Breast Path

Question 1

Skin changes

Answer 1

Nipple retraction or an eczematous rash that persists may indicate an underlying cancer
Retraction of the skin with or without movement of the arm may represent an underlying invasive cancer

Question 2

Mammogram 101

Answer 2

Mammogram may identify lesions not detected on clinical examination

Denser cysts and tumors: white on mammogram
Less dense fatty tissue: dark on mammogram
Cysts and benign tumors: well circumscribed

Malignant tumors
Have irregular borders
Frequently contain fine flecks of calcium

Question 3

Two of the most important mammographic indicators of breat cancers

Answer 3

Masses
Microcalcifications: Tiny flecks of calcium – like grains of salt – in the soft tissue of the breast that can sometimes indicate an early cancer.
Malignant masses have a more spiculated appearance

Question 4

Mammogram – Difficult Case

Answer 4

Heterogeneously dense breast
Cancer can be difficult to detect with this type of breast tissue
The fibroglandular tissue (white areas) may hide the tumor
The breasts of younger women contain more glands and ligaments resulting in dense breast tissue

Question 5

Introduction

Answer 5

Breast exam should be 7-8 days post menstrual period

Any dominant mass that remains stable throughout the menstrual cycle should be evaluated

A breast mass in a ♀ is likely to be due to:

• Fibrocystic change (40%), no disease (30%), other benign disease (13%), cancer (10%), or a fibroadenoma (7%)
• Fibroadenoma is the most common benign tumor in

Question 6

Nipple discharges

Answer 6

In a ♀ 50 yo, bloody discharge is associated with a malignancy
A greenish brown discharge in a premenopausal ♀ just prior to menstruation is usually due to mammary duct ectasia (the onset of plasma cell mastitis)
Galactorrhea (milky discharge) in a ♀ may be 2 to a prolactinoma in the anterior pituitary, 1 hypothyroidism, or ingestion of certain drugs
Purulent nipple discharge indicates subareolar abscess (commonly, Staphylococcus aureus)
Clear (serous) or milky discharges are frequently associated with OCs, especially prior to the onset of menses

Question 7

Pain in the breast

Answer 7

Most frequently due to hormonal imbalance rather than cancer
Painful masses are most commonly benign
Sometimes breast pain may be referred from the gallbladder, lung, or secondary to costochondritis
Noncylic breast pain likely to occur >40 yo
-Cyclic breast pain usually disappears with the onset of menopause

Question 8

Non-neoplastic (Inflammations)

Answer 8

Inflammation is uncommon
Involves only a few forms of acute and chronic disease
Acute mastitis
-Mammary duct ectasia (plasma cell mastitis)
-Periductal mastitis
-Traumatic fat necrosis
-Lymphocytic mastopathy (sclerosing lymphocytic lobulitis)
-Granulomatous mastitis

Question 9

Acute mastitis

Answer 9

Most important
Virtually limited to the lactation period
Bacteria (Staphylococcus aureus) enter through cracks in the nipple

Question 10

Mammary duct ectasia (plasma cell mastitis)

Answer 10

A chronic mastitis occurring in perimenopausal ♀s

Characterized by lactifierous duct ectasia (dilation) with inspissated cheesy material surrounded by fibrosis and a heavy infiltrate of plasma cells

Question 11

Periductal mastitis

Answer 11

♀s as well as ♂s present with a painful erythematous subareolar mass
Clinically thought to be infectious
> 90% are smokers
In ♀s, may lead to an inverted nipple
In recurrent cases, a fistula tract may open onto the skin at the edge of the areola
Possibly associated with vitamin A deficiency

Question 12

Traumatic fat necrosis

Answer 12

A unilateral , localized process characterized by necrotic fat cells, foamy macrophages, and granulation tissue
Associated with direct trauma to the breast
Lipases are not involved
There is induration, fibrosis, dystrophic calcification, and retraction of overlying skin associated with the healing process
-Thus, needs to be distinguished from cancer

Question 13

Fat Necrosis

Answer 13

Caused by trauma
Tender, firm mass with indistinct borders
May appear suspicious on physical exam
Benign breast calcification seen on mammography

Fat necrosis manifesting as a spiculated mass
Densely calcified 3-cm area of fat necrosis 2 years after blunt trauma to the breast.

