Body Mass Index and Outcomes in Breast Cancer Treated With Breast Conservation.

PURPOSE: Obesity is increasing in incidence in New Zealand. Maintaining locoregional control after breast cancer surgery is important, as this can improve overall survival. Although obesity has been associated with poorer survival in breast cancer, the correlation with locoregional control is less well evaluated and was the subject of this evaluation. METHODS AND MATERIALS: We used the New Zealand breast cancer registry to identify patients treated with breast conservation with body mass index (BMI) recorded. We retrieved patient demographic, tumor characteristic, and treatment-related information. We assessed local and locoregional control outcomes in addition to breast cancer and overall survival outcomes. RESULTS: Patients (2513) were identified. The median follow-up was 5.25 years. Of these patients, 38% were obese with a BMI of ≥30 kg/m2, 32% were overweight with a BMI of 25.0 to 29.9 kg/m2, and 29% were either normal or underweight with a BMI of ≤24.9 kg/m2. Most patients were postmenopausal (65%). The median tumor size was 16.0 mm (0.2-80 mm) and the majority were grade 2 or 3 tumors (45% and 33%). The majority (66%) were pathologically node negative and lymphovascular invasion was seen in 24%. There were 81% with estrogen receptor positivity and 358 (14.2%) were Her-2 positive. Local relapse free survival at 5 years was 91.5% (95% confidence interval [CI], 90.3-92.7) and at 10 years was 78.5% (95% CI, 75.9-81.1). Local relapse free rate at 5 years was 96.8% (95% CI, 96.0-97.6) and 10 years was 93.9% (95% CI, 92.5-95.3). We did not find BMI to be associated with local or locoregional relapse, disease free, breast cancer specific, or overall survival. CONCLUSIONS: Obesity was not associated with inferior locoregional control or survival outcomes. This supports the practice of continuing to offer breast conserving treatment to women regardless of BMI.

Radiation treatment in early stage triple-negative breast cancer in New Zealand: A national database study.

INTRODUCTION: We aimed to investigate the impact of radiation treatment in early-stage triple negative breast cancer (TNBC). METHODS: Patients with early stage (T1-3, N0-2, M0) TNBC were identified using the New Zealand breast cancer register. The outcomes of local recurrence (LRFR), local recurrence free survival (LRFS), loco-regional recurrence free rate (LRRFR), loco-regional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), metastasis free (MFS) and overall survival (OS) were determined. Predefined univariate and multivariate cox regression analyses were used to explore associations between known prognostic and treatment factors. RESULTS: 1209 patients were identified with a median follow-up of 3.88 years. The majority were post- menopausal. The mean tumour size was 26mm, the majority had grade III disease and a third were node positive. 625 patients had mastectomy and 584 had breast conservation surgery (BCS). 92% of BCS and 38% of mastectomy patients received radiation. 67% received adjuvant chemotherapy. The 5 year OS was 77.6% (95% CI 74.6-80.2), 5 year BSS was 82.1% (95%CI 79.1-84.7), 5 year LRRFS was 73.9% (95% CI 73.87-73.93), 5 year LRFS was 75.4 (75.37-75.43) and the 5 year LRFR was 92.4% (95% CI 90.6-94.2). The significant prognostic/predictive factors for OS were adjuvant radiation treatment, chemotherapy, T stage, lymph node involvement and lympho-vascular space invasion. Results were similar for BSS, DMFS, LRFS and LRRFS except that LVSI was not significantly associated with BCSS, LRFS or LRRFS. When analysed by surgical type, in the WLE group, radiation was found to be significantly associated with improvement in all outcomes. In mastectomy group, radiation was not found to be significant for BCSS, LRFS, LRRFS or OS. CONCLUSION: Radiation treatment is significantly associated with improved outcomes in early stage TNBC. This argues against the hypothesis that TNBC has inherent radiation resistance.

Activation of the hypoxia pathway in breast cancer tissue and patient survival are inversely associated with tumor ascorbate levels.

BACKGROUND: The transcription factor hypoxia inducible factor (HIF) -1 drives tumor growth and metastasis and is associated with poor prognosis in breast cancer. Ascorbate can moderate HIF-1 activity in vitro and is associated with HIF pathway activation in a number of cancer types, but whether tissue ascorbate levels influence the HIF pathway in breast cancer is unknown. In this study we investigated the association between tumor ascorbate levels and HIF-1 activation and patient survival in human breast cancer. METHODS: In a retrospective analysis of human breast cancer tissue, we analysed primary tumor and adjacent uninvolved tissue from 52 women with invasive ductal carcinoma. We measured HIF-1α, HIF-1 gene targets CAIX, BNIP-3 and VEGF, and ascorbate content. Patient clinical outcomes were evaluated against these parameters. RESULTS: HIF-1 pathway proteins were upregulated in tumor tissue and increased HIF-1 activation was associated with higher tumor grade and stage, with increased vascular invasion and necrosis, and with decreased disease-free and disease-specific survival. Grade 1 tumors had higher ascorbate levels than did grade 2 or 3 tumors. Higher ascorbate levels were associated with less tumor necrosis, with lower HIF-1 pathway activity and with increased disease-free and disease-specific survival. CONCLUSIONS: Our findings indicate that there is a direct correlation between intracellular ascorbate levels, activation of the HIF-1 pathway and patient survival in breast cancer. This is consistent with the known capacity of ascorbate to stimulate the activity of the regulatory HIF hydroxylases and suggests that optimisation of tumor ascorbate could have clinical benefit via modulation of the hypoxic response.

