Introduction: CYP2D6 protein activity can be inferred from the ratio of N-desmethyl-tamoxifen (ND... more Introduction: CYP2D6 protein activity can be inferred from the ratio of N-desmethyl-tamoxifen (NDMT) to endoxifen (E). CYP2D6 polymorphisms are common and can affect CYP2D6 protein activity and E level. Some retrospective studies indicate that E < 16 nM may relate to worse outcome. Materials and methods: A target NDMT/E ratio was defined as associated with an E level of 15 nM in the 161 patient Test cohort of tamoxifen-treated patients, dichotomizing them into 'Normal' (NM) and 'Slow' (SM) CYP2D6 metabolizer groups. This ratio was then tested on a validation cohort of 52 patients. Patients were phenotyped based on the standard method (ultrarapid/extensive, intermediate or poor metabolizers; UM/EM, IM, PM) or a simplified system based on whether any variant allele (V) vs wildtype (wt) was present (wt/wt, wt/V, V/V). Comprehensive CYP2D6 genotyping was undertaken on germline DNA. Results: A target NDMT/E ratio of 35 correlated with the 15 nM E level, dichotomizing patients into NM (<35; N ¼ 117) and SM (>35; N ¼ 44) groups. The ratio was independently validated by a validation cohort. The simplified system was better in predicting patients without slow metabolism, with specificity and sensitivity of 96% and 44% respectively, compared with the standard method-sensitivity 81% and specificity 83%. Conclusions: The simplified classification system based on whether any variant was present better identified patients who were truly not CYP2D6 slow metabolizers more accurately than the current system. However, as CYP2D6 genotype is not the only determinant of endoxifen level, we recommend that direct measurement of endoxifen should also be considered.
When the goal is not cure: A randomized trial of a patient decision aid in advanced colorectal cancer
Journal of Clinical Oncology, 2007
6509 Background: With improvements in treatment and supportive care, decisions in advanced cancer... more 6509 Background: With improvements in treatment and supportive care, decisions in advanced cancer are increasingly complex. To facilitate decision-making, we developed a decision aid (DA) for patients considering first-line chemotherapy for incurable colorectal cancer, reviewing treatment options, prognostic information and toxicities. We examined its impact on patient understanding, consultation and decision- making satisfaction, anxiety, decisional conflict, quality of life, information preferences, and treatment decisions made. Methods: 207 newly diagnosed advanced colorectal cancer patients at 5 cancer centers in Australia and Canada were randomized to receive either a standard medical oncology consultation, or the same plus the DA, (take-home booklet with audio-recording, selected review by oncologist). Results: 100 were randomized to the control arm, 107 to receive the DA. Sample characteristics: median age 62 years, 58% male, 89% PS 0/1, 36% prior adjuvant chemotherapy. Patie...
Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic v... more Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a coun...
Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving sur... more Background Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). Findings Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21•4% for NACT versus 15•9% for adjuvant chemotherapy (5•5% increase [95% CI 2•4-8•6]; rate ratio 1•37 [95% CI 1•17-1•61]; p=0•0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38•2% for NACT vs 38•0% for adjuvant chemotherapy; rate ratio 1•02 [95% CI 0•92-1•14]; p=0•66), breast cancer mortality (34•4% vs 33•7%; 1•06 [0•95-1•18]; p=0•31), or death from any cause (40•9% vs 41•2%; 1•04 [0•94-1•15]; p=0•45). Interpretation Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy.
The administration of endocrine therapy for 5 years substantially reduces recurrence rates during... more The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan-Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients' outcomes during the period from 5 to 20 years. Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrenc...
