Breast Cancer Risk Reduction: Strategies for Women at Increased Risk

OBJECTIVE: To conduct an evidence-based technology assessment to determine whether tamoxifen and raloxifene as breast cancer risk-reduction strategies are appropriate for broad-based conventional use in clinical practice. POTENTIAL INTERVENTION: Tamoxifen and raloxifene. OUTCOME: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefits. EVIDENCE: A comprehensive, formal literature review was conducted for tamoxifen and raloxifene on the following topics: breast cancer risk reduction; tamoxifen side effects and toxicity, including endometrial cancer risk; tamoxifen influences on nonmalignant diseases, including coronary heart disease and osteoporosis; and decision making by women at risk for breast cancer. Testimony was collected from invited experts and interested parties. VALUES: More weight was given to publications that described randomized trials. BENEFITS/HARMS/COSTS: The American Society of Clinical Oncology (ASCO) Working Group acknowledges that a woman's decision regarding breast cancer risk-reduction strategies will depend on the importance and weight attributed to the information provided regarding both cancer and non–cancer-related risks. CONCLUSIONS: For women with a defined 5-year projected risk of breast cancer of ≥ 1.66%, tamoxifen (at 20 mg/d for up to 5 years) may be offered to reduce their risk. It is premature to recommend raloxifene use to lower the risk of developing breast cancer outside of a clinical trial setting. On the basis of available information, use of raloxifene should currently be reserved for its approved indication to prevent bone loss in postmenopausal women. Conclusions are based on single-agent use of the drugs. At the present time, the effect of using tamoxifen or raloxifene with other medications (such as hormone replacement therapy), or using tamoxifen and raloxifene in combination or sequentially, has not been studied adequately. The continuing use of placebo-controlled trials in other risk-reduction trials highlights the current unanswered issues concerning the use of such interventions, especially when the influence on net health benefit remains to be determined. Breast cancer risk reduction is a rapidly evolving area. This technology assessment represents an ongoing process with existing plans to monitor and review data and to update recommendations in a timely matter. (See Table 1 for a summary of conclusions.) VALIDATION: The conclusions of the Working Group were evaluated by the ASCO Health Services Research Committee and by the ASCO Board of Directors. SPONSOR: American Society of Clinical Oncology.

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Preferences for breast cancer prevention among women with a BRCA1 or BRCA2 mutation

Hereditary Cancer in Clinical Practice ◽

10.1186/s13053-020-00152-z ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Carol A. Mansfield ◽

◽

Kelly A. Metcalfe ◽

Carrie Snyder ◽

Geoffrey J. Lindeman ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Risk Reduction ◽

Online Survey ◽

Brca2 Mutation ◽

Bilateral Mastectomy ◽

Reduction Strategies ◽

Risk Reduction Strategies ◽

Cancer Risk Reduction

Abstract Background Women with a BRCA1 or BRCA2 mutation have high lifetime risks of developing breast and ovarian cancer. The decision to embark on risk reduction strategies is a difficult and personal one. We surveyed an international group of women with BRCA mutations and measured choices and sequence of breast cancer risk reduction strategies. Methods Women with a BRCA1/2 mutation and no previous cancer diagnosis were recruited from the US, Canada, the UK, Australia, and from a national advocacy group. Using an online survey, we asked about cancer-risk reduction preferences including for one of two hypothetical medicines, randomly assigned, and women’s recommendations for a hypothetical woman (Susan, either a 25- or 36-year-old). Sunburst diagrams were generated to illustrate hierarchy of choices. Results Among 598 respondents, mean age was 40.9 years (range 25–55 years). Timing of the survey was 4.8 years (mean) after learning their positive test result and 33% had risk-reducing bilateral salpingo-oophorectomy (RRBSO) and bilateral mastectomy (RRBM), while 19% had RRBSO only and 16% had RRBM only. Although 30% said they would take a hypothetical medicine, 6% reported taking a medicine resembling tamoxifen. Respondents were 1.5 times more likely to select a hypothetical medicine for risk reduction when Susan was 25 than when Susan was 36. Women assigned to 36-year-old Susan were more likely to choose a medicine if they had a family member diagnosed with breast cancer and personal experience taking tamoxifen. Conclusions Women revealed a willingness to undergo surgeries to achieve largest reduction in breast cancer risk, although this would not be recommended for a younger woman in her 20s. The goal of achieving the highest degree of cancer risk reduction is the primary driver for women with BRCA1 or BRCA2 mutations in selecting an intervention and a sequence of interventions, regardless of whether it is non-surgical or surgical.

