Term
| what is the incidence of breast CA? theory for its prevalence in the US? |
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Definition
| breast CA is the 2nd most common invasive malignancy in american women, thought to be b/c here there are increased levels of pts w/no children/children later in life which exposes them to a wider flux of hormonal exposure. caucasians are more likely to get breast CA, but african-americans are more likely to die from it. |
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Term
| what are risk factors for breast CA? |
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Definition
| hormonal, increasing age, CA of contralateral breast/endometrium, radiation exposure, genetic susceptibility, diet, proliferative breast disease, and males w/klinefelters |
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Term
| what characterizes the hormonal risks for breast CA? |
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Definition
| early menarche and/or late menopause exposes women to hormones for a longer period of time. late childbirth/nulliparity leads to higher exposure to estrogen during reproductive life. OCPs may be a slight risk for breast CA, but they balance it out by decreasing ovarian/endometrial CA risk. |
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Term
| what characterizes increasing age as a risk for breast CA? |
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Definition
| this increases risk of all CA |
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Term
| what characterizes CA of contralateral breast/endometrium as a risk for breast CA? |
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Definition
| either would indicate increased hormonal exposure -> increased breast CA risk |
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Term
| what characterizes genetic susceptibility as a risk for breast CA? |
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Definition
| BRCA genes 1&2 are tumor *suppressor genes (chr 17, 13 respectively), mutations of which predispose pts to breast, ovarian, and prostate CA (BRCA2 more associated w/male breast CA). these genes are more common in ashkenazi jews/eastern european. |
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Term
| what determines protocol for BRCA testing? |
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Definition
| *non-ashkenazi: if 2 1st degree relatives are diagnosed at 50 or younger, if 3+ 1st/2nd degree relatives are dxed w/breast or ovarian CA independent of age, or if a 1st degree relative has b/l breast CA. *ashkenazi: if any 1st degree relative is dxed w/breast or ovarian CA or 2 2nd degree relatives on the same side are dxed w/the same. |
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Term
| what characterizes diet as a risk for breast CA? |
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Definition
| high calorie, high animal protein, alcohol coupled w/lack of exercise = increased breast CA risk. (increased adipose = increased estrogen). women w/o this mutation have a 12% lifetime risk of breast CA and 1.4% risk of ovarian CA. women w/this mutation have a 60% lifetime risk of breast CA and a 40% risk of ovarian CA. |
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Term
| what are the cellular changes in breast CA progression? |
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Definition
| there is a loss of regulation of normal cell number: *epithelial hyperplasia. genetic instability then can lead to clonal population of cells: *atypical hyperplasia. *increased oncogene expression (Her2/neu) then marks progression to CA. |
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Term
| what characterizes the HER2 gene's role in breast CA? |
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Definition
| HER2, an *oncogene encodes a transmembrane growth factor receptor which when growth factor binds = uncontrolled signal transduction (via tyrosine kinase) to the nucleus = unchecked protein production (cell division). |
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Term
| what are the clinical features of breast CA? |
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Definition
| breast lumps, nipple abnormalities, and discomfort. *50% occur in the upper outer quadrant and these are more likely to have *axillary node involvement. |
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Term
| what characterizes a breast self-exam? |
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Definition
| examine breasts in the shower. examine breasts in the mirror w/arms up, down, and on hips. press fingers on breast and work around in a circular fashion in both standing/supine positions. squeeze nipples and check for discharge. check under the nipple last. |
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Term
| how do malignant breast lesions appear on mammography? |
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Definition
| 64% stellate and circular. 17% stellate, circular w/calcifications. 19% calcifications only. if calcifications are seen on mammogram, but not bx - then the bx can be sliced smaller to look for them (even by x-ray if necessary). |
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Term
| if a breast lesion is palpable, how can it be dxed? |
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Definition
| fine needle aspiration (FNA), however this is slightly controversial as it may release tumor cells in the needle pathway and sporadic/calcified lesions may not aspirate well. |
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Term
| if a breast lesion is not palpable, how can it be dxed? |
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Definition
| stereotactic needle guided bx (x-ray guided) |
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Term
| what characterizes a lumpectomy w/needle localization? |
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Definition
| a guide wire is inserted to the center of the lesion, then this guides the surgeon in where to cut (want a wide margin). |
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Term
| where do most breast CAs arise? |
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Definition
| in the terminal duct-lobular unit |
