Risk factors for lymphoedema in women with breast cancer: A large prospective cohort.

A prospective study was conducted to identify women at increased risk for lymphoedema (LE) based on axillary surgery. Assessment occurred prior to surgery, within 4 weeks, and at 6, 12 and 18 months following surgery. Following post-surgery assessment, women were asked to complete weekly diaries regarding events that occurred in the previous week. Risk factors were grouped into demographic, lifestyle, breast cancer treatment-related, arm swelling-related, and post-surgical activities. Bioimpedance spectroscopy thresholds were used to determine presence of LE. At 18-months, 241 women with <5 nodes removed and 209 women with ≥5 nodes removed were assessed. For those with <5 nodes removed, LE was present in 3.3% compared with 18.2% for those with ≥5 nodes removed. There were insufficient events to identify risk factors for those with <5 nodes removed; for those with >5 nodes removed, independent risk factors included presence of arm swelling at 12-months (Odds Ratio (OR): 13.5, 95% CI 4.8, 38.1; P < 0.01), at 6-months (5.6 (2.0, 16.9); P < 0.01), and radiotherapy to the axilla (2.6 (0.7, 8.9); P = 0.14). Arm swelling at 6 and 12 months was associated with taxane-based chemotherapy, high body weight at diagnosis and arm swelling within 4 weeks post-surgery. Of the post-surgical events assessed in a sub-group of women with >5 nodes removed and who maintained weekly diaries, only blood drawn from the 'at-risk' arm was identified as a potential risk (OR 2.0; 0.8, 5.2). For women with ≥5 nodes removed, arm swelling in the first year poses a very strong risk for presence of LE at 18-months.

ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer.

Alanine, serine, cysteine-preferring transporter 2 (ASCT2; SLC1A5) mediates uptake of glutamine, a conditionally essential amino acid in rapidly proliferating tumour cells. Uptake of glutamine and subsequent glutaminolysis is critical for activation of the mTORC1 nutrient-sensing pathway, which regulates cell growth and protein translation in cancer cells. This is of particular interest in breast cancer, as glutamine dependence is increased in high-risk breast cancer subtypes. Pharmacological inhibitors of ASCT2-mediated transport significantly reduced glutamine uptake in human breast cancer cell lines, leading to the suppression of mTORC1 signalling, cell growth and cell cycle progression. Notably, these effects were subtype-dependent, with ASCT2 transport critical only for triple-negative (TN) basal-like breast cancer cell growth compared with minimal effects in luminal breast cancer cells. Both stable and inducible shRNA-mediated ASCT2 knockdown confirmed that inhibiting ASCT2 function was sufficient to prevent cellular proliferation and induce rapid cell death in TN basal-like breast cancer cells, but not in luminal cells. Using a bioluminescent orthotopic xenograft mouse model, ASCT2 expression was then shown to be necessary for both successful engraftment and growth of HCC1806 TN breast cancer cells in vivo. Lower tumoral expression of ASCT2 conferred a significant survival advantage in xenografted mice. These responses remained intact in primary breast cancers, where gene expression analysis showed high expression of ASCT2 and glutamine metabolism-related genes, including GLUL and GLS, in a cohort of 90 TN breast cancer patients, as well as correlations with the transcriptional regulators, MYC and ATF4. This study provides preclinical evidence for the feasibility of novel therapies exploiting ASCT2 transporter activity in breast cancer, particularly in the high-risk basal-like subgroup of TN breast cancer where there is not only high expression of ASCT2, but also a marked reliance on its activity for sustained cellular proliferation.

Quality of life of women treated with radiotherapy for breast cancer.

GOALS OF WORK: Radiotherapy is routinely used in the treatment of early breast cancer, particularly in women who have undergone lumpectomy. Its impact on the quality of life of patients is important and is taken into consideration when making informed choices about treatment from both a patient's and health professional's point of view. This study reports on the quality of life of women at baseline, the completion of radiotherapy and 7 months after the completion of radiotherapy. MATERIALS AND METHODS: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C-30 and BR-23 questionnaires were used to evaluate quality of life of 61 women treated with radiotherapy for breast cancer. Additionally, demographic and treatment variables were analysed in relation to quality of life outcomes to determine if there were any significant predictors of quality of life. MAIN RESULTS: There was no difference in quality of life of women at baseline, completion and 7 months after completion of radiotherapy. Fatigue and breast symptoms increased during radiotherapy but returned to baseline levels at 7 months. Fatigue was the strongest predictor of poor quality of life in women after radiotherapy. CONCLUSION: Women retain a high quality of life and return to baseline function by 7 months after radiotherapy. Treatment may best be targeted to alleviate fatigue and breast symptoms during radiotherapy.

Pectoral stretching program for women undergoing radiotherapy for breast cancer.

