What Is Breast Cancer?

Breast cancer starts when cells in the breast begin to grow out of control.
These cells usually form a tumor that can often be seen on an x-ray or felt
as a lump. The tumor is malignant (cancer) if the cells can grow into
(invade) surrounding tissues or spread (metastasize) to distant areas of the
body. Breast cancer occurs almost entirely in women, but men can get
breast cancer, too. Cells in nearly any part of the body can become cancer
and can spread to other areas.

Where breast cancer starts?

Breast cancers can start from different parts of the breast. Most breast
cancers begin in the ducts that carry milk to the nipple (ductal cancers).
Some start in the glands that make breast milk (lobular cancers). A small
number of cancers start in other tissues in the breast. These cancers
are called sarcomas and lymphomas and are not really thought of as breast
cancers.
Breast cancer can spread when the cancer cells get into the blood or lymph
system and are carried to other parts of the body.
Most of the lymph vessels of the breast drain into:

 Lymph nodes under the

arm (axillary nodes)
 Lymph nodes around
the collar bone
(supraclavicular [above
the collar bone] and
infraclavicular [below the
collar bone] lymph
nodes)
 Lymph nodes inside the
chest near the breast
bone (internal mammary
lymph nodes)

If cancer cells have spread to

your lymph nodes, there is a higher chance that the cells could have
traveled through the lymph system and spread (metastasized) to other
parts of your body.
Risk Factors You Cannot Change

 Getting older. The risk for breast cancer increases with age; most breast cancers are diagnosed
after age 50.
 Genetic mutations. Inherited changes (mutations) to certain genes, such as BRCA1 and BRCA2.
Women who have inherited these genetic changes are at higher risk of breast and ovarian cancer.
 Reproductive history. Early menstrual periods before age 12 and starting menopause after age 55
expose women to hormones longer, raising their risk of getting breast cancer.
 Having dense breasts. Dense breasts have more connective tissue than fatty tissue, which can
sometimes make it hard to see tumors on a mammogram. Women with dense breasts are more
likely to get breast cancer.
 Personal history of breast cancer or certain non-cancerous breast diseases. Women who have
had breast cancer are more likely to get breast cancer a second time. Some non-cancerous breast
diseases such as atypical hyperplasia or lobular carcinoma in situ are associated with a higher risk of
getting breast cancer.
 Family history of breast cancer. A woman’s risk for breast cancer is higher if she has a mother,
sister, or daughter (first-degree relative) or multiple family members on either her mother’s or
father’s side of the family who have had breast cancer. Having a first-degree male relative with
breast cancer also raises a woman’s risk.
 Previous treatment using radiation therapy. Women who had radiation therapy to the chest or
breasts (like for treatment of Hodgkin’s lymphoma) before age 30 have a higher risk of getting
breast cancer later in life.
 Women who took the drug diethylstilbestrol (DES), which was given to some pregnant women in
the United States between 1940 and 1971 to prevent miscarriage, have a higher risk. Women whose
mothers took DES while pregnant with them are also at risk.

Risk Factors You Can Change

 Not being physically active. Women who are not physically active have a higher risk of getting
breast cancer.
 Being overweight or obese after menopause. Older women who are overweight or obese have a
higher risk of getting breast cancer than those at a normal weight.
 Taking hormones. Some forms of hormone replacement therapy (those that include both estrogen
and progesterone) taken during menopause can raise risk for breast cancer when taken for more
than five years. Certain oral contraceptives (birth control pills) also have been found to raise breast
cancer risk.
 Reproductive history. Having the first pregnancy after age 30, not breastfeeding, and never having
a full-term pregnancy can raise breast cancer risk.
 Drinking alcohol. Studies show that a woman’s risk for breast cancer increases with the more
alcohol she drinks.

