SAN FRANCISCO—A number of interventions can help reduce breast cancer among women at high risk, but uptake is sluggish, and there can be confusion about which agent to prescribe to a given patient. Seema Khan, MD, professor of surgery at Northwestern University Feinberg School of Medicine, Chicago, addressed the topic of pharmacologic risk reduction at the 2011 Breast Cancer Symposium.
“It’s clear that selective estrogen receptor modulators [SERMs; tamoxifen and raloxifene] reduce risk, but uptake is poor. High on our priority list is better risk assessment of women at sufficiently high risk to benefit from such preventive therapy,” she said.
Even in high-risk women, fewer than 15% use any means of chemoprevention, and this rate falls to about 5% when patients in clinical trials are excluded.
But many women could benefit. An example is a 45-year-old woman with 1 first-degree relative with breast cancer and 1 biopsy showing atypical hyperplasia. Her 5-year risk is almost 5% (compared with 1% for an average-risk peer) and her lifetime risk is 37% (vs 12%), Khan noted.
Choosing an Agent
For such women, the type of pharmacologic intervention depends on menopausal status and age, hysterectomy status, bone mineral density status, mutation carrier status, and whether ductal carcinoma in situ (DCIS) has been found (Figure).
For premenopausal women, tamoxifen is the preferred agent. Tamoxifen has been shown to cut risk by at least two thirds in women with lobular carcinoma in situ or atypical hyperplasia. For postmenopausal women, raloxifene or the aromatase inhibitor exemestane are recommended (based on recent data); patients who have had a hysterectomy also may consider tamoxifen (because adverse effects on the uterus are moot).
“Women at risk for sporadic breast cancer are most likely to benefit from SERMs, and BRCA2 carriers are more likely to benefit than BRCA1 carriers. Data also are emerging to suggest that estrogen receptor (ER)-positive patients are more likely to benefit than ER-negative ones and, for women with DCIS, tamoxifen is marginally better than raloxifene,” she said.
A recent analysis determined the relative risks and benefits of tamoxifen and raloxifene in a variety of clinically relevant scenarios (Freedman AN, et al. J Clin Oncol. 2011;29:2327-2333). Over a 5-year period, postmenopausal women with an intact uterus had a better benefit–risk ratio for raloxifene than with tamoxifen, but for those without a uterus the ratio was similar.
In particular, the analysis showed that regardless of ethnicity, older women (aged 70-79 years) with a lower risk of breast cancer seem to derive little benefit from either agent. Non-Hispanic white women aged 50 to 70 years at high risk, with an intact uterus, have a more favorable benefit– risk ratio with raloxifene. In the absence of a uterus, both tamoxifen and raloxifene are reasonable options in many scenarios. In black women, the pattern is similar.
Freedman and colleagues summarized the benefits and risks into an index, which can complement clinical evaluation in deciding whether to initiate chemoprevention and in comparing the benefits and risks of raloxifene versus tamoxifen.
Based on recent data showing a 65% risk reduction for ER-positive breast cancer, “exemestane can certainly be introduced into the category of drugs to consider for chemoprevention,” Khan added, but she had concerns about adverse effects and short follow-up in the MA.3 trial (Goss PE, et al. N Engl J Med. 2011;364:2381-2391).
In the future, other options may prove effective for chemoprevention, she said, including low-dose tamoxifen, tamoxifen gel, the bisphosphonates, metformin, fenretinide, and poly [ADP-ribose] polymerase (PARP) inhibitors.