Outcome of inflammatory breast cancer in Moroccan patients: clinical, molecular and pathological characteristics of 219 cases from the National Oncology Institute (INO).

BACKGROUND: Usually misdiagnosed, Inflammatory Breast Cancer (IBC) is the most aggressive form of non-metastatic breast cancer. This orphan disease is more frequent in North Africa. Despite intensive treatment, the survival rate remains very low. METHODS: We have retrospectively studied all breast cancer cases diagnosed at the National Oncology Institute (INO), Rabat between 2005 and 2010. We have collected 219 cases of women with metastatic and non-metastatic IBC. Data have been obtained from patients' personal medical files over a follow-up period of 5 years. We have described IBC's clinicopathological features and analyzed its clinical outcome using SPSS software. HR (hazard Ratio) was calculated using Cox regression analysis. RESULTS: The frequency of IBC cases is 4.05%. The majority of our patients (65.3%) were under 50 years old. The most prevalent molecular subtype was Luminal A (38.7%) followed by Luminal B HER2+ (27.9%) and Triple negative (21.6%). During the follow-up period, 72 patients (32.9%) had recurrence and 40 patients (18.3%) died. The 3-year OS (Overall Survival) and EFS (Event Free Survival) of non-metastatic patients were 70.4 and 46.5% respectively, while in the metastatic disease, the 3-year OS was only 41.9%. In non-metastatic women, we observed a higher rate of EFS associated to Selective estrogen receptor modulation treatment (p = 0.01), and a lower rate EFS in triple negative breast cancer patients (p = 0.02). In univariate analysis, we found that EFS rate is lower in patients presenting Triple Negative tumors when compared to other molecular subtypes (HR: 3.54; 95%CI: 1.13-11.05; p = 0.02). We also found that Selective estrogen receptor modulation treatment is associated with higher EFS rate (HR: 0.48; 95%CI: 0.07-0.59; p = 0.01). CONCLUSIONS: IBC in Morocco shows similar characteristics to those in North African countries; however, survival rates are still the highest when compared with neighboring countries. Collaborative studies with prospective aspects are warranted to establish the epidemiological profile and understand the high frequencies of IBC in North Africa. More studies on molecular markers are also needed to improve IBC patients' management and eventually their survival rate.

Prediction of therapy response in ovarian cancer: Where are we now?

Therapy resistance is a major challenge in the management of ovarian cancer (OC). Advances in detection and new technology validation have led to the emergence of biomarkers that can predict responses to available therapies. It is important to identify predictive biomarkers to select resistant and sensitive patients in order to reduce important toxicities, to reduce costs and to increase survival. The discovery of predictive and prognostic biomarkers for monitoring therapy is a developing field and provides promising perspectives in the era of personalized medicine. This review article will discuss the biology of OC with a focus on targetable pathways; current therapies; mechanisms of resistance; predictive biomarkers for chemotherapy, antiangiogenic and DNA-targeted therapies, and optimal cytoreductive surgery; and the emergence of liquid biopsy using recent studies from the Medline database and ClinicalTrials.gov.

Prevalence of Polyomaviruses and Herpesviruses in Moroccan Breast Cancer.

Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide, accounting for 24.5% of total new cancer cases and 15.5% of total cancer deaths. Similarly, BC is the most common cancer among Moroccan women, comprising a noteworthy percentage of 40% of all cancers in women. Globally, 15% of cancers are attributable to infections; among them, viruses play a significant role. The present study aimed to explore the presence of a wide range of viral DNA in samples recovered from 76 Moroccan patients with BC and 12 controls using Luminex technology. The explored viruses were as follows: 10 polyomaviruses (PyVs): BKV, KIV, JCV, MCV, WUV, TSV, HPyV6, HPyV7, HPyV9, and SV40; and 5 Herpesviruses (HHVs): CMV, EBV1, EBV2, HSV1, and HSV2. Our results revealed the presence of PyVs DNA in both control (16.7%) and BC tissues (18.4%). Nonetheless, HHV DNA was detected exclusively in BC tissues (23.7%), with a predominance of Epstein-Barr virus (EBV) (21%). In conclusion, our study highlights the presence of EBV in human BC tissues, which may play an important role in its development and/or progression. Further investigations are needed to confirm the presence/co-presence of these viruses in BC.

Is HE4 Superior over CA-125 in the Follow-up of Patients with Epithelial Ovarian Cancer?

