The document discusses the role of reactive oxygen species (ROS) in breast cancer. It presents several studies that found: 1) Higher levels of oxidative stress markers like 8-OHdG and HNE in breast cancer tissues, indicating ROS contribute to breast cancer development. 2) ROS levels are increased in breast cancer cells with mitochondrial dysfunction, promoting cancer cell motility and invasive behaviors. 3) Antioxidants from foods or supplements may help reduce breast cancer risk by lowering oxidative stress. However, more research is still needed to better understand the complex role of ROS in breast cancer.

1. Role of in Breast cancerROS
By
Vamsy Krishna D
MSc Molecular Microbiology
University of Hyderabad |
Hyderabad | India |

2. •Investigated the presence of oxidative stress markers (8-OHdG and
HNE) in breast carcinoma in females, and to examine the growth
modulatory effects of HNE (induce cell growth inhibition) by measuring
the expression of Ki-67 protein (cell proliferation antigen).
•Furthermore, to record if there is any significant prognostic indicator of
these markers
•estrogen mediated oxidative DNA damage in mammary glandular
epithelium has been suggested in progression of breast neoplasia

3. •Reactive oxygen metabolites (ROMs), including superoxide anion (O−2 ),
hydrogen peroxide (H2O2) and hydroxyl radical (OH), play an important role in
carcinogenesis
•the present study to determine the rate of O−2 and H2O2 production, and
concentration of malondialdehyde (MDA), as an index of lipid peroxidation,
along with the SOD, GPx and CAT activities in 54 breast cancer (BC) patients

4. •The show that perturbation of the mitochondrial respiratory chain in breast
cancer cells leads to a generation of subclones of cells with increased ROS,
active proliferation, high cellular motility, and invasive behaviors in vitro and
in vivo
•Their data suggest that mitochondrial dysfunction and ROS stress promote
cancer cell motility through a novel pathway mediated by CXCL14
•Breast cancer metastasis represents a major challenge in clinical treatment
of this disease, and the detailed mechanisms that regulate breast cancer cell
motility and metastasis remain to be an important research area

5. •They hypothesis that viruses such as MMTV could be transmitted to
newborn human infants, remains to be tested. In their view, this hypothesis is
biologically feasible.
•It’s possible for the transmission of human milk borne
viruses.
•This is contrary to the widespread assumption that human milk borne viruses
cannot be associated with breast cancer.

9. Breast Anatomy

10. Female Breast Anatomy
 Breasts consist mainly of
fatty tissue interspersed
with connective tissue
 There are also less
conspicuous parts
 lobes
 ducts
 lymph nodes

11. Breast Gland
 Each breast has 15 to 20
sections (lobes) arranged like
the petals of daisy
 Inside each lobe are many
smaller structures called lobules
•At the end of each lobule are tiny
sacs (bulbs) that can produce milk

12. Ducts
 Lobes, Lobules and bulbs, are
linked by a network of thin
tubes (ducts)
 Ducts carry milk from bulbs
toward dark area of skin in the
center of the breast (areola)
Ducts join together into larger ducts ending at the nipple,
where milk is delivered
Duct
Areola

13. Lymphatic System
 Lymph ducts: Drain fluid that
carries white blood cells (that
fight disease) from the breast
tissues into lymph nodes under
the armpit and behind the
breastbone
 Lymph nodes: Filter harmful
bacteria and play a key role in
fighting off infection
A network of vessels
Lymph ductLymph node

14. Three Types of Vessels
Bacteria
Nourishment
Blood
Vessels
Cell life
2
Waste products
Lymph
Nodes
Lymph
Vessels
3
MilkLobules Ducts Nipple
1

15. Causes
Inherited
Risk Factors
Environmental Factors

16. Inherited Genes
BRCA1 (Breast Cancer 1)
BRCA2 (Breast Cancer 2)
TP53 gene
ATM gene

17. BRCA 1 and BRCA 2
Both of these genes code for DNA repair.
If a woman has a mutation on either one of these genes, the
risk of her getting breast cancer increases from 10% to 80%
in her lifetime.
Mutations in BRCA1 or BRCA2 account for 40-50% of all
cases of inherited breast cancer.
These genes are also associated with ovarian cancer in
women and prostate cancer in men.
These genes can be inherited either from the mother or the
father.