Surgery and radiotherapy commonly cause adverse musculoskeletal problems, particularly loss of strength and range of motion, in the upper quadrant of breast cancer patients. Few well-designed studies have investigated whether these impairments can be prevented. Stretching is an effective technique for increasing range of motion, hence the aim of this study was to investigate whether a stretching program reduced acute musculoskeletal impairments in patients undergoing radiotherapy for breast cancer. Sixty-four women were recruited prior to commencement of radiotherapy following breast cancer surgery. Participants were randomised to either a control or stretch group. Participants in both groups were reviewed by the physical therapist on a weekly basis for approximately 6 weeks, and were given general information about skin care and lymphedema. The control group received no advice about exercise. The stretch group received instruction on low-load, prolonged pectoral stretches, which were to be performed daily and were checked at weekly visits. Shoulder range of motion, strength, arm circumference, and quality of life measurements were taken prior to, and at completion of radiotherapy, and at 7 months after radiotherapy. There was no difference in any outcome between groups. Breast symptoms increased for both groups during radiotherapy, without loss of strength or range of movement. The incidence of lymphedema during the study was low for both groups and did not differ between groups. The pectoral stretching program did not influence the outcomes measured because the symptoms reported by patients were not a consequence of contracture.

Long-term follow-up of a randomised trial of combined chemoradiotherapy induction treatment, with and without maintenance chemotherapy in patients with small cell carcinoma of the lung.

The toxicity and efficacy of concomitant chemotherapy and radiotherapy as induction therapy was evaluated in patients with previously untreated small cell carcinoma of the lung (SCLC), and in responding patients the value of maintenance chemotherapy was examined. 202 patients received induction chemotherapy with cisplatin and etoposide (EP), in combination with cranial and local radiotherapy. 85 patients (42%) developed grades III and IV myelosuppression, the main toxicity of induction treatment. Of the 154 responding patients, 129 were randomised to maintenance chemotherapy with vincristine, doxorubicin and cyclophosphamide (VAC) or no further treatment. The response rate for the limited disease patients (LD) was 87%, 62% achieving a complete response (CR) and the response rate for extensive disease patients (ED) was 68%, with 26% achieving a CR. 17 patients (11%) completed 10 courses of maintenance chemotherapy. 32 patients (57%) developed grade III and IV neutropenia. Median survival for all patients was 53 weeks (LD, 70 weeks; ED, 42.5 weeks). There was no significant difference in overall survival (OS) or disease-free survival (DFS) in the two randomisation arms. This study shows that EP combined with radiotherapy is an effective induction regimen in SCLC. Maintenance chemotherapy with VAC is not associated with increased survival but has significant toxicity after such induction treatment.

Phase II study of high dose epirubicin in combination with cyclophosphamide in patients with advanced breast cancer.

BACKGROUND: Combination chemotherapy for metastatic breast cancer will palliate symptoms in the majority of patients but only a small percentage will have prolonged survival. Higher doses of doxorubicin lead to increased response rates in breast cancer and early studies have shown that epirubicin could be tolerated in higher doses with less relative toxicity than doxorubicin. AIMS: This study was initiated to assess the dose of epirubicin that could be tolerated by escalating its dose while maintaining a fixed dose of cyclophosphamide. Simultaneously tumour response rate, spectrum of toxicities, duration of response and overall survival in patients with metastatic breast cancer were assessed. METHODS: Patients with metastatic breast cancer commenced chemotherapy with a starting dose of epirubicin of 120 milligram per metre squared (mg/m2) and cyclophosphamide 600 mg/m2. The dose of epirubicin was to be escalated or reduced depending on toxicity. RESULTS: Forty female patients were entered into this study and three patients withdrew because of toxicity. Overall tumour response rate was 75% with 27.5% of patients obtaining a complete response. Median time to progressive disease was 35 weeks and median overall survival was 48 weeks, with median survival for complete responders being 103 weeks. Thirty-one (77%) patients completed five or more courses of treatment. Haematological toxicity was the main side effect and 70% of patients required a dose reduction. No patients were eligible for a dose escalation. One patient died as a consequence of neutropenic sepsis. Four (10%) patients had treatment ceased because of decrease in left ventricular ejection fraction and one patient died as a consequence of heart failure. Four patients remain alive. CONCLUSIONS: High dose epirubicin combined with cyclophosphamide is an effective treatment regimen for metastatic breast cancer obtaining higher overall response rates with increased percentage complete responses compared to conventional dose chemotherapy. Although toxicity was increased, high dose chemotherapy was well tolerated and mortality associated with treatment was not increased. No dose escalations of epirubicin were possible and a dose of 90 mg/m2 of epirubicin would be the maximum dose when used in combination with cyclophosphamide. Further trials are required to determine the influence of this high dose therapy on survival duration and whether comparable benefits can be achieved with shorter durations of therapy.

Subcutaneous zygomycosis due to Saksenaea vasiformis in an infant.

A case of localized, subcutaneous infection in the cheek of a three-month-old girl that was caused by the zygomycete Saksenaea vasiformis is reported. This is the fourth report of infection in Australia that was due to this fungus and, in contrast to all but one of the few previous reports in the literature, a cure was effected by surgical debridement alone.