Tailoring neoadjuvant systemic therapy in breast cancer: "The advent of a personalized approach"-The Breast-Gynecological and Immuno-Oncology International Cancer Conference (BGICC) consensus and recommendations.

BACKGROUND: The management of early breast cancer (BC) has witnessed an uprise in the use of neoadjuvant therapy and a remarkable reshaping of the systemic therapy postneoadjuvant treatment in the last few years, with the evolution of many controversial clinical situations that require consensus. METHODS: During the 14th Breast-Gynecological and Immuno-Oncology International Cancer Conference held in Egypt in 2022, a panel of 44 BC experts from 13 countries voted on statements concerning debatable challenges in the neo/adjuvant treatment setting. The recommendations were subsequently updated based on the most recent data emerging. A modified Delphi approach was used to develop this consensus. A consensus was achieved when ≥75% of voters selected an answer. RESULTS AND CONCLUSIONS: The consensus recommendations addressed different escalation and de-escalation strategies in the setting of neoadjuvant therapy for early BC. The recommendations recapitulate the available clinical evidence and expert opinion to individualize patient management and optimize therapy outcomes. Consensus was reached in 63% of the statements (52/83), and the rationale behind each statement was clarified.

Genomic Landscape of Advanced Solid Tumors in Middle East and North Africa Using Circulating Tumor DNA in Routine Clinical Practice.

INTRODUCTION: Next-generation sequencing (NGS) of tumor DNA can detect actionable drivers and help guide therapy for patients with advanced-stage cancers. While tissue-based genotyping is considered a standard of care, blood-based genotyping is emerging as a valid alternative. Tumor genomic profiles may vary by region, and data from the Middle East and North Africa (MENA) are not widely available. This study elucidates the genomic landscape of advanced solid cancers in patients from the MENA region by retrospectively analyzing results from NGS circulating tumor DNA (ctDNA) testing. METHODS: In routine clinical practice, 926 plasma samples from 767 patients with advanced cancers from the MENA region were profiled using a comprehensive NGS assay (Guardant360®). We conducted a pan-cancer analysis and sub-analyses focusing on lung, breast, and colorectal cancers. RESULTS: In the pan-cancer group, TP53 (58.5%), EGFR (20.4%), and KRAS (18.9%) were the most frequently mutated genes. EGFR (10.2%), FGFR1 (4.9%), and PIK3CA (4.9%) showed the most amplifications, while fusions were observed in 2.7% of patients, including ALK, FGFR2, and RET. For lung adenocarcinoma, EGFR (30.5%), KRAS (19.3%), and ERBB2 (4.6%) were the most frequently identified alterations among the genes recommended for evaluation by the National Comprehensive Cancer Network (NCCN). In patients with breast cancer, PIK3CA (35.3%), ESR1 (21.7%), and BRCA1/2 (13.3%) had the most prevalent alterations among NCCN-recommended genes. In colorectal cancer, KRAS (39.0%), NRAS (8.0%), and BRAF (V600E, 4.0%) were the most observed mutations among genes recommended by the NCCN. Comparing this cohort to publicly available Western and Eastern datasets also indicated similarities (including PIK3CA in breast cancer) and variances (including EGFR in lung adenocarcinoma) in key genes of interest in the analyzed cancer types. CONCLUSION: Overall, our findings provide insight into the genomic landscape of individuals with advanced solid organ malignancies from the MENA region and support the role of ctDNA in guiding therapeutic decisions.

BRCA testing and management of BRCA-mutated early-stage breast cancer: a comprehensive statement by expert group from GCC region.

BReast CAncer (BRCA)1 and BRCA2 gene pathogenic variants account for most hereditary breast cancers (BC). Identification of BRCA mutations can significantly influence both prognosis and treatment outcomes. Furthermore, it enables the identification of individuals who are at heightened risk of developing BC due to inherited genetic mutations. Many developing countries rely on western guidelines for BRCA testing and BC management; however, there exist wide disparities in the prevalence of risk factors, availability of medical resources, and practice patterns. Guidelines tailored to specific regions can help mitigate healthcare variations, promote consistency in treatment, and aid healthcare providers in identifying effective therapies for improving patient outcomes. Hence, oncologists from the Gulf Cooperation Council (GCC) congregated virtually in March 2023 and reviewed existing data on the epidemiology of BC, BRCA mutations, practices and challenges associated with BRCA testing and management of BRCA mutated early-stage BC in the GCC region. They also provided insights on the real-world diagnostic and treatment practices and challenges in the GCC region in the BRCA-mutated early-stage BC domain and suggested some variations to international guidelines to aid their uptake in this region.

