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Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas.

ABSTRACT: The aim of this study was to compare clinical and pathological outcomes after neoadjuvant chemotherapy between oestrogen receptor (ER)-positive invasive pure lobular carcinoma (ILC) and invasive ductal carcinoma (IDC).This analysis included 1895 patients (n=177 ILC; n=1718 IDC), with stage I-III breast cancer, who received neoadjuvant chemotherapy. Clinical and pathological response rates, the frequency of positive surgical margins and rate of breast-conserving surgery were compared.There was a trend for fewer good clinical responses in ILC compared with IDC. Tumour downstaging was significantly less frequent in ILC. Positive or close surgical resection margins were more frequent in ILC, and breast-conserving surgery was less common (P<0.001). These outcome differences remained significant in multivariate analysis, including tumour size, nodal status, age, grade and type of chemotherapy. Invasive pure lobular carcinoma was also associated with a significantly lower pathological complete response (pCR) rate in univariate analysis, but this was no longer significant after adjusting for tumour size and grade.Neoadjuvant chemotherapy results in lower rates of clinical benefit, including less downstaging, more positive margins and fewer breast-conserving surgeries in ER-positive ILC compared with ER-positive IDC. Pathological complete responses are rare in both groups, but do not significantly differ after adjusting for other variables.

SUBMITTER: Delpech Y

PROVIDER: S-EPMC3566807 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

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Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas.

Delpech Y Y Coutant C C Hsu L L Barranger E E Iwamoto T T Barcenas C H CH Hortobagyi G N GN Rouzier R R Esteva F J FJ Pusztai L L

British journal of cancer 20130108 2

<h4>Background</h4>The aim of this study was to compare clinical and pathological outcomes after neoadjuvant chemotherapy between oestrogen receptor (ER)-positive invasive pure lobular carcinoma (ILC) and invasive ductal carcinoma (IDC).<h4>Methods</h4>This analysis included 1895 patients (n=177 ILC; n=1718 IDC), with stage I-III breast cancer, who received neoadjuvant chemotherapy. Clinical and pathological response rates, the frequency of positive surgical margins and rate of breast-conserving ...[more]

PMID: 23299541

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Project description:Mixed ductal-lobular carcinomas (MDLs) show both ductal and lobular morphology, and constitute an archetypal example of intratumoural morphological heterogeneity. The mechanisms underlying the coexistence of these different morphological entities are poorly understood, although theories include that these components either represent 'collision' of independent tumours or evolve from a common ancestor. We performed comprehensive clinicopathological analysis of a cohort of 82 MDLs, and found that: (1) MDLs more frequently coexist with ductal carcinoma in situ (DCIS) than with lobular carcinoma in situ (LCIS); (2) the E-cadherin-catenin complex was normal in the ductal component in 77.6% of tumours; and (3) in the lobular component, E-cadherin was almost always aberrantly located in the cytoplasm, in contrast to invasive lobular carcinoma (ILC), where E-cadherin is typically absent. Comparative genomic hybridization and multiregion whole exome sequencing of four representative cases revealed that all morphologically distinct components within an individual case were clonally related. The mutations identified varied between cases; those associated with a common clonal ancestry included BRCA2, TBX3, and TP53, whereas those associated with clonal divergence included CDH1 and ESR1. Together, these data support a model in which separate morphological components of MDLs arise from a common ancestor, and lobular morphology can arise via a ductal pathway of tumour progression. In MDLs that present with LCIS and DCIS, the clonal divergence probably occurs early, and is frequently associated with complete loss of E-cadherin expression, as in ILC, whereas, in the majority of MDLs, which present with DCIS but not LCIS, direct clonal divergence from the ductal to the lobular phenotype occurs late in tumour evolution, and is associated with aberrant expression of E-cadherin. The mechanisms driving the phenotypic change may involve E-cadherin-catenin complex deregulation, but are yet to be fully elucidated, as there is significant intertumoural heterogeneity, and each case may have a unique molecular mechanism. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Project description:Invasive ductal and lobular carcinomas (IDC and ILC) are the most common histological types of breast cancer. Clinical follow-up data and metastatic patterns suggest that the development and progression of these tumors are different. The aim of our study was to identify gene expression profiles of IDC and ILC in relation to normal breast epithelial cells.We examined 30 samples (normal ductal and lobular cells from 10 patients, IDC cells from 5 patients, ILC cells from 5 patients) microdissected from cryosections of ten mastectomy specimens from postmenopausal patients. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. Samples were analysed upon Affymetrix U133 Plus 2.0 Arrays. The expression of seven differentially expressed genes (CDH1, EMP1, DDR1, DVL1, KRT5, KRT6, KRT17) was verified by immunohistochemistry on tissue microarrays. Expression of ASPN mRNA was validated by in situ hybridization on frozen sections, and CTHRC1, ASPN and COL3A1 were tested by PCR.Using GCOS pairwise comparison algorithm and rank products we have identified 84 named genes common to ILC versus normal cell types, 74 named genes common to IDC versus normal cell types, 78 named genes differentially expressed between normal ductal and lobular cells, and 28 named genes between IDC and ILC. Genes distinguishing between IDC and ILC are involved in epithelial-mesenchymal transition, TGF-beta and Wnt signaling. These changes were present in both tumor types but appeared to be more prominent in ILC. Immunohistochemistry for several novel markers (EMP1, DVL1, DDR1) distinguished large sets of IDC from ILC.IDC and ILC can be differentiated both at the gene and protein levels. In this study we report two candidate genes, asporin (ASPN) and collagen triple helix repeat containing 1 (CTHRC1) which might be significant in breast carcinogenesis. Besides E-cadherin, the proteins validated on tissue microarrays (EMP1, DVL1, DDR1) may represent novel immunohistochemical markers helpful in distinguishing between IDC and ILC. Further studies with larger sets of patients are needed to verify the gene expression profiles of various histological types of breast cancer in order to determine molecular subclassifications, prognosis and the optimum treatment strategies.

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Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas.

Publications

Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas.

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