Transcript Clinical Course of Breast Cancer Patients with Complete

Breast cancer:
why do people get it and
can we prevent it?
T. Kuan Yu, M.D., Ph.D.
Houston Precision Cancer Center
What is Cancer?
• Our own cells that grows without
control
– Grow (faster or slower than normal cells)
– Die (slower than normal cells)
– Proteins and structures that are very similar to
normal cell
Why do we get cancer?
???
Basics of Cells
DNA  RNA  Protein
DNA is Blueprint for Cells
• DNA is blue print
of cells.
• Its radius is 1 nm.
If you stretch DNA
into single strand, it
would be 1600 km
long.
• Only 1.5% of DNA
are genes (~20,000)
that encode proteins
Why do we get cancer?
• Different events can “change” (i.e. mutate)
the DNA and change the protein function
• With the “right” sets of mutations, the cells
stop listening to the control of the body
 Events that
cancer
mutate DNA leads to
Breast Cancer Statistics
•
•
•
•
•
200,000 new cases in 2003
40,200 breast cancer deaths in 2003
Most common female malignancy
Second leading cause of female ca mortality
SEER data:
– Lifetime risk of developing breast ca
• 13.1% in white American female
• 9.6% in African-American female
Breast Cancer Risk Factors
• Age
• Female sex
Non Modifiable
• Inherited Factors
• Family history
• Benign breast disease
• Hormones
Modifiable
• Dietary Factors
• Environmental factors
Largest Risk Factors
• Age
– DNA less stable
– Accumulation of previous changes
• Woman
– Hormone
– Breast tissue
( Courtesy of Dr. Arun Banu)
( Courtesy of Dr. Arun Banu)
0
1
Relative with Breast Cancer
RR* of breast cancer
Premenopausal
3.2
Postmenopausal
1.5
Premenopausal, b/l
8.8
Postmenopausal, b/l
4.0
( * RR = Relative Risk )
Family history of breast cancer
• Personal history: 0.5-1%/yr
• Family history:
Lifetime risk: 20-30%
Mother
Sister
• BRCA 1& BRCA 2: Lifetime risk: 50-80%
( Courtesy of Dr. Arun Banu)
( Courtesy of Dr. Arun Banu)
( Courtesy of Dr. Arun Banu)
( Courtesy of Dr. Arun Banu)
( Courtesy of Dr. Arun Banu)
Estrogen Exposure Can Drive
Breast Cancer Development
Estrogen Exposure
• Early menarche (< 12 yo)
• Late menopause (> 55 yo)
• Having no pregnancy
• Childbirth after 30 yo (RR: 4-5x)
• Exogenous estrogen use
• Obesity (post-menopausal)
Combined Oral Contraceptive May
Increase Risk of Breast Cancer
• 53 297 women with breast cancer and 100 239
women without breast cancer from 54 studies
• Combined oral contraceptives:
– current users  RR 1.24 [1.15-1.33]
– 1-4 years after stopping  RR 1.16 [1.08-1.23],
– 5-9 years after stopping  RR 1.07 [1.02-1.13]
– 10+ years after stopping use  RR 1.01 [NS]
(Lancet. (1996)22;347(9017):1713)
Combined Oral Contraceptive May
Not Increase Risk of Breast Cancer
• 4575 women with breast cancer and 4682 controls
• Combined oral contraceptives:
– current users  RR 1.0 [NS]
– Former users RR 0.9 [NS]
– No association with family history or use at
young age
(Lancet. (1996)22;347(9017):1713)
Risk from Hormone
Replacement after Menopause
What Can We Do to Prevent
Breast Cancer?
Estrogen Exposure Risk:
• Pregnancy
• Early Childbirth
• Breast Feed
• Limit Exogenous Estrogen
Western Lifestyle/Food Increase Breast
Cancer Risk in Asian-American
• >1500 Asian-American immigrants (1983)
• born in the West  60% higher risk than born in the East.
• Among those born in the West: women with three or four
grandparents born in the West  50% higher risk than
those with all grandparents born in the East.
• Among those born in the East: lived in the West for > 10
years  80% higher than more recent migrants.
• Risk was unrelated to age at migration for women
migrating at ages less than 36 years.
(JNCI (1993) 85 (22): 1819)
Obesity Increases Breast Cancer Risk in
Postmenopausal Woman
• Obesity leads to 11,000 to 18,000 deaths per
year from breast cancer in U.S. for women
over age 50
• Obesity increase the risk of breast cancer by
1.5 fold among postmenopausal women
who do not use menopausal hormones
• Due to increased levels of estrogen in obese
post-menopausal women, whose ovary is
not functioning
What Can We Do to Prevent
Breast Cancer?
