A pan-Canadian prospective study of young women with breast cancer: the rationale and protocol design for the RUBY study.

Introduction: The understanding of the biology and epidemiology of, and the optimal therapeutic strategies for, breast cancer (bca) in younger women is limited. We present the rationale, design, and initial recruitment of Reducing the Burden of Breast Cancer in Young Women (ruby), a unique national prospective cohort study designed to examine the diagnosis, treatment, quality of life, and outcomes from the time of diagnosis for young women with bca. Methods: Over a 4-year period at 33 sites across Canada, the ruby study will use a local and virtual recruitment model to enrol 1200 women with bca who are 40 years of age or younger at the time of diagnosis, before initiation of any treatment. At a minimum, comprehensive patient, tumour, and treatment data will be collected to evaluate recurrence and survival. Patients may opt to complete patient-reported questionnaires, to provide blood and tumour samples, and to be contacted for future research, forming the core dataset from which 4 subprojects evaluating genetics, lifestyle factors, fertility, and local management or delivery of care will be performed. Summary: The ruby study will be the most comprehensive repository of data, biospecimens, and patient-reported outcomes ever collected with respect to young women with bca from the time of diagnosis, enabling research unique to that population now and into the future. This research model could be used for other oncology settings in Canada.

Medical assistance in dying for cancer patients one year after legalization: a collaborative approach at a comprehensive cancer centre.

Medical assistance in dying (maid) is a new medical service in Canada. Access to maid for patients with advanced cancer can be daunting during periods of declining health near the end of life. In this report, we describe a collaborative approach between the centralized coordination service and a regional cancer centre as an effective strategy for enabling interdisciplinary care delivery and enhancing patient-centred care at the end of the patient's cancer journey.

Rates of cannabis use in patients with cancer.

Background: A comprehensive assessment of cannabis use by patients with cancer has not previously been reported. In this study, we aimed to characterize patient perspectives about cannabis and its use. Methods: An anonymous survey about cannabis use was offered to patients 18 years of age and older attending 2 comprehensive and 2 community cancer centres, comprising an entire provincial health care jurisdiction in Canada (ethics id: hreba-17011). Results: Of 3138 surveys distributed, 2040 surveys were returned (65%), with 1987 being sufficiently complete for analysis (response rate: 63%). Of the respondents, 812 (41%) were less than 60 years of age; 45% identified as male, and 55% as female; and 44% had completed college or higher education.Of respondents overall, 43% reported any lifetime cannabis use. That finding was independent of age, sex, education level, and cancer histology. Cannabis was acquired through friends (80%), regulated medical dispensaries (10%), and other means (6%). Of patients with any use, 81% had used dried leaves.Of the 356 patients who reported cannabis use within the 6 months preceding the survey (18% of respondents with sufficiently complete surveys), 36% were new users. Their reasons for use included cancer-related pain (46%), nausea (34%), other cancer symptoms (31%), and non-cancer-related reasons (56%). Conclusions: The survey demonstrated that prior cannabis use was widespread among patients with cancer (43%). One in eight respondents identified at least 1 cancer-related symptom for which they were using cannabis.

Peer Review of Radiotherapy Planning: Quantifying Outcomes and a Proposal for Prospective Data Collection.

