Jack: Hi, everyone.
In today's lecture,
we'll be discussing the epidemiology of breast cancer.
This lecture has several goals.
We'll begin by reviewing the anatomy and function
of the human breast and then describing the global impact
of breast cancer, including trends in breast cancer rates
in different parts of the world.
We'll continue to look at breast cancer detection
and tumor staging, studies of risk factors, genetics,
and breast cancer prevention and control.
So to begin with,
we see some interesting differences when we look at
the annual incidents and mortality rates
of breast cancer in 2012.
So on the left here,
we see incidents a rate increasing going from top to bottom
of the chart
with the US of all countries listed having
the highest incidence rate of breast cancer at 101.1 cases
per 100,000 women.
Though at the same time,
the US does not have the highest mortality rate.
That would be, it appears to be the Netherlands
with the rate of 27.5 deaths per 100,000 women
of breast cancer.
We also see that of the nations included
China has the lowest incidence of breast cancer
and that the nation with the lowest mortality
of breast cancer is also China.
When we look at global statistics for 2020,
we see that the age standardized incidents
of breast cancer is 47.8 cases per 100,000
and that the age standardized mortality is 13.6 cases
per 100,000.
So to begin with, let's discuss a little bit
of the anatomy of the female breast.
So the human female breast consists primarily
of fat and glandular tissue.
Each breast contains a complex network of saclike lobules
or milk glands that produce breast milk
and ducts that carry milk
from the lobules to the nipple openings
during breastfeeding.
Adult women have 15 to 20 distinct clusters of lobules
in each breast which are called the breast lobes
and each breast lobe can have 20 to 40 lobules.
There are also small ducts that emanate from the lobules
of the breast and join together in branch into
increasingly larger ducts that carry breast milk
to openings of the surface of the nipple.
Adipose tissue or fat furnishes the energy for lactation
and is the most abundant tissue of the human female breast.
There's also connective tissue
and ligaments that provide structural support
and nerves that provide sensation to the breast.
Finally, the breast also contains blood vessels,
lymph vessels, and lymph nodes
as depicted in the figure above.
Next we'll turn to look at incidents
and mortality of breast cancer globally in 2012.
So breast cancer was diagnosed in 1.68 million women
and caused 521,817 deaths
in the world population during 2012.
This makes breast cancer the most commonly diagnosed cancer
and the second leading cause of cancer death
among women, only lung cancer causes more deaths.
Breast cancer incidences also highly variable,
ranging from low rates of 19 per 100,000 in China,
Africa, and India to rates exceeding 80 cases per 100,000
in Scandinavian and European countries, the United States
and Great Britain, and then among income countries
the US is the highest annual incidence rates
of breast cancer exceeding 100 cases per 100,000.
In contrast, the lifetime risk of breast cancer is only
one in 66 for Chinese women,
where for American women the risk is one in eight.
Breast cancer mortality rates show a narrower range
than incidence rates, and as we previously mentioned,
they ranged from 5.5 deaths per 100,000 Chinese women
to 27.8 deaths per 100,000 Danish women.
The incidents and mortality rates
of breast cancer tend to be higher
for women in high income countries compared
to those in low and middle income countries.
And as we just discussed,
this map shows the mortality rates globally
for breast cancer in 2012.
Next, turning to the tumor staging of breast cancer
this chart depicts the five year survival rate
for the various stages of diagnosis for breast cancer.
So tumor staging refers to the microscopic evaluation
of tissues by a pathologist to assess size,
exact anatomic location, growth,
and spread of a cancerous lesion.
And the second column of this chart gives
a brief description for some factors that play a role
in determining what stage a tumor is at.
It's important to note that early stage breast cancer
so stage 0, I, or even IIA is effectively cured
by complete surgical excision with clear margins
while late stage disease is resistant to therapy
and treated by chemotherapy, radiation therapy,
and hormonal therapy and does not have nearly as high
a five-year survival rate as the lower staged cancers.
So there's three key aspects of breast cancer detection.
Those are self-examination, mammography,
and clinical examination.
So as some of you may have seen,
the breast cancer screening guidelines are different
according to what age someone is, and there recently was
a decision by the US Preventative Services Task Force
that encourages all women aged 40 and older to receive
mammograms every two years
if they're at regular risk of breast cancer.
As we'll discuss later on in this presentation
there are different genetic factors that can lead
to people being at elevated risk for breast cancer.
So these general guidelines may not apply to everyone
but typically those ages 20 to 29 are
at lower risk of breast cancer than those aged older.
So they're not recommended to have mammograms
and mammography is not recommended to start until age 40.
We also see that the risk of breast cancer increases
with exposure to high dose radiation.
So there is increased risk for atomic bomb survivors,
acute mastitis patients, and tuberculosis patients
due to their exposure to radiation.
However, there's no evidence to support adverse effects
of screening mammography.
So to discuss a little bit of the mechanisms
of breast carcinogenesis,
we see that breast cancer typically arises
from the epithelial cells that line the ductal
and glandular structures of the mammary gland.
So as you'll recall when we talked about
the anatomy of the breast, there's several different tissues
that are present in that zone of the body.
Breast carcinogenesis is most probably due
to excess stimulation of these epithelial cells by estrogen.
