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CH23 The Breast Flashcards

1
Q

What are the most common palpable lesions of the breast?

A

Cysts, fibroadenomas, invasive carcinomas

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2
Q

What’s the most common sx reported by women w/ a breast disorder?

A

Lumpiness or other > pain > palpable mass > nipple discharge

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3
Q

What’s the most common means to detect breast CA?

A

Mammogram

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4
Q

What is the word for pain of the breast?

A

Mastalgia or Mastodynia

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5
Q

What’s most commonly detected as mammographic calcifications?

A

Ductal carcinoma in situ (DCIS)

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6
Q

When does acute mastitis usually occur? What’s the most likely org involved? Tx?

A

Within the first month of breast feeding

Staphylococcus aureus

ATB

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7
Q

Pt p/w h/o smoking and an inverted nipple whose CC is some inflammation w/ a sub-areolar mass. What does she have? What’s the tx?

A

Squamous Metaplasia of Lactiferous Ductus

Lack of Vit A + tobacco toxic substances -> differentiation of the ductal squamous epi (keratinizing squamous metaplasia)

Surgical removal of involved duct

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8
Q

What does duct ectasia mimic?

A

Clinical and radiographic appearance of invasive carcinoma

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9
Q

The two possibilities in Granulomatous Mastitis?

A

Granulomatous lobular mastitis (parous women, steroid tx)

Cystic neutrophilic granulomatous mastitis (Corynebacteria, d/t IMS or foreign objections breast implant/nipple piercing, ATB tx)

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10
Q

What are the 3 types of non-proliferative breast/fibrocystic changes?

A

Cysts, Fibrosis, Adenosis (inc in # of acini per lobule)

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11
Q

What are the 5 types of proliferative breast dx w/o atypia? What type of risk do they carry for carcinoma of the breast?

A 
Epithelial hyperplasia
Sclerosing Adenosis
Papilloma
Complex Sclerosing lesion
Gynecomastia (males only)

Small inc risk

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12
Q

What is the only benign lesion seen in the male breast? What’s the etiology?

A

Gynecomastia

Imbalance between estrogens (too much) and androgens (too little) d/t cirrhosis of the liver (organ responsible for metabolizing estrogen)

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13
Q

What are the two types of atypical hyperplasia in proliferative breast dx w/ atypia?

A

Ductal (more common) & Lobular

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14
Q

What chromosomal aberrations are associated w/ prolierative breast dx w/ atypica (atypical ductal/lobular hyperplasia)?

A

Loss of 16q or gain of 17p

Lobular shows loss of E-cadherin

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15
Q

What is Tamoxifen?

A

And estrogen antagonist

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16
Q

Regarding breast cancer, almost all malignancies are what?

A

Adenocarcinomas (themselves based on expression of estrogen R and HER2)

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17
Q

Of the estrogen R/HER2 combinations for b-CA, what’s the most common combination?

A

Estrogen R-positive, HER2-negative (65%, most common subtype of b-CA in individuals w/ BRCA2 mutations)

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18
Q

Does estrogen inc or dec one’s risk of b-CA?

A

Increase

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19
Q

What are breast cancers?

A

Clonal proliferations that arise from cells with multiple genetic aberrations, acquisition of which is influenced by hormonal exposures and inherited susceptibility genes.

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20
Q

What percentage of b-CAs occur d/t inheritance of an identifiable susceptibility gene or genes?

A

~12%

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21
Q

What’s involved w/ an inc b-CA risk d/t an autosomal dominant trait?

A

An inheritance of a defective copy of a tumor suppressor gene, in this case BRCA1 or BRCA2 (90% of single gene familial b-CAs, 3% of all b-CAs)

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22
Q

What other CA is associated w/ BRCA1?

A

Ovarian CA

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23
Q

What chromosomes are the BRCA genes on? TP53?

