Carcinoma Of The Breast

Front 1

What is the most common non-skin malignancy in women?

Back 1

breast cancer

Front 2

When was mammographic screening introduced?

Back 2

early 1980s

Front 3

Which carcinoma is almost exclusively detected by mammography?

Back 3

DCIS

Front 4

currently what percentage of women with breast cancer are expected to die of the disease?

Back 4

20%

Front 5

Breast cancer is most common after what age?

Back 5

over 50 years of age

The average age at diagnosis is 64 years

Front 6

How is the age at menarche associated with the risk of developing breast cancer?

Back 6

Women who reach menarche when younger than 11 years of age have 20% increased risk compared to women who reach menarche when more than 14 years of age.

Front 7

Women with a first full-term pregnancy at younger than 20 years of age have half the risk of developing breast cancer than nulliparous women or women over the age of 35 at their first birth. T/F?

Back 7

True

Front 8

The majority of cancers occur in women with a family history. T/F?

Back 8

False. THe risk of breast cancer increases with the number of affected first degree relatives but the majority of cancers occur in women without such a history.

Over 87% of women with a family history will not develop breast cancer.

Front 9

Increased risk of breast cancer is associated with prior breast biopsies showing atypical hyperplasia. T/F?

Back 9

True

Front 10

Overall incidence of breast cancer is higher in women of African American ancestry. T/F?

Back 10

False. It is lower.

But women in this group present with a more advanced stage and have an increased mortality compared with white women.

Front 11

Describe Race as a risk factor for breast cancer.

Back 11

lower in african americans. but african americans present at a more advanced stage, have an increased mortality. A greater number of breast cancers are diagnosed in black women than in white women younger than 40 years of age, and breast carcinomas in black women have a higher nuclear grade, more frequently lack hormone receptors, and have different types of sporadic p53 mutations.

Front 12

Which race has the highest rates of breast cancer?

Back 12

Caucasian

Front 13

A 60 year old woman who first gave birth when she was more than 30 years of age. She has no other factors risk factors. Calculate her risk of developing breast cancer.

Back 13

2%

risk factors: first birth, age

Front 14

Which of the following women will have the lowest risk of developing breast cancer.

a) a woman on postmenopasual hormone replacement therapy
b) a young woman who underwent radiation for Hodgkin disease
c) A woman on oral contraceptives
d) An obese woman who is postmenopasual

Back 14

C

OCP are unlikely to increase the risk of breast cancer, and can decrease the risk of other malignancies such as ovarian carcinoma.

Front 15

Reducing endogenous estrogens by oophorectomy increases the risk of developing breast cancer by up to 75%. T/F?

Back 15

False. It decreased the risk

Front 16

Which of the following women has the highest risk of developing breast cancer?

a) Woman whose diet consists of very minimal fat
b) A coffee addict
c) A woman whose diet consists of high amounts of beta carotene
d) a premenopausal woman who works out everyday
e) A woman who drinks moderate amounts of alcohol daily.

Back 16

E

Higher estrogen and low folate associated with alcohol consumption might be an underlying mechanism

Front 17

Cigarette smoking is a risk factor for breast cancer. T/F?

Back 17

False.

Recall: smoking is associated with periductal mastitis or a subareolar mass.

Front 18

What are some Tx options for women at high risk for developing breast cancer?

Back 18

Bilateral prophylactic mastectomy and chemoprevention.

Front 19

All risk factors for the development of invasive breast cancer affect both breasts equally. Which carcinoma is an exception?

Back 19

DCIS

Front 20

What is the most widely used endocrine therapy for the Tx of breast cancer?

Back 20

Tamoxifen

Front 21

The mechanism of Tamoxifen

Back 21

Competes for binding to the ER and has both estrogenic and antiestrogenic effects.

Front 22

Side effects of Tamoxifen

Back 22

increases the risk of venous thromboembolism, endometrial cancer, and cataracts.

Front 23

About 25% of familiar cancers (3% of all breast cancers) can be attributed to which two highly penetrant autosomal dominant genes?

