Team 2 Slides - George Mason University

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Etiology of Breast Cancer:
with special attention to
environmental factors
By:
Saad Almasoud , Lamya Alomair, Amir Shams
George Mason University
Spring 2013
Breast anatomy I
1-ribs:
2-pectoralis muscle
3-chest wall
4-coopers ligaments
5-small ducts and acini
6-major ducts
7-nipple
8-lobule
Breast Anatomy II
The lymph node bearing area has been
divided into three axillary regions:
Level 1:
Lymph nodes lateral and inferior to the pectoralis minor muscle
Level 2:
Lymph nodes under the pectoralis minor muscle
Level 3:
Lymph nodes under and deep to the pectoralis minor muscle
Vascular and nervous system:
1-The lateral border of the Pectoralis Minor and Major muscle
2-The Latissimus Dorsi Muscle
3-The Axillary Vein
4-The Long Thoracic Nerve which innervates the Serratus Anterior Muscle
5-The Thoraco-Dorsal Nerve which innervates the Latissimus Dorsi Muscle
6-The Intercostal Brachial Nerve which is a sensory nerve for the inferior aspect of the arm
and the posterior aspect of the axilla
7-The Lateral Pectoral Nerve which innervates portions of the pectoralis muscle
Breast Development:
Pre and post pubertal development
CHANGES ASSOCIATED WITH
PREGNANCY

As the output of oestrogen and progesterone produced first by the corpus luteum and later by the placenta rises during
pregnancy, the intralobular ductal epithelium proliferates and the cells increase in size: the number and length of the
ductal branches therefore increase. Alveoli develop at their termini and expand as their cells and lumina fill with newly
synthesized and secreted milk.The myoepithelial cells, which are initially spindle-shaped, become highly branched stellate
cells, especially around the alveoli. Adjacent myoepithelial cells intermesh to form a basket-like network around the alveoli
and ducts, interposed between the basal lamina and the luminal cells. Their cytoplasm contains actin and myosin
filaments and they are contractile. There is a concomitant reduction in adipose tissue in the stroma. The numbers of
lymphocytes, including plasma cells, and eosinophils increase greatly. Blood flow through the breast increases.

Secretory activity in the alveolar cells rises progressively in the latter half of pregnancy. In late pregnancy, and for a few
days after parturition, their product is different from later milk and is known as colostrum, which is low in lipid but rich in
protein and immunoglobulins. Colostrum confers a measure of passive immunity to the neonatal alimentary tract; it also
has laxative properties. Proliferation of the glandular breast parenchyma results in an overall increase in breast size
through gestation.
CHANGES ASSOCIATED WITH
LACTATION

True milk secretion begins a few days after parturition as a result of a reduction in circulating oestrogen and
progesterone, a change which appears to stimulate production of prolactin by the anterior hypophysis.

Milk distends the alveoli so that the cells flatten as secretion increases . The alveolar cell cytoplasm accumulates
membrane-bound granules of casein and other milk proteins, and these are released from the apical plasma membrane
by membrane fusion (merocrine secretion; see Ch. 2). Lipid vacuoles are formed directly in the apical cytoplasm as small
lipid droplets which fuse with each other to create large ‘milk vacuoles' up to 10 μm across, that frequently protrude from
the cell surface. These are released as intact lipid droplets with a thin surround of apical plasma membrane and adjacent
cytoplasm (apocrine secretion). On hormonal stimulation by oxytocin, myoepithelial cells contract to expel alveolar
secretions into the ductal system in readiness for suckling.

After the onset of lactation there is a gradual reduction in the numbers of lymphocytes and eosinophils in the stroma,
although plasma cells continue to synthesize IgA for secretion into the milk. Alveolar cells take up IgA synthesized by
adjacent plasma cells by endocytosis at their basal surfaces and secrete it apically, as dimers complexed to epithelial
secretory component.
Engorged Vs. Non lactating
Breast abnormalities
Part I: non-proliferative lesion
What is mastalgia
(breast pain)?