What Causes Breast Cancer? (etiology)

Among the most significant factors are advancing age and a family history of breast
cancer. Risk increases for a woman who has certain types of benign breast lumps and
increases significantly for a woman who has previously had cancer of the breast or the
ovaries. A woman whose mother, sister, or daughter has had breast cancer is two
to three times more likely to develop the disease, particularly if more than one first-
degree relative has been affected. Researchers have identified two genes
responsible for some instances of familial breast cancer. These genes are known as
BRCA1 and BRCA2. About one woman in 200 carries the genes. Having one of them
predisposes a woman to breast cancer but does not ensure that she will get it.
Generally, women over age 50 are more likely to get breast cancer than younger
women, and African-American women are more likely than Caucasians to get
breast cancer before menopause. A link between breast cancer and hormones is
clear. Researchers think that the greater a woman's exposure to the
hormone estrogen, the more susceptible she is to breast cancer. Estrogen tells cells
to divide; the more the cells divide, the more likely they are to be abnormal in
some way, possibly becoming cancerous. Women who have taken birth control pills
in the recent past may have a slightly higher risk of developing breast
cancer.Heavy doses of radiation therapy may also be a factor.

Breast Cancer Pathophysiology

Breast cancer is a malignant tumor that starts in the cells of the breast. Like other
cancers, there are several factors that can raise the risk of getting breast cancer.
Damage to the DNA and genetic mutations can lead to breast cancer have been
experimentally linked to estrogen exposure. Some individuals inherit defects in the
DNA and genes like the BRCA1, BRCA2 and P53 among others. Those with a family
history of ovarian or breast cancer thus are at an increased risk of breast cancer.
The immune system normally seeks out cancer cells and cells with damaged DNA
and destroys them. Breast cancer may be a result of failure of such an effective
immune defence and surveillance. These are several signalling systems of growth
factors and other mediators that interact between stromal cells and epithelial cells.
Disrupting these may lead to breast cancer as well.

In breast cancer care, three tumor markers -- cancer antigen 15-3 (CA 15-3), cancer
antigen 27.29 (CA 27.29), and carcinoembryonic antigen (CEA) -- have been used to
help monitor metastatic breast cancer (advanced disease), but they have not been
found to be useful to find a breast cancer recurrence or lengthen lives in patients
who had early-stage breast cancer and who are now disease-free.

Tumor markers
We use tumor markers to detect the presence of certain types of cancer in the body, and to
monitor the progress of cancer treatment. Tumor markers are substances found in the blood,
body fluids, or tissues that are produced by cancer cells. If a certain tumor marker is found in the
body, it can indicate that the cancer is still present and ongoing treatment may still be
recommended.

Some of the signs and symptoms of breast cancer include:

 a change in size or shape

 a lump or area that feels thicker than the rest of the breast
 a change in skin texture such as puckering or dimpling (like the skin of an
orange)
 redness or rash on the skin and/or around the nipple
 your nipple has become pulled in or looks different, for example changed its
position or shape
 liquid that comes from the nipple without squeezing
 pain in your breast or your armpit that’s there all or almost all of the time
 a swelling in your armpit or around your collarbone

Types of Breast Cancer

There are many types of breast cancer. The most common types are ductal
carcinoma in situ, invasive ductal carcinoma, and invasive lobular
carcinoma.
The type of breast cancer is determined by the specific cells in the breast
that are affected. Most breast cancers are carcinomas. Carcinomas are
tumors that start in the epithelial cells that line organs and tissues
throughout the body. Sometimes, an even more specific term is used. For
example, most breast cancers are a type of carcinoma
called adenocarcinoma, which starts in cells that make up glands
(glandular tissue). Breast adenocarcinomas start in the ducts (the milk
ducts) or the lobules (milk-producing glands). There are other, less
common, types of breast cancers, too, such
as sarcomas, phyllodes, Paget disease, and angiosarcomas which start
in the cells of the muscle, fat, or connective tissue.
In situ cancers

Ductal carcinoma in situ (DCIS; also known as intraductal carcinoma) is a

non-invasive or pre-invasive breast cancer. See Ductal Carcinoma in Situ
(DCIS) for more information.