Notwithstanding important advances in the treatment of epithelial ovarian cancer (EOC), this disease is still a leading cause of global high mortality from gynecological malignancies. Recurrence in EOC is inevitable and it is responsible for poor survival rates. There is a critical need for novel effective biomarkers with improved accuracy compared to the standard carbohydrate antigen-125 (CA-125) for follow-up. The human epididymis protein 4 (HE4) is used for early detection of EOC (ROMA algorithm) as well as for predicting optimal cytoreduction after neoadjuvant chemotherapy and survival outcomes. Notably, the emerging HE4 is a promising prognostic biomarker that has displayed better accuracy in various recent studies for detecting recurrent disease. In this mini-review, we discussed the potential of HE4 as an accurate predictor of EOC recurrence.

Clinicopathological, Treatment and Event-Free Survival Characteristics in a Moroccan Population of Triple-Negative Breast Cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC) is a group of breast carcinoma characterized by the lack of expression of estrogen and progesterone hormone receptors (ER, PgR) and HER2. This form is also characterized by its aggressiveness, a low survival rate, and the absence of targeted therapies. This study was planned to evaluate the clinical features, treatment, and prognosis characteristics of TNBC in a population of Moroccan patients. METHODS: In this retrospective study, a total of 905 patients diagnosed with breast cancer at the National Institute of Oncology in Rabat, Morocco, have been included. Based on molecular subtype, patients were divided into 2 categories: TNBC and non-TNBC patients. Data were recorded from patients' medical files and analyzed using SPSS 13.0 software (IBM). RESULTS: Overall, 17% of the patients had TNBC. At diagnosis, the median age of TNBC cases was 47 years, with extreme ages of 40 and 55 years. The median follow-up time was 30 months (10-53 months) and the 3-year survival rate was 76%. No significant difference was observed among the patients in terms of age at diagnosis, age at menarche, age at the time of first birth, nulliparity, oral contraception, and family history of breast cancer. Menopausal status and the number of pregnancy were significantly higher in the non-TNBC group. The percentage of grade 3 (G3) tumors was higher in the TNBC group (P < .001). Using neoadjuvant, adjuvant chemotherapy and radiotherapy, a net benefit in the event-free survival was registered for the 2 groups. CONCLUSIONS: This retrospective study was very informative and showed that women with TNBC had a less favorable prognosis than non-TNBC cases. Clinical data demonstrated that risk factors including age, premenopausal status, parity, hormonal contraceptive use, advanced disease, and a high histologic grade were independently associated with TNBC. However, large tumors and high Scarff-Bloom and Richardson grade prevail in TNBC cases with a higher incidence of lymph node metastases.

Can the microbiota predict response to systemic cancer therapy, surgical outcomes, and survival? The answer is in the gut.

INTRODUCTION: The gut microbiota seems to play a key role in tumorigenesis, across various hallmarks of cancer. Recent evidence suggests its potential use as a biomarker predicting drug response and adding prognostic information, generally in the context of immuno-oncology. AREAS COVERED: In this review, we focus on the modulating effects of gut microbiota dysbiosis on various anticancer molecules used in practice, including cytotoxic and immune-modulating agents, primarily immune-checkpoint inhibitors (ICI). Pubmed/Medline-based literature search was conducted to find potential original studies that discuss gut microbiota as a prognostic and predictive biomarker for cancer therapy. We also looked at the US ClinicalTrials.gov website to find additional studies particularly ongoing human clinical trials. EXPERT COMMENTARY: Sequencing of stool-derived materials and tissue samples from cancer patients and animal models has shown a significant enrichment of various bacteria such as Fusobacterium nucleatum and Bacteroides fragilis were associated with resistant disease and poorer outcomes. Gut microbiota was also found to be associated with surgical outcomes and seems to play a significant role in anastomotic leak (ATL) after surgery mainly by collagen breakdown. However, this research field is just at the beginning and the current findings are not yet ready to change clinical practice.

Assessment of Enzymatic Browning and Evaluation of Antibrowning Methods on Dates.

