E-cadherin mutational landscape and outcomes in breast invasive lobular carcinoma.

Invasive lobular carcinomas (ILC) are characterized by a loss of E-cadherin expression and CDH1 gene inactivation. Diagnostic reproducibility for this tumor type is currently suboptimal and could be improved by a better understanding of its histomolecular and clinical heterogeneity. We have analyzed the relationship between presence, type or position of CDH1 mutations, E-cadherin expression and clinicopathological features (including outcome) in a retrospective series of 251 primary ILC with long follow-up (median: 9.5 years). The mutational status of E-cadherin gene (CDH1) was determined by RNA sequencing from frozen tumor samples. E-cadherin immunohistochemistry (IHC) was performed with antibodies directed against the intracellular domain (clone 4A2C7) and the extracellular domain (clone NCH38). IHC expression of p120 and ß-catenin was also assessed in E-cadherin diffusely positive cases. Three major patterns of E-cadherin membrane expression were identified by IHC, with good agreement between the two clones (overall concordance: 83.8%, Kappa 0.67): null/focal expression (≤10%) (72.8% of cases for 4A2C7, 83.8% for NCH38), heterogeneous expression (11-89%) (19.2% of cases for 4A2C7, 6.9% for NCH38) and diffuse expression (≥90%) (8% of cases for 4A2C7, 9.3% for NCH38). E-cadherin membranous expression, when present, was abnormal (incomplete labeling and/or reduced intensity). ILC with diffuse E-cadherin expression showed abnormal ß-catenin or p120-catenin staining in 21% of cases. Interestingly, these cases with diffusely expressed E-cadherin had a CDH1 mutation rate as high as the E-cadherin null/focal cases (∼70%), but were enriched in non-truncating mutations. Regarding CDH1 mutation location, intracytoplasmic domain mutations correlated with a divergent E-cadherin IHC phenotype between the two antibodies (4A2C7 ≤10% / NCH38 ≥10%). Clinico-pathological correlation analyses found that stromal amount (inversely correlated with tumor cellularity) and TILs were less abundant in ILC with E-cadherin null/focal cases. In addition, CDH1 truncating mutations were associated with radio-histological size discordance, and were identified in multivariate survival analysis as an independent poor prognosis factor in terms of metastasis risk and breast cancer related mortality. Overall, our study highlights the importance of the precise mutational status of CDH1 in the clinical, radiological, histological and phenotypic expression of lobular carcinomas. These findings should be taken into account in future attempts to improve diagnostic criteria or methods for ILC, as well as for clinico-biological studies dedicated to this tumor type.

Evaluating the satisfaction and utility of social networks in medical practice and continuing medical education.

BACKGROUND: Digital health has surged during the Covid health crisis, and the use of social media, already prevalent in medicine, has significantly increased. There are Social Networks groups dedicated to physicians with an educational purpose. These groups also facilitate peer discussions on medical questions and the sharing of training materials. OBJECTIVES: The aim of our study was to assess the value of these new tools and their contribution to medical education. METHODS: An anonymous questionnaire was conducted among members of a Social Networks community group for physicians. The survey received responses from 1451 participants. RESULTS: The majority of participants believed they had enriched their medical knowledge and accessed documents they would not have accessed without the group. Subgroup analysis showed that the contribution of this tool is more pronounced for general practitioners and doctors practicing in limited healthcare access. CONCLUSION: It is essential to develop digital tools that enhance physician training, and social networks represent a valuable educational tool.

[18F]FDG PET/CT for predicting triple-negative breast cancer outcomes after neoadjuvant chemotherapy with or without pembrolizumab.