AIMS: The Canadian Partnership for Quality Radiotherapy quality assurance guidelines recommend that radiation oncologist peer review of curative radiotherapy plans takes place ideally before the first fraction of treatment is delivered. This study documented and evaluated the outcomes of weekly, disease site-specific, radiotherapy peer review, quality assurance rounds at the Tom Baker Cancer Centre in Calgary, Canada with a view to making recommendations about the optimal timing and documentation of peer review during the radiotherapy planning processes. MATERIALS AND METHODS: Outcomes of each case reviewed at (i) breast, (ii) head and neck (including thyroid and cutaneous cases) and (iii) lung team quality assurance rounds from 6 January to 5 May 2015 were recorded prospectively. Each radiotherapy plan was assigned an outcome: A for plans with no suggested changes; B for satisfactory, but where issues were raised to consider for future patients; or C when a change was recommended before the first or next fraction. The B outcomes were further subdivided into B1 for a case-specific concern and B2 for a policy gap. Plans were assessed after contour definition and before the plan was formulated (post-contouring reviews) and/or assessed when the plan was complete (post-planning reviews). RESULTS: 209 radiotherapy plans prescribed by 20 radiation oncologists were peer reviewed at 43 quality assurance meetings. 93% were curative-intent and 7% were palliative. 83% of plans were reviewed before delivery of the first treatment fraction. There were a total of 257 case reviews: 60 at the post-contouring stage, 197 at the post-planning stage, including 46 patients reviewed at both time points. Overall rates of A, B1, B2 and C outcomes were 78%, 9%, 4% and 9%, respectively. The most common reason for a B or C outcome was related to target volume definition. Only 56% of C outcomes at the post-planning stage would have been detected at the post-contouring stage. Results varied between tumour site groups. CONCLUSIONS: 9% of radiotherapy plans reviewed had changes suggested before delivery to the patient. Review at the post-planning stage after plan completion was necessary to detect all suggested changes, but for head and neck cases, all C outcomes could have been detected at the post-contouring stage. More widespread implementation of radiotherapy peer review in the UK is recommended.

Patient preferences for timing and access to radiation therapy.

PURPOSE: Patient preferences for radiation therapy (rt) access were investigated. METHODS: Patients completing a course of rt at 6 centres received a 17-item survey that rated preferences for time of day; day of week; actual, ideal, and reasonable travel times for rt; and actual, ideal, and reasonable times between referral and first oncologic consultation. Patients receiving single-fraction rt or brachytherapy alone were excluded. RESULTS: Of the respondents who returned surveys (n = 1053), 54% were women, and 74% had received more than 15 rt fractions. With respect to appointment times, 88% agreed or strongly agreed that rt between 08h00 and 16h30 was preferred; 14%-15% preferred 07h30-08h00 or 16h30-17h00; 10% preferred 17h00-18h00; and 6% or fewer preferred times before 07h30 or after 18h00. A preference not to receive rt before 07h30 or after 18h00 was expressed by 30% or more of the respondents. When days of the week were considered, 18% and 11% would have preferred to receive rt on a Saturday or Sunday respectively; 52% and 55% would have preferred not to receive rt on those days. A travel time of 1 hour or less for rt was reported by 82%, but 61% felt that a travel time of 1 hour or more was reasonable. A first consultation within 2 weeks of referral was felt to be ideal or reasonable by 88% and 73% of patients respectively. CONCLUSIONS: An rt service designed to meet patient preferences would make most capacity available between 08h00 and 16h30 on weekdays and provide 10%-20% of rt capacity on weekends and during 07h30-08h00 and 16h30-18h00 on weekdays. Approximately 80%, but not all, of the responding patients preferred a 2-week or shorter interval between referral and first oncologic consultation.

Recommendations for the referral of patients for proton-beam therapy, an Alberta Health Services report: a model for Canada?

BACKGROUND: Compared with photon therapy, proton-beam therapy (pbt) offers compelling advantages in physical dose distribution. Worldwide, gantry-based proton facilities are increasing in number, but no such facilities exist in Canada. To access pbt, Canadian patients must travel abroad for treatment at high cost. In the face of limited access, this report seeks to provide recommendations for the selection of patients most likely to benefit from pbt and suggests an out-of-country referral process. METHODS: The medline, embase, PubMed, and Cochrane databases were systematically searched for studies published between January 1990 and May 2014 that evaluated clinical outcomes after pbt. A draft report developed through a review of evidence was externally reviewed and then approved by the Alberta Health Services Cancer Care Proton Therapy Guidelines steering committee. RESULTS: Proton therapy is often used to treat tumours close to radiosensitive tissues and to treat children at risk of developing significant late effects of radiation therapy (rt). In uncontrolled and retrospective studies, local control rates with pbt appear similar to, or in some cases higher than, photon rt. Randomized trials comparing equivalent doses of pbt and photon rt are not available. SUMMARY: Referral for pbt is recommended for patients who are being treated with curative intent and with an expectation for long-term survival, and who are able and willing to travel abroad to a proton facility. Commonly accepted indications for referral include chordoma and chondrosarcoma, intraocular melanoma, and solid tumours in children and adolescents who have the greatest risk for long-term sequelae. Current data do not provide sufficient evidence to recommend routine referral of patients with most head-and-neck, breast, lung, gastrointestinal tract, and pelvic cancers, including prostate cancer. It is recommended that all referrals be considered by a multidisciplinary team to select appropriate cases.

