In general cancer rates are predominantly
higher in more developed region of the globe. Lung and breast cancers are the
frequently most diagnosed cancer throughout the world both in more developed
and less developed region. Cervical and colorectal cancers also show high incidence
and mortality rate in both developed and less developed countries. Certain
cancers such as cervical, esophagus and stomach cancers tend to occur in high
rate mostly in less developed countries whereas other cancer incidence rate is
always higher in more developed countries (Torre et al.2015). The following
graphical presentation is based on global cancer statistics, 2012.
comparison of different cancer in more developed country vs less developed
country based on global cancer statistics, 2012.
Incidence of breast cancer can be linked
with increasing age. Before menopause, the risk of developing breast cancer is
found to be higher since risk increases two folds in every 10 years prior to
menopause. But after that age it slows down a bit. In some countries the
age-incidence curve seems to be flattened after menopause (McPherson et al.
2000). Another study has contested this proposition where it stated that 43% of
all breast cancer incidence were diagnosed in women above 65 years old and only
20% diagnosed in women younger than 50 years old (DeSantis et al. 2014 B).
and menstrual cycle:
The onset of menarche poses variable threats
to the development of breast cancer. late onset of menarche is considered to be
safer than early onset which means the younger a woman’s age at menarche, the
higher the risk (Kelsey et al. 1993). The
risk of developing breast cancer decreases by 5% with each one-year delay of
the first menstruation. A study conducted on 44 women comprising of 11 women
with early menarche showed higher concentration of estradiol concentration and
minimal concentration of sex hormone binding globulin during their follicular
phase of menstruation. In addition to this increased estrogen concentration,
enormous estrogenic exposure is believed to possess increased risk of
developing breast cancer in premenopausal women (Apter et al. 1989). In case of
post-menopausal women, similar types of studies are performed and the result
confirmed that endogenous concentration of sex hormones have strong association
with risk of ER + /PR + breast carcinomas (Missmer et al. 2004).
Natural menopause happens to occur at the
average age of 51.3 but different geographical factors change the average age
of menopause in different geographical region (McKinlay et al. 1992). A strong
association is established with the age of menopause and breast cancer risk.
Women experiencing menopause after 55 years of age are at doubled risk compared
to those who naturally terminate menstruation before 45 years. But the risk is
highest after age 70 (Trichopoulos et al. 1972). On the contrary, women who
terminate their menstruation cycle by bilateral oophorectomy before 35 years
have only 40% risk of breast cancer than women with natural menopause process
(McPherson et al. 2009).
seems to have baffling effect on the risk of developing breast cancer as it
increases sharply after giving a birth which eventually diminishes with time.
Ultimately giving birth to children lowers the risk and protects the mother
from developing breast cancer in her lifetime (Beral V and Reeves G, 1993). So number of parity as well as duration of
breastfeeding provides protective support against breast cancer. A study in
1989 revealed that women with more than one parity (usually four or more than
four parities in lifetime) showed lower risk in developing breast cancer
compared to women of parity one. Even it was successfully deduced from the
study that women who had breastfed more than average period of 25 months seems
to possess lower risk of breast cancer compared to those who never breastfed at
all (Layde et al. 1989). The protective
effect of breastfeeding on breast cancer risk may be higher in younger women
than in older women (Kelsey JL et al., 1993). An International
collaborative study covering women from seven areas of the world was conveyed
to propose an inverse relationship between the age of first birth and breast
cancer risk. The study concluded that women experiencing first confinement at
early age or below 18 years was found to have 40% risk in developing breast
cancer compared to normal women; in some cases, the risk is even lower (MacMahon
et al. 1970). Early first
full term pregnancy is considered to have protective effects like late menarche
in developing breast cancer although first full term pregnancy primarily
increases the risk but the incidence rate decreases slowly.
contraceptives and early abortion
Women who take combined oral
contraceptive or have taken anytime in the last decade, are at slightly higher
risk of developing breast cancer (Collaborative Group on Hormonal Factors in Breast Cancer,
1996). The association of breast cancer
and of oral contraception is strongest in case of young women below 35 years
and the risk increases with a relative risk of 2.2 for women who have been
using oral contraceptives for more than 10 years (Brinton et at. 1995).
