Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients

Background: Despite widespread use of repeated doses of potent bone-targeting agents (BTA) in oncology patients, relatively little is known about their in vivo effects on bone homeostasis, bone quality, and bone architecture. Traditionally bone quality has been assessed using a trans-iliac bone biop...

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Autores principales:	A. Beltran-Bless, M. Murshed, M. Zakikhani, I. Kuchuk, N. Bouganim, S. Robertson, N. Kekre, L. Vandermeer, J. Li, C.L. Addison, F. Rauch, M. Clemons, R. Kremer
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Bone-targeted agents Breast cancer Bone biopsy Bone microarchitecture Histomorphometry Bone turnover Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/cdead4ab59484a35bca513740eba4eb6
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spelling	oai:doaj.org-article:cdead4ab59484a35bca513740eba4eb62021-11-20T05:06:53ZHistomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients2352-187210.1016/j.bonr.2021.101145https://doaj.org/article/cdead4ab59484a35bca513740eba4eb62021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352187221004022https://doaj.org/toc/2352-1872Background: Despite widespread use of repeated doses of potent bone-targeting agents (BTA) in oncology patients, relatively little is known about their in vivo effects on bone homeostasis, bone quality, and bone architecture. Traditionally bone quality has been assessed using a trans-iliac bone biopsy with a 7 mm “Bordier” core needle. We examined the feasibility of using a 2 mm “Jamshidi™” core needle as a more practical and less invasive technique. Methods: Patients with metastatic breast cancer on BTAs were divided according to the extent of bone metastases. They were given 2 courses of tetracycline labeling and then underwent a posterior trans-iliac trephine biopsy and bone marrow aspirate. Samples were analyzed for the extent of tumor invasion and parameters of bone turnover and bone formation by histomorphometry. Results: Twelve patients were accrued, 1 had no bone metastases, 3 had limited bone metastases (LSM) (<3 lesions) and 7 had extensive bone metastases (ESM) (>3 lesions). Most of the primary tumors were estrogen receptor (ER)/progesterone receptor (PR) positive. The procedure was well tolerated. The sample quality was sufficient to analyze bone trabecular structure and bone turnover by histomorphometry in 11 out of 12 patients. There was a good correlation between imaging data and morphometric analysis of tumor invasion. Patients with no evidence or minimal bone metastases had no evidence of tumor invasion. Most had suppressed bone turnover and no detectable bone formation when treated with BTA. In contrast, 6 out of 7 patients with extensive bone invasion by imaging and evidence of tumor cells in the marrow had intense osteoclastic activity as measured by the number of osteoclasts. Of these 7 patients with ESM, 6 were treated with BTA with 5 showing resistance to BTA as demonstrated by the high number of osteoclasts present. 3 of these 6 patients had active bone formation. Based on osteoblast activity and bone formation, 3 out of 6 patients with ESM responded to BTA compared to all 3 with LSM. Compared to untreated patients, all patients treated with BTA showed a trend towards suppression of bone formation, as measured by tetracycline labelling. There was also a trend towards a significant difference between ESM and LSM treated with BTA, highly suggestive of resistance although limited by the small sample size. Discussion: Our results indicate that trans-iliac bone biopsy using a 2 mm trephine shows excellent correlation between imaging assessment of tumor invasion and tumor burden by morphometric analysis of bone tissues. In addition, our approach provides additional mechanistic information on therapeutic response to BTA supporting the current clinical understanding that the majority of patients with extensive bone involvement eventually fail to suppress bone turnover (Petrut B, et al. 2008). This suggests that antiresorptive therapies become less effective as disease progresses.A. Beltran-BlessM. MurshedM. ZakikhaniI. KuchukN. BouganimS. RobertsonN. KekreL. VandermeerJ. LiC.L. AddisonF. RauchM. ClemonsR. KremerElsevierarticleBone-targeted agentsBreast cancerBone biopsyBone microarchitectureHistomorphometryBone turnoverDiseases of the musculoskeletal systemRC925-935ENBone Reports, Vol 15, Iss , Pp 101145- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bone-targeted agents Breast cancer Bone biopsy Bone microarchitecture Histomorphometry Bone turnover Diseases of the musculoskeletal system RC925-935
