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TYPE
Original Research
PAGE NO.
52-64
10.37547/tajmspr/Volume07Issue02-08
OPEN ACCESS
SUBMITED
16 December 2024
ACCEPTED
18 January 2025
PUBLISHED
20 February 2025
VOLUME
Vol.07 Issue02 2025
CITATION
Muhammad Nouman, Hafiz Fazal Mahmood, Bashir Ahmad, Faiza Shams,
Saad Ahmad khan, Mian Waqar Ahmad, Hassan Zeb, Malaika Ahmed, &
Abdul Qadeer khan. (2025). Breast cancer in Pakistan: evaluating the
health crisis and the path forward for women’s wellbeing.
The American
Journal of Medical Sciences and Pharmaceutical Research, 7(02), 52
–
64.
https://doi.org/10.37547/tajmspr/Volume07Issue02-08
COPYRIGHT
© 2025 Original content from this work may be used under the terms
of the creative commons attributes 4.0 License.
Breast cancer in Pakistan:
evaluating the health crisis
and the path forward for
women's wellbeing
Muhammad Nouman
M.Phil Health Biotechnology, Department of Biotechnology, Faculty of
Chemical and Life Sciences Abdul Wali Khan University Mardan, Pakistan
Hafiz Fazal Mahmood
MPhil Medical laboratory Science, Khyber Medical university Peshawar,
Pakistan
Bashir Ahmad
M. Phil Biochemistry, Abdul Wali Khan University Mardan, Pakistan
Faiza Shams
M.Phil Biotechnology, Abdul Wali Khan University Mardan, Pakistan
Saad Ahmad khan
BS Biotechnology and Genetic Engineering, Hazara University Mansehra,
Pakistan
Mian Waqar Ahmad
M. Phil Biotechnology and Genetic Engineering, Hazara University
Mansehra, Pakistan
Hassan Zeb
M.Phil Medical Lab sciences (MLS), Iqra National University Peshawar,
Pakistan
Malaika Ahmed
M.Phil Biotechnology and Genetic Engineering, The University of
Agriculture Peshawar, Pakistan
Abdul Qadeer khan
Department of Allied Health Science, Iqra National University Peshawar,
Pakistan
Corresponding Author
: Abdul Qadeer khan
Abstract:
Breast cancer (BC) is the most prevalent
malignancy among women globally. Historically
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regarded as a disease affecting older, middle-aged
women, recent years have seen a growing incidence of
BC among younger females, a trend also observed in
studies conducted in Pakistan. This paper reviews the
mutant functions of tumor suppressor genes (BRCA1,
BRCA2, p53, ATM, and PTEN), epigenetic alterations,
and the role of estrogen receptors in breast cancer
development. Additionally, we examine the current BC
scenario in Pakistan, highlighting a notably higher
incidence among younger women. Data from SKMCH
and RC indicate that women aged 45-49 years exhibit
the highest incidence rate of 45.42%. Limited studies
have reported a high expression of ER, PR, and HER-
2/neu in Pakistani women. Furthermore, the presence
of the BRCA1 (c.1961dupA) mutation in Pakistan aligns
with global findings. However, no comprehensive
studies have been conducted to investigate epigenetic
transformations in breast tumors within the Pakistani
population. This critical area of research warrants
further exploration to provide a more complete
understanding of BC in Pakistan.
Keywords:
Breast Cancer, p53, BRCA1, BRCA2,
Epigenetic Transformation, Estrogen Receptor.
Introduction:
Breast Anatomy and Function
Breast development starts at puberty and is completed
during pregnancy. [1] The internal structure of the
breasts is unique in that it contains mammary glands for
the subsequent nourishment and immunity for a
newborn during lactation. [2] The mammary glands
continue to develop throughout the different ages of a
woman's life. The end buds of the primitive ductal
system in an infant's breast gradually evolve into a
branched ductal system with a concurrent decrease in
fatty tissue during puberty. Further development will
remain in a dormant state until pregnancy hormones
stimulate it.
The fundamental ductal system develops through the
differentiation of two cell types: luminal epithelial cells
and myoepithelial cells. These cells are the so-called
milk-producing structures. microcavities surrounded by
cells myoepithelial epithelium, luminal arteries
surround the breast milk sac with antibodies, nutrients,
and certain toxins. Alveoli bundle together to form
lobules, which connect to the nipple through the milk
ducts.
