Breast Cancer

Atiye Akbari

IN THE NAME OF GOD

Breast cancer (malignant breast neoplasm) is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk.

introduction

The breast is a glandular organ.

It is made up of a network of mammary ducts.

Each breast has about 15-20 mammary ducts that lead to lobes that are made up of lobules.

The lobules contain cells that secrete milk that are stimulated by estrogen and progesterone which are ovarian hormone.

Structure of breast

A. Breast Duct System B. Lobules C. Breast Duct System D. Nipple E. Fat F. Chest Muscle G. Ribs

A. Cells lining duct B. Basement membrane C. Open central duct

Normal Breast

A. Breast Duct System B. Lobules C. Breast Duct System D. Nipple E. Fat F. Chest Muscle G. Ribs

A. Cells lining duct B. Extra cancer like cells C. Intact basement

membrane D. Open central duct

Ductal carcinoma in situ(DCIS)

histopathological grade Stag Receptor statuse

Breast cancer classification

Although breast cancer has many different histologies, the considerable majority of breast cancers are derived from the epithelium lining the ducts or lobules, and are classified as mammary ductal carcinoma.

Invasive ductal carcinoma Ductal carcinoma in situ Invasive lobular carcinoma

Histopathology

Grading focuses on the appearance of the breast cancer cells compared to the appearance of normal breast tissue. Normal cells in an organ like the breast become differentiated, meaning that they take on specific shapes and forms that reflect their function as part of that organ. Cancerous cells lose that differentiation.

Grade

Stage 0 is a pre-cancerous or marker condition, either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).

Stages 1–3 are within the breast or regional lymph nodes. Stage 4 is metastatic cancer that has a less favorable

prognosis.

stage

Breast cancer cells may or may not have many different types of receptors.

estrogen receptor (ER) progesterone receptor (PR) human epidermal growth factor receptor 2 (HER2) HER2/neu

Receptor status

Cells with or without these receptors are called ER positive (ER+), ER negative (ER-), PR positive (PR+), PR negative (PR-), HER2 positive (HER2+), and HER2 negative (HER2-).

Cells with none of these receptors are called basal-like or triple negative.

ER receptors belong to a super-family of nuclear hormoneReceptors.The main function of the estrogen receptor is as a DNA-binding

transcription factor that regulates gene expression when they are bound to estrogens.

ER is generally expressed at low levels in normal breast epithelial cells.

ER interactions with a number of other DNA-bound transcription factors, such as the AP-1 complex or the SP-1 family of transcription factors.

estrogen receptor (ER)

The progesterone receptor (PR) also known as NR3C3 (nuclear receptor subfamily 3, group C, member 3), is an intracellular steroid receptor that specifically binds progesterone.

progesterone receptor (PR)

HER2/neu stands for "Human Epidermal growth factor Receptor 2" and is a protein giving higher aggressiveness in breast cancers. It is a member of the ErbB protein family, more commonly known as the epidermal growth factor receptor family.

human epidermal growth factor receptor 2 (HER2) HER2/neu

Inherited Risk Factors Environmental Factors

Causes

Only 5-10% of breast cancers are inherited. Families that do have genetic defects in one of two genes,

breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2), have a much greater risk of developing both breast and ovarian cancer.

Other inherited mutations – including the ataxia-telangiectasia mutation gene, the cell-cycle checkpoint kinase 2 (CHEK-2) gene and the p53 tumor suppressor gene – also make it more likely that will develop breast cancer.

Inherited

BRCA1 (Breast Cancer 1) BRCA2 (Breast Cancer 2) TP53 gene ATM gene

Inherited Genes

BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA.

BRCA1

BRCA2 (Breast Cancer 2 susceptibility protein) is a protein that in humans is encoded by the BRCA2 gene and belongs to the tumor suppressor gene family.

The BRCA2 gene is located on the long (q) arm of chromosome 13 at position 12.3 (13q12.3).