spellingShingle	Bone-targeted agents Breast cancer Bone biopsy Bone microarchitecture Histomorphometry Bone turnover Diseases of the musculoskeletal system RC925-935 A. Beltran-Bless M. Murshed M. Zakikhani I. Kuchuk N. Bouganim S. Robertson N. Kekre L. Vandermeer J. Li C.L. Addison F. Rauch M. Clemons R. Kremer Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients
description	Background: Despite widespread use of repeated doses of potent bone-targeting agents (BTA) in oncology patients, relatively little is known about their in vivo effects on bone homeostasis, bone quality, and bone architecture. Traditionally bone quality has been assessed using a trans-iliac bone biopsy with a 7 mm “Bordier” core needle. We examined the feasibility of using a 2 mm “Jamshidi™” core needle as a more practical and less invasive technique. Methods: Patients with metastatic breast cancer on BTAs were divided according to the extent of bone metastases. They were given 2 courses of tetracycline labeling and then underwent a posterior trans-iliac trephine biopsy and bone marrow aspirate. Samples were analyzed for the extent of tumor invasion and parameters of bone turnover and bone formation by histomorphometry. Results: Twelve patients were accrued, 1 had no bone metastases, 3 had limited bone metastases (LSM) (<3 lesions) and 7 had extensive bone metastases (ESM) (>3 lesions). Most of the primary tumors were estrogen receptor (ER)/progesterone receptor (PR) positive. The procedure was well tolerated. The sample quality was sufficient to analyze bone trabecular structure and bone turnover by histomorphometry in 11 out of 12 patients. There was a good correlation between imaging data and morphometric analysis of tumor invasion. Patients with no evidence or minimal bone metastases had no evidence of tumor invasion. Most had suppressed bone turnover and no detectable bone formation when treated with BTA. In contrast, 6 out of 7 patients with extensive bone invasion by imaging and evidence of tumor cells in the marrow had intense osteoclastic activity as measured by the number of osteoclasts. Of these 7 patients with ESM, 6 were treated with BTA with 5 showing resistance to BTA as demonstrated by the high number of osteoclasts present. 3 of these 6 patients had active bone formation. Based on osteoblast activity and bone formation, 3 out of 6 patients with ESM responded to BTA compared to all 3 with LSM. Compared to untreated patients, all patients treated with BTA showed a trend towards suppression of bone formation, as measured by tetracycline labelling. There was also a trend towards a significant difference between ESM and LSM treated with BTA, highly suggestive of resistance although limited by the small sample size. Discussion: Our results indicate that trans-iliac bone biopsy using a 2 mm trephine shows excellent correlation between imaging assessment of tumor invasion and tumor burden by morphometric analysis of bone tissues. In addition, our approach provides additional mechanistic information on therapeutic response to BTA supporting the current clinical understanding that the majority of patients with extensive bone involvement eventually fail to suppress bone turnover (Petrut B, et al. 2008). This suggests that antiresorptive therapies become less effective as disease progresses.
format	article
author	A. Beltran-Bless M. Murshed M. Zakikhani I. Kuchuk N. Bouganim S. Robertson N. Kekre L. Vandermeer J. Li C.L. Addison F. Rauch M. Clemons R. Kremer
author_facet	A. Beltran-Bless M. Murshed M. Zakikhani I. Kuchuk N. Bouganim S. Robertson N. Kekre L. Vandermeer J. Li C.L. Addison F. Rauch M. Clemons R. Kremer
author_sort	A. Beltran-Bless
title	Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients
title_short	Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients
title_full	Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients
title_fullStr	Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients
title_full_unstemmed	Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients
title_sort	histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/cdead4ab59484a35bca513740eba4eb6
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Histomorphometric and microarchitectural analysis of bone in metastatic breast cancer patients

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