Question 14

Lymphocytic mastopathy (sclerosing lymphocytic lobulitis)

Answer 14

Presents with a single or multiple HARD palpable masses

Most common in ♀s with Type 1 diabetes mellitus or autoimmune thyroid disease

Question 15

Granulomatous mastitis

Answer 15

An uncommon breast-limited disease distinguished by granulomas involving lobular epithelium
Only parous women are effected
Hypothesized to be a hypersensitivity reaction mediated by prior lactation

Question 16

Benign Epithelial Lesions

Answer 16

These lesions are categorized according to the risk of developing breast malignancy (see Table 23-1 on next slide)
In the vast majority of cases breast cancer does not develop
A wide variety of benign alterations in ducts and lobules are observed in the breast
Most present on mammography or as incidental findings
Less commonly, present as palpable masses
These changes are divided into three categories:
1) nonproliferative changes
2) proliferative changes
3) atypical hyperplasia

Question 17

Nonproliferative disorders

Answer 17

Formerly referred to as fibrocystic disease, now called fibrocystic changes (FCC)
Represent the common findings seen in “lumpy bumpy” breasts
Three principle patterns
-Cyst formation (often with apocrine metaplasia)
-Fibrosis
-Adenosis

Question 18

Cysts

Answer 18

Small cysts form by dilation and unfolding of lobules which can coalesce to form larger cysts
May be lined by flattened atrophic epithelium or by cells altered by apocrine metaplasia
Calcium may be present
-“Milk of calcium” is a radiologic term describing calcifications in large cysts that mammographically look as though they are lining the bottom of the cyst
Papillary projections may also be present

Question 19

Fibrocystic change

Answer 19

Large cysts contain brown black fluid
White tissue represents stromal fibrosis

1. Multiple cysts with secretions
2. Arrow indicates microcalcification in one of the cysts
3. Background fibrotic stroma

Question 20

Fibrosis

Answer 20

Cysts frequently rupture releasing secretory material into the adjacent stroma
There is subsequent chronic inflammation and scarring contributing to palpable firmness (fibrosis)

Question 21

Adenosis

Answer 21

Defined as an increase in the number of acini per lobule
-A normal diffuse occurrence in pregnancy
-In nonpregnant ♀s, can occur as a focal change
Calcifications are occasionally present

Question 22

Proliferative breast disease without atypia

Answer 22

Rarely form palpable masses; more commonly detected as:
-Mammographic densities (complex sclerosing lesions or sclerosing adenosis)
-Calcifications (sclerosing adenosis)
-Or incidental findings in biopsies
>80% of large duct papillomas present as nipple discharge; the rest as palpable masses or radiographic densities

Question 23

Proliferative breast disease without atypia 2

Answer 23

Characterized by proliferation of ductal epithelium and/or stroma without cellular abnormalities suggestive of malignancy
The following are included in this category:
Moderate or florid epithelial hyperplasia
Sclerosing adenosis
Complex sclerosing lesions
Papilloma
Fibroadenoma with complex features

Question 24

Intraductal papilloma

Answer 24

Unilateral bloody nipple discharge
Sub-areolar intraductal mass
Intraductal papillary neoplasm with fibrovascular cores lined by benign ductal and myoepithelial cells

Question 25

Epithelial hyperplasia of usual type

Answer 25

Duct lumina are almost completely filled with proliferating epithelium
No cytologic atypia present

Question 26

Proliferative breast disease and risk of Cancer

Answer 26

Atypical epithelial hyperplasia increases the risk by 4 - 5 times.
Epithelial hyperplasia of usual type increase risk by 1.5 -2 times.
Positive family history doubles these risks

Question 27

Proliferative breast disease with atypia

Answer 27

Includes atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH)
ADH is found in ~17% of biopsies performed for calcifications (more commonly is adjacent to a calcified lesion)
ADH also found in fewer biopsies performed for mammographic densities or palpable lesions
ALH is an incidental finding in

