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The Rodent Liver Undergoes Weaning-Induced Involution and Supports Breast Cancer Metastasis.

ABSTRACT: Patients with postpartum breast cancer are at increased risk for metastasis compared with age-matched nulliparous or pregnant patients. Here, we address whether circulating tumor cells have a metastatic advantage in the postpartum host and find the postlactation rodent liver preferentially supports metastasis. Upon weaning, we observed liver weight loss, hepatocyte apoptosis, extracellular matrix remodeling including deposition of collagen and tenascin-C, and myeloid cell influx, data consistent with weaning-induced liver involution and establishment of a prometastatic microenvironment. Using intracardiac and intraportal metastasis models, we observed increased liver metastasis in post-weaning BALB/c mice compared with nulliparous controls. Human relevance is suggested by a ?3-fold increase in liver metastasis in patients with postpartum breast cancer (n = 564) and by liver-specific tropism (n = 117). In sum, our data reveal a previously unknown biology of the rodent liver, weaning-induced liver involution, which may provide insight into the increased liver metastasis and poor prognosis of women diagnosed with postpartum breast cancer.We find that patients with postpartum breast cancer are at elevated risk for liver metastasis. We identify a previously unrecognized biology, namely weaning-induced liver involution, that establishes a prometastatic microenvironment, and which may account in part for the poor prognosis of patients with postpartum breast cancer. Cancer Discov; 7(2); 177-87. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 115.

SUBMITTER: Goddard ET

PROVIDER: S-EPMC5459606 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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The Rodent Liver Undergoes Weaning-Induced Involution and Supports Breast Cancer Metastasis.

Goddard Erica T ET Hill Ryan C RC Nemkov Travis T D'Alessandro Angelo A Hansen Kirk C KC Maller Ori O Mongoue-Tchokote Solange S Mori Motomi M Partridge Ann H AH Borges Virginia F VF Schedin Pepper P

Cancer discovery 20161214 2

Patients with postpartum breast cancer are at increased risk for metastasis compared with age-matched nulliparous or pregnant patients. Here, we address whether circulating tumor cells have a metastatic advantage in the postpartum host and find the postlactation rodent liver preferentially supports metastasis. Upon weaning, we observed liver weight loss, hepatocyte apoptosis, extracellular matrix remodeling including deposition of collagen and tenascin-C, and myeloid cell influx, data consistent ...[more]

PMID: 27974414

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Project description:Background: Breast cancer with liver metastasis consists of a group of heterogeneous diseases, and survival time may be significantly different, ranging from a few months to several years. The present study aimed to develop and externally validate a prognostic model for breast cancer with liver metastasis (BCLM). Methods: In total, 1022 eligible patients from January 2007 to December 2018 were selected from Fudan University Shanghai Cancer Center (FUSCC) and were temporally in the training (n = 715) and validation (n = 307) set. According to regression coefficients found in the multivariate Cox regression analysis, the final results were transformed into the prognostic scores. On the basis of these scores, patients were finally classified into three risk groups, including low-, intermediate-, and high-risk groups. Bootstrapping was used for internal validation. Then, time-dependent receiver operating characteristic (ROC) curves and calibration plots were used to assess discrimination and calibration of this prognostic model in the validation set. Results: Molecular subtypes, metastatic-free interval (MFI), extrahepatic metastasis, and liver function tests were identified as independent prognostic factors in the multivariate analysis. According to risk stratification, intermediate-risk (hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.74-2.58, P < 0.001) and high-risk groups (HR 6.94, 95% CI 5.25-9.16, P < 0.001) had significantly worse prognoses in comparison with the low-risk group regarding overall survival (OS) from the time of metastasis. The median OS in these three groups were 39.97, 21.03, and 8.80 months, respectively. These results were confirmed in the internal and external validation cohorts. Conclusions: Based on molecular classification of tumors, routine laboratory tests, and other clinical information easily accessible in daily clinical practice, we developed a clinical tool for BCLM patients to predict their prognosis. Moreover, it may be useful for identifying the subgroup with unfavorable prognosis and individualization of treatment.

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The Rodent Liver Undergoes Weaning-Induced Involution and Supports Breast Cancer Metastasis.

Publications

The Rodent Liver Undergoes Weaning-Induced Involution and Supports Breast Cancer Metastasis.

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