A 58 yo post-menopausal female
presents for F/U. She is concerned about her risk for breast
cancer and wants to know if there is preventative therapy. She is uptodate on
mammogram screening with normal results. Her sister was diagnosed with breast
cancer at age 65. She has no children and menarche was at age 11. What should
you do?
a. half-yearly mammograms
b. reassurance
c. discuss tamoxifen (correct answer)
d. prophylactic mastectomies
According to the Gail
model or Breast Cancer Risk Assessment Tool (BCRAT), this patient has a 3.1% risk of developing breast
cancer in the next 5 years. The Gail model is a clinical tool to help
physicians calculate a woman’s individual risk of developing breast cancer over
the next five years based on current age, age of menarche, age of first live
birth, first degree relatives with breast cancer, prior breast biopsies, and
race. The tool was created based on the Care Trial (looking specifically at
African Americans) and Breast Cancer Detection Demonstration
Project. The tool is not intended for women with a history suggesting inherited
breast cancer.
The SERMs tamoxifen and raloxifene
reduce the risk for new breast cancer by as much as 50%. For premenopausal
women, tamoxifen is the only Food and Drug Administration–approved SERM for
breast cancer prevention. For postmenopausal women, both tamoxifen and
raloxifene are Food and Drug Administration–approved therapies. Use of these
agents is approved for women with Gail model scores of greater than 1.7% for
the risk of breast cancer over the next 5 years. Side effect profiles dictate
whether tamoxifen or raloxifene should be used. Both the American Society of
Clinical Oncology and USPSTF recommend discussing the risks/benefts of breast
cancer prevention with these high risk women and starting a SERM if benefits outweigh
risks. There are many risks to these therapies which would warrant not starting
medication including but not limited to uterine cancer. Models have been
developed to estimate the risk/benefit ratio of raloxifene and tamoxifen for
postmenopausal women based upon their risk factors and can assist in risk
discussions
The American Breast Cancer Prevention Trial sponsored by
the National Surgical Adjuvant Breast and Bowel Project (NSABP) first
showed the benefits of tamoxifen for breast cancer prevention. Women were
eligible for the NSABP trial if they were considered to be "at increased
risk" for breast cancer (age;60yrs or age 35-59 with a Gail score of
at least 1.66%) and randomized to receive tamoxifen 20mg/daily vs. placebo. The
study was stopped early after a median follow-up of 48 months when an interim
analysis found that the benefit of tamoxifen was already statistically
significant showing a relative risk reduction of 43% (2.5% vs. 4.3%) of
invasive breast cancer and 37% for non-invasive breast cancer. The reduction
was entirely by a decrease in ER-positive tumors and thus there was no
significant change in occurrence of ER-negative tumors. Older women were found
to have derived the most benefit. However, there was no difference in overall
or breast cancer specific-survival between those receiving tamoxifen versus
those receiving placebo