Back 23

BRCA1 and BRCA2

Front 24

Match the description with a) carcinoma in situ or b) invasive carcinoma:

1) neoplastic population of cells limited to ducts and lobules by the basement membrane

2) involvement beyond the basement membrane

3) no invasion in lymph nodes or blood vessels

4) associated with metastasis

5) invasion into stroma

Back 24

1-a
2-b
3-a
4-b
5-b

Front 25

All carcinomas of the breast arise form?

Back 25

terminal duct lobular unit

Front 26

Among mammographically detected cancers, almost half are?

Back 26

DCIS

Front 27

The most frequent presentation of DCIS

Back 27

mammographic calcifications

Front 28

WHat does DCIS consist of?

Back 28

malignant population of cells limited to ducts and lobules by the basement membrane. The myoepithelial cells are preserved, although they may be diminished in number.

DCIS is a clonal proliferation and usually involves a single ductal system.

Front 29

5 types of DCIS

Back 29

comedocarcinoma
solid
cribiform
papillary
micropapillary

Front 30

Name the type of DCIS based on the morphology:

1) solid sheets of pleomorphic cells with high grade nuclei and large zones of central necrosis with calcified debris and periductal concentric fibrosis.

2) completely filled and distorted lobule with only a few remaining luminal cells visible. No calcifications.

3) Delicate fibrovascular cores extend into a duct and are lined by monomorphic population of tall columnar cells. myoepithelial cells are absent.

4) The papillae are connected to the duct wall by a narrow base and often have bulbous outgrowths. Fibrovascular cores are absent.

5) "cookie-cutter like"

Back 30

1- comedocarcinoma
2- solid
3- papillary
4- micropapillary
5- cribiform

Front 31

A woman presents with a palpable mass and a unilateral erythematous eruption with a scale crust. She also has pruritus. A nipple biopsy shows malignant cells that extend from the ductal system to the overlying nipple skin without crossing the basement membrane. What is the most likely diagnosis?

Back 31

Paget disease

Front 32

WHat gene is overexpressed in Paget disease?

Back 32

Her2/neu

Front 33

What plays a role in the pathogenesis of Paget disease?

Back 33

the production of keratinocytes of heregulin-alpha which acts via the Her2/neu receptor. The Her2/neu is overexpressed in the disease.

Front 34

Microinvasion is most commonly seen in in which type of DCIS?

Back 34

comedocarcinoma

Front 35

"comedone"-like appearance is associated with which kind of carcinoma?

Back 35

DCIS- comedocarcinoma

some cases of comedocarcinoma are associated with sufficient periductal fibrosis to produce a thickening of the tissue, and punctate areas of necrosis (comedone -like) can be seen grossly.

Front 36

The major risk factors for recurrence of DCIS are?

Back 36

grade
size
margins

Front 37

A curative Tx for DCIS?

Back 37

Mastectomy (curative in 95%)

Front 38

Benefit of Tamoxifen is restricted to which kind of DCIS?

Back 38

ER-positive DCIS

reduces the risk of local and distant recurrence

Front 39

Which type of carcinoma is always an incidental finding and not associated with calcifications or a stromal reaction?

Back 39

LCIS

Front 40

LCIS is more common in which age group?

Back 40

young women, 80-90% of cases occur prior to menopause.

Front 41

The cells of LCIS and invasive lobular carcinoma lack expression of which gene?

Back 41

e-cadherin

Front 42

What is the function of e-cadherin?

Back 42

It is a transmembrane protein responsible for epithelial cell adhesion.

Front 43

The abnormal cells of which three breast lesions are identical and consist of small cells that have oval or round nuclei with small nucleoli that do not adhere to one another?

Back 43

ALH, LCIS, and invasive lobular carcinoma

Front 44

Which hormones receptors are always expressed in LCIS?

Back 44

Estrogen and progesterone receptors

Front 45

Overexpression of HER2/neu is always observed in LCIS. T/F?

Back 45

False. not observed

Front 46

LCIS is a high risk marker for future development of invasive carcinoma. T/F?

