Association of the severity of diabetes-related complications with stage of breast cancer at diagnosis among elderly women with pre-existing diabetes

Purpose

This study assessed the association between the severity of diabetes complications using diabetes complications severity index (DCSI) and stage of breast cancer (BC) at diagnosis among elderly women with pre-existing diabetes and incident BC.

Methods

Using Surveillance, Epidemiology and End Results-Medicare data, we identified women with incident BC during 2004–2011 and pre-existing diabetes (N = 7729). Chi-square tests were used to test for group differences in stage of BC at diagnosis. Multinomial logistic regression was used to examine the associations between the severity of diabetes complications and stage of BC at diagnosis.

Results

Overall, women with a DCSI = 2 and a DCSI ≥ 3 were more likely to be diagnosed at advanced stages as compared to those with no diabetes complications. In full adjusted association (after adding BC screening to the analysis model), the severity of diabetes complications was no longer an independent predictor of advanced stages at diagnosis. However, women with a DCSI = 2 were 26% more likely to be diagnosed at stage I (versus stage 0) of BC at diagnosis as compared to those without diabetes complications (OR 1.26, 95% CI 1.03–1.53).

Conclusion

The increased likelihood of having advanced-stage BC at diagnosis associated with severity of diabetes-related complications appears to be mediated by lower rates of breast cancer screening among elderly women with pre-existing diabetes complications. Therefore, reducing disparity in receiving breast cancer screening among elderly women with diabetes may reduce the risk of advanced-stage breast cancer diagnosis.

     

Passive smoking,NAT2 polymorphism,and breast cancer risk in Israeli Arab women: a case–control study

Background

The effect of passive smoking (PS) on breast cancer (BC) is controversial, and may be modified by polymorphism of the N-Acetyl-transferase (NAT) 2 enzyme which is involved in tobacco carcinogen metabolism. We aimed to evaluate the relationship between PS and BC by NAT2 variants in Arab–Israeli women, a unique population with low active smoking rates, and high exposure to PS.

Methods

A population-based case-control study was carried out on non-smoking 137 prevalent breast cancer patients and 274 population-based controls, aged 30–70 years. Data on past and current PS, sociodemographic, and other characteristics were retrieved through interviews, and buccal smears were provided for NAT2 analyses. Logistic regression models adjusting for potential confounders assessed the odds ratios (ORs) and 95% confidence intervals (95% CI) of the association between PS and BC.

Results

Ever PS was associated with increased BC risk: OR = 2.22, 95% CI 1.28–3.87. Higher lifetime PS exposure was associated with higher BC risk: Compared to never exposed women, women exposed to PS most of their lives had a threefold higher BC risk (OR = 3.16, 95% CI 1.70–5.87, P _trend < 0.001). NAT2 polymorphism did not modify these associations.

Conclusions

PS exposure in non-smoking Israeli Arab women is significantly associated with increased risk for BC, potentially allowing for specific intervention; NAT2 polymorphism does not modify this association.

     

Time course of upper limb function and return-to-work post-radiotherapy in young adults with breast cancer: a pilot randomized control trial on effects of targeted exercise program

Purpose

Breast cancer (BC) diagnosis in young adults (YA) is rising, and both disease and treatments are aggressive in this population. Evidence supports the use of physical activity in reducing shoulder dysfunction, which is common among BC survivors. A pilot randomized clinical trial was performed to determine the effectiveness of a 12-week post-radiation exercise program in minimizing upper extremity dysfunction in YA with BC.

Methods

Participants were randomized to either an exercise arm or a control arm receiving standard care. Data was collected over six time points using: the Disability of Arm, Shoulder, and Hand (DASH); the Metabolic Equivalent of Task-hours per week (MET-hours/week), and a post hoc questionnaire on return to work.