Question 28

Proliferative breast disease with atypia 2

Answer 28

Atypical hyperplasia is a cellular proliferation resembling ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS)

• They lack the definitive features for a diagnosis of CIS
• ALH differs from LCIS in that the cells do not fill or distend >50% of the acini in a lobule
• Extension into ducts s risk of invasive carcinoma

Question 29

Clinical significance of benign epithelial changes

Answer 29

Nonproliferative changes DO NOT increase the risk of cancer
Proliferative disease without atypia is associated with a mild increase in risk of cancer
Proliferative disease with atypia (ADH and ALH) confer a moderate increase in risk
LCIS and DCIS are associated with a substantial increase in risk if left untreated (we will talk about this next).
Risk may be modified by a woman’s menopausal status, family history, and time since biopsy

Question 30

Carcinoma of the breast

Answer 30

The MOST COMMON MALIGNANCY OF THE BREAST
Breast cancer is the most common non-skin malignancy in ♀s
A ♀ who lives to age 90 has a 1 in 8 chance of developing breast cancer
-Diagnosis is expected to rise over the next 20 years because of the aging of the population
-Incidence of death exceeded only by lung cancer in ♀s

Question 31

Carcinoma of the breast Incidence and epidemiology

Answer 31

Mammographic screening has altered the incidence of diagnosis
-Screening results in increased detection of small invasive carcinomas and in situ carcinomas
-After screening started, the number of cases increased and after ~10 years of screening, the mortality rate began to decline
Currently, only ~20% of ♀s with breast cancer are expected to die from it

Question 32

Risk factors

Answer 32

Age :
Breast cancer rarely occurs prior to age 25, except in certain  familial cases
Incidence rises over lifetime
75% of cases occur in ♀> 50 years old
Average age of diagnosis is 64
Age of menarche :
There is a 20% increased risk for ♀ who reached menarche 14 yo
Late menopause also increases risk

Question 33

Risk factors 2

Answer 33

First live birth
-♀ with a first full-term pregnancy at 35 yo at their first birth
First-degree relatives with breast cancer
-The risk increases with the number of affected first-degree relatives (mother, sister, or daughter)
-Most cancers occur in ♀s without such a history
-Over 87% of ♀ with a family history will not develop breast cancer
NOTE: This model is not designed to calculate risk for ♀ with a high likelihood for BRCA1 or BRCA2

Question 34

Risk factors 3

Answer 34

Breast biopsies
-Increased risk is associated with prior breast biopsies showing atypical hyperplasia (model does not adjust for mild increase associated with proliferative breast changes without atypia)
Race
-Socioeconomic factors such as access to health care
-Genetic factors
-At age 50, the risk of developing breast cancer within the next 20 years is 1 in 15 for Caucasians, 1 in 20 for African-Americans, 1 in 26 for Asians/Pacific Islanders, and 1 in 27 for Hispanics
-Overall incidence is lower in African-American women
*However, more A-A ♀s

Question 35

Other risk factors

Answer 35

These have not been incorporated into the model owing to their rarity, difficulties in quantifying risk, or lack of definitive studies:
Estrogen exposure
Radiation exposure
Carcinoma of the contralateral breast or endometrium
Geographic influence
Diet, obesity
Exercise
Breast-feeding
Environmental toxins
Tobacco

Question 36

Treatment of ♀ at high risk for developing breast cancer

Answer 36

With the exception of DCIS, all other risk factors for the development of invasive breast cancer affect both breasts equally
Bilateral prophylactic mastectomy can prevent development of 89% of breast cancers in ♀ who are at moderate risk owing to family history
Chemoprevention is another option for ♀s who are at risk of developing invasive breast cancer
-Tamoxifen is a drug that competes for binding to the estrogen receptor (ER) and has both estrogenic and antiestrogenic effects (Most widely used endocrine therapy for breast cancer).
-In selected groups of ♀s, it has been shown to reduce the incidence of breast cancer
Aromatase inhibitors stop the production of estrogen in post-menopausal women

