What Factors Influence Decision-Making about Breast Cancer Chemoprevention among High-Risk Women?

1502 Background: More than 250,000 U.S. women have high inherited breast cancer risk; many develop hormone-receptor negative (ER/PR-) tumors, for which no chemoprevention exists. Pre-clinical data suggest that hydrophobic HMG-CoA reductase inhibitors (statins) may reduce risk of ER/PR- breast cancers. We report initial feasibility results of a phase II study of lovastatin for breast cancer chemoprevention. Methods: Study Design: Single-arm, non-randomized phase II study. Agent: Lovastatin 80 mg daily for 6 months. Primary Endpoint: Change in proportion of women with atypical cytology on 2-quadrant random periareolar fine needle aspiration (rpFNA) of breast duct cells before and after lovastatin. Secondary Endpoints: Changes in Ki-67, ER/PR, and elevated levels of oxidative DNA damage (ODD) measured by single-cell gel electrophoresis (Comet) assay of breast duct cells; changes in mammographic density; breast cancer incidence. Eligibility: BRCA1/2 mutation carrier, or estimated lifetime risk = 20% due to family history. Statistical Considerations: Planned sample size of 60, yielding 90% power to detect 50% change in proportion with atypia. Results: Twenty participants enrolled in Year 1; 15 have pre-study rpFNA and 5 have post-study rpFNA results to date. Pre-Study Cytology: N=15: 1 (7%, 95% confidence interval 0–32%) had insufficient, 11 (73%, 48–90%) had normal, and 3 (20%, 6–46%) had atypical cytology. Pre-Study Comet Assay: N=4 to date, 2 with atypical and 2 with normal pre-study cytology: 2 with atypical cytology (100%, 29–100%) had a positive Comet assay for elevated ODD, but 0 with normal cytology (0%, 0–71%) had a positive Comet assay. Post-Study Cytology: N=5, 1 with atypical cytology pre-study: 5 (100%, 51–100%) were normal post-study. Post-Study Comet Assay: N=1 to date, with atypical cytology and positive Comet assay pre-study: cytology was normal and Comet assay negative post-study. The study has been well-tolerated, with no drop-out. Conclusions: An early-stage chemoprevention study of lovastatin for 6 months, including 2 rpFNAs, appears feasible in high-risk women. Early results suggest a correlation between cytologic atypia and elevated levels of ODD, and the possibility that lovastatin might reverse these abnormalities. Accrual is ongoing. No significant financial relationships to disclose.

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Chemoprevention for Breast Cancer: Overcoming Barriers to Treatment

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2012.32.152 ◽

2012 ◽

pp. 85-90 ◽

Cited By ~ 4

Author(s):

Abenaa M. Brewster ◽

Nancy E. Davidson ◽

Worta McCaskill-Stevens

Keyword(s):

Breast Cancer ◽

High Risk ◽

Randomized Clinical Trials ◽

Cancer Chemoprevention ◽

The United States ◽

Develop Breast Cancer ◽

Net Benefit ◽

Eligibility Criteria ◽

High Risk Women ◽

Breast Cancer Chemoprevention

Overview: Evidence from placebo-controlled, randomized clinical trials supports the use of chemoprevention in women at high risk for developing breast cancer, and two agents—tamoxifen and raloxifene—are U.S. Food and Drug Administration (FDA)-approved for the indication. Despite clinical guidelines that recommend physicians counsel high-risk women about the use of chemoprevention and the estimated 2.4 million women in the United States who meet eligibility criteria for net benefit, the uptake of breast cancer chemoprevention has been exceedingly low. Assessments of the risks and benefits of chemoprevention are aided by the availability of models that can be used to estimate of the risk–benefit ratio. However, many physicians remain unaware of these resources to determine patient eligibility for chemoprevention and lack the time to provide informed counseling to their patients. The barriers for patients' acceptance of chemoprevention treatment include fear of side effects and the perception that chemoprevention will not substantially lower their risk of developing breast cancer. Despite these challenges, there are substantial opportunities to increase the utilization of chemoprevention. These strategies include education, dissemination of user-friendly risk–benefit models, and the support of research efforts focused on identifying biomarkers that can more accurately select women most likely to develop breast cancer and predict responsiveness of treatment.

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The Role of Breast Cancer Chemoprevention in High-Risk Women

Breast Cancer Management for Surgeons ◽

10.1007/978-3-319-56673-3_8 ◽

2017 ◽

pp. 79-87

Author(s):

Lynda Wyld

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cancer Chemoprevention ◽

High Risk Women ◽

Breast Cancer Chemoprevention

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Atypia in Random Periareolar Fine-Needle Aspiration Affects the Decision of Women at High Risk to Take Tamoxifen for Breast Cancer Chemoprevention

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-06-0910 ◽

2007 ◽

Vol 16 (5) ◽

pp. 1032-1034 ◽

Cited By ~ 18

Author(s):

V. K. Goldenberg ◽

V. L. Seewaldt ◽

V. Scott ◽

G. R. Bean ◽

G. Broadwater ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Fine Needle Aspiration ◽

Cancer Chemoprevention ◽

Needle Aspiration ◽

Fine Needle ◽

Breast Cancer Chemoprevention

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The Lack, Need, and Opportunities for Decision-Making and Informational Tools to Educate Primary-Care Physicians and Women about Breast Cancer Chemoprevention: Fig. 1.

Cancer Prevention Research ◽

10.1158/1940-6207.capr-10-0100 ◽

2010 ◽

Vol 3 (6) ◽

pp. 686-688 ◽

Cited By ~ 33

Author(s):

Peter M. Ravdin

Keyword(s):

Breast Cancer ◽

Primary Care ◽

Decision Making ◽

Primary Care Physicians ◽

Cancer Chemoprevention ◽

Breast Cancer Chemoprevention

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Addressing Barriers to Uptake of Breast Cancer Chemoprevention for Patients and Providers

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2015.35.e50 ◽

2015 ◽

pp. e50-e58 ◽

Cited By ~ 8

Author(s):

Katherine D. Crew

Keyword(s):

Breast Cancer ◽

Primary Prevention ◽

High Risk ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Chemoprevention ◽

The United States ◽

Cancer Risk Assessment ◽

Breast Cancer Risk Assessment ◽

Breast Cancer Chemoprevention

Breast cancer is the most common malignancy among women in the United States, and the primary prevention of this disease is a major public health issue. Because there are relatively few modifiable breast cancer risk factors, pharmacologic interventions with antiestrogens have the potential to significantly affect the primary prevention setting. Breast cancer chemoprevention with selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene, and with aromatase inhibitors (AIs) exemestane and anastrozole, is underutilized despite several randomized controlled trials demonstrating up to a 50% to 65% relative risk reduction in breast cancer incidence among women at high risk. An estimated 10 million women in the United States meet high-risk criteria for breast cancer and are potentially eligible for chemoprevention, but less than 5% of women at high risk who are offered antiestrogens for primary prevention agree to take it. Reasons for low chemoprevention uptake include lack of routine breast cancer risk assessment in primary care, inadequate time for counseling, insufficient knowledge about antiestrogens among patients and providers, and concerns about side effects. Interventions designed to increase chemoprevention uptake, such as decision aids and incorporating breast cancer risk assessment into clinical practice, have met with limited success. Clinicians can help women make informed decisions about chemoprevention by effectively communicating breast cancer risk and enhancing knowledge about the risks and benefits of antiestrogens. Widespread adoption of chemoprevention will require a major paradigm shift in clinical practice for primary care providers (PCPs). However, enhancing uptake and adherence to breast cancer chemoprevention holds promise for reducing the public health burden of this disease.

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