Nonbreast cancer incidence, treatment received and outcomes: Are there differences in breast screening attendees versus nonattendees?

While reductions in breast cancer mortality have been evident since the introduction of population-based breast screening in women aged 50-74 years, participation in cancer screening programs can be influenced by several factors, including health system and those related to the individual. In our study, we compared cancer incidence and mortality for several cancer types other than breast cancer, noncancer mortality and patterns of treatment amongst women who did and did not participate in mammography screening. All women aged 50-65 years enrolled on the Queensland Electoral Roll in 2000 were included. The study population was then linked to records from the population-based breast screening program and private fee-for-service screening options to establish screened and unscreened cohorts. Diagnostic details for selected cancers and cause of death were obtained from the Queensland Oncology Repository. We calculated incidence rate ratios and hazard ratios comparing screened and unscreened cohorts. Among screened compared to unscreened women, we found a lower incidence of cancers of the lung, cervix, head and neck and esophagus and an increase in colorectal cancers. Cancer mortality (excluding breast cancer) was 35% lower among screened compared to unscreened women and they were also about 23% less likely to be diagnosed with distant disease. Screened compared to unscreened women were more likely to receive surgery and less likely to receive no treatment. Our study adds further to the population data examining outcomes among women participating in mammography screening.

Development and implementation of a population-based breast cancer quality index in Queensland, Australia.

BACKGROUND: While quality indicators (QI) are relatively commonplace, QIs focusing on breast cancer treatment and outcomes have not been previously developed in Australia. We describe the development and implementation of the Queensland Breast Cancer Quality Index (BCQI) and report on trends in performance indicators over time. METHODS: Development of the BCQI was overseen by a clinician-led quality assurance committee covering several clinical disciplines. Using a population-based dataset of female patients diagnosed with breast cancer from 2007 to 2016 (n = 27,541) we examined trends in indicators over time. RESULTS: The BCQI includes two quality dimensions (Effective and Accessible) and 14 indicators for public and private cancer services. Rates of re-excision following breast conservation surgery (BCS) and conversion of BCS to mastectomy reduced over time (p < 0.001 and p = 0.005, respectively). BCS was less common for women living outside a major city (p < 0.001), who had their surgery in a public (p < 0.001) or low volume hospital (p < 0.001). CONCLUSIONS: Application of the BCQI at a population-level demonstrated our results are comparable to, and in some cases superior to other jurisdictions. We identified some areas where improvement over time has occurred, while also identifying some outcomes requiring further investigation. POLICY SUMMARY: The BCQI is a well-established and valuable tool for measuring and monitoring breast cancer care. Practice indicators provide useful information to assist with identifying services performing well as well as those that may benefit from improvement.

Breast-cancer mortality in screened versus unscreened women: Long-term results from a population-based study in Queensland, Australia.

OBJECTIVE: In the context of a mature mammographic screening programme, the aim of this population-based study was to estimate rates of breast-cancer mortality among participants versus non-participants in Queensland, Australia. METHODS: The Queensland Electoral Roll was used to identify women aged 50-65 in the year 2000 (n = 269,198). Women with a prior history of invasive or in situ breast cancer were excluded (n = 6,848). The study population was then linked to mammography records from BreastScreen Queensland together with the Wesley Breast Screening Clinic (the largest provider of private screening in Queensland) to establish a screened cohort (n = 187,558) and an unscreened cohort (n = 74,792). Cohort members were matched and linked to cancer notifications and deaths through the state-based Queensland Oncology Repository. Differences in breast-cancer mortality between the two cohorts were measured using Cox proportional hazards regression. RESULTS: After 16 years of follow-up, women in the screened cohort showed a 39% reduction in breast-cancer mortality compared to the unscreened cohort (HR = 0.61, 95%CI = 0.55-0.68). Cumulative mortality over the same period was 0.47% and 0.77% in the screened and unscreened cohorts, respectively. CONCLUSIONS: This study found a significant reduction in breast-cancer mortality for women who participated in mammographic screening compared to unscreened women. Our findings of a breast-cancer mortality benefit for women who have mammographic screening are in line with other observational studies.

Spontaneous apoptosis of blood dendritic cells in patients with breast cancer.

INTRODUCTION: Dendritic cells (DCs) are key antigen-presenting cells that play an essential role in initiating and directing cellular and humoral immunity, including anti-tumor responses. Due to their critical role in cancer, induction of DC apoptosis may be one of the central mechanisms used by tumors to evade immune recognition. METHODS: Spontaneous apoptosis of blood DCs (lineage negative HLA-DR positive cells) was assessed in peripheral blood mononuclear cells (PBMCs) using Annexin-V and TUNEL assays immediately after blood collection. The role of tumor products was assessed by culturing cells with supernatants derived from breast cancer cell lines (TDSN) or PBMCs (PBMC-SN, as a control). The capacity of DC stimulation to prevent apoptosis was assessed by incubating DC with inflammatory cytokines, poly I:C, IL-12 or CD40 ligand (CD40L) prior to culture with TDSN. Apoptosis was determined by flow cytometry and microscopy, and Bcl-2 expression determined by intracellular staining. RESULTS: In this study we document the presence of a significantly higher proportion of apoptotic (Annexin-V+ and TUNEL+) blood DCs in patients with early stage breast cancer (stage I to II; n = 13) compared to healthy volunteers (n = 15). We examined the role of tumor products in this phenomenon and show that supernatants derived from breast cancer lines induce apoptosis of blood DCs in PBMC cultures. Aiming to identify factors that protect blood DC from apoptosis, we compared a range of clinically available maturation stimuli, including inflammatory cytokines (tumor necrosis factor-alpha, IL-1beta, IL-6 and prostaglandin (PG)E2 as a cytokine cocktail), synthetic double-stranded RNA (poly I:C) and soluble CD40 ligand. Although inflammatory cytokines and poly I:C induced robust phenotypic maturation, they failed to protect blood DCs from apoptosis. In contrast, CD40 stimulation induced strong antigen uptake, secretion of IL-12 and protected blood DCs from apoptosis through sustained expression of Bcl-2. Exogenous IL-12 provided similar Bcl-2 mediated protection, suggesting that CD40L effect is mediated, at least in part, through IL-12 secretion. CONCLUSION: Cumulatively, our results demonstrate spontaneous apoptosis of blood DCs in patients with breast cancer and confirm that ex vivo conditioning of blood DCs can protect them from tumor-induced apoptosis.