Breast Cancer in Young Women: Is It Different? A Single-Center Retrospective Cohort Study.

Introduction: Breast cancer (BC) is one of the commonest cancers among women worldwide. Differences regarding tumor biology, presentation, genetics, and molecular subtypes may contribute to the relatively poorer prognosis among younger women. Limited information exists regarding pathologic characteristics and long-term outcomes among this group. Methods: This retrospective cohort study included 695 BC patients diagnosed over a 10-year period and investigated the clinicopathological characteristics and long-term disease outcomes among patients diagnosed at age less than or equal to 40 years compared with older ones. Cox regression analysis was performed, and Kaplan-Meier curves were generated to assess overall survival (OS). Results: Compared with the younger patients (⩽40 years) estrogen receptor (ER) and progesterone receptor (PR) expression was mainly positive in older patients (>40 years) (76.2% vs 61.3% and 64.2% vs 49.6%, respectively). The most common molecular subtype in both age groups was luminal B (44.1% in older and 40.3% in younger). A clinical complete remission after neoadjuvant therapy was observed more frequently in older patients (76.7%; N = 442) in comparison with the younger patients (66.4%; N = 79) (P = .018). Recurrence and disease progression were significantly more likely to occur among younger patients accounting for 12.6% and 29.4% of the cases, compared with 6.3% and 18.2% in older patients (P = .016 and P = .006, respectively). The overall mortality was 132 (19%) of 695, with 88% cancer-related deaths. Estrogen receptor and PR expression (P ⩽ .001 and P = .003, respectively), molecular subtype (P = .002), tumor grade (P = .002), and N stage (P = .038) were the variables that were found to be significantly influenced by age. The OS was not statistically different among 2 age groups, but younger patients with luminal A molecular subtype showed significantly poor outcome (P = .019). Conclusion: Overall survival in women diagnosed with BC at age less than or equal to 40 years is not significantly worse than older patients. However, among patients with luminal A subtype, younger women had relatively poor survival. Further research is needed to understand this age-based disparity in outcomes.

Assessing the Correlation of Rate of Pathological Complete Response and Outcome in Post Neoadjuvant Chemotherapy Setting and Molecular Subtypes of Breast Cancer.

Background Neoadjuvant chemotherapy (NAC) is being widely used in treating breast cancer (BC). This study aimed to analyze the correlation between clinicopathological features, immunohistochemistry (IHC)-based molecular subtypes, and the pathological response to NAC and its relationship with disease-free survival (DFS) and overall survival (OS). Materials and methods A retrospective analysis of 211 breast cancer patients who received NAC between 2008 and 2018 was performed. Tumors were classified by IHC into luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative subtypes. The chi-square test was used to assess the association between pathological response and clinicopathological parameters. Cox regression analysis was used to assess factors related to DFS and OS. Results Post NAC, 19.4% of patients achieved a pathologic complete response (pCR). Estrogen receptor (ER), progesterone receptor (PR), HER2 (p<0.001, 0.005, and 0.02), Ki67 (p=0.03), molecular subtypes (p<0.001), T stage (p=0.04), and N stage (p=0.01) were significantly associated with pathological response. The rate of pCR was highest among HER2-enriched and triple-negative tumors (45.2% and 28%, respectively) with OR=0.13 and p<0.001 for the HER2-enriched subtype. Patients with pCR were 61% less likely to develop metastasis (adjusted hazard ratio [aHR]=0.39, p=0.06, 95% CI=0.14-1.06) and were significantly associated with better OS (aHR=0.07, p=0.02, 95% CI=0.01-0.61). Patients who were ≤40 years old (aHR=2.1, p=0.01), with T4 (aHR=3.4, p=0.02), grade 3 (aHR=2.5, p=0.01), and node-positive disease (HR=2.24, p=0.02) were at an increased risk of developing metastasis. High Ki67 was found to be significantly associated with better DFS (p=0.006). Conclusion HER2-enriched and triple-negative BC were associated with a higher rate of pCR. Patients with pCR had significantly better DFS and OS. Younger age, advanced stage, higher grade, and lymph node involvement were risk factors for metastasis.

