Bone recurrence in early breast cancer patients: The paradox of aromatase inhibitors induced bone resorption

2021 ◽  
pp. 1-6
Author(s):  
Francesco Pavese ◽  
Alessandro Parisi ◽  
Silvia Rotondaro ◽  
Valentina Cocciolone ◽  
Giovanni Pierorazio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Resorption ◽  
Bone Metastases ◽  
Early Breast Cancer ◽  
Aromatase Inhibitors ◽  
Underlying Mechanism ◽  
Recurrence Risk ◽  
Disease Recurrence ◽  
Breast Cancer Patients ◽  
Mineral Density

BACKGROUND: Despite the increase in chances of cure for early breast cancer (EBC) patients, approximately 20–45% of them will experience a disease recurrence, particularly bone metastases in 60–80% of cases, which occur more frequently in luminal subtypes. Endocrine therapy (ET) has always been the milestone of adjuvant treatment for hormone receptor-positive EBC patients, leading to indubitable reduction of disease recurrence risk. However, adjuvant aromatase inhibitors (AIs) therapy may promote a progressive decrease in bone mineral density (BMD), which can lead to osteoporosis. The increased bone resorption associated with osteoporosis may provide fertile soil for cancer growth and accelerate the development of bone metastases. PATIENTS AND METHODS: In this single-institution cohort study, we performed a retrospective analysis of “luminal-like” EBC patients who experienced bone recurrence after a subsequent disease free interval. The aim of the study was to evaluate the median time to skeletal recurrence (TSkR). RESULTS: 143 patients experienced bone recurrence. Median TSkR was 54 months (95%CI: 45–65). Among patients who received adjuvant AIs median TSkR was 35 months (95%CI: 25–54), while among patients who did not was 61 months (95%CI: 50–80) (HR = 1.45 [95%CI: 0.97–2.17], p = 0.0644). After adjusting for TNM stage (AJCC 8th edition), adjuvant AIs treatment was significantly related to a shorter TSkR (HR = 1.60 [95%CI: 1.06–2.42], p = 0.0244). Adjuvant Tamoxifen, adjuvant AIs/Tamoxifen and no-treatment did not revealed to be associated to TSkR. CONCLUSIONS: In this cohort of EBC patients with bone recurrence, AIs treatment seems to be related to a shorter TSkR. AIs-induced bone resorption might represent the underlying mechanism.

Five-year follow-up results of aerobic and circuit training on bone mineral density in early breast cancer patients

2020 ◽  
Vol 138 ◽  
pp. S81
Author(s):  
C. Blomqvist ◽  
L. Vehmanen ◽  
H. Sievänen ◽  
P. Kellokumpu-Lehtinen ◽  
R. Nikander ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Mineral Density ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Bone Mineral ◽  
Breast Cancer Patients ◽  
Mineral Density ◽  
Circuit Training

Validation of IHC4 algorithms for prediction of risk of recurrence in early breast cancer using both conventional and quantitative IHC approaches.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 517-517 ◽  
Author(s):  
Jason Christiansen ◽  
John M. S. Bartlett ◽  
Mark Gustavson ◽  
David Rimm ◽  
Tammy Robson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Hormone Receptors ◽  
Proportional Hazards ◽  
De Novo ◽  
Recurrence Risk ◽  
Continuous Model ◽  
Disease Recurrence ◽  
Cox Proportional Hazards ◽  
Residual Risk

