Weight change in adulthood and risk of postmenopausal breast cancer: the HUNT study of Norway

Background:

Adult weight gain is associated with increased risk of postmenopausal breast cancer. Most previous studies are limited by using recalled or self-reported data, and it is not known if age-specific weight changes are important for breast cancer risk.

Methods:

In a Norwegian cohort of 28 153 women (and 900 incident breast cancers) with longitudinal anthropometric measurements over up to 30 years, we studied both overall and age-related weight changes in adulthood and risk of postmenopausal breast cancer.

Results:

Overall, weight gain in adulthood was associated with increased breast cancer risk (hazard ratio (HR) per kg per year 1.31, 95% confidence interval (CI) 1.11–1.54). Weight gain before (HR per kg per year 1.38, 95% CI 1.09–1.75) or around menopause (1.69, 95% CI 1.32–2.16) was associated with increased risk, but there was no clear risk increase associated with later weight gain (HR per kg per year 0.92, 95% CI 0.73–1.18).

Conclusion:

Weight gain in adulthood was associated with increased risk of breast cancer. Our results suggest that weight gain before and around menopausal age may be particularly important for breast cancer risk among postmenopausal women.     

Employment and social benefits up to 10 years after breast cancer diagnosis: a population-based study

Background:

Little is known about employment outcomes after breast cancer (BC) beyond the first years after treatment.

Methods:

Employment outcomes were compared with a general population comparison group (N=91 593) up to 10 years after BC for 26 120 patients, diagnosed before age 55 between 2000–2005, with income and social benefits data from Statistics Netherlands. Treatment effects were studied in 14 916 patients, with information on BC recurrences and new cancer events.

Results:

BC survivors experienced higher risk of losing paid employment (Hazard Ratio (HR): 1.6, 95% Confidence Interval (95% CI) 1.4–1.8) or any work-related event up to 5–7 years (HR 1.5, 95% CI 1.3–1.6) and of receiving disability benefits up to 10 years after diagnosis (HR 2.0, 95% CI 1.6–2.5), with higher risks for younger patients. Axillary lymph node dissection increased risk of disability benefits (HR 1.5, 95% CI 1.4–1.7) or losing paid employment (HR 1.3, 95% CI 1.2–1.5) during the first 5 years of follow-up. Risk of disability benefits was increased among patients receiving mastectomy and radiotherapy (HR 1.2; 95% CI 1.1–1.3) and after chemotherapy (HR 1.7; 95% CI 1.5–1.9) during the first 5 years after diagnosis.

Conclusions:

BC treatment at least partly explains the increased risk of adverse employment outcomes up to 10 years after BC.     

Concordance of National Cancer Registration with self-reported breast,bowel and lung cancer in England and Wales: a prospective cohort study within the UK Collaborative Trial of Ovarian Cancer Screening

Background:

It has been suggested that lower UK cancer survival may be due to incomplete case ascertainment by cancer registries.

Methods:

We assessed concordance between self-reported breast, bowel and lung cancer and cancer registration (CR) for 1995–2007 in England and Wales in the UK Collaborative Trial of Ovarian Cancer Screening.

Results:

Concordance of breast cancer CR was higher (94.7%:95% CI: 94.1–95.3%) than for bowel (85.1%:95% CI: 82.1–87.8%) and lung (85.4%:95% CI: 76.3–92.0%). CR concordance was lower in breast cancer (94.5% vs 98.8%) survivors compared with deceased but the difference was small. No difference was found for bowel (85.3% vs 94.6%) or lung (87.1% vs 90.5%) cancer.

Conclusion:

Concordance of CR and self-reported cancer is high. Incomplete registration is unlikely to be a major cause of lower UK survival rates.     

Vitamin C intake and breast cancer mortality in a cohort of Swedish women

Background:

Vitamin C may influence cancer progression through its antioxidant properties. However, the evidence from observational epidemiologic studies on vitamin C intake and survival following breast cancer diagnosis is not consistent, and the safety of vitamin C supplements following breast cancer diagnosis has not been extensively studied.

