Is mode of breast cancer detection associated with cancer treatment in the United States?

BACKGROUND: The prognosis for women who have breast cancer detected by mammography is more favorable than that for women who have breast cancer detected by other methods, even after controlling for tumor characteristics. In the current study, the authors explored whether detection by mammography was associated with greater use of guideline-consistent breast cancer treatment among patients with recently diagnosed breast cancer in the United States. METHODS: The authors evaluated the association between mode of breast cancer detection (mammography vs other) and use of guideline-consistent treatment in 1006 women aged > or =40 years who were diagnosed in 2000. These patients were sampled from the Surveillance, Epidemiology, and End Results Program as part of the Patterns of Care studies. The analyses controlled for the potential confounders of clinical, demographic, and health system characteristics in multivariate logistic regression models. RESULTS: Breast cancer patients who were diagnosed by mammography were more likely to be aged > or =55 years, to have lower stage disease, and to be treated in larger hospitals than patients who were diagnosed by other methods (P < .05). Women whose breast cancer was diagnosed by a method other than mammography were more likely to receive guideline-consistent treatment than women who were diagnosed by mammography in unadjusted (odds ratio, 1.39; 95% confidence interval, 1.07-1.80) and multivariate analyses (odds ratio, 1.43; 95% confidence interval, 1.05-1.95). CONCLUSIONS: The current results indicated that women who had breast cancer detected by methods other than mammography were slightly more likely to receive guideline-consistent therapy than women who had breast cancer detected by mammography. Future research exploring mode of detection, guideline-consistent treatment, and survival among patients with recently diagnosed breast cancer may inform understanding of factors associated with breast cancer prognosis.     

nextMONARCH Phase 2 randomized clinical trial: overall survival analysis of abemaciclib monotherapy or in combination with tamoxifen in patients with endocrine-refractory HR + , HER2– metastatic breast cancer

Breast Cancer Research and Treatment - Resistance to endocrine therapy poses a major clinical challenge for patients with hormone receptor-positive (HR?+), human epidermal growth factor...     

Presence of HER4 associates with increased sensitivity to Herceptin™ in patients with metastatic breast cancer

Introduction  

HER2 overexpression, or rather HER2 gene amplification, is indicative for Herceptin therapy in both metastatic and pre-metastatic breast cancer patients. Patient's individual sensitivity to Herceptin treatment, however, varies enormously and spans from effectual responsiveness over acquired insensitivity to complete resistance from the outset. Thus no predictive information can be deduced from HER2 determination so that molecular biomarkers indicative for Herceptin sensitivity or resistance need to be identified. Both ErbB receptor-dependent signalling molecules as well as HER2-related ErbB receptor tyrosine kinases, known to mutually interact and to cross-regulate each other are prime candidates to be involved in cellular susceptibility to Herceptin.     

Abemaciclib plus fulvestrant in East Asian women with HR+, HER2− advanced breast cancer: Overall survival from MONARCH 2

MONARCH 2 is a global, randomized, double-blind, phase 3 study of abemaciclib/placebo + fulvestrant in patients with hormone receptor positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The East Asian population comprised 212 (31.7%) of the 669 intent-to-treat population in the MONARCH 2 trial. Consistent with the primary analysis, this subpopulation analysis of East Asian patients indicated progression-free survival benefit in the abemaciclib arm. The median overall survival was not reached in the abemaciclib arm and was 48.9 months in the placebo arm (hazard ratio 0.80; 95% confidence interval 0.52–1.24; p = 0.377). In addition, other efficacy endpoints, including time to chemotherapy, chemotherapy free survival, and time to second disease progression, indicated benefit in the abemaciclib arm. This analysis found no new safety concerns with longer follow-up. These findings support the positive benefit–risk balance of the MONARCH 2 regimen in East Asian patients with hormone receptor positive, human epidermal growth factor receptor 2-negative advanced breast cancer.     

