Plasma phyto-oestrogens and prostate cancer in the European Prospective Investigation into Cancer and Nutrition

We examined plasma concentrations of phyto-oestrogens in relation to risk for subsequent prostate cancer in a case–control study nested in the European Prospective Investigation into Cancer and Nutrition. Concentrations of isoflavones genistein, daidzein and equol, and that of lignans enterolactone and enterodiol, were measured in plasma samples for 950 prostate cancer cases and 1042 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of these phyto-oestrogens were estimated by conditional logistic regression. Higher plasma concentrations of genistein were associated with lower risk of prostate cancer: RR among men in the highest vs the lowest fifth, 0.71 (95% confidence interval (CI) 0.53–0.96, P trend=0.03). After adjustment for potential confounders this RR was 0.74 (95% CI 0.54–1.00, P trend=0.05). No statistically significant associations were observed for circulating concentrations of daidzein, equol, enterolactone or enterodiol in relation to overall risk for prostate cancer. There was no evidence of heterogeneity in these results by age at blood collection or country of recruitment, nor by cancer stage or grade. These results suggest that higher concentrations of circulating genistein may reduce the risk of prostate cancer but do not support an association with plasma lignans.     

Plasma enterolactone and breast cancer risk in the Nurses’ Health Study II

Lignans are plant-based phytoestrogens with both estrogenic and anti-estrogenic properties that may be important for breast carcinogenesis. Retrospective studies have observed decreased breast cancer risk associated with high circulating enterolactone concentrations, a biomarker of lignan intake, but results from prospective studies are conflicting. To prospectively examine this association, we measured plasma enterolactone levels in 802 breast cancer cases and 802 matched controls nested among predominantly premenopausal women in the Nurses’ Health Study II cohort. We used conditional logistic regression and polytomous logistic regression models, adjusting for known breast cancer risk factors, to calculate relative risks (RR) and 95 % confidence intervals (CI). Compared to women with enterolactone concentrations ≤4 nmol/L, the multivariate-adjusted RRs for breast cancer were 1.18 (95 % CI 0.86–1.62), 0.91 (95 % CI 0.66–1.25), and 0.96 (95 % CI 0.70–1.33) for women with enterolactone levels in the second to the fourth quartiles, respectively; P _trend = 0.60. Results were similar across tumors defined by estrogen and progesterone receptor status. Among premenopausal women with follicular estradiol levels below the median (<47 pg/mL), women in the highest category of enterolactone levels had a 51 % lower breast cancer risk compared to those in the lowest category (95 % CI 0.27–0.91); P _trend = 0.02. No association was observed among women with high-follicular estradiol levels (≥47 pg/mL), (comparable RR = 1.39, 95 % CI 0.73–2.65; P _interaction = 0.02). We did not observe an overall association between plasma enterolactone and breast cancer risk in a large nested case–control study of US women. However, a significant inverse association was observed among premenopausal women with low-follicular estradiol levels, suggesting that enterolactone may be important in a low-estrogen environment. This should be confirmed in future studies.     

The association between physical activity and bladder cancer: systematic review and meta-analysis

Background:

Physical activity may protect against bladder cancer through several biologic pathways, such as enhanced immune function and decreased chronic inflammation. Physical activity may also indirectly prevent bladder cancer by reducing obesity. A sizeable number of epidemiologic studies have examined the association between physical activity and bladder cancer, but the available evidence has not yet been formally summarised using meta-analysis.

Methods:

We performed a systematic literature review and meta-analysis of English-language studies published from January 1975 through November 2013. We followed the PRISMA guidelines and used a random effects model to estimate the summary risk estimates for the association between physical activity and bladder cancer.

Results:

A total of 15 studies with 5 402 369 subjects and 27 784 bladder cancer cases were included. High vs low levels of physical activity were related to decreased bladder cancer risk (summary relative risk (RR)=0.85, 95% confidence interval (CI)=0.74–0.98; I²=83% P-value for heterogeneity across all studies<0.001). Results were similar for cohort studies (RR=0.89, 95% CI=0.80–1.00; I²=64%) and case–control studies (RR=0.71, 95% CI=0.43–1.16; I²=87% P-value for difference=0.108) and they were comparable for women (RR=0.83, 95% CI=0.73–0.94; I²=0%) and men (RR=0.92, 95% CI=0.82–1.05; I²=67; P-value for difference=0.657). Findings were also comparable for recreational (RR=0.81, 95% CI=0.66–0.99; I²=77%) and occupational physical activity (RR=0.90, 95% CI=0.76–1.0; I²=76% P-value for difference=0.374), and they were largely consistent for moderate (RR=0.85, 95% CI=0.75–0.98; I²=76%) and vigorous activity (RR=0.80, 95% CI=0.64–1.00;I²=87% P-value for difference=0.535).