The Level of Agreement Among Medical Oncologists on Adjuvant Chemotherapy Decision for Breast Cancer in Pre and Post-Oncotype DX Settings.

INTRODUCTION: The Oncotype DX assay plays an important role in the identification of the specific subset of hormone receptor (HR)-positive and node-negative breast cancer (BC) patients, who would benefit the most from adjuvant chemotherapy. The current study aimed at assessing the level of agreement among medical oncologists on adjuvant chemotherapy decisions before and after Oncotype DX, as well as the intra-observer agreement of each medical oncologist's decision of prescribing adjuvant chemotherapy based on clinicopathological and immunohistochemical parameters only and followed by Oncotype DX recurrence score (RS) results. METHODS: A retrospective analysis of data related to clinicopathological and immunohistochemical parameters, and Oncotype DX RS result for 145 female, estrogen receptor (ER)-positive, HER2 negative, and both node-negative and positive BC patients was performed. Initially, the data without Oncotype DX RS was sent to 16 oncologists in multiple centers in the Middle East. After one week, the same data with the shuffling of cases were sent to the oncologists with the addition of the Oncotype DX RS result for each patient. The inter and intra-observer agreement (kappa and Fleiss multi-rater kappa) among oncologists' decision of prescribing adjuvant chemotherapy pre and post-Oncotype DX RS results were assessed. Oncotype DX risk scores were used as continuous variables as well as based on old RS grouping, categorized into low (0-17), intermediate (18-30), and high risk (≥ 31) groups. A test with a p-value of < 0 .05 will be considered statistically significant. RESULTS: The mean age ± SD of the cohort was 51.9 ± 9.4 years. Sixty-nine patients (47.6%) were premenopausal whereas 76 patients (52.4%) were postmenopausal. The mean Oncotype DX RS was 17.8 ± 8.6 and 54.5% had low recurrence risk (RR), 37.9% had intermediate RR and only 7.6% had high RR. The majority of our cases were grade two (53.1%) and T stage one (49%), whereas 29.7% had positive one to three lymph nodes. The addition of Oncotype DX results improved the agreement among oncologists' decision from fair to moderate (kappa = 0.52; p <0.001). On average, an oncologist's decision of prescribing adjuvant chemotherapy pre and post-Oncotype DX had an agreement in 70.6% of the cases, with agreement observed mostly for cases where the initial decision of adjuvant chemotherapy was (no) and it was retained with post-Oncotype DX assay (46.1%), compared to 24.5% cases where the initial decision was (yes) and it was retained with post-Oncotype DX assay (kappa = 0.39; p <0.001). The addition of the Oncotype DX RS result avoided chemotherapy in 20.4% of cases and identified 9% of cases as candidates for adjuvant chemotherapy (kappa = 0.38; p <0.001). The disagreement was highest among cases with intermediate RR (33.6%) followed by high and low RR (31.3% and 21.6%) with a statistical significance of <0.001. CONCLUSION: We conclude that the Oncotype DX RS significantly influenced the decision to prescribe adjuvant chemotherapy among HR-positive, HER2 negative, and both node-negative and positive patients, as it increased the level of agreement among oncologists and led to a decrease in the use of adjuvant chemotherapy compared to the pre-Oncotype recommendations.

Response to Induction Neoadjuvant Hormonal Therapy Using Upfront 21-Gene Breast Recurrence Score Assay-Results From the SAFIA Phase III Trial.

PURPOSE: Luminal, human epidermal growth factor receptor 2-negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT). MATERIALS AND METHODS: The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2-negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31. RESULTS: At the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate (P = .05). CONCLUSION: The upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.

Breast-Gynaecological & Immuno-Oncology International Cancer Conference (BGICC) Consensus and Recommendations for the Management of Triple-Negative Breast Cancer.

Background: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when ≥75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.

Prevalence of BRCA1 and BRCA2 Mutations Among High-Risk Saudi Patients With Breast Cancer.

