Breastfeeding and breast cancer risk by receptor status—a systematic review and meta-analysis

BackgroundBreastfeeding is inversely associated with overall risk of breast cancer. This association may differ in breast cancer subtypes defined by receptor status, as they may reflect different mechanisms of carcinogenesis. We conducted a systematic review and meta-analysis of case–control and prospective cohort studies to investigate the association between breastfeeding and breast cancer by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status.DesignWe searched the PubMed and Scopus databases and bibliographies of pertinent articles to identify relevant articles and used random-effects models to calculate summary odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThis meta-analysis represents 27 distinct studies (8 cohort and 19 case–control), with a total of 36 881 breast cancer cases. Among parous women, the risk estimates for the association between ever (versus never) breastfeeding and the breast cancers negative for both ER and PR were similar in three cohort and three case–control studies when results were adjusted for several factors, including the number of full-term pregnancies (combined OR 0.90; 95% CI 0.82–0.99), with little heterogeneity and no indication of publication bias. In a subset of three adjusted studies that included ER, PR, and HER2 status, ever breastfeeding showed a stronger inverse association with triple-negative breast cancer (OR 0.78; 95% CI 0.66–0.91) among parous women. Overall, cohort studies showed no significant association between breastfeeding and ER+/PR+ or ER+ and/or PR+ breast cancers, although one and two studies (out of four and seven studies, respectively) showed an inverse association.ConclusionsThis meta-analysis showed a protective effect of ever breastfeeding against hormone receptor-negative breast cancers, which are more common in younger women and generally have a poorer prognosis than other subtypes of breast cancer. The association between breastfeeding and receptor-positive breast cancers needs more investigation.     

Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results

Cyclooxygenase-2 (COX-2) is overexpressed in lung cancer, especially in adenocarcinoma (ADC). Our aim was to determine the prognostic value of COX-2 on survival in patients with lung cancer. Studies evaluating the survival impact of COX-2 in lung cancer, published until December 2005, were selected. Data for estimation of individual hazard ratios (HR) for survival were extracted from the publications and combined in a pooled HR. Among 14 eligible papers, all dealing with non-small-cell lung cancer, 10 provided results for meta-analysis of survival data (evaluable studies). Cyclooxygenase-2 positivity was associated with reduced survival, improved survival or no statistically significant impact in six, one and seven studies, respectively. Combined HR for the 10 evaluable studies (1236 patients) was 1.39 (95% confidence intervals (CI): 0.97-1.99). In stage I lung cancer (six evaluable studies, 554 patients), it was 1.64 (95% CI: 1.21-2.24). No significant impact was shown in ADC. A slight detrimental effect on survival in patients with lung cancer is associated with COX-2 expression, but the statistical significance is not reached. This effect is statistically significant in stage I, suggesting that COX-2 expression could be useful at early stages to distinguish those with a worse prognosis.     

The impact of breast cancer surgery on functional status in older women – A systematic review of the literature

Primary endocrine therapy as treatment of breast cancer is only recommended in older women with limited life expectancy. However, many older women opt for endocrine therapy due to concerns regarding frailty and potential decline in function after surgery. A decline in functional status after surgery is documented in some cancer types, such as colorectal, however, the full impact of breast cancer surgery is less understood. A systematic review was performed to examine the evidence for impact of breast cancer surgery on functional status in older women. PubMed and Embase databases were searched. Studies were eligible if performed within the last 10 years; included patients over the age of 65 years undergoing breast cancer surgery; included stratification of results by age; measured functional status pre-operatively and at least six months following surgery. A total of 11 studies including 12 030 women were appraised. Two studies represented level-II and nine level-IV evidence. Overall, physical activity level was negatively impacted by breast cancer surgery and this was compounded by the extent of surgery. Evidence for impact of breast cancer surgery on quality of life, fatigue and cognition, was conflicting. The possibility of decline in functional status after breast cancer surgery should be discussed in all older women considering surgery. A structured exercise program may improve the negative effects of surgery on physical activity. Further work is required in the areas of quality of life, fatigability and cognition.     

