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ObjectivesAutologous stem cell transplantation following high-dose chemotherapy (HDC/ASCT) is the prime model to study the impact of HDC in HIV-1-infected participants. We analyzed the impact of HDC/ASCT on the resurgent reservoir composition and origin.DesignWe included retrospectively a homogenous group of HIV-1-infected patients treated for high-risk lymphoma in a reference center with similar chemotherapy regimens.MethodsThirteen participants treated with HDC/ASCT from 2012 to 2015 were included. A median seven longitudinal blood samples per participant were available. Total HIV-1 DNA levels in peripheral blood mononuclear cells (PBMCs) were quantified by quantitative PCR. In six participants with sustained viral suppression, the highly variable C2V3 viral region was subjected to next-generation sequencing. Maximum-likelihood phylogeny trees were generated from the reconstructed viral haplotypes. Lymphocyte subsets were studied by flow cytometry.ResultsPBMC-associated HIV-1 DNA levels were stable over time. Viral diversity decreased along lymphoma treatment, but increased promptly back to prechemotherapy numbers after HDC/ASCT. Blood viral populations from all time-points were intermingled in phylogeny trees: the resurgent reservoir was similar to pre-HDC circulating proviruses. Memory subsets were the main contributor to the early restoration of the CD4+ T-cell pool, with a delayed increase in naïve cell counts.ConclusionsThe characterization of HIV-1 reservoir in blood revealed a fast and consistent replenishment from memory CD4+ T cells after HDC/ASCT. As HDC/ASCT is increasingly involved in HIV cure trials with gene-modified hematopoietic stem cells, the management of infected T cells in HIV-positive autologous transplants will be critical.

Résumé: Chez la femme, le cancer du sein est le plus fréquent et la première cause de mortalité par cancer. Le carcinome mammaire de type lobulaire infiltrant en est un sous-type histologique représentant 10 à 15 % de l'ensemble des cancers du sein. Il est caractérisé par la perte de l'expression membranaire de la protéine d'adhésion E-cadhérine codée par le gène CDH1 , lui conférant des caractéristiques histologiques particulières. Son mode de dissémination métastatique est sensiblement différent, caractérisé par une moindre fréquence des localisations secondaires pleuro-pulmonaires, ganglionnaires et cérébrales et une plus grande fréquence des localisations digestives, péritonéales et ovariennes. Cependant, les atteintes digestives secondaires restent rares en pratique clinique et sont parfois non diagnostiquées. L'atteinte gastrique en est la localisation la plus fréquente avec pour la majorité des cas un tableau de linite gastrique secondaire. Le diagnostic différentiel avec les linites gastriques primitives peut être difficile devant une symptomatologie, une description endoscopique, écho-endoscopique et en imagerie non spécifiques, et en particulier lorsqu'il existe un très long délai entre le diagnostic initial de la lésion mammaire et celui de l'atteinte gastrique. Cependant, l'enjeu thérapeutique est majeur et leur pronostic différent. L'examen anatomopathologique et surtout l'étude immunohistochimique sont les éléments clés du diagnostic. L'atteinte d'autres segments digestifs est également possible, en particulier le côlon, le rectum et l'intestin grêle, isolée ou associée à une atteinte gastrique. Enfin, la cooccurrence chez une même patiente d'un carcinome lobulaire infiltrant et d'une linite primitive gastrique est rare et doit évoquer la possibilité d'une mutation constitutionnelle du gène CDH1. In women, breast cancer is the most common cancer and the leading cause of cancer death. Invasive lobular breast carcinoma is a histological subtype representing 10 to 15% of all breast cancers. It is characterized by the loss of membrane expression of the adhesion protein E-Cadherin encoded by the CDH1 gene, giving it specific histological characteristics. Its means of spread is significantly different, characterized by a lower frequency of secondary pleuropulmonary, lymph node and cerebral localizations and a higher frequency of digestive, peritoneal and ovarian localizations. However, secondary digestive involvement remains rare in clinical practice and sometimes goes undiagnosed. Gastric involvement is the first location, with in most cases presenting as secondary gastric linitis plastica. The differential diagnosis with primary gastric linitis plastica might be difficult in the face of a non-specific symptomatology, endoscopic, echo-endoscopic and imaging description, and in particular when there is a very long delay between the initial diagnosis of the breast lesion and that of the gastric involvement. However, the therapeutic issue is major and their prognosis different. Anatomopathological examination and especially immunohistochemical study are the key facts about the diagnosis. Involvement of other digestive segments is also possible, in particular the colon, rectum and small bowel, isolated or associated with gastric involvement. Lastly, the association of invasive lobular carcinoma and primary gastric linitis plastica in the same patient is rare and should raise the possibility of a constitutional mutation of the CDH1 gene. [ABSTRACT FROM AUTHOR]

