Zoledronic Acid Prevents Cancer Treatment–Induced Bone Loss in Premenopausal Women Receiving Adjuvant Endocrine Therapy for Hormone-Responsive Breast Cancer: A Report From the Austrian Breast and Colorectal Cancer Study Group

2007 ◽  
Vol 25 (7) ◽  
pp. 820-828 ◽  
Author(s):  
Michael F.X. Gnant ◽  
Brigitte Mlineritsch ◽  
Gero Luschin-Ebengreuth ◽  
Stephan Grampp ◽  
Helmut Kaessmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Loss ◽  
Endocrine Therapy ◽  
Premenopausal Women ◽  
Adjuvant Endocrine Therapy ◽  
Phase Iii ◽  
Endocrine Treatment ◽  
Mineral Density ◽  
T Score

Purpose Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients. Patients and Methods This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) ± zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin ± zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months. Results Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, −14.4% after 36 months; mean T score reduction, −1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, −17.3%; mean T score reduction, −2.6) compared with patients receiving tamoxifen/goserelin (BMD, −11.6%; mean T score reduction, −1.1). In contrast, BMD remained stable in zoledronic acid–treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted. Conclusion Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.

scholarly journals Zoledronic Acid Prevents Bone Loss in Premenopausal Women Undergoing Adjuvant Chemotherapy for Early-Stage Breast Cancer

2008 ◽  
Vol 26 (29) ◽  
pp. 4739-4745 ◽  
Author(s):  
Dawn L. Hershman ◽  
Donald J. McMahon ◽  
Katherine D. Crew ◽  
Serge Cremers ◽  
Dinaz Irani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Adjuvant Chemotherapy ◽  
Bone Loss ◽  
Repeated Measures ◽  
Early Stage ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Mineral Density ◽  
Percent Change

Purpose Adjuvant chemotherapy for breast cancer (BC) may be associated with increased rates of bone loss and decreased bone mineral density (BMD) and may lead to premature osteoporosis and increased fracture risk. We examined whether zoledronic acid (ZA) prevents bone loss in premenopausal women receiving chemotherapy for early-stage BC. Patients and Methods This study is a randomized, double-blind, multicenter, phase III trial comparing ZA (4 mg intravenously every 3 months) versus placebo for 1 year. Premenopausal women underwent serial BMD measurements before initiating chemotherapy and at 6 and 12 months. The primary outcome was percent change in lumbar spine (LS) BMD at 6 months. Secondary outcomes were percent change at any BMD site and markers of bone turnover at 12 months. Linear mixed model analysis for repeated measures was performed. Results Of 101 women who were randomly assigned and completed baseline evaluation, 96 completed the 6-month evaluation, and 85 completed the 12-month evaluation. Baseline characteristics were comparable between the groups. Mean age was 42 years. Placebo was associated with significant decline in LS BMD at both 6 (2.4%) and 12 (4.1%) months. Similarly, total hip BMD declined by 0.8% at 6 months and 2.6% at 12 months. In contrast, BMD remained stable in ZA patients (P < .0001 compared with placebo). Conclusion Premenopausal women receiving chemotherapy for BC sustained significant bone loss at the LS and hip, whereas BMD remained stable in women who received ZA. Administration of ZA during the first year of chemotherapy is an effective and well-tolerated strategy for preventing bone loss.

Evaluation of the protective effects of zoledronic acid on bone mass in premenopausal women undergoing adjuvant chemotherapy following treatment discontinuation

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 562-562
Author(s):  
D. L. Hershman ◽  
D. McMahon ◽  
K. D. Crew ◽  
T. Shao ◽  
S. Cremers ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Adjuvant Chemotherapy ◽  
Bone Loss ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Secondary Outcome ◽  
First Year ◽  
Mineral Density ◽  
Double Blind ◽  
One Year