Sentinel lymph node in oesophageal cancer—a systematic review and meta-analysis

Background

Sentinel lymph nodes (SLNs) have been used to predict regional lymph node metastasis in patients with melanoma and breast cancer. However, the validity of the SLN hypothesis is still controversial for oesophageal cancer. We performed this meta-analysis to evaluate the feasibility and accuracy of radio-guided SLN mapping for oesophageal cancer.

Methods

A systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents Connect, Cochrane library, Google scholar, Science Direct, and Web of Science. Original data was abstracted from each study and used to calculate a pooled event rates and 95% confidence interval (95% CI).

Results

The search identified 23 relevant articles. The overall detection rate was 0.93 (95% CI: 0.894-0.950), sensitivity 0.87 (95% CI: 0.811-0.908), negative predictive value 0.77 (95% CI: 0.568-0.890) and the accuracy was 0.88 (95% CI: 0.817-0.921). In the adenocarcinoma cohort, detection rate was 0.98 (95% CI: 0.923-0.992), sensitivity 0.84 (95% CI: 0.743-0.911) and the accuracy was 0.87(95% CI: 0.796-0.913). In the squamous cell carcinoma group, detection rate was 0.89 (95% CI: 00.792-0.943), sensitivity 0.91 (95% CI: 0.754-0.972) and the accuracy was 0.84 (95% CI: 0.732-0.914).

Conclusions

It is possible to identify and obtain a SLN before neoadjuvant therapy in oesophageal cancer. However, further work is needed to optimize radiocolloid type, refine the technique and develop a quick and accurate way to determine SLN status intraoperatively. This technique has to be further evaluated before it can be applied widely.     

Exposure to acrylamide and human cancer—a review and meta-analysis of epidemiologic studies

BackgroundAcrylamide has been associated to cancer risk in rodents, but data on humans are inconclusive. We thus carried out a critical review and meta-analysis of studies of exposure to acrylamide and cancer.MethodsWe identified 586 publications, 25 presented relevant results. We conducted meta-analyses of studies of dietary intake based on random-effects models by calculating pooled relative risks (RR) and the corresponding 95% confidence intervals (CI). We combined results of occupational studies according to a fixed-effect model.ResultsThe summary RRs for an increase of 10 μg/day of acrylamide intake were close to unity for all the cancers considered, ranging from 0.98 for esophageal cancer to 1.01 for colon, endometrial, ovarian and kidney cancer. None of the estimates was significant. Exclusion of one case–control study from Sweden resulted in a summary RR of kidney cancer of 1.04 (95% CI 1.00–1.08). The combined standardized mortality ratios for high occupational exposure were 1.67 (95% CI 0.83–2.99) for pancreatic cancer and 2.22 (95% CI 0.81–4.84) for kidney cancer.ConclusionsAvailable studies consistently suggest a lack of an increased risk of most types of cancer from exposure to acrylamide. The main association that requires further monitoring involves kidney cancer.     

Letter to the editor regarding: ‘Association between BRCA mutational status and survival in patients with breast cancer: a systematic review and meta-analysis’

Breast Cancer Research and Treatment -     

Anti-tumour activity of platinum compounds in advanced prostate cancer—a systematic literature review