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Breast Cancer Risk Reduction and Counseling: Lifestyle, Chemoprevention, and Surgery

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2007.0071 ◽

2007 ◽

Vol 5 (8) ◽

pp. 800-808 ◽

Cited By ~ 2

Author(s):

Martin C. Mahoney

Keyword(s):

Breast Cancer ◽

Risk Assessment ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Risk Reduction ◽

Assessment Tools ◽

Surgical Approaches ◽

Increased Risk ◽

Breast Cancer Risk Reduction ◽

Cancer Risk Reduction

Qualitative and quantitative approaches to risk assessment are useful for identifying women at increased risk for developing breast cancer for whom genetics consultation, individualized surveillance recommendations, or chemoprevention may be appropriate. A comprehensive medical and family history review can be used to stratify women into categories of breast cancer risk. A quantitative estimate of the probability of developing breast cancer can be determined using risk assessment tools, such as the Gail and Claus models. Women at increased risk for breast cancer may benefit from individualized approaches to breast cancer risk reduction. Prevention strategies for reducing breast cancer risk include lifestyle modifications, chemoprevention, surgical approaches, and pharmacotherapy.

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Use of Endocrine Therapy for Breast Cancer Risk Reduction: ASCO Clinical Practice Guideline Update

Journal of Clinical Oncology ◽

10.1200/jco.19.01472 ◽

2019 ◽

Vol 37 (33) ◽

pp. 3152-3165 ◽

Cited By ~ 20

Author(s):

Kala Visvanathan ◽

Carol J. Fabian ◽

Elissa Bantug ◽

Abenaa M. Brewster ◽

Nancy E. Davidson ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Postmenopausal Women ◽

Risk Reduction ◽

Endocrine Therapy ◽

Premenopausal Women ◽

Increased Risk ◽

Breast Cancer Risk Reduction ◽

Cancer Risk Reduction

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 .

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The STAR Trial: Evidence for Raloxifene as a Breast Cancer Risk Reduction Agent for Postmenopausal Women

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2007.0073 ◽

2007 ◽

Vol 5 (8) ◽

pp. 817-822 ◽

Cited By ~ 17

Author(s):

Therese B. Bevers

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Postmenopausal Women ◽

Risk Reduction ◽

Prophylactic Surgery ◽

Increased Risk ◽

Breast Cancer Risk Reduction ◽

Star Trial ◽

Cancer Risk Reduction

The 1998 approval of tamoxifen for breast cancer risk reduction opened the era of breast cancer chemoprevention. Women at increased risk for breast cancer now had an option other than healthy lifestyle and prophylactic surgery to reduce risk. However, women and their physicians were reluctant to use tamoxifen because of associated risks. Several trials investigating raloxifene suggested it may reduce breast cancer risk without having an apparent effect on the endometrium. The Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer trial opened in 1999 to directly compare raloxifene to tamoxifen for breast cancer risk reduction. Since the unblinding of the STAR trial in 2006, raloxifene has emerged as an option for reducing breast cancer risk for postmenopausal women at increased risk for the disease.

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Prophylactic Mastectomy - Evaluation and Treatment of High Risk Patients

Swiss Surgery ◽

10.1024/1023-9332.8.2.45 ◽

2002 ◽

Vol 8 (2) ◽

pp. 45-52 ◽

Cited By ~ 3

Author(s):

Remmel ◽

Harder

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Risk Reduction ◽

Prophylactic Mastectomy ◽

Interdisciplinary Approach ◽

Reconstructive Procedures ◽

Medline Search ◽

Breast Cancer Risk Reduction ◽

Cancer Risk Reduction

Prophylactic mastectomy is an aggressive strategy for breast cancer risk reduction. The indications and efficiency of this procedures are not yet clearly defined. Randomized, prospective studies, comparing different surgical procedures with other modalities of breast cancer risk reduction are lacking. The report evaluates the existing controversy, based on Medline search in the following sequence: risk factors, possibilities of risk reduction, effectiveness of risk reduction, technical considerations and recommendations. Patient selection is difficult and needs an interdisciplinary approach. The women have to be well informed about all treatment alternatives and various reconstructive procedures. An appropriate risk reduction strategy should be selected individually for each patient. Up to now, there exist only recommendations from different institutions but no definitive guidelines.

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