562 Background: Adjuvant chemotherapy is associated with a significant reduction in bone mineral density (BMD) in premenopausal women with breast cancer (BC). We previously showed that this loss of BMD can be prevented with zoledronic acid (ZA) every 3 months for a year. Since bone loss in women with osteoporosis is prevented with annual ZA, we examined whether protection from bone loss by ZA in women with BC persists following discontinuation of ZA. Methods: A randomized, double-blind, multicenter, phase III trial comparing ZA (4 mg every 3 months) versus placebo for 1 year in premenopausal women with BC undergoing adjuvant chemotherapy was conducted. Patients had serial BMD measurement at 0 (after surgery and before chemotherapy), 6, 12 and 24 months. Demographic, clinical, and tumor characteristics were collected. Serum was stored at -70°C and analyzed in batches. The secondary outcome of percent change in BMD at 24 months, one year following the last ZA/placebo, is presented. Intention-to-treat analyses with linear mixed models were performed using SAS version 9. Results: Of 101 patients randomized, 85 completed 12 month, and 62 completed 24 month evaluations; mean age 41 (SD 5.2). Demographic and baseline characteristics were similar between treatment groups. By 24 months, 38 (61%) had not regained their menses; 22 patients were on tamoxifen, 25 were on an aromatase inhibitor. Chemotherapy without ZA was associated with a significant decline from baseline in lumbar spine (LS) BMD after both 12 (-5.4%) and 24 (-6.3%) months. Similarly total hip (TH) and femoral neck (FN) BMD declined by 2.6% and 2.4% by 24 months, respectively. In contrast, BMD remained stable in ZA-treated patients (p < 0.0001 vs placebo). Patients who received ZA had stable BMD at 24 months (LS -0.58%, TH 0.83%, FN 0.04%). Analysis of bone turnover markers is ongoing. Conclusions: Premenopausal women receiving adjuvant chemotherapy for BC had significant bone loss in the first year that persisted in the second year. ZA every 3 months for a year effectively prevented bone loss during the first year and 1 year after completion of ZA treatment. One year of ZA maintains BMD in premenopausal BC patients for an additional year after discontinuation of ZA. [Table: see text]

Palbociclib combined with endocrine treatment in breast cancer patients with high relapse risk after neoadjuvant chemotherapy: Subgroup analyses of premenopausal patients in PENELOPE-B.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 518-518
Author(s):  
Frederik Marmé ◽  
Miguel Martin ◽  
Michael Untch ◽  
Herve R. Bonnefoi ◽  
Sung-Bae Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Endocrine Treatment ◽  
Hematologic Toxicity

