Breasts and Cancer Flashcards
(100 cards)
1
Q
Top 3 chief complaints of breast health
A
Breast tenderness
Breast mass or lump
Nipple discharge
2
Q
Orange peel sign
A
D/t retraction of suspensory ligaments > signs of lymphatic invasion
3
Q
Vertical strip method of palpation
A
While supine, use three middle fingers and apply three levels of pressure in a circular motion; Follow and up and down pattern
4
Q
Physical findings of breast cancer
A
- Irregular in contour
- firm to hard consistency
- not well delineated from surrounding tissue
- nontender
- dimpling
- retraction
- fixation
5
Q
Breasts during pregnancy
A
- ducts increase in size and number
- vascular engorgement
- increase in glandular tissue and vascularization
- tissue becomes softer and looser (firmer later on)
- lactation preparation (SD of ribs, vertebra, clavicles may interfere with success)
6
Q
Breasts post-menopausal
A
glandular tissue atrophies, fatty replacement of parenchyma
7
Q
Multiple ducts nipple discharge usually….
A
Hormonal
8
Q
Isolated ducts nipple discharge usually…
A
Local (intraductal papilloma - bloody; mammary duct ectasia - purulent)
9
Q
Meds that increase prolactin
A
BCP, Digoxin, antipsychotics, diuretics, steroids
10
Q
Breast pain
A
Mastalgia
11
Q
Breast cancer risk factors
A
Early menarche, late menopause, age, gender, personal or family hx of breast cancer, nulliparity, late age first birth, hormone therapy, proliferative breast disease, alcohol, etc.
12
Q
Key principles of spirituality
A
- Religion and spirituality are important to many of your patients
- When you explore the role of religion and spirituality in patients’ lives, this is usually helpful to them
- When patients make meaning of their medical condition in religious terms, this may have positive as well as negative consequences for their well being
- Clarifying patients’ religious interpretation of their suffering may help you offer additional support and/ or referral to an expert
- Strive to avoid imposing your religious/ spiritual beliefs on your patients, as this is a professional boundary violation
13
Q
1 imaging of breast
A
Mammography
14
Q
Secondary imaging of breast
A
Ultrasound
15
Q
Problem-solving or special study imaging of breast
A
MRI
16
Q
In what scenario would you might have to use ultrasound or MRI FIRST instead of mammography?
A
Dense breast tissue
17
Q
ACS guidelines for screening
A
- Yearly mammograns starting at age 40 and continuing as long as the woman is in good health
- CBE ~every 3 years for women in their 20s and 30s and every year for women 40+
- Women at high risk (>20%) should get an MRI and mammogram every year
18
Q
BIRADS
A
0 - needs assitional assessment 1 - NML - no further action 2 - benign - no further action 3 - probably benign - 6 month f/u 4 - suspicious - biopsy most of the time 5 - malignant - biopsy 6 - known malignancy
19
Q
Two categories of mammograms
A
Screening - no breast complaints, following guidelines
Diagnostic - pt either has symptoms or palpable mass OR abnormal finding on screening mammogram
20
Q
What is important about screening mammograms?
A
- CC and MLO views
- comparison of previous exam CRUCIAL (may look awful on exam, but if it’s been there for a while with no change > changes next steps)
- CAD improves accuracy
21
Q
What should you look out for on mammograms?
A
- Symmetry/Asymmetry**
- Nodule margins-regular vs irregular**
- Irregular clustered microcalcification**
- Interval nodule development or growth
- Skin thickening or nipple retraction (peau d’orange)
22
Q
Computer Assisted Diagnosis (CAD)
A
- Improve accuracy
- Useful in detecting subtle calcifications
- can identify potential abnormalities, but often over calls masses
23
Q
Signs of cystic lesion on ultrasound
A
Through transmission, no shadowing, no signs of vascular flow, well-defined border
24
Q
Signs of solid lesion on ultrasound
A
No through transmission, shadowing, irregular border, complex
25
What should be done with signs of a solid lesion on ultrasound?
Biopsy
26
On mammogram, what are bad signs indicative of a necessary biopsy?
Dense mass, spiculations, calcifications (sometimes)
27
What imaging modality is commonly used for biopsy?
Ultrasound
28
When would a biopsy be done?
Palpable mass and/or abnormal mammogram
29
Stereotactic biopsy
- Used for non-palpable mass
- Guided by imaging (usually ultrasound or mammogram)
- Local anesthetic, needle biopsy, bandaid surgery
30
Why are clips usually places post-Stereotactic biopsy?
For the radiologist to find again and for physicians to know there was a surgery there in future follow-ups
31
TNM staging
T - size of primary tumor
N - involvement of lymph nodes
M - presence of distant metastasis
32
T class
```
Tx - cannot evaluate
Ts - CA in situ; intraductal CA or lobar CA, Paget's of nipple w/o tumor
T1 - tumor <2 cm
T2 - tumor 2-5
T3 - >5
T4 - extends to chest wall or skin
```
33
N class
Nx - cannot assess
N0 - no regional node mets
N1 - mets to ipsilateral axillary nodes, moveable
N2 - mets to ipsilateral axillary nodes, fixed
N3 - mets to ipsilateral internal mammary nodes or beyond
34
M class
Mx - cannot asses
M0 - no distant mets
M1 - distant mets (including ipsilateral supreclavicular nodes)
35
What is the most important prognostic variable?