Lobular carcinoma in situ (LCIS) may also be called lobular neoplasia.

This breast change is not a cancer, though the name can be confusing. In
LCIS, cells that look like cancer cells are growing in the lobules of the milk-
producing glands of the breast, but they don’t grow through the wall of the
lobules. See Lobular Carcinoma in Situ (LCIS) for more information.

Invasive (infiltrating) breast cancer

Breast cancers that have spread into surrounding breast tissue are known
as invasive breast cancer. There are many different kinds of invasive
breast cancer, but the most common are called invasive ductal
carcinoma and invasive lobular carcinoma

Less common types of breast cancer

- Inflammatory breast cancer

Inflammatory breast cancer is an uncommon type of invasive breast cancer. It accounts for about
1% to 5% of all breast cancers.
 - Paget disease of the nipple

Paget disease of the nipple starts in the breast ducts and spreads to the skin of the nipple and
then to the areola(the dark circle around the nipple). It is rare, accounting for only about 1-3% of
all cases of breast cancer.

- Phyllodes tumor

Phyllodes tumors are rare breast tumors. They develop in the connective tissue (stroma) of the
breast, in contrast to carcinomas, which develop in the ducts or lobules. Most are benign, but
there are others that are malignant (cancer). See Phyllodes Tumors of the Breast for more
information.

- Angiosarcoma

Sarcomas of the breast are rare making up less than 1% of all breast
cancers. Angiosarcomastarts in cells that line blood vessels or lymph vessels. It can involve the
breast tissue or the skin of the breast. Some may be related to prior radiation therapy in that
area.

Imaging Methods Used to Find Breast Cancer

Breast ultrasound (or sonogram)
Breast ultrasound uses sound waves to make images of the breast. It is often used as a follow-
up test after an abnormal finding on a mammogram or clinical breast exam. Breast ultrasound
can tell the difference between a liquid-filled cyst and a solid mass (which may or may not be
cancer).
Breast MRI
A breast MRI uses magnetic fields to create an image of the breast. It can sometimes find
cancers in dense breasts that are not seen on mammograms. Breast MRI may be used with
mammography for screening some women at a high risk of breast cancer (such as those with
a BRCA1/2 gene mutation). It is not recommended for screening women at average risk.
Breast MRI is more invasive than a mammogram. It can also be costly

The breast cancer staging system, called the TNM system, is overseen by the American
Joint Committee on Cancer (AJCC).
In the past, stage number was calculated based on just three clinical characteristics, T,
N, and M:

 the size of the cancer tumor and whether or not it has grown into nearby tissue (T)

 whether cancer is in the lymph nodes (N)

 whether the cancer has spread to other parts of the body beyond the breast (M)

The TNM system

Here is a slightly simplified description of the TNM staging system for breast cancer.

Tumour (T)
Tumour describes the size of the tumour (area of cancer). This is a simplified description of the T
stage.

TX means that the tumour size can't be assessed.

Tis means ductal carcinoma in situ (DCIS).

 Find out about ductal carcinoma in situ

T1 means that the tumour is 2 centimetres (cm) across or less.

T1 is further divided into 4 groups:

 T1mi means the tumour is 0.1cm across or less

 T1a means the tumour is more than 0.1 cm but not more than 0.5 cm
 T1b means the tumour is more than 0.5 cm but not more than 1 cm
 T1c means the tumour is more than 1 cm but not more than 2 cm

T2 means that the tumour is more than 2 centimetres but no more than 5 centimetres across.
T3 means the tumour is bigger than 5 centimetres across.

T4 is divided into 4 groups:

 T4a means the tumour has spread into the chest wall (the structures surrounding and
protecting the lungs)
 T4b means the tumour has spread into the skin and the breast might be swollen
 T4c means the tumour has spread to both the skin and the chest wall
 T4d means inflammatory carcinoma – this is a cancer in which the overlying skin is red,
swollen and painful

 Read about inflammatory breast cancer

Node (N)
Node (N) describes whether the cancer has spread to the lymph nodes.

