Fabian, Carol J.

PURPOSE To update the ASCO guideline on pharmacologic interventions for breast cancer risk reduction and provide guidance on clinical issues that arise when deciding to use endocrine therapy for breast cancer risk reduction. METHODS An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS A randomized clinical trial that evaluated the use of anastrozole for reduction of estrogen receptor–positive breast cancers in postmenopausal women at increased risk of developing breast cancer provided the predominant basis for the update. UPDATED RECOMMENDATIONS In postmenopausal women at increased risk, the choice of endocrine therapy now includes anastrozole (1 mg/day) in addition to exemestane (25 mg/day), raloxifene (60 mg/day), or tamoxifen (20 mg/day). The decision regarding choice of endocrine therapy should take into consideration age, baseline comorbidities, and adverse effect profiles. Clinicians should not prescribe anastrozole, exemestane, or raloxifene for breast cancer risk reduction to premenopausal women. Tamoxifen 20 mg/day for 5 years is still considered standard of care for risk reduction in premenopausal women who are at least 35 years old and have completed childbearing. Data on low-dose tamoxifen as an alternative to the standard dose for both pre- and postmenopausal women with intraepithelial neoplasia are discussed in the Clinical Considerations section of this article. Additional information is available at www.asco.org/breast-cancer-guidelines .

LBA504 Background: Limited efficacy and serious toxicities have limited uptake of tamoxifen or raloxifene as preventatives of breast cancer. Aromatase inhibitors (AIs) prevent contralateral breast cancers more than tamoxifen in adjuvant trials and have fewer serious side effects. This is the first report of an AI used in primary prevention. Methods: NCIC CTG MAP.3 is a randomized trial designed to detect a 65% reduction in annual incidence of invasive breast cancer (IBC) on exemestane (E) versus placebo (P). Eligible postmenopausal women had ≥ one of the following risk factors: Gail score >1.66%, prior ADH, ALH, LCIS or DCIS with mastectomy, age over 60. Health-related and menopause-specific quality of life (QOL) were assessed by SF-36 and MENQOL questionnaires. Results: From 2004-2010, 4,560 women were randomized: age 62.5 yrs (37-90); Gail Score 2.3 % (0.6-21); BMI 28.0 kg/m2 (15.9-65.4). Risk factors included: age >60 yrs (49%); Gail score >1.66 (40%); and prior ADH, ALH, LCIS or DCIS with mastectomy (11%). At median follow-up of 35 months there were 11 IBCs on E and 32 on P (annual incidence 0.19% vs 0.55%; HR= 0.35, 95% CI 0.18-0.70, p = 0.002); ductal (10E/27P), lobular (1E/5P). Most tumors were ER positive (7E/27P); Her2/neu negative (10E/26P); TNM stage T1 (8E/28P), N0 (7E/22P), M0 (11E/30P). E was superior in all subgroups: by Gail score, age, BMI, prior LCIS and DCIS. The annual incidence rate of IBC or DCIS was 0.35% E and 0.77% P (HR=0.47;95% CI 0.27-0.79; p = 0.004) based on 64 IBCs or DCISs (20E/44P). Clinical bone fractures, osteoporosis, hypercholesterolemia or cardiovascular events were equal in both arms. No clinically meaningful differences in QOL were detected. Conclusions: Exemestane significantly reduced invasive and pre-invasive breast cancers in postmenopausal women at increased risk for breast cancer with no serious toxicities. Exemestane should be considered a new option for primary prevention of breast cancer. Supported by the Canadian Cancer Society; Pfizer Inc. PEG supported in part by Avon Foundation.

Purpose To assist in determining barriers to an oncology career incorporating cancer prevention, the American Society of Clinical Oncology (ASCO) Cancer Prevention Workforce Pipeline Work Group sponsored surveys of training program directors and oncology fellows. Methods Separate surveys with parallel questions were administered to training program directors at their fall 2013 retreat and to oncology fellows as part of their February 2014 in-training examination survey. Forty-seven (67%) of 70 training directors and 1,306 (80%) of 1,634 oncology fellows taking the in-training examination survey answered questions. Results Training directors estimated that ≤ 10% of fellows starting an academic career or entering private practice would have a career focus in cancer prevention. Only 15% of fellows indicated they would likely be interested in cancer prevention as a career focus, although only 12% thought prevention was unimportant relative to treatment. Top fellow-listed barriers to an academic career were difficulty in obtaining funding and lower compensation. Additional barriers to an academic career with a prevention focus included unclear career model, lack of clinical mentors, lack of clinical training opportunities, and concerns about reimbursement. Conclusion Reluctance to incorporate cancer prevention into an oncology career seems to stem from lack of mentors and exposure during training, unclear career path, and uncertainty regarding reimbursement. Suggested approaches to begin to remedy this problem include: 1) more ASCO-led and other prevention educational resources for fellows, training directors, and practicing oncologists; 2) an increase in funded training and clinical research opportunities, including reintroduction of the R25T award; 3) an increase in the prevention content of accrediting examinations for clinical oncologists; and 4) interaction with policymakers to broaden the scope and depth of reimbursement for prevention counseling and intervention services.