Results

In total, 59 young women participated in the study (n = 29 exercise; n = 30 control). No statistically significant differences were found in overall DASH results between groups; however, those who underwent total mastectomy had residual upper limb dysfunction (p < 0.05). Both groups returned to pre-diagnosis activity levels by 18 months. Final evaluation showed that 86% of the women returned to work, and 89% resumed prior work activities with a decrease of 8.5 h/week.

Conclusion

Although the short-term targeted exercise program had no effect on long-term upper limb function post-radiation, timing and program specificity may require consideration of tissue healing post-radiation and surgery type. The majority of participants returned to work, however not returning to pre-diagnosis work hours.

Implications for Cancer Survivors

Exercise interventions alone may not reverse the long-term sequelae of breast cancer treatment and allow young adult patients to return to work.

     

Use of exogenous hormones and the risk of breast cancer: results from self-reported survey data with validity assessment

Purpose

Main aim was to estimate the association between use of exogenous hormones and breast cancer (BC) risk in a large population-based survey, and to assess the representativeness and overall validity of the data.

Methods

The survey ‘Women’s Health and Use of Hormones’ was conducted in Finland in 2009, including 7,000 BC cases and 20,000 matched population controls. Conditional logistic regression was used to estimate odds ratios and their 95 % confidence interval. For validation, exposure prevalences were compared with population data from Statistics Finland and two large population-based surveys.

Results

We found positive associations with BC risk and exclusive use of hormone-releasing intrauterine device (HR IUD) in postmenopausal women (1.48, 95 % CI 1.10–1.99), when compared to never-users of any hormonal contraceptive and considering only prediagnostic use in cases. Regarding use of other hormonal contraceptives (HC), a positive association between long HC use (≥2 years) and BC was observed in both groups, OR being 1.37 (95 % CI 1.12–1.68) for premenopausal and 1.11 (95 % CI 1.03–1.20) for postmenopausal women, when compared to never-users of other HC.

Conclusions

Observed association between HR IUD use and risk of BC in postmenopausal women is worrying and deserves further attention. Selection bias seemed not to explain this result. Considering the increasing popularity of HR IUD use in, e.g., USA, impact of possible adverse effects in public health could be significant.

     

Examining the prevalence of metabolic syndrome among overweight/obese African-American breast cancer survivors vs. matched non-cancer controls

Purpose

Metabolic Syndrome (MetS) is more predominant in overweight, obese and minority populations. This study examined the prevalence of MetS in an exclusively African-American (AA) cohort of breast cancer (BC) survivors; an underrepresented group in previous studies demonstrating negative BC outcomes disparities for females with MetS.

Methods

Using a case-control design, overweight/obese AA women with treated Stage I–IIIa BC were matched 1:1 on age, race, sex, and body mass index (BMI) category with non-cancer population controls (n = 444). Three of the following conditions were used to define MetS: HDL cholesterol <50 mg/dL (1.3 mmol/L), serum triglycerides ≥150 mg/dL (1.7 mmol/L), blood glucose ≥100 mg/dL (or on treatment), waist circumference ≥88 cm, or ≥130 mmHg systolic or ≥85 mmHg diastolic blood pressure (or on treatment). Matched-pairs analyses were conducted.

Results

For BC cases, most women had self-reported Stage I (n = 76) or Stage II (n = 91) disease and were 6.9 (±5.2) years post-diagnosis. MetS was significantly lower in BC survivors vs. their non-cancer population controls (43.2 vs. 51.4 %, respectively; p < 0.05). The diagnosis of MetS did not differ by BMI stratification. A lower prevalence of ≥2 risk factors (80.2 vs. 85.6 %, p < 0.05) was observed for all cases vs. controls.

Conclusions

While MetS occurred less frequently in our BC cases vs. non-cancer controls, our estimates are nearly two times those reported in other BC survivors, suggesting important racial/ethnic differences.

Implications for cancer survivors

The prognostic implications of MetS among AA BC survivors remain unknown and warrant further investigation.