18. Other Inherited Genes that cause
Cancer
TP53 gene
This gene codes for the
tumor suppressor protein
p53.
Mutations of this gene cause
Li-Fraumeni syndrome,
which is a condition that is
associated with early onset
breast cancer.
ATM gene
Females with one
defective copy of the
ATM gene and one
normal copy of the gene
are at increased risk for
breast cancer.

19. Risk Factors that cause Breast Cancer
Factors that Cannot be
Prevented
Gender
Aging
Genetic Risk Factors
(inherited)
Family History
Personal History
Race
Menstrual Cycle
Estrogen
Lifestyle Risks
Oral Contraceptive Use
Not Having Children
Hormone Replacement
Therapy
Not Breast Feeding
Alcohol Use
Obesity
High Fat Diets
Physical Inactivity
Smoking

20. Environmental Factors
Exposure to Estrogen
Radiation
Electromagnetic Fields
Xenoestrogens
Exposure to Chemicals
This is a Breast Cancer
Cell
http://www.cellsalive.com/stock4.htm

21. Normal Breast
Breast profile
A ducts
B lobules
C dilated section of duct to hold milk
D nipple
E fat
F pectoralis major muscle
G chest wall/rib cage
Enlargement
A normal duct cells
B basement membrane (duct wall)
C lumen (center of duct)
Illustration © Mary K. Bryson

22. Ductal Carcinoma in situ (DCIS)
Illustration © Mary K. Bryson
Ductal
cancer
cells
Normal
ductal
cell

23. Invasive Ductal Carcinoma (IDC –
80% of breast cancer)
 The cancer has spread to the
surrounding tissues
 Carcinoma refers to any cancer that
begins in the skin or other tissues that
cover internal organs
Illustration © Mary K. Bryson
Ductal cancer cells
breaking through
the wall

24. Range of Ductal Carcinoma in situ
Illustration©MaryK.Bryson

25. Invasive Lobular Carcinoma (ILC)
Illustration © Mary K. Bryson
Lobular cancer
cells breaking
through the
wall

26. Cancer Can also Invade Lymph or Blood
Vessels
Illustration © Mary K. Bryson
Cancer cells
invade
lymph duct
Cancer cells
invade
blood vessel

27. Signs and Symptoms
Most common:
lump or
thickening in
breast. Often
painless
Change in color
or appearance
of areola
Redness or pitting
of skin over the
breast, like the
skin of an orange
Discharge
or
bleeding
Change in size
or contours of
breast

28. Stage 0 Breast Cancer
 Known as “cancer in situ,” meaning the
cancer has not spread past the ducts or
lobules of the breast (the natural boundaries)
 Also called noninvasive cancer
 Ductal carcinoma in situ (DCIS) is the most
common in situ breast cancer

29. Stage I Breast Cancer
 The tumor is small
and has not spread to
the lymph nodes

30. Stage IIa Breast Cancer
 Stage IIa breast cancer
describes a smaller tumor that
has spread to the axillary
lymph nodes (lymph nodes
under the arm), or a medium-
sized tumor that has not
spread to the axillary lymph
nodes
 Stage IIa may also describe
cancer in the axillary lymph
nodes with no evidence of a
tumor in the breast

31. Stage IIIa Breast Cancer
 Stage IIIa breast cancer
describes any size tumor
that has spread to the
lymph nodes

32. Stage IIIb Breast Cancer
 Stage IIIb breast cancer
has spread to the chest
wall, or caused swelling
or ulceration of the
breast, or is diagnosed as
inflammatory breast
cancer

33. Stage IIIc Breast Cancer
 Stage IIIc breast cancer
has spread to distant
lymph nodes but has not
spread to distant parts of
the body

34. Stage IV Breast Cancer
 Stage IV (metastatic)
breast cancer can be any
size and has spread to
distant sites in the body,
usually the bones, lungs
or liver, or chest wall

36. Prevention and Screening
 80 – 90% of all changes are discovered by
women themselves even though only 20%
examine themselves
 The examination should be done on a
monthly basis 5-7 days after menorrhoea
 In case of a palpated anomaly women should
consult their physician for a more detailed
examination

37. Mammography
 Is an x-ray examination with a special apparatus
 The breast is comprimed between two plates of
plexiglass to keep the breast in position (might
result in pain )
 The applied x-rays are rather soft (26-30 keV) to
increase the contrast  small neoplasmatic
tissue formations can be seen

38. Sonography
 Ultrasound-based technique done after
palpation of an anomaly to rule out possible
cysts and to estimate the size of the tumor
 Only in addition to mammography as neither
microcalcium nor tumors smaller than 5mm
can be detected

39. MRI
 An important imaging technique to find out if
the breast has been affected by more than
one tumor
 Multifocality: more than one tumor in the
same quadrant
 Multicentrality: other tumors in other
quadrants

40. What Mammograms Show
Two of the most important mammographic
indicators of breast cancers
 Masses
 Micro calcifications: Tiny flecks of calcium – like grains
of salt – in the soft tissue of the breast that can sometimes
indicate an early cancer.

