Breast Diseases tumors

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Pathological prognostic factors of breast cancer. : 

Pathological prognostic factors of breast cancer. Dr. Ahmad Laimoneh. Pathologist's.

Breast Architecture : 

Breast Architecture The female breasts are modified sweat glands composed of lobes and lobules interspersed with adipose tissue and connective tissue. *Ducts drain from each lobule. *These converge to form a lactiferous duct that drains from each lobe. *The lactiferous ducts merge just beneath the nipple to form a lactiferous sinus. The functional secretory unit in lactation is the terminal duct lobular unit. Here, each duct has a lining epithelium surrounded by a thin myoepithelial cell layer responsive to oxytocin, the hormone that stimulates lactation. Neoplasms may arise in either the ductular epithelium, lobules, or the stroma. However, the majority of cancers arise in the ducts.

Incidence of Breast Cancer : 

Incidence of Breast Cancer Breast cancer is very rare before age 20 and is rarely diagnosed in women younger than age 25. Past that age, the incidence rises steadily to reach a peak around the age of menopause. The rate of increase is lessened after menopause, but older women are still at increasing risk over time. About 1 in 8 women in the United States and Canada will develop breast cancer. This incidence is similar for many European countries. However, breast cancer is much less common in Asia. The incidence rate for breast cancer rose 24% in the U.S. between 1973 and 1991, while mortality from breast cancer did not increase. In addition, more localized cancers were diagnosed over time. These statistics indicate that screening for breast cancer, including mammography, probably played a role in detecting more cancers at an earlier stage.

Risks for Breast Cancer : 

Risks for Breast Cancer Maternal relative with breast cancer. Women whose mother or sister or aunt had breast cancer, particularly at a younger age, have a greater risk. BRCA1 and BRCA2 genes. The incidence of the BRCA1 gene on chromosome 17 may be 1 in 800 women. The BRCA2 gene on chromosome 13 is less frequent but associated with early onset breast carcinomas. The presence of these genes may explain some of the familial cases, and may be the etiology for about 1% of breast cancers overall. Longer reproductive span. Women who have an earlier menarche and/or a later menopause, increasing the length of reproductive years, are at greater risk. Obesity. Women who are overweight are at increased risk. In addition, increased dietary fat intake is a risk.

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Nulliparity. Women who have never borne children are at greater risk, while women who have been pregnant are at a lower risk. Later age at first pregnancy. Women who had their first child over age 30 are at greater risk. Atypical epithelial hyperplasia. Although fibrocystic changes that produce benign breast "lumps" are not premalignant, the presence of atypical changes in ductular epithelium does increase the risk. Previous breast cancer. Women who have had breast cancer in the opposite breast are at increased risk for cancer in the remaining breast. Previous endometrial carcinoma. Women who have had adenocarcinoma of the endometrium are at increased risk for breast cancer.

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Breast cancers can be classified histologically based upon the types and patterns of cells that compose them. Carcinomas can be invasive (extending into the surrounding stroma) or non-invasive (confined just to the ducts or lobules). The "NOS" categories contain carcinomas not easily classified into other histological types or carcinomas for which minimal tissue was available for diagnosis. Histological Classification of Breast Cancer

Invasive Carcinomas of the Breast : 

Invasive Carcinomas of the Breast

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Non-invasive Carcinomas of the Breast

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A completely uniform system of grading for breast cancers is not possible because of the wide variety of histologic cell types. The cell types themselves, along with the invasiveness of the cancer, help to predict the biologic behavior of the cancer. Grading of breast cancers

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NOTTINGHAM GRADING SYSTEM

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The stage of a breast cancer is based upon its size and degree of spread. The staging system goes from stage I to stage IV as follows: staging of a breast cancer

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Stages of breast cancer Stage I : Tumor 2 cm or less in greatest diameter and without evidence of regional (nodal) or distant spread. Stage II : Tumor more than 2 cm but not more than 5 cm in greatest dimension, with regional lymph node involvement but without distant metastases, OR > a tumor of more than 5 cm in diameter without regional (nodal) and distant spread Stage III : Tumors of any size with possible skin involvement, pectoral and chest wall fixation, and axillary or internal mammary nodal involvement, fixed, but without distant metastases. stage IV: Tumor of any size with or without regional spread but with evidence of distant metastases

