The variability of aggressiveness of grade 1 breast cancer.

BACKGROUND: Grade 1 breast cancer represents the lowest grade of invasive breast cancer and is associated with a low risk of recurrence and distant metastasis. However, when grade 1 breast cancer is associated with lymph node involvement, the prognosis may be worse than that of grade 1 breast cancer without lymph node involvement. METHOD: The study population included all patients who were managed in our institution between January 1, 2007 and December 31, 2013 for grade 1 breast cancer . We compared patients who had lymph node involvement to those who had no lymph node involvement. RESULTS: During the study period 291 grade 1 carcinomas were included of which 23% had associated positive lymph node involvement. Overall survival did not differ significantly between patients without lymph node involvement and those with lymph node involvement, nor was there a significant difference in the risk of local recurrence free survival. However, a significant difference was found in survival without distant metastasis with a significant level of a p at 0.029. CONCLUSION: Our findings confirm that tumor size and LVSI are strong predictors of axillary lymph node involvement, which is a key determinant of distant metastasis-free survival.

Total Polyunsaturated Fatty Acid Level in Abdominal Adipose Tissue as an Independent Predictor of Recurrence-Free Survival in Women with Ovarian Cancer.

Prognostic factors for epithelial ovarian cancers (EOCs) are in particular clinical factors such as pathology staging at diagnosis (FIGO stages), genetic mutation, or histological phenotypes. In the present study, FIGO stage, tumor residue after surgery, and body mass index were clinical predictors of recurrence-free survival (RFS). Nonetheless, a number of studies support a lipid metabolism disorder in ovarian cancer patients. The objective of this pilot study was to explore whether fatty acid composition of adipose reflecting the qualitative dietary intake and fatty acids metabolism may be associated with RFS. Forty-six women with EOCs and six with borderline ovarian tumors between March 2017 and January 2020 were included in this prospective study at Tours university teaching hospital (central France). The patients involved in the present study are part of the METERMUS trial (clinicaltrials.gov NCT03027479). Adipose tissue specimens from four abdominal locations (superficial and deep subcutaneous, visceral (pericolic), and omental) were collected during surgery or exploratory laparoscopy. A fatty acid profile of adipose tissue triglycerides was established by gas chromatography. Fatty acids composition was compared among the four locations using nonparametric Friedman's ANOVA test for repeated measures. Median follow-up of EOC patients was 15 months and patients' RFS was analyzed using Kaplan−Meier survival curves and log-rank test by separating patients into two groups according to median fatty acid levels. The content of long-chain saturated fatty acids (SFAs) was increased and that of long-chain polyunsaturated fatty acids (PUFAs) decreased in deep versus superficial subcutaneous adipose tissue in EOC patients. Nevertheless, the content of total SFAs was ~28%, monounsaturated fatty acids (MUFAs) ~55%, PUFAs n-6 ~11.5%, and PUFAs n-3 about 1.3%, whatever the adipose tissue. When EOC patients were separated into two groups by median fatty acid content, total PUFAs (n-6+n-3) levels, whatever the adipose tissue, were positively and independently associated with RFS. RFS was about two times longer in EOC patients with high versus low total PUFA content (median survival: 12 vs. 27 months, p = 0.01 to <0.0001 according to the tissue). Content of total PUFAs (n-6+n-3) in abdominal adipose tissue (visceral and subcutaneous) are new prognostic factors in EOC.

Malignant breast myoepithelioma: A systematic review.

