Correlation Between Oncotype Dx Recurrence Score and PREDICT Estimates in Early Breast Cancer: A Single Institution Experience.

PURPOSE: Oncotype Dx Recurrence Score (RS) is prognostic and predictive of chemotherapy benefit in women with node-negative and node-positive in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer. Nevertheless, its direct cost may be inhibitive. This study assesses the correlation between the RS and the free online PREDICT tools' estimations of adjuvant chemotherapy benefit. PATIENTS AND METHODS: A retrospective review of the electronic medical records of 112 patients with tumors tested for the RS and the PREDICT tool was used to estimate survival benefits. The correlation between RS and PREDICT estimations was analyzed using Spearman rank and McNemar tests. RESULTS: The median age of patients was 53 (95% CI, 50 to 55) years, with most patients having negative axillary lymph nodes (78%). While the absolute value for RS showed significant positive correlations with adjuvant chemotherapy's benefit as estimated by PREDICT, no significant correlations were found between the two methods in the percentage of chemotherapy gain. Notably, discordance rates between 48% and 67% between RS-based risk assignments and those based on PREDICT estimates were significant across the study population and subgroups. Only one disease recurrence and one breast cancer-related death were documented over a median follow-up of 23.5 (95% CI, 19.8 to 27.2) months. CONCLUSION: Our findings highlight a significant discordance between RS and PREDICT tools in predicting the benefits of adjuvant chemotherapy in patients with HR+, HER2- early breast cancer. While both tools aim to personalize cancer treatment, their discordance varies, suggesting that PREDICT could not substitute RS to predict adjuvant chemotherapy benefits regardless of patient risk classification. Further studies are needed to explore these relationships and optimize precision medicine approaches in breast cancer management.

Combination of palbociclib with adjuvant endocrine therapy for treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer: An experience at two cancer centers in Saudi Arabia.

The addition of palbociclib (a cyclin-dependent kinase 4/6 inhibitor) to endocrine therapy (ET) has been shown to significantly improve progression-free survival (PFS) and overall survival (OS) among patients with hormone receptor-positive (HR+) advanced breast cancer. The current study presents the local experience of using palbociclib at two cancer centers in Saudi Arabia. Electronic data of patients with metastatic HR+ and human epidermal growth factor receptor 2-negative breast cancer who progressed after prior ET and received at least one cycle of palbociclib plus ET, were retrospectively reviewed. A total of 97 patients were identified, and their data were included in the analysis. The median age of the patients was 55 years. Patients were heavily pretreated in the metastatic setting (55% received systemic chemotherapy and 49% received two or more lines of prior ET). In total, 29 (30%) and 50 (52%) patients achieved an objective response and clinical benefit, respectively. The median follow-up time was 31.0 months [95% confidence interval (CI), 16.9-44.9] and the median PFS time was 16.3 months (95% CI, 11.4-21.2), with 58% of patients remaining progression-free at 12 months. Upon multivariate regression analysis, liver involvement was the only significant independent variable that predicted a greater risk of progression or death (hazard ratio, 2.32; 95% CI, 1.22-4.40; P=0.010). The median OS time was 19.6 months (95% CI, 18.1-20.9), with 12- and 24-month OS rates of 75 and 30%, respectively. Overall, real-world data showed that administration of palbociclib in combination with ET in patients with advanced HR+ breast cancer achieved a favorable outcome that was comparable to that reported in clinical trials.

Energy and caloric restriction, and fasting and cancer: a narrative review.

Dietary interventions have a significant impact on body metabolism. The sensitivity of cancer cells to nutrient and energy deficiency is an evolving characteristic of cancer biology. Preclinical studies provided robust evidence that energy and caloric restrictions could hinder both cancer growth and progression, besides enhancing the efficacy of chemotherapy and radiation therapy. Moreover, several, albeit low-powered, clinical trials have demonstrated clinical benefits in cancer patients. Future research will inform and firmly establish the potential efficacy and safety of these dietary interventions. Here, we review the current evidence and ongoing research investigating the relationship between various dietary restriction approaches and cancer outcomes.

