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Pathoma- Chapter 16: Breast Cancer
Terms in this set (140)
What is the most common carcinoma in women by incidence (excluding skin cancer)?
What is the 2nd most common cause of cancer mortality in women?
What is the most common cause of cancer mortality in women?
The risk factors for breast cancer are mostly related to what?
Risk Factors for Breast Cancer
1) Female gender (99% of cases)
2) Age (peak incidence age 70-80)
3) Early menarche/late menopause
5) Age at 1st birth
-early age (<20) = protective
-older age (>35) = higher risk
6) Atypical Hyperplasia
7) First-degree relative with breast cancer (mother, sister, daughter)
8) Race - Non Hispanic WHITE women
9) Breast feeding = protective
What is the number one risk factor for breast cancer?
The classic woman that has breast cancer is what age?
-She will be a postmenopausal female
(peak incidence at 70-80)
Peak age of incidence for Breast cancer
What race has the highest incidence of breast cancer?
Why do women who have early menarche/late menopause have an increased risk for breast cancer?
-Because they will have an increased exposure to estrogen for a longer duration resulting in an increased risk for breast cancer
Why does obesity lead to an increased for breast cancer?
-Adipose tissue has the ability to convert androgen to estrone (a type of estrogen)- and therefore increase the risk for breast cancer
Why does the presence of atypical hyperplasia result in an increased risk for breast cancer?
-If atypical hyperplasia is seen on a biopsy it means that there is a 5x increased risk for breast cancer in both breasts
-The presence of atypical hyperplasia means that there must be excess estrogen on board or some sort of estrogen-related risk factor because that is why the hyperplasia is occurring
What sort of family history increases a person's risk for breast cancer?
-Having a first-degree relative with breast cancer, i.e., a sister, mother, or daughter
How does age at first live birth influence the risk of breast cancer?
1)Younger age <20 = protective
2) Older age >35 = higher risk
Breast feeding _________ the risk of breast cancer
(increases or decreases)
What is the functional unit of the breast?
-Terminal Duct Lobular Unit
Most common findings of breast cancer on PE and mammography?
Palpable breast mass with micro-calcifications
What is your differential Dx of a Mammogram showing microcalcifications?
1) Fat necrosis
2) Sclerosing adenosis
3) Ductal carcinoma
What are the 4 main types of breast cancer?
1) Ductal carcinoma in situ (DCIS)
2) Invasive ductal carcinoma
3) Lobular carcinoma in situ (LCIS)
4) Invasive lobular carcinoma
in situ = limited by basement membrane
Almost ALL Breast cancers are what histological type?
arise from what cells?
95% are adenocarcinomas
Arise from epithelial cells of the ducts/lobules
At Dx, most breast cancers are invasive or in situ?
INVASIVE :( >70%
What is ductal carcinoma in situ? (how it appears on histology)
-When you get a malignant proliferation of cells in the duct---> malignant cells fill the ductal lumen
-bound by basement membrane
What is the key feature of the malignant cells in DCIS (high-yield)?
-The malignant cells are bound by the basement membrane
If the malignant cells of DCIS move up the duct and come out on to the surface of the nipple, it is called what (high-yield)?
-Paget disease of the nipple/breast
What happens if the malignant cells of the DCIS invade through the basement membrane and into the surrounding stroma?
-Invasive Ductal Carcinoma
What is DCIS?
-Malignant proliferation of cells in the ducts
What is the key feature of DCIS?
-There is NO invasion of the basement membrane
How is DCIS detected?
-Because these cells are simply growing in ducts, you wouldn't be able to detect it as a mass
-Instead, it is going to be detected as calcification on mammography
Classic mammogram finding of DCIS?
Is this also present in LCIS?
DCIS = Microcalcifications
LCIS = NO calcifications
Which breast cancer type is associated with calcifications on mammogram?
Ductal carcinomas (NOT lobular)
Why will you be able to detect DCIS as calcification on mammography?