NX means that the lymph nodes can't be assessed (for example, if they were previously
removed).

N0 means there are no cancer cells in any nearby nodes.

Isolated tumour cells (ITCs) are small clusters of cancer cells less than 0.2 mm across, or a
single tumour cell, or a cluster of fewer than 200 cells in one area of a lymph node. Lymph nodes
containing only isolated tumour cells are not counted as positive lymph nodes.

N1

N1 means cancer cells are in the lymph nodes in the armpit but the nodes are not stuck to
surrounding tissues.

pN1mi means one or more lymph nodes contain areas of cancer cells called micrometastases
that are larger than 0.2mm. Or the nodes contain more than 200 cancer cells but are less than
2mm.

pN1a means that cancer cells have spread (metastasised) into 1 to 3 lymph nodes and at least
one is larger than 2mm.

pN1b means there are cancer cells in the lymph nodes behind the breastbone (the internal
mammary nodes) found with a sentinel node biopsy but the areas are too small to feel.
pN1c means there are cancer cells in 1 to 3 lymph nodes in the armpit and in the lymph nodes
behind the breastbone, but they are too small to feel.

N2

N2 is divided into 2 groups:

N2a means there are cancer cells in the lymph nodes in the armpit, which are stuck to each
other and to other structures.

N2b means there are cancer cells in the lymph nodes behind the breast bone (the internal
mammary nodes), which have been seen on a scan or felt by the doctor. There is no evidence of
cancer in lymph nodes in the armpit.

N3

N3 is divided into 3 groups:

N3a means there are cancer cells in lymph nodes below the collarbone.

N3b means there are cancer cells in lymph nodes in the armpit and behind the breastbone.

N3c means there are cancer cells in lymph nodes above the collarbone.

Metastasis (M)
Metastasis (M) describes whether the cancer has spread to a different part of the body.

M0 means that there is no sign that the cancer has spread.

cMo(i+) means there is no sign of the cancer on physical examination, scans or x-rays. But
cancer cells are present in blood, bone marrow, or lymph nodes far away from the breast cancer
– the cells are found by laboratory tests
M1 means the cancer has spread to another part of the body.

Regional lymph nodes (N)

Clinical

Regional lymph nodes cannot be assessed (eg,

NX
previously removed)

N0 No regional lymph node metastasis

Metastasis to movable ipsilateral level I, II axillary lymph

N1
node(s)

Metastases in ipsilateral level I, II axillary lymph nodes

that are clinically fixed or matted or in clinically detected*
N2
ipsilateral internal mammary nodes in the absence of
clinically evident axillary lymph node metastasis

Metastases in ipsilateral level I, II axillary lymph nodes

N2a
fixed to one another (matted) or to other structures

Metastases only in clinically detected* ipsilateral internal

N2b mammary nodes and in the absence of clinically evident
level I, II axillary lymph node metastases

Metastases in ipsilateral infraclavicular (level III axillary)

lymph node(s), with or without level I, II axillary node
involvement, or in clinically detected * ipsilateral internal
mammary lymph node(s) and in the presence of clinically
N3
evident level I, II axillary lymph node metastasis; or
metastasis in ipsilateral supraclavicular lymph node(s),
with or without axillary or internal mammary lymph node
involvement

N3a Metastasis in ipsilateral infraclavicular lymph node(s)

 Metastasis in ipsilateral internal mammary lymph node(s)
N3b
and axillary lymph node(s)

N3c Metastasis in ipsilateral supraclavicular lymph node(s)

Pathologic (pN)*

Regional lymph nodes cannot be assessed (for

pNX example, previously removed, or not removed for
pathologic study)

