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Endo/Repro > Carcinoma of the Breast > Flashcards

Carcinoma of the Breast Flashcards

1
Q

How can breast cancers be separated into groups?

A
  • Can be separated into three major groups defined by the expression of two proteins, ER and HER2
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2
Q

How do the three groups of breast cancer differ from each other?

A
  • Patient characteristics
  • Pathologic features
  • Treatment responses
  • Metastatic patterns
  • Time to relapse
  • Outcome
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3
Q

When does the incidence of breast cancer start to rise?

A
  • After age 30
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4
Q

Who is at low risk of having breast cancer?

A
  • Women younger than age 25
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5
Q

Who has the highest incidence of breast cancer?

A
  • Women of European descent
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6
Q

What is the average age of onset of breast cancer in women of european descent?

A
  • 63
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7
Q

What is the average age of onset of breast cancer in women of African descent?

A
  • 59
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8
Q

What is the average age of onset of breast cancer in women of Hispanic descent?

A
  • 56
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9
Q

Why has rate of mortality declined in breast cancer?

A
  • Mammographic screening as well as more effective treatment modalities
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10
Q

Why has the rate of mortality not decreased as much in African Americans?

A
  • Partly due to unequal access to healthcare

- Also more likely to be biologically aggressive and fall into molecular subtypes that are difficult to treat

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11
Q

What are some high rate risk factors for breast cancer?

A
  • Female gender
  • Increasing age
  • Germline mutations of high penetrance
  • Strong family history
  • Personal history of breast cancer
  • High breast density
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12
Q

What are some moderate rate risk factors for breast cancer?

A
  • Germline mutations of moderate penetrance
  • High-dose radiation to chest at young age
  • Family history
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13
Q

What are some low rate risk factors for breast cancer?

A
  • Early menarche
  • Late menopause
  • Late first pregnancy
  • Nulliparity
  • Absence of breastfeeding
  • Exogenous hormone therapy
  • Postmenopausal obesity
  • Physical inactivity
  • High alcohol consumption
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14
Q

What is believed to be the cause of 1/3 of breast cancers?

A
  • Inheritance of a susceptibility gene or genes
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15
Q

What is the most common gene that produces TNBCs?

A
  • BRCA1
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16
Q

What is the most common gene that produces luminal breast cancers (ER)?

A
  • BRCA2
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17
Q

What is the difference between hereditary and familial?

A
  • Hereditary: High penetrance genes

- Familial: Low penetrance genes

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18
Q

What is seen in hereditary cancers?

A
  • Autosomal dominant traits
  • Earlier age of onset
  • Bilateral or multifocal cancers
  • Multiple primary cancers
  • Clustering of rare cancers in family members
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19
Q

What is seen in familial cancers?

A
  • No classic features of hereditary cancer syndromes
  • Variable age of onset
  • More cases of a specific type of cancer in a family than statistically expected and no specific pattern
  • May result from chance clustering of sporadic cases
  • May result from common genetic background, similar environment, and/or lifestyle
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20
Q

What are the most important high penetrance susceptibility genes for breast cancer?

A
  • BRCA1 and BRCA2
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21
Q

What do BRCA1 and BRCA2 do?

A
  • Produce tumor suppressor proteins that help repair damaged DNA and, therefore, play a role in ensuring the stability of the cell’s genetic material
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22
Q

What happens when either BRCA1 or BRCA2 is damaged?

A
  • The protein product is not made or does not function correctly causing the DNA damage to not be repaired properly
  • As a result, cells are more likely to develop additional genetic alterations that can lead to cancer
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23
Q

What are the major risk factors for sporadic breast cancers?

A
  • Hormone exposure
  • Gender
  • Age at menarche and menopause
  • Reproductive history
  • Breastfeeding
  • Exogenous estrogens
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24
Q

What are some characteristics of the low proliferation ER+, HER2 luminal cancers?

A
  • 40-50%
  • Major type in older women and in men
  • Many detected at early stage
  • Usually low grade with lowest recurrence rate, often cured surgically
  • Metastasizes after long period of time and usually to bone
  • Responds well to anti estrogenic drugs
25
Q

What are some characteristics of the high proliferation ER+, HER2 luminal cancers?

A
  • 10%
  • Increased nuclear staining for Ki67
  • Most common form associated with BRCA2 mutation
  • Higher expression of genes related to cellular proliferation
  • 10% have complete response to chemotherapy
26
Q

What is the difference in growth between ER+/PR+ cancers and ER-/PR- cancers?

A
  • ER+/PR+ cancers are usually well differentiated and slow-growing
  • ER-/PR- cancers are usually poorly differentiated and have a high proliferative rate
27
Q

What is HER2?

A
  • Proto-oncogene ERBB2 encodes HER2

- Member of the RTK family (a family of growth factor receptors)

28
Q

How are HER2 carcinomas diagnosed?

A
  • By detecting HER2 overexpression by immunohistochemistry or HER2 gene amplification by in situ hybridization
29
Q

What does Herceptin do?

