11. BREAST CANCER:
Incidence and Mortality in the World
• Third most frequent cancer in world (Male + Female)
– 1990: 796,000 cases, 314,000 deaths
– 2002: 1,152,000 cases, 411,000 deaths
• Most common cancer among women worldwide
– 2002: Most common cause female cancer deaths
CA Cancer J Clin: 49:33, 1999
Globocan 2002 (IARC)
12. In 2008, breast cancer caused 458,503 deaths worldwide
- 13.7% of cancer deaths in women and
- 6.0% of all cancer deaths for men and women together.
13. Breast Cancer epidemiology
Variation among countries
Variation among populations
Variation among ethnic groups
16. By Region
The incidence of breast cancer varies greatly
around the world: it is lowest in less-developed
countries and greatest in the more-developed
countries.
18. By Region
In the twelve world regions, the annual
age-standardized incidence rates per 100,000
women are as follows:
19. Nr World Region Incidence
100,000
1 Eastern Asia 12
2 South Central Asia 22
3 Sub-Saharan Africa 22
4 South Eastern Asia 26
5 North Africa and Western Asia 28
6 South and Central America 42
7 Eastern Europe 49
8 Southern Europe 56
9 Northern Europe 73
10 Oceania 74
11 Western Europe 79
12 North America 90
28. Parameter: Race
It appears that there is no race with a special
genetic predisposition.
It is the socioeconomic conditions and the life-style
that make the difference.
29. Parameter: Gender
It is about 100 times more common in women
than in men (Veto, et al., 2009).
30. Parameter: Age
Breast cancer is strongly related to age,
with only 5% of all breast cancers occurring
in women under 40 years old
Older women are at higher risk,
particularly women aged 50 – 69
are most at risk, predominantly
those with a late menopause.
34. Estimated risk of developing breast cancer by Age
Females, UK, 2008
Adopted from: www.cancerresearch.uk
35. Reproductive Factors
Endogenous Sex Hormones
Oral Contraceptives
Postmenopausal Hormone Use
Dietary Factors and Energy Balance
Genetic Factors
Medical Factors
36. Reproductive Factors
Age at menarche
Pregnancy and age at first full-term pregnancy
Number and spacing of births
Lactation
Spontaneous and induced abortion
Age at menopause
37. Age at Menarche
• Earlier age at menarche has been consistently associated
with increased risk of both premenopausal and
postmenopausal breast cancer.
• Later age - lower risk
• Age 15 vs age 11 gives 30% lower risk to age 70
38. Pregnancy and age at first
full-term pregnancy
• Nulliparous women are at more of a risk of breast cancer
than parous women
• The susceptibility of mammary tissue to carcinogens
decreases after the first pregnancy, reflecting the
differentiation of the mammary gland.
39. Number and spacing of births
• A higher number of births is consistently related to lower
risk of breast cancer; each additional birth beyond the
first reduces long-term risk of breast cancer.
• In addition to a protective effect of higher parity, more
closely spaced births are associated with a lower lifetime
risk of breast cancer.
40. Lactation
• As early as 1926, it was proposed that a breast never used
for lactation is more predisposed to cancer.
• Research showed an overall 4% reduction in risk per 12
months of breastfeeding for all parous women.
• It is estimated that, if women in developed countries had
the number of births and lifetime duration of
breastfeeding of women in developing countries, the
cumulative incidence of breast cancer by age 70 years
would be reduced by as much as 60%
41. Spontaneous and induced abortion
• It is hypothesized to increase a woman’s risk of
developing breast cancer.
• By far the strongest study to date on the association
between breast cancer and abortion was a population-based
cohort study made up of 1.5 million Danish
women born April 1, 1935, through March 31, 1978.
42. Menopause
• Early menopause reduces risk
• Women who have undergone bilateral oophorectomy
at a young age have a greatly reduced risk of breast
cancer.
