The varied presentation of metastatic melanoma in fine needle aspiration cytology of the breast

Objective To identify cytomorphological patterns of metastatic melanoma (MM) in breast fine needle aspiration (FNA) specimens and highlight the differential diagnoses and features most useful in identifying MM. Methods The clinical, radiological and FNA findings of 16 cases were reviewed. Cytological features evaluated related to cell arrangement, size and shape of cells, nuclear and cytoplasmic features, and the presence or absence of necrosis. Results The series consisted of 14 females and two males, ranging in age from 24 to 83 years (mean = 50 years). A previous history of melanoma was available in 12/16 (75%) cases at the time of FNA reporting; however the clinical/radiological impression in 4/16 cases was of a breast cyst. The cases were classified into six morphological variants: classical (8/16), pseudopapillary (3/16), spindle-cell (1/16), melanin-rich (1/16), pleomorphic (2/16) and lymphoma-like (1/16). The varying patterns raised a wide range of differential diagnoses; however, discohesion, binucleation and granular cytoplasm were the major features seen in 94% of all cases. In 14/16 cases (88%), plasmacytoid cells, prominent nucleoli and cytoplasmic vacuolation were identified. Melanin and multinucleation were detected in 44% of cases and intranuclear cytoplasmic invaginations in 63%. Necrosis was present in more than half of the cases (56%). Conclusion MM should be considered in the differential diagnosis of breast FNA specimens when atypical cells are seen that present as plasmacytoid cells in a dispersed or pseudopapillary pattern, or as spindle, pleomorphic or pigmented cells. These features, combined with clinical history and immunocytochemistry, may assist in correctly identifying MM and directing optimal treatment.

Demographics and survivial of a cohort of blood and breast cancer patients who developed heart failure following cancer treatment

Background/Aim: Cardiotoxicity resulting in heart failure is a devastating complication of cancer therapy. It is possible that a patient may survive cancer only to develop heart failure (HF), which is more deadly than cancer. The aim of this project was to profile the characteristics of patients at risk of cancer treatment induced heart failure. Methods: Linked Health Data Analysis of Queensland Cancer Registry (QCR) from 1996-2009, Death Registry and Hospital Administration records for HF and chemotherapy admissions were reviewed. Index heart failure admission must have occurred after the date of cancer registry entry. Results: A total of 15,987 patients were included in this analysis; 1,062 (6.6%) had chemotherapy+HF admission (51.4% Female) and 14,925 (93.4%) chemotherapy_no HF admission. Median age of chemotherapy+HF patients was 67 years (IQR 58 to 75) vs. 54 years (IQR 44 to 64) for chemotherapy_no HF admission. Chemotherapy+HF patients had increased risk of all cause mortality (HR 2.79 [95% CI 2.58-3.02] and 1.67 [95% CI, 1.54 to 1.81] after adjusting for age, sex, marital status, country of birth, cancer site and chemotherapy dose). Index HF admission occurred within one year of cancer diagnosis in 47% of HF patients with 80% of patinets having there index admission with 3 years. The number of chemotherapy cycles was not associated with significant reduction in survival time in chemotherapy+HF patients. Mean survival for heart failure patients was 5.3 years (95% CI, 4.99 - 5.62) vs.9.57 years (95% CI, 9.47-9.68) for chemotherapy_no HF admission patients. Conclusion: All-cause mortality was 67% higher in patients diagnosed with HF following chemotherapy in adjusted analysis for covariates. Methods to improve and better coordinate of the interdisciplinary care for cancer patients with HF involving cardiologists and oncologists are required, including evidence-based guidelines for the comprehensive assessment, monitoring and management of this cohort.

Adverse breast cancer treatment effects: The economic case for making rehabilitative programs standard of care

Purpose: The purpose of this work was to evaluate the patient-borne financial cost of common, adverse breast cancer treatment-associated effects, comparing cost across women with or without these side-effects. Methods: 287 Australian women diagnosed with early-stage breast cancer were prospectively followed starting at six months post-surgery for 12 months, with three-monthly assessment of detailed treatment-related side effects and their direct and indirect patient costs attributable to breast cancer. Bootstrapping statistics were used to analyze cost data and adjusted logistic regression was used to evaluate the association between costs and adverse events from breast cancer. Costs were inflated and converted from 2002 Australian to 2014 US dollars. Results: More than 90% of women experienced at least one adverse effect (i.e. post-surgical issue, reaction to radiotherapy, upper-body symptoms or reduced function, lymphedema, fatigue or weight gain). On average, women paid $5,636 (95%CI: $4,694, $6,577) in total costs. Women with any one of the following symptoms (fatigue, reduced upper-body function, upper-body symptoms) or women who report ≥4 adverse treatment-related effects, have 1.5 to nearly 4 times the odds of having higher healthcare costs than women who do not report these complaints (p<0.05). Conclusions: Women face substantial economic burden due to a range of treatment-related health problems, which may persist beyond the treatment period. Improving breast cancer care by incorporating prospective surveillance of treatment-related side effects, and strategies for prevention and treatment of concerns (e.g., exercise) has real potential for reducing patient-borne costs.