Methods:

Using a food-frequency questionnaire we investigated whether vitamin C intake was associated with survival among 3405 women diagnosed with invasive breast cancer in the Swedish Mammography Cohort.

Results:

From 1987–2010, there were 1055 total deaths with 416 deaths from breast cancer. Women in the highest quartile of pre-diagnosis vitamin C intake had an adjusted HR (95% CI) of breast cancer death of 0.75 (0.57–0.99) compared with those in the lowest quartile (P_trend=0.03). There was a borderline significant association between vitamin C intake and total mortality (HR=0.84; 95% CI=0.71–1.00; P_trend=0.08). Among 717 breast cancer cases for whom post-diagnosis supplement use was available, there was no association between vitamin C supplement use (≈1000 mg) and breast cancer-specific mortality (HR=1.06; 95% CI=0.52–2.17).

Conclusion:

Our findings suggest that dietary vitamin C intake before breast cancer diagnosis may be associated with breast cancer survival. In addition, post-diagnosis vitamin C supplementation at the level observed in our population was not associated with survival.     

The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in breast cancer patients

Background:

The elevation of the platelet-to-lymphocyte ratio (PLR), an easily applicable blood test based on platelet and lymphocyte counts has been associated with poor prognosis in patients with different types of cancer. The present study was aimed to investigate the prognostic significance of the preoperative PLR in a large cohort of breast cancer patients.

Methods:

Data from 793 consecutive non-metastatic breast cancer patients, treated between 1999 and 2004, were evaluated retrospectively. The optimal cutoff values for the PLR were calculated using receiver operating curve analysis. Cancer-specific survival (CSS), overall survival (OS) as well as distant metastasis-free survival (DMFS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of PLR, multivariable Cox regression models were applied for all three different end points.

Results:

Univariable analysis revealed a significant association between the elevated preoperative PLR and CSS (hazard ratio (HR): 2.75, 95% confidence interval (CI): 1.57–4.83, P<0.001) that remained statistically significant in multivariable analysis (HR: 2.03, 95% CI: 1.03–4.02, P=0.042). An increased PLR was also significantly associated with decreased OS in univariable (HR: 2.45, 95% CI: 1.43–4.20, P=0.001) and in multivariable analysis (HR: 1.92, 95% CI: 1.01–3.67, P=0.047). Furthermore, univariable analysis showed a significant impact of increased PLR on DMFS (HR: 2.02, 95% CI: 1.18–3.44, P=0.010). Subgroup analysis revealed significant associations of the elevated PLR on the primary end point CSS for all breast cancer subtypes. This association retained its significance in multivariable analysis in patients with luminal B tumours (HR: 2.538, 95% CI: 1.043–6.177, P=0.040).

Conclusions:

In this study, we identified the preoperative PLR as an independent prognostic marker for survival in breast cancer patients. Independent validation of our findings is needed.     

Diabetes and breast cancer risk: a meta-analysis

Background:

The potential of an increased risk of breast cancer in women with diabetes has been the subject of a great deal of recent research.

Methods:

A meta-analysis was undertaken using a random effects model to investigate the association between diabetes and breast cancer risk.

Results:

Thirty-nine independent risk estimates were available from observational epidemiological studies. The summary relative risk (SRR) for breast cancer in women with diabetes was 1.27 (95% confidence interval (CI), 1.16–1.39) with no evidence of publication bias. Prospective studies showed a lower risk (SRR 1.23 (95% CI, 1.12–1.35)) than retrospective studies (SRR 1.36 (95% CI, 1.13–1.63)). Type 1 diabetes, or diabetes in pre-menopausal women, were not associated with risk of breast cancer (SRR 1.00 (95% CI, 0.74–1.35) and SRR 0.86 (95% CI, 0.66–1.12), respectively). Studies adjusting for body mass index (BMI) showed lower estimates (SRR 1.16 (95% CI, 1.08–1.24)) as compared with those studies that were not adjusted for BMI (SRR 1.33 (95% CI, 1.18–1.51)).

Conclusion:

The risk of breast cancer in women with type 2 diabetes is increased by 27%, a figure that decreased to 16% after adjustment for BMI. No increased risk was seen for women at pre-menopausal ages or with type 1 diabetes.     

Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-α-negative breast cancer

Background:

Although the androgen receptor (AR) is frequently expressed in breast cancer, its relevance in the disease is not fully understood. In addition, the relevance of AR in determining tamoxifen treatment efficiency requires evaluation.

Purpose:

To investigate the tamoxifen predictive relevance of the AR protein expression in breast cancer.

Methods

Patients were randomised to tamoxifen 40 mg daily for 2 or 5 years or to no endocrine treatment. Mean follow-up was 15 years. Hazard ratios were calculated with recurrence-free survival as end point.

Results:

In patients with oestrogen receptor (ER)-negative tumours, expression of AR predicted decreased recurrence rate with tamoxifen (hazard ratio (HR)=0.34; 95% confidence interval (CI)=0.14–0.81; P=0.015), whereas the opposite was seen in the AR− group (HR=2.92; 95% CI=1.16–7.31; P=0.022). Interaction test was significant P<0.001. Patients with triple-negative and AR+ tumours benefitted from tamoxifen treatment (HR=0.12; 95% CI=0.014–0.95 P=0.044), whereas patients with AR− tumours had worse outcome when treated with tamoxifen (HR=3.98; 95% CI=1.32–12.03; P=0.014). Interaction test was significant P=0.003. Patients with ER+ tumours showed benefit from tamoxifen treatment regardless of AR expression.

Conclusions:

AR can predict tamoxifen treatment benefit in patients with ER− tumours and triple-negative breast cancer.     

Supplemental folic acid in pregnancy and childhood cancer risk

Background:

We investigated the association between supplemental folic acid in pregnancy and childhood cancer in a nation-wide study of 687 406 live births in Norway, 1999–2010, and 799 children diagnosed later with cancer.

Methods:

Adjusted hazard ratios (HRs) compared cancer risk in children by approximated periconceptional folic acid levels (folic acid tablets and multivitamins (0.6 mg), only folic acid (0.4 mg), only multivitamins (0.2 mg)) and cancer risk in unexposed.

Results:

Any folic acid levels were not associated with leukemia (e.g., high-level folic acid HR 1.25; 95% CI 0.89–1.76, P_Trend 0.20), lymphoma (HR 0.96; 95% CI 0.42–2.21, P_Trend 0.51), central nervous system tumours (HR 0.68; 95% CI 0.42–1.10, P_Trend 0.32), neuroblastoma (HR 1.05; 95% CI 0.53–2.06, P_Trend 0.85), Wilms'' tumour (HR 1.16; 95% CI 0.52–2.58, P_Trend 0.76), or soft-tissue tumours (HR 0.77; 95% CI 0.34–1.75, P_Trend 0.90).

Conclusions:

Folic acid supplementation was not associated with risk of major childhood cancers.     

The prognostic value of CDKN2A hypermethylation in colorectal cancer: a meta-analysis

Background:

The prognostic value of CDKN2A promoter hypermethylation in colorectal cancer remains controversial. We systematically reviewed the evidence for assessment of CDKN2A methylation in colorectal cancer to elucidate this issue.

Methods:

Pubmed, Embase and ISI web of knowledge were searched to identify eligible studies to evaluate the association of CDKN2A hypermethylation and overall survival and clinicopathological features of colorectal cancer patients. Combined hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% CI) were pooled using a random-effects model.

Results:

A total of 11 studies encompassing 3440 patients were included in the meta-analysis. CDKN2A hypermethylation had an unfavourable impact on OS of patients with colorectal cancer (HR 1.65, 95% CI 1.29–2.11). Subgroup analysis indicated that CDKN2A hypermethylation was significantly correlated with OS in Europe (HR 1.49; 95% CI 1.28–1.74) and Asia (HR 3.30; 95% CI 1.68–6.46). Furthermore, there was a significant association between CDKN2A hypermethylation and lymphovascular invasion (OR 1.68, 95% CI 1.15–2.47), lymph node metastasis (OR 1.68, 95% CI 1.09–2.59) and proximal tumour location (OR 2.09, 95% CI 1.34–3.26) of colorectal cancer.