Poly(ADP-ribose) polymerase inhibitors as maintenance treatment in patients with newly diagnosed advanced ovarian cancer: a meta-analysis.

Aim: Poly(ADP-ribose) polymerase inhibitors (PARPIs) improved progression-free survival among patients with recurrent ovarian cancer. This meta-analysis examined the effectiveness of PARPIs as maintenance strategy for newly diagnosed patients with advanced high-grade ovarian cancer with or without mutations. Materials & methods: Using defined selection criteria, a literature search identified four eligible randomized clinical trials involving 2386 patients. Results: Compared with placebo maintenance, PARPIs achieved a 46% reduction in the risk of progression or death as compared with placebo (hazard ratio: 0.54; 95% CI: 0.39-0.73; p < 0.0001). That benefit was shown in all clinical subgroups: among those with BRCA mutation, with negative/unknown BRCA mutation, and in those with homologous recombination deficient tumors. Data about the effect on overall survival are still premature. Conclusion: In patients with newly diagnosed advanced ovarian cancer, PARPIs maintenance after standard therapy achieved a significant improvement in progression-free survival as compared with placebo, overall and in all subgroups.

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.

Hodgkin Lymphoma Outcome: A Retrospective Study from 3 Tertiary Centers in Saudi Arabia.

BACKGROUND: Hodgkin lymphoma (HL) exhibits considerable clinicopathological variations in different parts of the world. This study was prompted by the limited availability of HL data in developing countries (particularly long-term outcomes). METHODS: We performed a retrospective review of eligible adult HL patients treated at 3 tertiary centers in Saudi Arabia between January 1997 and December 2012. RESULTS: The review included 340 patients with a median age of 26 years (range 15-82 years); 53% were male, 74% had an advanced stage, 22% had bulky disease, and 70% had low-to-intermediate risk according to the International Prognostic Score. Nodular sclerosis was the most common histological subtype (59%). Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) was offered to 92% and radiotherapy to 43%. Initial therapy outcomes were complete response, partial response, and progressive disease in 91%, 5%, and 2% of patients, respectively. At a median follow-up of 39 months, the actuarial freedom from treatment failure at 5 years was 74%, with a 5-year overall survival of 91%. Multivariate analysis showed that advanced disease stage and high-risk international prognostic index independently predicted an adverse outcome. CONCLUSION: Our Saudi patient population exhibited outcomes that were comparable to those reported in developed countries.

Bleomycin pulmonary toxicity in adult Saudi patients with Hodgkin's lymphoma.

BACKGROUND: Bleomycin pulmonary toxicity (BPT) has been described in Hodgkin's lymphoma (HL) patients treated with bleomycin-containing chemotherapy regimens. METHODOLOGY: We reviewed the records of 164 consecutive HL patients. RESULTS: BPT was observed in 24 of 164 patients (15%). Older age and history of concomitant lung disease were significantly associated with approximately threefold (odds ratio: 3.38; 95% CI: 1.25-9.13; p = 0.02) and sevenfold (odds ratio: 7.19; 95% CI: 2.64-19.54; p < 0.0001) increase in BPT risk, respectively. The actuarial 5-year progression-free and overall survival for BPT and non-BPT groups, were not significantly different. CONCLUSION: In Saudi Arabian HL patients, the risk of BPT and its effect on survival outcome were comparable to that reported from developed countries.

The predictive and prognostic role of phosphatase phosphoinositol-3 (PI3) kinase (PIK3CA) mutation in HER2-positive breast cancer receiving HER2-targeted therapy: a meta-analysis.

