Gaëtan Macgrogan

Institut Bergonié · BioPathology

Antiandrogens (AA) have been tested in clinical trials in androgen receptor (AR) + triple-negative breast cancer (TNBC). We aim to assess the clinical benefit rate (CBR) of AA in real life. The primary end-point was CBR at 6 months. Twenty-four patients were assessable and received: abiraterone acetate (62 %), enzalutamide (8 %) and bicalutamide (3...

The neuropeptide-Y (NPY) family acts through four G protein-coupled receptor subtypes in humans, namely, Y1, Y2, Y4, and Y5. A growing body of evidence suggest the involvement of the NPY system in several cancers, notably the Y5 subtype, thus acting as a relevant target for the development of radiopharmaceuticals for imaging or targeted radionuclid...

Background: Very young premenopausal women diagnosed with hormone receptor-positive, HER2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. Patients and methods: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the SOFT clinical trial t...

Purpose Androgen Receptor (AR) + triple-negative breast cancer (TNBC) accounts for approximately 25% of all TNBC. Several trials using different antiandrogens (AA) found clinical benefit rates (CBR) ranging from 19 to 29%. The aim of this retrospective trial was to assess the clinical benefit of AA in real life. Methods Patients with metastatic AR...

Background: When triple-negative breast cancer (TNBC) patients have residual disease after neoadjuvant chemotherapy (NACT), they have a high risk of metastatic relapse. With immune infiltrate in TNBC being prognostic and predictive of response to treatment, our aim was to develop an immunologic transcriptomic signature using post-NACT samples to p...

Background The reverse sequence of neoadjuvant chemotherapy, preoperative radiotherapy, mastectomy then immediate breast reconstruction is currently proposed for selected patients with locally advanced breast cancer. Few studies have compared it to the standard sequence of neoadjuvant chemotherapy, mastectomy and radiotherapy with or without differ...

The similarities between sporadic basal-like breast cancer (BLBC) and BRCA1-mutated breast tumours raise the possibility that deregulation of the same pathway may underlie these tumour types. The aim of this study was to determine if PTEN aberrations are characteristic of both BRCA1 tumours and sporadic TN breast carcinomas with low BRCA1 expressio...

PurposeNeurotensin receptor-1 (NTS1) is increasingly recognized as a potential target in diverse tumors including breast cancer, but factors associated with NTS1 expression have not been fully clarified.Methods We studied NTS1 expression using the Tissue MicroArray (TMA) of primary breast tumors from Institut Bergonié. We also studied association b...

Objectives: Due to COVID-19, a lockdown took place between March 17 and May 1, 2020, in France. This study evaluates the impact of the lockdown on the diagnosis and staging of breast cancers in a tertiary cancer centre. Methods: Our database was searched for all consecutive invasive breast cancers diagnosed in our institution during the lockdown...

Treatment of patients with residual disease after neoadjuvant chemotherapy for breast cancer is an unmet clinical need. We hypothesised that tumour subclones showing expansion in residual disease after chemotherapy would contain mutations conferring drug resistance. We studied oestrogen receptor and/or progesterone receptor-positive, HER2-negative...

Résumé Les dernières recommandations internationales pour l’évaluation du statut HER2 dans les cancers du sein, basées sur vingt ans d’expérience et sur les résultats de nombreuses études cliniques, ont vu le jour en 2018. D’autre part, la notion émergente de catégorie HER2 faible pour les cancers du sein de score 1+ en immunohistochimie ou de scor...

Aims Breast hamartomas are an under-recognized lesion because they lack a distinctive microscopic appearance. Microscopic diagnosis can often conclude "no significant lesion" or "normal breast tissue", leading to repeated biopsies and diagnostic delay. We describe the histological, immunohistochemical and radiological features of breast hamartomas...

Expression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients....

Primary triple-negative invasive lobular breast carcinomas (TN-ILCs), which do not express hormone receptors and HER2 at diagnosis, are rare and poorly known. In this study, we analyzed the largest TN-ILC series ever reported in the literature, in comparison to phenotypically similar breast tumor subtypes: triple-negative invasive ductal carcinoma...

Background: Triple negative breast cancer (TNBC) is an heterogeneous disease and encompasses at least 4 subtypes. One of these expresses the androgen receptor (AR). Several prospective trials demonstrated antitumour efficacy with anti-androgen treatment in patients with advanced breast cancer. Darolutamide is an androgen-receptor antagonist with a...

