11 & 12 - Breast Cancer Flashcards
(93 cards)
1
Q
Most common cancer among women in the US
A
Breast Cancer
2
Q
Leading cause of cancer death among women in the US
A
Lung Cancer
3
Q
Second leading cause of cancer death among women in the US
A
Breast Cancer
4
Q
Lifetime risk a woman has of developing breast cancer
A
1 in 8
5
Q
Biggest risk factor for developing breast cancer (other than being a woman)
A
Age
6
Q
Breast Cancer - Stage 0
A
DCIS - Cancer cells present in either lining of a breast lobule or a duct, but have not spread to the surrounding fatty tissue
7
Q
Breast Cancer - Stage 1
A
Tumor
8
Q
Breast Cancer - Stage 2
A
Tumor can range from 2 - 5 cm in diameter
OR
9
Q
Breast Cancer - Stage 3
A
Locally advanced cancer
Tumor may be larger than 5 cm in diameter
OR >4 lymph nodes are involved
10
Q
Breast Cancer - Stage 4
A
Known as metastatic
Cancer has spread to other parts of the body such as bone, liver, lung or brain.
11
Q
Non-Metastatic Breast Cancer - Local Therapy
A
Surgery (lumpectomy)
Radiation therapy
If contraindications to this, then total mastectomy is treatment of choice
12
Q
Non-Metastatic Breast Cancer - Systemic Therapy
A
Endocrine manipulations
Chemotherapy
Novel Therapies
13
Q
Adjuvant Therapy
A
Chemotherapy after surgery
14
Q
Neo-Adjuvant Therapy
A
Chemotherapy before surgery
15
Q
Sentinel Lymph Node Biopsy
A
During surgery, surgeon injects dye
See lymph nodes that have uptake of that dye
Remove those lymph nodes to see if the cancer has spread there.
16
Q
Adjuvant Systemic Therapy for Breast Cancer - Prognostic Factors
A
Estimate outcome independent of systemic treatment
Reflect tumor biology - Who should be treated?
17
Q
Adjuvant Systemic Therapy for Breast Cancer - Predictive Factors
A
Reflect relative resistance or sensitivity to specific therapy
What specific treatments should be offered to an individual?
18
Q
Breast Cancer Prognostic Factors
A
TNM Stage Axillary nodal status Tumor size Tumor Grade Lymphatic or vascular invasion
19
Q
Breast Cancer Predictive Factors
A
Age
Estrogen Receptor
Grade
HER2
20
Q
Estrogen Receptor (+)
A
Estrogen Dependent
That means on immunohistochemistry, you have Estrogen & Progesterone recepters >1%
More slow-growing
Can recur decades later
21
Q
Estrogen Receptor (-)
A
Estrogen Independent
Commonly recurs within the first 5 years
If you hit the 5 year point without recurring, your likelihood of recurrence is very low.
22
Q
Tamoxifen
A
PO
Once per day
Can give regardless of menopausal status
Selective Estrogen Receptor Modulator (SERM)
Risks:
Increased risk of endometrial cancer (1/1000)
Thromboembolic phenomena
Cataracts
Benefits:
Bone health
Lipid
Decreases risk of breast cancer recurrence of 50%
Also likelihood of this helping your breast cancer is directly proportional to how much Estrogen Receptor is found in your immunohistochemistry.
23
Q
Aromatase Inhibitors (Anastrozole)
A
Decrease amount of systemic estrogen
Aromatase converts precursors to estradiol
Can only give to post-menopausal patients
Side effects: Hot flashes Vaginal dryness Fractures (unless their bone density was normal to begin with) Joint aches
24
Q
After 5 years of Tamoxifen
A
Still see benefits 15 years later in terms of decreased rates of recurrence.
25
Tamoxifen - Who
Effective in all hormone receptor positive women (ER+/PR+, ER-/PR+, ER+/PR-)
Regardless of age, stage, tumor grade, menopausal state
Optimal duration: 5 years (these days it's actually 10)
26
Anastrozole Vs Tamoxifen - Disease free survival
Anastrozole is better, when compared directly. You just can't give it to everyone.