OBJECTIVES: We performed a systematic review in order to describe the clinical presentation, therapeutic management and outcomes of malignant myoepitelioma of the breast. SEARCH STRATEGY: A systematic search of MEDLINE and EMBASE references from January 1980 to Marsh 2020 was performed. We included articles that reported cases of malignant breast myoepithelioma. Data from eligible studies were independently extracted onto standardized forms by two reviewers. RESULTS: 31 articles including 47 cases of malignant breast myoepithelioma and 3 other unpublished cases managed in our establishment were included in this systematic review. The average age at diagnosis was 60.7 years old [range 30-81]. The average size of the tumor was 46mm [range 10 -230]. 30 patients had a partial mastectomy and 18 a total mastectomy. Only 15% of patient (7/48) had an axillary sentinel lymph node biopsy of whom one was positive. 33% of patients (16/48) had an axillary lymph node dissection which was positive for one patient. 19% (n=9) had adjuvant radiotherapy and 15% (n=7) had adjuvant chemotherapy. 33% (n=10) of patients with partial mastectomy had at least one recurrence, versus 5.5% (n=1) after a total mastectomy. The average time between the diagnosis and the first recurrence was 25.4 months [range: 1-50]. 64% (n=7) had a second partial mastectomy and only 18% (n=2) had a total mastectomy. 27% of patient had chemotherapy after their first recurrence and 27% had radiotherapy if it was not received in first line treatment. 40% (n=4/10) of patients with partial mastectomy who recurred have had at least 2 breast recurrences. 28% (n=14) of all patients had distant metastases. 20% of patients (n=10) died whose 80% (n=8) had distant metastatic disease. CONCLUSIONS: This systematic review provided a precise summary of the clinical characteristics and treatment of patients presenting with Malignant breast myoepithelioma in the past 40 years. We anticipate that these results will help inform current investigations and treatment.

Presentation and Prognosis of Primary Expansile and Infiltrative Mucinous Carcinomas of the Ovary.

Objective: The aim of the present study was to evaluate evolution and prognosis of mucinous ovarian carcinomas (mOC), with respect to the two invasive patterns: expansile and infiltrative invasion. Methods: This was a descriptive, retrospective, multicenter study conducted in 13 French centres from 1 January 2001 to 31 December 2019. All patients operated on for epithelial ovarian neoplasia of the mucinous type (infiltrative/expansile) were included, whether the surgery was performed immediately or after neoadjuvant chemotherapy. Results: A total of 94 women with mucinous carcinomas were included in the present study. Mucinous tumours were divided into 35 expansile (37%) and 59 infiltrative (63%) mOC. There was a statistically significant difference in early and late stages at initial diagnosis between expansile and infiltrative mOC. None of the expansile mOC showed metastatic lymph nodes, whereas almost a quarter of the infiltrative mOC were metastatic to the pelvic/para-aortic region. There was a clear difference in RFS, in favour of expansile mOC, with 90% survival at 5 years, compared with 60% for infiltrative mOC. Conclusions: Although infiltrative and expansile mOC belong to the same histological family, they present many distinctions in clinical presentation, histological invasion, and disease course.

Accumulation of Arachidonic Acid, Precursor of Pro-Inflammatory Eicosanoids, in Adipose Tissue of Obese Women: Association with Breast Cancer Aggressiveness Indicators.

While obesity is linked to cancer risk, no studies have explored the consequences of body mass index (BMI) on fatty acid profiles in breast adipose tissue and on breast tumor aggressiveness indicators. Because of this, 261 breast adipose tissue samples of women with invasive breast carcinoma were analyzed. Fatty acid profile was established by gas chromatography. For normal-weight women, major changes in fatty acid profile occurs after menopause, with the enrichment of long-chain polyunsaturated fatty acids (LC-PUFAs) of both n-6 and n-3 series enrichment, but a stable LC-PUFAs n-6/n-3 ratio across age. BMI impact was analyzed by age subgroups to overcome the age effect. BMI increase is associated with LC-PUFAs n-6 accumulation, including arachidonic acid. Positive correlations between BMI and several LC-PUFAs n-6 were observed, as well as a strong imbalance in the LC-PUFAs n-6/n-3 ratio. Regarding cancer, axillary lymph nodes (p = 0.02) and inflammatory breast cancer (p = 0.08) are more frequently involved in obese women. Increased BMI induces an LC-PUFAs n-6 accumulation, including arachidonic acid, in adipose tissue. This may participate in the development of low-grade inflammation in obese women and breast tumor progression. These results suggest the value of lifestyle and LC-PUFAs n-3 potential, in the context of obesity and breast cancer secondary/tertiary prevention.

Cerebral localization of chronic myelomonocytic leukemia: a case report.