Breast cancer remains the first cause of death in women worldwide even if the average 10-year survival rate is 83%. It remains difficult to accurately evaluate the risk of recurrence, and consequently the need of chemotherapy, in estrogen receptor (ER)-positive, HER2-negative early breast cancers, at the individual level, leading to overtreatment f...

Few data are available on survival and predictive factors in early breast cancer (BC) patients treated with neoadjuvant endocrine therapy (NET). This is a pooled analysis of two multicentre, randomised non-comparative phase 2 clinical trials evaluating neoadjuvant anastrozole and fulvestrant efficacy for postmenopausal HR+/HER2- breast cancer patie...

Purpose There is a need to refine the prognosis of triple-negative breast cancer (TNBC) patients after neoadjuvant chemotherapy (NAC) and to study the influence of the tumor microenvironment. We evaluated the prognostic value of pathological and immune markers in TNBC with residual disease (RD) after NAC. Methods In a series of 186 TNBC patients t...

Adenoid cystic carcinoma (ACC) of the breast with a predominant solid pattern is difficult to diagnose with certainty and differentiate from more common triple-negative breast cancers (TNBCs) of basal-phenotype. To better characterize solid ACC, we performed a clinical, morphological, immunohistochemical, and molecular comparative analysis of 33 AC...

Purpose: Uterine leiomyosarcoma, which accounts for 7% of all soft-tissue sarcomas and 1-3% of all uterine malignancies, is an aggressive tumor responsible for a significant proportion of uterine cancer deaths. While FIGO stage is the most important prognostic factor, metastatic and relapse rates at stage I exceed 50% so it is currently impossible...

The process by which patients experience a series of recurrent events, such as hospitalizations, may be subject to death. In cohort studies, one strategy for analyzing such data is to fit a joint frailty model for the intensities of the recurrent event and death, which estimates covariate effects on the two event types while accounting for their de...

Introduction: Ductal carcinoma in situ (DCIS) accounts for 15% of all breast cancers and generally, the prognosis is good if treated optimally. The standard treatment includes breast conservative surgery along with adjuvant radiotherapy. Skin-sparing mastectomy (SSM) preserves the breast skin envelope but its oncological safety poses a few concern...

Résumé La chimiothérapie néoadjuvante est une option thérapeutique de plus en plus utilisée dans la stratégie de prise en charge des cancers du sein. La réponse histologique au traitement néoadjuvant, essentiellement sous la forme d’une réponse pathologique complète, est aujourd’hui utilisée comme facteur pronostique et comme critère validé d’évalu...

Neurotensin and its high-affinity receptor, NTR1 , are involved in the growth of various tumors. Few data are available regarding NTR1 expression in normal and tumoral human prostate tissue samples. NTR1 expression was assessed using immunohistochemistry in 12 normal prostate tissues, 11 benign prostatic hyperplasia (BPH), 44 prostate cancers, and...

Triple-negative breast cancer (TNBC) patients have an increased risk of developing visceral metastases and other primary nonbreast cancers, particularly lung cancer. The differential diagnosis of TNBC metastases and primary cancers from other organs can be difficult due to lack of a TNBC standard immunoprofile. We analyzed the diagnostic value of e...

Background: We explored, within the EORTC10994 study, the outcomes for patients with molecular apocrine (MA) breast cancer, and defined immunohistochemistry (IHC) as androgen-receptor (AR) positive, oestrogen (ER) and progesterone (PR) negative. We also assessed the concordance between IHC and gene expression arrays (GEA) in the identification of...

Background The EndoPredict (EP) test has been developed and validated for assessing recurrence risk in patients with estrogen receptor (ER)-positive HER2-negative breast cancer (BC). This test is based on the expression of 12 genes (molecular score), combined with clinicopathological criteria ( tumor size and nodal status) (EPclin risk score). For...

Background: Therapeutic options at diagnosis for metastatic breast cancers (MBC) differ largely according to cancer phenotype (namely, hormone receptor (HR) and HER2 status). Reported discordance rates between primary tumor and metastasis vary widely in literature, with a median of 18% for estrogen receptor, 31% for progesterone receptor and 10% fo...

Purpose: Our aim was to identify predictive factors of abiraterone acetate (AA) efficacy and putative new druggable targets in androgen receptor (AR)-positive triple-negative breast cancer (TNBC) treated in the UCBG 2012-1 trial. Material and methods: We defined AA response as either complete or partial response, or stable disease at 6 months. Usin...