A review of the Christchurch Hospital Breast Cancer Service in 2012: meeting the new Tumour Standards.

AIMS: To determine whether patients diagnosed with breast cancer in 2012 received timely access to services at Christchurch Hospital when audited against Ministry of Health Tumour Standards of Service Provision (TS) (2013) and the Faster Cancer Treatment (FCT) indicators, and to discover factors which impeded patient pathways, and which would need to be addressed in order to meet the standards. METHODS: Data on referrals, dates and treatment for patients diagnosed with breast cancer at Christchurch Hospital was extracted from the Christchurch Breast Cancer Patient Register and other hospital databases. RESULTS: In 2012, 288 breast cancer patients were treated at Christchurch Hospital, 60% referred by general practitioners, and 40% via the national screening programme. Some 2013 Tumour Standards were achieved. The FCT indicator 1 (TS 2.4) and 3 (TS 2.5) were met, with 87% (greater than or equal to 80%) receiving their first treatment within 62 days of referral, and 89% (greater than or equal to 80%) within 31 days of decision-to-treat. However, FCT indicator 2 (TS 2.1), requiring first specialist assessment within 14 days of referral, was met in 61% (greater than or equal to 90% required). Only 64% of women started adjuvant chemotherapy within 42 days of their surgery (TS 2.6, greater than or equal to 90%). CONCLUSION: The management of breast cancer patients by a multidisciplinary team is crucial to ensure patients receive timely and appropriate care. However, waiting for weekly multidisciplinary meetings and adequate anatomical pathology resource, together with other factors, were identified as delaying the patient pathway and solutions to resolve these are discussed.

Perioperative nutrition interventions for women with ovarian cancer.

BACKGROUND: Women with ovarian cancer have been shown to be at significant risk of malnutrition with incidence rates described as being between 28% to 67%. Nutrition interventions may improve clinical outcomes positively, nutritional status or quality of life measures in this patient group. OBJECTIVES: This review was conducted to assess the effects of nutrition interventions during the perioperative period for women with ovarian cancer. SEARCH METHODS: Electronic searches were conducted of the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 7), Medline (1946 to July week 4 2012), Embase (1980 to 2012 week 31), DARE (to 7th August 2012) AMED (1985 to April 2012), BNI (1992 to April 2012), CINAHL (to April 2012). We also searched trials databases, conference proceedings and related citation lists. Reference listings were handsearched. No restrictions were applied on language or date. SELECTION CRITERIA: Randomised controlled trials (RCTs) in which women 18 years and over with any stage of ovarian cancer, including recurrent cancer, were in the perioperative phase of treatment and received any type of nutrition intervention. DATA COLLECTION AND ANALYSIS: Titles and abstracts were screened by two review authors with study selection discussed by a team. Pairs of review authors worked independently on data collection and compared findings. MAIN RESULTS: A total of 4092 titles were screened and 14 full text reports reviewed; a single small study met the inclusion criteria. In the included RCT, 40 women (35 with ovarian cancer) had extensive elective surgery including bowel resection for treatment of gynaecological malignancy. Randomisation was made to either early oral feeding (oral fluids in the first 24 hours, solid foods on the following day) or to a 'traditional' feeding regimen where oral fluids and foods were delayed until there was evidence of bowel function. Most women in the early feeding group (14/18) were able to resume eating solid food one day after surgery. This resulted in a significantly shorter hospital stay with no increase in postoperative complications or change in quality of life measures in comparison with the women on the 'traditional' feeding regimen. The incidence of nausea and vomiting during the postoperative stay was similar in both groups and was noted in slightly more than half of the women. Overall survival was evaluated until 30 days following discharge from hospital; in this period, there was one death of a woman who had been in the 'traditional oral feeding' group, cause of death was not noted. We assessed risk of bias and found no high risk of bias was identified in the methodology and reporting of the included study, although there was an increased risk of bias due to the small size of the study in which not all of the women had ovarian cancer. AUTHORS' CONCLUSIONS: Although women with ovarian cancer have been shown to be at risk of malnutrition, there is a lack of evidence derived from RCTs evaluating the identification, assessment and treatment of malnutrition during the perioperative phase of treatment. There is evidence from one small study that some women with ovarian cancer undergoing surgery with associated bowel resection may safely commence oral fluids within 24 hours of surgery and solid foods on the following day. Further research is required, including a RCT, to generate guidance concerning the treatment of malnutrition in this patient group.