Estrogen is a steroid
and a powerful mitogen that stimulates cell proliferation
by activating estrogen receptors of
the cell surface membrane.
Sustained excessive estrogen stimulation may lead to
heightened proliferation and atypia
of the mammary epithelium,
which are believed to be forerunners of breast cancer.
While breast cancer primarily occurs in women,
it occasionally develops in men,
particularly in association with Klinefelter syndrome
where there's an extra X chromosome and the karyotype
or the chromosomal make up of the individual.
So rather than a man being XY,
his chromosomal make up will be XXY.
This also can, the risk can increase
by the ingestion of synthetic estrogens like diethyl,
diethylstilbestrol that can be used
for the treatment of cancer of the prostate.
There's two different theories that are important
to note here.
The first is the estrogen stimulus theory
which holds that the risk of breast cancer is enhanced
with a sustained continuum of estrogen cycles
unbroken by pregnancy or other mechanisms
of estrogen ablation like an ovariectomy.
Another important theory is the estrogen window hypothesis
or theory, which holds its susceptibility to breast cancer
is increased by unopposed estrogen stimulation
during the onset of puberty
and later in life with the onset of menopause.
By this theory, susceptibility to induction
of breast cancer declines with the establishment
of normal ludial phase progesterone secretion
and becomes very low during pregnancy.
So this theory holds
that becoming pregnant can actually serve
as a protective factor to breast cancer
due to the presence of another hormone called progesterone.
So as mentioned, there's several different key risk factors
for breast cancer.
These include family history, early menses,
late first pregnancy, late menopause,
estrogen replacement therapy, and high body mass obesity
or high body mass index or obesity.
And the first studies of breast cancer established
these classical risk factors and one key study in 1923
by Janet Elizabeth Lane-Claypon in the United Kingdom found
compared women with breast cancer to women without
breast cancer to determine their different risk factors.
This study, a case control study, was the first to elucidate
well-known profile of classical breast cancer risk factors
like familial and genetic predisposition, early menses,
delayed reproductive history, nolanparity,
absence of lactation, late menopause,
and natural process of aging.
There also is a genetic predisposition
to breast cancer in some cases.
So we see that a strong family history increases the risk
of breast cancer by three to five fold, and in fact,
in 5 to 10% of women who are diagnosed with breast cancer,
it's found that they have a genetic
or familial predisposition to having breast cancer.
Hallmarks of familial predisposition of breast cancer
include early age of onset and excess of bilateral disease
and breast cancer and familial association with
other malignancies like ovarian cancer
and endometrial cancer.
Approximately 75% of breast cancers are diagnosed
in women after they undergo menopause,
and there's a general consensus that estrogen replacement
therapy with or without progesterone elevates the risk
of postmenopausal breast cancer by two to threefold
as found in a 1992 study.
Results from the randomized clinical trials
and the prospective cohort of the Women's Health Initiative
in the US found that breast cancer risk doubles
after about five years of using exogenous hormones
but declined soon after discontinuation of hormone therapy.
It's important to note here
that there was no significant risk found in
individuals using hormone replacement therapy
after less than five years, and there's going to be a couple
of readings included in this week's module
about recent findings or recent articles dissecting
both the findings of the Woman Health Initiative
and the other studies that really probe this relationship
between estrogen replacement therapy
or hormone replacement therapy and breast cancer risk.
When we look at trends in breast cancer mortality,
we see that rates of breast cancer are increasing
in populations which historically have been at low risk
but have remained relatively constant
in populations at higher risk risk.
Breast cancer mortality rates among Japanese, Indian,
and Chinese women have increased approximately threefold
in the past two decades.
Whereas in the US, UK, and other European nations,
rates have remained constant or slightly declined.
Japanese, Indian, and Chinese diets have also changed
dramatically with higher intake of fat and calories.
Other risk factors may also be involved
since birth rates are declining,
age at first pregnancy is being delayed
and noloparity is increasing in these populations.
One well-known but controversial hypothesis
of breast cancer etiology is known
as the dietary fat hypothesis.
And this hypothesis holds that breast cancer development is
due to intake of certain types of essential polyunsaturated
fatty acids that increase inflammation
and estrogen biosynthesis
and thus promote breast cancer development.
Remember from before, that one theory of breast cancer holds
that increased estrogen production or increased estrogen
reaching the breast tissues will promote the development
of breast cancer.
There has been some supportive evidence
for the dietary fat hypothesis of breast cancer
and those have primarily come from chronological studies
of Japanese women.
Over the past half century, the age adjusted
breast cancer mortality rate among Japanese women has
increased more than twofold,
rising from five deaths per 100,000 in 1950
to 12 deaths per 100,000 in 2006.
The increase in breast cancer mortality
among Japanese women closely parallels a threefold increase
in per capita fat consumption over the same time period.
In 1950, less than 10% of kilo calories were derived
from fat, whereas in 2005 the level had risen to nearly 30%.
Other controversial risk factors of breast cancer include
alcohol consumption, oral contraceptive use,
preneoplastic lesions, and thyroid dysfunction.
The evidence for these risk factors is not clear,
so it can't be said definitively
that any of these are risk factors.