     

Differences in limb volume trajectories after breast cancer treatment

Purpose

Approximately 20 % of patients develop lymphedema (LE) following breast cancer (BC) surgery. An evaluation of distinct trajectories of volume change may improve our ability to diagnose LE sooner. The purposes of this study were to identify subgroups of women with distinct trajectories of limb volume changes following BC surgery and to evaluate for phenotypic differences among these classes.

Methods

In this prospective longitudinal study, 380 women were enrolled prior to unilateral BC surgery. Upper limb bioimpedance was measured preoperatively and serially for 1 year postoperatively. Resistance ratios (RRs) were calculated. A RR of >1 indicates affected limb volume?>?unaffected limb volume. Latent class growth analysis (LCGA) was used to identify classes of women with distinct postoperative RR trajectories. Differences among classes were evaluated using analyses of variance and chi-square analyses.

Results

Three distinct classes were identified as follows: RR <0.95 (37.9 %), RR ~1.00 (46.8 %), and RR >1.05 (15.3 %). Patients in the RR >1.05 class were more likely to have diabetes (p?=?0.036), were more likely to have BC on their dominant side (p?<?0.001), had higher RR ratios at the preoperative and 1-month assessments (p?<?0.001), and were more likely to be diagnosed with LE (p?<?0.001).

Conclusions

LCGA is a useful analytic technique to identify subgroups of women who may be at higher risk for the development of LE, based on trajectories of limb volume change after BC surgery.

Implications for Cancer Survivors

Assessment of preoperative and 1-month bioimpedance RRs may allow for the earlier identification of patients who are at higher risk for the development of LE.

     

A situational analysis of breast cancer early detection services in Trinidad and Tobago

Purpose

A situational analysis of breast cancer (BC) early detection services was carried out to investigate whether Trinidad and Tobago (T&T) has the framework for successful organized national screening.

Methods

An online survey was designed to assess the availability, accessibility, quality control and assurance (QC&A), and monitoring and evaluation (M&E) mechanisms for public and private BC early detection. A focus group with local radiologists (n = 3) was held to identify unaddressed challenges and make recommendations for improvement.

Results

Major public hospitals offer free detection services with wait times of 1–6 months for an appointment. Private institutions offer mammograms for TTD$240 (USD$37) at minimum with same day service. Both sectors report a lack of trained staff. Using 1.2 mammograms per 10,000 women ≥40 years as sufficient, the public sector’s rate of 0.19 mammograms per 10,000 women ≥40 years for screening and diagnosis is inadequate. Program M&E mechanisms, QC&A guidelines for machinery use, delays in receipt of pathology reports, and unreliable drug access are further unaddressed challenges.

Conclusion

T&T must first strengthen its human and physical resources, implement M&E and QC&A measures, strengthen cancer care, and address other impediments to BC early detection before investing in nationally organized BC screening.

     

Red meat,poultry, and fish intake and breast cancer risk among Hispanic and Non-Hispanic white women: The Breast Cancer Health Disparities Study

Purpose

There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women.

Methods

The study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case–control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels.

Results

When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05–1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95 % CI 1.18–1.71; trend p < 0.001), and between white meat (OR 0.80; 95 % CI 0.67–0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models and were restricted to estrogen receptor-positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups.

Conclusions

Our results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities.

     

Chemotherapy-induced amenorrhea and the resumption of menstruation in premenopausal women with hormone receptor-positive early breast cancer

Background

For premenopausal women with breast cancer, information on the effects of chemotherapy and the risk of infertility is important. In this study, the effect of chemotherapy on the ovarian function in premenopausal women with hormone receptor-positive breast cancer was investigated, with an age-stratified analysis of the appearance of amenorrhea and the resumption of menstruation after the use of chemotherapy with anthracyclines or taxanes.

