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in Breast Cancer

in Breast Cancer. Risk Factors. Statistical Terms. Life time risk an estimate of an individuals probability of developing cancer from birth until death. Incidence of a disease number of new cases diagnosed during a specific time period Prevelance

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in Breast Cancer

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  1. inBreast Cancer Risk Factors

  2. Statistical Terms • Life time risk • an estimate of an individuals probability of developing cancer from birth until death. • Incidence of a disease • number of new cases diagnosed during a specific time period • Prevelance • Number of rate of persons with the disease in the population at any one time • Relative risk • rate of a disease in an exposed group divided by the rate of a disease in an unexposed group. A relative risk of 1.0 indicates no effect. More than 1.0 indicates increased risk, less than 1.0 indicates a protective influence • Observed survival rate • proportion of cancer patients surviving for a specified length of time after diagnosis • Relative survival • ratio of observed survival of a patient group to the expected survival for people in the general population with similar age, sex, race and calander year of observation. Usually reported as five year survival rates.

  3. A few general observations • The majority of breast cancers occur above the age of 50. • The risk of developing breast cancer at the age of 30 is ten times less that getting breast cancer at the age of 50 • Patients developing breast cancers at a younger age often have a positive family history of the disease. • 99% of breast cancers occur in women. Only 1% of these malignancies occur in males. • 50 - 70% of breast cancer patients have no known risk factors.

  4. Personal history of breast cancer • Breast cancer is known to be multicentric, which means separate primaries can occur synchronously (at the same time) or metachronously (at a later time) in the ipsilateral or contralateral breast. • The risk of developing breast cancer in the contralateral breast in a known case of ca breast is about1% per year • This risk increases to 1.5% per year, if the patient is less than 55 years old or the tumor is of a lobular variety • The occurrence of a contralateral breast malignancy increases the risk of a distant recurrence.

  5. Estrogen • Estrogen is a known growth factor for breast cancer cells in the laboratory • Oral contraceptives (OC) • there is conflicting data on the breast cancer risk caused by taking OC. • Review of the data suggests that if at all OC increase breast cancer risk, the magnitude of risk is small. • This risk is larger for long term users (Relative risk ranges from 1.7 for use more than 8 years, to 4.1 for use more than 10 years5,6. • There is some concern regarding the widespread use of OC by very young women as the latent period between the taking of OC and the onset of breast cancer is not clear. • Hormonal replacement therapy (HRT) • a small increase of relative risk may be associated with taking moderated doses of unconjugated estrogen prepartions for a periods of 10-20 years7. • For this reason it is not prescribed to breast cancer women. It proven benefits in reducing osteoporosis and cardiac disease should be kept in mind when deciding on whether or not to give HRT.

  6. Diet and breast cancer • Dietary Fat Intake • There have been a number of studies attempting ot determine the possible connection between breast cancer and dietary fat intake. • Currently, however, there is no conclusive evidence that dietary modification reduces breast cancer incidence or alters its prognosis after diagnosis8. • Alcohol usage • A mild incidence increase in relative risk (1.4) is found in women who have more than 2 pegs of alcohol per day9. • There appears to be a clear dose-response relationship. • Occasional users have no increased risk • Alcohol has its greatest effect on breast cancer in women below the age of 3010, 11.

  7. Reproductive factors • Age of menarche • 10% reduced risk for each 2 year that menarche is delayed • the age-specific incidence of brest cancer rises sttply with age upto to the time of menopause and then slows to a rate one sixth that of premenopausal women. It is believed that this is largely due to ovarian over activity2. • Age of menopause • the relative risk of breast cancer in women who attain natural menopause before the age of 45 is .73 as compared with women who attain natural menopause between 45 and 543. • Oophorectomy before the age of 50 decreases breast cancer risk with increasing magnitude as the age of oophorectomy decreases4. • Parity • Nulliparous women have a greater risk with a relative risk of 1.4 • First term pregnancy after 30 has a 2-5 fold increased risk as compared to women who have their first preganancy before 19 • Abortion before term, does not confer the above benefits