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Term
| what are myoepithelial cells a sign of histologically? |
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Definition
| benignity, these cells are lost in malignancy because in malignancy you are overriding normal structures |
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Term
| what are the different types of breast CA? |
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Definition
| ductal, lobular, and less common types |
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Term
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Definition
| DCIS is a "bridging lesion", thought to be a CA precursor as it consists of neoplastic proliferation w/malignant features in the ductal phenotype - but it is limited to the epithelium. they are usually seen in pts 50-59 y/o and the likelihood of progression is based on nuclear grade. invasive breast CA risk: 8-10x, but progression to this is unpredictable. these are usually multifocal and excision, sometimes radiation is recommended. histologically, comedo necrosis may be seen (due to malignant cells outstripping their blood supply), but the myoepithelial cell layer is still maintained. |
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Term
| what characterizes ductal breast CA? |
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Definition
| this accounts for 75% of invasive breast CA and looks similar to benign scarring lesions: grossly white-tan, firm, often stellate, and surrounded by *puckering of surrounding tissue. ductal breast CA is considered a type of adenocarcinoma (b/c affecting ducts+glands). |
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Term
| how does ductal breast CA appear on FNA? bx? |
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Definition
| *FNA: the cells appear plump, cohesive, abundant in cytoplasm, and nuclei are low in pleomorphism (mostly low grade). *bx: the tumor cells are arranged in cords, clusters, trabeculae, and ductal structure may be lost. the cells may be in pure sheet form and tend to stream into the stroma haphazardly. DCIS is often found simultaneously on bx, which supports the theory that DCIS leads to invasive ductal CA. mitotic figures and necrosis: +/-. there may be a desmoplastic reaction surrounding the CA. |
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Term
| how can likelihood of metastasis w/ductal CA be evaluated? |
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Definition
| checking for vascular/lymphatic invasion - see if tumor cells are plugging these vessels. |
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Term
| where is ductal breast CA likely to metastasize? |
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Definition
| the lungs (close contact of lung and breast tissue). in pleural fluid on cytology, ductal CA has a cannonball appearance (very cohesive cells). |
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Term
| what is also considered a "bridging lesion" along w/DCIS? |
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Definition
| lobular CA in situ (LCIS), which is usually not associated w/microcalcifications. risk of invasive lobular CA after LCIS is 5x increased = watchful waiting (unless strong fam hx) |
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Term
| how can DCIS and LCIS be distinguished? |
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Definition
| LCIS will stain negative for E-cadherin (a calcium-dependent transmembrane epithelial protein that promotes intercellular adhesion = less likely to metastasize), therefore LCIS is more likely to metastasize. |
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Term
| what characterizes lobular CA? |
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Definition
| lobular CA represents a smaller percent (up to 15%) of all breast CA, but have a higher incidence of bilaterality (10-20%). because lobular CA lacks E-cadherin, it is less cohesive and harder to see on mammogram and will metastasize easier to bone marrow, cerebrospinal fluid/leptomeninges, GI tract, ovary, serosal surfaces, and uterus (lobular CA:most likely to met). |
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Term
| how does lobular CA appear histologically? |
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Definition
| the cells usually line up in straight lines rather than lobular structures. the *targetoid pattern is a classic formation, where single file cells have circular/arched patterns. *mucin may also be seen w/in the cytoplasm, to the point where the nucleus may be pushed aside. |
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Term
| how can invasive ductal CA be differentiated from invasive lobular CA? |
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Definition
| invasive lobular CA lacks E-cadherin |
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Term
| what characterizes lobular CA which metastasizes? |
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Definition
| b/c lobular CA metastasizes easily and its cells are smaller, its presence in other tissues may be very subtle (hx very important). cytokeratin stains can help ID lobular CA as they emphasize epithelial cells. |
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Term
| what is the signet ring variant of lobular CA? |
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Definition
| a variant of lobular CA where there is abundant cytoplasm and a single, large mucin vacuole pushing the nucleus aside - appearing as a "signet ring". these tend to be more aggressive. |
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Term
| what characterizes male breast CA? |
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Definition
| male breast CA tends to be *ductal, as males usually lack lobules or have atrophic lobules. males w/breast CA tend to be *BRCA2 mutation carriers. males w/breast CA are also more likely to have *chest wall invasion due to less fat presence. usually male breast CA is more advanced when dxed as males are less likely to self-examine (often found due to enlarged axillary lymph node, infected sore, inverted nipple, lump or discharge). histologically: identical to female breast CA. |
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Term