PURPOSE: To determine if pretreatment [18F]FDG PET/CT could contribute to predicting complete pathological complete response (pCR) in patients with early-stage triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy with or without pembrolizumab. METHODS: In this retrospective bicentric study, we included TNBC patients who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy (NAC) or chemo-immunotherapy (NACI) between March 2017 and August 2022. Clinical, biological, and pathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from the PET images. Cut-off values were determined using ROC curves and a multivariable model was developed using logistic regression to predict pCR. RESULTS: N = 191 patients were included. pCR rates were 53 and 70% in patients treated with NAC (N = 91) and NACI (N = 100), respectively (p < 0.01). In univariable analysis, high Ki67, high tumor SUVmax (> 12.3), and low TMTV (≤ 3.0 cm3) were predictors of pCR in the NAC cohort while tumor staging classification (< T3), BRCA1/2 germline mutation, high tumor SUVmax (> 17.2), and low TMTV (≤ 7.3 cm3) correlated with pCR in the NACI cohort. In multivariable analysis, only high tumor SUVmax (NAC: OR 8.8, p < 0.01; NACI: OR 3.7, p = 0.02) and low TMTV (NAC: OR 6.6, p < 0.01; NACI: OR 3.5, p = 0.03) were independent factors for pCR in both cohorts, albeit at different thresholds. CONCLUSION: High tumor metabolism (SUVmax) and low tumor burden (TMTV) could predict pCR after NAC regardless of the addition of pembrolizumab. Further studies are warranted to validate such findings and determine how these biomarkers could be used to guide neoadjuvant therapy in TNBC patients.

Impact of Vulvar Cancer Surgery on Quality of Sex Life: A Review of Literature.

OBJECTIVES: Vulvar cancer is a gynecological cancer for which posttreatment morbidity must be known to propose the appropriate medical strategy. The objectives of this article were to review and to summarize the available studies evaluating the impact of vulvar surgery on the quality of sex life. MATERIALS AND METHODS: We searched MEDLINE abstracts (source PubMed) and included all studies published between 1990 and 2020 that evaluated the impact of vulvar surgery on the patients' sex life. Articles were selected in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. We evaluated the quality of the studies using the "study quality assessment tools" established by the National Heart Lung and Blood Institute and the health-related quality-of-life score. Summary statistics were used to report the results of the studies selected. RESULTS: A total of 41 articles were screened, and 15 studies were included in this review. Two questionnaires, that is, European Organization for Research and Treatment of Cancer QLC C30 and Female Sexual Function Index, were used in 60% of the studies. The quality of the studies was heterogeneous. None of them had a high level of evidence. Eleven of the 16 studies reported an impairment of quality of sex life, mainly related to the size of the initial lesion and the type of surgery performed. Preoperative sexual status, that is, active sex life, age, and morbidity seemed to be important factors. CONCLUSIONS: None of the studies had a high level of evidence, and their methodological quality was heterogeneous. More powerful studies using validated questionnaires are necessary. Because this is essential surgery, patients should be informed that if it impacts their sexual life, management strategies will be part of their postoperative care.

A subset of activated fibroblasts is associated with distant relapse in early luminal breast cancer.