Conclusions:

Physical activity is associated with decreased risk of bladder cancer. Further studies are required to assess the relations of intensity, frequency, duration, and timing in life of physical activity to bladder cancer risk.     

Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk

Background:

Somatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer.

Methods:

A single-nucleotide polymorphism from the PIK3CA locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC).

Results:

Rs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR)=0.97, 95% confidence interval (CI) 0.95–0.99, P=4.6 × 10⁻³), but did not reach significance in the BCAC replication study alone (OR=0.98, 95% CI 0.96–1.01, P=0.139).

Conclusion:

Common germline variation in PIK3CA does not have a strong influence on the risk of breast cancer     

NT5E CpG island methylation is a favourable breast cancer biomarker

Background:

Relapse risk assessment and individual treatment recommendations remain suboptimal for breast cancer patients. In the light of existing preclinical and clinical data, we studied NT5E (5′-nucleotidase, ecto) expression and NT5E CpG island methylation in breast cancer.

Methods:

We used RT–PCR, qPCR, methylation-specific PCR and pyrosequencing to analyse NT5E in breast carcinoma cell lines and primary and breast carcinomas.

Results:

NT5E CpG island methylation was inversely associated with NT5E expression in breast carcinoma cell lines. In clinical series, patients whose primary tumours had NT5E CpG island methylation were less likely to develop metastasis (P=0.003, OR=0.34, 95% CI: 0.17–0.69). In 3/4 paired samples, NT5E was methylated in primary tumours and demethylated in CNS metastases. Patients progressing to non-visceral as compared with visceral metastases were more likely to have NT5E CpG island methylation in primary tumours (P=0.01, OR=11.8). Patients with tumours lacking detectable methylation had shorter disease-free survival (DFS) (P=0.001, HR=2.7) and overall survival (OS) (P=0.001, HR=3). The favourable prognostic value of NT5E methylation was confirmed in oestrogen receptor negative (P=0.011, HR=3.27, 95% CI: 1.31–8.12) and in triple negative cases (P=0.004; HR=6.2, 95% CI: 1.9–20). Moreover, we observed a more favourable outcome to adjuvant chemotherapy in patients whose tumours were positive for NT5E CpG island methylation: DFS (P=0.0016, HR=5.1, 95% CI: 1.8–14.37) and OS (P=0.0005, HR=7.4, 95% CI: 2.416–23.08).

Conclusion:

NT5E CpG island methylation is a promising breast cancer biomarker.     

Dietary acrylamide intake and risk of breast cancer in the UK women's cohort

Background:

No studies to date have demonstrated a clear association with breast cancer risk and dietary exposure to acrylamide.

Methods:

A 217-item food frequency questionnaire was used to estimate dietary acrylamide intake in 33 731 women aged 35–69 years from the UK Women''s Cohort Study followed up for a median of 11 years.

Results:

In all, 1084 incident breast cancers occurred during follow-up. There was no evidence of an overall association between acrylamide intake and breast cancer (hazard ratio=1.08 per 10 μg day⁻¹, 95% CI: 0.98–1.18, P_trend=0.1). There was a suggestion of a possible weak positive association between dietary acrylamide intake and premenopausal breast cancer after adjustment for potential confounders (hazard ratio=1.2, 95% CI: 1.0–1.3, P_trend=0.008). There was no suggestion of any association for postmenopausal breast cancer (hazard ratio=1.0, 95% CI: 0.9–1.1, P_trend=0.99).

Conclusions:

There is no evidence of an association between dietary acrylamide intake and breast cancer. A weak association may exist with premenopausal breast cancer, but requires further investigation.     