Milk ejection is initiated by the nipple stimulation that
triggers a nerve impulse that activates the release of
oxytocin through the hypothalamus and posterior
pituitary gland. Under the influence of oxytocin, the
myoepithelial cells contract and create intraductal
pressure to facilitate milk ejection. [2]
Figure 1
. Schematic representation of the human
female breast and the many kinds of interacting cells
found inside the breast tissue. The breast tissue
overlaps the ribs and chest muscles. The mature
woman’s breast includes glandular epithelium (~10–
15%) and this milk producing epithelia is housed inside
the surrounding adipose tissue. Multiple lobules
(terminal ductules, acini, milk producing lobules)
collectively make up the lobes of the breast. The
functional units of the breast are the terminal duct
lobular units. All lobules and lobes are linked to the
nipple by a branching system of ducts. Terminal ductal
lobular units (TDLUs), which is a cluster of ductules,
intralobular duct, loose intralobular connective tissue,
and extralobular terminal duct, are frequent sites of
genesis for numerous. Within the stroma, two kinds of
fibroblasts are found. Loosely linked intralobular
fibroblasts surround the epithelial cells and they are
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eventually surrounded by the more condensed
interlobular fibroblasts. The second key biological
component of the mammary stroma is adipocytes (i.e.,
fat cells). The parenchymal tissue comprises of
epithelial and myoepithelial cells. In addition, the
stromal compartment comprises vascular endothelial
cells and invading immune cells. Stromal cells release
components of the extracellular matrix (e.g., collagens,
hyaluronic acid, tenascins, fibronectins, proteoglycans)
that are vital for the breast’s three
-dimensional
architecture. Mammary ducts consist of polarized
apically directed columnar luminal epithelial cells that
line (within) ducts together with alveolar structures at
the ends, as well as contractile myoepithelial cells that
are orientated basally. This is contained by the
basement membrane (BM), which provides a physical
barrier that divides the epithelial and stromal
compartments. BM (i.e., basal lamina) largely consists
of laminin, collagen, entactin, and proteoglycans.
Myoepithelial cells that exhibit contractile qualities
and stem cells (i.e., mammary repopulating units)
compose the functionally different basal layer.
Constituents of milk are generated by secretory cells
that create the alveoli, followed by secretion into the
alveolar lumen.
Structure of the Breast
The breast is composed of adipose and glandular
tissues supported structurally by Cooper ligaments.
The glandular tissue is associated with 15
–
20 lobes
consisting of 10
–
100 alveoli (0.12 nm in diameter).
Each alveolus opens into 15
–
25 ducts that then
coalesce to form a single principal duct, ultimately
forming lactiferous sinuses which lead to the nipple
surface. There is some disagreement over the average
number of ducts per nipple. [3].
Breast relies on the internal mammary artery's blood
supply and the posterior mammal branches of the
lateral thoracic arteries, as well as other branches like
the pectoral branch of this vein and then the
intercostal vascular branch. The regulation of veneous
drainage is both deep and superficial systems. Deep
veins, as they follow the mammary arteries, drain
blood towards internal thoracic, cephalic, and other
vessels. Sub-areolar veins drain into surrounding
vasculature from the nipple to the surface and
communicate superficial and deep venous plexuses.
[4]. The breast receives supply from the 2nd to 6th
intercostal nerves. The nerves follow variable
penetration and courses, in that the anterior nerves
take a superficial course to provide innervation to
subcutaneous tissue, whereas the lateral nerves make
deeper connections. The areola and nipples receive
supply from the lateral and anterior cutaneous
branches of the 3rd to 5th intercostal nerves [1,3].
Lymph drainage of the breast is carried out through two
main pathways: the axillary and the internal mammary
nodes. The axillary nodes drain the majority (75%) of the
lymph from both the medial and lateral portions of the
breast, while the internal mammary nodes drain lymph
primarily from the deeper portions [5].
Breast Cancer
Cancer is a disease in which there is abnormal and
excessive cell growth, resulting in the formation of a
mass or lump called a tumor. Cancer is named based on
the affected cells. BC (Breast Cancer), one of the most
frequently reported cancers in the world can be invasive
or non-invasive. It arises because of mutations in the
cells of the lobules and linking ducts, while the rest of
the breast is made up of fatty connective and lymphatic
tissues.[6] Ductal carcinoma in situ (DCIS), a form of BC
arising from mutations in the ductal cells, is reported to
be non-invasive but may become an invasive form if not
treated (Allred).
Classification Systems of Breast Cancer
Invasive breast cancer invades cellular boundaries,
spreading to the nearby normal tissue, and its prognosis
is primarily based on the diagnosis of the tumor as well
as the extent of metastasis. Two principal cancer staging
systems are widely used for the disease classification.