The association between PIK3CA mutation and resistance to anti-HER2 therapy (AHT) is not precisely defined. This meta-analysis intended to explore the clinical utility of PIK3CA mutation in HER2-positive breast cancer treated with AHT. Literature search identified 19 eligible studies. There were 1720 patients with advanced, 828 with early and 1290 patients treated in the neoadjuvant setting. In metastatic breast cancer, AHT showed no differential objective response benefit between the wild type (WT) and the mutated type (MT) PIK3CA subgroups (odds ratio [OR] = 1.09; 95 % CI 0.60-2.00; P = 0.78). AHT favorable affected progression-free survival (PFS) irrespective of PIK3CA mutation. There was no PFS difference between WT and MT regardless of the offered therapy. In early breast cancer, trastuzumab combined with the same chemotherapy conferred consistent relapse-free survival benefit in WT and MT subgroups (WT: HR = 0.59; 95 % CI 0.44-0.80; P < 0.001 vs. MT: HR = 0.42; 95 % CI 0.24-0.74; P < 0.001). In the neoadjuvant setting, AHT-based therapy produced a 72 % higher pathologic complete response (pCR) rate in WT as compared with that in MT PIK3CA tumors (OR = 1.72; 95 % CI 1.29-2.13; P < 0.001). In that setting, there was no disease-free or overall survival difference based on PIK3CA mutational status. In this meta-analysis, AHT did not achieve differential benefit according to PIK3CA mutation in HER2-positive metastatic or early breast cancer; however, in the neoadjuvant setting, patients harboring WT PIK3CA tumors attained a higher pCR rate.

Prospective study of a molecular selection profile for RAS wild type colorectal cancer patients receiving irinotecan-cetuximab.

BACKGROUND: The aim of our study was to evaluate whether a panel of biomarkers, prospectively analysed might be able to predict patients' clinical outcome more accurately than RAS status alone. METHODS: K-RAS (exons 2, 3, 4) wild type colorectal cancer patients, candidates to second/third-line cetuximab with chemotherapy were prospectively allocated into 2 groups on the basis of their profile: favourable (BRAF and PIK3CA exon 20 wild type, EGFR GCN ≥ 2.6, HER-3 Rajkumar score ≤ 8, IGF-1 immunostaining < 2) or unfavourable (any of the previous markers altered or mutated). After the introduction of N-RAS status (exons 2, 3, 4) only RAS wild type patients were considered eligible. Primary aim was response rate (RR). To detect a difference in terms of RR among patients with an unfavourable profile (estimated around 25%) and patients with a favourable profile (estimated around 60%), with a probability alpha of 0.05 and beta of 0.05, required sample size was 46 patients. Secondary endpoints were progression free survival (PFS) and overall survival (OS). RESULTS: Forty-six patients were enrolled. Seventeen patients (37%) were allocated to the favourable and 29 patients (63%) to the unfavourable profile. RR in the favourable and unfavourable group was 11/17 (65%) and 2/29 (7%) (p = 0.007) respectively. The favourable group also showed an improved PFS (8 months vs. 3 months, p < 0.0001) and OS (15 months vs. 6 months, p < 0.0001). CONCLUSIONS: Our results suggest that prospective selection of optimal candidates for cetuximab treatment is feasible and may be able to improve clinical outcome.

The prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancer: a meta-analysis.

In a recent meta-analysis, we demonstrated that rich tumor-infiltrating lymphocytes (TILs) were significantly correlated to a favorable breast cancer (BC) outcome largely in estrogen receptor-negative tumors. It is known that TILs predominate in triple-negative (TN) BC, and to the best of our knowledge, there is no published meta-analysis that examined their prognostic value exclusively in that subtype. Therefore, we planned this meta-analysis to explore the clinical utility of rich TILs in TN-BC. According to predefined selection criteria, literature search identified eight eligible studies. The meta-analysis included data on 2,987 patients with early stage BC. The median percentage of lymph node positivity was 47% (95% confidence interval [CI] 23-82%). Over a median follow-up of 113 months (95% CI 80-144 months), it was found that rich TILs were associated with 30% (hazard ratio [HR] = 0.70; 95% CI 0.56-0.87; P = 0.001), 22% (HR = 0.78; 95% CI 0.68-0.90; P = 0.0008), and 34% (HR = 0.66; 95% CI 0.53-0.83; P = 0.0003), reduction in the risk of recurrence, distant recurrence, and death, respectively. In addition, for every 10% increments in rich TILs, there was an approximate 15-20% reduction in any recurrence, distant recurrence, or mortality. Moreover, rich TILs predicted superior overall survival (OS) benefit irrespective of the disease phenotype (TN-BC or core-basal phenotype), TILs location (intratumoral or stromal), or TILs qualification as either TILs-non-specified, cytotoxic (CD8+) or regulatory (forkhead box protein 3, FOXP3+) T cells. Data on 5-negative phenotype population were limited, and rich TILs failed to demonstrate a prognostic significance in this phenotype. To investigate the heterogeneity that was shown in the analyses of disease-free survival and OS, a set of meta-analyses showed that the method used in TILs detection (hematoxylin and eosin stains vs. immunohistochemistry) could explain most of the variability in the pooled estimates. Rich TILs were significantly associated with better survival outcome in early TN-BC and should be considered as a strong prognostic factor in this subtype. The results from the current meta-analysis support integrating immunotherapy with conventional therapy in future BC research.