A phase II study of S-1 in patients with metastatic breast cancer — A Japanese trial by the S-1 cooperative study group, breast cancer working group

BACKGROUND: S-1 is a newly developed novel oral dihydrouracil dehydrogenase inhibiting fluoropyrimidine drug consisting of 1 M tegafur (FT), 0.4 M 5-chloro-2, 4-dihydroxypyrimidine (gimeracil), and 1 M potassium oxonate (oteracil), with efficient antitumor activity and low gastrointestinal toxicity which is widely used in Japan against advanced gastric, head and neck cancers. We investigated its clinical efficacy against metastatic breast cancer. METHODS: A non-blind phase II study was carried out to evaluate the efficacy and toxicity in metastatic breast cancer patients. Patients with measurable metastasis foci (n=111) were enrolled, and 108 patients were regarded as eligible. S-1 was administered orally at a standard dose of 80 mg/m2/day b.i.d. One course consisted of 28 consecutive days of administration followed by a 14-day rest, and courses were repeated up to six times. RESULTS: Among the eligible patients, 10 had a complete response and 35 had a partial response, with an overall response rate (CR+PR) of 41.7% (95% confidence interval: CI, 32.3-51.5%). The incidences of toxicity (> or =grade 3) were neutropenia 9.1%, anemia 0.9%, anorexia 3.6%, stomatitis 1.8%, nausea/vomiting 1.8%, diarrhea 0.9%, and fatigue 2.7%, however no treatment-related deaths were observed. The median survival time was 872 days (95% CI, 572-1,110 days). There was no difference in response rate or toxicity between the under 65-year-old group and the older group. CONCLUSION: S-1 was demonstrated to have high efficacy with low gastrointestinal toxicity even in older patients and will be a promising new chemotherapy drug for metastatic breast cancer.     

Impact of screening on cervical cancer incidence: A population-based case–control study in the United States

Cervical cancer is widely preventable through screening, but little is known about the duration of protection offered by a negative screen in North America. A case–control study was conducted with records from population-based registries in New Mexico. Cases were women diagnosed with cervical cancer in 2006–2016, obtained from the Tumor Registry. Five controls per case from the New Mexico HPV Pap Registry were matched to cases by sex, age and place of residence. Dates and results of all cervical screening and diagnostic tests since 2006 were identified from the pap registry. We estimated the odds ratio of nonlocalized (Stage II+) and localized (Stage I) cervical cancer associated with attending screening in the 3 years prior to case-diagnosis compared to women not screened in 5 years. Of 876 cases, 527 were aged 25–64 years with ≥3 years of potential screening data. Only 38% of cases and 61% of controls attended screening in a 3-year period. Women screened in the 3 years prior to diagnosis had 83% lower risk of nonlocalized cancer (odds ratio [OR] = 0.17, 95% CI: 0.12–0.24) and 48% lower odds of localized cancer (OR = 0.52, 95% CI: 0.38–0.72), compared to women not screened in the 5 years prior to diagnosis. Women remained at low risk of nonlocalized cancer for 3.5–5 years after a negative screen compared to women with no negative screens in the 5 years prior to diagnosis. Routine cervical screening is effective at preventing localized and nonlocalized cervical cancers; 3 yearly screening prevents 83% of nonlocalized cancers, with no additional benefit of more frequent screening. Increasing screening coverage remains essential to further reduce cervical cancer incidence.     

Does regional treatment improve the survival in patients with operable breast cancer?

Background. The impact of regional therapy on survival of patients with invasive breast cancer remains controversial. Regional therapies discussed include axillary lymph node dissection (ALND), internal mammary node dissection, and locoregional radiotherapy. Methods. Prospective randomized clinical studies of regional therapy were reviewed using, as a source, Medline, main review articles on the related topic, and statements from consensus conference. Results. Although a number of randomized clinical studies have failed to demonstrate the benefits of regional treatment for survival, it is still a matter of debate whether ALND or regional radiotherapy alone can have a small but significant beneficial effect on the survival of breast cancer patients. However, recent studies have suggested that survival can be enhanced by interaction of postmastectomy locoregional radiotherapy with adjuvant systemic therapy. Conclusions. Locoregional control is important for enhancing survival in the presence of adjuvant systemic therapy. Although only a few randomized controlled trials show conclusively the survival benefit of local therapies, it is expected that in clinical practice, the node-positive or other high-risk breast cancer patients given systemic treatment will be more frequently treated with postmastectomy radiation.     

Is guideline adherence the key to increased survival in patients with breast cancer?

Recently, Varga et al. reported in an observational study that guideline adherence could prevent 56.3-78.9% of all deaths in patients with early onset breast cancer [Oncology 2010;78:189-195]. This would mean that nearly all deaths due to breast cancer can be avoided by guideline-adherent treatment. We argue that some methodological issues like immortal time bias or healthy adherer bias may have contributed to these implausible findings. However, the non-transparent reporting of the methods, especially regarding the operationalization of guideline adherence, hampers critical assessment of this study.     