Dietary lignan intakes and risk of pre- and postmenopausal breast cancer

Lignans are plant compounds metabolized in the mammalian gut to produce the phytoestrogens enterolactone and enterodiol. Because estrogens have been linked to breast cancer etiology, lignans could affect breast cancer risk through modulation of endogenous estrogen metabolism or competitive inhibition with estrogen receptors. We examined breast cancer risk and dietary lignan intake in a population-based case-control study of 1,122 women with primary, incident, histologically confirmed breast cancer and 2,036 controls frequency matched to cases on age and county of residence as part of the Western New York Exposures and Breast Cancer (WEB) Study. Diet was assessed with a self-administered 104-item food frequency questionnaire and other relevant data were collected by detailed in-person interviews. Lignans were expressed as the sum of the dietary precursors secoisolariciresinol and matairesinol. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression, adjusting for age, total energy and other breast cancer risk factors. Premenopausal women in the highest quartile of dietary lignan intake had reduced breast cancer risk (OR = 0.66; 95% CI = 0.44-0.98). No association was observed between lignan intakes and postmenopausal breast cancer. Our results suggest that dietary lignans may be important in the etiology of breast cancer, particularly among premenopausal women.     

Dietary intake of meat, fruits, vegetables, and selective micronutrients and risk of bladder cancer in the New England region of the United States

Background:

Despite many studies on diet and bladder cancer, there are areas that remain unexplored including meat mutagens, specific vegetable groups, and vitamins from diet.

Methods:

We conducted a population-based case–control study of bladder cancer in Maine, New Hampshire, and Vermont. A total of 1171 cases were ascertained through hospital pathology records and cancer registries from 2001 to 2004. Overall, 1418 controls were identified from the Department of Motor Vehicles (<65 years) and Center for Medicaid and Medicare Services (65–79 years) and were frequency-matched to cases by state, sex, and age (within 5 years). Diet was assessed with a self-administered Diet History Questionnaire. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).

Results:

Processed meat intake was positively associated with bladder cancer (highest vs lowest quartile OR: 1.28; 95% CI: 1.00–1.65; P_trend=0.035), with a stronger association for processed red meat (OR: 1.41; 95% CI: 1.08–1.84; P_trend=0.024). There were no associations between intake of fruits or vegetables and bladder cancer. We did, however, observe an inverse association with vitamin B12 intake (OR: 0.77; 95% CI: 0.61–0.99; P=0.019).

Conclusion:

Vitamin B12 from diet may be protective against bladder cancer, whereas consuming processed meat may increase risk.     

Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study

A diet high in isoflavonoids (soy) is associated with lower breast cancer risk in Asian populations. Due to the low soy intake, dietary lignans may be the more important phytoestrogen class in Western populations. We used a population-based case-control study of breast cancer by age 50 in southern Germany to evaluate the association between dietary intake of different phytoestrogens and premenopausal breast cancer risk. Dietary information was collected from 278 premenopausal cases and 666 age-matched controls, using a validated FFQ. Using multivariate logistic regression, the highest vs. lowest intake quartiles of daidzein and genistein yielded significantly reduced ORs (95% CI) for breast cancer risk of 0.62 (0.40-0.95) and 0.47 (0.29-0.74), respectively. The protective effects of daidzein and genistein were found only for hormone receptor-positive tumors. High intake of other isoflavonoids, e.g., formononetin and biochanin A, as well as the sum of isoflavonoids were not associated with a decrease in risk. Breast cancer risk significantly decreased with a high intake of the plant lignan matairesinol (OR = 0.58, 95% CI 0.37-0.94) but not secoisolariciresinol or the sum of plant lignans. However, both estimated mammalian lignans, enterodiol and enterolactone, were inversely associated with breast cancer risk, with ORs (95% CI) of 0.61 (0.39-0.98) and 0.57 (0.35-0.92), respectively. No effect was found for total phytoestrogen intake. Our results suggest an important role of dietary intake of daidzein and genistein, despite low levels, as well as of matairesinol and mammalian lignans to reduce premenopausal breast cancer risk in this study population.     

Red and processed meat consumption and risk of pancreatic cancer: meta-analysis of prospective studies

Background:

Whether red and processed meat consumption is a risk factor for pancreatic cancer remains unclear. We conducted a meta-analysis to summarise the evidence from prospective studies of red and processed meat consumption and pancreatic cancer risk.

Methods:

Relevant studies were identified by searching PubMed and EMBASE databases through November 2011. Study-specific results were pooled using a random-effects model.