Systematic review of pharmacologic and non-pharmacologic interventions to manage cognitive alterations after chemotherapy for breast cancer

Purpose Cognitive alterations are reported in breast cancer patients receiving chemotherapy. This has adverse effects on patients’ quality of life and function. This systematic review investigates the effectiveness of pharmacologic and non-pharmacologic interventions to manage cognitive alterations associated with breast cancer treatment. Methods Medline via EBSCOhost, CINAHL and Cochrane CENTRAL were searched for the period January 1999 to May 2014 for prospective randomized controlled trials related to the management of chemotherapy-associated cognitive alterations. Included studies investigated the management of chemotherapy-associated cognitive alterations and used subjective or objective measures in patients with breast cancer during or after chemotherapy. Two authors independently extracted data and assessed the risk of bias. Results Thirteen studies involving 1138 participants were included. Overall, the risk of bias for the 13 studies were either high (n=11) or unclear (n=2). Pharmacologic interventions included psychostimulants (n=4), epoetin alfa (n=1), and Ginkgo biloba (n=1). Non-pharmacologic interventions were cognitive training (n=5) and physical activity (n=2). Pharmacologic agents were ineffective except for self-reported cognitive function in an epoetin alfa study. Cognitive training interventions demonstrated benefits in self-reported cognitive function, memory, verbal function and language and orientation/attention. Physical activity interventions were effective in improving executive function and self-reported concentration. Conclusion Current evidence does not favor the pharmacologic management of cognitive alterations associated with breast cancer treatment. Cognitive training and physical activity interventions appear promising, but additional studies are required to establish their efficacy. Further research is needed to overcome methodological shortfalls such as heterogeneity in participant characteristics and non-standardized neuropsychological outcome measures.

A multimodal physiotherapy programme plus deep water running for improving cancer-related fatigue and quality of life in breast cancer survivors

The aim of the study was to assess the feasibility and effectiveness of aquatic‐based exercise in the form of deep water running ( DWR ) as part of a multimodal physiotherapy programme ( MMPP ) for breast cancer survivors. A controlled clinical trial was conducted in 42 primary breast cancer survivors recruited from community‐based P rimary C are C entres. Patients in the experimental group received a MMPP incorporating DWR , 3 times a week, for an 8‐week period. The control group received a leaflet containing instructions to continue with normal activities. Statistically significant improvements and intergroup effect size were found for the experimental group for P iper F atigue S cale‐ R evised total score ( d = 0.7, P = 0.001), as well as behavioural/severity ( d = 0.6, P = 0.05), affective/meaning ( d = 1.0, P = 0.001) and sensory ( d = 0.3, P = 0.03) domains. Statistically significant differences between the experimental and control groups were also found for general health ( d = 0.5, P < 0.05) and quality of life ( d = 1.3, P < 0.05). All participants attended over 80% of sessions, with no major adverse events reported. The results of this study suggest MMPP incorporating DWR decreases cancer‐related fatigue and improves general health and quality of life in breast cancer survivors. Further, the high level of adherence and lack of adverse events indicate such a programme is safe and feasible.

Association of the SNP rs2623047 in the HSPG modification enzyme SULF1 with an Australian Caucasian Breast Cancer Cohort

Breast cancer is the second most common cancer worldwide and the most common cancer reported in women. This malignant tumour is characterised by a number of specific features including uncontrolled cell proliferation. It ranks fifth in the world as a cause of cancer death in women. Early diagnosis increases 5 year survival rates up to 95%. Heparan sulfate proteoglycans (HSPGs) are complex proteins composed of a core protein to which a number of highly sulfated side chains are synthesised by a highly co-ordinated process resulting in distinct sulfation patterns, which determine specific interations with cell-signaling partners including growth factors, their receptors, ligands and morphogens. The enzymes responsible for chain initiation, elongation and sulfation are critical for creating HS chain variability conferring biological functionality. This study investigated single nucleotide polymorphism in SULF1, the enzyme responsible for the 6-0 desulfation of heparan sulfate side chains. We investigated this SNP in an Australian Caucasian case-control breast cancer population and found a significant association between SULF1 and breast cancer at both the allelic and genotypic level (allele, p=0.016; genotype, p=0.032). Our results suggest the res2623047 SNP in SULF1 may impact breast cancer susceptibility. Specifically, the T allele of rs2623047 in SULF1 is associated with a increased risk of developing breast cancer in our cohort. The identification of markers including SULF1 may improve detection of this disease at its earliest stages improving patient treatment and prognosis.