Either use of combined oral
contraceptives or progestin-only pills for 10 years or such results in high
content of progestogen that mainly increases the relative risk up to 4 (Pike et
al. 1983). Another study suggested that women who are yet to experience first
full-term pregnancy, if utilized oral contraceptives for a long time become
extensively prone to developing breast cancer and the risk increases 2.4 folds
with a first trimester abortion before a first full term pregnancy either
impromptu or induced (Pike et al. 1981).
Though hormone replacement therapy does
not increase breast cancer mortality but it plays significant role in the
development of breast cancer. There are higher chances of breast cancer in
women using combination of oestrogen and progestogen in their lifetime in
comparison to estrogen only HRT theraoies. HRT has propensity to increase the
breast density which potentiates the development of breast cancer
(McPherson et al. 2000).
A study was conducted to analyze the
relationship with ionizing radiation and the risk of breast cancer considering
three different populations of women exposing to radiation and a linear relationship
was established with dose dependent exposure to radiation and breast cancer
The study suggested that increasing the
dose of radiation, the age at exposure increases the risk of radiation-induced
breast cancers (Land et al. 1980).
Benign breast diseases also add high degree of risks in developing
radiation-associated breast cancers (Preston et al. 2002).
study was conducted on 100000 women receiving a dose of 3.7 mGy to both breasts
showed that at the age of 74 almost 86 of them were diagnosed with positive
results of radiation- induced breast cancer (Yaffe M.J. and Mainprize J.G.,
2011). X-ray scans and CT scans also increase the risk of breast at minimal
level. Previous chest radiation therapy used in treating childhood cancer can
potentially elevate the risk of developing breast cancer in future (Kenney et
Certain job contributes to the risk of
breast cancer where the employee undergoes extreme level of stress. Though
increased physical activities reduces breast cancer risk but workload and
psychological stress increases the risk. Rotating in a nightshift work worsen
the situation and the risk is elevated to moderate level (Schernhammer et al.
2006). Certain jobs ensuring direct or indirect contact with possible
carcinogens are linked to higher risk of breast cancer incidence. For example, bar/gambling, automotive plastics
manufacturing, metal-working, food canning etc.
history and inheritance
Higher chance of breast cancer
development was associated with a number of personal, familial and genetic
scenarios as well as various geographical and environmental factors.
Breast cancer among first degree
relatives which may be mother or sister have shown to escalate the risk of
developing cancer in young women. In case mother was diagnosed with breast
cancer before an age of 40 years or in case sister was diagnosed with the same,
the danger of developing breast cancer for a person became more than double, in
case of mother the relative risk in 2.0 where in case of sister diagnosed with
breast cancer the risk is even more than 2.3. this risk is only 5% if the
sister is diagnosed at 50-55 years age. Moreover, there is a striking increase
in the attributed risk by four to six times if the number of first degree
relative is more than one (McPherson et al. 2009).
A localized study estimated that about
17% to 19% of all breast cancer cases could be credited to family history which
might stretch as far as third degree relatives (Slattery and
Kerber 1993). A meta-analysis of 74 studies have indicated that the risk was
marginally higher in women younger than 50 years than in older women and also on the occasion that the
relative was diagnosed with breast cancer at an age below 50 years (Pharoah
et al. 1997).
risk increases by between four and six times if two first degree relatives
develop the disease. For example, a woman with two affected relatives, one who
was aged under 50 at diagnosis, has a 25% chance of developing breast cancer by
the age of 65.