A 
BRCA1 = chromosome 17
BRCA2 = chromosome 13

TP53 = chromosome 17

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24
Q

ER-positive, HER2-negative CA attributes: what % of cases, most common subtype of, chromosome gain, chromosome loss, activating mutation, precursor lesions, resemble what cells

A 
50-65%
BRCA2
Chromo 1
Chromo 16
PIK3CA -> PI3K -> GF Rs
Flat epi atypia, atypical ductal hyperplasia
Luminal
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25
HER2-positive attributes: chromosome, % of b-CA, most common subtype in what, precursor lesion
17 20% Pts w/ germline mutations of TP53 (Li-Fraumeni syndrome) Atypical apocrine adenosis
26
ER-negative, HER2-negative b-CA attributes: what % of b-CAs, observed in pts w/ what mutations, what group of women, cell pattern
20% TP53 > BRCA1 AA Myoepithelial cells ("basal-like" pattern)
27
What are the risk factors for sporadic b-CA dev?
Estrogen exposure, radiation exposure, gender, age at menarche and menopause, reproductive history, breast feeding history
28
What does DCIS and LCIS stand for?
Ductal carcinoma in situ (-> ductal CA that cannot be classified as special histologic type) Lobular carcinoma in situ (-> lobular carcinomas)
29
What % of carcinoma in situs are clinically detected after they've breached the basement membrane and invaded the stroma?
70%
30
What staining technique can be used to identify HER2?
Herceptin (Trastuzumab): monoclonal Ab that binds to and inhs HER2
31
What is preserved in carcinoma in situ (CIS)?
Myoepithelial cells
32
Can DCIS be detected via mammography?
Yes, often by calcifications
33
Does DCIS produce nipple discharge?
Not really, very rare
34
What are the two major architectural subtypes of DCIS? What may also arise from DCIS?
Comedo and non-Comedo Paget dx
35
What are the differences between the DCIS architectures?
Comedo: clustered or linear + braching calcifications, tumor cells w/ pleomorphic high-grade nuclei, areas of central necrosis Non-Comedo: lacks high-grade nuclei and central necrosis, cribriform (cookie cutter-like spaces in ducts), micropapillary (bulbous protrusions), calcifications
36
Pt presents w/ erythematous eruption and scaly crust on her left breast nipple. She's hesitant to itch it because it "looks bad". What dx is this? What's found on biopsy? What's likely present in this pt (details!)?
Paget dx Malignant Paget cells Palpable mass that's an underlying invasive carcinoma (ER-neg, HER2-positive)
37
What's lost in LCIS that's not in DCIS?
E-cadherin protein (possible mutation of CDH1)
38
Is LCIS detected by mammography?
No, incidental biopsy finding only d/t no calcifications or stromal reactions to produce densities
39
Which is more likely to be bilateral, DCIS or LCIS?
LCIS
40
What is the morphology of LCIS?
Uniform population of cells Mucin-positive signet rings Lack of E-cadherin -> rounded cell shape w/o attachment to adjacent cells Doesn't involve nipple skin No necrosis or calcifications present (can't be seen w/ imaging) ER-positive, PR-positive, HER2-negative
41
What is the most common tx plan for LCIS? DCIS?
Close clinical f/u and mammographic screening Surgical excision followed by radiation
42
Where do invasive breast CA metastasize to most often?
Bone
43
How are invasive (iniltrating) carcinomas divided up?
``` 1/3 = special histologic types 2/3 = ductal group (no special type, NST) ```
44
In invasive (infiltrating) carcinoma, the ER+ HER2- group is split into 2 groups, what are they? What's their freq %? What's their standard tx?
Low-proliferation (40-55%) - surgery, hormone tx, NO chemo (risks outweigh benefits) ``` High proliferation (10%) - chemo (only 10% respond completely -> cure) ```
45
What CA responds to Ki67 staining?
ER+ HER2- high proliferation invasive (infiltrating) carcinoma
46
What's associated w/ TP53 mutations?
Li-Fraumeni syndrome
47
What tx modality is used for HER2+ invasive carcinomas of the breast? What is HER2?
Antibodies that bind and block HER2 activity - Herceptin (Trastuzumab) An oncogenic driver
48
Why are ER- HER2- tumors (basal-like) likely to present as a palpable mass in the intervals between mamographic screenings?
Their high proliferation and rapid growth
49
What is the tx modality for ER- HER- invasive carcinomas?
Chemo (30% complete response)
50
What's the prognosis for ER- HER2- metastasized invasive carcinoma?