A comparison of surgical and radiotherapy breast cancer therapy utilization in Canada (British Columbia), Scotland (Dundee), and Australia (Western Australia) with models of "optimal" therapy.

BACKGROUND: Different jurisdictions report different breast cancer treatment rates. Evidence-based utilization models may be specific to derived populations. We compared predicted optimal with actual radiotherapy utilization in British Columbia, Canada; Dundee, Scotland; and Perth, Western Australia. DESIGN: Data were analyzed for differences in demography, tumor, and treatment. Epidemiological data were fitted to published Australian optimal radiotherapy utilization trees and region-specific optimal treatment rates were calculated. Optimal and actual surgery/radiotherapy rates from 2 population-based and 1 institution-based registries were compared for patients diagnosed with breast cancer between 2000 and 2004, and 2002 for British Columbia. RESULTS: Mastectomy rates differed between British Columbia (40%), Western Australia (44%), and Dundee (47%, p<0.01). Radiotherapy rates differed between British Columbia (60%), Western Australia (52%), and Dundee (49%, p<0.01). Actual radiotherapy utilization rates were lower than optimal estimates. Region-specific optimal utilization rates at diagnosis varied from 57% to 71% for radiotherapy and 62% to 64% when taking into account patient preference. Variation was attributed to local differences in demography and tumor stage. CONCLUSIONS: Actual treatment rates varied, and were associated with patterns of care and guideline differences. Actual radiotherapy rates were lower than optimal rates. Differences between optimal and actual utilization may be due to access shortfalls, and patient preference.

Does HER2 status influence locoregional failure rates in breast cancer patients treated with mastectomy for pT1-2pN0 disease?

BACKGROUND: The impact of HER2 overexpression on the locoregional control of breast cancer is controversial. PATIENTS AND METHODS: Data on 906 women diagnosed with pT(1-2)pN(0) breast cancer from 1986 to 1992 with known HER2 status and treated with a modified radical mastectomy without adjuvant radiotherapy or adjuvant trastuzumab were analyzed with respect to local relapse-free survival (LRFS), regional relapse-free survival (RRFS) and distant relapse-free survival (DRFS). Log-rank statistics were used to compare 10-year Kaplan-Meier curves of LRFS, RRFS and DRFS in HER2+ and HER2- patients. RESULTS: Median follow-up was 12.8 years. HER2+ patients had a worse DRFS (P = 0.028) but there was no statistically significant difference in LRFS or RRFS between HER2+ and HER2- patients (P = 0.32 and 0.24 for LRFS and RRFS, respectively). Ten-year LRFS estimates among HER2+ patients was 91.3% and 86.9% for HER2- patients. Ten-year RRFS estimates for HER2+ and HER2- patients were 88.0% and 93.0%, respectively. CONCLUSION: HER2 overexpression was not associated with higher local or regional recurrence risk in subjects with pT(1-2)pN(0) breast cancer following mastectomy and nodal dissection after a median follow-up of >12 years.

Impact of a reduced dose intensity of adjuvant anthracycline based chemotherapy in a population-based cohort of stage I-II breast cancers.

BACKGROUND: Reductions in the dose intensity (DI) of adjuvant anthracycline-based chemotherapy in early stage breast cancer are frequently required due to treatment toxicity or poor tolerance, but the implications of a minimal reduction in DI on clinical outcome remain uncertain. PATIENTS AND METHODS: Women with stage I-II breast cancer treated with adjuvant adriamycin and cyclophosphamide (AC) from 1990-95 were identified in a provincial breast cancer database. Cases were classified into four cohorts: (1) all cycles delivered at full dose and on time; (2) one single dose reduction or dose delay; (3) >1 dose reduction or dose delay; (4) <2 cycles of chemotherapy delivered. RESULTS: 484 eligible cases were identified (cohort (1): n = 268; (2): n= 88; (3): n= 89; (4) n= 39). Slight imbalances in lymph node status (p=0.05) and adjuvant hormonal therapy (p=0.05) were observed between the cohorts. Fifty-five per cent (267/484) of the patients had node-positive disease and 33% (158/484) were ER+. 45% of cases had a reduction in DI. With a median follow-up of 9.6 years, there were no significant differences in relapse-free survival (p=0.94), breast cancer-specific survival (p=0.87) or overall survival (p=0.86) between the four cohorts. Outcomes were independent of hormone receptor status. CONCLUSIONS: Although toxicity related reductions in the DI of adjuvant AC chemotherapy for early stage breast cancer are common, they did not appear to significantly impact on clinical outcomes in this population-based cohort of women with stage I-II breast cancers.

