Bone mineral density following surgical oophorectomy and tamoxifen adjuvant therapy for breast cancer

Abstract

BACKGROUND:In premenopausal women treated for breast cancer, loss of bone mineral density (BMD) follows from menopause induced by chemotherapy or loss of ovarian function biochemically or by surgical oophorectomy. The impact on BMD of surgical oophorectomy plus tamoxifen therapy has not been described. METHODS: In 270 Filipino and Vietnamese premenopausal patients participating in a clinical trial assessing the impact of the timing in the menstrual cycle of adjuvant surgical oophorectomy on breast cancer outcomes, BMD was measured at the lumbar spine and femoral neck before this treatment, and at 6, 12, and 24 months after surgical and tamoxifen therapies. RESULTS: In women with a pretreatment BMD assessment and at least 1 other subsequent BMD assessment, no significant change in femoral neck BMD was observed over the 2-year period (20.006 g/cm 2 , 20.8%, P 5.19), whereas in the lumbar spine, BMD fell by 0.045 g/cm 2 (4.7%) in the first 12 months (P <.0001) and then began to stabilize. CONCLUSIONS:Surgically induced menopause with tamoxifen treatment is associated with loss of BMD at a rate that lessens over 2 years in the lumbar spine and no significant change of BMD in the femoral neck. Cancer 2013;119:3746-52. V C 2013 American Cancer Society.KEYWORDS: bone mineral density; breast cancer; menopause; oophorectomy; tamoxifen; femoral neck; spine; adjuvant drug therapy. INTRODUCTIONIn high-income countries, premenopausal women with hormone receptor-positive tumors account for 15% of the case burden in breast cancer; however, in low-and middle-income countries this percentage is approximately 36%. 1 Globally, one-third of the case burden in breast cancer is in this group. With increasingly effective therapies and the associated increases in long-term survival, the total "costs" of therapies are of concern to afflicted women.Adjuvant ovarian ablation improves survival in premenopausal women with operable breast cancer unselected for hormonal receptor status.2 Meta-analysis data also suggest a trend favoring ovarian ablation over luteinizing hormonereleasing hormone (LHRH) agonist treatment.2 Adjuvant surgical oophorectomy plus tamoxifen improves survival with risk reduction of 0.54 in hormone receptor positive patients.3 A variety of direct but underpowered studies and indirect risk reduction data suggest that this combined hormonal adjuvant treatment may modestly improve results over oophorectomy or tamoxifen alone. [4][5][6][7][8] The direct adjuvant comparison of tamoxifen with or without ovarian ablation or ovarian function suppression is being tested in the SOFT trial, in which, however, the fraction of women treated with surgical oophorectomy may be too small to allow conclusions about this specific combined hormonal treatment. In this context, in high-income countries, many premenopausal women with hormone receptor-positive tumors are treated with chemotherapy and tamoxifen, because of the conclusion that current chemotherapy regimens, particularly with taxanes, provide greater benefits than any hormonal th...

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“…Aus diesem Grunde sind Unterschiede im Ausmaß des Tumortherapie-bedingten Knochenmassenverlusts und dem postmenopausalen zu sehen. Der Knochenmassenverlust ist bei prämenopausalen Frauen, die sich einer Chemotherapie unterziehen müssen und anschließend adjuvant mit Tamoxifen (in Kombination mit einem GnRH-Analogon oder nicht) behandelt werden, höher als bei Frauen, die keine Chemotherapie vor Beginn der adjuvanten endokrinen Therapie mit Tamoxifen erhielten (5,6). Auch wenn die Knochenmasse wegen des jüngeren Alters der prämenopausalen Tumorpatientinnen in der Mehrzahl einen höheren Ausgangswert als postmenopausal hat, ist insbesondere bei Patientinnen mit zusätzlichen Frakturrisikofaktoren ein Monitorieren der Knochenmasse unter adjuvanter Tumortherapie prämenopausal obligat (7).…”