Conclusion:

This meta-analysis indicated that CDKN2A hypermethylation might be a predictive factor for unfavourable prognosis of colorectal cancer patients.     

Physical function as a prognostic biomarker among cancer survivors

Background:

We tested the hypothesis that objectively measured physical function predicts mortality among cancer survivors.

Methods:

We assessed objectively measured physical function including the short physical performance battery (SPPB) and fast walk speed in older adult cancer survivors.

Results:

Among 413 cancer survivors, 315 (76%) died during a median follow-up of 11.0 years. In multivariable-adjusted analyses, each 1-unit increase in the SPPB score and 0.1 m s⁻¹ increase in fast walk speed predicted a 12% reduction in mortality (hazard ratio (HR): 0.88 (95% confidence interval (CI): 0.82–0.94); P<0.001, and HR: 0.88 (95% CI: 0.82–0.96); P=0.003, respectively).

Conclusions:

Objectively measured physical function may predict mortality among cancer survivors.     

Utility of pre-treatment neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as prognostic factors in breast cancer

Background:

Peripheral blood-derived inflammation-based scores such as the neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) have recently been proposed as prognostic markers in solid tumours. Although evidence to support these markers as unfavourable prognostic factors is more compelling in gastrointestinal cancers, very little is known of their impact on breast cancer. We investigated the association between the NLR and PLR, and overall survival after breast cancer.

Methods:

Data from the University of Malaya Medical Centre Breast Cancer Registry was used. Of 2059 consecutive patients diagnosed from 2000 to 2008, we included 1435 patients with an available pre-treatment differential blood count (∼70%). Patients were stratified into quintiles of the NLR/PLR. Multivariable Cox regression was used to determine the independent prognostic significances of the NLR/PLR.

Results:

Compared with the first quintile of the NLR, women in quintile 5 were younger, had bigger tumours, nodal involvement, distant metastases and higher tumour grades. Higher NLR quintiles were significantly associated with poorer survival with a 5-year relative survival ratio (RSR) of 76.4% (95% CI: 69.6–82.1%) in quintile 1, 79.4% (95% CI: 74.4–83.7%) in quintile 2, 72.1% (95% CI: 66.3–77.3%) in quintile 3, 65.6% (95% CI: 59.8–70.8%) in quintile 4 and 51.1% (95% CI: 43.3–58.5%) in quintile 5. Following adjustment for demography, tumour characteristics, treatment and the PLR, the adjusted hazard ratio (HR) for quintile 5 vs quintile 1 was 1.50 (95% CI: 1.08–1.63); P_trend=0.004. Results were unchanged when the NLR was analysed as a dichotomous variable using different cutoff points. Although patients in PLR quintile 5 had lower survival than in quintile 1 (5-year RSR: 53.2% (95% CI: 46.9–59.2%) vs 77.0% (95% CI: 70.9–82.2%)), this association was not significant after multivariable adjustment. However, a PLR >185 was significantly associated with poorer survival; adjusted HR: 1.25 (95% CI: 1.04–1.52).

Conclusions:

Both the NLR and PLR are independently associated with an increased risk of mortality in breast cancer. Their added value in the prognostication of breast cancer in clinical practice warrants investigation.     

High-risk features in radiation-associated breast angiosarcomas

Background:

Radiation-associated breast angiosarcoma (RT-AS) is an uncommon malignancy with an incidence of less than 1 % of all soft tissue sarcomas. The overall prognosis is quite dismal with high rates of recurrences and poor overall survival. There is an obvious paucity of data regarding clinical outcomes of patients with breast RT-AS.

Methods:

We identified all patients with RT-AS treated at the Memorial Sloan-Kettering Cancer Center between 1982–2011 and collected their correlative clinical information.

Results:

We identified 79 women with RT-AS with a median age of 68 (range 36–87). The median interval between radiation and development of RT-AS was 7 years (range 3–19). The median time to local and distant recurrence was 1.29 years (95 % CI 0.72–NA) and 2.48 years (95 % CI 1.29–NA), respectively. The median disease-specific survival was 2.97 years (95 % CI 2.21–NA). Independent predictors of worse disease-specific survival included age ⩾68 years (HR 3.11, 95 % CI 1.20–8.08, P=0.020) and deep tumors (HR 3.23, 95 % CI 1.02–10.21, P=0.046.)