Back 46

True

Front 47

A 45 year old woman undergoes a biopsy for what appears to be benign breast changes. The biopsy shows a monomorphic population of small, rounded, loosely cohesive cells that fill and expand the acini of the lobule. The underlying architecture can still be recognized. Signet ring cells are also present. What is the most likely cause of these morphologic changes?

Back 47

LCIS

Front 48

Recent studies suggest that in women with LCIS, the ipsilateral breast may be at greater risk for invasive carcinoma. T/F?

Back 48

True.

Front 49

By the time a cancer becomes palpable, over half the patients will have axillary lymph node metastases. T/F?

Back 49

True.

Front 50

dimpling of skin or peau d' orange is associated with which type of carcinoma?

Back 50

invasive (infiltrating) carcinoma.

Tethering of the skin to the breast by cooper ligaments mimics the appearance of an orange peel.

Front 51

In older women undergoing mammography, invasive carcinoma most commonly presents as what?

Back 51

Density

Front 52

What does the term "inflammatory carcinoma" refer to?

Back 52

Clinical presentation of a carcinoma extensively involving dermal lymphatics, resulting in an enlarged erythematous breast. The underlying carcinoma usually has a diffuse infiltrative pattern and typically does not form a discrete palpable mass. The Dx is made on clinical grounds and does not correlate with a specific histologic type of carcinoma.

Front 53

What is the most common type of invasive breast carcinoma?

Back 53

Carcinoma of NST

Front 54

What is the most common type of in situ carcinoma?

Back 54

DCIS

Front 55

Gross appearance of MOST invasive carcinomas, NST.

Back 55

firm to hard and have an irregular border. Within the center of the carcinoma, there are small pinpoint foci of streaks of chalky white elastotic stroma and occasionally small foci of calcification.

Front 56

Which type of carcinoma, when cut or scraped makes a characteristic grating sound (similar to cutting a water chestnut)?

Back 56

Invasive carcinoma, NST (Invasive ductal carcinoma)

Front 57

What is the difference between the well differentiated tumors and tumors composed of anastomosing sheets of pleomorphic cells in invasive ductal carcinoma?

Back 57

Well differentiated tumors consist of tubules lined by minimally atypical cells and can occasionally be difficult to distinguish from benign sclerosing lesions. They express hormones receptors and do not overexpress HER2/neu. The others are composed of anastomosing sheets of pleiomorphic cells and are less likely to express hormone receptors and more likely to overexpress HER2/neu.

Front 58

Most invasive carcinomas consist of tumors that are a hard consistency on palpation and are detectable as mammographic densities. What is the pathogenesis behind these findings?

Back 58

Most carcinomas induce a marked increase in dense, fibrous desmoplastic stroma, giving the tumor a hard consistency on palpation and replace fat, resulting in a mammographic density (scirrhous carcinoma).

Front 59

Carcinomas of NST are accompanied by varying amounts of which other type of carcinoma?

Back 59

DCIS

Front 60

Presentation of invasive lobular carcinoma?

Back 60

palpable mass or mammographic density.

Front 61

The incidence of lobular carcinomas has been reported to increase among which age group of women?

Back 61

post menopausal women owing to the use of post menopausal hormone replacement therapy.

Front 62

Gross appearance of invasive lobular carcinoma?

Back 62

most tumors are firm to hard with an irregular margin. Occasionally, the tissue may feel diffusely thickened and a discrete tumor mass cannot be defined.

Front 63

Histologic hallmark of invasive lobular carcinoma?

Back 63

pattern of single infiltrating tumor cells, often only one cell in width (in the form of a single file) or in loose clusters or sheets. The desmoplastic response may be minimal or absent. Signet ring cells are common. Tumors cells are frequently arranged in concentric rings surrounding normal ducts.

Hint 63

The cells have the same cytologic features as LCIS and lack cohesion, without formation of tubules or papillae.

Front 64

What is the difference between well differentiated invasive lobular carcinomas and poorly differentiated invasive lobular carcinomas?

