Breast Cancer Flashcards
1
Q
Breast Cancer
A
- Most common malignant neoplasm in women
- Mortality has declined from improvements in medical management and early diagnosis
2
Q
Breast Cancer Etiology
A
- Peak age of occurrence ~50 years old
- Variety of factors influence its development
3
Q
Breast Cancer Factors
A
- Family history
- Environment
- Hormonal influences (menopause/early menarche)
- Genetics
- Carriers
- erbB-2 proto-oncogene
- p53 - tumor suppression gene
4
Q
TDT
A
- Tumor doubling time
- Very heterogenous
- May be directly related to patient survival
- Early breast cancer has mean TDT of 25 days while late has ~129 days
- Quick TDT could mean that the tumor has been present for 2-17 years before diagnosis
5
Q
BC as Systemic Disease
A
- Often appears systemic by diagnosis
- May bypass lymph nodes and pass directly into blood
- Demonstrated with survival curves since disease-free survival is impacted several years after diagnosis
6
Q
Breast Cancer Pathology
A
- Most are adenocarcinomas
- Arise from ductal or lobular epithelium
- Infiltrating ductal carcinoma or lobular carcinoma and two most common forms and have a similar prognosis
- Inflammatory carcinoma has a poor prognosis
- Several other forms and pre-malignant lesions also exist
7
Q
BC Presentation
A
- Usually painless mass
- Sometimes has breast pain, skin changes, nipple discharge/retraction/erosion
- ~5% have signs/symptoms of distant metastasis when they first seek therapy
8
Q
BC Diagnostic Tests
A
- Mammogram
- Controversial for women <50 y.o.
- Recommended to start at 40 y.o.+ or by individual patient
- MRI may detect cancer in contralateral breast that is missed by mammography
- MRI mainly recommended for women at high risk for BC or who have undergone chest wall radiotherapy for Hodgkin’s disease
9
Q
BC Prognosis
A
- Determined using TNM system
- Stage is important for survival predictor
- Both estrogen and progesterone receptors are important
- Estrogen shown to have higher recurrence
- Triple negative cancer has the worst prognosis (ER-, PR-, HER2-)
- Positive nodal involvement is important to predict distant metastasis (more nodal involvement, less survivability)
- Most fatal cases involve bone, lung, or liver
10
Q
Stage 1/2 BC
A
- Goals: achieve local control and accurately stage disease; ultimate goal: cure
- Modified radical mastectomy or lumpectomy + radiotherapy for smaller, isoloated lesions
- Radiotherapy for 4-6 weeks with ~5000cGY
11
Q
Adjuvant Chemo
A
- Using systemic chemotherapy as an adjunct to surgery/radiation in patients with primary breast cancer
- Can also be neoadjuvant therapy for large stage IIA/IIB tumors
- Administered every 3 weeks, dose dense is administered every 2 weeks
12
Q
Adjuvant Chemo Examples
A
- FAC
- AC => paclitaxel
- ACTH
- TCH
- TAC
13
Q
AC
A
- (A) Doxorubicin 60 mg/m^2 + (C) Cyclophosphamide 600 mg/m^2
- Q21 days x 4 cycles
14
Q
Paclitaxel
A
- 175 mg/m^2
- Q3 weeks x 4 cycles
- Standard prophylaxis given prior to cycles
15
Q
Paclitaxel Prophylaxis
A
- Dexamethasone 40 mg PO/IV
- Diphenhydramine 50 mg IV
- H2 antagonist IV 30-60 min prior
16
Q
Dose Intensity Recommendations
A
- Important factor in patient outcome
- Give chemo on schedule as much as possible
- Do not reduce dosing for manageable toxicities
- Provide adequate supportive care (N/V protection, FN prevention/treatment, mucositis treatment)
17
Q
ACTH
A
- AC same as in AC => paclitaxel followed by…
- (H) Trastuzumab 8 mg/kg once, then 6 mg/kg IV Q3w (Can add pertuzumab as well)
- (T) Docetaxel 75-100 mg/m^2 IV day 1, Q21 days x 4 cycles (given with prophylaxis)
18
Q
HER-2+ Recommendation
A
- Add Trastuzumab 4 mg/kg IV once, then 2 mg/kg IV Qweek x 51 weeks
- Added with paciltaxel after doxorubicin is complete (CHF risk)
- Shown to improve disease-free survivability and overall survivability
- Monitor cardiac function at baseline and through treatment
- Can give with second HER2 antibody for additional coverage
19
Q
Docetaxel Prophylaxis
A
Dexamethasone 6 mg BID x 3 days starting 1 day prior to treatment
-Used to prevent fluid retention/hypersensitivity
20
Q
TCH + Pertuzumab
A
-(T) Doxetaxel 75 mg/m^2 + (C) carboplatin AUC6, Q3weeks x 6 cycles + same (H)/pertuzumab dosing/schedule as in ACTH
21
Q
AUC Carboplatin Dosing
A
(CrCl + 25) * AUC
22
Q
Adjuvant Regimens + G-CSF Therapy
A
- Dose dense AC => Paciltaxel
- TAC
- Give filgastrim 5 mcg/kg IV daily after chemo completion and continue until neutrophil recovery (~10 days)
- Alternative: PEG-filgastrim 6 mg SQ once on the day after chemo
23
Q
Anthracycline Toxicities
A
- Myelosuppression
- N/V
- Cardiotox.