BackgroundFor men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and the radionuclide (radium-223). However, cross-resistance is a clinically relevant problem. Platinum compounds have been tested in a number of clinical trials in molecularly unselected prostate cancer patients. Advances in CRPC molecular profiling have shown that a significant proportion of patients harbour DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents.ObjectiveTo systematically identify and analyse clinical trials that have evaluated platinum agents in advanced prostate cancer patients.MethodsPubMed was searched to identify published clinical trials of platinum agents in advanced prostate cancer. The PRIMSA statement was followed for the systematic review process. Identified trials are analysed for study design, statistical plan, assessments of anti-tumour activity and the potential value of predictive biomarkers.ResultsA total of 163 references were identified by the literature search and 72 publications that met the selection criteria were included in this review; of these 33 used carboplatin, 27 cisplatin, 6 satraplatin, 4 oxaliplatin and 2 other platinum compounds. Overall, anti-tumour activity varies in the range of 10%–40% for objective response and 20%–70% for PSA decline ≥50%. Response seemed highest for the combinations of carboplatin with taxanes or oxaliplatin with gemcitabine. The interpretation of the clinical data is limited by differences in response criteria used and patient populations studied.ConclusionPlatinum compounds have moderate anti-tumour activity in molecularly unselected patients with advanced prostate cancer. Translational evidence of DNA repair deficiency should be leveraged in future studies to select prostate cancer patients most likely to benefit from platinum-based therapy.     

Anthropometric factors and endometrial cancer risk: a systematic review and dose–response meta-analysis of prospective studies

BackgroundGreater body mass index (BMI) has been convincingly related to increased endometrial cancer risk, however, whether adiposity earlier in life or abdominal fatness is an independent risk factor and whether weight gain or greater height increases the risk is not clear.MethodsAs part of the Continuous Update Project of the World Cancer Research Fund International, we conducted a systematic review and meta-analysis of prospective studies of the association between anthropometric measures and endometrial cancer risk and searched PubMed and several other databases up to February 2015. Summary relative risks (RRs) were calculated using a random-effects model.ResultsThirty prospective studies of BMI and endometrial cancer risk with 22 320 cases among 6 445 402 participants were included. The summary RR for a 5-unit increment was 1.54 [95% confidence interval (CI) 1.47–1.61, I² = 81%]. Although the test for non-linearity was significant, P_{non-linearity} < 0.0001, and the curve was steeper within the overweight and obese BMI ranges, there was evidence of increased risk even within the high normal BMI range. The summary RR was 1.45 (95% CI 1.28–1.64, I² = 76%) per 5 BMI units for BMI in young adulthood, 1.18 (95% CI 1.14–1.23, I² = 67%) per 5 kg increase of weight, and 1.16 (95% CI 1.12–1.20, I² = 51%) per 5 kg of weight gained between young adulthood and study baseline, 1.27 (95% CI 1.17–1.39, I² = 71%) per 10 cm increase in waist circumference, 1.21 (95% CI 1.13–1.29, I² = 0%) per 0.1-unit increment in waist-to-hip ratio and 1.30 (95% CI 1.19–1.41, I² = 0%) per 10-cm increase in hips circumference. The summary RR was 1.15 (95% CI 1.09–1.22, I² = 61%) for a 10-cm increase in height.ConclusionsAll measures of adiposity were associated with increased risk of endometrial cancer, and in addition increasing height was associated with increased risk.     

Body mass index and aromatase inhibitors: a step forward in individualizing therapy for breast cancer patients?

Introduction: Progress made in breast cancer management along with treatment-related symptoms has drawn a lot of attention from both scientists and clinicians. Establishing predictive factors for treatment response facilitate tailoring of therapy to each individual patient and leads to a reduction in unnecessary treatments. Body mass index is confirmed to be a risk factor for breast cancer development as well as for disease recurrence, which additionally negatively influence the overall survival. Due to the increased level of fatty tissue in obese and overweight patients, their total level of body aromatase is elevated. This lead to the hypothesis about a worse response to aromatase inhibitors in these groups as compared to normal weight patients, due to incomplete aromatase blockage and thus higher peripheral androgen aromatization.

Areas covered: This review aims to summarize the data from clinical trials assessing the effect of BMI on response to AI-based therapy in the setting of breast cancer.

Expert commentary: Our conclusion made on the data available to date does not exclude BMI from the list of potential predictive factors however further research in this area is warranted.     