Results:

Eleven prospective studies, with 6643 pancreatic cancer cases, were included in the meta-analysis. An increase in red meat consumption of 120 g per day was associated with an overall relative risk (RR) of 1.13 (95% confidence interval (CI)=0.93–1.39; P_{heterogeneity}<0.001). Red meat consumption was positively associated with pancreatic cancer risk in men (RR=1.29; 95% CI=1.08–1.53; P_{heterogeneity}=0.28; five studies), but not in women (RR=0.93; 95% CI=0.74–1.16; P_{heterogeneity}=0.21; six studies). The RR of pancreatic cancer for a 50 g per day increase in processed meat consumption was 1.19 (95% CI=1.04–1.36; P_{heterogeneity}=0.46).

Conclusion:

Findings from this meta-analysis indicate that processed meat consumption is positively associated with pancreatic cancer risk. Red meat consumption was associated with an increased risk of pancreatic cancer in men. Further prospective studies are needed to confirm these findings.     

Lack of association between vitamin D receptor gene BsmI polymorphism and breast cancer risk: an updated meta-analysis involving 23,020 subjects

The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. A great number of studies regarding the association between BsmI polymorphism in the VDR gene and breast cancer have been published. However, the results have been contradicting. Therefore, we conducted a meta-analysis to re-examine the controversy. Published literatures from PubMed, Embase, and Chinese Biomedical Literature Database (CBM) were searched (updated to July 10, 2013). The principal outcome measure was the odds ratio (OR) with 95 % confidence interval (CI) for breast cancer risk associated with VDR BsmI polymorphism. With all studies involved, the meta-analysis results suggest no statistically significant association between VDR BsmI polymorphism and breast cancer risk (B vs. b, OR?=?0.922, 95 % CI?=?0.836–1.018, P?=?0.108, I ²? =?80.0 %; BB vs. bb, OR?=?0.843, 95 % CI?=?0.697–1.021, P?=?1.75, I ²? =?75.5 %; Bb vs. bb, OR?=?0.930, 95 % CI?=?0.814–1.063, P?=?0.31, I ²? =?73.1 %; BB+Bb vs. bb, OR?=?0.906, 95 % CI?=?0.787–1.043, P?=?1.37, I ²? =?78.7 %; BB vs. bb+Bb, OR?=?0.899, 95 % CI?=?0.786–1.028, P?=?1.56, I ²? =?61.0 %). The results were not changed when studies were stratified by ethnicity or source of controls. This meta-analysis suggested that there were no associations between VDR BsmI polymorphism and breast cancer.     

Impact of tumour size on axillary involvement and distant dissemination in breast cancer

Background:

Tumour size and nodal involvement are the two main prognostic factors in breast cancer (BC). Their impact on the natural history of BC is not fully captured by analyses that ignore their quantitative nature.

Method:

Data pertaining to 18 159 patients treated with primary surgery: 3661 at the Institut Gustave-Roussy (IGR, France) between 1954 and 1983, and 14 498 in the breast cancer registry in the Stockholm–Gotland Health Care region (SG, Sweden) between 1976 and 1999, were collected. The risks of distant metastases (DMs) and of nodal involvement were analysed according to tumour size with parametric models.

Results:

Using SG 1976–1990 as the reference group, relative risks (RRs) for DM were equal to 1.42 (95% CI: 1.29–1.56; P<10⁻¹⁰) in IGR and 0.61 (95% CI: 0.55–0.67; P<10⁻¹⁰) in SG 1991–1999. Differences in tumour size explained the increased risk in IGR (RR adjusted for tumour size 1.09; 95% CI: 0.99–1.20; P=0.07), but not the decreased risk in SG 1991–1999 (adjusted RR: 0.63; 95% CI: 0.57–0.69; P<10⁻¹⁰). The relationship between tumour size and DM risk changed significantly during the 1990s.

Conclusion:

Early diagnosis is sufficient to explain differences in the prognosis before 1990. After 1990, the use of adjuvant systemic therapies is the main reason for the reduction in DM.     

Venous thromboembolism is a relevant and underestimated adverse event in cancer patients treated in phase I studies

Background:

To investigate, retrospectively, the role of tumour histotype and antiangiogenic drugs for venous thromboembolism (VTE) development in advanced cancer patients treated in phase I studies.