BACKGROUND: Chronic myelomonocytic leukemia is a myelodysplastic/myeloproliferative neoplasm characterized by the infiltration of blood and bone marrow by immature monocytes. Cerebral localization of chronic myelomonocytic leukemia has never been described. CASE PRESENTATION: We report the case of a Caucasian 59 year-old man with multiorgan chronic myelomonocytic leukemia infiltration, associated with uncommon brain involvement. There was no evidence of evolution to acute myeloid leukemia. The evidence of cerebral infiltration by chronic myelomonocytic leukemia was made after autopsy. CONCLUSIONS: The fatal outcome of the patient raises the question of the potential benefit of early specific treatment, such as demethylating agents or intensive chemotherapy. Sharing such images of atypical and rapidly evolving chronic myelomonocytic leukemia and the disease history may help clinical decision-making in the future.

Total long-chain polyunsaturated n-3 fatty acids level is an independent predictive factor of breast cancer multifocality in women with positive hormone-receptors tumors.

In a previous pilot study, we showed that polyunsaturated n-3 fatty acids of breast adipose tissues were associated with breast cancer multifocality. In the present study, we investigated biochemical, clinical and histological factors associated with breast cancer focality in a large cohort of women with positive hormone-receptors tumors. One hundred sixty-one consecutive women presenting with positive hormone-receptors breast cancer underwent breast-imaging procedures including a Magnetic Resonance Imaging prior to treatment. Breast adipose tissue specimens were collected during surgery of tumors. A biochemical profile of breast adipose tissue fatty acids was established by gas chromatography. Clinicopathologic characteristics were correlated with multifocality. We assessed whether these factors were predictive of breast cancer focality. We found that tumor size (OR = 1.06 95%CI [1.02-1.09], p < 0.001) and decreased levels in breast adipose tissue of long-chain polyunsaturated n-3 fatty acids (OR = 0.11 95%CI [0.01-0.98], p = 0.03), were independent predictive factors of multifocality. Low levels of long chain polyunsaturated n-3 fatty acids in breast adipose tissue appear to contribute to breast cancer multifocality. The present results reinforce the link between dietary habits and breast cancer clinical presentation.

Identification of a Positive Association between Mammary Adipose Cholesterol Content and Indicators of Breast Cancer Aggressiveness in a French Population.

BACKGROUND: Several studies have recently highlighted important roles for adipose tissue in cancer. However, few have examined adipose tissue cholesterol, and no study has been performed in breast adipose tissue associated with breast tumors. OBJECTIVES: The present work was designed to determine if breast adipose tissue cholesterol from the tumor-surrounding area is associated with breast cancer aggressiveness. METHODS: Between 2009 and 2011, 215 breast adipose tissue samples were collected at the Tours University Hospital (France) during surgery of women (aged 28-89 y) with invasive breast cancer. Associations of free cholesterol (FC), esterified cholesterol (EC), and total cholesterol (TC) amounts with clinical variables (age, BMI, and treated or untreated hypercholesterolemia) and tumor aggressiveness parameters [phenotype, grade, presence of inflammatory breast cancer (IBC), and multifocality] were tested using Student's t test and after ANOVA. RESULTS: The predominant form of cholesterol in adipose tissue was FC, and 50% of patients had no detectable EC. The adipose tissue FC content (µg/mg total lipid) was 18% greater in patients >70 y old than in those 40-49 y old (P < 0.05) and the TC content tended to be 12% greater in untreated hypercholesterolemic patients than in normocholesterolemic patients (P = 0.06). Breast adipose cholesterol concentrations were increased in tissues obtained from patients with human-epidermal-growth-factor-receptor-2 (HER2) phenotype (+13% FC; P < 0.05 compared with luminal A), IBC (+15% FC; P = 0.06 compared with noninflammatory tumors), as well as with multifocal triple-negative tumors (+34% FC, P < 0.05; +30% TC, P < 0.05, compared with unifocal triple-negative tumors). Among patients with triple-negative tumors, hypercholesterolemia was significantly more common (P < 0.05) in patients with multifocal tumors (64%) than in patients with unifocal tumors (25%). CONCLUSIONS: This study is the first of this magnitude that analyzes cholesterol concentrations in adipose tissue from female breast cancer patients. An increase in breast adipose tissue cholesterol content may contribute to breast cancer aggressiveness (HER2 phenotype, multifocality of triple-negative tumors, and IBC).