Survival outcome and cost-effectiveness with docetaxel and paclitaxel in patients with metastatic breast cancer: a population-based evaluation.

BACKGROUND: A randomized controlled trial showed longer overall survival (OS) with docetaxel compared with paclitaxel in metastatic breast cancer patients with prior exposure to anthracycline. We report a similar comparison using population-based data. METHODS: Data on patients treated with single-agent paclitaxel or docetaxel were retrospectively reviewed. OS was compared using a two-tailed log-rank test and expressed as Kaplan-Meier plots. A cost-effectiveness analysis was carried out using cost/patient and OS. RESULTS: Four hundred and thirty-five patients met eligibility criteria. Prognostic factors were balanced between docetaxel and paclitaxel groups. Median OS was significantly longer for docetaxel versus paclitaxel [10.9 versus 8.3 months; hazard ratio 0.76; 95% confidence interval (CI), 0.62-0.92; P = 0.006]. The median number of cycles administered were four (docetaxel) and three (paclitaxel). The incremental cost-effectiveness ratio was $2434/per month of median survival gained. In the sensitivity analysis, the results were robust except that paclitaxel dominated when the low end of the 95% CI of survival for docetaxel was compared with the high end for paclitaxel. CONCLUSION: This population-based study corroborated the randomized trial's conclusion that for patients with metastatic breast cancer, docetaxel provided superior survival compared with paclitaxel. Each additional month of survival had an incremental cost of $2434.

Anemia is a common but neglected complication of adjuvant chemotherapy for early breast cancer.

In this study, we set out to determine the frequency and severity of anemia and the corrective interventions used during adjuvant chemotherapy for breast cancer.We conducted a retrospective electronic chart review of 702 patients who received adjuvant breast cancer chemotherapy at four BC Cancer Agency centres in 2002 and 2003. For these patients, we recorded the initial hemoglobin reading and the date of the first hemoglobin reading in the ranges 110-119 g/L, 100-109 g/L, 90-99 g/L, and <90 g/L. We also recorded any discussion about, or delivery of, interventions for anemia [transfusion, epoetin (epo) or both].Median age of the study population was 51 years, and it varied with chemotherapy type. Among the patients, 12% had a hemoglobin reading <120 g/L before the start of chemotherapy. Overall, the proportion of patients with at least one hemoglobin reading <120 g/L was 78%; <110 g/L, 54%; <100 g/L, 31%; and <90 g/L, 14%. Depending on chemotherapy type, a hemoglobin reading <100 g/L occurred in 5% to 54% of patients. Intervention rates increased as hemoglobin declined. For 99 patients with a hemoglobin reading <90 g/L, a discussion of anemia was documented in the treatment chart in 49% of cases, a transfusion was delivered in 23%, epo was used in 11%, and transfusion and epo were both delivered in 5%.Anemia was relatively common and varied with chemotherapy type. Documentation of a discussion of anemia occurred in fewer than 20% of the patients with a hemoglobin reading of 90-99 g/L and in only half the patients with a hemoglobin reading <90 g/L. Intervention rates were low at hemoglobin readings for which randomized trials have shown that intervention can improve quality of life.

Late risk of relapse and mortality among postmenopausal women with estrogen responsive early breast cancer after 5 years of tamoxifen.