BACKGROUND: Early luminal breast cancer (BC) represents 70% of newly diagnosed BC cases. Among them, small (under 2 cm) BC without lymph node metastasis (classified as T1N0) have been rarely studied, as their prognosis is generally favorable. Nevertheless, up to 5% of luminal T1N0 BC patients relapse with distant metastases that ultimately prove fatal. The aim of our work was to identify the mechanisms involved in metastatic recurrence in these patients. METHODS: Our study addresses the role that autonomous and non-autonomous tumor cell features play with regard to distant recurrence in early luminal BC patients. We created a cohort of T1N0 luminal BC patients (tumors between 0.5-2 cm without lymph node metastasis) with metastatic recurrence ("cases") and corresponding "controls" (without relapse) matched 1:1 on main prognostic factors: age, grade, and proliferation. We deciphered different characteristics of cancer cells and their tumor micro-environment (TME) by deep analyses using immunohistochemistry. We performed in vitro functional assays and highlighted a new mechanism of cooperation between cancer cells and one particular subset of cancer-associated fibroblasts (CAF). RESULTS: We found that specific TME features are indicative of relapse in early luminal BC. Indeed, quantitative histological analyses reveal that "cases" are characterized by significant accumulation of a particular CAF subset (CAF-S1) and decrease in CD4+ T lymphocytes, without any other association with immune cells. In multivariate analysis, TME features, in particular CAF-S1 enrichment, remain significantly associated with recurrence, thereby demonstrating their clinical relevance. Finally, by performing functional analyses, we demonstrated that CAF-S1 pro-metastatic activity is mediated by the CDH11/osteoblast cadherin, consistent with bones being a major site of metastases in luminal BC patients. CONCLUSIONS: This study shows that distant recurrence in T1N0 BC is strongly associated with the presence of CAF-S1 fibroblasts. Moreover, we identify CDH11 as a key player in CAF-S1-mediated pro-metastatic activity. This is independent of tumor cells and represents a new prognostic factor. These results could assist clinicians in identifying luminal BC patients with high risk of relapse. Targeted therapies against CAF-S1 using anti-FAP antibody or CDH11-targeting compounds might help in preventing relapse for such patients with activated stroma.

Comprehensive clinical and molecular analyses of neuroendocrine carcinomas of the breast.

Neuroendocrine breast carcinomas represent a rare subtype of breast cancer. Their definition, prevalence, and prognosis remain controversial in the literature. The 2012 WHO classification of breast cancer categorizes neuroendocrine carcinomas into three morphologically distinct subtypes: well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas, and invasive breast carcinomas with neuroendocrine differentiation. We aimed to gain insight into the clinical, morphologic, phenotypic, and molecular features of 47 neuroendocrine breast carcinomas. Targeted next-generation sequencing by an AmpliSeq 22 cancer gene hotspot panel and the Prosigna assay were performed on 42/47 and 35/47 cases, respectively. Average age at diagnosis was 69 years. All tumors were estrogen receptor-positive and the large majority expressed progesterone receptor (89%), GATA3 (98%), FOXA1 (96%), and CK8/18 (98%). There was an almost equal distribution of luminal A (52%) and B (48%) carcinomas. Almost half of the cohort (49%) displayed a high risk of recurrence score with the Prosigna test. Patients with a neuroendocrine carcinoma had a shorter disease-free survival compared with those affected by carcinomas of no special type matched for age, size, grade, and estrogen receptor status. No significant differences were observed in terms of overall survival. Stratification of neuroendocrine carcinomas using the 2012 WHO criteria did not reveal statistically significant differences among the distinct categories (well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinomas, and invasive breast carcinomas with neuroendocrine differentiation), in terms of either progression-free or overall survival. Our targeted sequencing analysis found three cases (7%) harboring a PIK3CA mutation, and in three other cases (7%) TP53 mutations were detected. This study showed that neuroendocrine breast carcinoma is a distinct subtype of luminal carcinoma with a low rate of PIK3CA mutations and with an aggressive clinical behavior. An accurate identification of neuroendocrine differentiation may be useful to better tailor patient adjuvant therapy within luminal carcinomas.

Surgical peritoneal stress creates a pro-metastatic niche promoting resistance to apoptosis via IL-8.

