Changes in bone turnover and in bone mass in women with breast cancer switched from tamoxifen to exemestane

Gonnelli, Stefano; Cadirni, Alice; Caffarelli, Carla; Petrioli, Roberto; Montagnani, A; Franci, Maria Beatrice; Lucani, Barbara; Francini, Guido; Nuti, Ranuccio

doi:10.1016/j.bone.2006.06.027

Cited by 60 publications

(38 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We chose these markers, and not other bone specific ones, because our first aim was to understand if OPG and RANK-L could improve upon the results obtained in clinical practice. Furthermore, we decided not to test other bone markers such as NTX, since recent data have shown that NTX levels are not bone metastases specific, and are similar in osteoporotic NEDP and BMP (19,20). OPG sensitivity was found to be higher than that of the routine markers, and further increased when evaluated in combination with either CEA or CA15-3.…”

Section: Discussionmentioning

confidence: 99%

Bone metastases detection by circulating biomarkers: OPG and RANK-L

et al. 2011

View full text Add to dashboard Cite

Abstract. Osteoprotegerin (OPG) is a decoy receptor of the receptor activator of nuclear factor-κB ligand (RANK-L) and plays an important role in the formation of metastatic bone lesions. We evaluated the usefulness of circulating OPG and RANK-L for the detection of bone metastases. We enrolled 143 individuals in the study: 30 healthy donors (HD) and 113 breast cancer patients. Among patients, 49 had no evidence of disease (NEDP), 54 had bone metastases (BMP) at first diagnosis, and 10 had visceral metastases (VMP). Both transcripts were determined in peripheral blood samples using quantitative PCR. Receiver operating characteristic (ROC) curve analysis was used to calculate the diagnostic accuracy of OPG, RANK-L, CEA and CA15-3. OPG and RANK-L median values were signifi cantly lower in BMP (median 0.5, range 0.1-5.7, p<0.001 and median 0.5, range 0.1-4.5, p=0.024, respectively) compared to NEDP (median 1.7, range 0.4-8.9 and median 0.8, range 0.2-3.8, respectively), regardless of the number and type of bone lesions or the presence of visceral metastases. The area under the ROC curve (NEDP vs. BMP) was higher for OPG (82.5, 95% CI 74.5-90.6) than for RANK-L (69.2, 95% CI 59.0-79.40). Specificity for OPG was 87.7% (95% CI 75.7-94.2) and sensitivity was 74.1% (95% CI 60.4-85.0), both values increasing when considered together with CEA and CA15-3. For VMP, OPG and RANK-L were expressed in only one patient. Our results highlight the potentially important role of circulating OPG in the diagnosis of bone metastases. A confirmatory study on a larger case series is ongoing.

show abstract

Section: Discussionmentioning

confidence: 99%

Bone metastases detection by circulating biomarkers: OPG and RANK-L

et al. 2011

View full text Add to dashboard Cite

show abstract

“…McCaig et al [25] reported that stopping tamoxifen and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naive patients. The measurement of bone turnover biomarkers also showed that the effect of AIs occurs relatively rapidly after initiation of the treatment [9,24,[26][27][28][29].…”

Section: Annals Of Oncology Original Articlesmentioning

confidence: 95%

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07)

et al. 2012

View full text Add to dashboard Cite

Background: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T].Patients and methods: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models.Results: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements.Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < 22.5 standard deviation).Conclusions: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherapy.

show abstract

“…Similarly, exemestane causes an increase in bone turnover markers and reduces BMD (Lønning et al 2005). The same decrease was recorded when patients were treated with letrozole (Perez et al 2006) or after completing 5 years of adjuvant tamoxifen therapy (Gonnelli et al 2007). For the latter study, bone loss could be explained firstly by the estrogen-reducing effect of exemestane and secondly by the loss of the protective effect of tamoxifen as well.…”

Section: Bone Metabolismmentioning

confidence: 84%

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Asten¹,

Neven²,

Lintermans³

et al. 2014

Endocrine-Related Cancer

View full text Add to dashboard Cite

Breast cancer is the most prevalent type of cancer in women and responsible for significant female cancer-related mortality worldwide. In the Western world, over 80% of breast cancers are hormone-receptor positive for which endocrine therapy is administered. The main anti-estrogen treatments in use consist of selective estrogen-receptor modulators, such as tamoxifen, and third-generation aromatase inhibitors (AIs), such as exemestane, letrozole, and anastrozole. In this review, the focus will lie on exemestane, its clinical use, and its side-effect profile. Exemestane is the only third-generation steroidal AI. Its efficacy as a first-line treatment in metastatic breast cancer has been demonstrated. Therefore, exemestane could be considered a valid first-line therapeutic option, but it also can be used in second-line or further situations. Exemestane is mostly used as part of sequential adjuvant treatment following tamoxifen, but in this setting it is also active in monotherapy. Furthermore, this AI has been studied in the neoadjuvant setting as presurgical treatment, and even as chemoprevention in high-risk healthy postmenopausal women. It may reverse side effects of tamoxifen, such as endometrial changes and thromboembolic disease but may also cause some inconvenient side effects itself. Additionally, there is a lack of total crossresistance between exemestane and nonsteroidal AIs as far as their anti-tumoral efficacy is concerned; moreover the two classes of AIs display a nontotal overlapping toxicity profile. Taking together, exemestane can be considered as a useful treatment option at all stages of breast cancer.

show abstract

Changes in bone turnover and in bone mass in women with breast cancer switched from tamoxifen to exemestane

Cited by 60 publications

References 23 publications

Bone metastases detection by circulating biomarkers: OPG and RANK-L

Bone metastases detection by circulating biomarkers: OPG and RANK-L

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07)

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Contact Info

Product

Resources

About