Question 37

Etiology and pathogenesis

Answer 37

The major risk factors for breast cancer are hormonal and genetic
Hereditary breast cancer
-A family history (1st degree relatives) is reported in ~13% of ♀s with breast cancer
-Only 1% of ♀s have >1 affected relative which suggests a highly penetrant germline mutation
-~25% of familial cancers (~3% of all breast cancers) can be attributed to 2 highly penetrant autosomal dominant genes: BRCA1 and BRCA2

Question 38

Hereditary breast cancer

Answer 38

The probablility of breast cancer associated with a mutation in these genes increases if there are multiple affected 1st degree relatives, if individuals are affected before menopause and/or have multiple cancers, if there is a case of male breast cancer, or if family members also develop ovarian cancer
The general lifetime risk for ♀ carriers is 60-85%
The penetrance varies with the type of mutation
-BRCA1 also increases the risk for ovarian cancer (20-40%)
-BRCA2 also inc risk of ovarian cancer (10-20%) but is more frequently associated with ♂ breast cancer
-Also inc risk for other cancers

Question 39

Hereditary breast cancer 2

Answer 39

Both genes act as tumor suppressors and loss of function confers risk of malignancy
BRCA1-associated tumors are more commonly poorly differentiated, do not express hormone receptors or overexpress HER2/neu (an epidermal growth factor receptor that is commonly overexpressed in breast cancer)
Many other genes are also involved (e.g., p53, CHEK2)
Many studies have confirmed that some of the genes (BRCA1 and p53) involved in hereditary breast cancer are also involved in sporadic cases

Question 40

Sporadic breast cancer (non-hereditary)

Answer 40

The major risk factors are related to hormone exposure:
Gender
Age at menarche and menopause
Reproductive history
Breast-feeding
Exogenous estrogen
-The majority of the cancers occur in postmenopausal
♀s and overexpress ER
-Estrogen metabolites cause mutations or generate DNA-damaging free radicals

Question 41

Classification of breast carcinoma

Answer 41

Almost all breast malignancies are ADENOCARCINOMAS

-All other types (i.e., squamous cell carcinomas, phyllodes tumors, sarcomas and lymphomas) are

Question 42

Carcinomas

Answer 42

Invasive carcinoma (synonymous with “infiltrating” carcinoma) has invaded beyond the basement membrane into the stroma
-Cells might also invade into the vasculature and then the lymph nodes and distant sites
-Even the smallest invasive carcinomas have some capacity to metastasize
All carcinomas are thought to arise from the terminal duct lobular unit
-The terms “ductal” and “lobular” do not imply a site or cell type of origin, but reflect differences in tumor cell biology, e.g., whether tumor cells express the cell adhesion protein E-cadherin or not
-“Lobular” refers to carcinomas of a specific type; “ductal” to adenocarcinomas that have no other designation

Question 43

Ductal Carcinoma in situ

Answer 43

The # of cases has risen sharply secondary to mammographic screening (15-30% of carcinomas)
Among mammographically detected cancers, ~½ are DCIS
Most commonly presents as mammographic calcifications
-20-30% of calcifications will be associated with DCIS and must be biopsied
Consists of a limited population of cells limited to ducts and lobules by the basement membrane
-It is a clonal proliferation and usually involves only a single ductule
-However, the cells can spread throughout ducts and lobules and produce extensive lesions involving an entire sector of the breast

Question 44

Historically, DCIS has been divided into subtypes:

Answer 44

Comedocarcinoma is characterized by solid sheets of pleomorphic cells with high grade nuclei and central necrosis
Noncomedocarcinoma consists of a monomorphic population of cells with nuclear grades ranging from low to high (includes solid, cribriform, papillary, and micropapillary)
Paget disease

Question 45

DCIS detection & cure

Answer 45

The majority of cases of DCIS cannot be detected by either palpation or visual inspection of the breast
Mastectomy is curative in >95% of cases
Breast conservation is appropriate for most ♀s but results in a slightly higher risk of occurrence
Major risk factors are grade, size, and margins