Introduction Neoadjuvant chemotherapy (NAC) is proposed for locally advanced breast cancer (LABC) to increase the breast conservative treatment (BCT). In France, mastectomy is the risk-reducing prophylactic surgical strategy only for pre-symptomatic germline -mutated (gm) patients. On the other hand, BCT is proposed to all patients following NAC ba...

The Gastrin-Releasing Peptide Receptor (GRPR) is over-expressed in estrogen receptor (ER) positive breast tumors and related metastatic lymph nodes offering the opportunity of imaging and therapy of luminal tumors. ⁶⁸Ga-RM2 binding and ¹⁸F-FDG binding in tumoral zones were measured and compared using tissue micro-imaging with a beta imager on 14 br...

68Ga-RM2 binding in 18F-FDG-positive (18F-FDG+) and 18F-FDG-negative (18F-FDG-) tumors. (TIF)

Cowden syndrome (CS) is an autosomal dominant mendelian disease related to germline pathogenic variants affecting the PTEN-gene. CS is characterized by macrocephaly, mucocutaneous lesions, and an increased risk of breast and thyroid cancers. Rare ovarian cancer cases (mostly embryonic tumors) associated with PTEN have been described in the literatu...

Purpose: Our aim was to identify predictive factors of abiraterone acetate efficacy and putative new druggable targets in androgen receptor (AR)-positive triple-negative breast cancer (TNBC) treated in the UCBG 2012-1 trial. Experimental Design: We defined abiraterone acetate response as either complete or partial response, or stable disease at 6 m...

Medullary breast carcinoma (MBC) is a rare subtype of triple-negative breast cancer with specific genomic features within the spectrum of basal-like carcinoma (BLC). In this study including 19 MBC and 36 non-MBC BLC, we refined the transcriptomic and genomic knowledge about this entity. Unsupervised and supervised analysis of transcriptomic profile...

Dermatofibrosarcoma protuberans is underlined by recurrent collagen type I alpha 1 chain-platelet-derived growth factor B chain (COL1A1-PDGFB) fusions but ~ 4% of typical dermatofibrosarcoma protuberans remain negative for this translocation in routine molecular screening. We investigated a series of 21 cases not associated with the pathognomonic C...

Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are i...

The diagnosis of a uterine smooth muscle lesion is, in the majority of cases, straightforward. However, in a small number of cases, the morphological criteria used in such lesions cannot differentiate with certainty a benign from a malignant lesion and a diagnosis of smooth muscle tumor with uncertain malignant potential (STUMP) is made. Uterine le...

Objective: To evaluate the ability of shear-wave elastography (SWE) to distinguish between benign and malignant palpable masses of the adult male breast. Methods: Clinical examination, mammography, B-mode and Doppler ultrasound (US) findings and SWE quantitative parameters were compared in 50 benign lesions (including 40 gynecomastias) and 15 ma...

Familial breast cancers (BCs) account for 10-20% of all diagnosed BCs, yet only 20% of such tumors arise in the context of a germline mutation in known tumor suppressor genes such as BRCA1 or BRCA2. The vast genetic heterogeneity which characterizes non BRCA1 and non BRCA2 (or BRCAx) families makes grouped studies impossible to perform. Next genera...

A growing body of evidence suggests that gastrin-releasing peptide receptor (GRPR) might be a valuable target in breast cancer. In order to understand which patients can be potential candidates for GRPR-based imaging or targeted therapy, we screened invasive breast cancers by immunohistochemistry (IHC) for the presence and intensity of GRPR express...

Triple-negative breast cancer (TNBC) remains a difficult-to-treat cancer with a need for new therapeutic target. The serine/threonine protein phosphatase 2A (PP2A) functions as a tumor suppressor and enhancing PP2A activity by PP2A-activating agents is a promising anti-cancer approach. There are intrinsic inhibitors of PP2A including SET and cancer...

Medullary breast carcinoma (MBC) is a rare subtype of triple negative breast cancer (TNBC)with specific genomic features within the spectrum of basal-like carcinoma. The frequent association between BRCA constitutive mutation and MBC phenotype has been reported previously. In this study including 19 MBC and 36 non-MMB basal-like carcinoma (BLC), we...

Introduction Neoadjuvant chemotherapy (NAC) is proposed in case of locally advanced breast cancer (LABC) to improve breast conservative treatment (BCT). In the case of germline mutated (gm) patients, risk-reducing prophylactic surgical strategies in France are mastectomy for pre-symptomatic. On the other hand, BCT is proposed to all patients after...