No regional lymph node metastasis identified

histologically. Note: Isolated tumor cell clusters
(ITCs) are defined as small clusters of cells ≤ 0.2
mm, or single tumor cells, or a cluster of < 200
cells in a single histologic cross-section; ITCs may
pN0 be detected by routine histology or by
immunohistochemical (IHC) methods; nodes
containing only ITCs are excluded from the total
positive node count for purposes of N
classification but should be included in the total
number of nodes evaluated

No regional lymph node metastases histologically,

pN0(i-)
negative IHC

Malignant cells in regional lymph node(s) ≤ 0.2

pN0(i+) mm (detected by hematoxylin-eosin [H&E] stain or
IHC, including ITC)

No regional lymph node metastases histologically,

pN0(mol-) negative molecular findings (reverse transcriptase
polymerase chain reaction [RT-PCR])
 Positive molecular findings (RT-PCR) but no
pN0(mol+) regional lymph node metastases detected by
histology or IHC

Micrometastases; or metastases in 1-3 axillary

lymph nodes and/or in internal mammary nodes,
pN1
with metastases detected by sentinel lymph node
biopsy but not clinically detected†

Micrometastases (> 0.2 mm and/or > 200 cells,

pN1mi
but none > 2.0 mm)

Metastases in 1-3 axillary lymph nodes (at least 1

pN1a
metastasis > 2.0 mm)

Metastases in internal mammary nodes, with

micrometastases or macrometastases detected by
pN1b
sentinel lymph node biopsy but not clinically
detected†

Metastases in 1-3 axillary lymph nodes and in

internal mammary lymph nodes, with
pN1c micrometastases or macrometastases detected by
sentinel lymph node biopsy but not clinically
detected†

Metastases in 4-9 axillary lymph nodes or in

clinically detected‡ internal mammary lymph
pN2
nodes in the absence of axillary lymph node
metastases

Metastases in 4-9 axillary lymph nodes (at least 1

pN2a
tumor deposit > 2.0 mm)

Metastases in clinically detected‡ internal

pN2b mammary lymph nodes in the absence of axillary
lymph node metastases
 Metastases in ≥ 10 axillary lymph nodes; or in
infraclavicular (level III axillary) lymph nodes; or in
clinically detected‡ ipsilateral internal mammary
lymph nodes in the presence of ≥ 1 positive level I,
II axillary lymph nodes; or in > 3 axillary lymph
pN3
nodes and in internal mammary lymph nodes, with
micrometastases or macrometastases detected by
sentinel lymph node biopsy but not clinically
detected†; or in ipsilateral supraclavicular lymph
nodes

Metastases in ≥ 10 axillary lymph nodes (at least 1

pN3a tumor deposit > 2.0 mm); or metastases to the
infraclavicular (level III axillary lymph) nodes

Metastases in clinically detected‡ ipsilateral

internal mammary lymph nodes in the presence of
≥ 1 positive axillary lymph nodes; or in > 3 axillary
pN3b lymph nodes and in internal mammary lymph
nodes, with micrometastases or macrometastases
detected by sentinel lymph node biopsy but not
clinically detected†

Metastases in ipsilateral supraclavicular lymph

pN3c
nodes

What Is Metastatic Breast Cancer?

Metastatic breast cancer is also classified as Stage 4 breast cancer. The cancer has spread to

other parts of the body. This usually includes the lungs, liver, bones or brain.
How does cancer spread, or metastasize?

The spread of cancer usually happens through one or more of the following steps:

 Cancer cells invade nearby healthy cells. When the healthy cell is taken over, it too can replicate more
abnormal cells.
 Cancer cells penetrate into the circulatory or lymph system. Cancer cells travel through the walls of
nearby lymph vessels or blood vessels.
 Migration through circulation. Cancer cells are carried by the lymph system and the bloodstream to
other parts of the body.
 Cancer cells lodge in capillaries. Cancer cells stop moving as they are lodged in capillaries at a distant
location and divide and migrate into the surrounding tissue.
 New small tumors grow. Cancer cells form small tumors at the new location (called micrometastases.)
Symptoms of metastasis may vary depending on where the cancer has spread
to.