Methods:

Patients enrolled and treated in phase I studies conducted by SENDO (Southern Europe New Drugs Organisation) were considered.

Results:

Data of 1415 patients were included in the analysis: 526 (37.2%) patients were males, median age was 57.3 years (range: 13–85). Fifty-six (3.96%) patients developed a VTE. At multivariate analysis gynaecologic (hazard ratio (HR): 2.8, 95% confidence interval (CI): 1.29–6.23, P=0.009) and gastrointestinal tumours (HR: 3.23, 95% CI: 1.18–8.87, P=0.023) as well as combination regimens of cytotoxic and antiangiogenic agents (HR: 2.6, 95% CI: 1.11–6.30, P=0.028), white blood cell >11 000 μl⁻¹ (HR: 2.59, 95% CI: 1.10–6.09, P=0.028) and haemoglobin<10 g dl⁻¹ (HR: 3.1, 95% CI: 1.07–8.94, P=0.037) were statistically correlated with VTE development. Venous thromboembolism was the fourth most common cause of drug discontinuation. The median time from first drug administration to discontinuation was 1.4 for VTE and 2.3 months for the other adverse events (P=0.02).

Conclusion:

Venous thromboembolism is a relatively common complication among patients treated in the context of phase I studies, and may lead to early drug discontinuation. A greater risk of developing VTE is associated with the diagnosis of gynaecologic and gastrointestinal tumours and the combined use of chemotherapy and antiangiogenic drugs.     

The impact of positive peritoneal cytology on prognosis in patients with cervical cancer: a meta-analysis

Background:

The impact of positive peritoneal cytology on the prognosis of cervical cancer is controversial. Thus, we performed a meta-analysis to determine its impact on recurrence, and to investigate correlations between abnormal cytology and/or lymph node metastasis in cervical cancer.

Methods:

A systematic literature review was conducted through July 2014. Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were calculated by standard meta-analysis techniques with the fixed-effects models, if there was no significant statistical heterogeneity across studies by using I².

Results:

Of 303 studies retrieved, 6 were included in the meta-analysis. These six case–control observational studies included 1360 cervical cancer patients who showed negative peritoneal cytology and 64 who showed positive peritoneal cytology. Over the combined study period, 20 of 45 in the positive peritoneal cytology group experienced recurrence, whereas 88 of 539 controls did. The meta-analysis based on the fixed-effects model indicated a significant increase in the risk of recurrence in the positive peritoneal cytology group relative to the control group (OR: 4.47; 95% CI: 2.33–8.58, P<0.001, I²=0.0%). Moreover, the results of our meta-analysis suggested that the positive peritoneal cytology group displayed more lymph node metastasis than the negative peritoneal cytology group (OR: 3.73; 95% CI: 2.13–6.53, P<0.001, I²=0.0%).

Conclusions:

Although based mainly on retrospective observational studies, our meta-analysis indicates that abnormal peritoneal cytology may be strongly associated with poor prognosis in patients with cervical cancer. Future research should verify this relationship through prospective observational studies over a longer term.     

FAS−1377 A/G polymorphism in breast cancer: a meta-analysis

FAS is a cell surface receptor involved in apoptotic signaling in many cell types including cells of the immune system. The ?1377 A/G polymorphism of FAS gene has been detected in breast cancer. However, the published evidence regarding the ?1377 A/G polymorphism and breast cancer risk has generated controversial results. We performed a meta-analysis of five case–control association studies totaling to 5,995 study subjects including 2,905 cases and 3,090 controls. The combined odd ratios (ORs) with its 95 % CIs were used to assess the association of the ?1377 A/G polymorphism correlated with breast cancer susceptibility with the fixed-effects model. The combined results showed significantly increased risk associated with the ?1377 A/G polymorphism under AA vs. GG genetic model (OR?=?1.28, 95 % CI?=?1.04–1.58; heterogeneity test: P?=?0.614, I ² ?=?0.0 %), AA vs. GA + GG genetic model (OR?=?1.24, 95 CI?=?1.02–1.51; heterogeneity test: P?=?0.349, I ² ?=?10.0 %), and allele model A vs. G (OR?=?1.10, 95%CI?=?1.02–1.20; heterogeneity test: P?=?0.422, I ² ?=?0.0 %). Similarly, significant association was found in Asians. In stratified analyses by control source, a higher risk was indicated in the hospital-based studies rather than the population-based studies. This meta-analysis suggests that the ?1377 A/G polymorphism is likely to be associated with the risk of breast cancer, especially the A allele in Asians.     