Mastalgia is breast pain and is generally classified as either cyclical (associated
with menstrual periods) or noncyclic. Noncyclic pain may come from the breast
or may come from somewhere else, such as nearby muscles or joints, and may
be felt in the breast. Pain can range from minor discomfort to severely
incapacitating pain in some cases. Many women with mastalgia worry more
about the consequences of cancer than about the pain itself.
What is mastitis?
Mastitis is inflammation of the breast. It is most often caused by a breast infection that affects women who
are breast-feeding, but it can happen in any woman. A break in the skin or an opening in the nipple can
allow bacteria to enter the breast duct, where they can grow.The body's white blood cells release substances
to fight the infection.This causes swelling and increased blood flow.The area may become painful, red, and
warm to the touch. Other symptoms can include fever and a headache.
Mastitis is treated with antibiotics. In some cases, a breast abscess (a collection of pus) may form. Abscesses
are treated by draining the pus, either by surgery or by using a needle (often guided by ultrasound), and then
giving antibiotics.
Having mastitis does not raise a woman's risk of developing breast cancer. But an uncommon type of cancer
known as inflammatory breast cancer has symptoms that are a lot like mastitis and can be mistaken for an
infection. If you are diagnosed with mastitis but antibiotic treatment does not help, a biopsy of the skin may
be needed to be sure it is not cancer. Inflammatory breast cancer can spread quickly, so do not put off going
back to the doctor if you still have symptoms after antibiotic treatment.
What is chronic sub areolar
abscess?

Chronic sub areolar abscess is a breast
infection that occurs infrequently. Surgery
may be needed to stop this repeating
infection.
Duct ectasia

Duct ectasia is also known as mammary duct ectasia. It is a common condition that tends
to affect women in their 40s and 50s. It occurs when a breast duct widens and its walls
thicken, which can cause it to become blocked and lead to fluid build-up.

Duct ectasia may cause a sticky green or black discharge, which is often thick. The nipple
and nearby breast tissue may be tender and red.The nipple may be pulled inward.
Sometimes scar tissue around the abnormal duct causes a hard lump that may be
confused with cancer.

This condition sometimes improves without treatment, or with warm compresses and
antibiotics. If the symptoms do not go away, the abnormal duct can be removed through an
incision (cut) at the edge of the areola (the darker colored area around the nipple).

Duct ectasia does not increase breast cancer risk.
What is fat necrosis?
Fat necrosis is a condition in which painless, round, firm lumps caused by damaged
and disintegrating fatty tissues form in the breast tissue. Fat necrosis often occurs in
women with very large breasts or in response to a bruise or blow to the breast. This
condition may also be the result of a lumpectomy and radiation from a previous
cancerous lump. In some cases, physicians/care providers will watch the lump
through several menstrual cycles, and may perform a mammogram before deciding
whether or not to remove it.These lumps are not malignant and there is no reason
to believe that they increase a woman's risk of cancer.
What is a cyst?

A cyst is a fluid-filled sac that develops in the breast tissue. Such cysts typically
occur in women between the ages of 35 and 50 and are most common in those
approaching menopause. They often enlarge and become tender and painful just
before the menstrual period and may seem to appear overnight. Cysts are rarely
malignant and may be caused by a blockage of breast glands.

Cysts can feel either soft or hard. When close to the surface of the breast, cysts
can feel like a large blister, smooth on the outside, but fluid-filled on the inside.
However, when they are deeply imbedded in breast tissue, cysts will feel like hard
lumps because they are covered with tissue.
Breast abnormalities
Type II: proliferative lesion
without atypia
What is a Fibroadenoma?

Fibroadenomas are solid, smooth, firm, benign lumps that are most commonly found in
women in their 20s and 30s. They are the most common benign lumps that occur in
women and can occur in women of any age. Increasingly, they are being seen in
postmenopausal women who are taking hormone therapy.

The painless lump feels rubbery and moves around freely and very often is found by the
woman herself. Fibroadenomas vary in size and can grow anywhere in the breast tissue.
What is Sclerosing Adenosis?