517 Background: Hormone receptors, HER2 and Ki67 are residual risk markers in early breast cancer. Combining these markers into a unified algorithm (IHC4) provides information on residual recurrence risk of patients treated with hormone therapies. This study aimed to independently investigate the validity of the IHC4 algorithm for residual risk prediction using both conventional (DAB)-IHC and quantitative immunofluorescence (QIF-AQUA). Methods: The TEAM pathology study recruited >4500 samples from patients treated in the TEAM trial. TMAs were stained for ER, PgR, HER2 and Ki67 using QIF-AQUA technology or DAB-based immunohistochemistry (DAB-IHC). Central HER2 FISH was performed. Quantitative image analysis was used to generate expression scores that were normalized to produce “IHC4 algorithm” as well as novel algorithm scores.  Algorithm scores were compared with disease recurrence in univariate and multivariate Cox Proportional Hazards models. Results: Both DAB-IHC and QIF-AQUA IHC4 continuous models were significant (P<0.0001) for prediction of disease recurrence with a continuous Hazard Ratio (HR) of 1.011 (1.010 – 1.013) for QIF-AQUA IHC4 versus 1.008 (1.007 – 1.010) for the DAB-IHC IHC4 model using the published IHC4 algorithm (Cuzick et al 2011).  Binning continuous model scores (4 bins) by Kaplan-Meier survival analysis was used to graphically illustrate these effects.  De novo models for both DAB-IHC and QIF-AQUA were also significantly (P<0.0001) predictive of residual risk in early breast cancer. Additionally, all 4 models were independent predictors of recurrence (P<0.0001) with other recognized clinical prognostic factors in multivariate analysis.  Although results from DAB and QIF-AQUA were modestly correlated, the QIF-AQUA model showed enhanced prediction of recurrence in both Cox Proportional Hazards Modeling and C-index calculations. Conclusions: Either conventional DAB or QIF-AQUA methods of IHC provided evidence supporting the clinical utility of IHC4 algorithms in the context of the TEAM study.  With careful standardization, either of these IHC4 assays should be considered for prediction of residual risk in early breast cancer.

1918 Impact of an osteoporosis unit in the incidence of fractures in early breast cancer patients with aromatase inhibitors

2015 ◽  
Vol 51 ◽  
pp. S305
Author(s):  
P. Novas Vidal ◽  
S. Fernandez ◽  
E. Galve ◽  
V. Arrazubi ◽  
M.A. Sala ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Aromatase Inhibitors ◽  
Breast Cancer Patients

Body Mass Index and Hormone Receptor Status Influence Recurrence Risk in HER2-Positive Early Breast Cancer Patients

2020 ◽  
Vol 20 (1) ◽  
pp. e89-e98 ◽  
Author(s):  
Luca Cantini ◽  
Mirco Pistelli ◽  
Filippo Merloni ◽  
Andrea Fontana ◽  
Ilaria Bertolini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Cancer Patients ◽  
Body Mass ◽  
Early Breast Cancer ◽  
Hormone Receptor ◽  
Recurrence Risk ◽  
Hormone Receptor Status ◽  
Breast Cancer Patients ◽  
Her2 Positive

Interaction between body mass index and bone turnover during aromatase inhibition: Evidence from the letrozole (L), exemestane (E), and anastrozole (A) pharmacodynamics (LEAP) trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
E. McCloskey ◽  
R. Hannon ◽  
G. Lakner ◽  
G. Clack ◽  
A. Miyamoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Bone Resorption ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Body Mass ◽  
Early Breast Cancer ◽  
Aromatase Inhibitors ◽  
Baseline Bmi ◽  
High Bmi

560 Background: High body mass index (BMI) protects against postmenopausal osteoporotic fracture, mediated in part by higher endogenous levels of oestradiol. Third-generation aromatase inhibitors (AIs) show superior efficacy and tolerability than tamoxifen in the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. We examined the interactions between BMI and bone turnover during treatment with 3 aromatase inhibitors in the LEAP trial, an open, randomized, pharmacodynamic study in postmenopausal women. Methods: Healthy volunteers from the UK and Hungary with normal bone density and BMI between 18 and 34 kg/m2 were randomized to receive A (1 mg/day), L (2.5 mg/day), or E (25 mg/day) orally, once daily for 24 weeks. Effects on bone resorption (log transformed serum C-telopeptide crosslinks, CTX) and bone formation (bone alkaline phosphatase and propeptide of type I procollagen, PINP) were compared. Changes in biochemical markers of bone resorption and formation during treatment were all statistically inter- correlated (p<0.01) with no notable differences between the 3 agents studied, so that the groups were pooled for analysis. Spearman correlation coefficients and the p-values were computed. Results: A total of 90 participants were evaluable at baseline and at 24 weeks (29 A, 29 L, 32 E). As expected, baseline BMI correlated with pre-treatment circulating endogenous oestradiol (r=0.28, p=0.007) and both BMI and oestradiol negatively correlated with baseline serum CTX (r=-0.32, p=0.0025 and r=-0.35, p=0.0007 respectively) and PINP (r=-0.30, p=0.004 and r=-0.26, p=0.016 respectively). Baseline BMI and oestradiol were significantly correlated with the increase in serum CTX (r=0.26, p=0.015 and r=0.23, p=0.032 respectively) and BMI also correlated significantly with the increase in serum PINP (r=0.23, p=0.030). Conclusions: Steroidal and non-steroidal AIs increase bone turnover with the greatest increase in women with high BMI and higher oestradiol levels at baseline. As increased bone turnover is an independent risk factor for fracture, a high BMI may not confer a reduced fracture risk in the setting of AI use in early breast cancer. No significant financial relationships to disclose.