• Women with bilateral oophorectomy before age 45 years
have approximately half the risk (50%) of breast cancer
compared to those with a natural menopause at age 55
years or older.
• On average, the risk of breast cancer increases by some
3% per year of delay in age at menopause.
43. Age at Menopause
Age at menopause
400
350
300
100,000
250
Incidence/200
150
100
50
0
Age 44%
45
55
30 35 40 45 50 55 60 65 70
Menopause
age 45
Menopause
age 55
Colditz and Rosner, Am J Epidemiology 2000;152:950-64
44. Pregnancy history
450
400
350
300
250
200
150
100
50
0
Pregnancy History
30
34
38
42
46
50
54
58
62
66
70
Age
Incidence/100,000
Age birth
35
Nulliparous
Age birth
20,23,26,29
17%
27%
Birth at 35 = 17% increase risk to age 70
Many births = 27% reduction in risk to age 70
46. Estrogens
• The risk of breast cancer increased with increasing
estrogen levels
47. Androgens
• Androgens have been hypothesized to increase breast
cancer risk either directly, by increasing the growth
and proliferation of breast cancer cells, or indirectly,
by their conversion to estrogen.
48. Prolactin
• Substantial laboratory evidence suggests that prolactin
could play a role in breast carcinogenesis.
• Prolactin receptors have been found on more than 50% of
breast tumors, and prolactin increases the growth of both
normal and malignant breast cells in vitro, although these
findings have not been entirely consistent.
• Prolactin administration is well documented to increase
mammary tumor rates in mice.
49. Insulin-like Growth Factor
• It is a polypeptide hormone with structural homology
to insulin, and it is regulated primarily by growth
hormone.
• There is increasing evidence that the growth hormone-
IGF-I axis stimulates proliferation of both breast cancer
and normal breast epithelial cells.
50. Oral Contraceptives
Any use of oral contraceptives
Duration of use and time since last use
Use before a first full-term pregnancy or at an early age
Type and dosage of oral contraceptives
Progestin-only contraceptives
51. Excess cases of breast cancer that would be generated in
a population of 10,000 women using oral contraceptives
Age (years)
at Starting Use
at different ages for 5 years.
Cases
Among Users
Cases
Among Nonusers
Cumulative Excess
Cases per 10,000
16 – 19 4.5 4 0.5
20 – 24 17.5 16 1.5
25 – 29 48.7 44 4.7
30 – 34 110 100 11.1
35 – 39 180 160 21
40 – 44 260 230 32
Use before a first full-term pregnancy or at an early age
52. Oral Contraceptives
• In several meta-analyses and a large pooled analysis,“ever” use of oral
contraceptives was not associated with breast cancer risk
• Most studies have observed no significant increase in breast cancer risk with
long durations of use.
• A slight increase in risk seen in some studies subsided within 10 years of
stopping oral contraceptive use.
• There is no evidence of a differential effect according to type or dose of either
estrogen or progestin.
• Data on specific formulations remain inconclusive
• Progestin-only contraceptives users were observed to have either a similar or
lower risk of breast cancer compared to never users
53. Oral Contraceptives
• Results of more than 50 studies have provided
considerable reassurance that there is little, if any,
increase in risk with past oral contraceptive use in
general, even among women who have used oral
contraceptives for 10 or more years. In the pooled
analysis, long-term use among young women was not
independently associated with an increase in breast
cancer risk, but current users and recent users (< 10 years
since last use) had a modest elevation in risk compared to
never users.
54. Post-menopausal hormonal use
Any use
Duration of use
Recency of use
Type, dosage, and mode of delivery of estrogen
Use of estrogen plus progestin
Receptor status and histologic subtypes of breast
cancer
55. Post-menopausal Hormonal Use
• In the meta-analyses, significant increases in risk of approximately
30%-45% with more than 5 years of use have been observed.
• RR for 10 or more years of use = 1.47; 95% CI, 1.22-1.76).
• Risk is greater for users of estrogen plus progestin compared to
users of estrogen alone.