Multivitamin and mineral use and breast cancer mortality in older women with invasive breast cancer in the women’s health initiative

Multivitamin use is common in the United States. It is not known whether multivitamins with minerals supplements (MVM) used by women already diagnosed with invasive breast cancer would affect their breast cancer mortality risk. To determine prospectively the effects of MVM use on breast cancer mortality in postmenopausal women diagnosed with invasive breast cancer, a prospective cohort study was conducted of 7,728 women aged 50–79 at enrollment in the women’s health initiative (WHI) in 40 clinical sites across the United States diagnosed with incident invasive breast cancer during WHI and followed for a mean of 7.1 years after breast cancer diagnosis. Use of MVM supplements was assessed at WHI baseline visit and at visit closest to breast cancer diagnosis, obtained from vitamin pill bottles brought to clinic visit. Outcome was breast cancer mortality. Hazard ratios and 95 % confidence intervals (CIs) for breast cancer mortality comparing MVM users to non-users were estimated using Cox proportional hazard regression models. Analyses using propensity to take MVM were done to adjust for potential differences in characteristics of MVM users versus non-users. At baseline, 37.8 % of women reported MVM use. After mean post-diagnosis follow-up of 7.1 ± 4.1 (SD) years, there were 518 (6.7 %) deaths from breast cancer. In adjusted analyses, breast cancer mortality was 30 % lower in MVM users as compared to non-users (HR = 0.70; 95 % CI 0.55, 0.91). This association was highly robust and persisted after multiple adjustments for potential confounding variables and in propensity score matched analysis (HR = 0.76; 95 % CI 0.60–0.96). Postmenopausal women with invasive breast cancer using MVM had lower breast cancer mortality than non-users. The results suggest a possible role for daily MVM use in attenuating breast cancer mortality in women with invasive breast cancer but the findings require confirmation.     

Should de-escalation of bone-targeting agents be standard of care for patients with bone metastases from breast cancer? A systematic review and meta-analysis

BackgroundDe-escalation of bone-targeted agents, such as bisphosphonates and denosumab, from 4- to 12-weekly dosing is an increasingly used strategy in patients with bone metastases from breast cancer. It is unclear whether there is sufficient evidence to support de-escalation as a standard of care.MethodsA systematic review of randomized trials comparing standard 4-weekly administration of bone-targeted agents with de-escalated (Q12-weekly) dosing in breast cancer patients was carried out. Medline, PubMed and the Cochrane Register of Controlled Trials were searched from inception until November 2014 for relevant studies. Outcomes of interest included skeletal-related event (SRE) rates, bone pain, adverse events (AEs) and bone turnover biomarkers. Random-effects meta-analyses were carried out.ResultsA total of nine citations representing seven unique studies were eligible. One study is ongoing with no reported data. Six studies reported data for at least one outcome of interest. Data were available comparing standard versus de-escalated therapy for pamidronate (1 study, 38 patients), zoledronate (3 studies, 1117 patients) and denosumab (2 studies, 284 patients). Meta-analysis of five trials reporting data for on-study SRE rates between standard (61/443 patients) and de-escalated (49/392 patients) arms produced a summary risk ratio of 0.90 (95% confidence interval 0.63–1.29). Meta-analyses of data for AEs and bone turnover biomarkers also showed no statistically significant differences between standard and de-escalated arms, though only limited numbers of patients and events were present for most analyses.ConclusionIn this systematic review of studies of bisphosphonates and denosumab, there appears to be no difference in SREs or pain with de-escalated therapy. While a large, hopefully definitive study is ongoing, the data presented so far are consistent with de-escalation of bone-targeting agents becoming a standard of care for patients with bone metastases from breast cancer.     

