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Breast cancer: why do people get it and can we prevent it?

Breast cancer: why do people get it and can we prevent it?. T. Kuan Yu, M.D., Ph.D. Houston Precision Cancer Center. Sam Houston Tollway. Gessner. Katy Fwy. Memorial City Mall. Attingham Dr. Beltway 8. We Are Here. Taste Of Texas. What is Cancer?.

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Breast cancer: why do people get it and can we prevent it?

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  1. Breast cancer: why do people get it and can we prevent it? T. Kuan Yu, M.D., Ph.D. Houston Precision Cancer Center

  2. Sam Houston Tollway Gessner Katy Fwy Memorial City Mall Attingham Dr. Beltway 8 We Are Here Taste Of Texas

  3. 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

  4. Why do we get cancer? ???

  5. Basics of Cells

  6. DNA  RNA  Protein

  7. 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

  8. 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 mutate DNA leads to cancer

  9. 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

  10. Breast Cancer Risk Factors • Age • Female sex • Inherited Factors • Family history • Benign breast disease • Hormones • Dietary Factors • Environmental factors Non Modifiable Modifiable

  11. Largest Risk Factors • Age • DNA less stable • Accumulation of previous changes • Woman • Hormone • Breast tissue

  12. ( Courtesy of Dr. Arun Banu)

  13. ( Courtesy of Dr. Arun Banu)

  14. 10Relative with Breast Cancer ( * RR = Relative Risk )

  15. 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%

  16. ( Courtesy of Dr. Arun Banu)

  17. ( Courtesy of Dr. Arun Banu)

  18. ( Courtesy of Dr. Arun Banu)

  19. ( Courtesy of Dr. Arun Banu)

  20. ( Courtesy of Dr. Arun Banu)

  21. Estrogen Exposure Can Drive Breast Cancer Development

  22. 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)

  23. 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)

  24. 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)

  25. Risk from Hormone Replacement after Menopause

  26. What Can We Do to Prevent Breast Cancer? • Estrogen Exposure Risk: • Pregnancy • Early Childbirth • Breast Feed • Limit Exogenous Estrogen

  27. 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)

  28. 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

  29. 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)

  30. 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

  31. 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.

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

  37. For Woman with BRCA1/2 Mutations ( Courtesy of Dr. Arun Banu)

  38. Eligible Women at High Risk (5-yr risk  1.66% or age over 60) Randomization n = 13,388 Tamoxifen 5 Years n = 6681 Placebo 5 Years n = 6707 NSABP-P1(BCPT): Schema Fisher et al. J Natl Cancer Inst 1998;90:1371-1388.

  39. Invasive Breast Cancer Cases by ER Status 1 5 0 130 P l a c e b o Tamoxifen 1 0 0 Number of Events 5 0 41 38 31 14 10 0 Negative Positive Unknown ER Status Adapted from Fisher et al. J Natl Cancer Inst 1998;90:1371-1388.

  40. Events Rate per 1000 4 0 Placebo 175 43.4 Tamoxifen 89 22.0 Placebo 3 0 P < 0.00001 49% reduction Rate/1000 2 0 Tamoxifen 1 0 0 0 1 2 3 4 5 Years Rate of Invasive Breast Cancer Adapted from Fisher B, Constantion JP, Wickerham DL, et al. J Natl Cancer Inst. 1998;90:1371-1388.

  41. 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).

  42. 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

  43. 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

  44. 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

  45. 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

  46. Thank You Acknowledgement for materials in slides: Dr. Arun Banu Dr. Hemangini Shah

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