-The malignant proliferation of cells within the duct cuts off the blood supply
-This results in some of the cells within the center of the duct to die off
-It is possible to get calcification on top of these dead cells- this is called dystrophic calcification
What type of calcification is seen in DCIS on mammograms?
What are two examples of changes in the breast that will result in calcification on the mammogram but are ultimately benign?
-Fat necrosis- due to the resulting saponification
-Sclerosing adenosis (a type of fibrocystic change)
Cribriform DCIS is characterized by what histological pattern?
Cookie cutter pattern w/ well defined circles
What is the most high-yield form of DCIS?
-Comedo-type = HIGH RISK
What is seen in the comedo type of DCIS (very high-yield)?
-Will see high-grade cells with necrosis and dystrophic calcification in the center of ducts
(large tumor cells w/ pleomorphic nuclei + central necrosis)
Histological finding of Comedy type DCIS?
HIGH-GRADE -Large tumor cells w/ pleomorphic nuclei, central necrosis + dystrophic calcification
What is Paget Disease of the nipple?
-This is DCIS that extends up ducts to the skin of the nipple
How will Paget Disease of the nipple present on PE?
-Presents as nipple ulceration and erythema + may cause bloody discharge
Classic PE appearance of Paget disease of the nipple?***
Nipple ulceration (scaling/flaking) w/ Erythema that may have bloody discharge
Mammary Paget disease causes what Key Sx?
Pain, Burning, Itchy nipple with ulceration
May mimic acute mastitis but does NOT resolve with abx/steroids
Mammary Paget disease may mimic what other disorder?
How is this distinguished?
Acute mastitis - BUT Paget disease does NOT resolve w/ Abx/Steroids
Paget Disease of the nipple is almost always associated with what (very high-yield)?
-Almost always associated with an underlying INVASIVE carcinoma
Pt experiences pain, itching, + burning w/ erythema to her left nipple. Sx do not resolve with Abx and steroids, Dx?
Mammary Paget disease - refer for biopsy + mammogram to explore INVASIVE carcinoma
Paget DCIS Biopsy Findings on Histology
-In between the normal squamous cells, you have all of these cells with this lighter-colored cytoplasm (Paget cells) - these are the malignant cells walking their way up to the epidermis
Paget cells are described as?
If these are detected on biopsy of the nipple, what is the pt at risk for?
Intraepithelial adenocarcinoma cells
Highly associated with underlying invasive carcinoma
What is the most common type of invasive breast carcinoma?
Invasive DUCTAL carcinoma
What is invasive ductal carcinoma?
-Have the malignant cells of DCIS invade through the basement membrane and enter into the CT
Invasive ductal carcinoma will classically form what on histology?
-Duct-like structures w/ stroma
What is the most common type of invasive carcinoma?
-Invasive ductal carcinoma
How will invasive ductal carcinoma classically present?
-As a mass detected by physical exam or mammography
Why is mammography a very good test?
-Allows us to detect breast cancer >1 cm- allowing us to detect it at a much earlier stage than we would be physical exam
What can happen as a result of the invasive ductal carcinoma traveling through the breast tissue? (affect on the nipples)
-Advanced tumors may result in dimpling of the skin or retraction of the nipple (important)
What will you see on biopsy of invasive ductal carcinoma?
-Will see duct-like structures in a desmoplastic stroma
Invasive Ductal Carcinoma
What do we mean by desmoplastic stroma?
-We have CT growing with the tumor- which is there to grow with the tumor and provide it structural support
What are the special subtypes of Invasive Ductal Carcinoma
Invasive Ductal Carcinoma
What is the characteristic feature of tubular carcinoma?
-The cancer produces tubules- which look very much like normal breast- making it hard to distinguish the two
Invasive Ductal Carcinoma
How will be able to determine whether or not a tubular carcinoma is malignant or not?***
-You will see a desmoplastic stroma
If you were to test the cells of a tubular carcinoma, what you find?
