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
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
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
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)
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)
6
Q
How does breast cancer present?
A
- Breast lump (sometimes inflammatory, sometimes skin changes at the lump)
- Axillary lymphadenopathy
- Metastatic disease
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
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
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
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
11
Q
What are the stages for metastasis?
A
- M0 = no metastases
- M1 = metastases found
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
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
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
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
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