Correlation of Fcγ receptors on peripheral blood mononuclear cells and survival in patients with metastatic breast cancer

Summary Patients with carcinomas have elevated levels of Fc receptors for IgG (FcR) on their peripheral blood mononuclear cells (PBMC). The purpose of the present study was to determine whether there is a correlation between FcR levels on PBMC and survival in patients with metastatic breast cancer. Binding assays were performed on PBMC using¹²⁵I-labeled fibrinogen complexed with rabbit IgG (or as a control F(ab)₂) anti-human fibrinogen. Twenty-two metastatic breast cancer patients had significantly (p<0.001) elevated FcR levels as compared to either 22 breast cancer patients receiving adjuvant chemotherapy following mastectomy without clinical evidence of tumor, or to 34 non-malignant controls. Significantly more metastatic patients with elevated FcR levels died at 6 months (p<0.001) as compared to those with low levels. A direct correlation between FcR levels and hazard probability was found (correlation coefficient = 0.3321, p<0.005). These results raise the possibility that FcR levels on PMBC from metastatic breast cancer patients may be clinically useful as a prognostic marker of disease activity.     

MR imaging features associated with distant metastasis-free survival of patients with invasive breast cancer: a case–control study

Purpose

Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer.

Methods

Of the 3536 patients with primary breast cancers who underwent preoperative MR imaging between 2003 and 2009, 147 patients with DM were identified and one-to-one matched with control patients (n = 147) without DM according to clinical–pathologic variables. Three radiologists independently reviewed the MR images of 294 patients, and the association of DM-free survival with MR imaging and clinical–pathologic features was assessed using Cox proportional hazard models.

Results

Of MR imaging features, rim enhancement (hazard ratio [HR], 1.83 [95% confidence interval, CI 1.29, 2.51]; p = 0.001) and peritumoral edema (HR, 1.48 [95% CI 1.03, 2.11]; p = 0.032) were the significant features associated with worse DM-free survival. The significant MR imaging features, however, were different between breast cancer subtypes and stages.

Conclusion

Preoperative breast MR imaging features of rim enhancement and peritumoral edema may be used as prognostic biomarkers that help predict DM risk in patients with breast cancer, thereby potentially enabling improved personalized treatment and monitoring strategies for individual patients.

     

Impact of diagnosis-to-treatment waiting time on survival in esophageal cancer patients – A population-based study in The Netherlands

Background

The aim of this study was to determine whether the waiting time from diagnosis to treatment with curative intent for esophageal cancer impacts oncologic outcomes.

Dose-escalation phase I study in metastatic breast cancer patients with combination of paclitaxel and tegafur·uracil

The study present the results of the dose-setting study of concomitant weekly administration of paclitaxel and tegafur·uracil (UFT) for metastatic breast cancer. Eligible patients who entered the study underwent two or more courses of weekly paclitaxel + UFT therapy as the protocol therapy. The initial dose (level 1) was paclitaxel, 80 mg/m(2) and UFT, 400 mg/day. At level 2, paclitaxel remained the same, but UFT was increased to 600 mg/day. At level 3, only paclitaxel was increased to 90 mg/m(2). Twelve patients were enrolled in this study between September 2000 and September 2002. Three patients were assigned to level 1. Grade 3 liver dysfunction (increased aspartate aminotransferase and alanine aminotransferase) was noted in one patient and grade 4 neutropenia was noted in one patient, showing that dose-limiting toxicity was detected in 2/3 patients. In accordance with the protocol, UFT was fixed at 400 mg/day and paclitaxel was decreased to 60 mg/m(2) at level -1, and then increased to 70 mg/m(2) at level 0. The overall effective rate after completion of two courses was 33% (3/9) including one case of complete response and two cases of partial responses. The remaining patients presented with stable diseases and no patient had progressive disease. In this study, weekly paclitaxel with concomitant UFT was administered. The recommended doses of paclitaxel and UFT were determined to be 70 mg/m(2) and 400 mg/day, respectively. As the toxicity profile shows, the highest toxicity level of this regimen was neutropenia and liver dysfunction, and dose-limiting toxicity was neutropenia.