BACKGROUND: Letrozole after 5 years of adjuvant tamoxifen results in a significant reduction in risk of recurrence from estrogen receptor (ER) positive breast cancer. An individualized estimate of the risk of relapse and death after 5 years of tamoxifen could improve decisions regarding extended hormonal therapy. METHODS: The British Columbia Breast Cancer Outcomes database was used to identify women aged 45 years or older at the time of diagnosis with early-stage (I-IIIA) breast cancer who received tamoxifen and were disease free 5 years after diagnosis. Ten-year breast cancer event rates and mortality were calculated as well as annualized hazard rates of recurrence. RESULTS: A total of 1086 women were identified with a median age of 64 years and follow-up of 10.5 years. The relative risk (RR) of death was 3.1 (P=0.003) and for recurrence was 1.7 (P=0.037) for N1 (one to three positive nodes) versus N0 (zero nodes positive) disease. N2 (four to nine nodes positive) had a RR of 5.8 (P<0.001) for death and 3.0 (P=0.002) for recurrence. Low tumor grade and high ER level subgroups had a more favorable prognosis. Annual breast cancer risk between years 6 and 10 was, respectively, 2.2%, 3.5% and 7.6% for N0, N1 and N2 disease and 2.6% and 4.5% for T1 and T2 breast cancer. CONCLUSION: T and N stages predicted late relapse and death from breast cancer in a population-based cohort of postmenopausal women. Risk estimates reported herein may be used to optimize decision making regarding adjuvant therapy after 5 years of tamoxifen.

Postmastectomy radiotherapy reduces locoregional recurrence in elderly women with high-risk breast cancer.

AIMS: Clinical trials of adjuvant radiotherapy after mastectomy have largely excluded women aged 70 years or over, even though they comprise 30% of the breast cancer population. This study examined outcomes in elderly women with high-risk breast cancer treated with or without postmastectomy radiotherapy (PMRT). MATERIALS AND METHODS: Data were analysed for 233 women aged 70 years or over with high-risk breast cancer (tumours > 5 cm or > or = 4 positive axillary nodes) treated with mastectomy and referred to the British Columbia Cancer Agency from 1989 to 1997. Tumour and treatment characteristics were compared between two cohorts: women treated with PMRT (n = 147) vs women treated without PMRT (n = 86). Univariate and multivariate analyses of 10-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence, breast cancer-specific survival and overall survival were carried out. RESULTS: Median follow-up time was 5.5 years. The distribution of tumour sizes was similar in the two groups. Compared with women treated without PMRT, higher proportions of women who underwent PMRT had four or more positive nodes (83% vs 67%, P = 0.01) and positive surgical margins (14% vs 4%, P = 0.02). Systemic therapy, used in 94% of women, was comparable in the two cohorts (P = 0.63). Elderly women treated with PMRT had significantly lower LRR compared with women treated without PMRT (16% vs 28%, P = 0.03). No differences in distant recurrence, breast cancer-specific survival or overall survival were observed in the two treatment groups (all P > 0.05). On multivariate analysis, the omission of PMRT and the presence of high-grade histology were significant predictors of LRR, whereas an increasing number of positive nodes was significantly associated with distant recurrence and overall survival. CONCLUSIONS: In women aged 70 years or over with tumours greater than 5 cm or four or more positive nodes, significantly lower LRR was observed in women treated with radiotherapy compared with women treated without radiotherapy. PMRT should be considered in the management of elderly women with these high-risk characteristics.

Short communication: Setup variations in locoregional radiotherapy for breast cancer: an electronic portal imaging study.

Recent trials demonstrating a survival benefit with locoregional radiotherapy (LRRT) to the chest wall and regional nodes in women with node-positive breast cancer have led to increased use of complex techniques to match three or more radiation fields, but information on setup reproducibility with LRRT for breast cancer is scarce. This study reports the magnitude and directions of random and systematic deviations in LRRT for breast cancer using an offline electronic portal imaging verification protocol. Electronic portal images (EPIs) of 46 consecutive women treated with LRRT for breast cancer from March 2001 to February 2002 with LRRT were analysed. Comparisons of EPIs to the corresponding digitally reconstructed radiographs were performed offline with anatomy matching. Displacements in mm were recorded in the superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP) directions. Random errors ranged from 2.0 mm to 2.5 mm for the breast/chest wall tangential treatments and 2.3 mm to 3.9 mm for the supraclavicular nodal treatments. Systematic errors occurred to a greater degree in the AP direction for the tangential fields and in the ML direction for the supraclavicular field. Displacements of > or =10 mm were found in 1.2% of breast/chest wall tangential treatments and in 6.2% of supraclavicular nodal treatments. These data demonstrate that EPI is a useful tool to verify setup reproducibility in LRRT for breast cancer.