A
  • MoAb that binds and inhibits HER2

- Not all HER2+ carcinomas respond to targeted therapy

30
Q

How do TNBCs arise?

A
  • Through an estrogen independent pathway that is not associated with HER2 gene amplification
31
Q

What are some characteristics of TNBCs?

A
  • Have a “basal-like” gene expression profile, so-called because many of the genes that comprise this signature are normally expressed in basally located myoepithelial cells
  • Almost all tumors are poorly differentiated and several typical histological patterns are recognized
32
Q

Who is most likely to have TNBCs?

A
  • Young premenopausal women
  • African Americans
  • Hispanics
33
Q

How does a TNBCs usually present?

A
  • As a palpable mass in the interval between mammogram screenings because they grow at such a fast rate
34
Q

What are all breast cancers?

A
  • Adenocarcinomas
35
Q

What do the terms ductal and lobular describe?

A
  • Subsets of both in situ and invasive carcinomas
36
Q

What was carcinoma in situ originally classified as?

A
  • Ductal carcinoma in situ or lobular carcinoma in situ depending on the resemblance of the involved spaces
37
Q

What does lobular refer to?

A
  • Invasive carcinomas that are biologically related to LCIS
38
Q

What does ductal refer to?

A
  • Used more generally for adenocarcinomas that cannot be classified as a special histologic type
39
Q

What is seen in LCIS and DCIS?

A
  • No extension beyond basement membrane
  • Myoepithelial cells preserved
  • Detected mammographically as micro Ca++ can present as a mass if periductal fibrosis or in some subtypes as nipple discharge
40
Q

What is the best treatment for DCIS?

A
  • Not 100% sure, could be lumpectomy or mastectomy, + chemo

- Post op radiation + Tamoxifen

41
Q

What can help decide the treatment in DCIS?

A
  • Nuclear grade and necrosis
  • Extent of disease
  • Positive surgical margins
42
Q

What is Paget disease of the nipple?

A
  • Rare manifestation of breast cancer that usually presents as a unilateral erythematous eruption with a scale crust
43
Q

What is common in Paget disease of the nipple?

A
  • Pruritus is common

- Lesion may be mistaken for eczema

44
Q

What occurs in Paget disease of the nipple?

A
  • Malignant cells extend from DCIS within the ductal system via the lactiferous sinuses into nipple skin without crossing the basement membrane
  • Tumor cells disrupt the normal epithelial barrier, allowing extracellular fluid to seep out onto the nipple surface
45
Q

Is there a palpable mass in Paget disease of the nipple?

A
  • Yes
46
Q

What is the genetic makeup of Paget disease?

A
  • ER- and overexpress HER2
47
Q

What is LCIS?

A
  • Clonal proliferation of cells that grow in a discohesive fashion due to mutation of CDH1 that leads to loss of tumor suppressor adhesion protein (E-cadherin negative)
48
Q

How does LCIS present?

A
  • Always an incidental finding

- BIlateral in 20-40% of cases

49
Q
  • What is LCIS a risk factor for?
A
  • Invasive lobular carcinoma (either breast)
50
Q

What does LCIS express?

A
  • Always expresses ER and PR

- Overexpression of HER2 is not observed

51
Q

What are some subtypes that are recognized with distinctive morphologies?

A
  • Lobular carcinoma
  • Carcinoma with medullary pattern
  • Mucinous carcinoma
  • Inflammatory
52
Q

What is lobular carcinoma?

A
  • Biallelic loss of CDH1 so loss of E-cadherin

- Most common type of breast cancer to present as an occult primary

53
Q

What are some characteristics of metastasis of lobular carcinoma?

A
  • Peritoneum and retroperitoneum
  • Leptomeninges
  • GI tract
  • Ovaries (Krukenberg) and uterus
54
Q

What is interesting about carcinomas with medullary pattern?

A
  • Over half of BRCA1 associated carcinomas have this appearance
  • Although the majority of carcinomas with medullary pattern are not assoicated with germline BRCA1 mutations, hypermethylation of the BRCA1 promoter leading to downregulation of BRCA1 expression is observed in 67% of tumors
55
Q

What is seen in carcinomas with medullary pattern?

A
  • These tumors have a better prognosis than other poorly differentiated carcinomas
  • Have unusually high number of infiltrating T lymphocytes, suggesting that improved outcomes may be related to a host immune response to tumor antigens
56
Q

What is inflammatory carcinoma?

A
  • Only 3% of breast cancers
  • Higher incidence in African Americans
  • Very poor prognosis
57
Q

What is a big clinical sign in inflammatory carcinoma? What causes it?

A
  • Peau d’orange

- Due to extensive plugging of lymphovascular spaces of the dermis with carcinoma cells

58
Q

What does the outcome of the breast cancer depend on?

A
  • Biologic features of the carcinoma

- Extent to which the cancer has spread at the time of diagnosis

Endo/Repro (31 decks)

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