Here are some symptoms that vary by locations commonly associated with breast cancer

metastasis.

Metastasis in the bone may cause: Roughly 70% of all patients living with advanced breast
cancer have bone metastases.

 Severe, progressive pain

 Swelling
 Bones that are more easily fractured or broken
Metastasis to the brain may cause: Brain metastasis is observed in 10% of breast
cancer patients with metastatic properties

 Persistent, progressively worsening headache or pressure to the head

 Vision disturbances
 Seizures
 Vomiting or nausea
 Behavioral changes or personality changes

Metastasis to the liver may cause:

 Jaundice
 Itchy skin or rash
 Abnormally high enzymes in the liver
 Abdominal pain, appetite loss, nausea, and vomiting

Metastasis to the lungs may cause:

 Chronic cough or inability to get a full breath
 Abnormal chest X-ray
 Chest pain
 Other nonspecific systemic symptoms of metastatic breast cancer can include fatigue, weight loss, and
poor appetite, but it’s important to remember these can also be caused by medication or depression.

BRCA1 Gene Function

The full name of the BRCA1 gene is “breast cancer 1, early onset” and it codes for a
tumor suppressor protein. Tumor suppressor proteins help repair DNA that has
become damaged in order to ensure stability of genetic material in cells. The BRCA1
protein also interacts with RNA polymerase II as well as histone deacetylase
complexes via the C-terminal domain. It therefore plays a role in DNA repair,
transcription and recombination. The BRCA1 protein prevents cells from dividing too
rapidly and growing in an abnormal way and mutations in the BRCA1 gene are
responsible for around 40% of familial breast cancers and over 80% of familial breast
and ovarian cancers.
The BRCA2 gene provides instructions for making a protein that acts as a tumor
suppressor. Tumor suppressor proteins help prevent cells from growing and dividing too
rapidly or in an uncontrolled way. The BRCA2 protein is involved in repairing damaged
DNA. In the nucleus of many types of normal cells, the BRCA2 protein interacts with several
other proteins to mend breaks in DNA. These breaks can be caused by natural and medical
radiation or other environmental exposures, and they also occur when chromosomes
exchange genetic material in preparation for cell division. By helping to repair DNA, the
BRCA2 protein plays a critical role in maintaining the stability of a cell's genetic
information. Researchers suspect that the BRCA2 protein has additional functions within
cells. For example, the protein may help regulate cytokinesis, which is the step in cell
division when the fluid surrounding the nucleus (the cytoplasm) divides to form two
separate cells. Researchers are investigating the protein's other potential activities.
PTEN acts as a tumor suppressor gene through the action of its phosphatase protein product.
This phosphatase is involved in the regulation of the cell cycle, preventing cells from growing and
dividing too rapidly.[8] It is a target of many cancer drugs. PTEN specifically catalyses
the dephosphorylation of the 3` phosphate of the inositol ring in PIP3, resulting in the biphosphate
product PIP2 (PtdIns(4,5)P2). This dephosphorylation is important because it results in inhibition
of the AKT signaling pathway, which plays an important role in regulating cellular behaviors such
as cell growth, surivival, and migration.

Roles of p53

The roles of p53 in growth arrest and apoptosis are illustrated in Figure 4-H-6. p53
is also directly involved in DNA repair. One of its transcriptional target gene,
p53R2, encodes ribonucleotide reductase, which is important for both DNA
replication and repair. p53 also interacts directly with AP endonuclease and DNA
polymerase which are involved in base excision repair.