27
Breast Cancer Chemo - Which Regimen?
Polychemotherapy is superior to single agent chemotherapy
Anthracycline-based therapy is superior to CMF-based therapy
All women gain benefit
Younger women and those with poorly differentiated hormone receptor-negative tumors are more likely to benefit.
28
Triple Negative
ER-
PR-
HER2-
Typically are a bit more aggressive
29
Oncotype test
Only done with hormone receptor (+) and HER2 (-)
| Tells us how well we'll do with chemo
30
Main side effect of taxanes
Peripheral neuropathy (microtubule inhbitors)
31
Biologic Therapies
Used in HER2 type
Tyrosine Kinase TM growth factor receptor
Drugs that target HER2:
Trastuzumab (Herceptin)
Pertuzumab
TDM1
32
Trastuzumab - Side effects
Reversible decrease in cardiac function
| Don't give with doxorubicin too!
33
Metastatic Breast Cancer - Goals of Therapy
```
Cure
Improve overall survival
Improve time to progression
Improve symptoms related to the disease
Improve quality of life
```
34
Trastuzumab - Mechanism of action
Suppresses HER2 activity
Does not inhibit HER2 heterodimerization
Flags cells for destruction by the immune system (ADCC)
35
Pertuzumab - Mechanism of action
Inhibits HER2-forming dimer pairs
More complete HER2 blockade
Flags cells for destruction by the immune system
36
Pertuzumab - Side effect
Reversible impairment in pumping of the heart
37
TDM1
Trastuzumab (Herceptin) that is LINKED to a microtubule inhibitor
38
Palbociclib
```
Hormone Receptor (+)
HER2 (-)
```
Give with aromatase inhibitor (Anastrozole) and it triples the time it takes for a tumor to grow
Interrupts cell cycle between G1 and S
39
HR(+), HER2(-) has only metastasized to the bone
Gurl can live for a decade
40
Functional unit of the duct
Terminal Duct Lobular Unit
| Lined by myoepithelial cells (can contract as well as serving epithelial functions)
41
If we see myoepithelial cells at the periphery
The cancer is bounded (in situ)
42
Fibrocystic Changes - General description
Most common breast lesion
Misc changes of breast tissue involving ducts, lobules, stroma in any combination
Manifests in 40 - 50% of patients as lumps
Pathological incidence greater than 60 - 80%
Path - Reflects exaggerated changes occurring normally in menstrual cycle
43
Fibrocystic changes - Specifics
```
Fibrosis
Cysts
Apocrine metaplasia
Adenosis (enlargement of TLDU) and sclerosing adenosis (scarring of TDLU)
Intraductal and epithelial hyperplasia
```
44
Mild Hyperplasia (2 - 4 cells) indicates
No increased risk
45
Apocrine metaplasia indicates
No increased risk
46
Cysts (macro & micro) indicate
No increased risk
47
Duct ectasia indicates
No increased risk
48
Fibroadenomas indicate
No increased risk
49
Atypical ductal and lobular hyperplasia - borderline lesions indicate
Moderately increased risk (4 - 5x)
50
Hyperplasia, moderate or florid (ductal and lobular) indicates
Mild increased risk (1.5 - 2x)
51
Papilloma with fibrovascular core indicates
Mild increased risk (1.5 - 2x)
52
Adenosis (Sclerosing or florid) indicates
Mild increased risk (1.5 - 2x)
53
Atypical Ductal Hyperplasia
Borderline lesion
A proliferative lesion
Some of the cytologic and architectural criteria of carcinoma in situ are met, but not fully satisfied
Non-obligatory precursor of cancer, may or may not progress
Found in ~5% of biopsies
Indicates 4 - 5x increased risk of invasive cancer
Risk for cancer is bilateral and persists for more than 20 years
Prognosis is same as for cancers without this ADH
30% who have ADH on biopsy have cancer on excision
54
Malignant - Epithelial Derived Tumors