518 Background: PENELOPE-B assessed efficacy of the CDK4/6 inhibitor 1-year palbociclib versus placebo added to endocrine therapy (ET) as post-neoadjuvant treatment in a high-risk breast cancer population. Palbociclib did not improve invasive disease-free survival (iDFS) compared to placebo (3-year iDFS 81.3% vs 77.7%) (Loibl et al. J Clin Oncol 2021). Here we report results from the subpopulation of premenopausal women. Methods: Patients with hormone receptor positive, HER2-negative breast cancer without pathological complete response after taxane‐containing neoadjuvant chemotherapy and at high risk of relapse (CPS‐EG score ≥3 or 2 and ypN+) were randomized (1:1) to receive 13 cycles of palbociclib 125mg daily or placebo on days 1-21 in a 28d cycle in addition to standard endocrine treatment including tamoxifen (TAM) +/- gonadotropin-releasing hormone analogue (GnRH) and aromatase inhibitor (AI) +/- GnRH. Randomization was stratified by nodal status at surgery, age ( < 50 vs ≥50 years), Ki-67, region, and CPS-EG score. Results: 616/1250 patients were premenopausal at the time of enrollment, 185 of these patients (30.0%) were younger than 40 years of age. 95.2% had ypN+ after surgery; 42.8% had ypT2 and 46.8% a CPS-EG score of 3. 23.1% of the premenopausal women had a Ki67 of > 15% in residual disease. 66.1% started with TAM alone; 19.3% with TAM and ovarian function suppression (OFS); and 13.6% received an AI+OFS. There was no difference in iDFS between palbociclib and placebo in the premenopausal women HR 0.948 (0.693-1.30). The 3-year iDFS was 80.6% and 78.3%, respectively. Palbociclib vs placebo in subgroups by endocrine treatment: TAM alone HR 1.05 (0.715-1.53) p = 0.817; TAM+GnRH HR 0.52 (0.267-1.02) p = 0.057 and AI+GnRH HR 1.58 (0.548-4.56) p = 0.397; pinteraction0.124. Hematologic toxicity was significantly more common with palbociclib. Non-hematological toxicity any grade palbociclib vs placebo were: fatigue 67.4% vs 51.3%; hot flushes 52.2% vs 54.8%; bone pain 15.6% vs 16.6%; and vaginal dryness 11.0% vs 11.5%. When receiving palbociclib fewer patients in the AI+GnRH group vs the TAM +/- GnRH cohort experienced anemia (54.1% vs 80.5%) and thrombocytopenia (37.8% vs 65.1%). Fatigue (75.7% vs 66.3%) and nausea (40.5% vs 24.9%) were more common with AI+GnRH than TAM +/-GnRH when palbociclib was added. Thromboembolic events were low with overall 9 events (4 vs 5; AI+GnRH 2.4% vs 1.3% TAM+/-GnRH). Conclusions: The addition of palbociclib to endocrine therapy did not improve iDFS in premenopausal women. These are the first safety results from a phase III study for the combination tamoxifen +/-GnRH and palbociclib. The addition of palbociclib to tamoxifen +/-GnRH in premenopausal women did not increase side effects compared to AI+GnRH and seems to be an alternative to AI+GnRH. Clinical trial information: NCT01864746.

Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial

2011 ◽  
Vol 12 (7) ◽  
pp. 631-641 ◽  
Author(s):  
Michael Gnant ◽  
Brigitte Mlineritsch ◽  
Herbert Stoeger ◽  
Gero Luschin-Ebengreuth ◽  
Dietmar Heck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Randomised Trial ◽  
Premenopausal Women ◽  
Adjuvant Endocrine Therapy ◽  
Early Stage Breast Cancer

scholarly journals Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Risedronate for the Prevention of Bone Loss in Premenopausal Women Undergoing Chemotherapy for Primary Breast Cancer

2009 ◽  
Vol 27 (7) ◽  
pp. 1047-1053 ◽  
Author(s):  
Stephanie L. Hines ◽  
Betty Anne Mincey ◽  
Jeff A. Sloan ◽  
Sachdev P. Thomas ◽  
Elaine Chottiner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Loss ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Mineral Density ◽  
Double Blind ◽  
Treatment Groups ◽  
The Mean ◽  
Prevention Of Bone Loss ◽  
To Receive

Purpose Risedronate prevents bone loss in postmenopausal women. The purpose of this study was to determine whether risedronate prevents bone loss in premenopausal women undergoing chemotherapy for breast cancer. Patients and Methods Premenopausal women undergoing chemotherapy for breast cancer were treated with oral calcium 600 mg and vitamin D 400 U daily and randomly assigned to receive oral risedronate 35 mg weekly or placebo, with all these therapies beginning within a month of the start of chemotherapy. Most chemotherapy regimens included anthracyclines, taxanes, or cyclophosphamide. Bone mineral density (BMD) was measured at baseline and 1 year. The primary end point was the change in lumbar spine (LS) BMD from baseline to 1 year. Results A total of 216 women enrolled; 170 women provided BMD data at 1 year. There was no difference in the mean change or percent change in LS BMD between groups, with a loss of 4.3% in the risedronate arm and 5.4% for placebo at 1 year (P = .18). Loss of BMD at the femoral neck and total hip were also similar between treatment groups. Risedronate was well tolerated, with no significant differences in adverse events compared with placebo, except that arthralgias and chest pain were worse in those receiving the placebos. Conclusion Risedronate did not prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.

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