ROLE IN DISEASE

If the p53 gene is damaged, tumor suppression is severely reduced. People who
inherit only one functional copy of p53 will most likely develop tumors in early
adulthood, a disease known as Li-Fraumeni syndrome. p53 can also be damaged in
cells by mutagens (chemicals, radiation or viruses), increasing the likelihood that
the cell will begin uncontrolled division. More than 50 percent of human tumors
contain a mutation or deletion of the p53 gene. In health p53 is continually
produced and degraded in the cell. The degradation of p53 is, as mentioned,
associated with MDM-2 binding. In a negative feedback loop MDM-2 is itself
induced by p53. However mutant p53s often don't induce MDM-2, and are
thusable to accumulate at very high concentrations. Worse, mutant p53 protein
itself can inhibit normal p53 (Blagosklonny, 2002).

Role of HER family in carcinogenesis HER 1 Receptor plays a role in cell survival by
activating PI-3/PKB pathway while HER 2 receptor helps in cell proliferation and
migration by activating MAPK and PI3K pathway. HER 3 and HER-4 promote
neovascularization and invasion through neuroglins respec- tively. ROLE OF HER
RECEPTORS IN ORAL SQUAMOUS CELL CARCINOMA EGFR/HER-1

Recepto r
Breast Calcifications
Breast calcifications are small calcium deposits that develop in a
woman's breast tissue. They are very common and are usually benign
(noncancerous). In some instances, certain types of breast calcifications may
suggest early breast cancer.

There are two types of breast calcifications: macrocalcifications and

microcalcifications.

Macrocalcifications look like large white dots on a mammogram (breast X-

ray) and are often dispersed randomly within the breast. Macrocalcifications
are common -- they are found in approximately half of women over age 50,
and one in 10 women under age 50 -- and are considered noncancerous.
require no further testing or follow-up.
Microcalcifications are small calcium deposits that look like white specks
on a mammogram. Microcalcifications are usually not a result of cancer. But
if they appear in certain patterns and are clustered together, they may be a
sign of precancerous cells or early breast cancer
Pengertian Fibroadenoma Mammae
Fibroadenoma atau fibroadenoma mammae (FAM) adalah salah satu jenis tumor jinak yang
paling umum terjadi pada payudara. Fibroadenoma berbentuk bulat dengan batas tegas dan
memiliki konsistensi kenyal dengan permukaan yang halus, serta ukurannya dapat
membesar pada masa kehamilan. Tumor jinak ini biasanya tidak terasa sakit dan mudah
bergeser saat disentuh. Fibroadenoma mammae adalah tumor jinak yang paling sering
terjadi pada wanita. Tumor ini terdiri dari gabungan antara kelenjar glandula dan fibrosa.
Fibroadenoma mammae (FAM), umumnya menyerang para remaja dan wanita dengan usia
di bawah 30 tahun. Adanya fibroadenoma atau yang biasa dikenal dengan tumor payudara
membuat kaum wanita selalu cemas tentang keadaan pada dirinya. Terkadang mereka
beranggapan bahwa tumor ini adalah sama dengan kanker. Yang perlu ditekankan adalah
kecil kemungkinan dari fibroadenoma ini untuk menjadi kanker yang ganas Fibroadenoma
mammae adalah tumor jinak yang sering terjadi dipayudara. FAM berukuran cukup kecil,
biasanya hanya 1 atau 2 cm dan jarang berukuran lebih besar dari 5 cm. Tumor ini terasa
seperti kelereng yang mudah digerakkan (mobile) di bawah kulit. Jika diraba teksturnya
bersifat kenyal dan halus (tidak berbonjol-bonjol). Tidak seperti kanker payudara,
fibroadenoma mammae tidak menyebabkan keluarnya cairan dari puting, bengkak,
kemerahan, atau iritasi kulit sekitar payudara. Jadi tidak ada gejala yang dirasakan oleh
penderitanya kecuali hanya adanya benjolan. Karena fibroadenoma mammae tidak terasa
nyeri, maka tumor ini pun kadang jarang disadari hingga anda meraba benjolan saat sedang
mandi atau saat melakukan pemeriksaan payudara sendiri (SADARI).