BACKGROUND: The mainstay of treatment of advanced ovarian cancer (AOC) involves chemotherapy, and debulking surgery. However, despite optimal surgical procedure and adjuvant chemotherapy, 60% of patients with AOC will relapse within 5 years. Most recurrences occur in the peritoneal cavity, suggesting the existence of occult sanctuaries where ovarian cancer cells (OCC) are protected. In murine models, surgical stress favors tumor growth; however, it has never been established that surgery may affect OCC sensitivity to subsequent chemotherapy. In this study, we investigated how the surgical stress could affect the chemosensitivity of OCC. METHODS: To avoid bias due to tumor burden in peritoneal cavity and duration of surgery, we used peritoneal biopsies from patients without a malignancy at precise time points. During laparotomies, peritoneal biopsies at the incision site were performed at the time of incision (H0 sample) and 1 h after initiation of surgery (H1 sample). We evaluated the chemoresistance to Taxol (0-20 µM) induced by H0 or H1 incubation (24 h) in two ovarian cancer cell lines OVCAR3 and SKOV3 and a primary cancer cell lines derived in our laboratory. RESULTS: Our results indicate that stressed peritoneum overexpressed cytokines, resulting in OCC increased resistance to therapy. Among these cytokines, IL8 was responsible for the resistance to apoptosis through the AKT pathway activation. Chemoresistance in OCC persists through the establishment of an autocrine IL8 loop. Finally, in a cohort of 32 patients, we showed an impact of IL8 tumoral overexpression on chemosensitivity and survival outcomes with a significant association to earlier recurrence. CONCLUSIONS: Our study demonstrated that precision surgery where targeted treatment would be used in combination with surgery is essential to obtain better tumor control.

Predictive markers of chemoresistance in advanced stages epithelial ovarian carcinoma.

OBJECTIVE: DNA repair mechanisms, environment-mediated drug resistance and cancer initiating cells (CIC) are three major research concepts that can explain the chemoresistance of epithelial ovarian cancer (EOC). The objective was to test if changes in the expression of potential markers associated with drug resistance before and after chemotherapy would correlate with platinum resistance, defined as a recurrence within the first year after chemotherapy cessation, and with survival, in advanced EOC. METHODS: We included 32 patients with stage IIIC-IV EOC who underwent laparoscopy to evaluate the extent of carcinomatosis, neoadjuvant chemotherapy (carboplatin/taxol) and interval surgery. Biopsies taken during the initial laparoscopies and interval surgeries were evaluated using immunohistochemistry for the expression of 7 proteins: CD117, CD44 and ALDH1 to evaluate CIC; IL-6, IL-8 and BMP2 to evaluate environment-mediated drug resistance; and ERCC1 to evaluate DNA repair. Expression measurements were correlated with platin resistance and survival. The markers' relevance was confirmed in vitro using chemoresistance tests and flow cytometric measurements of the proportion of CD44+ cells. RESULTS: 17 patients were chemoresistant and 15 patients were chemosensitive. We observed increases in CD44, IL-6 and ERCC1 expression and stable ALDH1, CD117, IL-8, and BMP2 expression. Reduced expression of cancer initiating cell markers and increased expression of environment-mediated drug resistance markers were associated with poor prognosis. We also demonstrated that CD44+ cells had survival advantages in vitro. CONCLUSIONS: Changes in CD44 and IL-8 expression on tumor cells appeared to correlate with overall survival and should be further tested as predictors of chemoresistance using larger cohort.

CA125 kinetic parameters predict optimal cytoreduction in patients with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy.

OBJECTIVE: To evaluate the different kinetic parameters of serum CA125 during neoadjuvant chemotherapy (NAC) to predict optimal interval debulking surgery (IDS). METHODS: The present retrospective multicenter study included patients with advanced ovarian cancer treated with neoadjuvant platinum-based chemotherapy followed by IDS between 2002 and 2009. Demographic data, CA125 levels, radiographic data, chemotherapy and surgical-pathologic information were obtained. Univariate and multivariate analyses were performed to evaluate variables associated with complete IDS. ROC analysis was used to determine potential cut-off values to predict the likelihood of complete cytoreduction via IDS. RESULTS: One hundred and forty-eight patients met the study criteria. Ninety-three patients (62.8%) had optimal cytoreduction with no residual macroscopic disease (CC-0) after IDS. In multivariate analyses, the CA125 level after the 3rd NAC was an independent predictor for optimal cytoreduction (odds ratio: 0.98 [0.97-0.99], p=0.04). The area under the ROC curve was 0.73. A threshold of 75 UI/ml displayed the most predictive power. The odds ratio to predict complete cytoreduction was 3.29 [1.56-7.10] (p=0.0008). CONCLUSION: Our data indicate that for advanced ovarian cancer, a CA125 level less than 75 UI/ml after the 3rd NAC was an independent predictor factor for complete IDS.

