Particularités en imagerie du cancer du sein de la femme jeune de moins de 35 ans / Particularities of breast cancer imaging in young women under 35 years of age

Objectif: Le cancer du sein chez la femme jeune est rare etprésente des caractéristiques épidémiologiques, diagnostiques et pronostiques propres. L'objectif de notre étude est d'évaluerles caractéristiques radiologiques (mammographiques, échographiqueset par résonnancemagnétique IRM du cancer du sein chez la femme jeune Algérienne, de moins de 35 ans. Matériels etméthodes: Etude prospective, descriptiveau sein du service d'imagerie médicale du Centre Pierre et Marie Curie,d'Algerincluant 204patientes âgées de moins 35ans, étalée sur 3 ans allantentre janvier 2015et janvier 2017,chez lesquelles undiagnostic de cancer du sein a été porté,Elles ont toutes bénéficiésd'une mammographie numérique, d'une échographie et d'une IRM mammaireet d'unprélèvement percutané.Résultats:La fréquence du cancer du sein chez la femme jeune de moins de 35 ans était de 10,6%. L'âge moyen était de 30.9 ans. L'autopalpation d'un nodule était prédominante (87.2%). La densité mammaire était de type c et d dans 67.7%. Contrairement à l'idée établie, la mammographie avait permis souvent le diagnostic de ces tumeurs. A la mammographie, la répartition des cas selon le stade BI-RADS révèle que plus de la moitié (53.9%) était classée BI-RADS 5 ; 35.5 % des cas classés en BIRADS 4, 7.2% classés en BI-RADS 3 et un faible pourcentage (3.6 %) en BI-RADS 0. Pour l'échographie, la répartition des cas selon les stades BI-RADS révèle que plus de la moitié était classée ACR5, ce qui représente 64 %, 32.7 % classée en ACR4 et 3.3% en ACR3.A l'IRM, 71.1 % des cas ont été classés en ACR 5, 28.4% en ACR4 et 0.5 des cas en ACR 3. Le type histologique était de type carcinome canalaire infiltrant de grade III et II selon Scarff-Bloom et Richardson (SBR) dans 96.11% descas.Conclusion: L'expression radiologique est souvent non spécifique et évocatrice d'une lésion suspecte néanmoins nous avons constaté une plus grande fréquence de tumeurs d'allure bénigne en mammographie par rapport à l'échographie mammaire et à l'IRM mammaire. L'IRM mammaire reste donc utile dans la caractérisation lésionnelle et le bilan d'extension

Objective: Breast cancer in young women is rare and has its own epidemiological, diagnostic and prognostic features. The aim of our study was to evaluate the radiological (mammographic, ultrasonographic and MRI) characteristics of breast cancer iMaterials and methods: Prospective, descriptive study in the medical imaging department of the CPMC in Algiers, including 204 patients under 35 years of age, over a 3-year period from January 2017 to January 2020, diagnosed with breast cancer. They all underwent digital mammography, ultrasound and MRI of the breast and percutaneous sampling.Results: The incidence of breast cancer in young women under 35 was 10.6%. The mean age was 30.9 years. Autopalpation of a nodule was predominant (87.2%). Breast density was type c and d in 67.7%. Contrary to popular belief, these tumorswere often diagnosed by mammography. On mammography, the distribution of cases according to BIRADS stage revealed that over half (53.9%) were classified as BIRADS 5; 35.5% of cases classified as BIRADS 4, 7.2% classified as BIRADS 3 and a small percentage (3.6%) as BIRADS 0.On ultrasonography, the distribution of cases according to BIRADS staging revealed that over half were classified as ACR5, representing 64%, 32.7% as ACR4 and 3.3% as ACR3. On MRI, 71.1% of cases were classified as ACR 5, 28.4% as ACR4 and 0.5 of cases as ACR 3. Histological type was infiltrating ductal carcinoma grade III and II according to Scarff-Bloom and Richardson (SBR) in 96.11% of cases.Conclusion: Radiological expression is often non-specific and suggestive of a suspicious lesion. Nevertheless, we found a greater frequency of benign tumorsin mammography than in breast ultrasound and breast MRI. Breast MRI therefore remains useful for lesion characterization and extension assessmenn young Algerian women under 35 years of age.

Differential effects of CD20+ B cells and PD-L1+ immune cells on pathologic complete response and outcome: comparison between inflammatory breast cancer and locally advanced breast cancer patients.

