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Year 3 - Clinical (Winter) > 29 - Oncology 3 > Flashcards

29 - Oncology 3 Flashcards

1
Q

Describe the effect that family hx has on occurrence of breast cancer

A
  • 15% significant family hx
    • 1st degree relative increases risk by 2x
  • Risk further increases:
    • If > 1 first degree relative
    • Relative is young at the time of diagnosis
    • Presented w/ bilateral breast cancer
  • No identifiable mutation in a gene to explain this family hx
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2
Q

What can increase and decrease the risk of estrogen exposure causing breast cancer?

A
  • Increased risk -> early menarche (< 12 y/o), late natural menopause, null parity or older age at first birth, obesity (postmenopausal), HRT
  • Decreased risk -> early induced menopause
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3
Q

Describe the progression genes of breast cancer

A
  • HER2 (human epidermal growth factor receptor-2) proto-oncogene
    • Amplified/ overexpressed in ~ 20-25% of all breast cancers
  • Imparts a poorer prognosis -> decreased chemotherapy sensitivity and endocrine therapy resistance
  • Used primarily to select px who will benefit from trastuzumab and other anti-HER2 therapy
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4
Q

Other risk factors for breast cancer

A
  • Age
  • Women w/ previous breast cancer (increased risk of contralateral breast cancer)
  • Px w/ hx of certain benign breast diseases
  • Environment, diet and alcohol use
  • Exposure to radiation (latency period of 10-15 years)
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5
Q

How is breast cancer detected?

A
  • Breast self-exam
  • Clinical breast exam
  • Mammograms (after 75 y/o, sensitivity of mammography decreases and breast tissue thickens, so no longer recommended b/c harder to detect cancer)
  • Breast ultrasound
  • Breast MRI (good for detecting abnormalities in breast, but can’t determine if its cancer or something else, so leads to the need to biopsy; not used often)
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6
Q

How does breast cancer present?

A
  • Breast lump (sometimes inflammatory, sometimes skin changes at the lump)
  • Axillary lymphadenopathy
  • Metastatic disease
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7
Q

Describe the types of biopsy techniques and what each is used for

A
  • FNA -> diagnostic and therapeutic in cystic lesions; unable to distinguish invasive vs. non-invasive
  • Core needle -> provides histologic specimen for ER, PR, and HER2 testing; 90% effective in establishing diagnosis
  • Excision biopsy -> reserved for imaging abnormalities that can’t be targeted by core biopsy
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8
Q

Surgical options for breast cancer

A
  • Modified radical mastectomy -> developed in 1950’s; entails the removal of entire breast plus axillary lymph nodes
  • Breast conserving surgery (lumpectomy) -> surgical removal of the tumour from the breast along w/ some surrounding tissue as well as axillary lymph node dissection; pt requires post-op radiation
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9
Q

What are the stages for a tumour?

A
  • Tis = in situ
  • T1 = < 2 cm
  • T2 = 2-5 cm
  • T3 = > 5 cm
  • T4 = invasion of skin or chest wall
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10
Q

What are the stages for lymph nodes?

A
  • N1 = 1-3 axillary nodes or internal mammary node
  • N2 = 4-9 axillary nodes or palpable internal mammary node
  • N3 = > 10 nodes or combo of axillary and internal mammary nodes
  • mic = microscopic positivity
  • mol = molecular positivity
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11
Q

What are the stages for metastasis?

A
  • M0 = no metastases

- M1 = metastases found

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12
Q

Breast cancer prognostic factors

A
  • Help to predict when px have a better disease prognosis
  • Extent of axillary lymph node involvement, w/ general rule “the number of affected nodes is inversely related to disease recurrence” (lower number of affected lymph nodes = lower percentage of disease recurrence at 10 years)
  • Px age, primary tumour size, tumour grade, tumour cell proliferation rate (ie: % of cells in the S-phase of the cell cycle), estrogen/ progesterone receptor status, HER-2/neu oncogene levels
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13
Q