Epidemiological studies were conducted in
order to manifest a positive association of different benign breast diseases
with successive development of breast cancer and a retrospective cohort study
proclaimed that women diagnosed with atypical lobular hyperplasia are at 3
times more risk to develop invasive breast cancer (Page et al. 2003). Depending
on the menstrual status, the immensity of risk tends to deviate as atypical
lobular hyperplasia seems to contribute high degree of risk in premenopausal
breast cancer than postmenopausal. But the association of atypical ductal
hyperplasia and breast cancer remains unaffected by the menstrual status of the
patient (Marshall et al. 1997).
Different studies were performed to
detect the association of breast density with breast cancer incidence by
systematically reviewing different mammographic patterns of breast tissues.
wolfe grade and percentage density of breast were performed to measure the
extent of radio dense fibro glandular tissues and a strong predictive
association was found between breast density and breast cancer (McCormack et al. 2006).
Data from seven prospective cohort
studies was analyzed and concluded with height being an independent risk factor
for breast cancer in post-menopausal women whereas in premenopausal women the
association remains unclear (Van et al. 2000).
Anthropometric factors such as BMI (body
mass index) and waist to hip ratio are assessed in order to measure the risk of
breast cancer. Relationship between
BMI and breast cancer is highly modified since it depends relatively on the
menstrual status. Hence, obesity remains as an established risk factor for
breast cancer in postmenopausal women. In premenopausal women, the risk
decreases with the increasing BMI ratio whereas risk elevates with increasing
BMI in postmenopausal women (Hunter D.J. and Willett W.C., 1993). BMI and other
anthropometric measures are not considered as risk factors for breast cancer in
women who have ever taken Hormone Replacement Therapy since HRT itself has the
propensity to increase the risk of breast cancer (Morimoto et al. 2002).
Certain food components have protective
effects on risk of breast cancer. This inverse relation is established via
certain case- control studies. Large intake of vegetables enriched with either
?-carotene or combined with lutein and zeaxanthin appears to lower the risk
sharply in premenopausal women (Freudenheim et al. 1996). On the
other hand, animal proteins and red meat intake increases the likelihood of
breast cancer in premenopausal women. High intake of polyunsaturated fatty
acids (PUFA), soya proteins, total soya products seems to show protective
measure against breast cancer in Singapore Chinese population (Lee et al. 1991).
Fruits containing vitamin C attenuates breast cancer risk to a relatively less
extent compared to vegetable consumption (Gandini
et al. 2000).
consumption and smoking
Alcohol intake both in early and later
adult life has independent risk in developing breast cancer. Risk moderately
increases with low level of alcohol consumption which is normally 3 to 6 drinks
per week. However, recent study suggested to reduce alcohol consumption to
increase the protective effects of macro and micro-nutrients against breast
cancer risk where 20gm alcohol per day was thought to be beneficial against
breast cancer risk (Horn-Ross et al. 2002). Previously assumption proposed that
risk increases about 10% per 10g alcohol consumed per day (Chen et al. 2011). In
developed countries alcohol consumption attributes to only 4% breast cancer
incidence whereas smoking has little or no significant effect on incidence
(Collaborative Group on Hormonal Factors in Breast Cancer, 2002).
Regular physical exercise decreases the
risk of breast cancer in premenopausal women but the effect of exercise on
postmenopausal women in not clearly defined (McTiernan et al. 2003).
The following table shows the magnitude
of effect of different nutrients and lifestyle on the development of breast
cancer in female according to American Cancer Society.
and lifestyle factors for breast cancer
for benefit vs harm
Increasing vegetables and fruit intake
A1. Convincing evidence for a benefit.
A2. Probable benefit.
A3. Possible benefit.
to conclude benefit or risk.
Evidence of lack of
Evidence of harm.
Consuming soy foods
Taking vitamin C supplements
Taking vitamin E supplements
Taking beta carotene supplements
Limiting intake of red meat
Limiting alcohol intake
Increasing physical activity
Table: Adopted from “American Cancer
Society Grades for Benefit Versus Harm (2001)” for breast cancer (Byers et al.
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