PURPOSE: This study evaluated epidemiologic and immune factors associated with pathologic complete response (pCR), breast cancer-specific survival (BCSS) and disease-free survival (DFS) outcomes in inflammatory (IBC) and locally advanced breast cancer (LABC) patients. METHODS: Tumor-infiltrating lymphocytes (TILs) and CD20+ B-cell frequencies (CD20+), and PD-L1 expression on tumor (PD-L1+carcinoma cells) and immune (PD-L1+TILs) cells were analyzed by immunohistochemistry along with clinicopathologic factors as modifiers of pCR and outcomes in 221 IBC and 162 LABC patients. Analysis included Kaplan-Meier curves and Cox proportional hazard models. RESULTS: IBC and LABC display similar levels of TILs, CD20+, and combined CD20+ and PD-L1+TILs (CD20+PD-L1+TILs), while LABC contained more PD-L1+TILs and PD-L1+ carcinoma cells. Absence of lymphovascular involvement, high TILs, PD-L1+ carcinoma cells, and combined CD20+ and PD-L1+ carcinoma cells correlated with pCR in IBC and LABC patients. High PD-L1+TILs correlated with pCR only in LABC; less lymph node involvement at diagnosis, CD20+ and CD20+PD-L1+TILs correlated with pCR only in IBC (P < 0.04, all comparisons). Achievement of pCR in IBC and LABC patients correlated with BCSS and DFS (P < 0.02). In multivariate analyses, pCR remained an independent prognostic factor of improved DFS in IBC and LABC patients, but of BCSS in only LABC. CD20+PD-L1+TILs remained an independent prognostic factor of improved DFS and BCSS only in IBC. CONCLUSION: CD20+PD-L1+TILs are an independent prognostic biomarker of improved outcomes in IBC, but not LABC. Selecting IBC patients by CD20 and PD-L1 status could stratify patients and potentially identify those in whom activating CD20 agents and anti-PD-1/PD-L1 therapy could be explored.

Comparative aspects of canine and human inflammatory breast cancer.

Inflammatory breast cancer (IBC) in humans is the most aggressive form of mammary gland cancer and shares clinical, pathologic, and molecular patterns of disease with canine inflammatory mammary carcinoma (CIMC). Despite the use of multimodal therapeutic approaches, including targeted therapies, the prognosis for IBC/CIMC remains poor. The aim of this review is to critically analyze IBC and CIMC in terms of biology and clinical features. While rodent cancer models have formed the basis of our understanding of cancer biology, the translation of this knowledge into improved outcomes has been limited. However, it is possible that a comparative "one health" approach to research, using a natural canine model of the disease, may help advance our knowledge on the biology of the disease. This will translate into better clinical outcomes for both species. We propose that CIMC has the potential to be a useful model for developing and testing novel therapies for IBC. Further, this strategy could significantly improve and accelerate the design and establishment of new clinical trials to identify novel and improved therapies for this devastating disease in a more predictable way.

Tumor stromal vascular endothelial growth factor A is predictive of poor outcome in inflammatory breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is a highly angiogenic disease; thus, antiangiogenic therapy should result in a clinical response. However, clinical trials have demonstrated only modest responses, and the reasons for these outcomes remain unknown. Therefore, the purpose of this retrospective study was to determine the prognostic value of protein levels of vascular endothelial growth factor (VEGF-A), one of the main targets of antiangiogenic therapy, and its receptors (VEGF-R1 and -R2) in IBC tumor specimens. PATIENTS AND METHODS: Specimens from IBC and normal breast tissues were obtained from Algerian patients. Tumor epithelial and stromal staining of VEGF-A, VEGF-R1, and VEGF-R2 was evaluated by immunohistochemical analysis in tumors and normal breast tissues; this expression was correlated with clinicopathological variables and breast cancer-specific survival (BCSS) and disease-free survival (DFS) duration. RESULTS: From a set of 117 IBC samples, we evaluated 103 ductal IBC tissues and 25 normal specimens. Significantly lower epithelial VEGF-A immunostaining was found in IBC tumor cells than in normal breast tissues (P <0.01), cytoplasmic VEGF-R1 and nuclear VEGF-R2 levels were slightly higher, and cytoplasmic VEGF-R2 levels were significantly higher (P = 0.04). Sixty-two percent of IBC tumors had high stromal VEGF-A expression. In univariate analysis, stromal VEGF-A levels predicted BCSS and DFS in IBC patients with estrogen receptor-positive (P <0.01 for both), progesterone receptor-positive (P = 0.04 and P = 0.03), HER2+ (P = 0.04 and P = 0.03), and lymph node involvement (P <0.01 for both). Strikingly, in a multivariate analysis, tumor stromal VEGF-A was identified as an independent predictor of poor BCSS (hazard ratio [HR]: 5.0; 95% CI: 2.0-12.3; P <0.01) and DFS (HR: 4.2; 95% CI: 1.7-10.3; P <0.01). CONCLUSIONS: To our knowledge, this is the first study to demonstrate that tumor stromal VEGF-A expression is a valuable prognostic indicator of BCSS and DFS at diagnosis and can therefore be used to stratify IBC patients into low-risk and high-risk groups for death and relapses. High levels of tumor stromal VEGF-A may be useful for identifying IBC patients who will benefit from anti-angiogenic treatment.