Negative estrogen receptors and positive progesterone receptors breast cancers.

CONTEXT: Hormone receptors (estrogen receptor ER and progesterone receptor PR) are prognostic and predictive factors of outcome for invasive breast cancer. Some tumors only express one of these hormone receptors (ER or PR). ER negative/PR positive breast cancer is a rare subtype (1-4 %) and its existence still controversial. The aim of this study was to evaluate characteristics of this group of tumors. METHODS: We collected data of all consecutive patients managed in our institution for invasive breast cancer between the 1st January 2007 and 31 December 2013. The aim of the study was to compare data of patients with ER-/PR+tumors with the three other subgroups. RESULTS: Of the 2071 patients included during the study period, 1.2 % were ER-/PR+. These patients were younger than those with the two ER+groups (p<0.0001). The ER-/PR+tumors differed from the ER+groups for several histological prognostic factors: greater histological size (p=0.0004), higher histological grade, more HER2 overexpression/amplification, more association with ductal carcinoma in situ, more lymphovascular invasion, more nodal metastasis (p<0.0001). Chemotherapy was more often used as an adjuvant treatment in addition of endocrine therapy. Survival was equivalent for patients with ER-/PR+tumors and ER+tumors and significantly higher than patients with ER-/PR- tumors (p<0.0001). CONCLUSION: Women with ER-/PR+breast cancer have worse prognostic factors than women with ER+cancers but have better overall survival than women with ER-/PR- tumors. We may think that the more frequent association of chemotherapy and endocrine therapy is responsible for this better outcome.

Low Levels of Omega-3 Long-Chain Polyunsaturated Fatty Acids Are Associated with Bone Metastasis Formation in Premenopausal Women with Breast Cancer: A Retrospective Study.

In the present study, we investigated various biochemical, clinical, and histological factors associated with bone metastases in a large cohort of pre- and postmenopausal women with breast cancer. Two hundred and sixty-one consecutive women with breast cancer were included in this study. Breast adipose tissue specimens were collected during surgery. After having established the fatty acid profile of breast adipose tissue by gas chromatography, we determined whether there were differences associated with the occurrence of bone metastases in these patients. Regarding the clinical and histological criteria, a majority of the patients with bone metastases (around 70%) had tumors with a luminal phenotype and 59% of them showed axillary lymph node involvement. Moreover, we found a negative association between the levels of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in breast adipose tissue and the development of bone metastases in premenopausal women. No significant association was observed in postmenopausal women. In addition to a luminal phenotype and axillary lymph node involvement, low levels of n-3 LC-PUFA in breast adipose tissue may constitute a risk factor that contributes to breast cancer bone metastases formation in premenopausal women.

Predictive factors of major deviation (>20 mm) between lesion sizes measured by magnetic resonance imaging and histology for invasive lobular breast cancer.

OBJECTIVE: To identify factors predictive of high discordance (>20 mm) between lesion sizes measured by magnetic resonance imaging (MRI) and histology for invasive lobular breast cancer. MATERIALS AND METHODS: Data for all women with invasive lobular breast cancer (pure or associated with a component of invasive ductal carcinoma) between 1st January 2007 and 31st December 2016 were included in this study. Logistic regression analysis was performed to determine factors predictive of high discordance (underestimation/overestimation by >20 mm) between tumour sizes measured by MRI and histology for invasive lobular breast cancer. RESULTS: For overestimation, significant factors on univariate analysis were: menopausal status [odds ratio (OR) 0.27, 95 % confidence interval (CI) 0.10-0.71]; p = 0.01], hormone receptor (HR) status (HR negative, OR 1.64, 95 % CI 0.27-9.89; HR positive, OR 0.64, 95 % CI 0.21-1.88; p = 0.09) and neoadjuvant chemotherapy (OR 10.33, 95 % CI 3.58-29.8; p < 0.001). On multivariate analysis, menopausal status and neoadjuvant chemotherapy were found to be independent predictive factors of overestimation. For underestimation, significant factors on univariate analysis were: histological size (OR 1.05, 95 % CI 1.02-1.08; p < 0.0001) and the presence of an in-situ component (OR 4.66, 95 % CI 1.01-21.5; p = 0.02). These two factors were independent predictive factors of underestimation. CONCLUSION: Independent predictive factors of overestimation/underestimation (threshold 20 mm) of tumour sizes measured by MRI compared with histology for invasive lobular breast cancer were identified.

