[Show abstract][Hide abstract] ABSTRACT: The role of gene-specific methylation in white blood cells (WBC) as a marker of breast cancer risk is currently unclear. We determined whether promoter hypermethylation in blood DNA of candidate tumor suppressor genes frequently methylated in breast tumors can be used as a surrogate biomarker for breast cancer risk. Promoter methylation of BRCA1, CDH1 and RARβ was analyzed in WBC DNA from a population-based sample of 1,021 breast cancer patients and 1,036 controls by the MethyLight assay. Gene-specific promoter methylation in the DNA of 569 tumor tissue samples was also analyzed to determine the correlation of methylation levels with blood from the same individual. Hypermethylation of BRCA1 (OR: 1.31; 95% CI: 0.98-1.75) in WBC was associated with an increased risk of breast cancer when positive methylation was defined as ≥0.1% methylated. There was lack of concordance between tumor tissue and paired WBC DNA methylation. These results provide limited support that hypermethylation of BRCA1 in WBC DNA may be useful for determination of breast cancer risk. Additional studies with larger numbers of genes are needed to fully understand the relationship between WBC methylation and breast cancer risk.
Full-text · Article · Aug 2015 · Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Although many patients with end-stage cancer are offered chemotherapy to improve quality of life (QOL), the association between chemotherapy and QOL amid progressive metastatic disease has not been well-studied. American Society for Clinical Oncology guidelines recommend palliative chemotherapy only for solid tumor patients with good performance status.
To evaluate the association between chemotherapy use and QOL near death (QOD) as a function of patients' performance status.
A multi-institutional, longitudinal cohort study of patients with end-stage cancer recruited between September 2002 and February 2008. Chemotherapy use (n = 158 [50.6%]) and Eastern Cooperative Oncology Group (ECOG) performance status were assessed at baseline (median = 3.8 months before death) and patients with progressive metastatic cancer (N = 312) following at least 1 chemotherapy regimen were followed prospectively until death at 6 outpatient oncology clinics in the United States.
Patient QOD was determined using validated caregiver ratings of patients' physical and mental distress in their final week.
Chemotherapy use was not associated with patient survival controlling for clinical setting and patients' performance status. Among patients with good (ECOG score = 1) baseline performance status, chemotherapy use compared with nonuse was associated with worse QOD (odds ratio [OR], 0.35; 95% CI, 0.17-0.75; P = .01). Baseline chemotherapy use was not associated with QOD among patients with moderate (ECOG score = 2) baseline performance status (OR, 1.06; 95% CI, 0.51-2.21; P = .87) or poor (ECOG score = 3) baseline performance status (OR, 1.34; 95% CI, 0.46-3.89; P = .59).
Although palliative chemotherapy is used to improve QOL for patients with end-stage cancer, its use did not improve QOD for patients with moderate or poor performance status and worsened QOD for patients with good performance status. The QOD in patients with end-stage cancer is not improved, and can be harmed, by chemotherapy use near death, even in patients with good performance status.
[Show abstract][Hide abstract] ABSTRACT: Using a nationwide database, 4,874 patients with hypercalcemia of malignancy were identified. The in-hospital mortality rate was 6.8%. Overall, 1,971 (40.4%) patients received pamidronate and 1,399 (28.7%) received zoledronic acid during hospitalization. Calcitonin was utilized in 1,337 (27.4%) patients while glucocorticoids were administered to 1,311 (26.9%). Use of contraindicated medications was noted in 136 (2.8%) patients who received thiazide diuretics and 12 (0.2%) who received lithium. Tumor site, presence of bone metastases, and severity of illness were predictors of treatment. There was no association between treatment with bisphosphonates, calcitonin, or glucocorticoids and morbidity or mortality.
Full-text · Article · Jun 2015 · Cancer Investigation
[Show abstract][Hide abstract] ABSTRACT: Although axillary lymph node evaluation is standard of care in the surgical management of invasive breast cancer, a benefit has not been demonstrated in ductal carcinoma in situ (DCIS). Despite uncertainty regarding the efficacy, axillary evaluation is often performed in women with DCIS.
To determine the incidence of axillary evaluation in women with DCIS and identify clinical, hospital, and surgeon-related factors associated with axillary evaluation.
Cross-sectional analysis conducted from January 2006 through December 2012 of medical records contained in the Perspective database for women with DCIS who underwent breast-conserving surgery (BCS) or mastectomy. A total of 35 591 women aged 18 to 90 years were included in the analysis.
Receipt or nonreceipt of surgical axillary evaluation, categorized as sentinel lymph node biopsy (SLNB), axillary lymph node dissection (ALND), or none. Analyses were stratified by surgery type, and multivariable regression analysis was used to identify factors associated with axillary evaluation.
Of women identified with DCIS, 26 580 (74.7%) underwent BCS while 9011 (25.3%) underwent mastectomy; 17.7% undergoing BCS and 63.0% undergoing mastectomy had an axillary evaluation. Rates of axillary evaluation increased over time with mastectomy (2006, 56.6%; 2012, 67.4%) and were relatively stable with BCS (2006, 18.5%; 2012, 16.2%). Rates of ALND decreased in women undergoing mastectomy (2006, 20.0%; 2012, 10.7%) and BCS (2006, 1.2%; 2012, 0.3%), with increasing use of SLNB. In a multivariable analysis, hospital factors including nonteaching hospital (risk ratio [RR], 1.17; 95% CI, 1.05-1.30) and urban location (RR, 1.15; 95% CI, 1.03-1.29) influenced axillary evaluation with mastectomy. Surgeon volume was the most significant predictor of axillary evaluation among women undergoing BCS (mid vs low volume: RR, 0.87; 95% CI, 0.70-0.94; high vs low volume: RR, 0.54; 95% CI, 0.44-0.65).