Molecular and epidemiological characteristics of inflammatory breast cancer in Algerian patients.

Inflammatory breast cancer (IBC) shows a high incidence in Tunisia and Egypt but epidemiological and molecular characteristics have not been described in Algeria. We compared 117 IBC and 59 non-IBC locally advanced breast cancers (LABC), for estrogen and progesterone receptors, HER2, and EGFR protein expression by immunohistochemistry, and HER2 gene amplification by chromogenic in situ hybridization. Demographic, clinico-pathological, and molecular variables were compared with chi-square and Fisher's exact tests to test for significance (P < 0.05, two-tailed). Overall survival (OS) and disease-free survival (DFS) were plotted using Kaplan-Meier curves and compared using the log-rank test. Tumor emboli were detected in 77% of IBC. Palpable masses were found in all LABC but only in 32% of IBC (P < 0.001). Recurrences were higher in LABC than in IBC (48 vs. 35%; P = 0.14) but OS was worse in IBC (68 vs. 71%; P = 0.06). There were no significant differences between IBC and LABC by demographics or by clinico-pathological parameters. The majority of IBC and LABC tumors were luminal A (62 and 64%), followed by basal (~18%, each), triple negative (~18%, each), and HER2+ (~10%, each) subtypes. In multivariate analyses, grade was associated with worse OS (P = 0.04), and DFS (P < 0.001) in IBC; chemo- and radio-therapy were associated with improved OS and DFS, respectively (P < 0.05 for each) in LABC. In conclusion, IBC in Algeria shows similar characteristics to IBC described for Egypt and Tunisia with subtle molecular differences. Current therapeutic treatments were not very effective in this population and new approaches are much needed.

GPR30 and estrogen receptor expression: new insights into hormone dependence of inflammatory breast cancer.

GPR30 is a novel G protein-coupled estrogen receptor (ER) associated with metastases in breast cancer (BC) and poor survival in endometrial and ovarian tumors. The association of GPR30 expression with inflammatory breast cancer (IBC), an aggressive and commonly hormone-independent form of BC, has not been studied. GPR30, ER, progesterone receptor (PR), epidermal growth factor receptor (EGFR), and HER-2 expression were assessed by immunohistochemistry (and FISH for HER-2) in 88 primary IBCs. GPR30 expression was correlated with patient overall survival (OS), disease-free survival (DFS), pathologic variables, and other biomarkers. GPR30 expression was found in 69% of IBC cases. ER, PR, HER-2, and EGFR were found in 43, 35, 39, and 34% of IBC cases, respectively. GPR30 expression correlated inversely with ER expression (P = 0.02). Co-expression of ER and GPR30 was found in 24% of IBC samples; 19% expressed only ER and 46% expressed only GPR30. Univariate analysis showed no association between GPR30 expression and OS or DFS. However, co-expression of ER and GPR30 was associated with improved OS (P < 0.03) and marginally with DFS (P < 0.06); the absence of both ER and GPR30 was associated with worse OS and DFS (P = 0.03 for both). Multivariate analysis identified ER as an independent prognostic factor of OS (P = 0.008) and DFS (P = 0.02). The majority of IBC tumors are GPR30-positive, suggesting that estrogen signaling may be active in ER-negative IBC patients. These findings suggest potential new therapeutic targets for IBC such as novel endocrine agents or direct modulation of GPR30.