The TNM system considers tumor size (T), spread to the
nearby lymph nodes (N), and the presence or absence
of distant metastasis (M) (Edge and Compton). Based on
these parameters, BC is staged from 0 to IV, with stage
0 indicating in situ cancer, stage I being early invasive
cancer, and stage IV being the highest stage. The system
is largely utilized for clinical purposes. Meanwhile, the
Surveillance, Epidemiology, and End Results (SEER)
system is utilized for public health research, planning,
and cancer registry statistics. SEER stages disease
progression into three levels from local to regional to
distant categories that reflect TNM stage I and some
parts of stage II thereby restricting cancer growth within
the breast. The TNM classification for stages II and III
belongs to the regional stage because the cancer
spreads to regional lymph nodes or tissue. The distant
stage of cancer matches the TNM stage IIIc and IV
definitions which indicate that cancer has spread to
distant lymph nodes and organs. BC holds different
categories which stem from analysis of gene expression
profiles. [7] while specific biomarkers such as ER+/ER-
receptors alongside PR+/PR- receptors alongside
HER2+/HER2- receptors serve as diagnostic and
therapeutic indicators. [5]
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Figure 2
Molecular classification of BC subtypes. BC can be
divided into three main subtypes depending on the
histological expression of four markers (ERα, PR, HER2,
and Ki-67): hormone receptor (HR)-positive, HER2-
positive, and triple-negative. This figure was created
with Biorender.com.
Epigenetic Transformation
Breast cancer develops because deregulated genes
build up and stimulate both uncontrolled cell
proliferation along with growth. Epigenetics together
with gene mutation functions as a fundamental
contributor to the development of BC. Scientists
actively investigate cancer molecular mechanisms yet
they also try to establish biomarkers for BC
aggressiveness assessment along with studying
epigenetic therapeutic potential. Cancer development
together with prognostic outlooks depends heavily on
epigenetic changes. These include DNA methylation,
which modifies CpG dinucleotides covalently at the 5'
position of the cytosine rings, and histone
modifications, which are post-translational covalent
modifications that occur on the N-terminal tails of the
four core histones. Gene expression can also be
modified by certain non-coding RNA molecules that
degrade target RNAs or inhibit their translation. [8]
Genes that regulate important cellular mechanisms
such as the cell cycle, angiogenesis, apoptosis, tissue
invasion, hormone signaling, and metastasis, are
fundamental in the development of BC when their
expression is inactivated through hypermethylation.
[4,6] Hypermethylation of tumor suppressor genes like
BRCA1 and p16 and DNA repair genes like GSTP1 and
CHD1 has been reported in breast tumors, in which
these genes have been involved in metastasis and
invasion.[8]
The research showed that high-stage tumors presented
increased ADAM23 gene hypermethylation which
affects cell surface adhesion molecule transcription.[9]
DSC3, KIF1 and NDRG1 genes from BC tumors undergo
epigenetic silencing. The environmental risk factor
estrogen receptor expression showed a positive
correlation with hypermethylation of the tumor
suppressor gene RASSF1A promoter. Research
conducted on hereditary BC revealed identical results.
[10] RASSF1A methylation serves as a potential
biomarker to diagnose BC. In addition, post-
translational histone modifications are a significant
epigenetic change, and they play a crucial role in the
development, aggressiveness, and prognosis of BC.
Histone proteins influence the expression of various
genes in different BC tumor subtypes. [11]
Histone modifications in invasive breast cancers have
been shown to have significant lysine acetylation
(H3K9ac, H3K18ac, H4K12ac, and H4K16ac), arginine
methylation (H4R3me2), and lysine methylation
(H3K4me2 and H4K20me3). Positive correlation of
H4R3me2, H3K9ac, and H4K16ac levels with lower
lymph node stage and negative correlation with tumor
size were observed. High levels of histone modifications
were also significantly associated with steroid receptor-
positive tumors. [3,5,6] However, in Pakistan, no true
studies have been identified that predict epigenetic
changes in breast cancer tumors in the local population.
The terminal duct-lobular unit contains estrogen- and
progesterone-sensitive stem cells, which proliferate
during the menstrual cycle and pregnancy. These have
the potential to form lactational lobules. During the
prepubertal period, the terminal ductal-lobular stem
cells in mutation carriers (germline or somatic) are
dormant but remain vulnerable to malignancy. When
the DNA of these cells becomes damaged, it proliferates
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under the influence of puberty hormones. Mutations
in p53 or other genes involved in the regulation of the
replication process allow these cells to grow
uncontrollably and activate proto-oncogenes. [12]
The oncogene activation in BC cells induces mutations
in one or more of the tumor suppressor genes. These
genes play roles in maintaining genomic integrity by
preventing the passage of damaged DNA. Mutations in
various tumor suppressor genes result in the loss of the
cells' ability to sense and repair DNA damage. Under
normal circumstances, these genes recognize damage
to the DNA and halt the cell cycle until repair is done.