Sclerosing adenosis is a breast condition that involves excessive growth of tissues in the
breast's lobules, often resulting in breast pain. While these changes in the breast tissue are
microscopic, they may show up on mammograms as calcifications and can produce lumps.
Usually a biopsy is necessary to distinguish this condition from cancer. In addition, because
the condition can be mistaken for cancer, the lumps are usually removed through surgical
biopsy.
What is intraductal papilloma?

An intraductal papilloma is a small, wart-like growth that projects into the breast ducts near
the nipple. This causes a bloody or sticky discharge. In addition, any slight bump or bruise
near the nipple can cause the papilloma to bleed. If the discharge becomes bothersome,
the duct can be surgically removed, often without changing the appearance of the breast.

While single papillomas most often affect women nearing menopause, multiple intraductal
papillomas -- which often occur in both breasts -- are more common in younger women.
Multiple intraductal papillomas are more likely to be associated with a lump than with
nipple discharge. Any papilloma associated with a lump is surgically removed.

Bloody discharge
Uncontrolled Cell growth
What is –plasia?
 What is benign growth?
 What is malignant growth?
 What is tumor?
 What is cancer?

What is Anaplasia?

Reversion of cells to an immature or a less
differentiated form, as occurs in most
malignant tumors.
What is Hypoplasia?
1. Incomplete or arrested development of an
organ or part.
 2. Atrophy due to destruction of some of the
elements of a tissue or organ.

What is Hyperplasia?

abnormal increase in the number of normal
cells in normal arrangement in an organ or
tissue, which increases its volume.
What is Dysplasia?
1. abnormality of development.
 2. in pathology, alteration in size, shape, and
organization of adult cells.

What is metaplasia?

the change in the type of adult cells in a
tissue to a form abnormal for that tissue
What is Desmoplasia?

The formation and proliferation of fibroblasts
and fibrous connective tissue, especially in
tumors.
Last but not least :
Neoplasia
Neoplasm is an abnormal mass of tissue as a result
of neoplasia.
 ‘neoplasm’ means new growth without qualifying the
nature of that growth .
 What is neoplasm?
any new and abnormal growth, specifically one in which
cell multiplication is uncontrolled and progressive.
Neoplasms may be benign or malignant.
 A neoplasm can be benign, potentially malignant
(pre-cancer), or malignant (cancer).

Types of neoplasm
Benign :do not transform into cancer.
 Potentially malignant: They do not invade and
destroy but, given enough time, will transform
into a cancer.
 Malignant neoplasms are commonly called
cancer.They invade and destroy the
surrounding tissue, may form metastases and
eventually kill the host.

What is tumor?

In modern medicine, the term tumor means
a neoplasm that has formed a lump.
Metastasis
Breast abnormalities
Type III: Atypical proliferative
lesion
Ductal Carcinoma In-Situ
(DCIS)
DCIS is a type of early breast cancer confined
to the inside of the ductal system.
Infiltrating(invasive) Ductal
Carcinoma (IDC)
IDC is the most common type of breast cancer representing
78% of all malignancies.These lesions appear as stellate (star
like) or well-circumscribed (rounded) areas on mammograms.
The stellate lesions generally have a poorer prognosis.
Infiltrating Lobular Carcinoma
(ILC)
Infiltrating lobular carcinoma is a type of breast cancer that usually appears
as a subtle thickening in the upper-outer quadrant of the breast. This breast
cancer type represents 5% of all diagnosis. Often positive for estrogen and
progesterone receptors, these tumors respond well to hormone therapy.
Rare breast cancer

What is Paget disease of the breast?

Paget disease of the breast (also known as Paget disease of the nipple and mammary Paget disease) is
a rare type of cancer involving the skin of the nipple and, usually, the darker circle of skin around it,
which is called the areola. Most people with Paget disease of the breast also have one or more tumors
inside the same breast.These breast tumors are either ductal carcinoma in situ or invasive breast cancer
Inflammatory Breast Cancer
(IBC)

Inflammatory breast cancer is a rare and very aggressive type of breast
cancer that causes the lymph vessels in the skin of the breast to become
blocked. This type of breast cancer is called "inflammatory" because the
breast often looks swollen and red, or "inflamed". IBC accounts for 1% to
5% of all breast cancer cases in the United States.
End of breast abnormalities
Hormone effects on breast
development
1-growth hormone(LH-FSH)
 2-estrogen(E1-E2-E3)
 3-progestrone
 4-prolactin
 5-oxytocin
 6-testostrone