Patients and methods

Premenopausal women diagnosed with operable Stage I–III hormone receptor-positive breast cancer and underwent neoadjuvant or adjuvant chemotherapy with the standard regimen of anthracyclines and/or taxanes were included. The patients were classified into age groups in 5-year increments, and the rates of chemotherapy-induced amenorrhea (CIA), resumption of menstruation, and duration of CIA after chemotherapy were analyzed.

Results

The subjects consisted of 101 patients (median age 45 years). CIA occurred in 97 (96%) patients and 40 patients resumed menstruation. In all patients aged ≤39 years menstruation restarted, whereas in all patients aged ≥50 years, menstruation did not restart. For the patients who resumed menstruation, the younger the patients, the sooner menstruation tended to restart. The resumption of menstruation occurred within 1 year for younger patients aged around 30 years, but for those aged ≥35 years, 60% of cases took around 2–3 years for resumption.

Conclusions

The incidence of CIA, the resumption of menstruation and duration of CIA after chemotherapy depend greatly on the patient’s age.

     

Preplanned safety analysis of the JFMC37-0801 trial: a randomized phase III study of six months versus twelve months of capecitabine as adjuvant chemotherapy for stage III colon cancer

Background

Six months of adjuvant chemotherapy is regarded as the standard of care for patients with stage III colon cancer. However, whether longer treatment can improve prognosis has not been fully investigated. We conducted a phase III study comparing 6 and 12 months of adjuvant capecitabine chemotherapy for stage III colon cancer, and report here the results of our preplanned safety analysis.

Methods

Patients aged 20–79 years with curatively resected stage III colon cancer were randomly assigned to receive 8 cycles (6 months) or 16 cycles (12 months) of capecitabine (2500 mg/m²/day on days 1–14 of each 21-day cycle). Treatment exposure and adverse events (AEs) were evaluated.

Results

A total of 1304 patients (642 and 636 in the 6-month and 12-month groups, respectively) were analyzed. The most common AE was hand-foot syndrome (HFS). HFS, leukocytopenia, neutropenia, and hyperbilirubinemia (any grade) occurred more frequently in the 12-month group than in the 6-month group. HFS was the only grade ≥3 AE to have a significantly higher incidence in the 12-month group (23 vs 17%, p = 0.011). The completion rate for 8 cycles was 72% in both groups, while that for 16 cycles was 46% in the 12-month group. HFS was the most common AE requiring dose reduction and treatment discontinuation.

Conclusions

Twelve months of adjuvant capecitabine demonstrated a higher cumulative incidence of HFS compared to the standard 6-month treatment period, while toxicities after 12 months of capecitabine were clinically acceptable.

Trial registration

UMIN-CTR, UMIN000001367.

     

A model for individualized risk prediction of contralateral breast cancer

Purpose

Patients diagnosed with invasive breast cancer (BC) or ductal carcinoma in situ are increasingly choosing to undergo contralateral prophylactic mastectomy (CPM) to reduce their risk of contralateral BC (CBC). This is a particularly disturbing trend as a large proportion of these CPMs are believed to be medically unnecessary. Many BC patients tend to substantially overestimate their CBC risk. Thus, there is a pressing need to educate patients effectively on their CBC risk. We develop a CBC risk prediction model to aid physicians in this task.

Methods

We used data from two sources: Breast Cancer Surveillance Consortium and Surveillance, Epidemiology, and End Results to build the model. The model building steps are similar to those used in developing the BC risk assessment tool (popularly known as Gail model) for counseling women on their BC risk. Our model, named CBCRisk, is exclusively designed for counseling women diagnosed with unilateral BC on the risk of developing CBC.

Results

We identified eight factors to be significantly associated with CBC—age at first BC diagnosis, anti-estrogen therapy, family history of BC, high-risk pre-neoplasia status, estrogen receptor status, breast density, type of first BC, and age at first birth. Combining the relative risk estimates with the relevant hazard rates, CBCRisk projects absolute risk of developing CBC over a given period.