Follow-up in breast cancer: does routine clinical examination improve outcome? A systematic review of the literature

Multiple guidelines exist for the follow-up of breast cancer, with no agreement on frequency or duration. The contribution of routine clinical examination for the detection of potentially treatable relapse, and the impact this has on survival, is unknown. In this study, we systematically review the literature to establish the proportion of potentially treatable locoregional relapses and new contralateral breast cancers detected by clinical examination, mammography and patient self-examination. We analyse whether method of detection of relapse influences outcome. The methods used were systematic review of the literature. MEDLINE, EMBASE, CancerLit, Web of Sciences and EBM reviews were the data sources for the systematic review. All studies with information on proportion of relapses detected by clinical examination, mammography and self-examination were included. A total of 30-40% of potentially treatable relapses are detected by patient self-examination. In studies published before 2000, 15% of such relapse is mammographically detected with 46% detected by routine clinical examination. In those published after 2000, 40% are mammographically detected with 15% detected on routine clinical examination. Patients with ipsilateral breast relapse detected clinically appear to do less well than those with relapse detected by self-examination or mammography. Routine clinical surveillance is responsible for detection of fewer potentially treatable relapses in more modern cohorts as experience with mammography increases. There is no evidence to suggest that clinical examination confers a survival advantage compared with other methods of detection. The data in this analysis suggest that a review of the guidelines on follow-up after breast cancer should be undertaken.     

Uptake and predictors of post-mastectomy reconstruction in women with breast malignancy – Systematic review

Purpose

There is enormous range in the reported rates of breast reconstruction. This study explored reasons for this variation by reviewing the published literature to examine rates of reconstruction, factors associated with uptake, and possible barriers.

Methods

A systematic review of the literature was performed. Eligible studies reported rates of breast reconstruction and variables associated with uptake in women undergoing mastectomy for early invasive or in situ breast malignancy.

Results

Twenty-eight eligible studies were included, reporting 159,305 cases of breast reconstruction in 940,678 women. In these studies 16·9% of women underwent immediate or delayed reconstruction (range 4·9–81·2%, median 23·3%). Variables associated with reconstruction were: patient/tumour factors (early stage, no adjuvant therapy, young age, white race, private insurance, higher education/income), surgeon/hospital factors and psychological/other factors (including patient choice).

Conclusion

Rates of breast reconstruction were highly variable. Reconstruction appeared to be offered to a minority of women; around half took up the offer. The main reasons reported for no reconstruction included patient-related and adjuvant therapy-related factors. Clinicians' beliefs about reconstruction may be an important factor. Rates of reconstruction could be increased with early discussion of the options when mastectomy is chosen or required.     

Maintenance treatment of trastuzumab for patients with advanced breast cancer to achieve long term survival： two case reports and literature review

Molecular subtyping of breast cancer may provide additional prognostic information regarding patient outcome. The epidermal growth factor receptor （HER2） overexpressing breast cancers are designated as HER2-postive （HER2＋） breast cancer and carry a particularly unfavorable prognosis. We present two cases of HER2-postive metastatic breast cancer （MBC） who are found to be a challenge to treat, especially due to the occurrence of brain metastasis. Trastuzumab-based therapy improves clinical outcomes, even if the patient has undergone multi-line treatment. These case reports also emphasize the importance of retesting HER2 status because it can be discordance in receptor status between primary and recurrent breast cancer.     

Does dietary counseling improve quality of life in cancer patients? A systematic review and meta-analysis

Results have been mixed as to whether dietary counseling improves clinical outcomes in cancer patients. This systematic review and meta-analysis of randomized trials assessed the effect of dietary counseling on quality of life (QOL). It included only randomized trials that focused on dietary counseling and that relied upon a standardized QOL measurement. Five trials that met these and all other a priori eligibility criteria were identified; they are the focus of this meta-analysis. When these five studies were examined in aggregate, the standardized mean difference in QOL scores among patients who received dietary counseling was 0.56 (95% confidence interval,-0.01-1.14; P = 0.06). Dietary counseling does not appear to improve QOL significantly in patients with cancer. However,an observed trend toward benefit underscores the need for further study.