Luetinizing hormone

Luteinizing hormone (LH, also known as lutropin [1] and sometimes
lutrophin [2]) is a hormone produced by the anterior pituitary gland. In females,
an acute rise of LH ("LH surge") triggers ovulation[3] and development of the
corpus luteum. In males, where LH had also been called interstitial cellstimulating hormone (ICSH),[4] it stimulates Leydig cell production of
testosterone.[3] It acts synergistically with FSH.
Follicle-stimulating hormone
(FSH)

Follicle-stimulating hormone (FSH) is a hormone found in humans and other animals.
It is synthesized and secreted by gonadotrophs of the anterior pituitary gland.[1] FSH
regulates the development, growth, pubertal maturation, and reproductive processes of the
body. FSH and luteinizing hormone (LH) act synergistically in reproduction. Specifically, an
increase in FSH secretion by the anterior pituitary causes ovulation.
Progesteron

Progesterone also known as P4 (pregn-4-ene-3,20-dione) is a C-21 steroid hormone
involved in the female menstrual cycle, pregnancy (supports gestation) and embryogenesis
of humans and other species. Progesterone belongs to a class of hormones called
progestogens, and is the major naturally occurring human progestogen.
prolactin


Prolactin (PRL) also known as luteotropic
hormone (LTH) is a protein that in humans is
encoded by the PRL gene.[1]
Prolactin is a peptide hormone discovered by
Henry Friesen. Although it is perhaps best known
for its role in lactation, prolactin already existed
in the oldest known vertebrates—fish—where
its most important functions were probably
related to control of water and salt balance.
Estradiol during menstrual
cycle
LOOKING FOR CLUES :

Very briefly
Epidemiology of breast cancer

Studying the factors that are thought to
increase the risk of breast cancer by Statistics
1-Gender

A-From the available evidence, breast cancer is predominantly a disease, which develops in women
although in rare circumstances the condition can be diagnosed in males.

B-It seems likely that estrogen has some role in the development of breast cancer, which would explain
why there is almost a 100 -fold difference in breast cancer incidence between males and females.

C-However the difference in incidence may be because in females estradiol is able to exert a direct
biological effect on breast cells, whereas in males testosterone needs to be converted to estradiol before
exerting any biologic effect
2-Age

A-breast cancer is relatively rare in young women who are younger than 40 years
of age. Some 161 cases were diagnosed in women under the age of 40 years
during 1996, and the incidence increases with increasing age .
3-Menarche-establishment of
regularity
A-The establishment of regular menstrual
cycles within one year of the first menstrual
cycle has been found to double the risk of
breast cancer, compared to a situation where
menstrual cycles establish regularity in five or
more years
 rapid establishment of regularity in
menstrual cycles increased the risk of
developing breast cancer four-fold
(Henderson et ah, 1981).

4-Menarche-Length
A-The length of the menstrual cycle and the
duration of menstrual activity have been
positively correlated with breast cancer risk.
 B-regular menstrual cycle of 28 days is
not only associated with the regular
cycling of estrogen and progesterone
but also the cycle of cell multiplication
(mitosis) and cell death (apoptosis).

5-Parity-Age at full term
pregnancy

The same researchers also found that if a
woman gave birth to her first child under
the age of eighteen, that she would only
have 40 percent of the breast cancer risk
of a nulliparous woman (MacMahon et
al., 1970). This decrease in risk, (compared to
the risk for a woman with a first full term birth
after the age of thirty years), is widely supported
throughout the literature, even though the
strength of the association varies from one study
to another (MacMahon et aI., 1970; Kelsey et
al., 1993).
6-Parity-high number of birth
A-high parity (or a high number of births)
provides additional protection against the
risk of developing breast cancer, independent
of the age at first birth.
 B-If a woman's second birth occurred under
the age of 25 years, the risk of developing
breast cancer was only one third of that of a
woman who had only one birth under the
same age (MacMahon et al., 1982).

