How does the breast develop in the embryo?
The skin involutes and begins developing from sweat glands. The breast tissue can arise anywhere along the milk line (axilla to vulva).
What is the functional unit of the breast?
Terminal duct-lobular unit. Lobules make milk and ducts drain the milk to the nipple.
What does histology of normal lobules and ducts look like?
2 layers of epithelium: columnar lumenal cell layer (protects duct and makes milk in lobule) + myoepithelial layer (squeezes duct to push milk forward).
What hormone receptors are present in breast tissue?
Estrogen and progesterone. This is why there is breast development after menarche, tenderness during the menstrual cycle, hyperplasia during pregnancy and atrophy after menopause.
Where is the highest density of breast tissue located?
The upper outer quadrant of the breast.
What things can cause galactorrhea?
Galactorrhea is milk production outside of lactation. Causes include nipple stimulation, prolactinomas and drugs.
A breast-feeding mother presents with a warm, erythematous and tender breast. There is purulent discharge and a tender mass on the right side. How do you treat her?
Breast feeding causes fissures around the nipple that allow infection by S. aureus and results in mastitis. You treat this with continued drainage and dicloxacillin to prevent abscess formation.
A 33 year old woman presents with a subareolar mass and nipple retraction. She has a history of smoking. What is likely causing her condition?
Periductal mastitis. Smoking causes a relative vitamin A deficiency. This results in squamous metaplasia in the lactiferous ducts (normally highly-specialized columnar cells that require vitamin A) and keratin production that plugs the ducts. In the plugged tube you get an inflammatory response that increases fibroblast activity, causing fibrosis and nipple retraction.
A 60 year old post-menopausal woman with a history of multiple pregnancies presents with a warm, tender, erythematous subareolar mass. There is a green-brown nipple discharge. What is likely causing her condition?
Mammary Duct Ectasia. Inflammation in wall of the subareolar duct causes dilation (ectasia) of the duct. Inflammatory products come out of the duct as a green-brown discharge. Note that this is a rare condition.
A 60 year old post-menopausal woman with a history of multiple pregnancies presents with a warm, tender, erythematous subareolar mass. There is a green-brown nipple discharge. If you were worried about breast cancer in a post-menopausal woman what would you likely see on your biopsy?
Chronic inflammation with plasma cells is characteristic of mammary duct ectasia.
A 35 year old woman has a mass on breast examination and calcification on mammography. To be safe you do a biopsy and see necrotic fat with calcifications and giant cells. What caused her condition?
Necrosis of breast fat after trauma. Trauma to the fat causes inflammation, necrosis, fibrosis and giant cell formation. Calcification is a result of saponification from fat necrosis. Note that trauma like a softball to the chest is sufficient to cause this condition.
A 26 year old woman presents with a vague, irregular and lumpy breast in the upper outer quadrant of both breasts. What would you likely see on biopsy of these small lumps?
In fibrocystic change you would see dilation of the lobular acini and ducts. Dilation causes inflammation and you would see connective tissue and fibrosis. Grossly the cysts would have a blue-domed appearance.
A 26 year old woman presents with a vague, irregular and lumpy breast in the upper outer quadrant of both breasts. You do a biopsy and diagnose her with fibrocystic change. What is the cause of this and what is her risk for cancer?
The rising a falling of estrogen and progesterone is a likely cause of fibrocystic changes, which most often occur in premenopausal women. This is benign in its pure form and carries no additional risk for cancer.
What characteristics of fibrocystic change increases risk for invasive breast carcinoma for both breasts regardless of which breast it was found in?
1) Fibrosis + Cysts + Apocrine metaplasia = NO increased risk 2) Ductal hyperplasia (excess lumenal epithelium) and/or Sclerosing Adenosis (too many mammary glands w/connective tissue fibrosis/calcification) = 2x risk 3) Atypical hyperplasia (ductal or lobular atypical cells) = 5x risk
A 30 year old woman presents with bloody nipple discharge. You do an intraductal biopsy and tell her that her condition is benign. What did you see on biopsy?