Tumor suppressor genes also induce apoptotic cell
death Mutations in the BRCA1 and BRCA2 genes are
linked to approximately 80-90% of the familial BC
cases. Inactivation of these tumor suppressor genes
results not only in the development of BC but also in
ovarian and prostate cancer. [13] BRCA1 is a very large
17q21 chromosome gene, spanning 100 kb, and
encodes a protein of 1863 amino acids. BRCA1
expression is especially high in the thymus, testis,
breast, and ovary. The gene products are involved in
DNA repair, transcriptional transactivation, apoptosis,
and cell cycle control. [13,14] There are two isoforms
of BRCA1, BRCA1a and BRCA1b, that are
phosphoproteins containing phosphoserine residues.
Both BRCA1a and BRCA1b are p53 gene coactivators,
and both were found to interact with p53 in vitro and
in vivo studies. [15]
The BRCA2 gene, which is much larger than BRCA1,
maps to chromosome 13q12-13, covers 10,254 base
pairs, has 26 coding exons, and encodes a 3,418 amino
acid protein. [8,12] Like BRCA1, BRCA2 proteins play
regulatory roles in transcription and DNA repair. The
BRCA2 mutations are moderately in the prostate and
mammary glands and highly in the thymus and testis,
indicating that they may be involved in differentiation
and development. [16] One of the best-known genes in
human cancer is the p53 tumor suppressor gene. It is
located on chromosome 17p13.1 and acts as a
transcription factor for regulating growth signals in
damaged cells. Mutations of the p53 gene are found in
approximately 20-40% of human breast cancers.
Individuals who have a germline mutation of the p53
gene (Li-Fraumeni syndrome) are at high risk of getting
breast cancer and other cancers as a result of the loss
of growth-suppressive gene function. [17] p53 also
shares extensive homology with p63 and p73, which
encode transactivation and DNA-binding proteins with
tetramerization domains identical to p53. Ataxia
Telangiectasia (AT) gene or ATM, which is involved in
DNA repair and cell-cycle checkpoints, can also be
involved in breast cancer formation. The mutation of
tumor suppressor gene PTEN results in improper PIP3
pathway activation that promotes uncontrolled cell
growth while inhibiting apoptosis. [18]
Genetic and Reproductive Factors
Genetic predisposition plays a crucial role in
determining BC risk among Pakistani females.
Mutations in the BRCA1 and BRCA2 genes are relatively
prevalent in this population, significantly increasing the
likelihood of hereditary breast and ovarian cancers.
Studies suggest that over one-third of early-onset BC
cases in Pakistan may be linked to these genetic
alterations.
Moreover,
reproductive
factors
substantially influence BC susceptibility. [19] Initial
onset of menstruation, delayed menopause, and
nulliparity have been associated with an elevated risk,
while higher parity and younger maternal age at first
childbirth have been correlated with a protective effect.