Purpose Over the past three decades, the incidence rate of breast cancer (BC) among Arab women has continually increased. However, data on the prevalence of BRCA1/2 mutations are scarce. Although the population in Saudi Arabia is at large homogeneous and consanguinity is common, especially in the central, eastern, and southern regions of the country, the prevalence of BRCA1 and BRCA2 mutations and the characteristics of BC are not well studied in the country. Methods This prospective observational study intended to determine the prevalence of BRCA1 and BRCA2 mutations and sought to examine the clinicopathologic features of BC associated with these mutations. Results Of 310 patients, 270 (87%) had no mutation. BRCA mutations were identified in 40 patients; BRCA1 mutations were found in 11% of patients, and BRCA2 mutations were found in 2% of patients. Variants of unknown significance were found in 15% of patients (45 patients). Triple-negative BC (TNBC) accounted for 86% of all patients with BC and mutations. The following three recurrent deleterious founder BRCA1 mutations were observed: c.4136_4137delCT was observed in five unrelated patients, c.5530delC was observed in three unrelated patients, and c.4524G>A mutations were observed in five unrelated patients. One novel mutation was identified in the BRCA1 gene (c.5512 dup [p.Glu1838Glyfs*42]). Conclusion Among high-risk Saudi patients with BC, BRCA1 mutations are prevalent (11%). TNBC is the most common BC subtype. Furthermore, age alone does not have a significant association with mutation, but a combination of risk factors such as age, familial history, and TNBC has a significant association with BRCA mutation.

The clinical impact of using complex molecular profiling strategies in routine oncology practice.

Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests. The resulting information was interpreted and personalized treatments for each patient were suggested. Our data showed that NGS alone provided the oncologist with useful information in 10-50% of cases (depending on cancer type), whereas the addition of IHC/other tests increased extensively the usefulness of the information provided. Using internet surveys, we investigated how therapy recommendations influenced treatment choice of the oncologist. For patients who were still alive after the provision of the molecular information (76.8%), 60.4% of their oncologists followed report recommendations. Most treatment decisions (93.4%) were made based on the combination of NGS and IHC/other tests, and an approved drug- rather than clinical trial enrolment- was the main treatment choice. Most common reasons given by physicians to explain the non-adherence to recommendations were drug availability and cost, which remain barriers to personalised precision medicine. Finally, we observed that 27% of patients treated with the suggested therapies had an overall survival > 12 months. Our study demonstrates that the combination of NGS and IHC/other tests provides the most useful information in aiding treatment decisions by oncologists in routine clinical practice.

Extended adjuvant endocrine therapy in early breast cancer: a meta-analysis of published randomized trials.

Adjuvant endocrine therapy for 5 years is the standard adjuvant treatment for estrogen receptor-positive breast cancer while the benefits of extended adjuvant endocrine therapy (EAET) beyond 5 years are still controversial. That controversy prompted this meta-analysis to compare 5 years of adjuvant endocrine therapy only versus EAET. Eligible 11 randomized, controlled trials comprising 29,000 women were included. EAET showed no advantage in overall survival (OS) from all causes mortality (odds ratio [OR] = 0.98 (95% confidence interval [CI], 0.87-1.09); P = 0.67). On the other hand, compared with standard therapy, the pooled effects showed that EAET was associated with improvement in breast cancer-specific survival (OR = 0.87; 95% CI 0.79-0.96; P = 0.004), disease-free survival (DFS) (OR = 0.87; 95% CI 0.75-0.99; P = 0.002), disease recurrence (OR = 0.76; 95% CI 0.64-0.90; P = 0.001), and contralateral breast recurrence (OR = 0.74; 95% CI 0.59-0.93; P = 0.008). Improvement in DFS or disease recurrence was not shown in studies that compared 5 years of tamoxifen versus tamoxifen beyond 5 years. Subgroup analysis showed that EAET conferred more benefit for patients with positive lymph nodes. Rates of positive lymph nodes, the study size, and the median duration of follow-up were identified as variables that explained most of the demonstrated data heterogeneity. EAET should be considered as a preferred strategy for high-risk hormone-positive early breast cancer patients with positive lymph nodes; however, the benefit on OS could not be demonstrated.

ESO-ESMO 3rd international consensus guidelines for breast cancer in young women (BCY3).

The 3rd International Consensus Conference for Breast Cancer in Young Women (BCY3) took place in November 2016, in Lugano, Switzerland organized by the European School of Oncology (ESO) and the European Society of Medical Oncologists (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY2 with incorporation of new evidence to inform the guidelines, and areas of research priorities were identified. This manuscript summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

Vitamin D levels and breast cancer characteristics: Findings in patients from Saudi Arabia.