Intraductal and invasive ductal carcinoma
| In situ and invasive lobular carcinoma
55
Malignant - Mesencymal neoplasm (sarcoma)
Cystosarcoma phyllodes
Angiosarcoma
Others
56
Breast carcinoma pathology
```
Most cancers (90%) show ductal epithelium differentiation
10% referred to as lobular type
In situ and invasive components
```
57
Ductal Carcinoma In Situ (DCIS)
Neoplastic transformation of epithelium within ducts or lobules surrounded by myoepithelial cells
Non obligatory precursor to invasive cancer
Characterized by nuclear grade & histo patterns:
Comedo, Solid, Cribiform, Clinging, Papillary
May be detected by association with microcalcifications
May represent up to 25% of breast carcinoma
High grade and large size → multifocality & propensity for invasion
Relative risk for development of invasive carcinoma 8 - 10 fold greater than general population
Risk is primarily ipsilateral
58
Invasive Ductal Carcinoma
Infiltrative malignant epithelial cell process
Resembles cells lining TDLU
Most common breast carcinoma
Lacks myoepithelial cells at the periphery
59
Invasive Ductal Carcinoma - Histologic Classifications
Carcinoma no special type - Majority
Special good prognosis subtype including medullary carcinoma, colloid (mucinous) carcinoma & tubular carcinoma
Poor prognosis - inflammatory, metaplastic CA
Grade: Modified Scarff-Bloom Richardson based on extent of tubular formation, pleomorphism & mitoses
60
Inflammatory Breast Carcinoma
Poor prognosis
Orange peel appearance to the skin
Association with dermal lymphatic invasion
61
Lobular Carcinoma In Situ (LCIS)
Neoplastic transformation of epithelial cells lining terminal ducts and acini of small size
ER/PR+
E-cadherin negative
Surrounded by myoepithelium
Typically multifocal and bilateral
6 - 9 fold increased risk for development of invasive cancer
Bilateral risk of development of invasive cancer
3/4 of invasive cancers that ensue are DUCTAL. Weirdsies
Considered primarily a marker for invasion but is also non-obligatory precursor for invasive lobular carcinoma at a low rate.
62
Invasive Lobular Carcinoma
Infiltrating carcinoma resembling cells of LCIS
Histo - "Indian file" pattern and targetoid "bulls eye" pattern
Small cells with scanty cytoplasm, sometimes vacuolated
E-Cadherin negative
Represents 10% of breast cancer with higher-than-usual incidence of bilaterality (20%)
63
Prognostic Factors of Breast Cancer
Size of primary tumor (larger = worse)
Lymph node involvement and extent, distant metastasis (stage)
Grade - high grade worse
Histologic type
Oncotype Dx (for ER/PR+) predicting distant recurrence
HER2/NEU
ER/PR status
64
Luminal A Breast Cancers
```
Resembling normal luminal epithelium
CK8/18
ER+ and associated genes
Low Grade
Excellent Prognosis
Low p53 mutation rate (12%)
PIK3CA Mutation (45%)
```
65
Luminal B Breast Cancers
```
ER+, but less than Luminal A
Low-to-moderate expression of luminal specific genes
Tumors have higher grade
Proliferation
Worse prognosis compared to Luminal A
Some are HER2+
p53 mutation rate 29%
PIK3CA Mutation 29%
```
66
HER2-Enriched Breast Cancers
```
Overexpression of HER2 & associated pathway genes
ER (-)
Poor prognosis
72% mutated for p53
39% PIK3CA
```
67
Basal-Like Cancers (Triple Negative)
```
Primitive
High histologic grade
Highly proliferative
Pushing borders
May contain necrosis
Metaplastic changes
Atypical medullary features
Seen in the majority of BRCA1 carrier breast tumors
80% mutated for p53
```
68
Gynecomastia
Button-like subareolar swelling
Generally bilateral
Corresponds to intraductal epithelial hyperplasia & increased periductal stromal cellularity & edema