7-Parity-Incomplete pregnancy
A-Some researchers have investigated the link
between incomplete pregnancies, arising from
spontaneous or induced abortions, and breast cancer.
 B-Their research is based on the assumption that the
risk of breast cancer may be increased because the
birth does not go to term, and would no
longer have a protective effect (pike et al.,
1981; Hadjimichael et al., 1986; Parazzini et
al., 1991).
 C-women who had at least one abortion before their
first full term pregnancy, had approximately 20%
greater risk of developing breast cancer, than women
who did not have any incomplete pregnancies.

8-pregnancies not followed by
breastfeeding

A-The fact that these women did not
breastfeed when their breasts had
developed for nursing, resulted in a
greater likelihood of breast cancer
development (Wainwright, 1931).
9-Early menstrual and late
Menopause

A combination of early age at menarche
and a late age at menopause would
therefore prolong the time o f the menstrual
cycling o f sex hormones, and thus would
substantially increase a woman's risk of
breast cancer development (Henderson et al.,
1985; Rosner et al., 1994).
10-Family History-Kinship


A-Data from the Nurse's Health Study, which
began in 1976 and recruited biannually until
1990, suggested that the degree of kinship and
the number of closely affected relatives forms a
strong relationship with breast cancer
development (Colditz et al., 1996).
B-there was a 2.3 fold higher risk (relative risk;
1.9 - 2.7, 95% confidence intervals) of
developing breast cancer if the participant had a
first degree relative affected, as compared to
women with no family history of the disease.
Genetics clues
HER2
 RAS
 PI3K
 AKT
 Cyclin D1
 C-myc
 C-fos
 4e-elf

•
•
•
•
•
•
•
•
P53
P27
BRCA-1
BRCA-II
BRCA-III
CHK-2
ATM
PTEN
11-Oral Contraceptive
A-The very long use of oral contraceptives by
young women before first full term pregnancy
may be a very important factor that puts
them at great risk of breast cancer.
 B-For a pill containing a combination of
progesteron and greater than 50micro.g of
estrogen, the relative risk of breast cancer is
lower than if the combination pill contains
less than 50microg of estrogen

12-hormone replacement
therapy

A-studies have suggested that HRT use may
increase the risk of some cancers, especially
endometrial, ovarian, cervical, and breast
cancers ( ARONSON-et.al)
13-Life style-weight


A-In women there are three main lifetime
periods in which substantial weight gain occurs;
during menarche fatty deposits accumulate in
the hips and buttocks; and during pregnancy
and menopause there is an increase in body fat
distribution centrally and in the breasts .
B-Some researchers suspect that a greater
weight gain during adolescence, accompanied by
little physical activity, is related to a greater risk
of breast cancer.
14-Life style-Alcohol Consumption
A-Alcohol consumption is one of the only
established dietary factors that has been
associated with breast cancer risk.
 B-light alcohol intake was associated with a
weak to modest correlation with breast
cancer risk, whilst intakes of 24 grams per
day or more, was associated with a significant
increased risk.

End of Part two
What did we describe so far
Breast
Anatomy
&
Breast
Development
Breast
Abnormalities
&
Breast Cancer
Looking for
clues
NEXT Step :
Cure and
Prevention
How Bad is it?
2009 Estimated US Cancer Deaths*
Lung & bronchus
30%
Men
292,540
Women
269,800
26%
Lung & bronchus
15%
Breast
Prostate
9%
Colon & rectum
9%
9%
Colon & rectum
Pancreas
6%
6%
Pancreas
Leukemia
4%
5%
Ovary
Liver & intrahepatic
bile duct
4%
4%
Non-Hodgkin
lymphoma
Esophagus
4%
3%
Leukemia
Urinary bladder
3%
3%
Uterine corpus
Non-Hodgkin
lymphoma
3%
2% Liver & intrahepatic
bile duct
Kidney & renal pelvis
3%
2%
25%
25%
All other sites
ONS=Other nervous system.
Source: American Cancer Society, 2009.
Brain/ONS
All other sites
Trends in the Number of Cancer Deaths Among Men and
Women, US, 1930-2006
300,000
295,000
290,000
Men
285,000
250,000
280,000
Women
275,000
200,000
270,000
Women
265,000
150,000
20
00
20
01
20
02
20
03
20
04
20
05
20
06
Number of Cancer Deaths
Men
100,000
50,000
0
1930
1940
1950
1960
1970
1980
1990
2000
Source: US Mortality Data, 1930-2006, National Center for Health Statistics, Centers for Disease
Control and Prevention, 2009.
The puzzle of breast cancer
Very complex disease
 No one single factor associated
with causing the disease
 Breast cancer develops over a long
period of time, usually 10 to 30
years