| what are the less common breast CAs? |
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Definition
| tubular CA, invasive cribiform CA, mucinous CA, medullary CA, invasive papillary CA, apocrine CA, secretory CA, metaplastic CA, inflammatory breast CA, paget's disease, malignant phyllodes tumor, and angiosarcoma. |
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Term
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Definition
| a well-differentiated CA which is grossly firm and poorly circumscribed. < 1 cm and seen in pts > 50 y/o. histologically, these consist of bland glands/nuclei, lack of necrosis/mitoses, and *pinched/angulated ducts due to compression. tubular CA can be mistaken for a radial scar/sclerosing adenosis (due to background fibrosis). tubular CA has an *excellent prognosis, but 50% recur. |
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Term
| what is invasive cribriform CA? |
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Definition
| this rare CA is related to tubular CA and can mimic DCIS. invasive cribriform CA is characterized by an almost solid pattern w/"cookie-cutter" holes punched out. excellent prognosis (responds well to therapy). |
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Term
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Definition
| mucinous breast CA is grossly well-circumscribed and crepitant to palpation. histologically, mucinous CA appears as a jelly-like mass w/thin septations and clusters of tumor cells floating in mucin. this occurs usually in postmenopausal women, has a low incidence of metastasis, and an excellent short-term prognosis (can have late recurrences 12+ yrs later - need good f/u). |
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Term
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Definition
| these well circumscribed lesions may mimic fibroadenomas and can grow large quickly. histologically, infiltration of lymphocytes/plasma cells is seen, growth is diffuse, and differentiation is minimal. medullary CA is more common in japanese, BRCA1 carriers < 50 y/o. metastasis to axillary lymph nodes is common but prognosis is better than invasive ductal CA. |
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Term
| what is invasive papillary CA? |
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Definition
| invasive papillary CA is called such b/c papillary structures on fibrovascular cores project into the duct lumen. if the duct looks normal, think possible papilloma, but if multiple projections - think CA. avg age: 63-67 y/o and 5 yr survival is 90%. |
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Term
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Definition
| apocrine CA is very rare. tumor cells have distinct cell margins, eosinophilic granular cytoplasm, round nuclei, and prominent nucleoli. there may be glandular differentiation w/snouts. prognosis is similar to ductal CA. |
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Term
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Definition
| these are rare, but primarily are seen in children. they appear well-circumscribed, small (hard/unlikely to palpate), and histologically cells have vacuolated cytoplasm forming secondary lumina w/eosinophilic secretions and *push the basement membrane margins. prognosis is excellent (100% 5 yr survival). excision is recommended. |
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Term
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Definition
| this refers to a ductal CA w/sarcoma-like stroma (more spindle cells and less ductal/lobular structures). grossly, there may also be cartilaginous and/or osseous areas. metaplastic CA is very aggressive w/hematogenous mets often. |
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Term
| what is inflammatory breast CA? |
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Definition
| clinically this presents as peau de orange (skin w/obvious pores), redness, edema, and induration = all indicative of *dermal lymphatic invasion. histologically, CA cells are seen plugging dermal lymphatics. this is often associated with ductal CA. inflammatory breast CA has a poor prognosis, so irritation on older pts' breasts needs to be taken very seriously. |
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Term
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Definition
| paget's disease presents as a crusted lesion of the nipple due to CA. this may mimic mastitis, but is usually seen in older women (usually past lactation). generally invasive ductal CA or DCIS is associated (*most important). histologically, large clear cells are seen in the epidermis (which can be stained for w/epithelial membrane antigen). also, normally there are a few toker cells (component of basal breast epithelium) in breast tissue, and these may show mild atypia - can mimic the large clear cells associated w/paget's. |
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Term
| what characterizes the malignant phyllodes tumor? |
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Definition
| 10% of phyllodes tumors can become malignant, but these are rare under 20 (helps distinguish from fibroadenoma). grossly they will appear cauliflower-like and lobulated (similar to benign variant), and histologically, an arborizing pattern like w/fibroadenoma is seen, but with more stroma and spindled cells. malignant phyllodes tumors are *aggressive w/local recurrence and may metastasize to lung, bone, and CNS. they do however have a *better prognosis than invasive ductal CA. |
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Term
| what characterizes angiosarcoma of the breast? |
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Definition
| these are very rare as primary breast tumors, but may be seen in *women 5-10 yrs post-radiation therapy for breast CA or pts w/chronically edematous arms after axillary lymph node dissection (edema promotes angiosarcoma formation). median survival: 3-6 yrs. grossly they appear very vascular and round. histologically, anastomosing vascular channels lined by atypical endothelial cells w/pleomorphic, hyperchromatic nuclei are seen w/infiltrative margins. mitotic activity is variable even though these tumors are very aggressive. post radiation tumors are typically higher grade than de novo angiosarcomas. |