-There would be no 2nd cell type
-The normal ducts and lobules of the breast have 2 cell types- an epithelial cell layer (luminal) and a myoepithelial cell layer
-However, cancer would not have 2 cell types- so if you only see 1 cell type- you know that you are dealing with a tubular carcinoma
What is the prognosis of tubular carcinoma?
-It has a very good prognosis
What is the key feature of mucinous carcinoma?
-You have malignant cells floating around in pools of mucous
What are the 2 important things to know about the mucinous carcinoma?
-It has an excellent prognosis- the tumor cells are stuck in mucous so they can't go anywhere
-This usually occurs in elderly women
What is the prognosis of mucinous carcinoma?
-It has an excellent prognosis- the tumor cells are stuck in mucous so they can't go anywhere
What demographic is most affected by mucinous carcinoma ?
-This usually occurs in elderly women
Subtype of invasive ductal carcinoma that presents similarly to acute mastitis?
Inflammatory carcinoma - presents as erythema, swelling of breast
How will pts. with inflammatory carcinoma present?
mimics what condition?
-Present with a breast that is highly erythematous and swollen- so it looks like the pt. has acute mastitis
How can you tell the difference between inflammatory carcinoma and acute mastitis?***
-If you put the pt. on antibiotics, the inflammatory carcinoma will not resolve
How is an inflammatory carcinoma characterized?
-Characterized by the presence of cancer within the dermal lymphatics
-This decreases the drainage of the breast- resulting in a swollen erythematous breast
Inflammatory carcinoma develops when the tumor invades where?
invades skin (dermal) lymphatic vessels
How do you diagnose Inflammatory Carcinoma (very high-yield)?
-It is a clinical pathologic entity
-You need to see inflammatory changes within the breast clinically and then you must prove that there is tumor within the dermal lymphatics pathologically
What is the prognosis of inflammatory carcinoma (very high-yield)?
-It has a very poor prognosis
-Because the tumor is already sitting within the dermal lymphatic spaces- and has access to the lymph nodes and potentially the rest of the body
What tumor should you always think about in a patient that has acute mastitis (especially on an exam)?
-Think about an inflammatory carcinoma
-On an exam, they will give you a woman who is breast feeding and presents with what appears to be acute mastitis- but the infection doesn't resolve after a course of antibiotics
-If you have a woman with acute mastitis and you give her antibiotics, it is important to see that woman 5-10 days later to ensure that the antibiotics took care of the problem
Classic appearance of Inflammatory carcinoma?
Peau d'orange ~ orange rind
If a swollen, erythematous breast is described as an orange, what should you be concerned for?
Peau d'orange = Inflammatory carcinoma
orange peel appearance of breast due to edema
Dx = Inflammatory carcinoma
How is medullary carcinoma characterized?
-Characterized by large, high-grade cells growing in sheets with associated lymphocytes and plasma cells
What type of Invasive ductal carcinoma is associated with BRCA1 carriers?
Pts. with what mutation have an increased propensity for the development of medullary carcinoma (very high-yield)?
What is lobular carcinoma in situ?
Malignant proliferation of cells in lobules with no invasion of the basement membrane
How is LCIS characterized?
-There is no invasion of the basement membrane
How is LCIS usually detected?
-It is usually detected incidentally- you find it by accident
-It does not produce a mass or calcification
T/F LCIS produces calcifications + a mass like DCIS
FALSE - LCIS does NOT produce a mass NOR calcification - hence why it is usually detected incidentally
How will the cells in LCIS appear on histology?
-They are often dyscohesive- which means that they are not stuck together
What is the adhesion molecule that LCIS LACK (very high-yield)?
How does this affect the cells histologically?
-This is why the cells appear dyscohesive
What is the function of E-cadherin?
-It is essentially the glue that allows cells to stick together
Classic histological finding of LCIS?
Dyscohesive growth of cells
Why: LOSS of E-cadherin --> loose intercellular connections
How will LCIS present?