A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expressio...

HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full...

There is a paucity of models for hormone receptor positive (HR+) breast cancer because of the difficulty of establishing xenografts from these tumours. We show that this obstacle can be overcome by injecting human tumour cells directly into the mammary ducts of immunodeficient mice. Tumours from 31 patients were infected overnight with a lentiviral...

Background Several expression array studies identified molecular apocrine breast cancer (BC) as a subtype that expresses androgen receptor (AR) but not estrogen receptor α. We carried out a multicentre single-arm phase II trial in women with AR-positive, estrogen, progesterone receptor and HER2-negative (triple-negative) metastatic or inoperable lo...

Polarity defects are a hallmark of most carcinomas. Cells from invasive micropapillary carcinomas (IMPCs) of the breast are characterized by a striking cell polarity inversion and represent an interesting model for the analysis of polarity abnormalities. In-depth investigation of polarity proteins in 24 IMPCs and a gene expression profiling, compar...

Background: HER2-positive (HER2+) breast cancers are defined by the amplification and/or overexpression of the human epidermal growth factor receptor (HER2/ERBB2) gene on chromosome region 17q12. Although anti-HER2 targeted therapies have greatly improved treatment of HER2+ breast cancer, the magnitude of benefit varies widely between patients. Dec...

Introduction La CGH array (aCGH) est une technique moléculaire pangénomique détectant des réarrangements chromosomiques (gains ou pertes). Nous en présentons une nouvelle indication pour établir un possible lien entre deux tumeurs synchrones (découvertes ou survenues en même temps) ou métachrones (survenues successivement). Observations Une patien...

The SOFT and TEXT randomized phase III trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) early breast cancer. We investigated the prognostic and predictive value of centrally assessed levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 expression in women with HER2-neg...

Significant morphological, clinical and biological prognostic factors vary according to molecular subtypes of breast tumors, yet comprehensive analysis of such factors linked to survival in each group is lacking. Clinicopathological and micro-environmental criteria, estrogen (ER), progesterone (PR) receptors, HER2, Ki67, basal markers, CD24, CD44,...

Background: We investigated the outcomes of postmenopausal women with hormone receptor-positive, early breast cancer with special histotypes (mucinous, tubular, or cribriform) enrolled in the monotherapy cohort of the BIG 1-98 trial. Patients and methods: The intention-to-treat BIG 1-98 monotherapy cohort (5 years of therapy with tamoxifen or le...

The diagnosis and management of uterine smooth muscle tumors with uncertain malignant potential (STUMP) is often challenging, and genomic data on these lesions as well as on uterine smooth muscle lesions are limited. We tested the hypothesis that genomic profile determination by array-CGH could split STUMP into a benign group with scarce chromosoma...

Secretory breast carcinoma (SBC) is a rare breast carcinoma with distinctive morphologic features and a recurrent specific chromosomal translocation t(12;15)(p13;q25), usually of low histologic grade and favorable prognosis. We describe the morphologic and genetic characteristics of 11 cases of SBC from 10 patients. Histologic and immunohistochemic...

Neoadjuvant systemic therapy is being used increasingly in the treatment of early-stage breast cancer. Response, in the form of pathological complete response, is a validated and evaluable surrogate end point of survival after neoadjuvant therapy. Thus, pathological complete response has become a primary end point for clinical trials. However, ther...

The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment. One hundred and twenty post-menopausal patients were random...

Résumé La place des signatures moléculaires dans la prise en charge adjuvante des cancers du sein reste un sujet largement débattu. Les discussions doivent tenir compte des modalités de validation scientifique, de l'impact sur les pratiques, des bénéfices attendus ainsi que des questions de financement. Cet article expose les principales limites à...

The role of molecular signatures in the adjuvant management of breast cancer remains a debated topic. Discussions should take into account the level of scientific validation, the impact on practice, the expected benefits and financing issues. This article presents the limits to be clarified before using commercial molecular signatures. Copyright ©...

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working g...

Ovarian small cell carcinoma of the hypercalcemic type (SCCOHT)/ovarian rhabdoid tumor is a rare and highly malignant tumor that typically occurs in young women. Up until now the diagnosis has been made on the basis of morphology without any specific immunohistochemical (IHC) markers. However, several authors have shown recently that SCCOHTs are ch...