Question 46

Lobular carcinoma in situ (LCIS)

Answer 46

Always an incidental finding in a biopsy performed for another reason
-LCIS is not associated with calcifications or a stromal reaction that would form a density
Remains infrequent (1-6%) with or without mammographic screening
Is bilateral in 20-40% of ♀s when both breasts are biopsied (compared to 10-20% for DCIS)
More common in young ♀s (80-90% of cases prior to menopause)
Almost always express estrogen and progesterone receptors
Treatment consists of bilateral mastectomy, tamoxifen, or close clinical observation

Question 47

Invasive (infiltrating) carcinoma

Answer 47

In young ♀s or older ♀s not undergoing mammographic screenings, almost always presents as a palpable mass
-By the time it becomes palpable, > 50% of patients will have axillary lymph node metastasis
*May have lymphedema and skin changes called peau d’orange (looks like an orange peel)
-If central portion of breast involved, may have nipple retraction
-In older ♀s, presents as a density on mammography, and, on average, are ½ the size of a palpable cancer
*

Question 48

Invasive carcinoma, no special type (NST; invasive ductal carcinoma)

Answer 48

These include the majority of carcinomas (70-80%) that cannot be classified as any other type
Recently developed techniques that examine the DNA, RNA, and proteins of carcinomas globally have provided a framework for new molecular classifications of this group of breast cancers
Gene expression profiling, which can measure the relative quantities of mRNA for essentially every gene, has identified five major patterns of gene expression in the NST group: luminal A, luminal B, normal, basal-like, and HER2 positive
-These molecular classes correlate with prognosis and response to therapy, and thus have taken on clinical importance

Question 49

Invasive Ductal Carcinoma

Answer 49

Commonest form of breast cancer especially in poorer populations
higher sing incidence of screen- detected cancer in developed countries (usually smaller; much better prognosis)
Hard, irregular palpable lump
Peau d’orange (lymphatic obstruction thickening/dimpling of the skin)
Paget’s disease of the nipple
(ulceration/inflammation due to
intraductal spread to the nipple)
Tethering of the skin
Retraction of the nipple
Axillary mass (spread to regional lymph nodes)
Distant metastasis (lung, brain, bone)

Question 50

Invasive carcinoma, no special type (NST; invasive ductal carcinoma) Luminal A” (40% to 55% of NST cancers)

Answer 50

This is the largest group and consists of cancers that are ER positive and HER2/neu negative
The majority are well- or moderately differentiated, and most occur in postmenopausal women
These cancers are generally slow growing and respond well to hormonal treatments
Conversely, only a small number will respond to standard chemotherapy

Question 51

Invasive carcinoma, no special type (NST; invasive ductal carcinoma)
“Luminal B” (15% to 20% of NST cancers)

Answer 51

This group of cancers also expresses ER but is generally of higher grade, has a higher proliferative rate, and often overexpresses HER2/neu, and also expresses PR (progesterone receptor)
They are sometimes referred to as “triple-positive cancers”, i.e., expess ER, Her2/neu, and PR
They compose a major group of ER-positive cancers that are more likely to have lymph node metastases and that may respond to chemotherapy

Question 52

Invasive carcinoma, no special type (NST; invasive ductal carcinoma) Normal breast–like” (6% to 10% of NST cancers)

Answer 52

This is a small group of usually well-differentiated ER-positive, HER2/neu-negative cancers characterized by the similarity of their gene expression pattern to normal tissue
It is not yet clear whether or not this is a specific tumor expression pattern

Question 53

Invasive carcinoma, no special type (NST; invasive ductal carcinoma)
“Basal-like” (13% to 25% of NST cancers)

Answer 53

These cancers are notable for the absence of ER, PR, and HER2/neu but the expression of markers typical of myoepithelial cells
By strict definition this group is defined by their gene expression profile
-Basal-like cancers are a subgroup of ER-PR-HER2/neu “triple-negative” carcinomas
They are associated with an aggressive course, frequent metastasis to viscera and the brain, and a poor prognosis