Conclusion:

RT-AS has high local/distant recurrence rates, limited duration on standard chemotherapy and poor disease-specific survival.     

The preoperative lymphocyte to monocyte ratio predicts clinical outcome in patients with stage III colon cancer

Background:

Inflammation has a critical role in the pathogenesis and progression of cancer. The lymphocyte to monocyte ratio (LMR) could be shown to be prognostic in haematologic neoplasia. In this study, we analysed the LMR with clinical outcome in stage II and III colon cancer patients.

Methods:

Three hundred and seventy-two patients with stage II and III colon cancer were included in this retrospective study. Kaplan–Meier curves and multivariate Cox-regression analyses were calculated for time to recurrence (TTR) and overall survival (OS).

Results:

Including all patients, the elevated preoperative LMR was significantly associated with increased TTR and OS in multivariate analysis (HR: 0.47, 95%CI: 0.29–0.76, P=0.002; HR: 0.51, 95%CI: 0.31–0.83, P=0.007; respectively). In subanalyses, the association was limited to patients with stage III (HR: 0.40, 95%CI: 0.22–0.72, P=0.002), in contrast to patients with stage II (HR: 0.40, 95%CI: 0.28–1.66, P=0.397). When the subgroup of patients with ‘high-risk'' LMR⩽2.83 was analysed, no benefit of adjuvant 5-FU-based chemotherapy could be found (HR: 0.99; 95%CI: 0.60–1.63; P=0.953).

Conclusion:

The LMR might be an independent prognostic marker for TTR in stage III colon cancer patients. Our results further suggest that high-risk patients based on the LMR do not benefit from adjuvant chemotherapy. Independent validation of our findings is warranted.     

Dietary patterns and survival in German postmenopausal breast cancer survivors

Background:

Research on the association between dietary patterns and breast cancer survival is very limited.

Methods:

A prospective follow-up study was conducted in Germany, including 2522 postmenopausal breast cancer patients diagnosed in 2001–2005 with available food frequency questionnaire data. Vital status, causes of death, and recurrences were verified through the end of 2009. Principle component factor analysis was used to identify pre-diagnostic dietary patterns. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazards models.

Results:

Two major dietary patterns were identified: ‘healthy'' (high intakes of vegetables, fruits, vegetable oil, sauces/condiments, and soups/bouillons) and ‘unhealthy'' (high intakes of red meat, processed meat, and deep-frying fat). Increasing consumption of an ‘unhealthy'' dietary pattern was associated with an increased risk of non-breast cancer mortality (highest vs lowest quartile: HR, 3.69; 95% CI, 1.66–8.17; P-trend <0.001). No associations with breast cancer-specific mortality and breast cancer recurrence were found. The ‘healthy'' dietary pattern was inversely associated with overall mortality (HR, 0.74; 95% CI, 0.47–1.15; P-trend=0.02) and breast cancer recurrence (HR, 0.71; 95% CI, 0.48–1.06; P-trend=0.02) in stage I–IIIa patients only.

Conclusion:

Increasing intake of an ‘unhealthy'' pre-diagnostic dietary pattern may increase the risk of non-breast cancer mortality, whereas increasing intake of a ‘healthy'' pattern may reduce the risk of overall mortality and breast cancer recurrence.     

The association of waiting times from diagnosis to surgery with survival in women with localised breast cancer in England

Background:

Survival from breast cancer in the United Kingdom is lower than in other developed countries. It is unclear to what extent waiting times for curative surgery affect survival.

Methods:

Using national databases for England (cancer registries, Hospital Episode Statistics and Office of National Statistics), we identified 53 689 women with localised breast cancer, aged ⩾15 years, diagnosed between 1996 and 2009, who had surgical resection with curative intent within 62 days of diagnosis. We used relative survival and excess risk modelling to determine associations between waiting times and 5-year survival.