During their follow-up, patients with cancer can experience several types of recurrent events and can also die. Over the last decades, several joint models have been proposed to deal with recurrent events with dependent terminal event. Most of them require the proportional hazard assumption. In the case of long follow-up, this assumption could be v...

Résumé Le diagnostic de lésions prolifératives bénignes telles la cicatrice radiaire et le papillome, et de lésions prolifératives avec atypies ont augmenté ces dernières années avec la multiplication du nombre de prélèvements percutanés. De nombreux progrès ont été faits dans leur diagnostic histologique, leur classification et leur pathogenèse. M...

The diagnosis and management of uterine smooth muscle tumors with uncertain malignant potential (STUMP) is often challenging, and genomic data on these lesions as well as on uterine smooth muscle lesions are limited. We tested the hypothesis that genomic profile determination by array-CGH could split STUMP into a benign group with scarce chromosoma...

Tumor immune escape mechanisms are being regarded as suitable targets for tumor therapy. Among these, tryptophan catabolism plays a central role in creating an immunosuppressive environment, leading to tolerance to potentially immunogenic tumor antigens. Tryptophan catabolism is initiated by either indoleamine 2,3-dioxygenase (IDO-1/-2) or tryptoph...

Cancer relapses may be useful to predict the risk of death. To take into account relapse information, the Landmark approach is popular. As an alternative, we propose the joint frailty model for a recurrent event and a terminal event to derive dynamic predictions of the risk of death. The proposed prediction settings can account for relapse history...

When invasive components are discovered at mastectomy for vacuum-assisted biopsy (VAB)-diagnosed ductal carcinoma in situ (DCIS), the only option available is axillary lymph node dissection (ALND). The primary aim of this prospective multicenter trial was to determine the benefit of performing upfront sentinel lymph node (SLN) biopsy for these pati...

Using surrogate endpoints for overall survival, such as disease-free-survival (DFS) is increasingly common in randomized controlled trials (RCTs). However, the definitions of several of these time-to-event (TTE) endpoints are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly aff...

While the addition of targeted therapy to neoadjuvant chemotherapy (NACT) dramatically increases the rate of pathological complete response in HER2-positive breast cancer, no reduction in the rate of mastectomy has been observed in randomised studies. A retrospective single centre analysis of all patients treated with anti HER2-based NACT for T2-4...

(online only) – Tissue micro array and Immunohistochemical assay

Comparison of clinicopathologic features between LA and LBH− groups.

Univariate analyses for associations between clinicopathological, microenviromental and immunohistochemical phenotypes and distant metastasis-free survival (DMFS) after five years according to luminal A and luminal B groups* (for patients with no events at 5 years).

IntroductionThe cell of origin for estrogen receptor ¿ (ER¿) positive breast cancer is probably a luminal stem cell in the terminal duct lobular units. To model these cells we have used the murine myoepithelial layer in the mouse mammary ducts as a scaffold upon which to build a human luminal layer. To prevent squamous metaplasia, a common artifact...

Objective To examine outcomes of neoadjuvant endocrine therapy in daily practice to inform decision making. Methods We retrospectively selected 204 patients who received neoadjuvant endocrine therapy with T2 (≥ 30mm) or T3 tumors, examining subsequent breast-sparing surgery and long term outcomes. Results Neoadjuvant endocrine therapy was adminis...

Biomarker assessment of breast cancer tumor samples is part of the routine workflow of pathology laboratories. International guidelines have recently been updated, with special regards to the pre-analytical steps that are critical for the quality of immunohistochemical and in situ hybridization procedures, whatever the biomarker analyzed. Fixation...

De nouvelles recommandations internationales pour l’évaluation du statut HER2 dans les cancers du sein, basées sur plus de dix ans d’expérience et sur les résultats d’études cliniques et de concordance entre les différentes techniques de détection, viennent tout juste de voir le jour. Le présent article a pour objet de faire le point sur ces nouvel...

Breast adenosquamous carcinomas are rare tumors that are categorized as subtypes of metaplastic carcinoma. They are composed of well-developed gland formation intimately admixed with solid nests of squamous cells immersed in a highly cellular spindle cell stroma. A low grade variant has been described to have a relatively indolent clinical course a...

Background: The molecular apocrine breast cancer subset has recently been identified. These tumours are estrogen receptor (ER) negative but are characterised by the expression of many genes expressed by ER-positive luminal tumours and, interestingly, are androgen receptor (AR) positive. One third of these tumours are HER2-negative. Abiraterone acet...