Conclusions

By providing individualized CBC risk estimates, CBCRisk may help in counseling of BC patients. In turn, this may potentially help alleviate the rate of medically unnecessary CPMs.

     

Docetaxel,cyclophosphamide, and trastuzumab as neoadjuvant chemotherapy for HER2-positive primary breast cancer

Background

The standard primary systemic therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancer is anthracyclines and/or taxanes combined with trastuzumab, which demonstrates a high pathological complete response (pCR). A pCR is a predictive marker of prognosis. However, results slightly differ, depending on the hormone receptor status. The efficacy and tolerability of docetaxel, cyclophosphamide, and trastuzumab (HER-TC) as neoadjuvant chemotherapy (NAC) remain unclear. We performed a prospective multicenter study of HER-TC NAC for HER2+ primary breast cancer.

Methods

Eligible patients had a clinical diagnosis of HER2+ invasive breast cancer greater than 1 cm but less than 7 cm and a tumor stage of N0 or N1. They were diagnosed between July 2011 and February 2014. For NAC, four cycles of HER-TC (6 mg/kg loading dose, 8 mg/kg, 75, and 600 mg/m²) were administered intravenously every 3 weeks. We investigated the pCR of the primary breast tumors. A pCR was defined as no histological evidence of invasive carcinoma or the appearance of only ductal carcinoma in situ.

Results

We enrolled 42 patients. The completion rate for four cycles of HER-TC was 97.6 % (41/42 patients). The overall pCR rate was 43.9 % (18/41 patients). The pCR rate for patients with the luminal HER2 subtype [estrogen receptor (ER)-positive+, HER2+] and the HER2-enriched subtype (ER?, HER2+) was 40.0 % (8/20 patients) and 47.6 % (10/21 patients), respectively. A pCR was achieved with nearly the same probability for each subtype.

Conclusions

Four cycles of HER-TC may be a NAC option for HER2-positive breast cancer.

     

Do patients with metastatic urothelial carcinoma benefit from docetaxel as second-line chemotherapy?

Purpose

To evaluate the efficacy and toxicity of docetaxel regimen as second-line after failure of a platinum-based chemotherapy.

Methods

Between May 2005 and June 2008, we retrospectively analyzed the data of 22 patients who had evidence of disease progression after one prior platinum-based regimen for metastatic urothelial carcinoma. Patients were treated with two different docetaxel dose schedules: (1) docetaxel 60 mg/m² every 21 days for unfit patients or (2) docetaxel 75 mg/m² every 21 days for fit patients.

Results

Median number of docetaxel cycles was three. Overall disease control rate was 18 %. Of the 22 patients, no patient achieved complete or partial response and four patients had stable disease. Median progression-free survival was 1.67 months and median overall survival was 3.12 months. Neutropenia was the most common adverse event.

Conclusions

This study identifies that docetaxel as second-line chemotherapy has low activity and was associated with significant toxicity.

     

Assessment of the predictive role of pretreatment Ki-67 and Ki-67 changes in breast cancer patients receiving neoadjuvant chemotherapy according to the molecular classification: a retrospective study of 1010 patients

Purpose

Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer-related death among women. Given the availability of approved therapies and abundance of phase II and III clinical trials, historically few BC patients have been referred for consideration of participation on a phase I trial. We were interested in determining whether clinical benefit rates differed in patients with BC from other patients enrolled in phase I trials.

Methods

We performed a retrospective analysis of all Cancer Therapy Evaluation Program (CTEP) sponsored phase I trials from 1993 to 2012. We report an analysis of demographic variables, rates of response to treatment, grade 4 toxicities, and treatment-related deaths.