Back 64

Well differentiated: diploid, express hormones receptors. HER2/neu overexpression is very rare.

Poorly differentiated: aneuploid, lack hormone receptors, and may overexpress HER2/neu.

Front 65

A biopsy of a palpable mass reveals parallel arrays of small, regular cells with scant cytoplasm infiltrate singly in linear arrays or as small clusters of cells. What is the most likely diagnosis?

Back 65

Invasive lobular carcinoma

Front 66

Genetics of invasive lobular carcinoma

Back 66

loss of region on chromosome 16 (16q22.1). The gene for e-cadherin on the opposite chromosome is inactivated by mutations, methylation on the promoter, or decreased expression of transcripion factors.

Front 67

How is invasive lobular carcinoma different from other beast cancers in terms of metastases?

Back 67

Metastases to the peritoneum and retroperitoneum, the leptomeninges, the GI tract, and the ovaries and uterus are more frequently observed. These carcinomas are less likely to metastasize to the lungs and pleura.

Front 68

What genetic abnormality is observed in 67% of medullary carcinomas?

Back 68

hypermethylation of the BRCA1 promoter.

Front 69

HER2/neu overexpression is not observed in medullary carcinoma. T/F?

Back 69

TRUE

Front 70

What are the 3 morphological characteristics of medullary carcinoma?

Back 70

1) solid syncytium-like sheets (occupying more than 75% of the tumor) of large cells with vesicular, pleomorphic nuclei, containing prominent nucleoli and frequent mitosis
2) a moderate to marked lymphoplasmacytic infiltrate surrounding and within the tumor
3) a pushing (non-infiltrative) border.

Front 71

A 58 year old woman has a screening mammography and is found to have a 4-cm circumscribed mass, without calcifications, in her left breast. An excisional biopsy is performed. A frozen section shows solid ness and sheets of highly pleomorphic cells, with many mitotic figures, surrounded by a dense infiltrate of lymphocytes. What is the most likely Dx?

Back 71

Medullary carcinoma

Front 72

The incidence of mucinous carcinoma is slightly higher in women with a mutation in what gene?

Back 72

BRCA1

Front 73

Mucinous carcinomas and tubular carcinomas are usually diploid and the majority express hormone receptors. T/F?

Back 73

TRUE

Front 74

A 60 year old woman presents with a papable breast mass that she palpated 1 month earlier. Physical examination reveals a soft, pale, gray-blue jelly-like tumor measuring 5 cm in diameter. The tumor cells are seen as clusters and small islands of cells within large lakes of mucin that push into the adjacent stroma. What is the most likely Dx?

Back 74

Mucinous (Colloid) carcinoma

Front 75

The clinical presentation of invasive papillary carcinomas is similar to which other type of carcinoma?

Back 75

carcinomas of NST

Front 76

A 48 year old woman presents will a palpable mass which is detected as an irregular density on a mammogram. An excisional biopsy reveals a tumor that is completely composed of well-formed tubules lined by a single layer of well differentiated cells. What is the most likely Dx?

Back 76

Tubular carcinoma

Front 77

Morphology of tubular carcinoma?

Back 77

Tumors consist exclusively of well-formed tubules and are sometimes mistaken for benign sclerosing lesions. However, a myoepethelial cell layer is absent. and tumor cells are in direct contact with stroma. Cribiform spaces may also be present. Apocrine snouts are typical, and calcifications may be present within the lumens.

Front 78

Metastases to the breast most commonly arise from?

Back 78

the contra-lateral breast

Front 79

The most frequent non-mammary metastases to the breast are from?

Back 79

melanomas and lung cancers

Front 80

List a few stromal tumors of the breast.

Back 80

Fibroadenomas
Sarcomas
Phyllodes tumors

Front 81

Mutations in what gene are found in patients with familial adenomatous polyposis (FAP) and sporadic cases of breast fibromatosis?

Back 81

APC gene (adenomatosis polyposis coli)

Front 82

Which tumors arise in the intralobular stroma of the breast?

