Unopposed estrogen and estrogen plus progestin menopausal hormone therapy and lung cancer risk in the NIH–AARP Diet and Health Study Cohort

Purpose  

Previous studies have reported that lung cancer risk may be decreased, increased, or unaffected by prior use of menopausal hormone therapy (MHT).     

Is estrogen plus progestin menopausal hormone therapy safe with respect to endometrial cancer risk?

Given the strong link between use of unopposed estrogens and development of endometrial cancers, estrogens are usually prescribed with a progestin, particularly for women with intact uteri. Some studies suggest that sequential use of progestins may increase risk; however, the moderating effects of usage patterns or patient characteristics, including body mass index (BMI), are unknown. We evaluated menopausal hormone use and incident endometrial cancer (n = 885) in 68,419 postmenopausal women with intact uteri enrolled in the National Institutes of Health‐American Association of Retired Persons Diet and Health study. Participants completed a risk factor questionnaire in 1996–1997 and were followed up through 2006. Hazard rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Among 19,131 women reporting exclusive estrogen plus progestin use, 176 developed endometrial cancer (RR = 0.88; 95% CI = 0.74–1.06). Long‐duration (≥10 years) sequential (<15 days progestin per month) estrogen plus progestin use was positively associated with risk (RR = 1.88; 95% CI = 1.36–2.60], whereas continuous (>25 days progestin per month) estrogen plus progestin use was associated with a decreased risk (RR = 0.64; 95% CI = 0.49–0.83). Increased risk for sequential estrogen plus progestin was seen only among thin‐to‐normal weight women (BMI < 25 kg/m²; RR = 2.53). Our findings support that specific categories of estrogen plus progestin use increases endometrial cancer risk, specifically long durations of sequential progestins, whereas decreased endometrial cancer risk was observed for users of short‐duration continuous progestins. Risks were highest among thin‐to‐normal weight women, presumably reflecting their lower endogenous estrogen levels, suggesting that menopausal hormones and obesity increase endometrial cancer through common etiologic pathways.     

Was race a factor in the outcomes of the women's health eating and living study?

BACKGROUND:

The objective of this study was to determine whether women who were participating in the Women's Healthy Eating and Living (WHEL) Study exhibited similar dietary changes, second breast cancer events, and overall survival regardless of race/ethnicity.

METHODS:

For this secondary analysis, the authors used data from 3013 women who were self‐identified as Asian American, African American, Hispanic, or white and who were assigned randomly to a dietary intervention or a comparison group. Changes in dietary intake over time by race/ethnicity and intervention status were examined using linear mixed‐effects models. Cox proportional hazards models were used to examine the effects of the intervention on the occurrence of second breast cancer events and overall survival. Statistical tests were 2‐sided.

RESULTS:

African Americans and Hispanics consumed significantly more calories from fat (+3.2%) and less fruit (?0.7 servings daily) than Asians and whites at baseline (all P < .01). Overall, intervention participants significantly improved their dietary pattern from baseline to the end of Year 1, reducing calories from fat by 4.9% and increasing intake of fiber (+6.6 grams daily), fruit (+1.1 servings daily), and vegetables (+1.6 servings daily; all P < .05). Despite improvements in the overall dietary pattern of these survivors, the intervention did not significantly influence second breast cancer events or overall survival.

CONCLUSIONS:

Overall, all racial groups significantly improved their dietary pattern over time, but the maintenance of these behaviors were lower among African‐American women. More research and larger minority samples are needed to determine the specific factors that improve breast cancer‐specific outcomes in diverse populations of survivors. Cancer 2011. © 2011 American Cancer Society.     

Estrogen receptor-beta: why may it influence clinical outcome in estrogen receptor-alpha positive breast cancer?

In the previous issue of the journal, Lin and coworkers present data demonstrate that increased expression of estrogen receptor (ER)-beta in ER-alpha-positive breast cancer cells antagonizes a defined group of ER-alpha/estrogen stimulated genes that are involved in cell cycle regulation and DNA replication. Similar expression patterns for these genes were found human ER-alpha positive breast tumors expressing higher levels or ER-beta, and this correlated with better clinical outcome. The implications for these data, which suggest that ER-beta is a positive actor and diagnostic marker for therapeutic outcome, are discussed.     

Glycemic index,glycemic load,and the risk of pancreatic cancer among postmenopausal women in the women’s health initiative observational study and clinical trial

Background  

Several reports have suggested that conditions associated with hyperinsulinemia and insulin resistance, such as diets high in carbohydrates, may influence the risk of pancreatic cancer, although results from prior studies have been mixed.     

Is there any difference in PBPC mobilization between cyclophosphamide plus G-CSF and G-CSF alone in patients with non-Hodgkin's Lymphoma?

