Just over two years have passed since findings of the Mammary Prevention Trial (MAP.3) of the aromatase inhibitor exemestane (Aromasin) were presented at ASCO and greeted with unabashed enthusiasm.
The study included more than 4,500 postmenopausal women in the United States, Canada, Spain, and France identified as being at increased risk for breast cancer. Results, reported by lead investigator Paul Goss, MD, of Massachusetts General Hospital, Boston, were indeed dramatic.
After a follow-up period of three years, exemestane had achieved a 65 percent relative reduction in the annual incidence of invasive breast cancer. Thus, exemestane was shown to be more effective than the selective estrogen-receptor modulators (SERMs) tamoxifen and raloxifene, the two agents most often used for chemoprevention. Moreover, exemestane was not associated with any of the significant side effects of SERMs, including vasomotor symptoms, venous thrombosis, and cataracts, nor with increased risk of uterine cancer, which can occur with tamoxifen.
Aromatase inhibitors, however, decrease bone density, often a major concern for postmenopausal women. Goss said exemestane was studied in MAP.3 because it causes less bone loss than other aromatase inhibitors. No differences were observed in incidence of clinical bone fractures and self-reported osteoporosis between women who received placebo and those who received exemestane, he noted.
At the 2011 ASCO meeting, MAP.3 was hailed by discussant Andrea DeCensi, MD, of E.O. Ospedali Galliera, Genoa, Italy, as a “landmark study” that would “change the paradigm of breast cancer prevention." Up to now chemoprevention has not been a major part of the paradigm. Only a small percentage of women, even those considered to be at high risk, opt to receive chemoprevention medication.
Needless to say it is too early to gauge whether the availability of exemestane will lead more women to choose chemoprevention. But a poster presented at ASCO last month (Abstract 1565) reported findings of a small study that shed light on some of the challenges.
“Clinical use and uptake of exemestane in the clinical setting has not been reported to date,” noted the investigators, led by Erin W. Hofstatter, MD, of the Yale Cancer Center, New Haven, Conn. “The purpose of this study was to assess exemestane use in a breast cancer prevention clinic and obtain a descriptive clinical overview of this patient population.” Findings were presented by coauthor Mia Sorkin, MPH, of the Yale School of Public Health.
A retrospective chart review was used to determine patient characteristics, medical history, and chemoprevention uptake of all postmenopausal women presenting to the Yale Breast Cancer Prevention Clinic between November 2011 and November 2012. Postmenopausal women without prior SERM use and with no medical contraindications to chemoprevention therapy were eligible for initiation of chemoprevention and analysis. Risk categories included 22 women (39 percent) diagnosed with breast atypia, 7 (12 percent) with lobular carcinoma in situ, 4 (7 percent) with prior ductal carcinoma in situ, 41 (73 percent) with family history of breast cancer, and 8 (14 percent) with a deleterious BRCA1 or BRCA2 mutation. Twenty-two (39 percent) had osteopenia or osteoporosis.
Thirteen (23 percent) of the 56 eligible women opted to start a chemoprevention medication; 8 opted for raloxifene, 4 for exemestane, and 1 for tamoxifen. The investigators noted:
While exemestane comprised 30.7 percent of chemoprevention medication uptake, only 4 (7 percent) of the entire sample of 56 eligible candidates decided to take exemestane. Chemoprevention uptake rates of postmenopausal women in the setting of a breast cancer prevention clinic (23 percent) are higher than those reported in the general population, but remain low overall… A large proportion (39 percent) of postmenopausal women have osteopenia or osteoporosis, which limits exemestane uptake in breast cancer prevention setting.
Although interpretation of the data is limited by the small sample size, the investigators said the results “provide practical implications for the clinical use of exemestane in a prevention setting." Further investigations, they concluded, “should focus on understanding factors that influence and predict chemoprevention uptake, including perceptions of risk-benefit ratios among patients and their providers.”
ASCO has just announced the addition of exemestane to its updated guidelines on use of pharmacologic interventions to reduce risk for breast cancer. Exemestane is now included for prevention of breast cancer in postmenopausal women at risk for estrogen receptor (ER)-positive disease. Previous guidelines, published in 2009, cautioned that exemestane only be used for prevention of breast cancer in a clinical trial setting.
Will the updated guidelines have much effect? Will there be a “new paradigm” for chemoprevention of breast cancer any time soon? Or is there still so much fear of the dreaded “chemo” among the general population that it unduly influences the choices made by those told they are at risk?
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