Results:

The median diagnosis to curative surgery waiting time among breast cancer patients was 22 days (interquartile range (IQR): 15–30). Relative survival was similar among women waiting between 25 and 38 days (RS: 93.5% 95% CI: 92.8–94.2%), <25 days (RS: 93.0% 95% CI: 92.5–93.4%) and between 39 and 62 days (RS: 92.1% 95% CI: 90.8–93.4%). There was little evidence of an increase in excess mortality with longer waiting times (excess hazard ratio (EHR): 1.06; 95% CI: 0.88–1.27 comparing waiting times 39-62 with 25–38 days). Excess mortality was associated with age (EHR 65–74 vs 15–44 year olds: 1.23; 95% CI: 1.07–1.41) and deprivation (EHR most vs least deprived: 1.28; 95% CI: 1.09–1.49), but waiting times did not explain these differences.

Conclusion:

Within 62 days of diagnosis, decreasing waiting times from diagnosis to surgery had little impact on survival from localised breast cancer.     

Do type 1 receptor tyrosine kinases inform treatment choice? A prospectively planned analysis of the TEAM trial

Background:

Epidermal growth factor receptors contribute to breast cancer relapse during endocrine therapy. Substitution of aromatase inhibitors (AIs) may improve outcomes in HER-positive cancers.

Methods:

Tissue microarrays were constructed. Quantitative analysis of HER1, HER2, and HER3 was performed. Data were analysed relative to disease-free survival and treatment using outcomes at 2.75 and 6.5 years.

Results:

Among 4541 eligible samples, 4225 (93%) had complete HER1–3 data. Overall, 5% were HER1-positive, 13% HER2-positive, and 21% HER3-positive; 32% (n=1351) overexpressed at least one HER receptor. In the HER1–3-negative subgroup, the hazard ratio (HR) for upfront exemestane vs tamoxifen at 2.75 years was 0.67 (95% confidence interval (CI), 0.52–0.87), in the HER1–3-positive subgroup, the HR was 1.15 (95% CI, 0.85–1.56). A prospectively planned treatment-by-marker analysis demonstrated a significant interaction between HER1–3 and treatment at 2.75 years (HR=0.58; 95% CI, 0.39–0.87; P=0.008), as confirmed by multivariate regression analysis adjusting for prognostic factors (HR=0.55; 95% CI, 0.36–0.85; P=0.005). This effect was time dependent.

Conclusion:

In the 2.75 years prior to switching patients initially treated with tamoxifen to exemestane, a significant treatment-by-marker effect exists between AI/tamoxifen treatment and HER1-3 expression, suggesting HER expression could be used to select appropriate endocrine treatment at diagnosis to prevent or delay early relapses.     

Vitamin D intake,blood 25(OH)D levels,and breast cancer risk or mortality: a meta-analysis

Background:

Experimental studies suggest potential anti-carcinogenic properties of vitamin D against breast cancer risk, but the epidemiological evidence to date is inconsistent.

Methods:

We searched MEDLINE and EMBASE databases along with a hand search for eligible studies to examine the association between vitamin D status (based on diet and blood 25-hydroxyvitamin D (25(OH)D)) and breast cancer risk or mortality in a meta-analysis. A random-effect model was used to calculate a pooled adjusted relative risk (RR).

Results:

A total of 30 prospective studies (nested case-control or cohort) were included for breast cancer incidence (n=24 studies; 31 867 cases) or mortality (n=6 studies; 870 deaths) among 6092 breast cancer patients. The pooled RRs of breast cancer incidence for the highest vs the lowest vitamin D intake and blood 25(OH)D levels were 0.95 (95% CI: 0.88–1.01) and 0.92 (95% CI: 0.83–1.02), respectively. Among breast cancer patients, high blood 25(OH)D levels were significantly associated with lower breast cancer mortality (pooled RR=0.58, 95% CI: 0.40–0.85) and overall mortality (pooled RR=0.61, 95% CI: 0.48–0.79). There was no evidence of heterogeneity and publication bias.

Conclusions:

Our findings suggest that high vitamin D status is weakly associated with low breast cancer risk but strongly associated with better breast cancer survival.