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There are some general guidelines as to the potential biologic behavior of a breast carcinoma. In general, a better prognosis will accompany cancers: Less than 2 cm in size. Without axillary lymph node involvement. That are non-invasive ductal carcinoma and LCIS. With ER and PR positivity. Better prognosis

ER Receptors positive : 

ER Receptors positive

PR Receptors positive : 

PR Receptors positive

New breast cancer classifications : 

New breast cancer classifications

New technology called DNA microarray hybridization that looks at a wide array of genes to identify disease-associated patterns in the human genome (complete set of human genes) has resulted in a new classification of breast cancer according to gene expression profiles. : 

New technology called DNA microarray hybridization that looks at a wide array of genes to identify disease-associated patterns in the human genome (complete set of human genes) has resulted in a new classification of breast cancer according to gene expression profiles. The use of microarray technology

The current types of breast cancer are based largely on how tumors look under a microscope. A newer classification, based on molecular features, may be better able to predict prognosis and response to several types of breast cancer treatment. : 

The current types of breast cancer are based largely on how tumors look under a microscope. A newer classification, based on molecular features, may be better able to predict prognosis and response to several types of breast cancer treatment.

New research suggests there are 4 basic types of breast cancers: 1- Luminal A. 2- luminal B. 3- HER2 type. 4- Basal like type. : 

New research suggests there are 4 basic types of breast cancers: 1- Luminal A. 2- luminal B. 3- HER2 type. 4- Basal like type.

ER+ and/or PR+, HER2- tumors were termed "luminal A"; usually low grade, and tend to grow fairly slowly. The gene expression patterns of these cancers are similar to normal cells that line the breast ducts and glands (the lining of a duct or gland is called its lumen). Luminal A cancers have the best prognosis. : 

ER+ and/or PR+, HER2- tumors were termed "luminal A"; usually low grade, and tend to grow fairly slowly. The gene expression patterns of these cancers are similar to normal cells that line the breast ducts and glands (the lining of a duct or gland is called its lumen). Luminal A cancers have the best prognosis. 1 - Luminal A

ER+ and/or PR+, HER2+ Luminal B cancers generally grow somewhat faster than the luminal A cancers and their prognosis is not quite as good. : 

ER+ and/or PR+, HER2+ Luminal B cancers generally grow somewhat faster than the luminal A cancers and their prognosis is not quite as good. 2 - luminal B types

HER2 type: These cancers have extra copies of the HER2 gene and several other genes. They usually have a high-grade appearance under the microscope. These cancers tend to grow more quickly and have a worse prognosis, although they often can be treated successfully with targeted therapies such as trastuzumab (Herceptin) and lapatinib (Tykerb). : 

HER2 type: These cancers have extra copies of the HER2 gene and several other genes. They usually have a high-grade appearance under the microscope. These cancers tend to grow more quickly and have a worse prognosis, although they often can be treated successfully with targeted therapies such as trastuzumab (Herceptin) and lapatinib (Tykerb).

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Tests of HER2 status Determining a breast cancer's HER2 status is important, both to get an idea of how aggressive the cancer might be and to find out if certain drugs that target HER2 can be used to treat the disease.

Her-2 score-1 : 

Her-2 score-1

T7 C-erb B-2, Breast Ca : 

T7 C-erb B-2, Breast Ca

Her-2 score-3 : 

Her-2 score-3

Fibrocystic Changes of the Breast : 

Fibrocystic Changes of the Breast Another example of microscopic fibrocystic changes of the breast are shown here. Fibrocystic changes account for the majority of "breast lumps" that are found in women of reproductive years, particularly between age 30 and menopause.