Furthermore, the use of combined oral contraceptives
has been associated to a minor increase in BC risk, which
diminishes after discontinuation. [16,17]
Lifestyle and Environmental Factors
Breast cancer risks heavily depend on lifestyle
preferences people make. The trio consisting of physical
inactivity and elevated BMI values and smoking habits
proves to be essential danger elements. A div mass
index higher than 25 kg/m² shows a positive correlation
with breast cancer development risk. Former and active
smokers show sensitive breast cancer risk. Scientists
have linked breast cancer susceptibility to both
excessive consumption of fats in diet and inadequate
consumption of fruits and vegetables. [18,20] The
assessment of risk factors becomes complex because of
exposure to environmental substances including
chemicals that disrupt endocrine function and radiation
elements. The limited research on environmental
carcinogens in Pakistan's population needs expansion
because it lacks data about their contribution to BC
frequency. [21]
Estrogen-Receptor Positive (ER+) Breast Cancer
Estrogen receptor (ER) is both a nuclear hormone
receptor and a transcribing transcription factor upon
activation by its ligand. Ligand binding induces receptor
conformational changes which allow the receptor to
dimerize into homodimers. The receptor binds to
special DNA sequences referred to as estrogen response
elements to activate transcription of target genes. The
functional regions of the ER include the N-terminally
positioned
hormone-independent
transactivation
domain (AF1) followed by the highly conserved central
DNA-binding domain (DBD) that specifically binds to ERE
DNA sequences and ends in the C-terminal LBD-
followed by the hormone-dependent transactivation
domain (AF2). A hinge domain divides the ligand-
binding domain from the DNA-binding domain. There is
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a hormone-binding pocket within the LBD and then
comes the ligand-activated second transactivation
domain (AF2) at the C-terminal end. [22]
Genes which control estrogen metabolism and
intracellular transport operate through enzymes or
receptors while mutations within these genes lead to
an increased breast cancer (BC) risk. Three critical
genes include 17β
-hydroxysteroid dehydrogenase 2
(EDH17B2) and cytochrome P450c17a (CYR17) and
estrogen receptor (ER). Through hormone-to-hormone
response elements (HREs) DNA targets ER manages
transcription by acting as a steroid receptor. Gene
expression results in upregulation or downregulation
following receptor-HRE binding which depends on the
active state of tissue-specific auxiliary factors that bind
to target genes. Polymorphisms of the ER and
inefficient binding of estrogen to its receptor may
affect gene transcription. Moreover, the AIB1 protein,
a nuclear receptor coactivator, may be involved in the
development of steroid-dependent cancers by binding
to the estrogen receptor in a ligand-dependent
manner and in the stimulation of estrogen-dependent
transcription. [23]
Epidemiology of Breast Cancer in Pakistan
Cancer is the leading cause of death in economically
developed countries and the second leading cause in
developing countries. [16] Breast cancer is the most
commonly diagnosed cancer globally, accounting for
23% (1.38 million) of all new cancer cases and 14%
(458,400) of cancer-related deaths in 2008. The burden
of cancer is rising in developing nations due to factors
such as population aging, growth, and the adoption of
cancer-related lifestyle habits, including smoking,
physical inactivity, and "westernized" diets. [24] BC is
most prevalent in middle-aged women (40
–
59 years).
[14] The typical incidence curve for BC shows a rapid
rise until the age of 40, after which the rate slows, but
continues to increase with age until around 50, after
which it begins to decline, especially in low-risk
populations. Pakistan reports the highest BC incidence
in Asia, excluding Israel, according to available data.
[25] BC stands as the most frequently occurring cancer
in females throughout Karachi where it represents
one-third of all female cancer cases. The incidence of
BC in Karachi represents the highest rates throughout
Asia. BC ranks as a leading threat region in Pakistan,
while it constitutes 40% of all female malignant
tumors. [23,26] Patients diagnosed with BC in Pakistan
usually develop the cancer after their 49th birthday but
Western societies show median detection around 54
years of age. Based on data from Shaukat Khanum
Memorial Cancer Hospital and Research Center
(SKMCH & RC) from December 29, 2014 to December
31, 2023 BC emerged as the main cancer type among
Pakistani females with a total occurrence rate of 45.42%
of cases. Most breast cancer cases documented for 2023
occurred within the 45
–
49-year age group. BC detected
in younger patients shows higher aggressive behavior
and inferior prognoses compared to BC diagnosed in
older women. [27] The frequency of BC diagnosis in
Pakistani women under 50 years old shows a continuous
upward trend. Rise in Karachi's mean age of cancer
diagnosis from 50.0 years old to 45.75 years old during
the last decade emerged. Study in Karachi
demonstrated that women received an average BC
diagnosis at age 44.07 years while representing the
ethnic groups of Sindhi 9%, immigrants 17%, Balochi 2%,
KPK 2%, Minorities 2%, and Punjabi 2%. [22,28]
The study at Lady Reading Hospital Peshawar
established that breast cancer (BC) predominantly
affected 30.4% of women in the 40-49 years age group.
[29] The disease spectrum of breast cancer in Pakistani
women consists of a wide variety of different breast
cancer types. Different regions of Pakistan show varied
distributions of BC subtypes according to Table 1. A
study documented the occurrence of invasive ductal
carcinoma (IDC) at 88.7% while invasive lobular
carcinoma (ILC) appeared at 5.4% and lymph node
metastasis rates amounted to 80.8% among women
aged 30 and above. The grading of tumors
predominantly showed grade II (57.1%) with grade III
(29.8%) while tumor dimensions were below 5 cm in
23.2% of cases, [27,30] identified IDC as the main cancer
type in 82.6% of patients whose average age reached
56.52 years. Research showed IDC occurred in 78% of
patients primarily affecting stages II and III tumor
grades. Data shows Infiltrating ductal carcinoma (IDCA)
represents the primary subtype of BC in Pakistan. [31]
Revealed a substantial increase in IDCA prevalence
compared to previous hospital data through their study
which found 81% of patients diagnosed with tumor
grading type II while their tumor sizes remained below
5 cm. A retrospective assessment of 3,279 BC specimens
at Aga Khan University Hospital found IDCA affected
37% of patients while fibroadenoma occurred in 16.95%
of cases and fibrocystic changes in 13.96% patients.
