Managing the Risk of Osteoporosis in Women With a History of Early Breast Cancer

October 1, 2004
Kathleen I. Pritchard, MD, FRCP

Oncology, ONCOLOGY Vol 18 No 11, Volume 18, Issue 11

This excellent and practical articleby Dr. Ravdin is worthwhilereading for every physician involvedin the long-term care of womenwith a previous diagnosis of breastcancer. Dr. Ravdin clearly outlinesthe theoretical rationale underlying theincreased risk of osteopenia and osteoporosisin women with a history ofbreast cancer. The fact that such womencommonly undergo prematuremenopause either deliberately, as partof treatment for breast cancer, or as asecondary effect of chemotherapy, andthat estrogen-replacement therapywith or without progesterone remainscontraindicated for fear of increasingthe risk of recurrence, clearly contributesto the increased possibility ofdeveloping osteopenia or osteoporosis.New data supporting the role ofaromatase inhibitors in adjuvant therapy[

This excellent and practical articleby Dr. Ravdin is worthwhilereading for every physician involvedin the long-term care of womenwith a previous diagnosis of breastcancer. Dr. Ravdin clearly outlinesthe theoretical rationale underlying theincreased risk of osteopenia and osteoporosisin women with a history ofbreast cancer. The fact that such womencommonly undergo prematuremenopause either deliberately, as partof treatment for breast cancer, or as asecondary effect of chemotherapy, andthat estrogen-replacement therapywith or without progesterone remainscontraindicated for fear of increasingthe risk of recurrence, clearly contributesto the increased possibility ofdeveloping osteopenia or osteoporosis.New data supporting the role ofaromatase inhibitors in adjuvant therapy[1-4] will undoubtedly lead to theincreased use of these agents in theadjuvant therapy of breast cancer, withthe probability of increasing the riskof decreased bone density.Underestimate of Risk
It seems clear from the adjuvantstudies of aromatase inhibitors citedabove that there may well be an increasedincidence of osteopenia, osteoporosis,and/or fractures associatedwith even the short-term use of theseagents in adjuvant therapy. The Arimidex,Tamoxifen Alone or in Combination(ATAC) trial reports an increasedincidence of fracture, while the Canadian-led MA.17 study and the IntergroupExemestane Study (IES) reportmarginally increased self-reported orphysician-elicited incidences of osteoporosisand/or fracture. Since osteoporosisdevelops gradually overseveral years and fractures may be asymptomatic-or, if symptomatic, areoften seen only 5 to 10 years or moreinto the natural history of this disease-reports from studies with a median follow-up of 3 to 5 years likely representan underestimate of the risk of fracturein women receiving this therapy.Thus, Dr. Ravdin's succinct summaryof a practical approach to suchpatients is both timely and useful. Intruth, however, there is little evidencedemonstrating that the use of approachesthat are effective in osteoporosisin general are equallyeffective in women with a prior diagnosisof breast cancer. Theoretically,it would seem that these approachesshould work in a similar fashion, butfew studies have been conducted inthese women up to the present time.Ongoing Trials
Currently, several ongoing trialsare exploring the role of zoledronicacid (Zometa) in women receivinganastrozole (Arimidex), and of otherbisphosphonates in women receivingexemestane (Aromasin). Specific resultsof such trials are not as yet available.Hopefully, these powerfulbisphosphonates will work as well insuch women as they have been shownto do in osteoporotic and osteopenicwomen without a history of breastcancer.In the meantime, Dr. Ravdin's articlewill provide a scientifically basedand practical approach to the managementof this situation in postmenopausalwomen with the diagnosis ofbreast cancer.

Disclosures:

Dr. Pritchard is a consultantfor Aventis, AstraZeneca, Roche,Pharmacia Inc, Ortho-Biotech, Pfizer, YM Bioscience,and Biomira; has received researchfunding from and/or through the National CancerInstitute of Canada Clinical Trials Group,Pharmacia Inc, AstraZeneca, Bristol MyersSquibb, Aventis, Amgen, Ortho-Biotech, andPfizer; has given paid expert testimony forAventis and AstraZeneca; and has been anadvisory committee member for Aventis,AstraZeneca, Ortho-Biotech, Roche, andPharmacia Inc.

References:

1.

The ATAC Trialists Group: Anastrozolealone or in combination with tamoxifen versustamoxifen alone for adjuvant treatment of postmenopausalwomen with early breast cancer:First results of the ATAC randomized trial. Lancet359:2131-2139, 2002.

2.

The ATAC Trialists Group: Anastrozolealone or in combination with tamoxifen versustamoxifen alone for adjuvant treatment of postmenopausalwomen with early-stage breastcancer: Results of the ATAC (Arimidex,Tamoxifen Alone or in Combination) Trial efficacyand safety update analyses. Cancer98:1802-1810, 2003.

3.

Goss PE, Ingle JN, Martino S, et al: Arandomized trial of letrozole in postmenopausalwomen after five years of tamoxifen therapyfor early-stage breast cancer. N Engl J Med349:1793-1802, 2003.

4.

Coombes RC, Hall E, Gibson L, et al: Arandomized trial of exemestane after two tothree years of tamoxifen therapy in postmenopausalwomen with primary breast cancer. NEngl J Med 350:1081-1091, 2004.