BRCA2

Structure of Brca1 & Brca2

BRCA1 and BRCA2 proteins are involved in control of homologous recombination and double-strand break repair in response to DNA damage .

Modulation of chromatin and DNA structure Activation of DNA damage checkpoints.

Function of BRCA

Role of BRCA2 in homologous recombination

p53 (also known as protein 53 or tumor protein 53), is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer.

p53

The p53 protein structure

Cell Cycle Regulation Cell Senescence Apoptosis Autophagy Mitotic Catastrophe Angiogenesis

Role of p53

Ataxia telangiectasia mutated (ATM) is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis.

ATM

Factors that Cannot be PreventedGender

AgingGenetic Risk Factors

(inherited)Family History

Personal HistoryRace

Menstrual CycleEstrogen

Lifestyle RisksOral Contraceptive Use

Not Having ChildrenHormone Replacement

TherapyNot Breast Feeding

Alcohol UseObesity

High Fat DietsPhysical Inactivity

Smoking

Risk Factors that cause Breast Cancer

Exposure to Estrogen Radiation Electromagnetic Fields Xenoestrogens Exposure to Chemicals

Environmental Factors

definitive surgery

adjuvant chemotherapy

adjuvant radiotherapy

adjuvant hormonal therapy

Treatment

Surgery is usually the first line of attack against breast cancer. Lumpectomy Mastectomy Lymph node removal Prophylactic mastectomy Prophylactic ovary removal Cryotherapy

surgery

Chemotherapy treatment uses medicine to weaken and destroy cancer cells in the body, including cells at the original cancer site and any cancer cells that may have spread to another part of the body.

Chemotherapy is used to treat: early-stage invasive breast cancer to get rid of any cancer cells

that may be left behind after surgery and to reduce the risk of the cancer coming back.

advanced-stage breast cancer to destroy or damage the cancer cells as much as possible.

Chemotherapy

Radiation therapy (radiotherapy) is a highly targeted, highly effective way to destroy cancer cells in the breast.

Radiation therapy

Hormonal therapy medicines treat hormone-receptor-positive breast cancers in two ways:

by lowering the amount of the hormone estrogen in the body by blocking the action of estrogen on breast cancer cells

Hormonal therapy

There are several types of hormonal therapy medicines, including:

aromatase inhibitors selective estrogen receptor modulators estrogen receptor downregulators.

types of hormonal therapy

Aromatase inhibitors stop the production of estrogen in post-menopausal women

There are three aromatase inhibitors: Arimidex (chemical name: anastrozole) Aromasin (chemical name: exemestane) Femara (chemical name: letrozole)

Aromatase inhibitors

SERMs work by sitting in the estrogen receptors in breast cells.There are three SERMs: tamoxifen (also called tamoxifen citrate; brand name:

Nolvadex) Evista (chemical name: raloxifene) Fareston (chemical name: toremifene)

SERMs (Selective Estrogen Receptor Modulators)

ERDs work in a similar way to SERMs.ERDs also: reduce the number of estrogen receptors. change the shape of breast cell estrogen receptors so they

don't work as well.

There is one ERD available to treat hormone-receptor positive breast cancer:

Faslodex (chemical name: fulvestrant)

ERDs (Estrogen-Receptor Downregulators)

1)Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation.Simon N Powell*,1 and Lisa A Kachnic2

2)Pathology of hereditary breast cancer.Leonard Da Silva and Sunil R Lakhani.

3)TP53 Status and Response to Treatment in Breast Cancers.Mariana Varna,1, 2 Guilhem Bousquet,1, 2 Louis-Franc¸ois Plassa,3 Philippe Bertheau,1, 2, 4and Anne Janin1, 2, 4.

4)The Role of Estrogen Receptors in Breast Cancer Metastasis.Suzanne A.W. Fuqua1.

5)New Molecular Classifications of Breast Cancer.Mary Cianfrocca, DO1 and William Gradishar.

references

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