-It is often multifocal and bilateral
How does LCIS present on PE + Mammogram?
INCIDENTAL finding - typically clinically occult
-NEVER forms a mass
-does NOT produce calcifications (like DCIS)
-multifocal + b/l
What do believe LCIS to be?
-A risk factor for the future development of breast cancer in BOTH breasts
(if found, has LOW possibility to become invasive itself but signifies future increased risk of breast carcinoma for BOTH breasts)
How do we treat LCIS?
-We don't try to excise it
-We use pharmacologic agents like tamoxifen- which is an anti-estrogen agent- in the hopes of decreasing the risk of those cells progressing to become invasive carcinoma
What drug do we use to treat LCIS?
-Tamoxifen and close follow-up
(do NOT excise since it has a LOW risk of progression to invasive carcinoma)
What is the clinical course of LCIS?
(risk of progression to invasive carcinoma)
-It has a low risk of progression to invasive carcinoma
(represents more of a risk factor for future invasive carcinoma)
LCIS is regarded as a risk factor for?
Risk factor for invasive carcinoma in both breasts
Which breast cancer type is a true precursor lesion for invasive carcinoma: DCIS or LCIS?
(LCIS rarely becomes invasive; only serves as a risk factor)
What is invasive lobular carcinoma?
-Is a tumor of lobular cells that invades beyond the basement membrane of the lobules and into the actual CT of the breast
What is the classic pattern of invasion of the Invasive lobular carcinoma (super high-yield)?
-Grows in a single-file pattern
Why do the cells in invasive lobular carcinoma grow in a _________ pattern (super high-yield)?
SINGLE File Pattern
-There is no duct formation because the cells lack E-cadherin
Invasive lobular carcinoma typically presents as?
1) BILATERAL w/ MULTIPLE lesions (both breasts are equally affected)
2) Histo = single file pattern cells (LACK E-Cadherin)
What is the main way by which we determine the prognosis of breast cancer?
-TNM staging system
-Tumor- size of the tumor
-Nodes- metastasis to local lymph nodes (would assess the axillary lymph nodes to determine this)
-Metastasis- refers to distant metastasis
What is the most important prognostic factor?
-If a patient has metastasis outside of the region (outside of the breast and the axillary lymph nodes)- it would be a very poor prognostic sign
Breast cancer would spread to what node first?
Most patients don't often present with metastasis, so what is the most useful factor (very high-yield)?
-The spread to axillary lymph nodes
How do we determine spread to the axillary lymph nodes?
-This is done via sentinel node biopsy
-The determination of cancer in these nodes affects whether or not to give these pts. chemotherapy
Lymph Node Biopsy complications? (if we biopsied the entire axillary lymph node chain)
-One way to do it is to remove all of the axillary lymph nodes
-However, the problem with this method is the fact that if the patient doesn't have any cancer in those lymph nodes- they now lack drainage of the arms- and will develop swelling of the arms as a complication
-Around 75% of pts. with breast cancer don't even have cancer in their lymph nodes- so we were causing arm swelling in pts. that we didn't even need to
Sentinel Node Biopsy procedure?
-You inject the breast with a blue dye or a radioactive substance and allow that blue dye/radioactive substance to go to the lymph nodes
-The axillary lymph nodes are arranged in tiers- and this allows for the very first line of lymph nodes that are drained by the breast to be assessed
-You then open up and remove the lymph nodes that have been marked by the blue dye/radiotracer
-If those lymph nodes are negative, you can make the assumption that the rest of the lymph nodes behind them are also negative
-If those sentinel nodes are (+), you will go back and remove all of the other lymph nodes at this time
What are the 3 most important predictive markers for breast cancers response to treatment?
location of these markers in the cells?
-ER (+) = cytoplasm (estrogen)
-PR (+) = cytoplasm (progesterone)
-HER2/neu (+) = cell surface
If a tumor is ER/PR (+), what does it mean for therapy?