Intraductal papilloma: a papillary lesion (finger-like projection w/fibrovascular core lined by one layer of epithelial cells and one layer of myoepithelial cells) in the alveolar ducts that often bleeds and causes a bloody nipple discharge.
A 30 year old woman presents with bloody nipple discharge. You do an intraductal biopsy and tell her that her condition is malignant. What did you see on biopsy?
A papillary carcinoma is more common as women age and more often seen in a post-menopausal woman. Papillary carcinomas lack myoepithelial cells.
Most common benign neoplasm of the beast? (Also most common tumor in premenopausal females)
Fibroadenoma. Note that it is not as common in postmenopausal females because the fibroadenomas are estrogen sensitive.
A 30 year old woman presents with a well-circumscribed, mobile, marble-like mass in her right breast. She says that it has grown since her last pregnancy. Biopsy is shown below. What is the most likely diagnosis? What is her prognosis?
Fibroadenoma. Note the fibrous tissue and glands sharply demarcated from adjacent breast tissue. These are the most common tumor in premenopausal women, is benign and is estrogen sensitive. Note that there is no increased risk for breast cancer.
A 60 year old woman presents with a well-circumscribed, mobile, marble-like mass in her right breast. Biopsy is shown below. What is the most likely diagnosis? What is the prognosis?
Note the overgrowth of the fibrous component and leaf-like projections in a postmenopausal woman. This is a phyllodes tumor. These can be malignant.
Most common carcinoma in women by incidence? What is the major risk factor for this?
Breast cancer. It is also the 2nd most common cause of cancer mortality. The most common risk factor is estrogen exposure (being female, early menarche & late menopause and obesity). Additional risk factors include atypical hyperplasia and 1st degree relative w/breast cancer (sister, mother and daughter).
Ductal carcinoma in situ that has walked its way up the duct and out onto the nipple.
Paget’s disease of the nipple
Ductal carcinoma in situ that has invaded the ductal basement membrane into the surrounding stroma.
Invasive ductal carcinoma
Lobular carcinoma in situ that has invaded through the lobular basement membrane and into connective tissue.
Invasive lobular carcinoma
Breast cancer that is more commonly detected as calcification on mammography than a mass?
Ductal carcinoma in situ (Comedo type). When the malignant cells proliferate within the ducts, the center of the proliferation becomes necrotic. It also undergoes dystrophic calcification and shows up on mammography. It does not present as a mass because it is confined to the ducts.
Non-malignant presentations of calcification on mammography
Fat necrosis and sclerosing adenosis
A 35 year old woman presents with nipple ulceration and erythema. Nipple biopsy is shown below. What is your diagnosis?
Paget disease of the nipple occurs when ductal carcinoma in situ walks its way up the duct onto the nipple. Note the squamous cells with the lighter colored cytoplasm invading through the epidermis from the ducts.
A 30 year old woman presents with a breast mass on physical exam. You also note dimpling of the skin and retraction of the nipple. Biopsy shows duct-like tissue in a desmoplastic stroma with supporting CT growing with the mass. What is your diagnosis?
Invasive ductal carcinoma.
Most common type of invasive breast carcinoma
Invasive ductal carcinoma.
What are the subtypes of invasive ductal carcinoma?
Tubular CA, mucinous CA, medullary CA and inflammatory CA.
Which subtype of invasive ductal carcinoma is shown below?
Tubular CA. Note that there is a desmoplastic stroma (blue-grey connective tissue) and despite proliferation of normal-looking ducts, you would only see one cell type (no myoepithelial cells) on higher power.
What is the prognosis of tubular invasive ductal CA?
Which subtype of invasive ductal carcinoma is shown below? What is the prognosis? What is the population that you most often see this in?
Mucinous CA. Note malignant cells floating in pools of mucus. Prognosis is excellent. Most often seen in elderly population.
Tumor to always have in mind in a patient with acute mastitis.
Inflammatory breast CA.
A woman presents with a breast that is highly erythematous and swollen. You put her on antibiotics and her condition does not resolve. Her biopsy is shown below. What is your diagnosis? What is the prognosis?