Physiological gynecomastia most common in puberty and old age
No clear cut association with development of carcinoma
69
Gynecomastia - Associated with
```
Relative estrogen excess
Cirrhosis of the liver
Klinefelter's
Estrogen secreting tumor
Estrogen therapy
Digitalis therapy
```
70
Male Breast Carcinoma
Rare
Ratio of Male : Female breast cancer is 1 : 125
Occurs in advanged age
Identified in peri-nipple/areolar region
Presents in advanced stage
Resembles morphologically and biologically invasive carcinomas of the female breast
Associated with BRCA2 germ line mutations
71
Two benign tumors of the breast
Fibroadenoma
| Intraductal papilloma
72
Fibroadenoma
Most common benign tumor or the female breast
Usually appears in young women
Peak incidence in third decade of life
Benign fibroepithelial tumor usually solitary, may be multiple
Rarely associated with carcinoma
Ball-like mass
Increased stroma in lobules
73
Intraductal Papilloma
Benign papillary neoplasm within a duct
Fibrovascular cores lined by benign epithelium and myoepithelium
Identified peripherally or centrally (nipple duct)
If central, may be associated with bloody nipple discharge
Mild increased risk (1.5 - 2x) of development of invasive cancer if you have multiple
74
Breast Cancer Risk Factors - Highest to Lowest
```
BRCA Mutation
Prior chest wall irradiation
Atypical hyperplasia
Increased breast density
Family history
Nulliparity/Age at first birth > 30
Early menarche 55
Hormone replacement therapy >5 years
Postmenopausal obesity
Alcohol servings/day >2
```
75
Majority of breast cancer is
Sporadic
76
Hereditary Breast Cancers
5 - 10% of all breast cancer
1/2 of those are BRCA1
1/3 are BRCA2
77
BRCA1 & BRCA2
78
Red flags for Hereditary Breast and Ovarian Cancer Syndrome (HBOC) - Personal
Breast cancer
79
Red flags for Hereditary Breast and Ovarian Cancer Syndrome (HBOC) - Family History
Non-Ashkenazi Jewish:
| 2 first-degree relatives with breast cancer, 1 diagnosed
80
BRCA Genetic Testing Options
```
Multisite 3 (Ashkenazi mutations)
Comprehensive (Full sequencing)
BART (Large rearrangement test)
```
81
BRCA+
High risk
82
BRCA- but family member BRCA+
Average risk
83
No known mutation in family, BRCA-
Moderate risk
84
No known mutation & Variant of uncertain significance
Moderate risk
85
BRCA mutation carriers are at increased risk for
```
Breast Cancer
Ovarian Cancer
Prostate Cancer
Male breast cancer
Melanoma
Pancreatic Cancer
```
86
Intensive screening - Self Breast Exam
Begin at age 18
| Screen monthly
87
Intensive screening - Clinical Breast Exam
Begin at age 25
| Screen every 6 - 12 months
88
Intensive screening - Mammogram
Begin at age 25
| Screen yearly
89
Intensive screening - Breast MRI
Begin at age 25
Screen yearly
Who?
BRCA mutation carriers
Other hereditary breast cancer syndromes (Li-Fraumeni, Cowden's)
Lifetime breast cancer risk >20 - 25% based on family history
Prior chest irradiation
90
Intensive screening - Pelvic exam
Begin at age 30 (No BSO)
| Screen every 6 months
91
Intensive screening - Transvaginal ultrasound and CA-125
Begin at age 30 (No BSO)
| Screen every 6 months
92
Risk-reducing surgery
Mastectomy reduces breast cancer risk by 90%
| Oophorectomy reduces ovarian cancer risk by 79% and breast cancer risk by 55%
93
Chemoprevention
Tamoxifen
Risk reduction in BRCA (-) with high risk 45%
Risk reduction in BRCA (+) without cancer 62%
Risk reduction in BRCA (+) contralateral breast cancer (50%)
Only reduces the risk of hormone receptor positive cancers
OCPs reduce risk of ovarian cancer by 50%