Tx of stage 0 breast cancer

A
  • Ductal carcinoma in situ (DCIS) – premalignant lesion
    • Lumpectomy + radiation (radiation decreases local recurrence by 50%)
    • Mastectomy -> 1% breast cancer mortality; for large tumours, multicentric, positive margins after re-excision
    • Tamoxifen (decreases recurrence)
    • Role of aromatase inhibitors not yet established
  • Lobular carcinoma in situ (LCIS) – not a premalignant lesion but a risk factor for breast cancer
    • Can watch and wait or tamoxifen for premenopausal, or tamoxifen, raloxifene, or examestane for post-menopausal
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14
Q

Tx of early stage (1-3) breast cancer

A
  • Surgery (lumpectomy or mastectomy)
    • Sentinel lymph node biopsy or axillary lymph node dissection
  • Radiation
  • Chemotherapy (adjuvant and sometimes neoadjuvant)
  • Endocrine therapy -> tamoxifen for premenopausal, aromatase inhibitor for postmenopausal
  • Trastuzumab for HER2-positive
  • Goals of tx = long term remission or cure
  • Px may receive all of the above or any combination depending on the cancer and pt specific factors
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15
Q

Tx of metastatic stage (4) breast cancer

A
  • Typically, systemic therapy -> chemotherapy, endocrine therapy, trastuzumab, targeted therapy (bevacizumab, palbociclib)
  • Palliative radiation
  • Balance sx relief w/ chemotherapy toxicities
  • Expose pt to what they have not been given before
  • Goal of tx = palliation
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16
Q

How to choose a chemotherapy regimen for breast cancer

A
  • Most regimens in early breast cancer are combinations of 2 or more drugs and contain an anthracycline, a taxane, or both
  • More aggressive disease = more aggressive chemotherapy
  • Consider pt specific factors
  • Metastatic regimens are often single agent or combined w/ targeted therapies where appropriate
17
Q

Doxorubicin for breast cancer (MOA, SE, role)

A
  • Anthracycline antibiotic w/ lifetime cumulative dosage
  • Most serious dose limiting SE = cardiomyopathy
  • Usually the first agent of choice for px w/ metastatic disease, unless pt has received an anthracycline in the adjuvant setting
18
Q

Epirubicin advantages over doxorubicin

A
  • Enantiomer of doxorubicin
  • Considered more lipophilic than doxorubicin
  • Higher lifetime cumulative dosage (~1000 mg/m2)
19
Q

Paclitaxel for breast cancer – use and AE

A
  • Cell cycle specific
  • Possibility of developing hypersensitivity reactions; require pre-medications (histamine blockade and corticosteroids)
  • Used for adjuvant tx of breast cancer; used in combo w/ doxorubicin
20
Q

Docetaxel for breast cancer – role and AE

A
  • Second taxane available w/ activity after doxorubicin
  • Cell cycle specific, promoting microtubule stabilization
  • Used instead of paclitaxel in many centers
  • Has been used as 2nd line metastatic tx after anthracycline therapy
  • Generally, considered to have higher response rates than paclitaxel
  • *Causes a lot of neutropenia (70% of px)
21
Q

Cyclophosphamide for breast cancer – MOA, SE

A
  • Alkylating agent
  • Activated and metabolized by CYP3A4 enzymes
  • Dose limiting SE = myelosuppression
  • Hemorrhagic cystitis in higher doses
22
Q

Trastuzumab for breast cancer – MOA, AE

A
  • Murine MAb directed at metastatic breast cancer over-expressing the HER2 antigen
  • Only ~20% of metastatic breast cancers over-express HER2
  • Response rates as monotherapy are ~15-20%; combined w/ chemotherapy can increase to 45-50%
  • Implicated in development of cardiomyopathy; need to consider when combined w/ other chemotherapy
23
Q

Adjuvant TC for breast cancer

A
  • Docetaxel + cyclophosphamide q21days x 4 cycles
  • Lowest intensity adjuvant chemotherapy
  • Typically used in px w/ negative lymph node status, unless there are high risk factors that would support use of a more aggressive regimen
  • Can also be used in lymph node positive setting (generally w/ < 4 lymph nodes positive) if anthracycline-containing regimens would be considered unsafe/inappropriate based on pt factors
24
Q