Basal type: triple-negative, CK 5/6+ and/or HER1+ "basal-like"; myoepithelial cells, most notably cytokeratins (CK) 5/6 and 17) Most of these cancers are of the so-called "triple negative" type -- that is, they lack estrogen or progesterone receptors and have normal amounts of HER2. The gene expression patterns of these cancers are similar to cells in the deeper basal layers of breast ducts and glands. This type is more common among women with BRCA1 gene mutations. For reasons that are not well understood, this cancer is also more common among younger and African-American women. basal" type to be significantly associated with p53 mutation status, mitotic index, nuclear pleomorphism and higher histological grade. Carey et al. study breast cancer subtypes, and survival in the Carolina Breast cancer study. JAMA 295: 2492­2502, 2006. : 

Basal type: triple-negative, CK 5/6+ and/or HER1+ "basal-like"; myoepithelial cells, most notably cytokeratins (CK) 5/6 and 17) Most of these cancers are of the so-called "triple negative" type -- that is, they lack estrogen or progesterone receptors and have normal amounts of HER2. The gene expression patterns of these cancers are similar to cells in the deeper basal layers of breast ducts and glands. This type is more common among women with BRCA1 gene mutations. For reasons that are not well understood, this cancer is also more common among younger and African-American women. basal" type to be significantly associated with p53 mutation status, mitotic index, nuclear pleomorphism and higher histological grade. Carey et al. study breast cancer subtypes, and survival in the Carolina Breast cancer study. JAMA 295: 2492­2502, 2006.

Immunohistochemical detection of Cytokeratin 5/6 in breast cancer. Intense reaction in most tumor cells, as opposed to surrounding stroma. : 

Immunohistochemical detection of Cytokeratin 5/6 in breast cancer. Intense reaction in most tumor cells, as opposed to surrounding stroma. Immunoperoxidase x250.

Immunohistochemical detection of Cytokeratin 5/6 in myoepithelial cells of normal breast ducts. : 

Immunohistochemical detection of Cytokeratin 5/6 in myoepithelial cells of normal breast ducts. Immunoperoxidase x400.

Bcl-2 inhibits most kinds of programmed cell death and provides a selective survival advantage to various cell types. Bcl-2 is physiologically expressed in ductal epi-thelia of the normal breast. The biological significance of Bcl-2 (over)expression for the development and progression of breast cancer has still to be evaluated. 133 primary breast cancers was investigated for expression of the Bcl-2 protein by immunohistochemistry of paraffin-embedded tissue sections. C. Binder1,, D. Marx2, R. Overhoff2, L. Binder3,, A. Schauer2 and W. Hiddemann1 1Department of Haematology/Oncology2Department of Pathology II3Department of Clinical Chemistry, Georg-August-University Göttingen, Germany 1995. A significant positive correlation was observed between Bcl-2 expression and positivity for estrogen and progesterone receptors (p < 0.001). High proliferative activity as assessed by Ki-67 staining correlated inversely with Bcl-2 expression (p < 0.001). Bcl-2 immunostaining was not related to positivity for c-erbB-1. It was negatively associated with overexpression of c-erbB-2 (p = 0.04)

Expression of Bcl-2 protein in breast cancer. : 

Expression of Bcl-2 protein in breast cancer. a case with a normal expression of Bcl-2 protein in breast cancer cells. a case with a decreased expression of Bcl-2 protein.

An additional interesting finding was that mutant p53 expression was significantly higher in the "basal like" group than in the luminal A group (35% vs. 6%), but was even higher in the pure HER2 group (60%). This may have clinical implications, since HER2+/hormone-receptor-negative tumors are by definition only amenable to chemotherapeutic treatment (besides surgery), and p53 is a major factor in the molecular mechanisms of resistance to chemotherapy, a problem recently addressed by Sorlie et al. (8) when studying chemotherapy response rates in relationship to gene expression profiles. Sorlie et al ;Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer. Mol Cancer Ther 5: 2194-2198, 2006. : 

An additional interesting finding was that mutant p53 expression was significantly higher in the "basal like" group than in the luminal A group (35% vs. 6%), but was even higher in the pure HER2 group (60%). This may have clinical implications, since HER2+/hormone-receptor-negative tumors are by definition only amenable to chemotherapeutic treatment (besides surgery), and p53 is a major factor in the molecular mechanisms of resistance to chemotherapy, a problem recently addressed by Sorlie et al. (8) when studying chemotherapy response rates in relationship to gene expression profiles. Sorlie et al ;Gene expression profiles do not consistently predict the clinical treatment response in locally advanced breast cancer. Mol Cancer Ther 5: 2194-2198, 2006.

The End : 

The End

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