Despite guidelines recommending against axillary lymph node evaluation in women with DCIS undergoing BCS and uncertainty regarding its use with mastectomy, SLNB or ALND is performed frequently. Given the additional morbidity and cost of these procedures, alternative surgical approaches or prospective evaluation of the clinical benefit of axillary evaluation in women with DCIS is needed.
[Show abstract][Hide abstract] ABSTRACT: Breast cancer, the leading cancer diagnosis among American women, is positively associated with postmenopausal obesity and little or no recreational physical activity (RPA). However, the underlying mechanisms of these associations remain unresolved. Aberrant changes in DNA methylation may represent an early event in carcinogenesis, but few studies have investigated associations between obesity/RPA and gene methylation, particularly in postmenopausal breast tumors where these lifestyle factors are most relevant.
We used case-case unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the associations between body mass index (BMI=weight [kg]/height [m(2)]) in the year prior to diagnosis, or RPA (average hours/week), and methylation status (methylated vs. unmethylated) of 13 breast cancer-related genes in 532 postmenopausal breast tumor samples from the Long Island Breast Cancer Study Project. We also explored whether the association between BMI/RPA and estrogen/progesterone-receptor status (ER+PR+ vs. all others) was differential with respect to gene methylation status. Methylation-specific PCR and the MethyLight assay were used to assess gene methylation.
BMI 25-29.9kg/m(2), and perhaps BMI≥30kg/m(2), was associated with methylated HIN1 in breast tumor tissue. Cases with BMI≥30kg/m(2) were more likely to have ER+PR+ breast tumors in the presence of unmethylated ESR1 (OR=2.63, 95% CI 1.32-5.25) and women with high RPA were more likely to have ER+PR+ breast tumors with methylated GSTP1 (OR=2.33, 95% CI 0.79-6.84).
While biologically plausible, our findings that BMI is associated with methylated HIN1 and BMI/RPA are associated with ER+PR+ breast tumors in the presence of unmethylated ESR1 and methylated GSTP1, respectively, warrant further investigation. Future studies would benefit from enrolling greater numbers of postmenopausal women and examining a larger panel of breast cancer-related genes.
[Show abstract][Hide abstract] ABSTRACT: Little is known about how modifiable lifestyle factors interact with the epigenome to influence disease. Body mass index (BMI, weight kg/height m2) and physical activity are associated with postmenopausal breast cancer, but the mechanisms are not well-understood. We hypothesized that BMI or physical activity may modify the association between markers of global DNA methylation and postmenopausal breast cancer risk.
Resources from a population-based case-control study (~1300 postmenopausal women) were used to construct logistic regression models. We explored whether the association between breast cancer and global methylation, assessed using the luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) methylation in white blood cell DNA, was modified by BMI or recreational physical activity (RPA).
The LUMA-breast cancer association was modified by BMI (multiplicative p=0.03) and RPA (p=0.004). Non-obese women in the highest quartile of LUMA experienced a greater than two-fold increased risk of postmenopausal breast cancer (BMI<25kg/m2: OR=2.16; 95% CI=1.35, 3.57 and BMI 25-29.9kg/m2: OR=2.96; 95% CI=1.69, 5.19) compared to women in the lowest LUMA quartile. Similar increases in the LUMA-breast cancer association were observed among women who were physically active (moderate RPA: OR=2.62; 95% CI=1.44, 4.75 and high RPA: OR=2.62; 95% CI=1.53, 4.49). Estimates among obese and inactive women were less pronounced and imprecise. Although we observed statistical interactions (p<0.05) between BMI and RPA with LINE-1, we were unable to discern any clear associations with breast cancer.
The association between LUMA and postmenopausal breast cancer risk may be modified by postmenopausal body size and physical activity.
Full-text · Article · May 2015 · Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Although colonoscopy is predominant among the selection of colorectal cancer screening tests, stool testing (particularly fecal immunochemical testing) has also carved out an important niche for itself. Its simplicity and low cost make it ideal for mass population screening both in the United States and abroad, and it is an alternative choice for those reluctant to undergo endoscopy.
[Show abstract][Hide abstract] ABSTRACT: To examine relative survival (a metric that incorporates changes in survival within a population) in women with ovarian cancer from 1975 to 2011.
Women diagnosed with ovarian cancer from 1975 to 2011 and recorded in the National Cancer Institute's Surveillance, Epidemiology, and End Results database were examined. Relative survival, estimated as the ratio of the observed survival of cancer patients (all-cause mortality) to the expected survival of a comparable group from the general population, was matched to the patients with the main factors that are considered to affect patient survival such as age, calendar time, and race. Hazard ratios were adjusted for age, race, year of diagnosis, time since diagnosis, and the interaction of age and years since diagnosis (except for stage II).
A total of 49,932 women were identified. For stage I ovarian cancer, the adjusted excess hazard ratio for death in 2006 was 0.51 (95% confidence interval [CI] 0.41-0.63) compared with those diagnosed in 1975. The reduction in excess mortality remained significant when compared with 1980 and 1985. For women with stage III-IV tumors, the excess hazard of mortality was lower in 2006 compared with all other years of study ranging from 0.49 (95% CI 0.44-0.55) compared with 1975 to 0.93 (95% CI 0.87-0.99) relative to 2000. For women aged 50-59 years, 10-year relative survival was 0.85 (99% CI 0.61-0.95) for stage I disease and 0.18 (99% CI 0.10-0.27) for stage III-IV tumors. For women aged 60-69 years, the corresponding 10-year relative survival estimates were 0.89 (99% CI 0.58-0.98) and 0.15 (99% CI 0.09-0.21).
Relative survival has improved for all stages of ovarian cancer from 1975 to 2011.
No preview · Article · May 2015 · Obstetrics and Gynecology