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Term
| what are prognostic factors for breast CA? |
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Definition
| sentinel lymph nodes, estrogen/progesterone receptors, ploidy, and Her2/neu |
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Term
| what characterizes sentinel lymph nodes as prognostic factors for breast CA? |
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Definition
| sentinel lymph nodes are the first lymph nodes to be reached by metastasizing CA cells, the presence of which may be determined by injection of radioactive/blue dye tracers near the tumor. nodes showing the tracer are then identified via scanner and removed to be made into frozen sections for pathology to examine. cytokeratin can also be used to stain permanent slides made from sentinel nodes for atypical cells. if the sentinel nodes are negative, there is no need for axillary node dissection. |
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Term
| what is the correlation between axillary lymph node involvement and breast CA survival? |
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Definition
| there is an inverse relationship |
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Term
| what is the controversy w/sentinel lymph nodes? |
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Definition
| micrometastasis: isolated, PCR/immunohistochemically detected CA cells - not H+E detectable alone may have some significance, but do not currently upstage the CA. |
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Term
| where are common sites of breast CA metastasis? |
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Definition
| lung, bone, and direct extension into the chest wall, ribs, and pleura. |
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Term
| what characterizes estrogen/progesterone receptors as risk factors for breast CA? |
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Definition
| this can help determine effective tx, as these receptors allow hormones to stimulate proliferation. estrogen/progesterone receptors are found in benign breast epithelial cells as well as 1/2 breast CAs, particularly low grade tumors in older pts w/a better prognosis. presence of these receptors indicates a good response to anti-estrogenic therapy and oophorectomy. |
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Term
| what characterizes ploidy as a risk factor for breast CA? |
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Definition
| increased proliferative capacity (higher DNA content) is associated with a poorer prognosis (more rapid proliferation). ploidy can be judged based on mitotic index, histology, numbers of cells in S phase (flow cytometry), and immunohistochemical staining for nuclear proteins expressed in actively proliferating cells (ie Ki67). |
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Term
| what characterizes Her2/Neu as a risk factor for breast CA? |
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Definition
| expression of Her2/Neu (oncogene) has prognostic significance, as tumors w/this tend to be *more aggressive - but they are *amenable to trastuzmab therapy (blocks HER2/Neu receptor signaling). positive FISH (fluorescence in situ hybridization) or histochemical membrane staining (grade 2 or 3) can be used to detect upregulation of this gene (more than 2 copies is atypical). |
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Term
| what is the benefit of anti-Her2 therapy (trastuzumab)? |
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Definition
| trastuzumab reduces recurrence, metastases, mortality, and may improve survival in metastatic breast CA disease. |
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Term
| what are poor prognostic factors? |
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Definition
| high stage (tumor size/nodal+distant metastases), high histologic grade (pleomorphic state/high mitotic activity), younger age (greater chance or recurrence), skin invasion (easier spread to lymphatics), nipple invasion, and angiolymphatic invasion (indicates higher grade). |
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Term
| what are the favorable histologic types of breast CA? (*know these) |
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Definition
| tubular, cribriform, medullary, colloid, papillary, and adenoid cystic/secretory/juvenile |
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Term
| what are the unfavorable histologic types of breast CA? (*know these) |
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Definition
| signet ring, basal-like, and inflammatory |
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Term
| what are therapy induced changes? |
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Definition
| if a pt has had chemo/radiation therapy, this can lead to: cell enlargement, vacuolization, and pleomorphism (though this would be more diffuse after therapy and more focal in CA). this makes it harder to determine level of CA after tx by histology. |
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Term
| what does grading of invasive CA depend on? |
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Definition
| tubule/gland formation (architecture lost = worse grade), nuclear pleomorphism (more = worse grade), mitotic counts (higher counts = more proliferation = worse grade), and lymph node metastasis (always worsens grade). |
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Term
| what benign lesions may mimic breast CA? |
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Definition
| fibroadenoma (very common, whirling pattern, smooth borders), intraductal papilloma (complex arborizing histology: different appearance than CA - as long as single papilloma, *bloody nipple discharge, hyalinization may *look suspicious), lactating adenoma (largely concerning due to size, will generally recede - careful dxing pregnant pts), sclerosing adenosis, radial scar (often due to previous bx/sx), and traumatic fat necrosis (may be due to trauma - hx important) |
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