Question 54

Invasive carcinoma, no special type (NST; invasive ductal carcinoma
“HER2 positive” (7% to 12% of NST cancers)

Answer 54

This group comprises ER-negative carcinomas that overexpress HER2/neu protein
These cancers are usually poorly differentiated, have a high proliferation rate, and are associated with a high frequency of brain metastasis

Question 55

Invasive ductal carcinoma

Answer 55

1 . Small nests and cords of neoplastic cells
2.Dense collagenous stroma in between cells

Much less common than IDC
Can present with similar features
More likely to be bilateral and/or 
multicentric (multiple lesions 
within the same breast) 

1. Indian file strands of neoplastic cells
2. Cells are small and uniform
3. Dense stroma

Question 56

Invasive lobular carcinoma

Answer 56

Usually present like carcinomas of NST as a palpable mass or a mammographic density
Reported to have a greater incidence of bilaterality
Demonstrate different metastatic patterns than other breast cancers:
-Metastasize to peritoneum, retroperitoneum, leptomeninges, GI tract, ovaries and uterus vs. lungs and pleura

Question 57

Medullary carcinoma

Answer 57

Presents as a well circumscribed mass and may be mistaken clinically and radiogically as a fibroadenoma
There can be a history of rapid explosive growth

Question 58

Invasive Breast Cancers

Answer 58

Favorable histologic types (85% 5-year survival rate)
-Tubular carcinoma (grade 1 intraductal), colloid or mucinous carcinoma, and papillary carcinoma
Less favorable types
-Medullary , invasive lobular, and invasive ductal carcinoma
Least favorable type
-Inflammatory breast carcinoma
Staging, prognosis, and treatment

Question 59

Favorable histologic types

Answer 59

Tubular carcinoma

• 2% of all invasive breast cancers
• Generally diagnosed by mammography
• Distinctive under microscope
• Long-term survival aproaches 100%

Mucinous (colloid) carcinoma

• 3% of all invasive breast cancers
• Generally confined to elderly population
• Bulky, mucinous tumor with characteristic microscopic features
• 5 and 10 year survival rates are 73 and 59 percent, respectively

Question 60

Less Favorable Histologic Types

Answer 60

Medullary carcinoma

• 4% of all invasive breast cancers
• Soft, hemorrhagic bulky presentation
• Diagnosed microscopically (lymphocytic infiltration)
• Metastases to axillary nodes in 44%
• 5 and 10 year survival rates are 63 and 50 percent respectively

Invasive ductal carcinoma

• Most common and occurs in 78% of all invasive breast cancers.
• Metastases to axillary nodes in 60%
• 5 and 10 year survival rates are 54 and 38 percent respectively

Invasive lobular carcinoma

• 9% of all invasive breast cancers
• Metastases to axillary nodes in 60%
• 5 and 10 year survival rates are 50 and 32 percent respectively
• Higher incidence of bilaterality

Question 61

Mucinous carcinoma

Answer 61

1. Abundant bluish staining mucin with small groups of carcinoma cells

Question 62

Prognostic and predictive factors

Answer 62

The outcome varies widely
Some ♀s have a normal life expectancy as those without any breast cancer
Other have only a 13% chance of 5 year survival

Prognosis is determined by the pathologic examination of the primary carcinoma and the axillary lymph nodes
-Important for counseling patients, choosing treatment, and classifying similar patients for clinical trials

Question 63

Axillary lymph nodes

Answer 63

Breast cancer spreads through lymphatic channels to axillary lymph nodes.
When axillary content is removed, all nodes are searched and embedded for microscopy

Question 64

Major prognostic factors are the strongest predictors of death and are incorporated into the American Joint Committee on Cancer (AJCC) staging system

Answer 64

Invasive carcinoma vs in situ disease
-By definition, in situ cannot metastasize

Distant metastases

• Once present, cure is unlikely, although long-term remissions and palliations can be achieved (especially for hormone responsive tumors)
• Favored sites: lungs, bone, liver, adrenals, brain, and meninges

Question 65

Routes of spread

Answer 65

Local -skin, nipple , chest wall
Lymphatic- lymph nodes
Blood – lungs, liver, bones