Outcome of patients with breast cancer in the oldest old (≥80 years).

PURPOSE: In the present study, we present a large institutional study to determine the influence of age≥ 80 years on breast cancer presentation and prognosis. METHODS: The study is a retrospective analysis of our prospectively maintained breast cancer database study using data from of women managed from January 2007 through December 2013. Clinicopathologic characteristics were correlated with outcomes according to age (<80 years and ≥ 80 years). RESULTS: During the study period, 2083 women with invasive breast cancer were included of which 160 women aged ≥ 80 years (7.7 %). Overall survival was lower in the oldest old than in younger counterparts (p < 0.0001) as was distant metastasis free survival (p = 0.004). Differences in management included more radical surgeries and less chemotherapy and radiotherapy in case of age≥ 80 years. By multivariate analysis, age ≥ 80 years was an independent predictive factor of poor overall survival. CONCLUSION: In the present study, age ≥ 80 years was an independent predictive factor of poor overall survival.

Characteristics, combinations, treatments, and survival of second primary hematological neoplasm: a retrospective single-center cohort of 49 patients (Hemo2study).

The coexistence of dual hematological neoplasms is very rare. Sequential or synchronous neoplasms in hematology are an uncommon and complex clinical situation. The aim of the Hemo2 study was to describe the clinical characteristics and analyze the outcome of these patients. We performed a retrospective review of all patients diagnosed with sequential or synchronous hematological malignancies in the university hospital of Tours, between 2007 and 2018. We identified 49 patients in our study, with a prevalence of 0.89%. Sequential and synchronous combinations were found in 36 (73%) and 13 (27%) patients, respectively. One patient presented three sequential neoplasms. The median cumulative incidence was 6 years (95% CI 3-7). Among all neoplasms diagnosed (n = 99), we found 79 lymphoid neoplasms (LNs) (80%) and 20 myeloid neoplasms (MNs) (20%). Sex ratio was 1.88 with 65% of males and 35% of females. The most common LNs were Hodgkin lymphoma (n = 16; 16%) and multiple myeloma (n = 11; 11%). The most frequent MN was essential thrombocythemia (n = 5; 5%). The most common combination was Hodgkin lymphoma and follicular lymphoma in five (10%) patients. The overall survival from the first diagnosis (OS1) at 5 years was 82.4% (95% CI 72.1-94.3). The median overall survival from the second diagnosis (OS2) was 98 months (95% CI 44-NR) and 5-year OS2 was 58.7% (95% CI 45.5-75.7). Median progression-free survival from the second diagnosis (PFS) was 47 months (95% CI 27-NR) with 5-year PFS of 49% (95% CI 35.9-67). OS and PFS did not statistically differ between synchronous and sequential dual neoplasms. In this cohort, that the death relative risk (RR) was significantly lower if the second neoplasm appeared after more than 4 years following the first diagnosis (OR 0.37 (95% CI 0.16-0.90)). The Hemo2study confirmed the rarity of dual hematological neoplasms. In this cohort, HL and FL were the most frequent combinations. Our results may support that synchronous and sequential dual neoplasms bear the same prognosis. Further studies are needed to better characterize these uncommon clinical situations.

Morphologic and immunophenotypical features distinguishing Merkel cell polyomavirus-positive and negative Merkel cell carcinoma.