Breast cancer screening: review of benefits and harms, and recommendations for developing and low-income countries.

Breast cancer is the most common cancer in women worldwide. The disease remains a public health concern as recent evidence indicates that the breast cancer burden has increased mainly in developing and low-income countries (DLICs). Despite the demonstrated benefits, the debate about the real benefits and harms of breast cancer screening is ongoing. Many experts believe that the benefits of screening, in terms of reduced breast cancer mortality, outweigh the harms, whereas others think the opposite. In this review, we assess the clinical utility of available screening modalities, present evidence, overdiagnosis, cost-effectiveness, and other pertinent issues. We also examine relevant data from DLICs to underscore the barriers and challenges that impede implementation of screening strategies in those populations. We also provide recommendations concerning rational preventive strategies for breast cancer control for women in DLICs.

Sunitinib adverse events in metastatic renal cell carcinoma: a meta-analysis.

BACKGROUND: Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, has demonstrated survival benefit in patients with metastatic renal cell carcinoma (mRCC); however, significant adverse events (AEs) have been associated with its use. The significant variation in the reported incidences of AEs has prompted this meta-analysis to quantify the risk and explore associated predictors. METHODS: According to predefined selection criteria, a literature search identified 12 studies that were included in the analyses. RESULTS: The meta-analysis included 5,658 patients; 66 % patients had prior systemic therapy whereas the remaining patients (34 %) received sunitinib in the first-line setting. For any grade toxicity, skin rash, fatigue, diarrhea, and mucositis were the most frequently encountered events (81, 52, 45, and 33 %, respectively). Anemia, neutropenia, or thrombocytopenia of any grade occurred in more than one-third of patients, although grades 3 or 4 were less common. Any grade raised by liver enzymes or serum creatinine occurred in 40 and 44 % of patients, respectively. Meta-regression analyses showed that study size was inversely related to the risk of experiencing fatigue, diarrhea, mucositis, anemia, and thrombocytopenia. In particular, the incidence of AEs was higher when sunitinib was used in pretreated versus naive patients; however, there was no significant difference between the two groups concerning the incidence of laboratory abnormalities. We addressed the limitations of reporting AEs in clinical studies. CONCLUSIONS: The present meta-analysis quantified sunitinib-associated AEs. The derived estimates would be similar to that to be expected from the use of sunitinib in community practice in unselected patients with metastatic renal cell carcinoma (mRCC).

Increased risk of second lung cancer in Hodgkin's lymphoma survivors: a meta-analysis.

