What makes a normal cell turn cancerous?

A normal cell can become a cancer cell if it undergoes damage to the DNA. Since it is
the DNA that regulates the cells cycle of growth and death and any changes or
damage to DNA affects the cell.

For most cells if the DNA is damaged the cell either repairs the damage or the cell
dies. In cancer cells, the damaged DNA is not repaired and the damage is propagated
to newer abnormal cells that are born of the defective cell.

Damaged DNA by mutation can also be inherited from parents or relatives. DNA
damage can also occur due to exposure to toxins like cigarette smoking, alcohol etc.

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.

Serum biomarker testing is an ideal form of cancer detection because it is minimally

invasive, cost effective, easily administered, nonsubjective, and is not contingent upon
primary ovarian involvement. The most well-studied ovarian cancer biomarker is CA-
125, a high molecular weight transmembrane glycoprotein expressed by coelomic-
and Mllerian-derived epithelia, including that of the fallopian tube, endometrium,
and endocervix [19]. It is not expressed by normal ovarian epithelium [20]. CA-125 is
detected at low levels ( 35 U/mL) in the serum of healthy individuals but is elevated
in 50% of stage ovarian cancer patients and 90% of advanced-stage patients [2124].
CA-125 elevation is predominantly associated with serous tumors, the most common
and most lethal subtype of ovarian carcinoma [25]. Serum levels directly correlate
with the level of CA-125 protein production in tumor cells and appear to reflect a
state of active tumor growth [2527]. Following its discovery in 1981 [28], CA-125
was intensely studied to evaluate its potential for detecting early-stage ovarian cancer,
and many encouraging results were reported. For example, a study of prediagnostic
serum samples found that CA-125 was elevated in 25% of ovarian cancer patients 5
years prior to their diagnoses [29]. However, it was later discovered that serum CA-
125 levels can be increased by a range of benign conditions (such as pelvic
inflammatory disease, endometriosis, uterine fibroids, and ovarian cysts) making false
positivity a problem [30]. So far, CA-125 has not demonstrated adequate sensitivity to
support its use in screening asymptomatic women for early-stage ovarian cancer [31],
but longer-term studies are still underway. In the meantime, CA-125 remains a
valuable tool for monitoring response to chemotherapy and for detecting disease
relapse following treatment [32, 33].

What are BRCA1 and BRCA2?

BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins. These
proteins help repair damaged DNA and, therefore, play a role in ensuring the stability
of the cells genetic material. When either of these genes is mutated, or altered, such
that its protein product either is not made or does not function correctly, DNA damage
may not be repaired properly. As a result, cells are more likely to develop additional
genetic alterations that can lead to cancer.

Specific inherited mutations in BRCA1 and BRCA2 increase the risk of female breast
and ovarian cancers, and they have been associated with increased risks of several
additional types of cancer. Together, BRCA1 and BRCA2 mutations account for about
20 to 25 percent of hereditary breast cancers (1) and about 5 to 10 percent of all
breast cancers (2). In addition, mutations in BRCA1 and BRCA2 account for around
15 percent of ovarian cancers overall (3). Breast and ovarian cancers associated with
BRCA1 and BRCA2 mutations tend to develop at younger ages than their
nonhereditary counterparts.

A harmful BRCA1 or BRCA2 mutation can be inherited from a persons mother or

father. Each child of a parent who carries a mutation in one of these genes has a 50
percent chance (or 1 chance in 2) of inheriting the mutation. The effects of mutations
in BRCA1 and BRCA2 are seen even when a persons second copy of the gene is
normal.
How much does having a BRCA1 or BRCA2 gene mutation increase a womans risk of
breast and ovarian cancer?

A womans lifetime risk of developing breast and/or ovarian cancer is greatly

increased if she inherits a harmful mutation in BRCA1 or BRCA2.

Breast cancer: About 12 percent of women in the general population will develop
breast cancer sometime during their lives (4). By contrast, according to the most
recent estimates, 55 to 65 percent of women who inherit a harmful BRCA1
mutation and around 45 percent of women who inherit a harmful BRCA2 mutation
will develop breast cancer by age 70 years (5, 6).

Ovarian cancer: About 1.3 percent of women in the general population will
develop ovarian cancer sometime during their lives (4). By contrast, according to
the most recent estimates, 39 percent of women who inherit a harmful BRCA1
mutation (5, 6) and 11 to 17 percent of women who inherit a harmful BRCA2
mutation will develop ovarian cancer by age 70 years (5, 6).

It is important to note that these estimated percentages of lifetime risk are different
from those available previously; the estimates have changed as more information has
become available, and they may change again with additional research. No long-term
general population studies have directly compared cancer risk in women who have
and do not have a harmful BRCA1 or BRCA2 mutation.

It is also important to note that other characteristics of a particular woman can make
her cancer risk higher or lower than the average risks. These characteristics include
her family history of breast, ovarian, and, possibly, other cancers; the specific
mutation(s) she has inherited; and other risk factors, such as her reproductive history.
However, at this time, based on current data, none of these other factors seems to be
as strong as the effect of carrying a harmful BRCA1 or BRCA2 mutation.

Certain factors may

increase your risk of
ovarian cancer:

Age. ...

Inherited gene
mutation. ...
 Estrogen hormone
replacement
therapy, especially
with long-term use
and in large doses.

Age when
menstruation started
and ended. ...

Never being
pregnant.

Fertility treatment.

Smoking.

Use of an
intrauterine device.

Data from the National Cancer Registry of Malaysia for 2004 provide an age-
standardised incidence rate (ASR) of 46.2 per 100,000 women. This means that
approximately 1 in 20 women in the country develop breast cancer in their lifetime.
However, the rate differs between the three main races, the Malays, Chinese and
Indians. The age standardized incidence in Chinese is the highest, with 59.7 per
100,000, followed by the Indians at 55.8 per 100,000. The Malays have the lowest
incidence of 33.9 per 100,000. This translates into 1 in 16 Chinese, 1 in 16 Indian and
1 in 28 Malay women developing breast cancer at some stage in their lives. The
commonest age at presentation is between 40-49 years, with just over 50% of the
cases under the age of 50 years, 16.8% below 40, and 2% under 30. Some 55.7% of
all cases were found to be ER positive. The commonest presenting symptom was a
lump in the breast in over 90% of cases, generally felt by the woman herself. The
mean size of the lump was 4.2 cm, and on average, the women waited 3 months
before seeking medical attention. Over the 12-year period from 1993 to 2004, about
60-70% of women presented with early stage (Stages 1-2) while 30-40% presented
with late breast cancer (Stages 3-4). Especially Malays present at later stages and with
larger tumours. Consequently their survival is worse than with Chinese and Indian
women. The challenge in Malaysia is to be able to provide a comprehensive service in
the diagnosis and treatment of breast cancer, and this requires training of a team of
health professionals dedicated to breast health, such as breast surgeons, radiologists
specializing in breast imaging, breast pathologists, plastic surgeons specializing in
breast reconstruction, medical and radiation oncologists, psycho-oncologists,
counselors, and breast nurses. Advocacy can play a role here in galvanizing the
political will to meet this challenge.