WO
A proto-oncogene is a normal gene that could become an oncogene due to mutations or
increased expression. Proto-oncogenes code for proteins that help to regulate the cell
growthand differentiation. Proto-oncogenes are often involved in signal transduction and
execution of mitogenic signals, usually through their protein products. Upon acquiring an
activating mutation, a proto-oncogene becomes a tumor-inducing agent, an oncogene.[
An oncogene is a gene that has the potential to cause cancer.[1] In tumor cells, they are
often mutated or expressed at high levels.[2] Most normal cells will undergo a programmed form
of rapid cell death (apoptosis) when critical functions are altered and malfunctioning. Activated
oncogenes can cause those cells designated for apoptosis to survive and proliferate
instead.[3] Most oncogenes began as proto-oncogenes, normal genes involved in cell growth and
proliferation or inhibition of apoptosis. If normal genes promoting cellular growth, through
mutation, are up-regulated, (gain of function mutation) they will predispose the cell to cancer and
are thus termed oncogenes. Usually multiple oncogenes, along with mutated apoptotic or tumor
suppressor genes will all act in concert to cause cancer.

Cell Cycle Regulation

G1 cyclins
G1 cyclins bind to Cdk proteins during G1. Once bound and activated, the Cdk
signals the cell's exit from G1 and entry into S phase. When the cell reaches an
appropriate size and the cellular environment is correct for DNA replication, the
cyclins begin to degrade. G1 cyclin degradation deactivates the Cdk and leads to
entry into S phase.
Mitotic Cyclins
Mitotic cyclins accumulate gradually during G2. Once they reach a high enough
concentration, they can bind to Cdks. When mitotic cyclins bind to Cdks in G2, the
resulting complex is known as Mitosis-promoting factor (MPF). This complex acts as
the signal for the G2 cell to enter mitosis. Once the mitotic cyclin degrades, MPF is
inactivated and the cell exits mitosis by dividing and re- entering G1. The cellular
signals that we described earlier (cell size, completion of DNA replication, and
cellular environment) provide the signals that regulate the synthesis and degradation
of cyclins
 Beberapa jenis karsinogen yang paling mungkin menyebabkan kanker
1. Asap tembakau

Zat kimia yang digunakan untuk produksi tembakau dapat menyebabkan kanker. Merokok
terkait langsung dengan kanker paru-paru, kanker tenggorokan, gangguan pada saluran
kemih dan kanker pankreas.

2. Pola makan

Makanan sangat mungkin meningkatkan peluang kanker. Makanan yang bisa menyebabkan
kanker adalah makanan yang banyak melalui proses pengolahan dan diawetkan
seperti makanan dalam kaleng, daging merah panggang, gula rafinasi, makanan yang
diasinkan, acar dan makanan yang diasap, minuman berkarbonasi, dan minyak
hidrogenisasi.

3. Patogen

Beberapa virus, bakteri dan parasit dapat menyebabkan kanker. Contoh dari patogen yang
bersifat karsinogenik pada tubuh manusia meliputi hepatitis B dan C, human papilomavirus
(HPV) dan Epstein-Barr.

4. Radiasi

Kelompok faktor ini meliputi materi radioaktif (X-ray, contohnya) dan sinar ultraviolet (UV)
yang berbahaya.

5. Karsinogen dari lingkungan dan tempat kerja

Polusi udara, air dan tanah dapat menyebabkan kanker paru-paru dan kanker saluran
kemih. Bahaya pada tempat kerja memberikan risiko pada para pekerja yang terlibat
pekerjaan dengan karsinogen penyebab kanker seperti asbestos, timah, benzena dan vinil
klorida.

Karsinogen lainnya yang diketahui menyebabkan kanker pada manusia meliputi:

 Asbestos
 Benzena
 Tar batubara
 Formaldehida
 Mustard gas
 Radiasi solar
 Debu kayu