61. Family History
A woman who has a family member with
breast cancer increases to double the risk
of getting breast cancer in comparison
to a woman with no family history
(Lancet, 2001)
62. Medical Factors
Precursor neoplastic lesions
Mammograms and breast density
Antibiotic use
Silicone breast implants
Ionizing Radiation
Electromagnetic fields
Active and passive smoking
63. Precursor Neoplastic Lesions
• 1/ Nonproliferative lesions
• 2/ Proliferative lesions without atypia
• 3/ Proliferative lesions with atypia
64. Precursor Neoplastic Lesions
• 1/ Nonproliferative lesions (cysts)
• Women with these lesions are at the
same risk of breast cancer as women
without a breast biopsy.
65. Precursor Neoplastic Lesions
• 2/ Proliferative lesions without atypia
(eg, intraductal papilloma, sclerosing adenosis,
moderate hyperplasia of usual type)
• These conditions are associated with a 1.5- to 2-fold
increased risk of breast cancer compared to
nonproliferative lesions.
66. Precursor Neoplastic Lesions
• 3/ Proliferative lesions with atypia
(Atypical ductal hyperplasia and atypical
lobular hyperplasia)
• These lesions are associated with a 3.5 – 6.0
fold increased risk of subsequent breast cancer
67. Mammograms and Breast density
• Mammographic density is the strongest risk factor for the
development of breast cancer.
• Women with dense breasts have 4 times the likelihood of
developing breast cancer compared to women without dense
breasts.
• It is also well known that breast tissue density increases in about
25%-30% of women who begin hormone replacement therapy and
that, conversely, breast density decreases in some women who are
placed on tamoxifen or raloxifene.
68. Antibiotic Use
• No relation even with over a total of 1,000 days of use
69. Silicone Breast Implants
• Most studies examining the relation of silicone breast
implants with breast cancer risk have actually reported
lower rates of breast cancer among women with
implants.
• Reported reductions in risk in some of these studies have
been large (on the order of 50% or 60%).
• There is strong epidemiologic evidence that breast
implants do not lead to increased risk of breast cancer
70. Ionizig Radiation
• Depends on dose and age at irradiation, being highest for
women exposed before age ten years. (<10y)
• For women exposed after age 40 years (>40y), there was
no significant elevation in subsequent breast cancer risk.
71. Electromagnetic Fields
• Electromagnetic fields (EMF) have been proposed to alter breast
cancer risk, perhaps by altering melatonin secretion by the pineal
gland. In case-control studies designed specifically to study
occupational exposure to EMF and breast cancer in women, small
increases in risk have been inconsistently observed.
72. Synthetic Chemicals
• (Organochlorines, synthetic chemicals, DDT, Dioxins)
• Many of these chemicals are weak estrogens and may act as
estrogenic agents in breast tissue, thereby hypothesized to increase
breast cancer risk by mimicking endogenous estradiol.
73. Smoking
• No causal relationship between active smoking and
breast cancer.
• Same for passive smoking
74. Dietary Factors and Energy Balance
Alcohol
Caffeine
Physical activity
Obesity
Height
Weight and weight change during adulthood
75. Alcohol
• Women consuming 35-44 g/day of alcohol (about 3
drinks per day) have a RR of 1.32 compared to
nondrinkers.
• The risk increased by 7.1% for each 10 g/day.
One alcoholic drink each day increases the risk
of breast cancer by around 12%
76. Caffeine & Tea
• Most case-control studies have not observed evidence of
a positive association with breast cancer.
• In prospective studies, no increase in breast cancer risk
has been seen.
• Similarly, no evidence for an association between tea
consumption and risk of breast cancer has been seen in
epidemiologic studies.
77. Physical Activity
• Among postmenopausal women, physical activity may
lower breast cancer risk by reducing fat stores, which
convert androstenedione to estrone.