Adjuvant FEC-D for breast cancer

A
  • Fluorouracil + epirubicin + cyclophosphamide q21days x 3 cycles, then docetaxel q21days x 3 cycles = 6 cycles total
  • Typically used in lymph node positive px, but can be used in lymph node negative disease if high risk features and/or pt has triple negative disease
  • Docetaxel has been associated w/ permanent alopecia in rare cases
  • ECHO must be done prior to cycle 1 (LVEF > 50%) and post-FEC
    • Less cardiotoxic, but want to make sure the pt has adequate cardiac function before starting and continue to test them after
25
Q

Adjuvant AC-T for breast cancer

A
  • Doxorubicin + cyclophosphamide q21days x 3 cycles, then paclitaxel weekly x 12 doses
  • Alternative to FEC-D, although AC-T has increased risk of cardiotoxicity
  • Paclitaxel can be administered q21days instead of weekly, but studies have shown that “dose dense” schedule provides better outcomes
26
Q

Adjuvant DCH for breast cancer

A
  • Docetaxel + carboplatin + trastuzumab q21days x 6 cycles (continue trastuzumab until total 18 doses completed)
  • Similar efficacy to FEC-D
  • DCH less cardiotoxic (b/c doesn’t include anthracycline) and has lower risk of causing leukemia in future as a secondary malignancy
    • May have benefit in ER/PR negative setting
  • Trastuzumab starts w/ cycle 1 of DCH, rather than having to wait until cycle 4 w/ FEC-D
  • ECHO monitoring
27
Q

Risks associated w/ chemotherapy

A
  • Anthracycline -> myelosuppression, N/V, cardiotoxicity, stomatitis/diarrhea, alopecia-
  • Taxane -> myelosuppression, hypersensitivity reactions, peripheral neuropathy, fluid retention, arthralgia/myalgias, skin/nail changes, total body alopecia
  • Trastuzumab -> increased cardiotoxicity
28
Q

Tamoxifen use in breast cancer (MOA, role, standard dose, SE)

A
  • Selective estrogen receptor modulator (SERM)
  • Antagonist effect in breast -> inhibits ER
  • Agonist effect in bone, lipids, endometrium
  • Agent of choice in tx of hormone receptor positive, premenopausal breast cancer
  • Can also be used in certain post-menopausal women
  • Standard dose = 20 mg PO daily
  • Not given concurrently w/ chemotherapy b/c may antagonize benefit of chemotherapy
  • SE = hot flashes (can’t be treated w/ HRT), N/V, vaginal bleeding/discharge
  • Goal = to continue for 5 years
29
Q

Aromatase inhibitors for breast cancer (MOA, SE)

A
  • MOA = inhibition of CYP450 enzymes responsible for estrogen production through peripheral aromatization of adrenal steroids
  • Non-steroidal aromatase inhibitors = anastrozole and letrozole
  • Steroidal aromatase inhibitor = exemestane
  • SE = myalgias/arthralgias, headache, N, vaginal dryness, weight gain, hot flashes, bone fractures
    • Can use bisphosphonates and calcium and vit D supplementation for fractures
30
Q

Postmenopausal breast cancer – adjuvant setting

A
  • ATAC trial showed that anastrozole is superior to tamoxifen
  • BIG 1-98 trial showed letrozole is superior to tamoxifen
  • Tamoxifen x 5 years for stage 0
    • 10 years if continue to be pre or postmenopause (can change to AI after 5 years of tamoxifen; 10 years total)
  • For T2 or greater, or if N+
    • Exemestane + ovarian suppression (Goserelin) or leuprolide x 5 years
31
Q

Describe the premenopausal endocrine regimens for breast cancer

A
  • Upfront tamoxifen = tamoxifen x 5 years
  • Upfront AI = AI x 5 years
  • Early switch = AI x 2-3 y, then tamoxifen x 2-3 years (5 years total) or vice versa
  • Extended therapy = tamoxifen x 10 y, or tamoxifen x 5 years then AI for up to 5 years (max. 10 y total)
32
Q

Premenopausal breast cancer endocrine regimen

A
  • Tamoxifen 20 mg once daily x 5 years remains the tx of choice
  • Risk vs. benefit begins to change after 5 years
  • No role at present for an AI outside of a clinical trial
33
Q

Postmenopausal breast cancer – metastatic setting

A
  • Tamoxifen still remains a choice for px

- All 3 of the aromatase inhibitors have been shown to be effective either after progression on tamoxifen or as 1st line

Year 3 - Clinical (Winter) (30 decks)

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