Food Risk:
• Western diet/lifestyle
• Weight control (post-menopausal)
• Soy isoflavones may be protective
for prememopausal breast cancer
(RR 0.41)
Chemicals May Increase Breast
Cancer risk
• Many chemicals led to cancer developments
in lab animal
• No association seen with DDT, DDE,
polychlorinated biphenyls and High power
line in population studies
Radiation Increases Breast
Cancer risk
• Woman of the atomic bombings in Japan during
World War II;
• Women with Hodgkin’s disease treated with
radiation therapy
• Girls treated with RT for non-malignant
conditions
• Young women with large numbers of diagnostic
x-ray to monitor treatment for TB or severe
scoliosis.
Prior RT to breast
• Mantle RT
– Relative risk of breast ca depends on the age at
which she received RT
• 56% for women 19 yrs of age at RT
• 7% for women b/ 20-29 yrs of age at RT
• 1% for women 30 yrs of age at RT
– Cancer develops 10-15 yrs later
– Usually medial portion of the breast
What Can We Do to Prevent
Breast Cancer?
Chemical Risk:
• Not clear
Radiation Risk:
• Avoid unnecessary exposure of RT
such as diagnostic X-ray that are not
needed
What Can We Do to Prevent
Breast Cancer?
Early Detection:
• Self Breast Awareness
• Annual Mammogram (≥ 40)
• Clinical breast exam about every 3
years for women in their 20s and
30s and every year for women ≥ 40
Screening Mammography
• HIP (Health Insurance plan of NY) Study
– 61,000 women, age 0-64 yrs
– Randomization:
• Screening mammo vs. routine medical care
– Results:
• Mortality rate was reduced by 33% in screened
women 50-59 yrs of age
• Survival difference was higher by 7 to 10 yrs after
diagnosis in women who had screening
mammography
The Gail Model
Calculates a woman’s 5-year and lifetime risk of
developing breast cancer
Includes:
• Current age
• Number of 1st-degree
female relatives with a
history of breast cancer
• Age at first live birth,
or nulliparity
• Number of breast
biopsies
• History of atypical
hyperplasia
• Age at menarche
• Race
For Woman with BRCA1/2 Mutations
( Courtesy of Dr. Arun Banu)
NSABP-P1(BCPT): Schema
Eligible Women at High Risk
(5-yr risk  1.66% or age over 60)
Randomization
n = 13,388
Tamoxifen
5 Years
n = 6681
Fisher et al. J Natl Cancer Inst 1998;90:1371-1388.
Placebo
5 Years
n = 6707
Invasive Breast Cancer Cases by ER Status
150
130
Number of Events
Placebo
Tamoxifen
100
50
31
38
41
14
10
0
Negative
Positive
ER Status
Adapted from Fisher et al. J Natl Cancer Inst 1998;90:1371-1388.
Unknown
Rate of Invasive Breast Cancer
Events
Rate/1000
40
Placebo
Tamoxifen
175
89
Rate per 1000
43.4
22.0
Placebo
30
P < 0.00001
49%
reduction
20
Tamoxifen
10
0
0
1
2
3
4
5
Years
Adapted from Fisher B, Constantion JP, Wickerham DL, et al. J Natl Cancer Inst. 1998;90:1371-1388.
Why Not Just Treat All High-Risk
Women With Tamoxifen?
• Less than 5% of high-risk women elect to take tamoxifen when
offered.
• Tamoxifen has some serious side effects (particularly for
women ≥ age 50).
Type of event
Endometrial
cancer
Stroke
Pulmonary
embolism
Deep vein
thrombosis
Risk Ratio
(all ages)
2.53
Risk Ratio
(ages ≥ 50)
4.01
1.59
3.01
1.75
3.19
1.60
1.71
Breast Cancer Prevention
• Raloxifene (MORE Trial)*
– Post menopausal female with osteoporosis
– Breast cancer reduction by 62%
– Invasive breast cancer by 72%
– Invasive ER+ive breast cancer
– No associated with uterine cancer
– Side Effects:
• Increased risk of thromboembolic event
• 28% hot flashes with raloxifene vs. 21% in placebo
• 40% reduction in cardiovascular events
*Breast Cancer Res Treat 65:125-134, 2001
Prophylactic Mastectomy for High risk Woman
• Removes most but not all breast tissue
• Total (simple) mastectomy appears more
effective than subcutaneous mastectomy
• Shown to reduce risk of breast cancer by
90% in women with BRCA mutations
Hartmann LC, Sellars TA, Schaid DJ, et al. J Natl Cancer
Inst. 2001;93:1633-37.
New Engl J Med 2001;345:159-64
Oophorectomy for Woman with High Risk for
Breast cancer
• Oophorectomy
– Prevents breast ca in BRCA 1 and 2
– RR reduction is 50% in premenopausal pts
– RR reductions may be higher if done before the
age of 40 yrs and that the duration of protection
is approx. 15yrs
JCO 23(8):1656-1663; 2005
Conclusions
• Many Non-Modifiable risk factors for
breast cancer
– Early dectection
• Many Modifiable risk factors for breast
cancer
– Reduce estrogen exposure
– Adjust diet and weight
– Prevent exposure from unnecessary chemical
and radiation
Thank You
Acknowledgement for materials in slides:
Dr. Arun Banu
Dr. Hemangini Shah