Very poor, prolonged survival is rare
51
The sheriff of Nottingham was a boob in Robin Hood. What is the grading score used for invasive carcinomas? Explain the details!
Nottingham Histologic Score - score based on: tubule formation, nuclear pleomorphism, mitotic rate - grade 1 (well-diff), grade 2 (mod-diff), grade 3 (poorly-diff)
52
What do grade 1 invasive carcinomas show morphologically?
Tubular pattern Small round nuclei Low proliferation rate
53
What do grade 2 invasive carcinomas show morphologically?
Some tubule formation + other cells More nuclear pleomorphism vs grade 1 Mitotic figures present
54
What do grade 3 invasive carcinomas show morphilogically?
Ragged nests or solid sheets of cells Enlarged irregular nuclei High proliferation rate Necrosis
55
What subtype of invasive carcinomas has the most well-diff carcinomas? What subtype is made up almost entirely of poorly-diff carcinomas?
ER+ HER2- ER- HER2-
56
What are the special subtypes within the ER/HER2 groups?
``` Lobular (CDH1, E-cadherin) Medullary (BRCA-1) Micropapillary (no adherence to stroma, hollow balls of cells) Mucinous (lakes of mucin) Tubular Apocrine (sweat gland-like cells) Papillary (papillae) Secretory (mimics lactating breasts) Inflammatory (lymphatic invasion) ```
57
What percentage of male breast CA is ER+?
81%
58
How do male b-CAs present?
Palpable sub-areolar mass 2-3 cm in size w/ nipple discharge Axillary node involvement present in 50% of pts Metastases common
59
Prognostic factors are important, factors related to the extent of carcinoma include:
Invasive carcinoma vs carcinoma in situ (excellent prog) Distant metastases (cure unlikely, prog varies) Axillary nodal metastases (MOST IMPORTANT) Tumor size (inc size is bad, inc risk for metastases) Inflammatory carcinoma (poor prog) Molecular subtype (ER and HER2 expression) Histologic grade (NHS) Proliferation rate (mitotic counts, Ki-67) E and PRs HER2 (overexpression = poorer survival)
60
What nodes should be tested in axillary node biopsies?
First one or two sentinel nodes
61
DCIS vs LCIS treatment:
DCIS tx'd locally | LCIS confers bilateral risk
62
What are the two types of stroma in the breast? What tumors do they give rise to?
Intra and interlobular Intra -> fibroadenoma, phyllodes Inter -> lipomas, angiosarcomas, psuedoangiomatous stromal hyperplasia, myofibroblastomas, fibrous tumors
63
What is the most common benign tumor of the female breast?
Fibroadenoma
64
What is the most common stromal malignancy?
Angiosarcoma (consists only of stromal cells, poor prog)
65
What are the 6 inflammatory disorders of the breast?
ASD-FLG ``` Acute mastitis Squamous metaplasia of lactiferous ducts Duct ectasia Fat necrosis Lymphocytic mastopathy Granulomatous mastitis ```
66
What's the normal function of BRCA1/2?
Repairing dsDNA breaks
67
What factor determines where breast CAs occur?
Areas of greatest mammographic density (inc amounts of fibrous stroma)
68
Duct ectasia presents w/ what?
Thick white nipple secretions, no pain
69
What are the 6 inflammatory disorders of the breast?
ASD-FLG Acute mastitis, squamous metaplasia of lactiferous ducts, duct ectasia Fat necrosis, lymphocytic mastopathy, granulomatous mastitis
70
What are the 3 groups of benign lesions of the breast?
Non-proliferative breast changes Proliferative w/o atypia Proliferative w/ atypia
71
List the 3 groups of breast disorders AND their contents.
Non-proliferative fibrocystic breast changes (3): cysts, fibrosis, adenosis Prolierative w/o atypia (5): epithelial hyperplasia, sclerosing adenosis, complex sclerosing lesion, papilloma, gynecomastia Proliferative w/ atypia (2): atypical ductal hyperplasia, atypical lobular hyperplasia
72
What are the risks of benign epi lesions of the breast CA-wise?
Non-prolif = no risk Prolif w/o atypia = little risk Prolife w/ atypia = moderate risk
73
What is the ER/HER2 pattern of Li-Fraumeni carcinomas?
HER2+/ER+
74
What are the intra-lobular stromal tumors? What age groups?
``` Fibroadenoma (20s to 30s) Phyllodes Tumor (60s) ```
75
What are the chromosomal mutations in Phyllodes tumors?
Gain of chromo 1q | HOXB13 in more aggressive tumors
76
What are some features of male breast CA?
BRCA2 > BRCA 1 80% are ER+ Metastases are common and pt often (50% of pts) presents w/ axillary node involvement at diagnosis

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