Question 66

Lymph node metastases

Answer 66

AXILLARY LYMPH NODE STATUS IS THE MOST IMPORTANT PROGNOSTIC FACTOR FOR INVASIVE CARCINOMA (in the absence of distant metastases)
Biopsy is necessary for accurate assessment
With no involvement, the 10 year, disease-free survival rate is 70-80%
Rate falls to 35-40% with 1-3 + nodes, and 10-15% with >10

Question 67

Major prognostic factors

Answer 67

Tumor size

• The second most important prognostic factor
• ♀s with node-negative carcinomas

Question 68

Minor prognostic factors

Answer 68

Can be used to determine treatment regimens for ♀s with nodal invovlement and/or carcinomas >1 cm in diameter and node-free women with small carcinomas
Three of these factors (estrogen receptor, progesterone receptor, and HER2/neu) are most useful as predictive factors for response to specific therapeutic agents
Histologic subtypes
-The 30-year survival rate of ♀s with special types of invasive carcinomas (tubular, mucinous, medullary, lobular, and papillary) is > 60%
-Survival rate for NST cancers is

Question 69

Estrogen and progesterone receptors (ER and PR)

Answer 69

Assays use immunohistochemistry to detect receptors in the nucleus
50-85% of tumors express estrogen receptors (more commonly seen in post menopausal ♀s)
-Receptor positivity yields a slightly better prognosis
80% of tumors with both ERs and PRs respond to hormonal stimulation with hormonal therapy such as tamoxifen (only ~40% of tumors with one receptor respond)
Tumors with neither receptor have a

Question 70

Her2/neu

Answer 70

Human epidermal growth factor receptor or c-erb B2 or neu is a transmembrane glycoprotein involved in cell growth control
Acts as a cofactor for multiple growth factors
Overexpressed in 20-30% of breast carcinomas
-In many studies, shown to be associated with a poor prognosis
Trastuzumab (Herceptin) is a humanized monoclonal Ab developed specifically to target tumor cells and spare normal cells

Question 71

Proliferative Rate & DNA content

Answer 71

Proliferative rate
-Proliferation can be measured by a variety of means
-Most reliable method to assess proliferation not yet established
-High proliferation rates yield a worse prognosis
DNA content
-Tumors with a DNA index of 1 have a normal amount of DNA but with karyotypic changes
-Aneuploid tumors have abnormal DNA indices and a slightly worse prognosis

Question 72

The two types of stroma in the breast (intralobular and interlobular) give rise to distinct neoplasms

Answer 72

The breast-specific tumors fibroadenoma and phyllodes tumor arise in the intralobular stroma
-This stroma may elaborate growth factors for epithelial cells resulting in the non-neoplastic components of these tumors

-Interlobular stroma is also the source of the same types of tumors found in connective tissue in other sites of the body (e.g., lipomas and angiosarcomas)

Question 73

Fibroadenoma

Answer 73

The MOST COMMON BENIGN TUMOR OF THE FEMALE BREAST
Occurring at any age within the reproductive period of life
Frequently multiple and bilateral
Young ♀s present with a palpable mass and older ♀s with a mammographic density or calcifications
The epithelium is hormonally responsive and may  in size during the late phase of the menstrual cycle
-inc in size during lactation or infarction leading to inflammation may lead a fibroadenoma to mimic a carcinoma
Grow as spherical nodules , usually sharply circumscribed, and freely movable in the surrounding breast substance

Question 74

Phyllodes tumor

Answer 74

The term “cystosarcoma” phyllodes is sometimes used
-The majority of these tumors behave in benign fashion and most are not cystic
Can occur at any age, but most present in the 6th decade
Most present as palpable masses but a few are detected mammographically
Must be excised widely or with mastectomy to avoid recurrence
Majority are low-grade tumors that recur locally but rarely metastasize