Inverse relationship between vitamin D status and risk of breast cancer has been previously reported in the literature. We conducted this study to determine the association between vitamin D levels and breast cancer characteristics in patients from Saudi Arabia. Newly diagnosed breast cancer patients (N=406) were recruited. Serum levels of 25-hydroxyvitamin D [25 (OH) D] were measured at baseline. A significantly higher percentage of patients with triple negative status (18%) had 25 (OH) D levels ≤25nmol/L, compared to only 8% with 25 (OH) D levels >25nmol/L (p=0.009). Patients with 25 (OH) D levels ≤25nmol/L were 2.54 times more likely to present with triple negative status compared to those with 25 (OH) D levels >25nmol/L (p=0.02). Our findings suggest an association between low 25 (OH) D levels and increased risk of triple negative breast cancer.

A multicenter prospective phase II trial of neoadjuvant epirubicin, cyclophosphamide, and 5-fluorouracil (FEC100) followed by cisplatin-docetaxel with or without trastuzumab in locally advanced breast cancer.

PURPOSE: To evaluate the efficacy and safety profile of the (FEC100) followed by cisplatin/docetaxel with and without trastuzumab as primary chemotherapy for patients with locally advanced breast cancer (LABC). METHODS: Eighty patients with LABC (T2-T4, N0-N2, M0) were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin, cyclophosphamide, and 5-fluorouracil (FEC100) followed by cisplatin and docetaxel, plus trastuzumab if HER2 positive. The primary endpoint was pathologic complete response (pCR) in breast and axilla in separate HER2-negative and HER2-positive cohort. RESULTS: Eighty patients were evaluable for analysis of which 51 were HER2 negative and 29 HER2 positive: median age: 43 years, premenopausal: 82%, median tumor size: 7.0 cm (4-10), stage IIB: 25% and IIIA/IIIB: 75%, both ER/PR positive: 56%, HER2 positive (3+) by IHC staining: 36%. Clinical complete response was seen in 48%, and clinical partial response was seen in 52%. Overall the pathologic complete response (pCR) was 36% in breast, 64 % in axilla, and 32% in both breast and axilla. Analysis of pCR in breast and axilla, as a function of the hormonal receptor (HR) and HER2, was as follows: HR(+)/HER2(-): 11%; HR(+)/HER(+): 56 %; HR(-)/HER2(-): 36%; HR(-)/HER2(+): 62%. CONCLUSION: In this series of locally advanced breast cancer, the combination of (FEC100) followed by cisplatin/docetaxel with and without trastuzumab was very active obtaining an impressive rate of pCR, particularly in HER2-positive and triple negative disease, which merits further investigation.

First international consensus guidelines for breast cancer in young women (BCY1).

The 1st International Consensus Conference for Breast Cancer in Young Women (BCY1) took place in November 2012, in Dublin, Ireland organized by the European School of Oncology (ESO). Consensus recommendations for management of breast cancer in young women were developed and areas of research priorities were identified. This manuscript summarizes these international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

Clinicopathologic features and prognosis of triple-negative breast cancer in patients 40 years of age and younger in Saudi Arabia.

BACKGROUND AND OBJECTIVES: Triple-negative breast cancer (TNBC) has a poor prognosis and overall survival (OS) compared to other types of breast cancer tumors. However, there is to date no evidence that this is also the case in Saudi Arabia. DESIGN AND SETTING: Retrospective review of breast cancer patients who were treated from January 2001 to December 2008 (517 patients) at the King AbdulAziz Medical City, Riyadh, Saudi Arabia. PATIENTS AND METHODS: Patients were selected as TNBC if all three markers of estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor (HER2) tested by immunohistochemistry as negative. They were then age- and stage-matched, and compared with non-TNBC patients to examine differences, if any, in their clinicopathologic features, prognosis and OS. RESULTS: Twenty-six patients with a follow up time of at least three years were identified as TNBC. Thirty-three patients who were age- and stage-matched were selected as the non-TNBC controls. Clinicopathologic results illustrated significantly more grade 3 tumors (P=.02) and CK 5/6 expression (P<.001) in the TNBC group compared to the non-TNBC group. TNBC patients aged ≤40 years showed a significantly worse prognosis and OS compared to TNBC patients aged >40 years (P=.01), and when compared to the non-TNBC group (P=.04). CONCLUSION: The incidence of TNBC in our cohort is similar to what has been illustrated in previous studies in Western population. There was no significant difference in 3-year survival between TNBC and non-TNBC groups. However, the aggressiveness of this type of tumor and OS is significantly higher in younger patients aged ≤40 years, compared to those over 40 years of age.