Back 82

The breast specific biphasic tumors fibroadenoma and phyllodes tumor.

Front 83

What is the most common benign tumor of the female breast?

Back 83

fibroadenoma

Front 84

Fibroadenomas occur at what age?

Back 84

more common before age 30

Front 85

"popcorn" calcifications are a characteristic of what?

Back 85

Large calcifications in fibroadenomas

Front 86

What is the relationship between the epithelium of fibroadenomas and the menstrual cycle?

Back 86

The epithelium of the fibroadenomas is hormonally responsive, and a slight increase in size may occur during the late phase of each menstrual cycle.

Front 87

Fibroadenomas commonly enlarge during pregnancy and cease to grow after menopause. T/F?

Back 87

TRUE

Front 88

A 22 year old woman presents with a painless nodule in the lower outer aspect of her right breast. The nodule appears to be freely movable, sharply demarcated from the surrounding parenchyma and firm. An excisional biopsy reveals 2 cm rubbery tumor. On microscopic examination, the tumor is composed of a mixture of fibrous connective tissue and ducts. The connective is compressing the proliferated ducts which are reduced to curvilinear slits. What is the most likely Dx?

Back 88

Fibroadenoma

Front 89

About 50% of women receiving cyclosporin A after renal transplantations develop which kind of breast tumor?

Back 89

fibroadenomas

Front 90

Phyllodes tumors most commonly present at what age?

Back 90

most present in the sixth decade. Most present as palpable masses, but few are detected mammographically.

Front 91

"leaf-like" architecture?

Back 91

phyllodes tumor

Front 92

How are phyllodes tumors distinguished from fibroadenomas?

Back 92

In phyllodes tumors there is usually increased stromal cellularity, cytologic atypia, and stromal overgrowth.

Front 93

Why is axillary lymph node dissection not indicated in stromal malignancies?

Back 93

b/c the incidence of nodal metastases is exceedingly small.

Front 94

Hematogenous spread to the lungs is commonly seen in which type of stromal tumor?

Back 94

sarcomas

Front 95

Which type of stromal tumor arises as a complication of radiation therapy?

Back 95

angiosarcoma

Front 96

What is Stewart-Treves syndrome?

Back 96

When angiosarcoma arises in the skin of a chronically edematous arm after mastectomy.

Front 97

What is the most important prognostic factor for invasive carcinoma in the absence of distant metastases.

Back 97

Axillary lymph node status

Front 98

Which procedure can spare women the increased morbidity of a complete axillary dissection?

Back 98

sentinel node biopsy.

Most breast carcinomas drain to one or two sentinel nosed that can be identifies by radiotracer, colored dye, or both. The sentinel node is highly predictive of the status of the remaining nodes.

Front 99

Invasive carcinoma under 5 cm or less in diameter with up to 3 involved axillary nodes or invasive carcinoma greater than 5 cm without nodal involvement will be classified as what stage?

Back 99

Stage II

Front 100

Which therapy can improve response in patients with carcinomas overexpressing HER2/neu

Back 100

Trastuzumab and chemotherapy

Front 101

What is Trastuzumab?

Back 101

The first gene targeted therapeutic agent for a solid tumor. It is a humanized monoclonal antibody to HER2/neu developed to specifically target tumor cells and spare normal cells.

Front 102

Limitations of Trastuzumab?

Back 102

cardiac toxicity

Front 103

What is HER2/neu

Back 103

a transmembrane glycoprotein involved in cell growth control. It is overexpressed in 20-30% of breast cancers and in 90% of cases, the overexpression is associated with amplification of the gene on 17q21.

Front 104

about 50-85% of carcinomas express estrogen receptors and such tumors are more common in which age group?

Back 104

post-menopausal women

Front 105

Women with hormone receptor positive carcinomas have a slightly worse prognosis than women with hormone receptor-negative carcinomas. T/F?

Back 105

FALSE.

Women with hormone receptor positive carcinomas have a slightly BETTER prognosis than women with hormone receptor-negative carcinomas