• In our study, the presence of a pretherapeutic associated suspicious NME at MRI was predictive of pCR after NST. • This finding was confirmed in a second cohort treated during the same period. • The interobserver reproducibility of the assessment for the presence or absence of an additional suspicious NME at MRI was in good agreement. This study aimed to determine if initial MRI findings could predict a pathological complete response (pCR) following neoadjuvant systemic therapy (NST) in HER2-positive breast cancers. The study retrospectively included 111 patients (Center 1, training set) and 71 patients (Center 2, validation set) with HER2-positive cancer who underwent NST. Initial clinicopathological data and MRI findings were recorded. Continuous variables were analyzed using the Mann–Whitney and Student's t-tests, while categorical variables were analyzed using the χ2 or Fisher's exact test. Univariate analysis was conducted to determine the associations between these variables and pathological complete response (pCR), defined as the absence of invasive malignant cells in the breast and lymph nodes. Interobserver reproducibility was assessed for associated non-mass enhancement (NME) parameter by analyzing 50 MR studies (intraclass correlation coefficient). pCR was achieved in 67 patients, 51 (46 %) from Center 1 and 16 (23%) from Center 2 (p = 0.003), with significant differences between Centers 1 and 2 in tumor-infiltrating lymphocyte levels and lymphovascular invasion (p < 0.001). The initial presence of suspicious associated NME was the only significant parameter predictive of pCR (p < 0.001 for Center 1 and 0.04 for Center 2). The inter-observer reproducibility for this MRI feature was good, with an intraclass correlation coefficient of 0.872 (95 % CI: 0.73–1.00). The presence of suspicious associated NME in HER2-positive cancers on the initial MRI study was predictive of achieving pCR after NST. This significant preliminary finding warrants confirmation through prospective multicenter studies. [ABSTRACT FROM AUTHOR]

The last international guidelines on HER2 determination in breast cancer have been updated in 2018 by the American Society of Clinical Oncology and College of American Pathologists, on the basis of a twenty-year practice and results of numerous clinical trials. Moreover, the emerging HER2-low concept for 1+ and 2+ non amplified breast cancers lead to refine French practices for HER2 status assessment. The GEFPICS group, composed of expert pathologists, herein presents the latest French recommendations for HER2 status evaluation in breast cancer, taking into account the ASCO/CAP guidelines and introducing the HER2-low concept. In the era of personalized medicine, HER2 status assessment remains one of the most important biomarkers in breast cancer and its quality guaranties the optimal patients' care. French pathologists' commitment in theranostic biomarker quality is more than ever required to provide the most efficient cares in oncology., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Breast cancers occurring in the context of a hereditary mutation of a predisposition gene represent 5 to 10% of all breast cancers, 20 to 25% of which being due to a mutation in the BRCA1 or BRCA2 genes. Authorization to market PARP inhibitors for breast cancer patients with hereditary BRCA1 and 2 mutations has recently been obtained. Given the annual frequency of breast cancer, morphological identification could facilitate the patient care process to limit the search for BRCA1 and 2 mutations to patients whose tumors have very specific characteristics. However, only a few morphological features have been recognized and differ depending on the mutated genes. Breast cancer occurring as part of a mutation in the BRCA1 gene is in 85% of cases of high-grade non-specific type invasive carcinomas with very limited contours, contain numerous lymphocytes in the stroma and are of triple-negative phenotype. Carcinomas associated with mutations in the BRCA2 genes and genes more recently recognized as associated with a risk of development of breast cancer (CHECK2, BMPR1A, BRIP1, PALB2, MUTYH) are most often non-specific invasive carcinomas, although other histological types are possible, grade III, luminal B phenotype. Breast cancer occurring in the context of a constitutional mutation of TP53 occurs in women under 35 years old are of non-specific histological type and with an amplification of HER2 in two thirds of the cases. Those associated with a PTEN mutation are readily of the apocrine type. Finally, very rarely, certain lobular-type breast cancers can occur in the context of a constitutional mutation of the CDH1 gene, which codes for the protein E-cadherin. The morphological and phenotypic characteristics may suggest to the pathologist a carcinoma of the breast occurring in a context of hereditary mutation. However, at the present time the only situations where a morphological sorting makes it possible to accelerate the genetic analysis are those of an invasive carcinoma of non-specific type of triple-negative phenotype in a woman of less than 50 years or that of a diagnosis of HER2 breast cancer amplified in a woman under 31 years of age (Chompret criteria). Family background and personal history are of great importance in the genetic counseling indication decision trees. Unfortunately, to date, no quality antibody has been developed against BRCA1 and 2 to help the pathologist identify hereditary cases. The immunohistochemical analysis of RAD51 could facilitate the identification of tumors possibly sensitive to PARP inhibitors. Progress to identify hereditary cancers is expected thanks to the development of artificial intelligence algorithms from digitized histological slides., (Copyright © 2020. Published by Elsevier Masson SAS.)