Value of ultrasonography and magnetic resonance imaging for the characterization of uterine mesenchymal tumors.

OBJECTIVE: To evaluate ultrasonography and magnetic resonance imaging (MRI) performance in differentiating benign leiomyomas from malignant mesenchymal or mixed tumors (MMT) and smooth muscle tumors of uncertain malignant potential of the uterus (STUMP). DESIGN: Retrospective cohort study. SETTING: University hospital, France. POPULATION: One hundred and eight women who underwent imaging before surgery for uterine mesenchymal tumor (85 with benign leiomyomas and 23 with MMT/STUMP). METHODS: The ultrasonography reports were reviewed. Conventional, perfusion and diffusion MRI were blindly analyzed. Recursive partitioning analysis (RPA) was performed to construct diagnostic flowcharts. MAIN OUTCOME MEASURES: Accuracy of a diagnostic flowchart. RESULTS: At ultrasonography, single tumor, non-myometrial origin, absence of acoustic shadowing, thickened endometrium and ascites were associated with MMT/STUMP (p = 0.001, p < 0.001, p = 0.03, p < 0.0001 and p = 0.03, respectively). For conventional MRI, single tumor, non-myometrial origin, large tumor, poorly defined margins, thickened endometrium, peritoneal implants, intermediate or high signal intensity in T1 or T2 sequences, heterogeneous T1 signal, cystic alteration of the tumor and heterogeneity of the tumor's enhancement were significantly associated with MMT/STUMP. Perfusion weighted imaging and perfusion curve types were not discriminant. For diffusion weighted imaging, a high signal intensity at b = 1000 s/mm² was associated with MMT/STUMP (p < 0.001). RPA resulted in a model that ultimately included age, number of tumors and the aspect of the endometrium (both evaluated by MRI) and that had an area under the curve of 0.95. CONCLUSIONS: Simple criteria, such as single tumor, non-myometrial tumor, abnormal endometrium and age, should question the diagnosis of benign leiomyoma. MRI enhanced the sensitivity of detecting MMT/STUMP.

Surgical and clinical impact of extraserosal pelvic fascia removal in segmental colorectal resection for endometriosis.

STUDY OBJECTIVE: To describe the characteristics of patients with colorectal endometriosis and extraserosal pelvic fascia (EPF) involvement and to assess the effect of EPF resection. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Two hundred twenty-seven patients who underwent segmental colorectal resection to treat symptomatic deep infiltrating endometriosis between 2001 and 2011, with or without EPF resection. INTERVENTIONS: Segmental colorectal resection with or without EPF resection. MEASUREMENTS AND MAIN RESULTS: One hundred twelve patients (49.4%) required EPF resection. In these patients the total American Society for Reproductive Medicine endometriosis scores were higher (p = .004), there were more associated resected lesions of deep infiltrating endometriosis (p <.001), and the operative time was longer (p <.001). They were more likely to require blood transfusion (p = .003) and to experience intraoperative complications (p = .01) and postoperative voiding dysfunction (p = .04). CONCLUSION: EPF infiltration reflects disease severity in patients with colorectal endometriosis. Its removal affects intraoperative morbidity and leads to a higher rate of voiding dysfunction.

[Epidemiology and risk factors for cancer of the uterus]. / Epidémiologie et facteurs de risque des cancers de l'utérus.