Antiproliferative properties of methanolic extract of Nigella sativa against the MDA-MB-231 cancer cell line.

Breast cancer is the most commonly diagnosed cancer in women in the world and is one of the leading causes of death due to cancer. Health benefits have been linked to additive and synergistic combinations of phytochemicals in fruits and vegetables. Nigella sativa has been shown to possess anti-carcinogenic activity, inhibiting growth of several cancer cell lines in vitro. However, the molecular mechanisms of the anti-cancer properties of Nigella sativa phytochemical extracts have not been completely understood. Our data showed that Nigella sativa extracts significantly inhibited human breast cancer MDA-MB-231 cell proliferation at doses of 2.5-5 µg/mL (P<0.05). Apoptotic induction in MDA-MB-231 cells was observed in a dose-dependent manner after exposure to Nigella sativa extracts for 48 h. Real time PCR and flow cytometry analyses suggested that Nigella sativa extracts possess the ability to suppress the proliferation of human breast cancer cells through induction of apoptosis.

Use of complementary and alternative medicine by patients with cancer in Saudi Arabia.

BACKGROUND: The use of complementary and alternative medicine (CAM) is common among patients with cancer. However, the issue is not well-studied among the Saudi patient population. Our study aimed at determining the patterns of CAM use among patients with cancer in Saudi Arabia. METHODS: A cross-sectional study using interview-administered questionnaire was conducted in patients with cancer in the Oncology Department of King Abdulaziz Medical City for National Guards, Riyadh, Kingdom of Saudi Arabia. Patients were asked about CAM use including dietary supplement (DS) and non-DS remedies. Univariate and multivariate analyses were conducted to identify predicting factors for CAM use. RESULTS: A total of 453 adult patients were enrolled in the study, with a median age of 53.5 years (14.7-94.6), and the ratio of females to males was 271/182 (59.8%/40.2%). Of those, 410 patients (90.5%) used some type of CAM remedy. Non-DS remedies were used by 399 patients (88%) and were mainly of a religious nature including reciting the Quran (74.8%), prayer (16%), supplication (13%), and others (3.7%). However, 386 patients (85.2%) used DS including: Zamzam water (59.8%), honey (54.3%), black seed (35.1%), water with the Quran recited over it (29.8%), and other remedies. The majority of patients (90%) used CAM as a cancer treatment and the rest used it for various reasons, such as symptom control or supportive treatment. Only 18% of the patients discussed CAM use with their physicians, compared to 68% discussing it with religious clergypeople (Sheikhs).The univariate analysis revealed that only female gender is a predictor of CAM use, which remained significant in a multivariate analysis, in addition to current employment. CONCLUSIONS: The use of complementary therapies among Saudi patients with cancer is highly prevalent, with a predominance of interventions of religious background, indicating the strong influence of religion on peoples' lives, especially when people are faced with life-threatening illnesses.

Delayed Paclitaxel-trastuzumab-induced interstitial pneumonitis in breast cancer.

Pneumonitis is a rare but serious complication associated with paclitaxel and/or trastuzumab treatment. We report a 51-year-old female patient with locally advanced breast cancer who presented with shortness of breath, fever, dry cough and pulmonary infiltrates. She had been treated without complications for 10 weeks with paclitaxel (Taxol®) and trastuzumab (Herceptin®) as neoadjuvant therapy, with complete clinical and pathological response. Infections and cardiomyopathy were excluded as causes of her symptoms. Bronchoscopy and biopsy were performed and a diagnosis of drug-induced interstitial pneumonitis was made. After treatment with steroids, the patient showed a significant response in less than 24 h; she was discharged home without the need for oxygen less than 48 h after therapy initiation. Although no causative association could be found between either trastuzumab or paclitaxel and this patient's pulmonary syndrome, the potential for such toxicity should be considered, especially as paclitaxel/trastuzumab is a vey common combination therapy for breast cancer.