Presence or absence of clinical lymph nodes
36
Sentinel lymph node biopsy (SLN)
- For pts with clinically negative (non-palpable) lymph nodes, a less morbid method of staging
- Consistently identify the migration of tumor cells
37
Axillary lymph node dissection (ALND)
- Benefit on axilllary recurrence and survival & prognostic value
- Anatomic disruption may cause lymphedema, nerve injury, shoulder dysfunction
- If there is palpable abnormal lymph nodes these may be biopsied more simply
38
What are other prognostic indicators of poor prognosis?
- Large primary tumor
- Negative ER and PR
- high grade
- high proliferative rate
- certain histologic subtypes
- over-expression of certain oncogenes (esp. HER2)
39
Metastatic work-up
- Blood tests (esp. compare to THEIR normal)
- Chest X-ray
- bone scan
- If indicated, CT of brain, abdomen
- PET scan for full body
40
General treatment categories
- Surgery
- Radiation
- Chemo
- Hormone
- Biologic
41
What is TARGIT?
single-dose targeted intraoperative radiotherapy
42
Goals of surgery
Remove cancer fully and stage surgically the extent of the disease locoregionally
43
Lumpectomy benefits
- breast is preserved
- quicker recovery period with the more limited surgery
- cosmetically generally good
44
Lumpectomy disadvantages
-Have to get radiation (6-7 weeks)
45
Mastectomy benefits
- one surgery
- usual recovery period of 1 week
- usually no radiation is needed, although this is being reevaluated
46
Mastectomy disadvantages
- long recovery in some women
- emotional/sexual implications of loss of breast
- cosmetically less acceptable for some
47
Simple mastectomy
Removes all breast tissue
48
Modified radical mastectomy (MRM)
Removes all breast tissue and contents of axilla
49
Radical mastectomy
Removes breast, axilla, pec major and minor
50
Goal of radiation
Targets cells in its path so DNA is destroyed
51
Side effects of chemo
-fatigue, nausea, diarrhea, hair loss, weight loss, depression, suppression of the body’s immune system (usually temporary); “chemo brain”
52
Complications of chemotherapy
Infection, bleeding, secondary cancers (leukemia)
53
SERMs
Selective estrogen receptor modulators (Tamoxifen and raloxifene)
54
Tamoxifen characteristics
- Typically administer for five years after surgery
- It is not a primary/sole treatment
- Also has use prophylactically to prevent first and second breast cancers
- May use both pre- and post- menopause
- Serious risk of endometrial cancer, thrombotic events (do not use if h/o PE, DVT)
55
Raloxifene characteristics
- As effective in prophylaxis of invasive breast cancer
- fewer uterine side effects
- Bone benedits
56
SERDs (selective estrogen receptor downregulators)
Fulvestrant
57
Aromatase inhibitors
- Prevent the production of estradiol by blocking enzyme aromatase
- For post-menopausal women with estrogen receptor positive breast cancers
- Given as first-line post-tx prophylaxis OR after SERM tx
58
Examples of aromatase inhibitors
- Arimedex (anastrazole)
- Aromasin (exemestane)
- Femara (letrozole)
- Fadozole (third generation)
59
How can you tell if a cancer is estrogen/progesterone related or stimulated by estrogen/progesterone
Immunostaining
60
What drug blocks estrogen from binding ER by acting as an antagonist?
Tamoxifen
61
What drugs prevent estrogen production in the first place?