BACKGROUND: Patients treated for Hodgkin's lymphoma (HL) have a higher risk of developing second lung cancer (SLC) compared with the general population. The aim of this meta-analysis was to quantify such risk and to analyze contributing risk factors in HL survivors. METHODS: According to predefined selection criteria, a literature search identified 21 studies that were included in the analysis. RESULTS: After eliminating overlapping or duplicate data, 793 (76 % males) incidences of SLC were encountered in 74,831 patients (58 % males) with HL over a median follow-up of 11.5 years. The median age at HL diagnosis and the median age at SLC diagnosis were 33.0 and 45.9, respectively. The mean latency between treatment of HL and development of SLC was 11.5 years. The pooled relative risk (RR) of SLC was 4.62 (95 % confidence interval [CI], 3.18-6.70], I (2) = 98 %), with a median absolute excess rate of 10.4 per 10,000 person-years. RR was positively related to study size, male-to-female ratio, institutional versus population-based data sets, and the use of any radiotherapy (RT) or combined modality therapy (CMT), while age at diagnosis of HL was not significant. The highest risk was shown among patients aged 15-24 years (RR = 8.76 [95 % CI, 4.55-16.89]), while the lowest risk occurred in patients ≥55 years at primary treatment (RR = 2.88 [95 % CI, 2.33-3.56]). RR increased by increasing duration of follow-up, reaching the highest value at 10-14 years (RR = 4.17 [95 % CI, 3.62-8.81]), but did not increase after ≥15 years (RR = 4.01 [95 % CI, 2.68-5.98]). RT only, CMT, or chemotherapy only was associated with RR (95 % CI) of 4.88 (3.14-7.60), 5.15 (4.08-6.50), and 2.39 (1.60-3.55), respectively. Patients with SLC demonstrated poor prognosis. CONCLUSIONS: The current meta-analysis provided a detailed estimate of the risk of SLC among HL survivors. The obtained results may provide guidelines concerning lung cancer screening for this population.

Risk of second breast cancer in female Hodgkin's lymphoma survivors: a meta-analysis.

BACKGROUND: Women treated for Hodgkin's lymphoma (HL) have an elevated risk of developing second breast cancer (SBC) compared with the general population. We planned this meta-analysis to quantify the long-term risk of SBC and analyze the contributing risk factors among HL survivors. METHODS: According to predefined selection criteria, literature search identified 34 studies that were included in the analyses. RESULTS: After eliminating overlapping or duplicate data, 957 incidences of SBC were encountered in 24,505 females with HL over a median follow-up of 14.9 years. The medians: age at the diagnosis of HL, age at diagnosis of SBC, and latency since HL treatment to the development of SBC were 23.7, 35.0, and 17.7 years, respectively. The pooled relative risk (RR) of SBC was 8.23 (95% CI, 5.43-12.47, I² = 96%), with a median absolute excess rate of 22.9 per 10,000 person-years. The RR was found inversely related to age at diagnosis of HL with the highest rate (68.7; [95%CI, 28.08-168.11], I² = 79%), occurred in young patients (≤ 15 years old), where the RR in older women (≥ 40 years old) was not significant (0.55; [95% CI, 0.09-3.52]). Analysis of RR by 5-year increments since the treatment of HL showed that the risk was highest after 15-19 years of latency (13.87; [95% CI, 7.91-24.30], I² = 89%). Analysis of the effect of treatment modalities showed that the RR rates were (4.70; [95% CI, 3.28-6.75], I² = 74%), (5.65; [95%CI, 2.94-10.88], I² = 91%), and (1.19; [95% CI, 0.50-2.82], I2 = 65%), for radiotherapy (RT) only, combined RT and chemotherapy (CT), and CT only, respectively. To investigate the demonstrated heterogeneity, meta-regression analysis was performed when feasible. In most such analyses, the natural logarithm of RR was inversely associated with age at HL diagnosis. CONCLUSIONS: We conclude that, the current meta-analysis provided the most recent comprehensive estimate of the risk of SBC in a broad-range of HL survivors. Younger age at diagnosis proved to be a dominant risk factor. The obtained results would serve providing breast cancer screening recommendations for HL survivors.

Cetuximab-based therapy is effective in chemotherapy-naïve patients with advanced and metastatic non-small-cell lung cancer: a meta-analysis of randomized controlled trials.

