Breast cancer & biomarkers, their types, novelty of breast cancer biomarkers. Detailed study of her2, p53, BRCA1, BRCA2, DPD, 21-Gene signature, 70-Gene signature, cd106, vcam1, nlr, bFGF, mammaglobin, ER, PR, CEA. Pthological samples for biomarkers test, Ranges of various biomarkers, breast cancer diagnosis, prognosis, occurance, selection of breast caner treatment like targeted therapy.

1. Cancer Research
BREAST CANCER
BIOMARKERS

2. BREAST CANCER
BIOMARKERS
Mr. Shaktiprasad Pradhan
M.Pharm, Ph.D*
Research Professional, UDPS
shakti.pharma16@gmail.com
Utkal University, Bhubaneswar
Odisha, India

3. .
INTRODUCTION
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4. Breast Cancer
Cancer is the most dreaded disease of the current time &
caused by abnormalities in the genetic material of the
cells due to the effects of carcinogens, such as tobacco
smoking & chewing, radiation, chemicals or infectious
agents etc.
Cancer is usually classified according to the tissue from
which the cancerous cells originate that is location as well
as the normal cell type they most resemble which is
histology.
Breast cancer is the cancer that starts in the cells of the
breast & the most common cause of cancer among
women worldwide, both in incidence and death.
(Cont.)
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5. Breast cancer causes change in the size or shape of the
breast, a lump or thickening in the breast or armpit,
discharge from the nipple, change in the colour or texture
of the skin of the breast or areola such as scaly, dimpled,
puckered or wrinkled.
Simple Breast Cancer
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6. .
Breast cancer is the second most common type of
cancer and the fifth most common cause of cancer
death globally apart from sexes.
In India Breast cancer, is the most extensive cancer
category contributing about 18% of all cancers & 27% of
all women malignancies worldwide according to the
World Health Organization (WHO).
Breast cancer is increasing particularly in developing
countries where the majority of cases are diagnosed in
late stages.
However, breast cancer is the most detectable & most
treatable kind of cancer among all human malignancies.
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7. .
BIOMARKERS
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8. Biomarkers
Biomarkers are molecules that indicate normal or
abnormal process taking place in our body linked to a
disease or particular health condition like multiple
sclerosis, cancer, heart disease etc.
Biomarkers are also known as serum marker, molecular
marker, signature molecule etc.
Various types of molecules such as DNA (genes), proteins
or hormones, can serve as biomarkers since they are
used to monitor how well the body responds to a
treatment for a disease or certain condition.
Antibodies are very common example of biomarker,
developed by the body to help in fighting against diseases
or infectious conditions. (Cont.)
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9. .
However biomarker is often used to cover any molecular,
biochemical, physiological or anatomical property that can
be quantified or measured.
Biomarkers are used in diagnosis, prognosis & treatment
predictions, developing drug targets, monitoring
treatment response, risk assessment, recurrence etc.
Particularly in cancer research & medicine biomarkers are
used in three primary ways as:
• Diagnostic: To help diagnose conditions, as in the case of
identifying early stage cancers.
• Prognostic: To forecast how aggressive a condition is, as in
the case of determining a patient's ability to fare in the
absence of treatment.
• Predictive: To predict how well a patient will respond to
treatment. 9