Mastitis affected 6.83% of patients and duct ectasia
occurred among 5.33% with diverse tumor sizes. [32]
A clinic study operating at the National Cancer Institute
in Karachi surveyed various breast cancer presentation
types during 2014-2020 using clinical-pathological
examination criteria. The study reported 91% invasive
ductal carcinoma (IDCA), 6% intraductal carcinoma, and
3% lobular carcinoma. Invasive intraductal carcinoma
was found in 94% of patients with a mean age of
41.9±10.9 years and tumor grades III and IV, [33] which
aligns with previous findings where the prevalence of
intraductal carcinoma was 90%. Ductal carcinoma in
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situ, commonly abbreviated as DCIS, refers to the
malignant proliferation of epithelial cells in the duct-
lobular system of the breast that cannot be detected
with a light microscope. In the developing world like
Pakistan, diagnosis of DCIS is very infrequently
reported in contrast to the developed world mainly
due to inadequate availability of the advance medical
setups to detect DCIS. [34] Two Karachi-based studies
documented DCIS rates of 1% and 1.2%, respectively.
In addition, a high prevalence of palpable masses
(92.1%) was also documented in Pakistani women. [34]
Germline mutations in the BRCA1 and BRCA2 genes are
established lifetime risk factors for developing BC. The
BRCA1 c.1961dupA mutation has been identified in
several families from different parts of the world. It
was identified in Oman, China, Western Europe, Latin
America, and the Caribbean. Very recently, this same
mutation in BRCA1 has also been reported among
Pakistani families, who have a history of a very high
consanguineous marriages. [35]
A study conducted in 2005 reported that 9.17% of
tumors in Pakistan were estrogen receptor positive
(ER+ve). The behavior of ER and progesterone receptor
(PR) positive tumors in the Pakistani female population
is similar to that observed in Western data. Sharif MA et
al. reported the expression of HER-2/neu, ER, and PR in
481 cases of invasive ductal carcinoma (IDCA) with a
mean age of 48 years and a tumor size of 4.4 cm. Their
findings showed high expressions of ER (72.3%), PR
(62.6%), and 31% HER-2/neu. They also found an inverse
association between ER and PR with HER-2/neu, while a
positive association was observed with lymph node
metastases (p < 0.05). A similar trend is observed in
India, which shares genetic similarities with Pakistan.
Breast cancer affects 100,000 Indians each year with
projections suggesting this number will reach 131,000
by 2020. [37] The incidence of breast cancer in Indian
women under 45 years shows a rising trend which
mirrors a similar pattern reported in Pakistan.
Table
Breast Cancer Awareness and Early Detection in
Pakistan
Breast cancer is still the most common cancer in
women in Pakistan, and it has a high burden in areas
such as Peshawar and Islamabad. Breast cancer is
responsible for about 38.8% of all female cancers in the
country, with 56,250 cases reported. In KP, which
comprises Peshawar, breast cancer is 31.1% of all
female cancers, with 1,000 cases in 2018. In Islamabad,
breast cancer is 45% of all female cancers, with 1,500
cases in 2018. The above statistics demonstrate the
high incidence of breast cancer in both KP and
Islamabad, emphasizing the need for increased
awareness and early detection in these areas. [36,38]
Awareness of breast cancer among Pakistani women is
very low. A survey of 9,766 women in 18 studies
revealed that 42.7% knew risk factors, 41.8% knew
symptoms, and 36.3% knew diagnostic modalities.
Furthermore, only 28.7% had ever done regular breast
self-examination (BSE), and 15.3% had ever had a
clinical breast exam (CBE). In Lahore, 80.2% of the
population was not aware of the prevalence of breast
cancer worldwide, and 65.3% thought that not everyone
is at risk. Only 42.1% were aware of symptoms, and
13.9% did self-examination. These results highlight the
need for specific educational interventions to enhance
knowledge and practices regarding breast cancer. [39]
The World Health Organization (WHO) stresses self-
examination to enable early detection of breast cancer.
In Pakistan, there are about 90,000 new cases every
year and 40,000 deaths resulting from delayed
detection. Survival can be highly improved with early
diagnosis, at 90% for early-stage invasive breast cancer.