Results

De-identified data from 8087 patients were analyzed, with 1,376 having a diagnosis of BC. The median time from initial cancer diagnosis to enrollment in a CTEP-sponsored phase I clinical trial was 614 days for all patients. Breast cancer patients were enrolled on average 790 days after initial diagnosis, while non-BC patients had a median enrollment time of 582 days (p < 0.001). Breast cancer patients had more clinical responses than non-BC patients (18.3% vs. 4.3%, respectively). Along with the higher rate of response, BC patients remained on phase I trials longer than non-BC patients with a median of 70 days while the latter were on trial for a median of 57 days. The overall rate of death related to the treatment drugs was 0.47%.

Conclusions

Our data confirm our hypothesis that when compared to a general population of patients with cancer enrolled on phase I clinical trials, BC patients tend to derive clinical benefit from these therapies with similar toxicity profile. This evidence further supports enrollment of BC patients on phase I trials.

     

Comparison of tumor-infiltrating lymphocytes of breast cancer in core needle biopsies and resected specimens: a retrospective analysis

Purpose

Few studies evaluated the prognostic value of the presence of lymphovascular invasion (LVI) after neoadjuvant chemotherapy (NAC) for breast cancer (BC).

Methods

The association between LVI and survival was evaluated in a cohort of BC patients treated by NAC between 2002 and 2011. Five post-NAC prognostic scores (ypAJCC, RCB, CPS, CPS + EG and Neo-Bioscore) were evaluated and compared with or without the addition of LVI.

Results

Out of 1033 tumors, LVI was present on surgical specimens in 29.2% and absent in 70.8% of the cases. Post-NAC LVI was associated with impaired disease-free survival (DFS) (HR 2.54; 95% CI 1.96–3.31; P < 0.001), and the magnitude of this effect depended on BC subtype (P_interaction = 0.003), (luminal BC: HR 1.83; P = 0.003; triple negative BC: HR 3.73; P < 0.001; HER2-positive BC: HR 6.21; P < 0.001). Post-NAC LVI was an independent predictor of local relapse, distant metastasis, and overall survival; and increased the accuracy of all five post-NAC prognostic scoring systems.

Conclusions

Post-NAC LVI is a strong independent prognostic factor that: (i) should be systematically reported in pathology reports; (ii) should be used as stratification factor after NAC to propose inclusion in second-line trials or adjuvant treatment; (iii) should be included in post-NAC scoring systems.

     

Candidate miRNAs in human breast cancer biomarkers: a systematic review

Background

Breast cancer (BC) is the most prevalent cancer and the main cause of cancer deaths among females around the world. For early diagnosis of BC, there would be an immediate and essential requirement to search for sensitive biomarkers.

Methods

To identify candidate miRNA biomarkers for BC, we performed a general systematic review regarding the published miRNA profiling researches comparing miRNA expression level between BC and normal tissues. A miRNA ranking system was selected, which considered frequency of comparisons in direction and agreement of differential expression.

Results

We determined that two miRNAs (mir-21 and miR-210) were upregulated consistently and six miRNAs (miR-145, miR-139-5p, miR-195, miR-99a, miR-497 and miR-205) were downregulated consistently in at least three studies. MiR-21 as the most consistently reported miRNA was upregulated in six profiling studies.

Conclusions

Although these miRNAs require being validated and further investigated, they could be potential candidates for BC miRNA biomarkers and used for early prognosis or diagnosis.

     

Short stature in retinoblastoma survivors: a cross-sectional study of 138 patients

Purpose

Short stature has been reported in pediatric cancer survivors. Data on retinoblastoma survivors are limited. We conducted a cross-sectional study to assess the height in retinoblastoma survivors.

Method

The recorded height was compared with median height for age and sex as per the Indian Academy of Pediatrics. Z-score less than ?2 was considered short statured.

Result

Thirty percent of the survivors were short statured. The mean height was shorter than the mean 50th percentile height (119.7 ± 14.8 vs 128.7 ± 15 cm, p < 0.001). Previous chemotherapy showed a trend toward association (p = 0.09).

Conclusion

Short stature affects a significant number of retinoblastoma survivors.