A comparative analysis of radiotherapy use and patient outcome in males and females with breast cancer.

BACKGROUND: The aim was to determine whether gender was a significant prognostic factor for post-mastectomy relapse, after accounting for known prognostic factors and delivery of radiotherapy. PATIENTS AND METHODS: All patients diagnosed with invasive breast cancer between 1 January 1989 and 31 December 1998 who had undergone total mastectomy as primary therapy were identified from the British Columbia Cancer Agency's Breast Cancer Outcomes Unit database. Patients with pT4 or M1 disease were excluded. A comparison of patient, tumour and treatment factors was made between males and females. Outcomes were analysed in terms of locoregional-relapse free survival, breast cancer-specific survival and overall survival. RESULTS: Sixty males and 4181 females were identified. Multivariable analysis revealed increased tumour size, positive margin status, delivery of chemotherapy, positive nodal status and male gender to be significantly associated with the use of post-mastectomy radiotherapy. Multivariable analysis revealed tumour size, nodal status, tumour grade and presence of vascular space invasion to be significantly associated with locoregional recurrence. Gender was not a prognostic factor for locoregional recurrence, breast cancer-specific survival or overall survival on univariable or multivariable analysis. CONCLUSIONS: These data suggest that gender is not a prognostic factor in patients undergoing mastectomy for early stage breast cancer. Men having mastectomy for breast cancer should receive adjuvant radiotherapy following guidelines similar to those developed for females.

Comparison of 1- and 2-year screening intervals for women undergoing screening mammography.

We compared the long-term impact of 1- and 2-year screening mammography intervals using prognostic, screening, and outcome information for women aged 50-74 years obtained from the Screening Mammography Program of British Columbia in two time periods, prior to 1997 (policy of annual mammography) and after 1997 (biennial mammography). Survival was estimated for both periods using a prognostic model and the expected rate of interval and screen-detected cancers. The likelihood of a screen-detected cancer with annual screening was 2.32 per thousand screens and with biennial screening was 3.32 per thousand screens. The prognostic profile of screen-detected cancers was better than that of interval cancers. Among both screen-detected and interval cancers, the prognostic profiles with annual and biennial screening were similar. The estimated breast cancer-specific survival rates for women undergoing annual and biennial screening mammography were 95.2 and 94.6% at 5 years, and 90.4 and 89.2% at 10 years, respectively. Annual compared to biennial mammography was associated with a 1.2% increase in the estimated 10-year breast cancer-specific survival for women aged 50-74 years, diagnosed with invasive breast cancer after screening programme attendance.

The difference between study recommendations, stated policy, and actual practice in a clinical trial.

BACKGROUND: We determined whether physicians involved in a clinical trial adhere to the study recommendations or the stated policy of their treatment centre with respect to the administration of boost radiation after breast conserving surgery. PATIENTS AND METHODS: Boost radiation treatment policy was determined by survey at 25 oncology centres involved in a randomised trial of breast or breast plus nodal radiation in Canada. Actual practice was compared with stated policy and study recommendations. RESULTS: Among 248 subjects, 201 (81%) were treated according to stated policy [kappa=0.40, 95% confidence intervals (CI) 0.27-0.52; P<0.0001], indicating only a fair to moderate agreement between stated and actual practice, while 232 (94%) were treated according to study recommendations (kappa=0.59, 95% CI 0.40-0.77; P<0.0001), indicating moderate to near substantial agreement between study recommendations and actual practice (P=0.88 for z-test of difference). In a multivariate analysis, subjects who had invasive disease at a resection margin were more likely to get a boost than those with margins clear of invasive tumour by 2 mm [odds ratio (OR) 49, 95% CI 7.6-322; P<0.0001]. CONCLUSIONS: Physicians appear compliant with study recommendations for a non-randomised manoeuvre in a clinical trial, possibly at the expense of compliance with stated local policy. Clinical trial protocols should incorporate standard practice.

Mega-dose vitamins and minerals in the treatment of non-metastatic breast cancer: an historical cohort study.

