Raloxifene Hydrochloride

Bisphosphonates are the first-line pharmacologic treatment for postmenopausal osteoporosis and the most commonly prescribed medication for this condition.1 Bisphosphonates, classified as antiresorptive agents, have a very high affinity for bone mineral and bind to hydroxyapatite crystals on bony surfaces, where they inhibit osteoclast-mediated bone resorption.

Author/s:

Ensrud, KE, Crandall, CJ

Final Update Summary: Breast Cancer: Medication Use to Reduce Risk

John Bayhi — Wed, 04 Sep 2019 17:50:29 +0000

Date Added:

September 4, 2019

Journal/Publication:

US Preventative Services Task Force / JAMA

Publisher:

American Medical Association

Publication Date:

September 3, 2019

Issue:

322

Volume:

Pages:

857-867

URL:

Final Update Summary: Breast Cancer: Medication Use to Reduce Risk

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2019.11885

Keywords

PMID (1):

31479144

MeSH

breast neoplasms

risk reduction behavior

biopsy

risk assessment

tamoxifen

Raloxifene Hydrochloride

aromatase inhibitors

It looks like all women need to be assessed for risk of breast cancer so that high-risk women can be offered medications to reduce risk. James W. Mold, MD, MPH

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IMPORTANCE:

Breast cancer is the most common nonskin cancer among women in the United States and the second leading cause of cancer death. The median age at diagnosis is 62 years, and an estimated 1 in 8 women will develop breast cancer at some point in their lifetime. African American women are more likely to die of breast cancer compared with women of other races.

OBJECTIVE:

To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on medications for risk reduction of primary breast cancer.

EVIDENCE REVIEW:

The USPSTF reviewed evidence on the accuracy of risk assessment methods to identify women who could benefit from risk-reducing medications for breast cancer, as well as evidence on the effectiveness, adverse effects, and subgroup variations of these medications. The USPSTF reviewed evidence from randomized trials, observational studies, and diagnostic accuracy studies of risk stratification models in women without preexisting breast cancer or ductal carcinoma in situ.

FINDINGS:

The USPSTF found convincing evidence that risk assessment tools can predict the number of cases of breast cancer expected to develop in a population. However, these risk assessment tools perform modestly at best in discriminating between individual women who will or will not develop breast cancer. The USPSTF found convincing evidence that risk-reducing medications (tamoxifen, raloxifene, or aromatase inhibitors) provide at least a moderate benefit in reducing risk for invasive estrogen receptor-positive breast cancer in postmenopausal women at increased risk for breast cancer. The USPSTF found that the benefits of taking tamoxifen, raloxifene, and aromatase inhibitors to reduce risk for breast cancer are no greater than small in women not at increased risk for the disease. The USPSTF found convincing evidence that tamoxifen and raloxifene and adequate evidence that aromatase inhibitors are associated with small to moderate harms. Overall, the USPSTF determined that the net benefit of taking medications to reduce risk of breast cancer is larger in women who have a greater risk for developing breast cancer.

CONCLUSIONS AND RECOMMENDATION:

The USPSTF recommends that clinicians offer to prescribe risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women who are at increased risk for breast cancer and at low risk for adverse medication effects. (B recommendation) The USPSTF recommends against the routine use of risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, in women who are not at increased risk for breast cancer. (D recommendation) This recommendation applies to asymptomatic women 35 years and older, including women with previous benign breast lesions on biopsy (such as atypical ductal or lobular hyperplasia and lobular carcinoma in situ). This recommendation does not apply to women who have a current or previous diagnosis of breast cancer or ductal carcinoma in situ.

