotherapy No role in surveillance unless you are the high risk group

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11
Q

Difference between multifocal and multicentric.

A

multifocal- same quadrant multicentric- multiple quadrants

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12
Q

Brands of aromatase inhibitors?

A

Anastrozole (Arimidex) Exemestane (Aromasane) Letrozole (Femara)

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13
Q

BRCA-1 BRCA-2 Which chromosomes are these genes found on?

A

BRCA-1: Chromsome 17 BRCA-2: Chromosome 13

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14
Q

Three categories of chemotherapy agents?

A

1) anthracyclines -topoisomerase II inhibitor, impairs DNA replication -Doxorubicin, Epirubicin 2) taxanes -microtubule inhibitors -good in metastatic setting, also anthracycline resistant tumours Docetaxel, Paclitaxel 3) anti-metabolite based regimens (Cyclophosphamide, Methotrexate, Fluorouracil) Also cisplatin, carboplatin (platinum based chemo group)

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15
Q

Name the chromosomal abnormality associated with each syndrome: a) Li-Fraumeni b) Cowden c) Lynch d) Muir-Torre e) Hereditary Diffuse gastric cancer (HDGC) f) Peutz-Jeghers Syndrome

A

Li-Fraumeni: p-53 Cowden: PTEN Lynch- MMR genes Muir-Torre- attenuated form of Lynch (MLH-1, MSH-2, MSH-6) HDGC: CDH-1 Peutz-Jeghers: STK11

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16
Q

contraindications to RT?

A

Absolute contraindications: -pregnancy Relative contraindications: -connective tissue disorders (i.e. scleroderma, SLE) -prior radiation to chest wall or breast -severe pulmonary disease -severe cardiac disease (if tumour left sided) -inability to lie supine -inability to abduct arm on affected side -p53 mutation (these patients are highly susceptible to radiation induced cancers)

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17
Q

Side effects of RT

A

altered pigmentation (like a sunburn) breast discomfort firmness low risk of cardiac disease

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18
Q

Extended adjuvant therapy with AI- indications?

A

AI x 3-5 years more Additional 5 years of adjuvant Tamoxifen, if an AI is contraindicated

19
Q

According to Oct 2016 AHS guidelines, what are the criteria for low, intermediate and high risk for lymph node negative breast cancer?

A

Lower Risk: - <2 cm - grade 1, with no other risk adverse prognostic factor - <0.5 cm with any other feature - genomic test score low (18 or less) Higher risk: > 3 cm, with or without prognosticators High genomic test score > 2 cm with 1+ adverse prognosticators > 1 cm with 2+ adverse prognosticators Genomic test score high (>31) Intermediate risk: anything in between low and high -Genomic test score intermediate (19-30)

20
Q

How much % risk reduction occurs with: a) bilateral prophylactic mastectomy b) bilateral prophylactic salpinogo-oopherectomy? c) Tamoxifen x 5 years (ER positive cancers)

A

a) 90-95% reduction in breast cancer b) BSO 53-68% reduction in breast cancer 85-95% reduction in ovarian cancer c) 50% reduction in breast cancer with Tamoxifen

21
Q

Subtypes of DCIS

A

cribriform comedo papillary solid

22
Q

Indications for using Oncotype Dx?

A

Three things: 1) ER positive 2) Her-2 negative 3) node negative breast cancer Determines which low risk people could benefit from chemo in addition to endocrine therapy

23
Q

According to Oct 2016 AHS guidelines, what are the adverse prognostic factors for lymph node negative breast cancer?

A

Acronym: “GO HEAL” Grade III Oncotype DX >31 (high risk) HER-2 positive ER/PR negative Age <35 years Lymphovascular invasion

24
Q

Aromatase inhibitors- indications? Mechanism?

A

A - Aromatase inhibitors = After menopause mechanism: inhibiting aromatase enzyme- which converts androgens to estrogens peripherally

25
Q

Tamoxifen- mechanism of action? Indications?

A

Mechanism: estrogen antagonist in breast (inhibits binding of estradiol to estrogen receptors on breast) Indications: ER-positive women, can be used in pre-menopausal or post-menopausal women

26
Q

What % of BRCA carriers have hormone receptor positivity?

A

Only 20% are ER positive Therefore 80% ER negative and hormonal therapy is not beneficial for most carriers

27
Q

What are factors favouring good response to neoadjuvant chemotherapy?

A

younger non lobular histology higher grade ER/PR negative HER-2 positive

28
Q

For lymph node negative breast cancer, classify treatment option for chemotherapy based on low, intermediate or high risk.

A

Lower risk- observation Intermediate risk- chemo Higher risk- chemo

29
Q

Lifetime risk of breast and ovarian cancer in BRCA-1 and 2 carriers?

A

BRCA-1: -55-70% women breast -40% ovarian BRCA-2: -45-70% women breast -15% ovarian

30
Q

Indications for Neoadjuvant chemotherapy?

A

Determinants: 1) Lymph node status Divide into lymph node positive and lymph node negative patients. LN positive: all LN negative: intermediate, and high risk group depending on prognostic factors 2) inflammatory breast cancer 3) locally advanced breast cancers -inoperable LABC ( >5 cm, fixed or matted nodes) -operable LABC (downstage to convert mastectomy to lumpectomy, tumour to size ratio)

31
Q

What other cancers are BRCA-1 and 2 associated with?

