Breast Flashcards
What is the general structure of the breast?
• Two major structures, ducts and lobules.
• Two types of epithelial cells, luminal and myoepithelial.
• Two types of stroma, interlobular and intralobular.
The superficial layers are lined by keratinized squamous cells, the duct and lobular system are made of double layers consisting in myoepithelial cells with a contractile system and luminal cells which are highly responsive to estrogen and progesterone.
Why is pregnancy considered a protective factor?
At the end of pregnancy massive epithelial apoptosis occurs, this explains why pregnancy is considered a protective factor for the development of breast cancer.
What are some general clinical features of breast disease?
• Pain : It is associate to benign cases. Only 10% of breast cancers present pain.
• Palpable masses : Most commonly include cysts, fibroadenomas and invasive carcinomas.
• Nipple discharge : Worrisome if spontaneous and unilateral. Milky discharge is not associated with cancer. Bloody or serous discharge are associated to papilloma.
Epidemiology of breast cancer?
Each woman in the span of a lifetime will have a 1/8 chance of developing this disease. It is rare in women younger than 25 but the incidence increases rapidly after 30. For what concerns ER positive cancers they continue to increase with age where is the incidence of ER negative cancers and HER2 positive cancers remain relatively constant.
What are some genetic involvements in breast cancer? Risk factors?
Approximately 12% of breast cancer’s occur due to inheritance of an identifiable susceptibility gene. The main ones are BRCA1, BRCA2, TP53 and CHEK2. There are also cases of sporadic breast cancer which are related to hormone exposure, reproductive history, breast-feeding and other environmental risks like radiation exposure, hormone therapy and alcohol.
What are the three major pathways of carcinogenesis involving breast cancer?
• ER+. HER2- cancer, luminal type : represents 50 to 65% of cases and it is the most common subtype found in individuals inheriting BRCA2.This subtype most closely resembles normal breast luminal cells therefore the name. Associated with flat epithelial atypia and atypical ductal hyperplasia.
• HER2+ cancer : This type constitutes about 20% of all breast cancer’s. It is strongly associated with the amplification of the HER2 gene and it is the most common some type of found in patients with TP 53 mutation. Most associated with atypical apocrine adenosis lesions.
• ER-,HER2- cancer : It’s compromises 15% of breast cancer’s and it is the most common type of cancer observed in BRCA1 mutation.
How does breast cancer spread? What is a sentinel lymph node and how is it identified?
Breast cancer spreads in three different ways : via lymphatics which is the most common, hematogenously, or via direct infiltration into adjacent structures.
Identification of the Sentinel Lymph Node, which is the first lymph node where cancer cells might spread, is very important during surgical removal. A radio labeled agent prior to surgery is injected into the skin allowing x-ray image of lymph nodes. During the operation a gamma counter will permit to recognize the sentinel lymph node thanks to its high radioactive count. In addition a blue dye is injected into the breast that stimulates lymphatic flow, this way it is possible to visually follow the sentinel lymph node and remove it.
Classification of breast cancers according to WHO?
According to WHO there are 7 categories of breast tumors : Epithelial tumors, Fibroepithelial Tumors, Myoepithelial Tumors, Mesenchymal Tumors, Tumors of the nipple, Lymphomas and Male Breast Cancer.
Epithelial breast tumors?
95% of breast malignancies are adenocarcinoma’s that arise in the duct/lobular system as carcinoma in situ. Carcinoma in situ refers to a neoplastic proliferation of epithelial cells that is confined to duct and lobules by the basement membrane. Invasive carcinoma instead has penetrated through the basement membrane and grows it within the stroma.
What are some carcinoma in situ and invasive carcinomas of the breast?
• Ductal Carcinoma In Situ : DCIS, It is a malignant clonal proliferation of epithelial cells limited to ducts and lobules and resembling small ducts. Associated to calcification and found with mammography.
• Lobular Carcinoma In Situ : LCIS Is a clonal proliferation of cells within ducts and lobules that grow in the disco adhesive fashion usually due to an acquired loss of the tumor suppressor adhesion protein E cadherin. It is always an incidental Biopsy finding since it is not associated with Calcification a Stromal reaction to produce mammographic densities.
What are some special histologic types of invasive carcinomas of the breast?
• Lobular Carcinoma : Due to loss of E cadherin it appears discohesive. Monophormic cells. Difficult to localize in mammography as there are no calcifications.
• Medullary Carcinoma : BRCA1 associated. Negative for ER and PR and has no amplification of HER2. It is a poorly differentiated neoplasm, without glandular formation. Good prognostic factor.
• Tubular Carcinoma : Well formed tubules, sometimes mistaken for a benign sclerosing lesion.
What are Fibroepithelial breast tumors? Examples?
From intralobular stroma fibroadenomas and phyllodes tumors arise while from the interlobular stroma classic CT tumors arise like lipomas and angiosarcomas.
• Fibroadenomas : Most common benign tumor of the female breast. They are multiple and bilateral. Tumors are well circumscribed. Grayish white nodules. They have both epithelial and mesenchymal components.
• Phyllodes Tumor : Less common. They can be benign, borderline or malignant. In general they have a high cellularity, higher mitotic rate, nuclear polymorphism and infiltrative borders.
What is HER2? How is it detected and what are some therapies?
It is a human epidermal growth factor receptor 2. It is detected by immunohistochemistry or by Fluorescence in situ hybridization. Target therapy is known as trastuzumab.
What are some prognostic and predictive markers in breast carcinoma?
Invasive carcinoma vs CIS, metastasis, LNs, and tumor size related to stage. Histology, molecular class, grade, proliferation, ER and PR regarding tumor biology.
A prognostic biomarker provides information about the patients overall cancer outcome, regardless of therapy, whilst a predictive biomarker gives information about the effect of a therapeutic intervention.