Risks related to breast cancer
Risks related to breast cancer
Risks related to breast cancer
Therapy and Drug
Drugs which target Breast Cancer
all drugs that have been approved by the
U.S. Food and Drug Administration for use
as a breast cancer treatment.
Chemotherapy: stop cancer cells
from dividing and growing
1-Cyclophosphamide ex.Cytoxan
2-Doxorubicin ex.Doxil
3-Carboplatin ex.Paraplatin
4-Paclitaxel ex.Taxol
5-Vinorelbine ex. Navelbine
6-Other Chemotherapy drugs
 Adrucil® / Fluorouracil (5-FU)
 Gemzar ®/ Gemcitabine
 Camptosor ® / Irinotecan
 Ixempra® / Ixabepilone
 Methotrexate
 Temodar® / Temozolomide
 Topotecan
 Vincristine
 Vinblastine
 Xeloda® / Capecitabine
 High dose chemotherapy with stem cell rescue
Hormone Therapy: prevent positive cells
from being exposed to the hormones that
cause them to grow











Evista® / Raloxifene
Fareston® / Toremifine
Faslodex® / Fulvestrant
Nolvadex® / Tamoxifen
Arimidex / Anastrozole
Aromasin / Exemestane
Femara / Letrozole
Lupron® / Leuprolide
Plenaxis® / Abarelix
Suprefact® / Buserlin
Zoladex® / Goserelin
Bisphosphonate Therapy
treat breast cancer that has spread to the
bone.
 Actonel® / Risedronate
 Aredia® / Pamidronate
 Boniva® / Ibandronate
 Fosamex® /Alendronate
 Xgeva® /Denosumab
 Zometa® / Zoledronate
Targeted Biological Therapy
focus on blocking the actions of certain
normal body proteins that allow cancer
cells to grow and divide.
 Herceptin® / Trastuzumab
 Lapatinib® / Tykerb
 Avastin® / Bevacizumab
Only Practical method
Prevention :

One logical response to the growing
breast cancer burden is to develop
effective prevention strategies [1-3]
Why Prevention is Virtually
Impossible?
What is hard to prevent:

Although many breast cancer risk factors
have been identified that might form the
basis of such strategies, prevention
remains challenging, and virtually
impossible due to practical difficulties in
modifying risk-increasing factors like
nulliparity, late age at first full-term
pregnancy, early age at menarche, and late
age at menopause [1,2].
One Example is Environmental Risk
Factors
Do environmental chemicals affect the
risk of cancer?
 This is a question being asked by
scientists, cancer advocates, educators,
policy makers, and those exposed to
environmental chemicals in their homes
and workplaces.[3-4]

One of the first publications
Studies in migrants have shown increases in breast cancer incidence and mortality
following migration from a lower- to a higher-risk country.(12–14)
For example, Japanese immigrants in Los Angeles County had a clearly higher rate of
breast cancer than Japanese in Japan.(12)
Furthermore, the incidence of breast cancer in first-generation Japanese immigrants
in Sao Paulo from 1968 to 1978 was higher than that among Japanese living in Japan
, whereas mortality increased from 1979 to 2001 to a rate intermediate between that
of Japanese living in Japan and Brazilians living in the state of Sao Paulo.(13,14)
These findings strongly suggest that breast cancer risk is influenced by factors
associated with the lifestyle or environment of the destination country[2].
Do environmental chemicals affect the
risk of cancer?
NCI will prioritize geneenvironmental studies in 2002
81
Environment factors
1-Occupational Exposure
Including nurses, teachers, beauticians, airline attendants, lab
technicians, telephone and telegraph operators, electronic workers,
agriculture workers, leather and fur processors, glass manufacturing
workers, and metal fitters and assemblers (Aronson et al., 1999; Band
et al., 2000; Gardner et al., 2002; Peplonska et al., 2007; Teitelbaum et
al., 2003).

