14 maart 2010: British Journal of Cancer. 2010 Mar 2;102(5):799-802. Epub 2010 Feb 16

Vrouwen die na de overgang bisfosphonaten (bv. Zometa) gebruiken om osteoporose tegen te gaan blijken daarmee het risico op het ontwikkelen van borstkanker behoorlijk te verkleinen met ruim 30%. Dit blijkt uit een zogeheten casecontrol studie onder 6000 vrouwen van 2003 tot 2006 in Wisconsin waarvan de helft invasieve borstkanker ontwikkelde. Het gebruik van bisphosphonaten verminderde het risico op borstkanker dus met ruim 30%. Dit is conform twee andere nog grotere studies (resp. 150.000 en 4575 deelnemende vrouwen na de overgang) die aantoonden dat bisphosphonaatgebruik het risico op borstkanker en het risico op een recidief met resp. 32 en 34% verminderde.

Wel blijk uit de laatste studie dat dit alleen opgaat voor vrouwen met een min of meer normaal lichaamsgewicht. Bij te zware, te dikke vrouwen bleek dit effect niet op te treden. Artsen verklaren dit dat bisphosphonaten blijkbaar een rol spelen in de hormoonhuishouding: "Zwaarlijvige vrouwen kunnen verhoogde oestrogeen niveaus hebben, waardoor de onderliggende hormonen invloed kunnen hebben op het vermogen van bisfosphonaten het risico op borstkanker te verminderen," aldus studieleider Dr Newcomb

Br J Cancer. 2010 Mar 2;102(5):799-802. Epub 2010 Feb 16.

Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk.

Newcomb PA, Trentham-Dietz A, Hampton JM.

Paul P Carbone Comprehensive Cancer Center, University of Wisconsin, 610 Walnut Street, Madison, WI 53726, USA. pnewcomb@fhcrc.org

BACKGROUND: Bisphosphanates are used primarily for the prevention and treatment of osteoporosis, and are also indicated for osseous complications of malignancy. In addition to their bone resorption properties, the most commonly used nitrogen-containing bisphosphonate compounds also inhibit protein prenylation, and thus may exert anti-tumour properties.

METHODS: To evaluate whether the use of these drugs may be associated with cancer, specifically breast cancer, we conducted a population-based case-control study in Wisconsin from 2003 to 2006. Participants included 2936 incident invasive breast cancer cases and 2975 population controls aged < 70 years. Bisphosphonate use and potential confounders were assessed by interview.

RESULTS: Using multivariable logistic regression, the odds ratio for breast cancer in current bisphosphonate users compared with non-users was 0.67 (95% confidence interval 0.51-0.89). Increasing duration of use was associated with a greater reduction in risk (P-trend=0.01). Risk reduction was observed in women who were not obese (P-interaction=0.005).

CONCLUSION: These results are suggestive of an additional benefit of the common use of bisphosphonates, in this instance, the reduction in breast cancer risk.

PMID: 20160722 [PubMed - in process]

Enkele citaten uit een toelichting op Medscape van dr. Newcomb:

"This large study provides new evidence that the use of bisphosphonates is associated with a potentially important reduction in breast cancer risk," lead author Polly Newcomb, PhD, MPH, head of the Cancer Prevention Program at the Fred Hutchinson Cancer Research Center in Seattle, Washington, said in a statement.

This reduction in breast cancer risk is similar to that already reported in 2 other studies, both of which were presented in December 2009 at the San Antonio Breast Cancer Symposium. One was an analysis of more than 150,000 postmenopausal women participating in several Women's Health Initiative studies, which found that bisphosphonate use reduced the risk for invasive breast cancer by 32%. The other involved an analysis of 4575 postmenopausal women in Israel, which found a 34% reduction.

The researchers therefore conclude that "these findings may reflect real benefits due to antitumor mechanisms" of bisphosphonates.

However, the association with a reduction in the risk for breast cancer was seen only among women who were not obese; they were not seen among obese women. This suggests that the inhibitory action of these drugs is related to some threshold effect of hormonal or other growth factors, which are known to be important etiological exposures in breast cancer, the researchers write in their paper.

"Obese women may have elevated estrogen levels, so underlying hormones may influence the ability of bisphosphonates to reduce breast cancer risk," Dr. Newcomb added in a statement.

How bisphosphonates could prevent breast cancer is not known, but these drugs have several actions that might be relevant; they have been shown to cause tumor apoptosis, inhibit angiogenesis, and prevent tumor-cell adhesions. "These drugs may affect cell function and be important in cell growth and death — specifically the death of tumors or even premalignant disease," Dr. Newcomb noted.

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