10. .
BREAST CANCER
BIOMARKERS
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11. Breast Cancer Biomarkers
The breast cancer biomarkers are produced by the breast
cancer cells and/ or by other cells in the body in response
to breast cancer, but at higher amounts by the breast
cancer cells.
Test for breast cancer biomarker is needed if one is
currently being treated for breast cancer or has finished
breast cancer treatment or has a high risk of getting breast
cancer because of family history or other reasons.
These biomarkers can be found in the blood, stool, urine,
tumor tissue, or other tissues or bodily fluids & they affect
how the breast cancer cells grow, multiply, die and
respond to other compounds in the body.
(Cont.)
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12. .
The breast cancer biomarkers have traditionally been
proteins or other substances including gene mutations
(changes), gene rearrangements, extra copies of genes,
missing genes etc.
The breast cancer biomarkers are used to:
• diagnose, stage, and/or classify type of breast cancer
• estimate prognosis (likely outcome or course of
disease)
• select an appropriate treatment (treatment with
a targeted therapy)
So breast cancer biomarkers should be measured
periodically in patients for better management &
treatment.
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13. .
TYPES OF
BREAST CANCER
BIOMARKERS
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14. Types of Breast Cancer Biomarkers
Cancer biomarkers are of two main types as circulating tumor
markers and tumor tissue markers having different uses.
Circulating tumor markers are found in the blood, urine, stool,
or other bodily fluids of some patients with cancer.
Tumor tissue markers are found in the actual tumors
themselves, typically in a sample of the tumor that is removed
during a biopsy.
But there are a number of breast cancer biomarkers available
and they each work differently within the body and react
differently to different types of treatments.
• Serum markers: CA 15-3, CA 27/29, CEA
• Oncoproteins: Her2
• Tumor suppressor: TP53 or p53
• Hormone receptors: ER, PR
• Gene mutations: BRCA1, BRCA2, DPD, 21-Gene signature, 70-Gene
signature
• Potential proteins (Highly expressed): Mammaglobin
• Other nonspecific: E-selectin or CD62E or ELAM1, VCAM-1 or CD106,
Cytokeratin, NLR, bFGF, IGF-R (Cont.) 14

15. .Cancer antigen 15-3 (CA 15-3) is used to monitor
response to breast cancer treatment and disease
recurrence.
 Blood is analyzed & the reference range of serum CA 15-3
is <30 U/mL.
Cancer antigen 27/29 (CA 27/29) is used to predict early
recurrence of disease in women with treated carcinoma of
the breast also to detect metastasis.
 Blood is analysed & the reference range of serum CA
27/29 is <38 U/mL.
Carcino-embryonic antigen (CEA) is used to determine
stages, prognosis, monitor treatment & recurrence of B C.
 Blood sample is analyzed and the normal range is <2.5
ng/ml in non-smoker adult and <5.0 ng/ml in a smoker.
(Cont.) 15

16. .
Human epidermal growth factor receptor 2 (HER2) helps
to guide treatment and predict the course of the disease
(prognosis), sometimes to monitor treatment and for breast
cancer recurrence.
 Sample of tumor tissue is obtained by fine needle aspiration
(FNAC), needle biopsy or surgical biopsy (a tumor removed
surgically).
 The IHC test gives a score of 0 to 3+ that measures the amount
of HER2 receptor protein on the surface of cells in a breast
cancer tissue sample.
 If the score is 0 to 1+, it’s called HER2 negative, if the score is
2+, it's called borderline, & a score of 3+, is called HER2
positive.
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17. .Tumor protein 53 (TP53 or p53) mutation analysis is used to
detect and type mutations in the DNA-binding domain of the
TP53 tumor suppressor gene for diagnosis of Li-Fraumeni
syndrome and for prognosis (generally poor prognosis) and
therapy selection.
 Mutations are more frequent in advanced stage or in cancer
subtypes with aggressive behaviour. 10-30 mL peripheral blood
is used for test sample.
Hormone receptor (Estrogen receptor & progesterone
receptor) is used to determine an invasive breast cancer is
positive for estrogen and progesterone receptors, helping to
guide treatment.
 Sample of breast cancer cells or tissue obtained by a fine
needle aspiration, needle biopsy or surgical biopsy or when
a tumor is removed surgically during a lumpectomy or
mastectomy.
 Typical approximate response rates of ER & PR include ER-
positive, PR-positive: 75-80%, ER-positive, PR-negative: 40-
50%, ER-negative, PR-positive: 25-30%. (Cont.)
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18. .
Breast cancer susceptible genes 1 & 2 (BRCA1 & BRCA2)
detect mutations in these genes, that are linked mainly with
hereditary breast cancer also to determine whether
treatment with a particular type of targeted therapy is
appropriate or not.
 Blood sample is drawn from an arm vein or from an oral rinse
that collects cells from mouth.
Dihydro pyrimidine dehydrogenase (DPD) mutation is found
in the gene of patients with severe 5-FU-associated toxicity, in
which the body cannot break down the nucleotides thymine
and uracil. Blood is used as test sample.
21-Gene signature & 70-Gene signature are used to evaluate
risk of distant recurrence and to help plan treatment.
 Cells or tissue obtained from breast tumors are used as test
samples. (Cont.) 18