Randomized controlled trails (RCTs) where cetuximab added to first-line platinum-based chemotherapy for patients with advanced/metastatic non-small-cell lung cancer (NSCLC) have yielded conflicting results. This meta-analysis intended to evaluate the efficacy and safety of cetuximab-based therapy (CBT) in that setting. We analyzed four eligible RCTs that included 1,003 and 1,015 patients randomized to CBT and control intervention, respectively. As compared with the noncetuximab group, CBT demonstrated an 9% reduction in the risk of disease progression [hazard ratio (HR) = 0.91; (CI = 0.83-1.00); p = 0.06], a 13% reduction in the risk of death [HR = 0.87; (CI = 0.78-0.96); p = 0.005], and an approximately 50% increase in objective response rate [odds ratio (OR) = 1.48; (CI = 1.22-1.80); p < 0.0001]. CBT-related adverse events were similar across comparisons except for toxicities known to be associated with anti-EGFR therapy. CBT produced significant clinical benefit with acceptable toxicity as a first-line strategy in patients with advanced/metastatic NSCLC. Further research is needed to identify markers predictive of cetuximab benefit in that disease.

Clinical outcome of panitumumab for metastatic colorectal cancer with wild-type KRAS status: a meta-analysis of randomized clinical trials.

Panitumumab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that has a favorable effect on patients with metastatic colorectal cancer (mCRC) harboring wild-type (WT) KRAS gene. This meta-analysis was planned to quantify the benefit and assess safety. Selected for the analysis were randomized clinical studies that have used panitumumab-based therapy (PBT) for patients with mCRC and where the outcome of patients with WT KRAS was reported. Four eligible studies were analyzed including 1,010 and 1,105 patients who received PBT and the control intervention, respectively. Used in subsequent-line setting, PBT was associated with 42% improvement in progression-free survival (PFS) (hazard ratio [HR] = 0.58; 95% CI, 0.36-0.93; P = 0.02), a non-significant overall survival (OS) benefit (HR = 0.90; [95% CI, 0.76-1.05]; P = 0.18), and a significant increase in objective response rate (ORR) (odds ratio (OR) = 0.67 [95% CI, 1.15-77.98]; P = 0.04). PBT showed no benefit in the first-line setting. Restricted analysis to two studies (first- and second-line setting), where the treatment effect of PBT was prospectively analyzed according to tumor KRAS status, showed significant PFS (HR = 0.77), OS (HR = 0.84), and ORR (OR = 2.06) advantage. Almost all patients' subgroups attained clinical benefit. PBT-related adverse events were similar across comparisons with the exception of toxicities known to be associated with anti-EGFR therapy. This meta-analysis showed significant clinical benefit for PBT for patients with WT KRAS mCRC predominantly when used following prior chemotherapy exposure. The benefit was demonstrated in most subgroup analyses. Further research to better define potential responders is needed.

An eight-year snapshot of geospatial cancer research (2002-2009): clinico-epidemiological and methodological findings and trends.

Geographic information systems (GIS) offer a very rich toolbox of methods and technologies, and powerful research tools that extend far beyond the mere production of maps, making it possible to cross-link and study the complex interaction of disease data and factors originating from a wide range of disparate sources. Despite their potential indispensable role in cancer prevention and control programmes, GIS are underrepresented in specialised oncology literature. The latter has provided an impetus for the current review. The review provides an eight-year snapshot of geospatial cancer research in peer-reviewed literature (2002-2009), presenting the clinico-epidemiological and methodological findings and trends in the covered corpus (93 papers). The authors concluded that understanding the relationship between location and cancer/cancer care services can play a crucial role in disease control and prevention, and in better service planning, and appropriate resource utilisation. Nevertheless, there are still barriers that hinder the wide-scale adoption of GIS and related technologies in everyday oncology practice.

Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies.

Published data have shown that physical activity (PA) has a positive role on the primary prevention of breast cancer risk. However, the role of PA on breast cancer outcome has been controversial with inconsistent data. The lack of a meta-analysis that addresses that issue prompted the current report. A comprehensive literature search identified eight studies, of which two studies were excluded. The remaining six studies (12,108 patients with breast cancer) were included in this meta-analysis. Pre-diagnosis PA reduced all causes mortality by 18% but had no effect on breast cancer deaths. Post-diagnosis PA reduced breast cancer deaths by 34% (HR=0.66, 95% CI, 0.57-0.77, P<0.00001), all causes mortality by 41% (HR=0.59, 95% CI, 0.53-0.65, P<0.00001), and disease recurrence by 24% (HR=0.76, 95% CI, 0.66-0.87, P=0.00001). Breast cancer mortality was reduced by pre-diagnosis PA in women with body mass index (BMI)<25 kg/m2, while post-diagnosis PA reduced that risk among those with BMI≥25 kg/m2. On the other hand, post-diagnosis PA reduced all causes mortality regardless of the BMI. The analysis showed that post-diagnosis PA reduced breast cancer deaths (HR=0.50, 95% CI, 0.34-0.74, P=0.0005), and all causes mortality (HR=0.36, 95% CI, 0.12-1.03, P=0.06) among patients with estrogen receptor (ER)-positive tumor, while women with ER-negative disease showed no gain. The current meta-analysis provides evidence for an inverse relationship between PA and mortality in patients with breast cancer and supports the notion that appropriate PA should be embraced by breast cancer survivors.