Dates' color is known to play a crucial role in determining the value and quality of the fruit. The color changes from the natural accepted golden color to unfavorable dark brown color during storage. In this study, the effect of different color preservation methods (modified atmosphere packaging, cold storage (4°C), sulfur dioxide gas (SO2), and blanching) and its relation to darkening due to action of the browning enzymes and melanin production were investigated. Polyphenol oxidase was shown to be active in all treatments except the samples treated with SO2 gas and steam blanching for ten minutes. Likewise, peroxidase activity showed a similar trend in all samples, but a decrease in activity was observed in sulfated samples and total inactivation in steam blanching for ten minutes. Moreover, sulfated samples have shown improvement in color compared to all other treatments, whereas the steamed samples showed the highest color deterioration. Concurrently, melanin content increased in all samples over the period of storage except in the sulfated samples. FTIR analyses of dates' melanin have revealed similar structural feature to the reference melanin; however, some differences were noticed in the regions 2850-2950 cm-1 and 1690-1705 cm-1 which indicated major structural difference between the two melanin samples. More work is suggested to reveal structural and functional properties of dates' melanin.

Status of p16(INK4a) and E-cadherin gene promoter methylation in Moroccan patients with cervical carcinoma.

Aberrant methylation of tumor suppressor gene promoters has been extensively investigated in cervical cancer. Transcriptional silencing, as a main consequence of hypermethylation of CpG islands, is the predominant mechanism of p16(INK4a) and E-cadherin gene inactivation in malignant epithelial tumors. This study was conducted to evaluate the promoter methylation status of p16(INK4a) and E-cadherin genes in 22 specimens of cervical carcinomas, four cervical cancer cell lines (HeLa, SiHa, Caski, C33A), and 20 human papillomavirus negative specimens, obtained from normal cervical swabs, using the methylation-specific PCR approach. Hypermethylation of the 5' CpG island of the p16(INK4a) and E-cadherin genes were found in 13 (59.1%) and 10 (45.5%) of 22 cervical cancer samples, respectively. Furthermore, our findings did not show any correlation between promoter methylation of p16(INK4a) and E-cadherin genes and clinicopathological parameters, including HPV infection, phenotypic distribution, and stage of the disease. However, hypermethylation of E-cadherin gene promoter appears to be age related in cervical cancer, whereas the frequency of aberrant methylation of p16(INK4a) gene promoter is unchanged according to the age of patients. Thus, caution must be made to use these markers in the diagnosis of cervical cancer. However, dietary or pharmaceutical agents that can inhibit these epigenetic events may prevent or delay the development of cervical cancer.

The arrival of predictive biomarkers for monitoring therapy response to natural compounds in cancer drug discovery.

Intrinsic or acquired drug resistance, adverse drug reactions and tumor heterogeneity between and within cancer patients limit the efficacy of clinical management of advanced cancers. To overcome these barriers, predictive biomarkers have recently emerged to guide medical oncologists in the selection of cancer patients who will respond to various anticancer treatments and to improve the toxicity to benefit ratio. Notably, targeted therapy has significantly benefited from these advances, but the application of predictive biomarkers have been a bit slower with some drugs derived from natural sources such as trabectedin, cabazitaxel and alvocidib. In this paper, we discuss some recent advances regarding the use of cancer biomarkers to predict efficacy of some selected natural compounds with a focus on human clinical studies.

Starvation tactics using natural compounds for advanced cancers: pharmacodynamics, clinical efficacy, and predictive biomarkers.

The high mortality associated with oncological diseases is mostly due to tumors in advanced stages, and their management is a major challenge in modern oncology. Angiogenesis is a defined hallmark of cancer and predisposes to metastatic invasion and dissemination and is therefore an important druggable target for cancer drug discovery. Recently, because of drug resistance and poor prognosis, new anticancer drugs from natural sources targeting tumor vessels have attracted more attention and have been used in several randomized and controlled clinical trials as therapeutic options. Here, we outline and discuss potential natural compounds as salvage treatment for advanced cancers from recent and ongoing clinical trials and real-world studies. We also discuss predictive biomarkers for patients' selection to optimize the use of these potential anticancer drugs.

Emerging diagnostic, prognostic and therapeutic biomarkers for ovarian cancer.