Aromatase inhibitors
62
Herceptin (trastuzumab)
- Now for early and late stage tx
| - Ab targets HER2 protein
63
Avastin (bevacizumab)
- Used in tx of metastatic disease
| - Binds a substance required for growth of new blood vesels in tumor
64
Tykerb (lapatinib)
- To tx advanced cancer, usually with chemo
- Disrupts HER2/neu protein and interferes with growth signal on the tumor
- Often used when herceptin becomes ineffective
65
Adjuvant therapy
Medical treatment using endocrine therapy, chemo, and/or biologic therapy
66
Neoadjuvant therapy
treatment before surgery with goal of inducing tumor response/shrinkage, possibly enabling breast conserving surgery; also provides information on response if the pt should have a recurrence
67
Recurrence risk
- Related to extent of disease; tumor size & nodes
- May recur 20-40 years after dx
- Lowest risk with tumor size < 1cm and no nodes
- Tools to calculate specific risk range based on genetics and tumor characterisitcs—therapy guide
68
Risk of second primary malignancy
- 7-8% overall occurrence in contralateral breast
- Breast cancer risk lowered by tamoxifen use
- Slight increased risk of colon & ovarian cancer
69
Survivors' risk of complications with tx
- Secondary malignancy - endometrial cancer with Tamoxifen, sarcoma of chest wall/UE (rare)
- Ovarian failure/menopause - with adjuvant cytotoxic agent, SERMs
- Lymphedema
- Cardiovascular toxicities
- Brachial plexopathies
- Venous & arterial thrombosis
- “Chemo brain”
70
F/U for survivors
-History and physical
(q 3 months x 3 years, q 6-12 months x 2 yrs, then yearly)
-Mammography yearly
-Self breast /scar exam monthly
-Pelvic exam yearly
-Chest film/ bone scan when clinically indicated
-Blood counts/ chemistries when indicated
71
Luminal A cancer subtypes
- ER+ and/or PR+, HER2-, low Ki67 index
- most common, low grade and proliferation, good prognosis, low relapse
- endocrine therapy +/- chemo
72
Luminal B cancer subtypes
- ER+ and/or PR+, HER2+ or HER2-, high Ki67 index
- higher proliferation and worse prognosis compared to A
- endocrine therapy +/- chemo, +/- HER2 (if HER2 present)
73
HER2+ cancer subtype
- HER2+, ER/PR-
- aggressive, poor prognosis
- HER2 targeted therapy +/- chemo
74
Triple negative cancer subtype
- HER2/ER/PR-
- aggressive, high metastasis, poor prognosis
- chemo
75
Estrogen sources
Estradiol, estriol, estrone
76
Estrogen main functions
Development of sex organs, maintenance of secondary sex characteristics, metabolic effects
77
Progesterone main functions
Regulates luteal phase, regulates implantation, maintains early pregnancy, lobular-alveolar development in preparation of milk secretion
78
Mifepristone
For abortion
79
Ulipristal
For emergency contraception
80
What type of receptors are the ER and PR?
Nuclear/intracellular
81
HER2
Human epidermal growth factor receptor 2
82
What kind of receptor is HER?
Tyrosine kinase
83
What does increased HER2 activity and expression do?
- Enhances metastatic potential and inhibits apoptosis
| - Associated with disease aggression/progression and increased resistance to endocrine therapy and chemo
84
HER2 signaling pathways
- RAS>Raf>MEK>MAPK
| - PI3K>AKT>mTOR
85
HER2 targeted therapy drug
Trastuzumab > Herceptin
86
Trastuzumab MOA
- Humanized monoclonal Ab to HER2 receptor
- Targets extracellular domain of the HER2 transmembrane tyrosine kinase receptor
- Binds to and blocks HER2 receptor activity
- internalizes and degrades HER2, stimulates apoptosis, cell cycle arrest, inhibits tumorigenic signaling pathways
87
Side effects of trastuzumab
Increased risk of cardiotoxicity
88
No chemo if...
Low risk of recurrence > lymph node negative, small tumor (T1)
89
When would chemo always be used as adjuvant therapy?
Triple negative
90
Characteristics of high risk recurrence
High tumor grade, large tumor size (> 2 cm), positive lymph
91
Oncotype Dx characteristics
PCR, 21 genes, prognostic and predictive
92
MammaPrint characteristics
Microarray, 70 genes, only prognostic
93
Oncotype Dx
- Gene expression pattern translated into quantitative recurrence score (low, intermediate, or high risk)
- Used to estimate risk of recurrence (prognostic) and likely benefit of chemo after breast cancer surgery (predictive)
- Suggested for decision of adjuvant chemo in ER+, node- breast cancer pt
94
MammaPrint
- Expression of the selected genes defines prognostic classification of patients (low risk or high risk)
- NOT for decisions on adjuvant therapy
- Approved as prognostic assay for node - pt younger than 61 with tumor smaller than 5 cm
95
Sanger sequencing
- First generation sequencing
- determination of base sequences in nucleic acids
- Chain-terminating nucleotides lack a 3'-OH group, causing DNA polymerase to stop extension of DNA when a modified (fluorescently or radioactively labeled) ddNTP is incorporated and detected
96
Next generation sequencing (NGS)
Uses array-based sequencing which combines the techniques developed in Sanger method to process a very large of reactions in parallel (much quicker and cheaper)
97
Three steps of NGS
1. Library preparation: libraries are created using random fragmented DNA, followed by ligation with custom adaptors (e.g., short, synthetic dsDNA) which enable the sequence to bind its complementary counterpart.
2. Amplification: library is amplified using clonal amplification methods and PCR
3. Sequencing: DNA is sequenced using different methods (e.g. pyrosequencing)
98
Application of NGS
- Study whole genome
- Sequence RNA
- Study epigenetic changes
- In cancer, identify gene mutations
99
Cre-LoxP system
- Site specific recombinase technology for controlling gene expression
- Enzyme Cre can recognize loxP DNA sequences and the orientation of the loxP sites determines how the targeted gene will be modified (same direction = excised/deleted)
100
CRISPR-Cas9
- Consists of synthetic gRNA that detects the specific sequence in the genome and Cas9 binds gRNA and cleaves DNA at target site > cell DNA repair machinery fill the gap through non-homologous end joining (NHEJ - direct ligation without template)
- Used for knock-out or knock-in genes, gene therapy