Frontline gefitinib in advanced non-small cell lung cancer: Meta-analysis of published randomized trials.

OBJECTIVE: Gefitinib, a small molecule tyrosine kinase inhibitor, showed a substantial effect as a salvage treatment for patients with advanced non-small cell lung cancer (NSCLC) who had failed prior chemotherapy. Subsequent phase III trials in previously untreated patients have failed to demonstrate such benefit. It was later reported that gefitinib had a positive outcome when used in selected population. RATIONAL: The inconsistent results and the lack published meta-analysis that systematically examined the overall efficacy of gefitinib in the frontline setting in such patients, have prompted the current meta-analysis. METHODS: We selected for analysis only those randomized, peer-reviewed clinical studies where the efficacy of gefitinib-based therapy (GBT) was investigated in chemotherapy naïve patients with locally advanced or metastatic NSCLC. We also included studies where patients were randomized between gefitinib vs. placebo or none after initial chemoradiation or chemotherapy induction offered to all included patients. RESULTS: We identified seven eligible studies involving 2,646 and 1,939 patients randomized to GBT and to control arms, respectively. In mostly unselected population, GBT was not associated with higher objective response rate (ORR), progression-free survival (PFS) (hazard ratio [HR] = 0.97, 95% CI: 0.78-1.20, P = 0.78), or overall survival (OS) (HR = 1.04, 95% CI: 0.95-1.13, P = 0.45) as compared with control interventions. In a fraction of patients with known EGFR mutation status, GBT showed significantly higher ORR among patients with mutant EGFR (odds ratio [OR] = 2.81, 95% CI: 1.71-4.62, P < 0.0001); however, EGFR mutation was not associated with better PFS or OS with GBT. Nevertheless, patients receiving GBT experienced significant improvement in quality of life as compared with those in the control arms. CONCLUSION: We conclude that GBT cannot be recommended for frontline management of patients with advanced NSCLC in unselected patient population.

Prognostic value of lymph node ratio in poor prognosis node-positive breast cancer patients in Saudi Arabia.

AIM: Women in Saudi Arabia develop breast cancer at a young age with high prevalence of poor prognostic features. Because of such features, it is necessary to examine prognostic factors in this population. One such factor is the prognostic role of lymph node ratio (LNR). METHODS: We performed retrospective analyses of patients with invasive non-metastatic breast cancer who underwent axillary lymph node dissection and had one or more positive axillary lymph nodes. RESULTS: Two hundred and seventeen patients were considered eligible for the analysis. The median age was 46 years. At a median follow-up of 39.8 months, the median disease-free survival (DFS) was 67.3 months (95% CI, 50.4 to 84.3 months). Neither the classification of patients based on positive lymph node (pN) staging system, nor the absolute number of pN prognosticated DFS. Conversely, age 0.20 to 0.65) LNR categories were the only variables that were independently associated with adverse DFS. Using these variables in a prognostic model allowed the classification of patients into three distinctive risk strata. The overall survival (OS) in this series was 92.5 months (95% CI, 92.1-92.6). Only ER negative tumor adversely influenced OS. CONCLUSION: Analysis of survival outcome of mostly young patients with early breast cancer identified adverse prognostic variables affecting DFS. If the utility of the derived model including LNR is proven in a larger patient population, it may replace the use of absolute number of positive axillary lymph nodes.