  8. Family history • Women with a family history of breast cancer in a first- or second degree relative are at increased risk for developing breast cancer. • The risk of developing breast cancer is increased by 1.5 - 3.0 times if a mother or sister has breast cancer12,13. • Bilateral breast cancer in a pre-menopausal relative has been associated with the highest risk of development of breast cancer. • For most of these patients the lifetime probability of developing breast cancer is rarely greater than 30% • About 5-10% of breast cancer cases will have an inherited genetic predisposition to breast cancer, these patients have a lifetime probability of developing breast cancer as high as 80%.

  9. Genetic Factors • 1in 20 breast cancer cases will have a highly penetrant, autosomal dominant genetic predisposition to breast cancer. This translates to 1 in 200 women in the general population. • The majority of these are due to alterations in the genes BRCA1 and BRCA2. • Other genes involved in heriditary breast cancer are p53 and pTEN which are associated with the rare syndromes of Li Fraumini and Cowen disease. • It is possible that alterations in other genes could also increase breast cancer risk. However it is felt these probably effect a weaker influence on breast cancer risk. • Over 1000 different mutations have been detected with BRCA1 and BRCA2. • All are not harmful. • Different mutations may confer a different ammount of risk • The genetic alterations may be transmitted through males as well

  10. Benign Breast Disease • Benign breast disease are the changes seen in the breast secondary to the effect of cyclic monthly ovarian hormonal changes. • These changes are divided into the following categories: • Non proliferative (70%) • Proliferative without atypia (26%) • Proliferative with atypia (4%) • Studies have shown that non-proliferative disease does not increase breast cancer risk (eg fibroadenomas, cysts, mastitis etc.) • Proliferative disease without atypia, marginally increases breast cancer risk; relative risk=1.5. (e.g.. hyperplasia without atypia.) • Proliferative disease with atypia moderately increases breast cancer risk relative risk =5. (e.g. atypical hyperplasia • Carcinoma in situ imparts a relative risk of 8-10

  11. References MacMohan B, Cole P, Brown H. etiology of the human breast cancer: A review. JNCI 1973; 50 21-42 Henderson B, Ross R, Bernstein L. Estrogens as a case of human Cancer. The Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 1998; 48:246-253 Stoll BA, Ed Risk Factors in breast cancer. Chicago: Heinemann Medical Books, 1976: 25-53 S S Falkenberry, R D Legare, Risk factors for Breast Cancer. Obstetrics And Gunecology Clinics Vol29 No1 march 2002 Trichopoulos D, MacMahon B, Cole P. Menopause and breast cancer risk. Bull WHO 1970; 43: 209-221 Miller D, Rosenberg L, Kaufman D. Breast cancer before the age of 45 and oral contraceptive use. New findings. Am J Epidemiol 1989;129 269-280 Bernstein L, Pile M, Krailo M, Henderson B. Update of the Los Angeles study of oral cancer London: Parthenon Publishing Group 1990:169 Henderson I, What can a woman do about her risk of dying of breast cancer? Curr Probl Cancer 1990; 14 166-230 Zollinge T, Phillips R, Kuzma J. Breast cancer survival rates among Seventh Day Adventists and non-Seven Day Aventists. Am J epidemiol; 1984; 119: 503-509 Longnecker P, Berlin J, Orz M. A metaanalysis of alcohol consumption in relation ot brst cancer risk. JAMA 1988; 206 Harvey E Schairer C, Brinton L. Alcohol consumption and breast cancer. JNCI 1987; 78:657 Veer P, Kok F, Hermus R, Sturmans F. Alcohol dose frequency and age at first exposure in relation to the risk of breast cancer. Int J Eidemiol 1989 ;18:511-517 Ottoman R, King M, Pile M, Henderson B. Rractical guide fo estimating risk for familial breast cancer. Lancet 1983; 2: 556-558 Anderson D. Genetic study of breast cancer: Identification of a high risk group. Cancer 1974;34:1090-1097

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