19. .
Mammaglobin expresses stages of breast cancer, tumor size
etc.
 Circulating mammaglobin protein is almost exclusively
expressed in breast epithelial cells and also over expressed in
primary & metastatic breast cancer tissues.
 RT-PCR & ELISA tests are used for the mammaglobin detection
in blood samples.
E-selectin or cluster of differentiation 62E (CD62E) or
endothelial leukocyte adhesion molecule-1 (ELAM-1) elevated
expression is associated with metastasis breast cancer & poor
survival in breast cancer patients.
 It is also related with the management of post-operative
patients to monitor the occurrence of metastases B.C.
 Blood sample is used to detect E-selectin, typically performed
by conventional ELISA. (Cont.)
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20. .
Vascular cell adhesion molecule 1 (VCAM-1) or cluster of
differentiation 106 (CD106) is found in early breast cancer
tumors.
 The increased plasma level is associated to lymph node-
positive and high-grade breast tumors with circulating
cancer cells.
 Immunohistochemical studies demonstrate that VCAM-1
and E-selectin are found on the membranes of malignant
breast endothelial cells & are not found on breast epithelial
cells. Blood sample is used for detection.
Cytokeratin immunoexpression of Cytokeratin 5/6 and
Cytokeratin 8/18 are basal and luminal markers of breast
cancer having prognostic significance in breast cancer.
 Blood sample is used for the detection. (Cont.) 20

21. .
Neutrophil to lymphocyte ratio (NLR), basic fibroblast
growth factor (bFGF) & Insulin-like growth factor (IGF-
R) biomarkers can be identified through diagnostic
blood tests & by getting regularly tested, breast cancer
can be discovered at an early stage.
NLR is involved in inflammatory response which is
shown to be higher in presence of breast tumors.
bFGF helps malignant cells reproduce at faster rates, so
anti-bFGF antibodies can be used to help treating breast
tumors from origins.
IGF-R elevated level is found in breast cancer as it
inhibits apoptosis & programmed cell death.
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22. .
NOVELTY OF
BREAST CANCER
BIOMARKERS
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23. Novelty of Breast Cancer Biomarkers
Biomarkers of breast cancer affect the planning of
treatment, if tumor marker levels go down, then it usually
means that the treatment is working.
They help in finding out if a cancer has spread to other
tissues & screen people at high risk including family
history for breast cancer.
They are used to check if the breast cancer has come back
(recurrence) after successful treatment.
Circulating breast cancer biomarkers are important as
they are used to:
Estimate prognosis.
Detect cancer that remains after treatment (residual
disease) or that has returned after treatment (recurrence).
Assess the response to treatment.
Monitor whether a cancer has become resistant to
treatment. (Cont.)
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24. .
Breast cancer tumor tissue markers are significant having
utilization in:
Breast cancer diagnostics
Detecting stage and type of breast cancer
Estimating prognosis (outcome of disease),
Selection of suitable treatment for breast cancer like
targeted therapy.
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25. .
REFERENCES
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26. References
 World Health Organization, International Agency for Research on
Cancer, 2020.
 American Cancer Society: Breast cancer overview. 2020.
 Pradhan, Tripathi, Pradhan, Nature an Immunobooster for Breast
Cancer, Book. Partridge India Publication, 2015.
 www.nationalbreastcancer.org/about-breast-cancer/
 www.cancer.net/cancer-types/breast-cancer/introduction.
 Pradhan D., et al., Inhibition of proteasome activity by the dietary
flavonoid Quercetin associated with growth inhibition in cultured
breast cancer cells and xenografts. JYP.2015, 7(3): 225-233.
 Pradhan S., et al., Antiproliferation activity of Ocimum gratissimum
aqueous extract on human breast cancer MCF-7 cell line. WJPR,
2018, 7(9): 421-428.
 Zaha D., Significance of immunohistochemistry in breast cancer.
World J Clin Oncol 2014 August, 5(3): 382-392. 26

27. .
Thank You
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