- Mucositis
- Alopecia
24
Q
Taxane Toxicities
A
- Myelosuppression
- Hypersensitivity reaction
- Peripheral neuropathy
- Myalgia/arthralgia
- Fluid retention
- Skin/nail changes
- Total body alopecia
25
Q
Trastuzumab/Pertuzumab Toxicities
A
- Increased cardiotox. risk
- Interstitial pneumonitis
26
Q
Cyclophosphamide or Carboplatin Toxicities
A
- Myelosuppression
- N/V
- Cystitis (give adequate hydration to prevent)
27
Q
Adjuvant Hormonal Therapy
A
- Consider in cancers with at least 1% of ER and/or PR+ cells by IHC
- More controversial in premenopausal patients
- Don’t give with chemo
- Adjuvant tamoxifen 20 mg/day reduces annual odds of death/recurrence by ~30-40%
- Better results when given long term
- Antiestrogenic effect on breast cancer cells while giving positive estrogen effect in bones and LDLs
- Possible may need to type of CYP2D6
- AE: hot flashes, bleeding, increase uterine cancer risk, thromboembolism
28
Q
Aromatase Inhibitors
A
- Anastrozole 1 mg/d, letrozole 2.5 mg/d, and exemestane 25 mg/d
- All mainly options in postmenopausal women
- May be better tolerated than tamoxifen, but greater risks of myalgias/arthralgias and fractures
- Recommended as component of adjuvant hormone therapy for women with ER and/or PR+ disease
- Ideally use for 5 year or along with tamoxifen for a total of 5 years
- May also give with bisphosphonates or denosumab to prevent bone loss while on AI
29
Q
Stage III/Inflammatory BC
A
- Goal: prolong survival
- Benefit from pre-op chemo/radiation and post-op chemo
- Same chemo/hormone regimens as Stage I/II
- Evidence supports use of a anthracycline + taxane regimen
- High dose chemo with bone marrow transplant or progenitor cell support isn’t recommended
30
Q
Stage IV BC
A
- Goal: palliation and extended survival
- Treatment with chemo/endocrine therapy often results in disease regression
- Hormone receptor status is important to its response to hormonal therapy
- Slowly progressing disease generally utilizes hormone therapy while rapidly advancing disease would consider chemotherapy use instead
- Use different hormonal therapy than utilized previously especially in recent exposure
31
Q
Premenopausal HER2- Treatment
A
- Hormone therapy (SERM or AI) +/- CDK inhibitor +/- ovarian ablation or suppression with LHRH analogue
- Additionally add an HER2 agent of wanted when HER2+
32
Q
Secondary Hormonal Therapy
A
- Consider additional type of hormone therapy if not refractory
- Fulvestrant ~equivalent to AIs
- Recommend palbociclib + fulvestrant for women with HR+/HER- who progressed on prior hormonal therapy
33
Q
Stage IV BC + Chemo
A
Candidates include:
- Patients with disseminated disease who fail hormonal manipulation
- Patients with rapidly advancing and widespread disease
- Patients with estrogen receptor negative metastatic disease
- Note: Patients who have even a partial response (PR) to chemo or hormonal therapymay have a significant reduction in symptoms (e.g. bone pain)
- *Chemo continued until progression or unacceptable toxicity**
- *Chemo options and single/combination agents vary based on HR status and patient’s previous response**
34
Q
Control of Symptomatic Metastasis
A
- Radiotherapy for local symptoms and make remaining days more tolerable
- Bisphosphonates, give with calcium/vitamin D3
- Denosumab if bisphosphonates are toelrated