We attempted to analyze whether the use of high-dose cyclophosphamide (CTX 7g/m2, group A) plus hematopoietic growth factor (G-CSF) or G-CSF alone (10 microg/Kg, group B) as a mobilizing regimen, could result in harvesting different numbers of CD34+ cells, committed progenitors and CD34+ cells subsets. The number of CD34+ cells considered as the target for each high-dose chemotherapy was > or = 2 x 10(6) /Kg/bw. Fifteen leukaphereses procedures were necessary in group A, while 16 procedures were performed in group B. We did not observe any difference between the two groups in terms of CD34+ cells/microl in the peripheral blood (117 vs 78; p = NS), whereas in the aphereses product we found a significant difference between the two groups of patients in terms of CD34+ cells (6.41 vs 2.89 x 10(6) /Kg/bw; p = .009), CFU-GM (82.5 vs 52.3 x 10(4) /Kg/bw; p = .04). Interestingly, we noted a different distribution of CD34+/33- cells between the 2 groups (mean value 39% vs 65%; p < .05), whereas we did not find any differences regarding CD34+/38-, CD34+/Thy1+, CD34+/HLADR-. The higher number of CFU-GM/Kg/bw collected in the former group did not translate into a superior plating efficiency (27.75 vs 30.29). Furthermore, we observed a strong correlation between CD34+ cells/microl in the peripheral blood and the total number of CD34+ cells in the leukaphereses product (r = 0.97), whereas this correlation was not found in group B (r = 0.15). In both groups of patients the number of CD34+ cells collected correlated well with CFU-GM (r = 0.93; r = 0.94), but definitely we did not observe any correlation between CD34+ cells/microl and CFU-GM in patients mobilized with G-CSF alone and this did not allow us to predict the harvest accurately. Finally, we evaluated the engraftment kinetics and we did not observe any statistically significant difference between the two groups of patients.     

High-dose radiotherapy plus prolonged hormone therapy in CT2-3 prostatic carcinoma: is it useful?

AIMS AND BACKGROUND: Clinical studies published in the last decade have shown the possible improvement in prognosis of patients with prostatic carcinoma undergoing radiation therapy with dose escalation or in combination with hormone therapy. However, in studies on hormone therapy, moderate doses of radiation therapy have been used, whereas in studies with high-dose radiotherapy, hormone therapy usually was not administered. Therefore, it is not clear whether the concomitant use of high doses and prolonged hormone therapy could determine an additional beneficial effect. The aim of the present study was therefore to evaluate the relative prognostic role of different dose levels (< 70 versus > or = 70 Gy) of external beam radiotherapy and of different hormone therapies (neoadjuvant only versus neoadjuvant + adjuvant). METHODS: A total of 426 patients (median age, 71 yrs; range, 51-87 yrs) underwent external beam radiotherapy (70 Gy median dose to prostate volume +/- 45 Gy to pelvic lymph nodes) and neoadjuvant hormone therapy (bicalutamide for 30 days; goserelin, 3.6 mg every 28 days starting two months before radiotherapy and for its entire duration). Dose to the prostate was < 70 Gy in 44.8% of patients and > or = 70 Gy in 55.2%. A total of 244 patients received adjuvant hormonal therapy. The distribution according to the clinical stage was 48.1% T2 and 51.9% T3. The distribution according to the Gleason score was 14.3% grades 2-4, 66.7% grades 5-7 and 19.0% grades 8-10. The distribution according to pretreatment prostate-specific antigen levels (in ng/mL) was 7.0% for 0-4, 29.3% for 4-10, 30.3% for 10-20, and 33.3% for > 20. RESULTS: With a median follow-up of 35 months (range, 1-151), 81 patients (19.0%) showed biochemical recurrence, 17 patients (4.0%) showed local disease progression, and 12 patients (2.8%) showed distant metastases. Overall, 23 patients (5.4%) showed disease progression. Four patients (0.9%) died. At the time of this writing, no patient has died from prostatic carcinoma. At univariate analysis, the radiation dose delivered to the tumor and the administration of adjuvant hormone therapy were shown to be significantly correlated with biochemical disease-free survival. At multivariate analysis, the single parameter significantly correlated with biochemical disease-free survival was the radiation dose delivered to the tumor. In the subset of patients not treated with adjuvant hormone therapy, there was a significant correlation between radiation dose and biochemical disease-free survival at univariate and multivariate analysis. A similar correlation between adjuvant hormone therapy and biochemical disease-free survival was observed in the subset of stage cT3 patients at univariate and multivariate analysis. In patients undergoing combined treatment without adjuvant hormone therapy, a significant correlation was observed between clinical stage and biochemical disease-free survival, at univariate and at multivariate analysis. CONCLUSIONS: The results of the study confirmed the positive impact of radiotherapy doses > 70 Gy and of adjuvant hormone therapy in patients with locally advanced prostatic carcinoma. Owing to the lack of evidence of a correlation between radiation dose and biochemical outcome in patients undergoing prolonged hormone therapy, the role of further dose escalation in patients undergoing combined hormone and radiation therapy is still unclear.     

Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study

Background  

Diagnosing colorectal cancer (CRC) at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear.     

Do children and adults differ in survival from medulloblastoma? A study from the SEER registry

Studies investigating whether adults have diminished survival from medulloblastoma (MB) compared with children have yielded conflicting results. We sought to determine in a population-based registry whether adults and children with MB differ in survival, and to examine whether dissimilar use of chemotherapy might contribute to any disparity. 1,226 MB subjects were identified using the Surveillance Epidemiology and End Results (SEER-9) registry (1973–2002) and survival analysis performed. MB was defined strictly to exclude non-cerebellar primitive neuro-ectodermal tumors. Patients were stratified by age at diagnosis: <3 years (infants), 3–17 years (children) and ≥18 years (adults). Because the SEER-9 registry lacks treatment data, a subset of 142 patients were identified using the San Francisco-Oakland SEER registry (1988–2003) and additional analyses performed. There was no significant difference in survival between children and adults with MB in either the SEER-9 (P = 0.17) or SFO (P = 0.89) cohorts but infants fared worse compared to both children (P < 0.01) and adults (P < 0.01). In the SFO sample, children and adults who received chemotherapy plus radiation therapy (XRT) did not differ in survival. Among patients treated with XRT alone, children showed increased survival (P = 0.04) compared with adults. Children and adults with MB do not differ with respect to overall survival, yet infants fare significantly worse. For children and adults with MB treated with both XRT and chemotherapy, we could not demonstrate a survival difference. Similar outcomes between adult and childhood MB may justify inclusion of adults in pediatric cooperative trials for MB.     

Salvage surgery in head and neck cancer: Does it improve outcomes?

BackgroundStudies reporting outcomes of salvage surgery in locally advanced head and neck squamous cell carcinoma (LAHNSCC) have inherent biases like biological and temporal selection. Our study considered all patients deemed fit for salvage surgery and compared to those who underwent surgery versus those who refused it thus throwing light on the real world benefit of salvage surgery.MethodsThis was a post hoc analysis of a phase 3 randomized trial conducted between 2012 and 2018. Out of 536 LAHNSCC patients randomised in the study, 113 patients had residual disease or recurrent disease and were planned for salvage surgery in a multidisciplinary clinic. Patients were divided into 2 cohorts for comparison, willing for salvage surgery (n = 91) and unwilling for salvage surgery(n = 22). The primary endpoint was overall survival.ResultsThe median follow up was 28.7 months (95%CI 23.9–33.5 months). Out of the 91 patients who were willing for salvage surgery, 78 underwent same. The median survival in cohort of patients willing for salvage surgery was 22.0 months (95%CI 10.1–33.9) while it was 9.7 months (95%CI 6.6–12.8) in patients who were unwilling for salvage surgery (HR = 0.262 95%CI HR 0.147–0.469, p = 0.000).ConclusionSalvage surgery leads to a substantial improvement in outcomes in head and neck cancers and should be the de facto standard of care in patients who are eligible for the same.     

Challenging the current norm: Does health related quality of life data from reference populations accurately reflect baseline values in breast cancer patients? An observational cohort study comparing EORTC QLQ-C30 scores between the general Swedish population and baseline scores in breast cancer patients

BackgroundIncreased overall survival in breast cancer patients has led to a growing recognition of long-term effects of cancer treatment of patients’ quality of life. Health related quality of life (HRQoL) data, as measured by patient reported outcome measures (PROMs), is increasingly incorporated into clinical practice and research. A commonly used method current available to interpret HRQoL PROMs data is by comparison to reference values, often obtained from sampling of the general population. The aim of this study was to assess whether HRQoL reference values derived from the general population are an accurate representation of the baseline values of an outpatient breast clinic population.MethodsA prospective observational cohort study was conducted by obtaining EORTC QLQ-C30 values for all patients offered an appointment in the outpatient breast clinic. These results were then compared to published baseline values in the general Swedish population, matched by gender and age.Results568 questionnaires were returned with a response rate of 81,1 %. The outpatient breast clinic cohort reported a higher grade of symptoms, lower function and lower quality of life compared to the equivalent reference population.ConclusionThis study challenges the assumption that the reference values accurately reflect those of the study population which clinicians and researchers need to account for in study design and clinical practice.     