Environment factors

2- Ionizing Radiation
High exposures to ionizing radiation related to medical diagnosis or treatment was associated with breast cancer (Doody et al., 2000; National
Academy of Sciences, 2005). Women with benign breast disease or a family
history of breast cancer may have increased breast cancer risk following
relatively low-level exposure to ionizing radiation (Hill et al., 2002).
Environment factors

3-Environmental Contaminants
Old Contaminant Story :DDT
Deep Impact
The Other :Atrazine
Most widely used herbicide in the US
 First registered for use in 1959
 Annual crop land usage
◦ Up to 77.3 million lbs active ingredient*
*Source: Asplein, 1999
Other Environmental Contaminants










1-Polychlorinated Biphenyls (PCBs)
2-p,p′-DDE and p,p′-DDT
3-Mirex
4-Hexachlorobenzene (HCB)
5-Dieldrin
6-Chlordane
7-TCDD
8-Triazine herbicides
9-Cadmium (Cd)
10- Polycyclic aromatic hydrocarbons (PAHs)
Systematic review of environmental
risk factors of Breast Cancer
Case study Analysis
Statistical Analysis
Logistic Regression Analysis on NHANES Questionnaire
Some of our results
• Analysis 1: Analysis of environmental Risk
Factors as predictor for Breast Cancer 2008
Some of our results

Analysis 2: Analysis of environmental
Risk Factors as predictor for Breast
Cancer 2007
Some of our results

Analysis 3: Analysis of environmental
Risk Factors as predictor for Breast
Cancer 2006
Thank you !
Question?
Reference:
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News-medical. [http://www.news-medical.net/health/Breast-CancerEpidemiology.aspx].
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Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN
2008. Int J Cancer 127:2893–2917
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Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008, Cancer Incidence and Mortality Worldwide: IARC
CancerBase No. 10. Lyon: International Agency for Research on Cancer, 2010. [Cited 14 Apr 2011.] Available from URL:
http://globocan.iarc.fr/
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The oncology channel. [http://www.oncologychannel.com/breastcancer/index.shtml].
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Salehi, F., et al., Review of the etiology of breast cancer with special attention to organochlorines as potential endocrine disruptors. J
Toxicol Environ Health B Crit Rev, 2008. 11: p. 276 - 300.
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Ferlay J, Parkin DM, Curado MP et al. Cancer Incidence in Five Continents,Volumes I–IX: IARC CancerBase No. 9. Lyon: International
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Ferlay J. World Health Organization, Mortality Database. [Cited 7 Jan 2010.]Available from URL: http://www.who.int/whosis/whosis/
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Hirabayashi Y, Zhang M. Comparison of time trends in breast cancer incidence (1973–2002) in Asia, from cancer incidence in five
continents, Vols IV–IX. Jpn J Clin Oncol 2009; 39: 411–12.
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Shin HR, Boniol M, Joubert C et al. Secular trends in breast cancer mortality in five East Asian populations: Hong Kong, Japan, Korea,
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Matsuda T, Marugame T, Kamo K, Katanoda K, Ajiki W, Sobue T. Cancer incidence and incidence rates in Japan in 2005: based on data
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Shimizu H, Ross RK, Bernstein L, Yatani R, Henderson BE, Mack TM. Cancers of the prostate and breast among Japanese and white
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Tsugane S, de Souza JM, Costa ML Jr et al. Cancer incidence rates among Japanese immigrants in the city of Sao Paulo, Brazil, 1969–78.
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Iwasaki M, Mameri CP, Hamada GS, Tsugane S. Secular trends in cancer mortality among Japanese immigrants in the state of Sao
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