BACKGROUND: In spite of various treatment options currently available, ovarian cancer (OC) still remains a leading cause of death in women world-wide. Diagnosis at an early stage is one of the most important factors that determines survival. Current clinical diagnostic tools have, however, a limited efficacy in early OC detection. Therefore, there is a critical need for new (early) diagnostic biomarkers and tools. Through advances in genomic, proteomic and metabolomic techniques, several novel molecular OC biomarkers have recently been identified. These biomarkers are currently subject to validation. In addition, integration of genomic, proteomic and metabolomic data, in conjunction with epidemiologic and clinical data, is considered essential for obtaining useful results. Interesting recent work has already shown that specific diagnostic biomarkers, such as BRCA mutations, may have profound therapeutic implications. Here, we review the current state of OC research through literature and database searches, with a focus on various recently identified biomarkers via different technologies for the (early) diagnosis, prognosis and treatment of OC. CONCLUSIONS: Multi-biomarker panels accompanied by a meticulous determination of their sensitivity and specificity, as well their validation, using multivariate analyses will be critical for its clinical application, including early OC detection and tailor-made OC treatment.

Recent Progress in Triple Negative Breast Cancer Research.

Triple-negative breast cancer (TNBC) is defined as a type of breast carcinoma that is negative for expression of oestrogene and progesterone hormone receptors (ER, PR) and HER2. This form of breast cancer is marked by its aggressiveness, low survival rate and lack of specific therapies. Recently, important molecular characteristics of TNBC have been highlighted and led to the identification of some biomarkers that could be used in diagnosis, as therapeutic targets or to assess the prognosis. In this review, we summarize recent progress in TNBC research focusing on the genetic and epigenetic alterations of TNBC and the potential use of these biomarkers in the targeted therapy for better management of TNBC.

Outcome of Breast Cancer in Moroccan Young Women Correlated to Clinic-Pathological Features, Risk Factors and Treatment: A Comparative Study of 716 Cases in a Single Institution.

BACKGROUND: Breast cancer in young women is quite uncommon and shows more aggressive characteristics with major disparities between worldwide populations. Prognosis and outcome of breast cancer in young patients are widely studied, but still no consensus is available. METHODS: We retrospectively included 716 cases of breast cancer women diagnosed in 2009 at the National Institute of Oncology of Rabat. Patients were divided into two groups according to their age: women aged ≤40 years (Group 1) and women aged >40 years (Group 2). Data were recorded from patients' medical files and analyzed using SPSS 13.0 software (IBM). RESULTS: Young patients represent 24.9% of all patients with breast cancer. The comparison between the two groups displayed significant differences regarding nulliparity (p = 0.001) and progesterone receptor negativity (p = 0.01). Moreover, more progression (Metastases/Relapse) was registered in young women as compared to older women with breast cancer (p = 0.03). The estimated median follow-up period was 31 months. The 5-years Event-Free Survival (EFS) of patients with local disease was 64.6% in young women and 71.5% in older women with breast cancer (p = 0.04). Multivariate analysis in young women showed that nulliparity (HR: 7.2; 95%CI: 1.16-44.54; p = 0.03), T3 tumors (HR: 17.39; 95%CI: 1.74-173.34; p = 0.01) and negative PgR status (HR: 19.85; 95%CI: 1.07-366.54; p = 0.04) can be considered as risk factors for poorer event free survival while hormone therapy was associated with better EFS (HR: 0.11; 95%CI: 0.00-0.75; p = 0.03). In Group 2, multivariate analysis showed that patients with inflammatory breast cancer, N+ status, absence of radiotherapy, absence of chemotherapy, and absence of hormone therapy are at increased risk of recurrence. CONCLUSIONS: In Morocco, breast cancer is more frequent in young women as compared to western countries. Breast cancer in young women is more aggressive and is diagnosed late, leading to an intensive treatment. Moreover, the main factors associated with breast cancer development in young women would be hormonal and reproductive status. Analysis of other genetic biomarkers is needed to explain the high prevalence of breast cancer in young women to improve breast cancer management in Morocco.

Molecular detection of human papillomavirus in 594 uterine cervix samples from Moroccan women (147 biopsies and 447 swabs).