Cancers of the uterus correspond to cervical cancers and uterine corpus cancers. Cervical cancer is common among young women, especially in immunocompromised populations. Its carcinogenesis is induced by the human papilloma virus (HPV). All factors promoting the HPV contamination and/or limiting the clearance of HPV or promoting its progression are risk factors for cervical cancer: sex at an early age, multiple sexual partners, multiparty, smoking, hormonal contraceptives, immunosuppression or certain infections. Cancers of the uterine corpus, substantially represented by endometrial cancers, represent the fourth leading cause of cancer in women in France. Risk factors are related to hyperestrogenism with early age of menarche and late menopause, obesity, diabetes, inadequate hormone-replacement therapy for menopause. Endometrial cancers fall in the scope of familial cancers making evoke a Lynch syndrome/HNPCC.

[Life after uterine cancer]. / La vie après un cancer de l'utérus.

This overview focuses on the follow up after uterine cervix and corpus cancers. At early stage, both are associated with good prognosis. Screening for recurrence is mainly based on clinical examination. Screening for a second cancer after endometrial cancer is already planned according to the French recommendations for systematic breast and colon cancer screening. Screening for a second cancer after cervical cancer requires a close examination of organs close to the cervix receiving high doses of radiations and HPV exposed (anus, vulva, vagina and perineum). Late chemotherapy related toxicity after both cancers is rarely encountered and mainly comprise neurological peripheral effects. Late surgical and/or radiation related side effects are more frequent. However, no more than 10% of patients are affected and in such cases, digestive, urinary and lymphatic systems are impaired. Prevalence of sexual dysfunction in patients with uterine cancers is particularly high but the radiotherapy related anatomical modifications (vaginal stenosis for example) might not be the sole reason. Fertility preservation is possible for uterine cancers but requires a rigorous selection of candidates and should be coordinated by specialized team.

Residual ANTXR1+ myofibroblasts after chemotherapy inhibit anti-tumor immunity via YAP1 signaling pathway.

Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. Here we address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global content in stroma increases in HGSOC after chemotherapy, the proportion of FAP+ CAF (also called CAF-S1) decreases. Still, maintenance of high residual CAF-S1 content after chemotherapy is associated with reduced CD8+ T lymphocyte density and poor patient prognosis, emphasizing the importance of CAF-S1 reduction upon treatment. Single cell analysis, spatial transcriptomics and immunohistochemistry reveal that the content in the ECM-producing ANTXR1+ CAF-S1 cluster (ECM-myCAF) is the most affected by chemotherapy. Moreover, functional assays demonstrate that ECM-myCAF isolated from HGSOC reduce CD8+ T-cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, efficient inhibition after treatment of YAP1-signaling pathway in the ECM-myCAF cluster could enhance CD8+ T-cell cytotoxicity. Altogether, these data pave the way for therapy targeting YAP1 in ECM-myCAF in HGSOC.

How to differentiate benign from malignant myometrial tumours using MR imaging.

PURPOSE: To retrospectively evaluate the ability of magnetic resonance imaging (MRI) to differentiate malignant from benign myometrial tumours. METHODS: Fifty-one women underwent MRI before surgery for evaluation of a solitary myometrial tumour. At histopathology, there were 25 uncertain or malignant mesenchymal tumours and 26 benign leiomyomas. Conventional morphological MRI criteria were recorded in addition to b 1,000 signal intensity and apparent diffusion coefficient (ADC). Odds ratios (OR) were calculated for each criterion. A multivariate analysis was performed to construct an interpretation model. RESULTS: The significant criteria for prediction of malignancy were high b 1,000 signal intensity (OR = +∞), intermediate T2-weighted signal intensity (OR = +∞), mean ADC (OR = 25.1), patient age (OR = 20.1), intra-tumoral haemorrhage (OR = 21.35), endometrial thickening (OR = 11), T2-weighted signal heterogeneity (OR = 10.2), menopausal status (OR = 9.7), heterogeneous enhancement (OR = 8) and non-myometrial origin on MRI (OR = 4.9). In the recursive partitioning model, using b 1,000 signal intensity, T2 signal intensity, mean ADC, and patient age, the model correctly classified benign and malignant tumours in 47 of the 51 cases (92.4 %). CONCLUSION: We have developed an interpretation model usable in routine practice for myometrial tumours discovered at MRI including T2 signal, b 1,000 signal and ADC measurement. KEY POINTS: • MRI is widely used to differentiate benign from malignant myometrial tumours. • By combining T2-weighted, b 1,000 and ADC features, MRI is 92.4 % accurate. • DWI may limit misdiagnoses of uterine sarcoma as benign leiomyoma. • Patient age is important when considering a solitary myometrial tumour.