Cancer risks in first-degree relatives of CHEK2 mutation carriers: effects of mutation type and cancer site in proband

It is important to have accurate knowledge of the range of cancers associated with various CHEK2 mutations, and of the lifetime risks of cancer associated with each. We wished to establish the relationship between family history, mutation type and cancer risk in families with a CHEK2 mutation. We obtained a blood sample and pedigree information from 2012 unselected women with breast cancer, from 2007 men with prostate cancer and from 1934 patients with colon cancer, from hospitals throughout Poland. Genetic testing was carried out for four founder CHEK2 mutations on all 5953 specimens and 533 carriers were identified. We estimated the risk to age 75 for any cancer in the 2544 first-degree relatives to be 22.3%. After adjusting for mutation type, the risk of breast cancer was much higher among relatives of probands with breast cancer than among relatives of patients with prostate or colon cancer (HR=3.6; 95% CI=2.1–6.2; P=0.0001). Similarly, the risk of prostate cancer was higher among relatives of probands with prostate cancer than among relatives of patients with breast or colon cancer (HR=4.4; 95% CI=2.2–8.7; P=0.0001) and the risk of colon cancer was higher among relatives of probands with colon cancer than among relatives of patients with prostate or breast cancer (HR=4.2; 95% CI=2.4–7.8; P=0.0001). These analyses suggest that the risk of cancer in a carrier of a CHEK2 mutation is dependent on the family history of cancer.     

Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers

Purpose:

The objective of this study was to estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers; and measure the extent to which host, family history, and cancer treatment-related factors modify the risk.

Patients and methods:

Patients were 810 women, with stage I or II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up.

Results:

Overall, 149 subjects (18.4%) developed a contralateral breast cancer. The 15-year actuarial risk of contralateral breast cancer was 36.1% for women with a BRCA1 mutation and was 28.5% for women with a BRCA2 mutation. Women younger than 50 years of age at the time of breast cancer diagnosis were significantly more likely to develop a contralateral breast cancer at 15 years, compared with those older than 50 years (37.6 vs 16.8% P=0.003). Women aged <50 years with two or more first-degree relatives with early-onset breast cancer were at high risk of contralateral breast cancer, compared with women with fewer, or no first-degree relatives with breast cancer (50 vs 36% P=0.005). The risk of contralateral breast cancer was reduced with oophorectomy (RR 0.47; 95% CI 0.30–0.76; P=0.002).

Conclusion:

The risk of contralateral breast cancer risk in BRCA mutation carriers declines with the age of diagnosis and increases with the number of first-degree relatives affected with breast cancer. Oophorectomy reduces the risk of contralateral breast cancer in young women with a BRCA mutation.     

Dietary Patterns and Risk of Invasive Ductal and Lobular Breast Carcinomas: A Systematic Review and Meta-analysis

The histopathologic subtypes of breast cancer, including invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC), differ in terms of risk factors, progression, and response to treatment. The PubMed/Medline, Web of Science, and Scopus databases were searched up to February 2020 for published studies on the association between dietary patterns (Western diet [WD] or Mediterranean diet [WD]) and the risk of IDC/ILC of breast. Multivariable adjusted relative risk (RR) and 95% confidence intervals (CIs) comparing the highest and lowest categories of WD and MD patterns were combined by using the random-effects meta-analyses. After searching the databases, 10 eligible studies on the association of diet and IDC (7 articles) and ILC (3 articles) were included in the analysis. A statistically significant adverse association was observed between MD and IDC in case–control studies (RR = 0.47; 95% CI, 0.39-0.55; I² = 85.1%; P < .001). However, the association was nonsignificant in cohort studies (RR = 0.98; 95% CI, 0.92-1.05; I² = 88.8%; P = .003). The pooled analysis also suggested a significant and direct association between the WD and the risk of IDC (RR = 1.36; 95% CI, 1.18-1.53; I² = 63.7%; P = .017). The risk of ILC for the highest compared to the lowest category of MD was highly protective (RR = 0.76; 95% CI, 0.64-0.87; I² = 89.2%; P < .001), and a marginally significant association was found between the WD and risk of ILC (RR = 1.45; 95% CI, 1.04-1.86), with no heterogeneity (I² = 0; P = .52). This meta-analysis provides supporting evidence for the association between MD decreased risk of IDC and ILC of the breast and the association between WD and increased risk of IDC and ILC. Further investigations are needed to better understand the reasons behind the etiologic mechanisms of how dietary patterns affect patients differently by common breast cancer subtypes, including IDC and ILC.     

Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer

Background:

The potential prognostic value of several commonly investigated immunohistochemical markers in resected pancreatic cancer is variably reported. The objective of this study was to conduct a systematic review of literature evaluating p53, p16, smad4, bcl-2, bax, vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression as prognostic factors in resected pancreatic adenocarcinoma and to conduct a subsequent meta-analysis to quantify the overall prognostic effect.

Methods:

Relevant literature was identified using Medline, EMBASE and ISI Web of Science. The primary end point was overall survival assessed on univariate analysis. Only studies analysing resected pancreatic adenocarcinoma were eligible for inclusion and the summary log_e hazard ratio (logHR) and variance were pooled using an inverse variance approach. Evidence of heterogeneity was evaluated using the χ² test for heterogeneity and its impact on the meta-analysis was assessed by the I² statisic. Hazard ratios greater than one reflect adverse survival associated with positive immunostaining.

Results:

Vascular endothelial growth factor emerged as the most potentially informative prognostic marker (11 eligible studies, n=767, HR=1.51 (95% confidence interval, CI=1.18–1.92)) with no evidence of any significant publication bias (Egger''s test, P=0.269). Bcl-2 (5 eligible studies, n=314, HR=0.51 (95% CI=0.38–0.68)), bax (5 studies, n=274, HR=0.63 (95% CI=0.48–0.83)) and p16 (3 studies, n=229, HR=0.63 (95% CI=0.43–0.92)) also returned significant overall survival differences, but in smaller patient series due to a lack of evaluable literature. Neither p53 (17 studies, n=925, HR=1.22 (95% CI=0.96–1.56)), smad4 (5 studies, n=540, HR=0.88 (95% CI=0.61–1.27)) nor EGFR (4 studies, n=250, HR=1.35 (95% CI=0.80–2.27)) was found to represent significant prognostic factors when analysing the pooled patient data. There was evidence of significant heterogeneity in four of the seven study groups.

Conclusion:

These results support the case for immunohistochemical expression of VEGF representing a significant and reproducible marker of adverse prognosis in resected pancreatic cancer.     

Aspirin Use and Risk of Breast Cancer: A Meta-analysis of Observational Studies from 1989 to 2019

BackgroundSome evidence shows that aspirin can reduce the morbidity and mortality of different cancers, including breast cancer. Aspirin has become a new focus of cancer prevention and treatment research at present, however, clinical studies found conflicting conclusions of its anticancer characteristics.Materials and MethodsA systematic literature search was performed in 8 electronic databases. The pooled relative risk (RR) with 95% confidence interval (CI) was calculated using the random effects model to estimate the effect of aspirin on breast cancer.ResultsForty-two published articles with 99,769 patients were identified. The meta-analysis showed a significant decrease in breast cancer risk with aspirin use (RR, 0.92; 95% CI, 0.89-0.96; I² = 72%). Aspirin use decreased the risk of hormone receptor–positive tumors (estrogen receptor [ER]-positive RR, 0.89; 95% CI, 0.82-0.97; I²=54%; progesterone receptor [PR]–positive RR, 0.86; 95% CI, 0.78-0.95; I²=32%; ER- and PR-positive RR, 0.92; 95% CI, 0.85-1.00; I²=45%) and reduced the risk of breast cancer in postmenopausal women (RR, 0.92; 95% CI, 0.86-0.98; I²=59%). Further analysis showed that for the in situ breast cancer, regular-dose and more than 3 years use of aspirin were associated with the reduced risk of breast cancer.ConclusionThis meta-analysis suggested that aspirin may reduce the overall risk of breast cancer, reduce the risk of breast cancer in postmenopausal women, hormone receptor–positive tumors, and in situ breast cancer. Larger, multicenter clinical studies are needed to find the optimal dose range, frequency, and duration of the aspirin use to explore the best benefit–risk ratio.