Uterine cervix cancer is the second most frequent female cancer after breast cancer in Morocco and represents a public health problem. Cervical cancer is highly linked to human papillomavirus (HPV) especially types 16 and 18 which are the highly oncogenic genotypes. To identify the contribution of HPV testing in the prevention of cervical cancer in Morocco, 147 biopsies collected at the Institut National d'Oncologie and 447 swabs from pathology laboratories and gynaecologist offices in Rabat were HPV analysed. HPV testing were made without any presumption of the histopathological diagnosis. A total of 147 paraffin-embedded biopsies and 447 exfoliated cervical samples were included. Based on histopathology results of the 147 biopsies, most cervical lesions were invasive carcinomas and non specific inflammations (NSI). With the molecular assay, HPV was detected in 91/147 (62%) patients. The high risk types 16 and 18 were found in 45% of the cases (41/91) and HPV 18 in 19% of the cases (17/91). Double infection with HPV 16 and 18 was found in 3 cases. Among the 447 swabs tested, 28 were HPV positives. Cytology results showed that 46% were inflammations (13/28). Among them, 10 patients had a NSI and only 3 patients had a cytology diagnosis of HPV infection. Based on these data, HPV testing should be associated to cervical cytology screening according to two algorithms established in function of the age of the patient and viral natural history. Combination of cytology and HPV testing allow identification of patient with high risk for development of high grade cervical lesions and improve cervical cancer prevention.

[Begnin naevus cell inclusions in two patients treated for cancer]. / Inclusions naeviques ganglionnaires chez deux patients traités pour cancer.

In 1897, Reis was the first to describe benign nevus inclusions in the lymph node of patients undergoing surgery for genital neoplasia. These inclusions are very rarely encountered and can be misleading in the absence of careful analysis. We report on two cases of nevus cell inclusions in axillary and inguinal lymph nodes dissected in the context of breast cancer and thigh sarcoma respectively. Cautious morphological analysis should be compared with histochemistry and immunohistochemistry data to avoid erroneous diagnosis of metastasis. We also should bare in mind the possible occurrance of primitive lymph node melanoma.

Significant correlation between salivary and serum Ca 15-3 in healthy women and breast cancer patients.

The tumor marker CA 15-3 is one of the most import reliable for metastatic breast cancer monitoring. While it is generally assessed in serum of patients, blood sampling is an invasive method compared to saliva sampling which is simple and could be an alternative to blood according to many studies. The aim of this investigation was to assess the relationship between serum and salivary concentrations of the protein CA 15-3 in patients with breast cancer and healthy asymptomatic volunteers. A case-control study was conducted with 60 women: 29 breast cancer patients from the Maternity Hospital Souissi Rabat (Morocco) and 31 healthy asymptomatic women. The CA 15-3 concentrations in saliva and serum samples were assessed using an enzyme immune assay (EIA kits) and comparison between cases and controls was made by the Mann-Whitney test. The correlation between serum and saliva CA 15-3 concentration was tested using Pearson correlation. The comparison result of CA15-3 concentration in saliva and serum level in cases and controls was not statistically significant (p>0.05). However, the correlation between salivary and serum CA 15-3 concentration was positive and statistically significant (r=0.27, p=0.03). In conclusion, the positive correlation between salivary and serum expression found in our study suggests that saliva could be an alternative to blood sampling to help breast cancer monitoring.

Detection of MMTV-Like sequences in Moroccan breast cancer cases.

INTRODUCTION: The mouse mammary tumor virus (MMTV) like sequences have been reported to be present in some human breast cancers, but their association with breast cancer development is still controversial. METHODS: In this retrospective study, we investigated the status of MMTV-like in 42 tumor biopsies and 18 paired normal tissues from Moroccan patients with breast cancer. MMTV-like env sequences were identified by PCR and confirmed by direct DNA sequencing. RESULTS: Specific MMTV-like env sequences were found in 24 (57.14%) cases of breast carcinomas, and 6 (33.3%) cases of matched normal breast tissues. Comparison to sociologic and clinicopathological parameters showed no significant association between the presence of MMTV-like sequences and age, menopausal status, histological subtype, histological grade, tumor size and the expression of hormone receptors (estrogen ER and/or progesterone PgR) and Her 2. However, a significant correlation was found between MMTV-like presence and parity (p = 0.024). CONCLUSIONS: This present study confirms the presence of MMTV-like env sequences in breast cancer in Moroccan women, prompting further evaluation, on large sampling, to elucidate the probable causal roles of MMTV-like in breast cancer development.

Breast cancer in Morocco: a literature review.

In Morocco, breast cancer is the most prevalent cancer in women and a major public health problem. Several Moroccan studies have focused on studying this disease, but more are needed, especially at the genetic and molecular levels. It is therefore interesting to establish the genetic and molecular profile of Moroccan patients with breast cancer. In this paper, we will highlight some pertinent hypotheses that may enhance breast cancer care in Moroccan patients. This review will give a precise description of breast cancer in Morocco and propose some new markers for detection and prediction of breast cancer prognosis.