Inflammatory invasive breast CA. Note that there is cancer within the dermal lymphatics. This decreases drainage of the breast and causes the swelling and erythema. This has a poor prognosis because the tumor is already sitting in the dermal lymphatics.
What pieces are essential for diagnosis of inflammatory breast CA?
Clinical inflammation of the breast and cancer present in the lymphatics.
A patient presents with a biopsy showing high grade malignant tumor cells with lots of lymphocytes and plasma cells in breast tissue. What is a common genetic association with her condition?
Invasive medullary breast CA is often associated with BRCA1 mutations.
A 30 year old woman comes in for biopsy of a breast mass. On biopsy you see dyscohesive cells filling lobules away from the mass biopsied. The cells are confined by the basement membrane. What is most likely causing her condition and where else might it be found?
Lobular carcinoma in situ cells lack E-cadherin that normally allows cells to stick together, this is why they are dyscohesive. LCIS rarely produces a mass or calcification and is found incidentally. Finally it is often multifocal and bilateral.
A 30 year old woman comes in for biopsy of a breast mass. On biopsy you see dyscohesive cells filling lobules away from the mass biopsied. The cells are confined by the basement membrane. How do you treat her?
LCIS is a low risk factor for invasive carcinoma and is not a malignant proliferation itself. . You treat with tamoxifen and close follow-up.
A 30 year old woman comes in for biopsy of a breast mass. On biopsy you see invasive malignant cells that do not form ducts, but grow in a single-file pattern. What is the most likely diagnosis?
Invasive lobular carcinoma. They don’t form ducts because they lack E-cadherin and cannot form ducts due to lack of cohesion.
How is prognosis of invasive lobular carcinoma determined?
T (tumor) N (axillary node metastasis) M (distant metastasis).
What indicates a very poor prognostic sign for invasive lobular carcinoma. How is prognosis typically determined?
Distant metastasis indicates a very poor prognosis but happens rarely. The most useful factor in determining prognosis is sentinel node biopsy of the axillary lymph nodes.
Why do a sentinel lymph node biopsy instead of complete nodal removal?
75% of patients with breast cancer don’t have breast cancer in the lymph nodes and do not need the arm swelling from nodal removal. By injecting radioactive dye you can visualize the very 1st lymph nodes that are drained by the breast. If the 1st lymph nodes are negative, you can conclude that the rest of the nodes are negative for metastatic breast cancer.
What are predictive factors that predict response to treatment?
Estrogen Receptor, Progesterone Receptor and HER2/neu. If the tumor expresses ER and PR you give anti-estrogenic agents like tamoxifen. If the tumor is associated with HER2/neu gene amplification, then you treat with trastuzumab/herceptin (antibody against HER2/neu receptor).
How does HER2/neu amplification cause cancer?
It is a cell surface growth factor receptor. If these receptors are amplified then there is excess cell growth and proliferation of tumors.
A patient presents with a lump in her breast and sentinel lymph node biopsy shows malignant cells. Immunohistochemical staining reveals cells that are negative for ER, PR and HER2/neu. What demographic is at highest risk for this type of breast cancer?
These patients are triple negative and have a poor prognosis. Note that African-American women have an increased propensity for this.
A 30 year old woman presents with breast cancer. Her mother and sister both got breast cancer around age 30 also. She has a history of multiple tumors. What gene mutations could be causing her condition? How do you treat her?
10% of breast cancers are hereditary which seems evident in her history. BRCA1 mutations cause breast, ovarian (most often serous) and fallopian tube carcinoma. You may treat her with prophylactic mastectomy.
What hereditary gene mutation can cause breast carcinoma in males? How does it typically present?
BRCA2, also associated with Klinefelter. Remember that male breast cancer is rare. It typically presents as a subareolar mass (most breast tissue is under the nipple in males) in older males with nipple discharge. They type of cancer is usually invasive ductal carcinoma because men don’t have lobules.
What type of breast cancer has an increased incidence in patients with BRCA1, although it is not the most common type of breast cancer in these people?
Medullary breast carcinoma.