September 03, 2014
   
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The Genetics of Breast and Associated Cancers
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The Genetics of Breast and Associated Cancers

 
Ms. Barrick is Genetic Counselor, Division of Hematology and Oncology; Ms. Petrucellil is Clinical Assistant Professor, Senior Genetic Counselor/Coordinator, Division of Hematology and Oncology and Population Studies and Prevention Program; Michael S. Simon is Professor of Medicine and Oncology, Division of Hematology and Oncology and Population Studies and Prevention Program; all at the Karmanos Cancer Institute at Wayne State University, Detroit, MI.

The American Cancer Society estimates that in 2009 there were 192,370 new cases and 40,170 deaths from breast cancer, making breast cancer the most common cancer and the second leading cause of cancer death among women in the United States(1). The average lifetime risk of breast cancer in women is 1 in 8 or 12.6%.(2)

Breast Cancer Risk Factors

Your risk of developing breast cancer is strongly influenced by:

  • Your age
  • Family history(3)
  • Reproductive factors(4)
  • Exposure to exogenous estrogen(5)
  • Exposure to alcohol(6)
  • An abnormal breast biopsy showing atypical cells(7)
  • A hereditary predisposition due to mutations in one of several breast cancer genes(8)(9)(10)(11)(12)(13)

Rates Are Going Down
Between 1980 and 1987, the number of new cases (incidence) of breast cancer increased about 3.7% each year.(14) It is believed that this was due to the increasing use of mammograms.(15) From 1987 to 2001 the rate of increase dropped to 0.5% per year, and between 2001 and 2004 rates decreased by 3.5% per year.(14) This recent decline is thought to reflect a decline in the use of hormone therapy, the result of the publication of the Women’s Health Initiative trial showing a 26% increase in breast cancer risk associated with postmenopausal estrogen and progesterone use.(16)

The reason for this much higher death rate among African-American women may be the result of socioeconomic, cultural and behavioral factors that affect access to screening and treatment, both of which are highly correlated with survival.

In the United States, the incidence of breast cancer is higher among white compared to African-American women, except among younger women where the trends are reversed.(17)(18)(19) But the death rates are higher among African-American women.(19)(20)(21) The reason for this much higher death rate among African-American women may be the result of socioeconomic, cultural and behavioral factors that affect access to screening (22) and treatment,(23) both of which are highly correlated with survival. In addition, African-American women are more likely to have certain breast cancers that are tougher to treat.(24)

Family history — having several first or second degree relatives with breast cancer, and/or relatives with breast cancer diagnosed before age 50— is one of the strongest risk factors for the development of breast cancer. There are a number of different methods used to assess lifetime risk estimates for breast cancer. These estimates are then used for counseling patients, and determining eligibility for chemo-prevention trials;(25)(26)(27)(28) and determining eligibility for MRI screening as an adjunct to mammography.(29)(30)

Bodily Clues to Breast Cancer Risk
From 5-10% of women with breast cancer have mutations in genes that make it more likely they will get the disease. The helpful news is that many breast cancer patients have genetic changes which both predict the likelihood of cancer recurrence and how well they’ll do if it recurs.(31) Oncotype DX® and MammaPrint are two genetic tests for women with early stage breast cancer which help doctors decide which therapies (chemotherapy or other therapies) might work best.(32) One gene is called HER2, which stands for human epidermal growth factor receptor 2. Researchers have found that it is over-expressed in 10-20% of women with breast cancer(33) causing tumor cells to grow at an abnormally high rate and to increase the chance of metastasizing.(34)(35) There are some treatments that are designed to target HER2-positive breast cancers specifically – Trastuzumab is an example of one therapy that inhibits HER235 and leads to better prognosis and survival.(32)(36)(37)(38)

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