41. Mammogram – Difficult Case
 Heterogeneously dense breast
 Cancer can be difficult to detect
with this type of breast tissue
 The fibroglandular tissue (white
areas) may hide the tumor
 The breasts of younger women
contain more glands and ligaments
resulting in dense breast tissue

42. Punching Biopsy
 A needle is shot at
high velocity into the
neoplasmatic tissue
 Done in locally
sedated state
 (At least 3 samples
are taken to avoid
mistakes

43. Needle Biopsy
 With a syringe and a special needle tissues
are drawn from a palpable tissue formation
 As painful as venipuncture
 In case of a malign tumor the result is sure
wheras it is only 90% sure for a benign tumor

44. Advanced Breast Biopsy
Instrumentation (ABBI)
 Biopsy with relatively large
probe (6-20 mm)
 Done with x-ray to ensure
localisation of target
 Mostly used for analysis of
microcalcification
 Has only been in use for a
few years  many
unexperienced physicians

46. Chemotherapy

47. DRUG INTERACTIONS
Cyclophosphamide + Aprepitant
• Cyclophosphamide4
– Effective anti-tumor agent
– Prodrug bioactivation (via CYP3A4 to 4-OH-cyclophosphamide)
– Autoinducer
– High emetogenic potential
• Aprepitant (Emend)
– Effective for acute and delayed emesis
– Dosing 1hr prior to several days post-chemo
– CYP3A4 substrate, inhibitor (moderate)
4
de Jonge et al. Clinical Pharmacokinetics. 2005(44)11; 1135-1164

48. DRUG INTERACTIONS
Chemotherapy + Digoxin
• Chemotherapy
– Inhibits growth of rapidly dividing cells
– Affects epithelial cells, hair follicle cells
– Alter GI mucosa lining  alter absorption
• Digoxin
– Effective use in heart failure, arrhythmias
– Strengthens heart contractions
– Therapeutic serum levels 0.8- to 2ng/ml

49. DRUG INTERACTIONS
Tamoxifen + Warfarin
• Tamoxifen
– Selective estrogen receptor modulator (SERM)
– Effect for breast cancer prevention & treatment
– Metabolized primarily by CYP 2D6, 3A4
• Warfarin
– Oral anticoagulant
– Effective for stroke, DVT/PE prophylaxis
– Narrow therapeutic window (usual INR 2-3)
– Metabolized primarily by CYP 2C9, 3A4
Cozza et al. Drug Interaction Principles. 2003 ed

50. Alternative medicine
 Also Astragalus acts as an anti-viral and enhances the natural killer cells
 Cur cumin turmeric (is an anti tumor) increases you leukocyte production
 And Caud’ Arco is a mild herb that acts as an anti tumor
Therapeutic massage, acupuncture, and stress relieving techniques are also
used.
Treat the whole person not just the illness

51. Alternative medicines
 Perhaps the most amazing of them all is the 5 mushrooms also known as
the :
 “5 precious mushrooms”
 Coroxlus versicolor also known as cloud fungus
 Ganoderma lucidum also known as reishi
 Grifolia frondosus also known as maitke
 Lentinus edodes also known as shiitake
 Poria cocos also known as poria
 These are classified as anti tumors, anti cancer, and anti growth naturalistic
medicines.

52. Alternative medicines
 There is also currently a Chinese herbal remedy on the market, called
“canelim capsules”
 They contain radix curcume, herba agrimonia, and fructus aurantil
 It works by inhancing the immune system
 It reduces the tumor
 Quickly releases the side effects of radiotherapy and chemotherapy
 It can prolong a patients life and enhanse their quality of life
 Enhances blood circulation to reduce pain
 Helps to strengthen the body

53. " There is no chance for the welfare of the world
unless the condition of women is improved."
- Swami Vivekananda
“Prevention is Better than Cure”

54. ThankQ All