Sexuality after breast cancer, how to provide a global and contemporary approach.

Patients' sexuality is one of the major and most neglected impact of breast cancer (BC) and its treatment. Even though research is ongoing on the subject, sexuality issues are rarely taken into account and efficiently dealt with in clinical practice. The objective is to review the impact of BC and its treatment on modern women sexuality. In the literature, a heterogeneous level of advancement is notable in the different publishing countries depending on the cultural background; some countries simply do not publish on the matter, others mainly discuss the male partners and practicians experience, and lastly, the most progressive countries have moved up to studying niches of patients such as sexual and gender minorities. A multidisciplinary approach, including pharmacologic and nonpharmacologic management, appears most efficient. There is a need for greater inclusion of partners and for providing a specific training to first-line health care providers. This review provides a general contemporary worldwide overview of the state of the art in sexuality issues in BC patients and survivors.

[Bisphenol A and breast cancer: State of knowledge and meta-analysis]. / Bisphénol A et cancer du sein : état des lieux des connaissances et méta-analyse.

INTRODUCTION: Bisphenol A is an endocrine disruptor used in the composition of food containers. It was partially banned in France in 2015 and classified as a "very high-risk substance" in 2017. Bisphenol A's carcinogenic effects have been demonstrated in animal testing. Bisphenol A acts through estrogen-dependent and estrogen-independent pathways. It induces epigenetic changes and impacts the microenvironment of the mammary gland. However, the role of bisphenol A exposure in the development of breast cancer in humans remains controversial. This study documents the current thinking on bisphenol A with an analysis of the mechanisms and a meta-analysis. MATERIALS AND METHODS: A literature review and a statistical analysis of linear regression type, with the creation of a Forest plot, were used to perform the meta-analysis of 9 studies including 10,695 patients. RESULTS: Nine case-control studies, published between 1990 and 2021, investigating the association between breast cancer and mean urinary, blood or tissue bisphenol A levels were selected. The meta-analysis did not find a significant association between bisphenol A exposure and the development of breast cancer with an OR=(1 IC95% [0.92-1.08]). DISCUSSION: This meta-analysis does not show a link between breast cancer and bisphenol A exposure. Nevertheless, the analysis of a pathogenic link between bisphenol A and breast cancer requires additional cohort studies to conclude because of methods of available studies.

Phase II study of intrathecal administration of trastuzumab in patients with HER2-positive breast cancer with leptomeningeal metastasis.

BACKGROUND: Patients with HER2-positive breast cancer (HER2 + BC) develop central nervous system metastases twice as often as patients with luminal HER2-negative breast cancer. Leptomeningeal progression results in a drastically altered prognosis with limited therapeutic options. This phase II study was conducted to assess the efficacy of intrathecal (IT) trastuzumab in HER2 + BC patients with leptomeningeal metastasis (LM), based on a phase I dose-escalation study that had determined the recommended weekly dose of 150 mg for phase II. METHODS: Eligible patients received weekly administrations of 150 mg of IT trastuzumab. The primary endpoint was clinical neurologic progression-free survival (LM-related-PFS) after 8 weeks. Overall survival (OS), toxicities, and quality of life (QoL) were secondary endpoints. RESULTS: Among the 19 enrolled patients, 16 (84%) had concomitant brain metastases, 15 of them had received prior radiotherapy to the brain. All patients had received at least one line of systemic anti-HER2 therapy. After 8 weeks, 14 patients (74%) were free of neurological progression. The median LM-related-PFS was 5.9 months and the median OS was 7.9 months. According to the QLQ-C30 and BN20 scales, the global health-related QoL status seemed preserved and no toxicity above grade 3 was observed. CONCLUSIONS: Conducting studies on patients with LM poses significant challenges and ethical dilemmas inherent to this population. Despite some limits, this phase II study's findings in terms of clinical neurologic response and QoL's control confirms weekly administration of 150 mg of IT trastuzumab as a valuable option for HER + BC patients with LM and support the interest for further investigations.