The Christchurch Breast Cancer Patient Register: the first year.

AIMS: The aim of this article is to present the first year's findings of the Christchurch Breast Cancer Patient Register (CBCR) to establish the incidence and management of breast cancer in the Canterbury region. METHODS: CBCR commenced recruitment of breast cancer patients in Canterbury from June 2009. Ethical approval was granted by regional ethics committees to collect data. Patient data is recorded onto the database once informed consent is obtained. RESULTS: A total of 337 patients (including one male) consented. At diagnosis, 231 (68.5%) were aged 50 years or over. 48 (14.2%) patients had carcinoma in situ with no invasive component. 289 (85.8%) patients had invasive carcinoma with 47.4% undergoing mastectomy and 44.6% breast conserving surgery whereas 8% had no primary surgery. Nodes were positive in 102 (38.8%), and the predominant tumour type was Ductal NST (no special type) in 68.9% (199) of patients with invasive carcinoma. Additional data incorporating ethnicity, oncology, additional surgical management and pathological variables are also presented in detail. CONCLUSION: Findings on 337 patients recruited and recorded on CBCR database in the first year are discussed. Due to the short follow up, outcome data is not analysed.

A profile of prognostic and molecular factors in European and Maori breast cancer patients.

BACKGROUND: New Zealand Maori have a poorer outcome from breast cancer than non-Maori, yet prognostic data are sparse. The objective of this study was to quantify levels of prognostic factors in a cohort of self-declared Maori and European breast cancer patients from Christchurch, New Zealand. METHODS AND RESULTS: Clinicopathological and survival data from 337 consecutive breast cancer patients (27 Maori, 310 European) were evaluated. Fewer tumours were high grade in Maori women than European women (p = 0.027). No significant ethnic differences were detected for node status, tumour type, tumour size, human epidermal growth factor receptor, oestrogen and progesterone receptor (ER/PR) status, or survival.In addition, tumour and serum samples from a sub-cohort of 14 Maori matched to 14 NZ European patients were analyzed by immunohistochemistry and enzyme linked immunosorbent assay for molecular prognostic factors. Significant correlations were detected between increased grade and increased levels of hypoxia inducible factor-1 (HIF-1α), glucose transporter-1 (GLUT-1), microvessel density (MVD) and cytokeratins CK5/6 (p < 0.05). High nodal status correlated with reduced carbonic anhydrase IX (CA-IX). Negative ER/PR status correlated with increased GLUT-1, CA-IX and MVD. Within the molecular factors, increased HIF-1α correlated with raised GLUT-1, MVD and CK5/6, and CK5/6 with GLUT-1 and MVD (p < 0.05). The small number of patients in this sub-cohort limited discrimination of ethnic differences. CONCLUSIONS: In this Christchurch cohort of breast cancer patients, Maori women were no more likely than European women to have pathological or molecular factors predictive of poor prognosis. These data contrast with data from the North Island NZ, and suggest potential regional differences.

Evaluation of the effectiveness of imiquimod and 5-fluorouracil for the treatment of actinic keratosis: Critical review and meta-analysis of efficacy studies.

BACKGROUND: Actinic keratosis lesions occur frequently on sun-exposed skin of Caucasians. They become more prevalent with advancing age and are important in identifying the risk factor of those people possibly predisposed to invasive squamous cell carcinoma. Topical therapies are useful alternatives to cryotherapy for treating diffuse actinic damage and a number of preparations have been developed for treating actinic keratosis. OBJECTIVES: A cumulative meta-analysis was performed to determine the efficacy of imiquimod 5% cream, which presents a new alternative topical therapy for actinic keratosis, and to compare it to 5-fluorouracil for the treatment of actinic keratosis lesions of the face and scalp. METHODS: We searched MEDLINE (1966 to October 2004) for relevant studies evaluating the efficacy of actinic keratosis topical agents imiquimod and 5-fluorouracil (0.5%, 1%, and 5%). Studies included in this meta-analysis required a dosage regimen that was not significantly different from that approved by Health Canada and the U.S. FDA. Studies also required a well-defined treatment duration and followup period, with the primary efficacy variable being the complete (100%) clearance of all actinic keratosis lesions defined as the proportion of patients at followup with no clinically visible lesions in the treatment area. To determine the average efficacy rate for both drugs, the data from each study were combined for that drug. RESULTS: Ten studies were included in the analysis. The average efficacy rate for each drug (with 95% confidence interval) was 5-fluorouracil, 52 +/- 18% (n = 6 studies, 145 subjects) and imiquimod, 70 +/- 12% (n = 4 studies, 393 subjects). CONCLUSIONS: The results of this meta-analysis show that both imiquimod and 5-fluorouracil are effective methods for the treatment of actinic keratosis and provide a useful alternative to cryotherapy. However, this analysis suggests that imiquimod may have higher efficacy than 5-fluorouracil for actinic keratosis lesions located on the face and scalp and therefore provides another option to dermatologists.