Despite this, cultural beliefs, fear, and cost prevent a lot
of women from accessing timely medical care. [40]
To address these issues, a number of initiatives have
Breast Cancer Subtype
%
Area
Age Range
Infiltrating ductal carcinoma
82.60%
Peshawar
40-59
81%
Rawalpindi/Islamabad
36-60
45.41%
Lahore
>18
Mucinous carcinoma
2.17%
Peshawar
40-59
Infiltrating lobular carcinoma
6.50%
Peshawar
40-59
Papillary carcinoma
4.35%
Peshawar
40-59
Invasive lobular carcinoma
6.50%
Peshawar
40-59
Medullary carcinoma
2.17%
Peshawar
40-59
Benign lumps
30.91%
Rawalpindi/Islamabad
36-60
Luminal B (Grade 3)
60%
Lahore
>18
Luminal A (Grade 2)
37%
Lahore
>18
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been implemented. To encourage early detection, the
Women's Parliamentary Caucus and the WHO have
arranged awareness seminars. with an emphasis on
the local community, the Shaukat Khanum Memorial
Cancer Hospital and Research Centre is also carrying
out research to provide more effective methods of
cancer
detection
and
treatment.
[41,44]
Notwithstanding these initiatives, more thorough
public education and awareness campaigns about
breast cancer risk factors and the need of early
diagnosis are still required. Mortality may be
decreased and early detection rates greatly increased
by putting in place routine screening programs and
encouraging self-examination.
Causes of Breast Cancer
The spreading western lifestyle choices of smoking
alongside alcohol use and unbalanced diets are
thought to fuel the rising numbers of breast cancer
cases in developing countries like Pakistan.[42] Obesity
together with physical inactivity both increase BC risk
through elevated extra-glandular estrogen and its
metabolites along with hyperinsulinemia levels often
found in obese women. The combination of decreased
breastfeeding practices together with timing
irregularities of menstruation and childbirth age
throughout Pakistan and Bangladesh and India shows
a connection to rising breast cancer incidence. The use
of assisted reproductive technology (ART) produces
hormonal exposure and delayed childbearing and
serves as risk factors for BC development. Clinical
evidence shows that assisted reproductive technology
through VEGF upregulation stimulates tumor
angiogenesis. [43,45]
Risk Factors for Breast Cancer in Pakistani Women
Multiplicity of risk factors are assumed to be related in
getting BC in Pakistan [46]; Fig. 3. Breasts were related
with personal modesty, humiliation and timidity
among women in Lahore, where breasts were needed
to be veiled at all times [47, 56, 58]. This reinforced the
stigma linked to publicly discussing breast issues
among women, mothers and daughters, husbands,
and extended family members. BC may be seen as
socially undesirable illness as a consequence of this
[48]. It is also suggested that women are hesitant to do
breast self-examination, either owing to lack of
understanding and/or cultural concerns [49, 64]. As a
consequence, fundamental social prejudice against the
condition, based on shared beliefs has emerged. This
technique has the potential to permeate society and
dramatically alter breast wellness behavior, especially
self-examination practice [50]. Social bias and
misconceptions about screening criteria, family
history, and sentiments of vulnerability are all
impediments to breast health practices and self-
examination, may also occur [54].
Worryingly, research reveal that women in Pakistan only
seek medical care when their cancer has advanced to a
critical level owing to an inability to recognize at an early
stage [55, 67, 85]. According to several research, cancer
victims are urged to study spirituality in order to
properly manage the physical and psychological
symptoms [14, 62]. Although not reporting BC has the
potential to be catastrophic, it may signify the societal
stigmatization connected with a BC diagnosis [14].
Emotional, bodily anguish, psychological, social, and
spiritual sorts of suffering are all encountered by
women [75].
The average age at which white American women
acquire BC is 61 years, whereas the average age at which
Pakistani women suffer the illness has been shown to be
51.4 years [68]. In compared to other parts of the globe,
notably Western countries, it is roughly a decade
sooner. Thus, it is vital to delve more into the reasons of
this early age occurrence among Pakistani women.
Apart from age, additional risk variables include tobacco
use, physical inactivity, obesity and div mass index,
and menopausal status [70]. Furthermore, reproductive
characteristics such as parity and breastfeeding have
previously been demonstrated to give protection
against BC [56]. Encouraging results from a recent
investigation found that the life expectancy for both
sexes improved in Pakistan, yet these increases differed
throughout the provinces and federal territories.
Between 2014 and 2023, the life expectancy of women
grew by 82%, while that of males climbed by 76% [42].
