Reducing the risk of breast cancer: A personalized approach
Although primary care physicians often use the same screening schedule and preventive measures for all the women they see, optimal breast cancer risk reduction requires an individualized approach.
How to proceed? Talk to patients in the 40- to 50-year age range about the benefits and risks of earlier, more frequent screening vs waiting until 50 to start mammography and opting for screening every 2 years. Breast health awareness and the role of clinical breast exams also should be included in a balanced discussion of early detection of breast cancer. A review of the patient’s reproductive status and use of hormone preparations is appropriate, as well.4,5
Patients at high risk (a Gail model score >1.66%; a history of ADH, ALH, or lobular carcinoma in situ; or a family history of breast cancer)3 should be advised to have a clinical breast exam every 6 months and annual mammograms. High-risk patients should also be offered the option of chemoprevention with tamoxifen, raloxifene,27,28 or exemestane29 if the benefits of treatment outweigh the risk of potential adverse effects. The merits of MRI breast surveillance have not been defined for women with this level of risk.14
For very high-risk patients (those with a family history that strongly suggests a genetic predisposition, a confirmed gene mutation, evidence of hereditary breast and ovarian cancer, or a personal history of chest wall irradiation between the ages of 10 and 30 years), a discussion of more aggressive risk-reduction strategies is recommended.4 A clinical breast exam and mammogram should be performed beginning at age 25—or 5 to 10 years before the earliest age at which a first-degree relative was diagnosed.
Starting at age 30, patients at very high risk should undergo annual mammography and breast MRI, either simultaneously or staggered every 6 months, along with a twice-yearly clinical breast exam.14 Breast health awareness and lifestyle modification should be emphasized, and the benefits and risks of chemoprevention should be discussed. Surgical risk-reduction strategies, such as prophylactic mastectomy and oophorectomy, should also be discussed, along with the offer of a referral to a surgeon for consultation.5
What to tell patients about chemoprevention
The USPSTF has issued a grade B recommendation to a discussion of chemoprevention for women who are at high risk for breast cancer and low risk for an adverse event.30 Counseling a patient regarding the risks and benefits of chemoprevention will depend on her age, comorbidities, whether or not she has had a hysterectomy, and her willingness to take the suggested medication.
Selective estrogen receptor modulators (SERMs). The American Society of Clinical Oncology Clinical Practice Guideline Update has reviewed the benefits and potential adverse effects of the SERMs tamoxifen and raloxifene. The Society supports the use of tamoxifen in pre- and postmenopausal women for breast cancer risk reduction; it also supports the use of raloxifene for postmenopausal women, the only patient population for which raloxifene has been approved.27
In a review of 7 placebo-controlled, randomized clinical trials and one head-to-head trial, both drugs reduced the risk for invasive, estrogen receptor–positive breast cancer by about 40% compared with placebo. Breast cancer deaths, however, did not decrease.31
Both tamoxifen and raloxifene were found to increase bone mineral density and reduce fracture risk.31 Thromboembolic events—which occurred less frequently with raloxifene than tamoxifen—was the chief adverse effect, with an incidence of 0.4% to 0.7%. In addition, fewer cases of endometrial cancer were reported with raloxifene compared with tamoxifen, making raloxifene the preferred treatment for postmenopausal women with an intact uterus.31
The National Surgical Adjuvant Breast and Bowel Project STAR study—one of the trials included in the review—initially reported that tamoxifen and raloxifene were equivalent in reducing breast cancer risk in postmenopausal women at increased risk.28 In an updated analysis based on 81 months of use, however, tamoxifen resulted in a 50% reduction in the incidence of breast cancer vs a reduction of 38% for raloxifene.32
The greater reduction in breast cancer risk seen with tamoxifen comes at a potential cost. Tamoxifen was found to have a worse adverse effect profile, leading to a higher risk for endometrial hyperplasia and hysterectomy, as well as thromboembolic events. The difference in all-cause mortality, however, was not statistically significant.32
Aromatase inhibitor therapy. The National Cancer Institute of Canada recently published a major chemoprevention trial, evaluating the effectiveness of aromatase inhibition in breast cancer risk reduction.29 This randomized, double-blind trial of exemestane vs placebo included more than 4500 women with a median follow-up of 3 years, and found that the exemestane reduced the incidence of invasive breast cancer in postmenopausal women at moderate risk by 65% (hazard ratio=0.35; 95% confidence interval, 0.18-0.70; P=.002).29
IBIS-II, a multicenter study in the United Kingdom, randomly assigned 6000 women at increased risk for breast cancer to placebo or anastrozole, an alternative aromatase inhibitor. This trial is ongoing, and breast cancer incidence is the primary endpoint.33 Aromatase inhibitors have not been approved by the US Food and Drug Administration for breast cancer prevention.34