Expression of estrogen receptor-beta in normal mammary and tumor tissues: is it protective in breast carcinogenesis?

Using messenger RNA (mRNA) in situ hybridization, we investigated estrogen receptor- (ER) mRNA levels in normal mammary, benign breast tumor (BBT), breast cancer (BC), and metastatic lymph node tissues to verify the role of ER in BC development and progression. ER expression was significantly decreased in BC and metastatic lymph node tissues compared with normal mammary and BBT tissues (p < 0.01). The intensity and extent of ER mRNA signals were also significantly lower in BC and metastatic lymph node tissues than in the normal mammary and BBT tissues (p < 0.01). An inverse relationship was found between ER mRNA level and both histologic grade (p = 0.091) and progesterone receptor expression (p = 0.052) with marginal significance, but no significant association was noted between ER expression in cancer tissues and the other clinico-pathologic data. The 3-year distant relapse-free survival probability was found to be independent of ER expression. Collectively, ER mRNA decreases in the process of BC development, but seems to be associated with poor differentiation.     

Anthropometric factors, physical activity, and breast cancer risk in relation to hormone receptor and menopausal status in Japanese women: a case–control study

Purpose

The associations between anthropometric factors, physical activity (PA), and breast cancer risk in terms of estrogen-receptor/progesterone-receptor (ER/PgR) status have been unclear in Japanese women. This case–control study was designed to evaluate these associations.

Methods

From among female patients aged 30 years and over admitted to a single hospital in Japan between 1997 and 2009, 1,017 breast cancer cases (538ER+/PgR+, 125ER+/PgR?, 23 ER?/PgR+, 249 ER?/PgR?, and 82 missing) and 2,902 controls were selected. Height, weight, body mass index (BMI) (kg/m²), and time spent exercising (hours/week) were assessed using a self-administered questionnaire. Polytomous logistic regression analysis and tests for heterogeneity across ER+/PgR+ and ER?/PgR? were conducted.

Results

Higher BMI was associated with a higher risk of ER+/PgR+ cancer among women overall [odds ratio (OR) = 2.41, 95 % confidence interval (CI) 1.37–4.23 for BMI ≥30.0; P _trend = 0.0001] and postmenopausal women (OR = 6.24, 95 % CI 2.68–14.53 for BMI ≥30.0; P _trend < 0.0001). A longer time spent exercising (more than 5 h/week) showed a decreased risk for any type of breast cancer among overall and pre- and postmenopausal women, although this did not reach statistical significance. Height was not associated with any risk.

Conclusions

Higher BMI is associated with an increased risk of ER+/PgR+ cancer among women overall and postmenopausal women. PA might be associated with a decreased risk of any type. To prevent breast cancer, weight control and PA are important.     

Illness-related Distress: Does it Mean the Same for Men and Women?: Gender Aspects in Cancer Patients' Distress and Adjustment

Gender differences were investigated in a sample of 149 married cancer patients (82 males, 67 females) undergoing outpatient chemotherapy. A cross-sectional design was used and evaluation included medical assessments and self-rating questionnaires. Tumour sites varied, and advanced stages of disease were predominant. Overall, the results suggest gender differences as well as some similarities. Although female patients reported symptoms and higher overall distress because of illness more frequently than male patients did, general satisfaction with life did not differ between genders, suggesting comparable adjustment. From the results of multivariate analyses physical impairment, such as older age, primarily explained female patients' distress, whereas men's distress was closely linked to their psychological condition. Men and women also differ in the way they make use of social support. Assessment of the distinctive aspects contributing to male and female cancer patients' distress could improve the provision of adequate support adapted to gender-specific requirements.     

The effect of genetic variants on the relationship between statins and breast cancer in postmenopausal women in the Women’s Health Initiative observational study

Purpose

Statins have been postulated to have chemopreventive activity against breast cancer. We evaluated whether germline genetic polymorphisms modified the relationship between statins and breast cancer risk using data from the Women’s Health Initiative. We evaluated these interactions using both candidate gene and agnostic genome-wide approaches.

Methods

To identify candidate gene–statin interactions, we tested interactions between 22 SNPS in nine candidate genes implicated in the effect of statins on lipid metabolism in 1687 cases and 1687 controls. We then evaluated statin use interaction with the remaining 30,380 SNPs available in this sample from the CGEMS GWAS study.

Results

After adjusting for multiple comparisons, no SNP interactions with statin usage and risk of breast cancer were statistically significant in either the candidate genes or genome-wide approaches.

Conclusions

We found no evidence of SNP interactions with statin usage for breast cancer risk in a population of 3374 individuals. These results suggest that genome-wide common genetic variants do not moderate the association between statin usage and breast cancer in the population of women in the Women’s Health Initiative.