The leading risk factors for mortality and disability-
adjusted life years at the national level in 2019 were
smoking, air pollution, high systolic blood pressure,
dietary risks, and malnutrition, which might be
contributing factors to cancer as well [47].
In terms of lifestyle and diet, new evidence suggested
that vitamin D deficiency may have a role in BC [63,65].
According to epidemiological study and laboratory data
[74], vitamin D may have anti-cancer capabilities [84,
86]. Considering Karachi’s low latitude (about 67°00′36″
east longitudes and 24°51′36″ north latitudes), vitamin
D insufficiency was detected in 60.2% of study
respondents, with severe deficiency (12 ng/ml) in 34.8%
of Pakistani women [81, 82]. This is despite the fact that
Karachi gets substantial quantities of sunlight [81].
Public health initiatives are required to address high
deficiency rates, including dietary fortification, with
increased exposure to sunshine.
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The American Journal of Medical Sciences and Pharmaceutical Research
Figure 3
Despite a scarcity of data, a study of Pakistani women
showed a relationship between endogamy (genetic
related ness) and the incidence of BC [58]. Additionally,
it has been argued that, owing to a lack of cosmetics
regulatory monitoring, there are hundreds of cheap,
unlicensed, and accessible products, some with high
concentrations of parabens that may be involved in
developing breast cancer [66]. Moreover, irrigating
crops using sewage water is a widespread approach in
underdeveloped nations. Heavy metal deposition in
vegetables may be enhanced as a consequence of
sewage water irrigation. Human health may be
threatened if such polluted vegetables are ingested
[78]. The crops planted with sewage irrigation are
inappropriate for human consumption owing to the
presence of hazardous components such as lead,
cadmium and chromium. Chromium in high
concentration may generate urogenital issues, heart
difficulties, and carcinogenic repercussions [79]. When
compared to non-cancerous persons, the hazardous
element, cadmium was larger in female breast cancer
patients in Pakistan [76,80].
Furthermore, poor dietary habits that cause
inflammation contribute to both communicable and
noncommunicable illnesses [82]. Obesity increases the
risk of mortality by around 30% on average and the
chance of BC by 35-40%. Not only should eating
behaviours be prioritized, but also div weight control
[83]. Physical activity, age, smoking, marital status,
breastfeeding, menopausal status, oral contraceptives,
div mass index, and parity may all increase risks [52,
54, 82].
The gut microbiome is well known to regulate the
host’s health and physiology. The gut microbiota and
their metabolites stimulate cellular and immunological
processes counter factors detrimental to human
health [60]. Recent evidence points to a potential
involvement for gut microbial dysbiosis in the
development, management, and prognosis of BC. A
recent study designated the “Biota Cancer Survivors”
study sought to determine whether the gut microbiota
of cancer survivors differed from a database of healthy
controls [63]. Through comparison of differences
between BC survivors and healthy controls, significant
taxonomic differences were elucidated between the
two groups. How ever, additional research is required to
elucidate the contributing mechanisms and investigate
the connection between microbiome and BC survival.
The role of gut microbiome and dysbiosis, as well as the
research of the microbiota-gut axis in cancer is not fully
under passed in Pakistan, and is a valuable field of
exploration. A preliminary investigation of the oral
microbiota (bacteria) and gastrointestinal tract (gut) in
32 urban Pakistani adults was recently completed
utilizing 16S ribosomal RNA gene sequencing [65].
Interestingly, gender differences were detected in the
gut microbiomes of Pakistani individuals, as well as a
skewness toward Firmicutes and particularly large
quantities of Proteobacteria in the males, which may
lead to gut dysbiosis. It was also noticed that Pakistani
women have considerably more Firmicutes [69].
Without a question, BC is a difficult condition, with
various risk factors contributing to the disease’s
eventual appearance.
CONCLUSION
Current healthcare challenges and literacy issues persist
in the diverse Pakistani population structure. The
majority of breast cancer cases in Pakistan appear at
higher stages because patients delay seeking medical
assistance. Illiteracy along with fear and the absence of
screening programs and cultural and economic factors
are the main drivers behind this issue. Urban residents
consume large amounts of inexpensive throwaway
plastic products that consist primarily of bisphenol-A
compounds with estrogenic activity thus leading to
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The American Journal of Medical Sciences and Pharmaceutical Research
premature menarche, obesity, cancer and problems
with reproductive organ function. The traditional
barbecuing practices in KPK increase the risk of BC and
other cancer types through exposure to heterocyclic
amines with carcinogenic potential. National screening
programs require both awareness and cost-effective
access to appropriate medical services following these
important health statistics.
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