HLA-DR+ immature cells exhibit reduced antigen-presenting cell function but respond to CD40 stimulation.

Dendritic cells (DC) have been implicated in the defective function of the immune system during cancer progression. We have demonstrated that patients with cancer have fewer myeloid (CD11c+) and plasmacytoid (CD123(hi)) DC and a concurrent accumulation of CD11c(-)CD123- immature cells expressing HLA-DR (DR(+)IC). Notably, DR(+)IC from cancer patients have a reduced capacity to stimulate allogeneic T-cells. DR(+)IC are also present in healthy donors, albeit in smaller numbers. In this study, we assessed whether DR(+)IC could have an impact on the immune response by comparing their function with DC counterparts. For this purpose, DR(+)IC and DC were purified and tested in the presentation of antigens through major histocompatibility complex (MHC) II and MHC-I molecules. DR(+)IC were less efficient than DC at presenting antigens to T-cells. DR(+)IC induced a limited activation of T-cells, eliciting poor T-helper (Th) 1 and preferentially inducing Th2-biased responses. Importantly, despite DR(+)IC's poor responsiveness to inflammatory factors, in samples from healthy volunteers and breast cancer patients, CD40 ligation induced phenotypic maturation and interleukin 12 secretion, in turn generating more efficient T-cell responses. These data underscore the importance of inefficient antigen presentation as a mechanism for tumor evasion and suggest an approach to improve the efficacy of DC-based immunotherapy for cancer.

A population of HLA-DR+ immature cells accumulates in the blood dendritic cell compartment of patients with different types of cancer.

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c+) and plasmacytoid (CD123+) DC, and a concurrent accumulation of CD11c(-)CD123(-) immature cells that expressed high levels of HLA-DR+ immature cells (DR(+)IC). Although DR(+)IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR(+)IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-gamma secretion by T-lymphocytes. Importantly, increased numbers of DR(+)IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR(+)IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR(+)IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.

Shoulder movement after breast cancer surgery: results of a randomised controlled study of postoperative physiotherapy.

Breast screening programmes have facilitated more conservative approaches to the surgical and radiotherapy management of women diagnosed with breast cancer. This study investigated changes in shoulder movement after surgery for primary, operable breast cancer to determine the effect of elective physiotherapy intervention. Sixty-five women were randomly assigned to either the treatment (TG) or control group (CG) and assessments were completed preoperatively, at day 5 and at 1 month, 3, 6, 12 and 24 months postoperatively. The CG only received an exercise instruction booklet in comparison to the TG who received the Physiotherapy Management Care Plan (PMCP). Analyses of variance revealed that abduction returned to preoperative levels more quickly in the TG than in the CG. The TG women had 14 degrees more abduction at 3 months and 7 degrees at 24 months. Functional recovery at 1 month was greater in those randomised to the TG, with a dominant operated arm (OA) or receiving breast-conserving surgery. However, it was not possible to predict recovery over the 2 years postoperatively on the basis of an individual woman's recovery at 1 month postoperatively. The eventual recovery of abduction or flexion range of movement was not related to the dominance of the OA nor to the surgical procedure performed. The PMCP provided in the early postoperative period is effective in facilitating and maintaining the recovery of shoulder movement over the first 2 years after breast cancer surgery.

Physiotherapy after breast cancer surgery: results of a randomised controlled study to minimise lymphoedema.

The development of secondary arm lymphoedema after the removal of axillary lymph nodes remains a potential problem for women with breast cancer. This study investigated the incidence of arm lymphoedema following axillary dissection to determine the effect of prospective monitoring and early physiotherapy intervention. Sixty-five women were randomly assigned to either the treatment (TG) or control group (CG) and assessments were made preoperatively, at day 5 and at 1, 3, 6, 12 and 24 months postoperatively. Three measurements were used for the detection of arm lymphoedema: arm circumferences (CIRC), arm volume (VOL) and multi-frequency bioimpedance (MFBIA). Clinically significant lymphoedema was confirmed by an increase of at least 200 ml from the preoperative difference between the two arms. Using this definition, the incidence of lymphoedema at 24 mo. was 21%, with a rate of 11% in the TG compared to 30% in the CG. The CIRC or MFBIA methods failed to detect lymphoedema in up to 50% of women who demonstrated an increase of at least 200 ml in the VOL of the operated arm compared to the unoperated arm. The physiotherapy intervention programme for the TG women included principles for lymphoedema risk minimisation and early management of this condition when it was identified. These strategies appear to reduce the development of secondary lymphoedema and alter its progression in comparison to the CG women. Monitoring of these women is continuing and will determine if these benefits are maintained over a longer period for women with early lymphoedema after breast cancer surgery.