Prevalence of sexual dysfunction after breast cancer compared to controls, a study from CONSTANCES cohort.

PURPOSE: Sexuality, a substantial factor in quality of life, may be altered after breast cancer (BC) treatments as they intimately afflict femininity. This study aimed to assess the prevalence of sexual dysfunction in women with a history of BC and to compare it with women without a BC history. METHODS: The French general epidemiological cohort CONSTANCES includes more than 200,000 adults. All inclusion questionnaires from CONSTANCES non-virgin adult female participants were analyzed. Women reporting a history of BC were compared to controls in univariate analysis. Multivariate analysis was performed to highlight any demographic risk factor for sexual dysfunction. RESULTS: Among the 2,680 participants who had a history of BC, 34% did not engage in sexual intercourse (SI) in the month preceding the completion of the questionnaire (n = 911), 34% had pain during SI (n = 901) and 30% were not satisfied with their sex life (n = 803). Sexual dysfunction was significantly more frequent in women who had a history of BC: they had less sexual interest (OR 1.79 [1.65;1.94], p < 0.001), experienced more pain during SI (OR 1.10 [1.02;1.19], p < 0.001) and were more dissatisfied with their sex life (OR 1.58 [1.47;1.71], p < 0.001). This stayed true after adjustment on multiple demographic factors such as age, menopausal status, body mass index and depression. CONCLUSIONS: Overall, in this real-life study in a large national cohort, history of BC appeared to be a risk factor for sexual disorders. IMPLICATIONS FOR CANCER SURVIVORS: Efforts to detect sexual disorders in BC survivors and offer quality support must be pursued.

Clinical Utility of Pre-Therapeutic [18F]FDG PET/CT Imaging for Predicting Outcomes in Breast Cancer.

BACKGROUND: [18F]FDG PET/CT is used for staging and could also provide information associated with clinical outcomes. The objective of this study was to determine the clinical utility of biomarkers measured using [18F]FDG PET/CT to predict the absence of pathological complete response (no-pCR) and recurrence. METHODS: In this retrospective study, we included patients with non-special-type breast carcinoma who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy between 2011 and 2019. Clinicopathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from PET images. The association between biomarkers and no-pCR was studied using logistic regression. The cut-off value was determined using the area under the ROC Curve. To predict 3-year recurrence-free survival (RFS), we used a multivariable Cox model, and the cut-off value was determined using time-dependent ROC and predictiveness curves. RESULTS: Two hundred and eighty-six patients were included in the analysis. One hundred and twelve patients had a pCR (39.2%). The pCR rate was significantly higher in patients with a high nuclear grade (p < 0.01), HER2+ and TNBC subtypes (p < 0.01), high Ki67 (p < 0.01), and low TMTV (p < 0.01). A high TMTV value (>9.0 cm3) was significantly associated with no-pCR in the whole cohort (OR = 2.4, 95% CI: 1.3-4.2, p < 0.01). After a median follow-up of 4.5 years, 65 patients experienced recurrence and 39 patients died. High TMTV (>13.5 cm3) was associated with shorter RFS (HR = 4.0, 95% CI: 1.9-8.4, p < 0.01). CONCLUSION: High TMTV in pre-therapeutic imaging is associated with no-pCR and recurrence. It can help in identifying high-risk patients and be considered as an intensified or alternative adjuvant therapy for closely monitoring patients.