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Receptor conversion in carcinoma breast metastatic to the bone marrow.

ABSTRACT: Breast cancer is the first in the incidence of malignancies among women. The documented frequency of osseous metastasis from breast cancer is about 12.8 %. Although breast cancer cells have been documented in the bone marrow in autopsy, haematological manifestations due to metastatic disease to the marrow is rare. The prognosis of these cases is dismal and improper management worsen the condition further. IHC for ER, PR & Her 2/neu status plays a vital role in ascertaining the treatment protocol both in primary tumors as well as metastatic or recurrent tumors. Receptor conversion has been documented in metastatic and recurrent cases. We report a case of 65 year female with a history of ER, PR positive and Her 2/neu negative carcinoma breast 3½ years back, presented with anemia and low back ache diagnosed as metastatic breast carcinoma to bone marrow with receptor conversion.

SUBMITTER: Santosh T

PROVIDER: S-EPMC4192187 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Receptor conversion in carcinoma breast metastatic to the bone marrow.

Santosh T T Patro M K MK Nayak J J Bal A K AK Choudhury A A Behera B B Mishra D P DP

Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 20140601 Suppl 1

Breast cancer is the first in the incidence of malignancies among women. The documented frequency of osseous metastasis from breast cancer is about 12.8 %. Although breast cancer cells have been documented in the bone marrow in autopsy, haematological manifestations due to metastatic disease to the marrow is rare. The prognosis of these cases is dismal and improper management worsen the condition further. IHC for ER, PR & Her 2/neu status plays a vital role in ascertaining the treatment protocol ...[more]

PMID: 25332613

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Project description:Effective treatment of cancer metastasis to the bone relies on bone marrow drug accumulation. The surface proteins in the bone marrow vascular endothelium provide docking sites for targeted drug delivery. We have developed a thioaptamer that specifically binds to E-selectin that is overexpressed in the vasculature of tumor and inflammatory tissues. In this study, we tested targeted delivery of therapeutic siRNA loaded in the E-selectin thioaptamer-conjugated multistage vector (ESTA-MSV) drug carrier to bone marrow for the treatment of breast cancer bone metastasis. We evaluated tumor type- and tumor growth stage-dependent targeting in mice bearing metastatic breast cancer in the bone, and carried out studies to identify factors that determine targeting efficiency. In a subsequent study, we delivered siRNA to knock down expression of the human STAT3 gene in murine xenograft models of human MDA-MB-231 breast tumor, and assessed therapeutic efficacy. Our studies revealed that the CD31(+)E-selectin(+) population accounted for 20.8%, 26.4% and 29.9% of total endothelial cells respectively inside the femur of mice bearing early, middle and late stage metastatic MDA-MB-231 tumors. In comparison, the double positive cells remained at a basal level in mice with early stage MCF-7 tumors, and jumped to 23.9% and 28.2% when tumor growth progressed to middle and late stages. Accumulation of ESTA-MSV inside the bone marrow correlated with the E-selectin expression pattern. There was up to 5-fold enrichment of the targeted MSV in the bone marrow of mice bearing early or late stage MDA-MB-231 tumors and of mice with late stage, but not early stage, MCF-7 tumors. Targeted delivery of STAT3 siRNA in ESTA-MSV resulted in knockdown of STAT3 expression in 48.7% of cancer cells inside the bone marrow. Weekly systemic administration of ESTA-MSV/STAT3 siRNA significantly extended survival of mice with MDA-MB-231 bone metastasis. In conclusion, targeting the overexpressed E-selectin provides an effective approach for tissue-specific drug delivery to the bone marrow. Tumor growth in the bone can be effectively inhibited by blockage of the STAT3 signaling.

Project description:Background99mTechnetium labeled methylene diphosphonate bone scans (BSs) are commonly used to monitor disease progression in bone for patients with metastatic breast cancer (MBC). However, new BS lesions may represent osteoblastic bone healing, which we now define as bone pseudoprogression. In this study, we aimed to assess the clinical significance and determination methods of bone pseudoprogression.MethodsThis retrospective analysis was conducted among 48 patients with hormone receptor-positive MBC treated with first-line endocrine therapy. Four months after initiating therapy, all the participants did not show extraosseous disease progression. Participants were divided into two groups according to the presence of new BS lesions. All the patients continued on treatment until explicit disease progression (extraosseous disease progression or progressive lysis on bone lesions). Explicit progression-free survival (PFS) and extraosseous objective response rate were analyzed between the two groups.ResultsNew BS lesions were observed in 11 of 48 (22.9%) patients. All the new BS lesions appeared as osteoblastic bone lesions on computed tomography. For patients with new BS lesions, the median PFS was 26.57 months [95% confidence interval (CI) 15.46-37.68], which was similar to that (29.57 months; 95% CI 19.24-39.90) in patients without new BS lesions [hazard ratio: 1.098 (95% CI 0.482-2.503), p = 0.818]. Notably, 82.9% of patients without new BS lesions showed an extraosseous objective response, whereas 85.7% of patients with new BS lesions demonstrated an extraosseous objective response [odds ratio: 0.806 (95% CI 0.061-5.682), p = 0.999]. The median interval between bone pseudoprogression and true disease progression was 21.26 months (95% CI 10.11-32.42).ConclusionsOsteoblastic new BS lesions detected on follow-up BSs may represent bone pseudoprogression. Clinicians should raise awareness of bone pseudoprogression, thereby avoiding premature discontinuation of therapy and maximizing the opportunity to benefit from endocrine therapy. Due to the small sample size and retrospective nature of the study, large prospective clinical trials are needed to confirm our findings.

Dataset Information

Receptor conversion in carcinoma breast metastatic to the bone marrow.

Publications

Receptor conversion in carcinoma breast metastatic to the bone marrow.

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