Author/s:

US Preventive Services Task Force, Owens, Douglas K., Davidson, Karina W., Krist, Alex H., Barry, Michael J., Cabana, M, Caughey, AB, Doubeni, Chyke A., Epling, John W. Jr., Kubik, M, Landefeld, CS, Mangione, Carol M., Pbert, L, Silverstein, Michael, Tseng, Chien-Wen, Wong, JB

Long-Term Drug Therapy and Drug Holidays for Osteoporosis Fracture Prevention: A Systematic Review

Brian Desmarais — Thu, 23 May 2019 13:11:29 +0000

Date Added:

May 23, 2019

Journal/Publication:

Annals of Internal Medicine

Publisher:

U.S. Department of Health & Human Services

Publication Date:

April 23, 2019

URL:

https://www.ncbi.nlm.nih.gov/pubmed/?term=Long-Term%20Drug%20Therapy%20and%20Dru…

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.7326/M19-0533.

Keywords

MeSH

Raloxifene Hydrochloride

Databases, Bibliographic

National Institutes of Health (U.S.)

Information Storage and Retrieval

bias

Health Services Research

Femoral Fractures

This is a systematic review of current evidence regarding medications for post-menopausal osteoporosis. James W. Mold, MD, MPH

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BACKGROUND:

Optimal long-term osteoporosis drug treatment (ODT) is uncertain.

PURPOSE:

To summarize the effects of long-term ODT and ODT discontinuation and holidays.

DATA SOURCES:

Electronic bibliographic databases (January 1995 to October 2018) and systematic review bibliographies.

STUDY SELECTION:

48 studies that enrolled men or postmenopausal women aged 50 years or older who were being investigated or treated for fracture prevention, compared long-term ODT (>3 years) versus control or ODT continuation versus discontinuation, reported incident fractures (for trials) or harms (for trials and observational studies), and had low or medium risk of bias (ROB).

DATA EXTRACTION:

Two reviewers independently rated ROB and strength of evidence (SOE). One extracted data; another verified accuracy.

DATA SYNTHESIS:

Thirty-five trials (9 unique studies) and 13 observational studies (11 unique studies) had low or medium ROB. In women with osteoporosis, 4 years of alendronate reduced clinical fractures (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.82]) and radiographic vertebral fractures (both moderate SOE), whereas 4 years of raloxifene reduced vertebral but not nonvertebral fractures. In women with osteopenia or osteoporosis, 6 years of zoledronic acid reduced clinical fractures (HR, 0.73 [CI, 0.60 to 0.90]), including nonvertebral fractures (high SOE) and clinical vertebral fractures (moderate SOE). Long-term bisphosphonates increased risk for 2 rare harms: atypical femoral fractures (low SOE) and osteonecrosis of the jaw (mostly low SOE). In women with unspecified osteoporosis status, 5 to 7 years of hormone therapyreduced clinical fractures (high SOE), including hip fractures (moderate SOE), but increased serious harms. After 3 to 5 years of treatment, bisphosphonate continuation versus discontinuation reduced radiographic vertebral fractures (zoledronic acid; low SOE) and clinical vertebral fractures (alendronate; moderate SOE) but not nonvertebral fractures (low SOE).

LIMITATION:

No trials studied men, clinical fracture data were sparse, methods for estimating harms were heterogeneous, and no trials compared sequential treatments or different durations of drug holidays.

CONCLUSION:

Long-term alendronate and zoledronic acid therapies reduce fracture risk in women with osteoporosis. Long-termbisphosphonate treatment may increase risk for rare adverse events, and continuing treatment beyond 3 to 5 years may reduce risk for vertebral fractures. Long-term hormone therapy reduces hip fracture risks but has serious harms.

PRIMARY FUNDING SOURCE:

National Institutes of Health and Agency for Healthcare Research and Quality. (PROSPERO: CRD42018087006).

Author/s:

Fink, Howard A., MacDonald, Roderick, Forte, Mary L., Rosebush, Christina E., Ensrud, Kristine E., Schousboe, John T., Nelson, Victoria A., Ullman, Kristen, Butler, M., Olson, Carin M., Taylor, Brent C., Brasure, Michelle, Wilt, Timothy J.