A

Breast and Ovarian are the big two BRCA-1: -pancreatic cancer (1% lifetime risk) BRCA-2: -prostate cancer (33% lifetime risk) -pancreatic cancer (5% lifetime risk) -uveal melanoma -stomach, gallbladder, biliary tree (small) inconsistent associations of BRCA gene with colorectal cancer

32
Q

Adjuvant radiation therapy- indications?

A

Lumpectomy vs mastectomy patients Lumpectomy: -standard for all except women >70 years old with clinically node negative, stage I breast cancer treated with surgery and endocrine therapy (risk of in situ breast cancer really low may not benefit from RT) Mastectomy patients: -size (>5 cm or chest wall invasion)- T3/T4 -positive margins -inflammatory breast CA -lymph nodes positive (yes, except for isolated tumour cells (no RT)

33
Q

Recommended surveillance for BRCA- carriers with intact breasts? (AHS Guidelines, 2011)

A

1) Mammography and MRI annually from age 25-30 years old to 65-69 years old 2) US can possibly replace MRI in patients who cannot have it (due to logistics or patient claustrophobia, etc) 3) clinical breast exam q6 months starting at age 25 4) males- clinical breast exam q12 months. Surveillance imaging not recommended. 5) pregnant/lactating females- clinical breast exam q6 months

34
Q

What is Oncotype Dx?

A

Molecular gene assay (21 genes reverse transcriptase PCR) -used as adjunct to other markers to determine which patients will benefit from chemotherapy in addition to endocrine therapy

35
Q

Classification of primary breast cancer?

A

Non-invasive epithelial CA: LCIS or DCIS Invasive epithelial CA: invasive lobular, invasive ductal Mixed connective and epithelial tumours: -Phyllodes -carcinosarcoma -angiosarcoma -adenocarcinoma

36
Q

TNM staging for breast cancer- What are the components for T-stage?

A

T1 = ≤2 cm in greatest dimension T2 = tumour 2-5 cm in greatest dimension T3 = tumour >5 cm in greatest dimension T4 = any size with invasion into chest wall or skin (ulceration or skin nodules) T4d- inflammatory CA

37
Q

Clinical TNM staging for breast cancer- Components for N stage?

A

N1 = mets to movable ipsilateral Level I, II axillary LN N2 = mets to fixed or matted ipsilateral axillary Level I/II LN OR isolated ipsilateral internal mammary nodes N3 = ipsilateral Level III (infrraclavicular) - N3a or ipsilateral internal mammary and axillary (N3b) or ipsilateral supraclavicular (N3c)

38
Q

TNM staging for breast cancer- Components for M stage?

A

M0- no distant mets M1- distant mets

39
Q

Difference between Luminal A and Luminal B molecular subtype of breast cancer?

A

-two main ER-positive molecular subtypes -luminal derived from similar molecular expression of these tumours in comparison with luminal epithelium of normal breast tissue -genes associated with luminal epithelial cells of normal breast tissue and overlap with ER positive breast cancers (luminal CK 8 and 18) Prognostic Distinction between A and B: -A: -high expression ER-related genes, low expression Her-2 -best response to endocrine therapy -best prognosis of all breast cancer subtypes -40% of all breast cancers -B: -lower expression ER-related genes, variable expression HER-2 -worse prognosis than A tumours -usually high Oncotype Dx -20% of all breast cancers -higher grade, higher Ki-67 expression, lower response to endocrine therapy but improved response rate to chemotherapy

40
Q

Breast cancer screening in general population- Canadian guidelines?

A

39 years and under: not recommended 40-49 years: balance of benefits and risk not great enough to recommend routine screening -for those choosing to be screened, optimal interval is 1 year 50-74 years: screening recommended every 2 years 75 years+: consider individual health factors and woman’s preference to continue screening; every 2 years if warranted

41
Q

What % of cancers detected with mammography are not palpable? What % of cancers are not visualized mammographically?

A

10-50% of cancers detected with mammo are not palpable 10-30% of palpable cancers not visualized mammographically

42
Q

BiRads system for breast cancer?

A

0- incomplete assessment; needs additional imaging or prior mammos for comparison 1- negative- nothing to comment on; usually recommend annual screening 2- benign finding 3- probably benign finding 4- suspicious abnormality consider biopsy 5- highly suggestive of malignancy (>95% malignant)- biopsy must be taken 6- known biopsy- proven malignancy

43
Q

HER-2? What is it? In what % of cancers is it found?

A

member of epidermal growth factor receptor (EGFR) of transmembrane tyrosine kinase -involved in regulation of cell proliferation HER-2: proto-oncogene, can be activated to be malignant overexpressed in 20% of invasive breast cancers HER-2 positive women have more aggressive form of breast cancer

44
Q

Differentiate between:

a) isolated tumour cells in axillary LN
b) micrometastases in axillary LN
c) macrometastases in axillary LN

A

a) isolated tumour cells (ITCs): small clusters of cells <0.2 mm or nonconfluent or nearly confluent clusters of cells not exceeding 200 cells in single histological LN cross section
b) micrometastases: tumour >0.2 mm and <2 mm
c) macrometastases: >2 mm

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