Question 75

Other tumors

Answer 75

May arise from skin of the breast, sweat glands, sebaceous glands and hair shafts
Tumors of the extrinsic connective tissue of the breast include the same types of benign and malignant tumors found elsewhere in the body
-Malignant lesions include angiosarcoma, rhabdosarcoma, liposarcoma, leiomyosarcoma, chondrosarcoma, and osteosarcoma
Lymphomas may arise in the breast or be secondarily involved
Metastases usually arise from contralateral breast tumors
-Most frequent nonmammary metastases are from LUNG AND MELANOMAS

Question 76

Gynecomastia

Answer 76

Defined as enlargement of the male breast
-Presents as a buttonlike subareolar enlargement
May be unilateral or bilateral
Must be differentiated from the RARE carcinoma
Chiefly of importance as an indicator of hepatic cirrhosis (liver metabolizes estrogen) or a functioning testicular cancer (Leydig cell tumors or, rarely, Sertoli cell tumors)

Question 77

Gynecomastia 2

Answer 77

The male breast is subject to hormonal influences
-Gynecomastia may occur as a result of an imbalance between estrogens (which stimulate breast tissue) and androgens (which counteract these effects)
It is encountered in a variety of normal and abnormal circumstances
-May be found at the time of puberty, in the very aged, or at any time in adult life when there is cause for hyperestrinism
*Most important is cirrhosis (liver metabolizes estrogen)
*In older males, may occur owing to a relative  in adrenal estrogens as the androgenic function of the testes fails

Question 78

Gynecomastia circumstances

Answer 78

Drugs
-Alcohol, marijuana, heroin, antiretroviral therapy, anabolic steroids, some psychoactive agents
Rarely, may occur in association with Klinefelter syndrome
Presence of functioning testicular cancers (Leydig cell tumors or, rarely, Sertoli cell tumors)

Question 79

Carcinoma in male

Answer 79

A RARE occurrence in the male breast

Frequency ratio relative to female breast cancer is

Question 80

Carcinoma risk factors

Answer 80

Gynecomastia does not seem to be a risk factor
4-14% of cases in males are attributed to germline BRCA2 mutations
-A breast cancer family with at least 1 affected male has a 60-76% chance of having a BRCA2 mutation
-Male breast cancer is less commonly observed in BRCA1 families
3-8% of cases are associated with Klinefelter syndrome

Question 81

Carcinoma Path

Answer 81

Remarkably similar to that of ♀s
The same histologic subtypes of invasive cancer are present
-Although papillary carcinomas are more common and lobular carcinomas less common
The expression of molecular markers is similar except that ER positivity is more common (81%of male tumors)
Unlike ♀s, incidence of ER-positive tumors does not  with age
Prognostic factors are similar

Question 82

Carcinoma clinical presentation

Answer 82

Usually present as a palpable subareolar mass (2-3 cm)
Nipple discharge is common
Because they are situated close to the overlying skin and chest wall, even small carcinomas can invade these structures
Ulceration through skin more common in males
Dissemination pattern is similar to that of females
-Distant metastases to lung, brain, bone, and liver common

Question 83

FACTS WORTH REPEATING

Answer 83

More than 90% of all breast lumps are discovered by women themselves.
The majority of all breast lumps are benign.
About one women in eight (12%) will develop breast cancer sometime in her life.
90% of women with breast cancer have no family history

Question 84

Bottom Line Concepts

Answer 84

It is important to evaluate breast complaints thoroughly to ensure that breast cancers, as well as benign breast lesions, are diagnosed and treated promptly.
Evaluation of a woman presenting with a breast complaints requires careful assessment of symptoms and risk factors for developing breast cancer.
The clinical breast exam include inspection and palpation of the breast tissue, chest wall, and regional lymph nodes. Documentation should included both positive and negative findings.
Women with breast problems can present with any combination of symptoms including breast mass or thickening, breast pain, nipple discharge, or skin changes.
Typically, women presenting with a suspicious breast mass who are > 30 yrs should receive a diagnostic mammogram, whereas women younger than 30 should receive a diagnostic ultrasound.
Negative imaging should not stop further investigation is a suspicious lump is felt on clinical exam.
Masses that are solid on ultrasound imaging require biopsy to exclude cancer and provide a histological diagnosis.