BACKGROUND: Alternative therapies such as mega-dose vitamins and minerals are commonly used by women with breast cancer, but their effect on recurrence and survival have rarely been evaluated. METHODS: Survival and recurrence outcomes for 90 women with unilateral non-metastatic breast cancer diagnosed between 1989 and 1998, and who had been prescribed mega-doses of beta-carotene, vitamin C, niacin, selenium, coenzyme Q10, and zinc in addition to standard therapies were compared with matched controls. The 90 treated patients were prescribed combinations from three to six of the vitamins and minerals listed above. The controls were matched (2:1) to the vitamin/mineral patients for age at diagnosis, presence of axillary lymph node metastasis, tumor stage, grade, estrogen receptor status, year of diagnosis, and prescription of systemic therapy. All subjects were patients of the British Columbia Cancer Agency, Vancouver Island Centre. FINDINGS: Median follow-up of surviving patients was 68 months (minimum 20 months, 133 months maximum). The vitamin/mineral patients and controls were well matched. Two endpoints were considered. Breast cancer-specific survival (p = 0.19) and disease-free survival (p = 0.08) times for the vitamin/mineral treated group were shorter, after adjusting for diagnostic variables using a Cox proportional hazards model. The hazard ratios for the vitamin/mineral treated group versus the control group were estimated at 1.75 (95% CI = 0.83-2.69) for disease-specific survival and 1.55 (95% CI = 0.94-2.54) for disease-free survival. Overall survival was similar for the two groups (log-rank test, p = 0.36). INTERPRETATION: Breast cancer-specific survival and disease-free survival times were not improved for the vitamin/mineral treated group over those for the controls.

Prognostic significance of the number of axillary lymph nodes removed in patients with node-negative breast cancer.

PURPOSE: The objective of the study was to evaluate the association between the number of lymph nodes removed at axillary dissection and recurrence and survival for patients with node-negative invasive breast cancer. PATIENTS AND METHODS: Subjects were 2,278 women with pathologically node-negative invasive breast cancer, diagnosed from 1989 to 1993 in British Columbia, Canada. Women aged > or = 90 years, with pure in-situ, bilateral invasive breast cancer or T4, N1, N2, or M1 stage, or who had axillary radiation were excluded. Two groups were defined for analysis: node-negative with no systemic therapy (n = 1,468) and node-negative with systemic therapy (n = 810). Median follow-up was 7.5 years. Prognostic variables assessed were age at diagnosis, tumor size, tumor grade, invasion of lymphatics, veins, or nerves, estrogen receptor status, and number of nodes removed. RESULTS: For patients not receiving systemic therapy, regional relapse was significantly increased with smaller numbers of nodes removed (P =.03). There was a trend toward shorter overall survival with fewer nodes removed (P =.06). Node-negative patients who received systemic therapy did not have a higher regional relapse rate or shorter overall survival when fewer nodes were recovered. CONCLUSION: Recovery of a small number of negative lymph nodes at axillary dissection likely understages patients and leads to undertreatment, resulting in an increased regional relapse rate and poorer survival. The use of systemic therapy may overcome this effect. The number of nodes removed, in conjunction with other prognostic factors, may be useful in selecting node-negative patients for systemic therapy.

Improving the time to diagnosis after an abnormal screening mammogram.

INTRODUCTION: Five community-specific interventions to reduce the time to diagnosis after an abnormal breast screen have been evaluated. METHODS: Subjects with abnormal screening mammograms in 1998 were assessed through five community pilot projects (N = 1137) and a control random sample assessed elsewhere in BC (N = 1053). The number, types, dates and physician costs of breast-related interventions after an abnormal screen were compared between pilots and control. RESULTS: The median time to diagnosis for women without a biopsy was reduced from 23 days to 7 days (p = 0.001) in the pilot with facilitated referral to diagnosis. The median time to diagnosis for women with a biopsy was reduced from 57 days to 22-43 days in the pilots. Median physician costs per subject were lower (p = 0.02) in pilots that more frequently used core biopsy to obtain a diagnosis. CONCLUSIONS: Process changes can improve the time to diagnosis after an abnormal breast screen, with similar or lower physician costs per subject. Facilitating the referral process had the greatest impact.