• Physical activity may also increase levels of sex hormone-binding
globulin (SHBG), which would reduce
bioavailable estrogens.
• Increased physical activity also reduces insulin resistance
and hyperinsulinemia, which has been hypothesized to be
related to breast cancer.
• Evidence was sufficient to establish that physical activity
is protective against breast cancer.
• Risk may be reduced by approximately 40% among those
who were consistently most active.
78. Obesity
• Postmenopausal adiposity is an established risk for
postmenopausal breast cancer.
• Components of energy balance have been evaluated in
numerous studies indicting that highest energy intake,
highest body mass index (BMI), and lowest energy
expenditure may combine to more than double the
risk of breast cancer.
•
Obesity increases the risk of postmenopausal
breast cancer by up to 30%, since levels of
hormones rise with excess body fat.
81. BREAST CANCER EPIDEMIOLOGY:
Stage at diagnosis: United States vs. India
STAGE EXTENT 5 year
SURVIVAL
DISTRIBUTION
USA INDIA
0 Noninvasive 100% 16% ----
I Early stage
disease 100% 40% 1%
II Early stage
disease 86% 34% 23%
III Locally
advanced 57% 6% 52%
IV Metastatic
USA:
90% DCIS or
early staged
invasive
disease at
diagnosis
disease 20% 4% 24% INDIA:
SSoouurrcceess:: SSEEEERR SSuurrvviivvaall MMoonnooggrraapphh,, 22000077
76% locally
advanced or
metastatic at
diagnosis
84. Metastatic breast cancer is a heterogeneous disease with
a variety of different clinical scenarios, ranging from
solitary metastatic lesion to diffuse involvement.
Between 6 to 10% of breast cancer patients present
with metastasis at diagnosis.
Once metastases are detected, median survival ranges
between 18 and 24 months, depending on number and
site of metastatic lesions, and tumor characteristics.
The five-year overall survival rarely exceeds 20%.
Overall, survival of patients with MBC is slowly but steadily
improving. This improvement is most probably related to
the development and widespread availability of modern
systemic therapies.
85. Long term survival can be obtained in approximately
50% of women with LABC who are treated with a
multimodal approach.
The addition of systemic therapy to the traditional
local treatment has improved prognosis.
Prognostic factors include age, histological type,
grade, hormone receptor status and response to
neoadjuvant therapy.
86. WORLD BREAST CANCER STATISTICS:
Incidence and 5-Year Survival
Southern Africa
Southeastern Asia
CA Cancer JJ CClliinn:: 5500::3377,, 22000000
90
80
70
60
50
40
30
20
10
0
North America
Northern Europe
Western Europe
Southern Europe
Northern Africa
South Central Asia
INCIDENCE (per 100,000) 5-YEAR SURVIVAL (%)
89. Breast Cancer is a major Public Health problem.
In several parts of the world, it remains the most
common cancer among women.
Most breast cancer deaths occur in less
developed countries
90. The number of cases worldwide has
significantly increased since the 1970s,
a phenomenon partly attributed to the
modern lifestyles
91. Given the resources disparities between countries,
impacting on both incidence and mortality, it is
difficult to adopt a common strategy for cancer care.
However, efforts might be made to improve the
health care system in every country, by facilitating
the access to both care and screening structures.
Editor's Notes
Mechanism of Action
- Competitively block LHRH receptors in the pituitary
- Initial stimulation of LHRH receptors followed by down-regulation of the receptor leading to a
decreased production of FSH and LH
- Estradiol and progesterone levels reduced
Birth at 35 = 17% increase risk to age 70
Mult births = 27% reduction in risk to age 70
Mechanism of Action
- Competitively block LHRH receptors in the pituitary
- Initial stimulation of LHRH receptors followed by down-regulation of the receptor leading to a
decreased production of FSH and LH
- Estradiol and progesterone levels reduced
Sources: SEER Survival Monograph, 2007;
Chopra, Cancer Institute Chennai, India, 2001