Abstract
Metachronous (MBC) and synchronous bilateral breast tumors (SBC) are mostly distinct primaries, whereas paired primaries and their local recurrences (LRC) share a common origin. Intra-pair gene expression variability in MBC, SBC, and LRC derives from time/tumor microenvironment-related and tumor genetic background-related factors and pairs represents an ideal model for trying to dissect tumor-related from microenvironment-related variability. Pairs of tumors derived from women with SBC (n = 18), MBC (n = 11), and LRC (n = 10) undergoing local-regional treatment were profiled for gene expression; similarity between pairs was measured using an intraclass correlation coefficient (ICC) computed for each gene and compared using analysis of variance (ANOVA). When considering biologically unselected genes, the highest correlations were found for primaries and paired LRC, and the lowest for MBC pairs. By instead limiting the analysis to the breast cancer intrinsic genes, correlations between primaries and paired LRC were enhanced, while lower similarities were observed for SBC and MBC. Focusing on stromal-related genes, the ICC values decreased for MBC and were significantly different from SBC. These findings indicate that it is possible to dissect intra-pair gene expression variability into components that are associated with genetic origin or with time and microenvironment by using specific gene subsets.
Highlights
In the last decades efforts done to guide treatment decision in the adjuvant setting or to predict breast cancer recurrence have been mainly focused on the development of distant metastases [1]
Contralateral breast cancer is regarded as a new primary; it is the most common second primary cancer in women diagnosed with breast cancer and it is not associated to the type of surgery [4,5,6,7]
In patient with synchronous bilateral cancers (SBC), Metachronous bilateral cancers (MBC), and local recurrences (LRC) the objective estimation of the variability in gene expression within tumor pairs with respect to the global variability allows for drawing interesting biological conclusions
Summary
In the last decades efforts done to guide treatment decision in the adjuvant setting or to predict breast cancer recurrence have been mainly focused on the development of distant metastases [1]. Despite a set of criteria being established for a diagnostic distinction between contralateral second breast cancer and metastatic spread to the contralateral breast, sometimes it is still difficult to reach a clear diagnostic assessment Such diagnostic difficulties justify the constant appearance of reports, mainly based on genetic criteria, which exploit new cutting-edge techniques to define the differences or similarities between bilateral primaries [11,12,13,14,15]. These type of studies are important since distinction between new primary and metastasis is not purely a classification issue, but has prognostic and treatment implications. If considered metastatic, a systemic treatment could be the only type of treatment taken into consideration
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