scholarly journals Efficacy of denosumab for restoring normal bone mineral density in women receiving adjuvant aromatase inhibitors for early breast cancer

Medicine ◽  
2019 ◽  
Vol 98 (32) ◽  
pp. e16770 ◽  
Author(s):  
Koichi Sakaguchi ◽  
Hisako Ono ◽  
Katsuhiko Nakatsukasa ◽  
Takashi Ishikawa ◽  
Yoshie Hasegawa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Mineral Density ◽  
Early Breast Cancer ◽  
Bone Mineral ◽  
Aromatase Inhibitors ◽  
Mineral Density ◽  
Normal Bone ◽  
Normal Bone Mineral Density

Cost Effectiveness of Fracture Prevention in Postmenopausal Women Who Receive Aromatase Inhibitors for Early Breast Cancer

2012 ◽  
Vol 30 (13) ◽  
pp. 1468-1475 ◽  
Author(s):  
Kouta Ito ◽  
Victoria S. Blinder ◽  
Elena B. Elkin
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Postmenopausal Women ◽  
Early Breast Cancer ◽  
Aromatase Inhibitors ◽  
Fracture Prevention ◽  
Bisphosphonate Therapy ◽  
Oral Bisphosphonates ◽  
Mineral Density ◽  
Life Years

Purpose Aromatase inhibitors (AIs) increase the risk of osteoporosis and related fractures in postmenopausal women who receive adjuvant AIs for hormone receptor (HR) –positive early breast cancer (EBC). We compared the cost effectiveness of alternative screening and treatment strategies for fracture prevention. Methods We developed a Markov state transition model to simulate clinical practice and outcomes in a hypothetical cohort of women age 60 years with HR-positive EBC starting a 5-year course of AI therapy after primary surgery for breast cancer. Outcomes were quality-adjusted life-years (QALYs), lifetime cost, and incremental cost-effectiveness ratio (ICER). We compared the following strategies: no intervention; one-time bone mineral density (BMD) screening and selective bisphosphonate therapy in women with osteoporosis or osteopenia; annual BMD screening and selective bisphosphonate therapy in women with osteoporosis or osteopenia; and universal bisphosphonate therapy. Results ICERs for annual BMD screening followed by oral bisphosphonates for those with osteoporosis, annual BMD screening followed by oral bisphosphonates for those with osteopenia, and universal treatment with oral bisphosphonates were $87,300, $129,300, and $283,600 per QALY gained, respectively. One-time BMD screening followed by oral bisphosphonates for those with osteoporosis or osteopenia was dominated. Our results were sensitive to age at the initiation of AI therapy, type of bisphosphonates, post-treatment residual effect of bisphosphonates, and a potential adjuvant benefit of intravenous bisphosphonates. Conclusion In postmenopausal women receiving adjuvant AIs for HR-positive EBC, a policy of baseline and annual BMD screening followed by selective treatment with oral bisphosphonates for those diagnosed with osteoporosis is a cost-effective use of societal resources.

Vitamin D deficiency and bone mineral density in postmenopausal women receiving aromatase inhibitors for early breast cancer

Maturitas ◽  
2010 ◽  
Vol 66 (3) ◽  
pp. 291-297 ◽  
Author(s):  
Xavier Nogues ◽  
Sonia Servitja ◽  
Maria Jesus Peña ◽  
Daniel Prieto-Alhambra ◽  
Rosa Nadal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Mineral Density ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Postmenopausal Women ◽  
Early Breast Cancer ◽  
Bone Mineral ◽  
Aromatase Inhibitors ◽  
Mineral Density
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