-Means that we can expect a response when we give them anti-estrogenic agents (tamoxifen)
What is HER2/neu?
-Is a cell surface growth factor TYROSINE KINASE receptor
What type of gene is HER2?
growth promoter proto-oncogene
Why would a breast cancer have excess HER2/neu?
-Classically due to gene amplification
-And this excess amplification can result in excess growth of the cell- and drive the proliferation of the tumor
What type of receptor is HER2?
cell surface tyrosine kinase growth factor receptor (EGFR)
What drug has been used to treat HER2/neu (+) breast cancer?
Where is the estrogen receptor complex initially located?
-It is initially present in the cytoplasm
-But when it binds its substrate- it moves to the nucleus
-Progesterone receptor is also a receptor that translocates itself to the nucleus
Where is HER2/neu present (high-yield)?
-It is present on the surface of the cells
-It is a proto-oncogene that, when amplified, becomes an oncogene
What is 'triple negative' breast cancer?
-Negative for ER, PR, and HER2/neu receptors
What is the prognosis of 'triple negative' breast cancer?
associated highly with what race?
-It has a poor prognosis - African American women
What race has an increased propensity to develop Triple negative breast carcinoma?***
(3) types of breast cancer based on markers?
Therapy for each?
Which is HIGHLY Aggressive?
1) ER+, PR+
3) ER-, PR-, HER2- (triple negative)
-HIGHLY aggressive associated with African American women
Features Suggesting Hereditary Breast Cancer (3)
1) Multiple first-degree relatives with breast cancer
2) Tumor at PRE-menopausal age
3) Multiple tumors
What are the 2 most important single-gene mutations that result in hereditary breast cancer?
BRCA1 pts. have an increased risk for what type of cancer?
-Breast, Serous ovarian, + Fallopian tube carcinoma
BRCA1 mutations lead to an increased risk of what subtype of breast cancer?
-Increased propensity for medullary carcinoma of the breast
(subtype of invasive ductal carcinoma)
BRCA1 mutations classically lead to what type of ovarian carcinoma?
-Classically a serous carcinoma
BRCA1 doesn't only increase the risk for a serous ovarian carcinoma but also increases the risk of what other type of gynecological cancer (very high-yield)?
-Fallopian tube carcinoma
1) Medullary Breast carcinoma
2) Serous Ovarian carcinoma
3) Fallopian tube carcinoma
BRCA2 is classically associated with breast cancer in what gender (very high-yield)?
-Breast carcinoma in males
Cancers associated with BRCA2?
- breast (both genders- MALES)
- ovary (epithelial)
What type of genes are BRCA?
what do they encode for?
Tumor suppressor genes that encode for DNA repair proteins
BRCA1 and BRCA2 mutations are more common among what ethnicity?
Mode of inheritance of BRCA mutations?
how is the phenotype expressed?*
Expresses IN-complete penetrance - not all pts who have the gene develop cancer.
Pts. with a genetic predisposition for breast cancer may elect to undergo what?
-A prophylactic mastectomy
-Even if both breasts are removed, a small risk still remains for the development of breast cancer (important to remember)- due to the fact that we can sometimes have excess breast tissue that can extend into the axilla or subcutaneous tissue of the chest wall- so these pts. still need to be watched carefully
How common is male breast cancer?
-It is rare (1% incidence)
How does male breast cancer present?
-Presents as a subareolar mass under the nipple in older males
Where is the vast majority of breast tissue located in the male?***
-In the subareolar region
(vs lateral upper outer quadrant in females)
How can male pts. with breast cancer present?
-May produce nipple discharge w/ subaerolar mass
What is the most common form of male breast cancer?
-It is a ductal carcinoma
-Because the male breast do develop terminal ducts but do not develop lobules
Male breast cancer is associated with which BRCA mutation?***
Male breast cancer is associated with what syndrome?
(2) Key associations with Male Breast cancer?
2) Klinefelter syndrome
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