In 2008, Feng et al. identified Merkel cell polyomavirus integration as the primary oncogenic event in ~80% of Merkel cell carcinoma cases. The remaining virus-negative Merkel cell carcinoma cases associated with a high mutational load are most likely caused by UV radiation. The current study aimed to compare the morphological and immunohistochemical features of 80 virus-positive and 21 virus-negative Merkel cell carcinoma cases. Microscopic evaluation revealed that elongated nuclei-similar to the spindle-shape variant of small cell lung cancer-were less frequent in Merkel cell polyomavirus-positive Merkel cell carcinoma compared to the virus-negative subset (p = 0.005). Moreover, virus-negative cases more frequently displayed a "large-cell neuroendocrine carcinoma" phenotype with larger cell size (p = 0.0026), abundant cytoplasm (p = 4×10-7) and prominent nucleoli (p = 0.002). Analysis of immunohistochemical data revealed frequent positivity for thyroid transcription factor 1 and cytokeratin 7, either absence or overexpression of p53, as well as frequent lack of neurofilament expression in virus-negative cases. By contrast, cytokeratin 8, 18 and 20 and a CD99 with a dot pattern as well as high EMA expression were identified as characteristic features of virus-positive Merkel cell carcinoma. In particular, the CD99 dot-like expression pattern was strongly associated with presence of the Merkel cell polyomavirus in Merkel cell carcinoma (sensitivity = 81%, specificity = 90%, positive likelihood ratio = 8.08). To conclude, virus-positive and -negative Merkel cell carcinoma are characterized by distinct morphological and immunohistochemical features, which implies a significant difference in tumor biology and behavior. Importantly, we identified the CD99 staining pattern as a marker indicating the virus status of this skin cancer.

Risk scoring system for predicting breast conservation after neoadjuvant chemotherapy.

We developed a risk scoring system (RSS) for predicting breast conservative surgery (BCS) in women receiving neoadjuvant chemotherapy(NAC) for breast cancer. BCS rate in the training set was 32.6%, associated with five variables: age < 50years, primary radiological tumor diameter < 60mm, absence of multifocality, absence of breast inflammation and hormone receptor status. These variables were assigned scores ranging from 0 to 9. The discrimination of the RSS was 0.78(95%CI 0.69-0.86) in the training set. The area under the curve of the receiver operating characteristics for predicting BCS after internal and external validation was 0.77(95%CI 0.68-0.85) and 0.75(95%CI 0.66-0.84), respectively.

Nonlinear pharmacokinetics of rituximab in non-Hodgkin lymphomas: A pilot study.

AIMS: Rituximab is an anti-CD20 monoclonal antibody approved in non-Hodgkin lymphoma (NHL). This study aimed to assess the relationship between antigen mass and nonlinear pharmacokinetics of rituximab in NHL patients. METHODS: In a retrospective cohort of 25 NHL patients treated with rituximab, antigen mass was assessed at baseline by measuring metabolic tumour volume (MTV) by positron emission tomography. Rituximab pharmacokinetics was described using a semimechanistic 2-compartment model including a latent target antigen. Rituximab target-mediated elimination was described as irreversible binding between rituximab and it target. Histology (follicular or diffuse large B-cell lymphomas), initial MTV and body weight were tested as covariates on pharmacokinetic parameters. RESULTS: The model allowed a satisfactory description of rituximab serum concentrations. Target-mediated elimination was maximum at the beginning of treatment and became negligible towards the end of follow-up. The second-order elimination of rituximab due to target binding and complex elimination increased with baseline MTV. Central volume of distribution increased with body weight (P = .022) and baseline MTV (P = .005). CONCLUSIONS: This study quantified for the first time the target-mediated elimination of rituximab in NHL patients and confirmed rituximab retention by antigen mass.

Low eicosapentaenoic acid and gamma-linolenic acid levels in breast adipose tissue are associated with inflammatory breast cancer.

OBJECTIVE: Since it is thought that breast adipose tissue could influence breast cancer clinical presentation, we wanted to characterize specifically the relationship between breast adipose tissue fatty acid profile and Inflammatory Breast cancer (IBC). METHODS: Two hundred thirty-four women presenting with breast cancer were managed in our centre between January 2009 and December 2011. Breast adipose tissue specimens were collected during breast surgery. We established the biochemical profile of adipose tissue fatty acids (FA) by gas chromatography and assessed whether there were differences in function of the presence of breast inflammation or not. RESULTS: We found that IBC was associated with decreased levels in breast adipose tissue of eicosapentaenoic acid (EPA), one of the two main polyunsaturated n-3 fatty acids (n-3 PUFA) of marine origin, but also with decreased levels of Gamma Linolenic acid (GLA). Inversely, an increase in palmitic acid levels was associated with IBC. CONCLUSION: These differences in lipid content may contribute to the occurrence of breast cancer inflammation.