We compared the results of randomised trials comparing taxane-containing chemotherapy regimens wi... more We compared the results of randomised trials comparing taxane-containing chemotherapy regimens with regimens not containing a taxane in women with metastatic breast cancer. The specialised register of the Cochrane Breast Cancer Group was searched in March 2004. Eligibility was assessed and data extracted from eligible studies by two reviewers. Hazard ratios (HR) were derived for time-to-event outcomes, and a fixed-effect model was used for meta-analysis. Tumour response rates were analysed as dichotomous variables. Of 21 eligible trials, 16 had published some results and 12 data on overall survival. An estimated 2621 deaths among 3643 women suggest a significant difference in overall survival in favour of taxane-containing regimens (HR 0.93, 95% confidence interval (CI) 0.86-1.00, P ¼ 0.05). The treatment effect on survival was similar if only trials of first-line chemotherapy were included, although not statistically significant. There appeared to be an advantage for taxanes in time to progression (HR 0.92, 95% CI 0.85-0.99, P ¼ 0.02) and overall response (odds ratio (OR) 1.34, 95% CI 1.18-1.52, Po0.001). There was significant heterogeneity across the trials (Po0.001), partly because of the varying efficacy of the comparator regimens. Taxane-containing regimens improved overall survival in women with metastatic breast cancer. Taxane-containing regimens are more effective than some, but not all, nontaxanecontaining regimens.
A prospective cohort study of fatigue after adjuvant therapy for breast cancer: Association with hematologic, endocrine, and immune parameters
Journal of Clinical Oncology, 2008
A meta-analysis of chemotherapy duration in metastatic breast cancer (MBC)
Journal of Clinical Oncology, 2008
1067 Background: Ten years ago, a systematic review of 4 randomised trials comparing longer with ... more 1067 Background: Ten years ago, a systematic review of 4 randomised trials comparing longer with shorter chemotherapy duration in MBC showed a 20% reduction in the risk of death with more chemotherapy cycles, supporting the policy of prolonging treatment in the absence of progressive disease or unacceptable toxicity. Since this analysis, new studies on different chemotherapy durations have been reported, with conflicting results. With these premises, the aim of this study was to review all the available evidence on this subject. Methods: The criteria used to identify relevant studies, through literature search, were 1) randomised trials, 2) investigation of longer versus shorter chemotherapy duration, 3) overall survival data. Eight studies comprising 1,942 randomised patients were retrieved. Pooled estimates, based on published data, of overall survival HRs were obtained according to standard meta-analysis procedures. Sensitivity analyses were performed to examine whether the overall effect on survival w...
Influence of fatigue after breast cancer adjuvant therapy on health care utilization and perceived needs
Journal of Clinical Oncology, 2010
9047 Background: We have previously reported a post-cancer fatigue (PCF) case rate of 24% post su... more 9047 Background: We have previously reported a post-cancer fatigue (PCF) case rate of 24% post surgery, 42% at end-treatment, 19% at 6 months (mo), and 14% at 12 mo in a prospective cohort of over 200 women with early stage breast cancer, with approximately half having comorbid psychological disorder (Psych) at each time point. We now examine rates of health care utilization (HCU) and perceived health care needs (PHCN) and their associations with fatigue and Psych disorders. Methods: Structured interviews and self-report questionnaires identified PCF and Psych; HCU by self-report of number of visits to medical, mental health and complementary and alternative medicine (CAM) practitioners; PHCN by the Perceived Need for Care Questionnaire (PCNQ). Predictors of HCU were sought by linear regression, while PCNQ data was assessed by contingency analysis. Results: Data from 206 women (mean age 53 years, range 26-82) followed to 12 mo post therapy. Predictors of increased HCU were Psych at end-treatment (p = 0.01...
Impact of first-line chemotherapy duration in metastatic breast cancer: A systematic review
Journal of Clinical Oncology, 2010
1023 Background: Prolonging chemotherapy (CT) until disease progression is a common practice in t... more 1023 Background: Prolonging chemotherapy (CT) until disease progression is a common practice in the management of MBC. This approach is based on available evidence from randomized trials comparing ...
Abstract P5-11-05: Making a difficult conversation easier: Estimating and explaining scenarios for survival time in patients with HER2 positive, metastatic breast cancer
Cancer Research, 2016
Aim Advances in the treatment of HER2 positive metastatic breast cancer (MBC) have resulted in si... more Aim Advances in the treatment of HER2 positive metastatic breast cancer (MBC) have resulted in significant improvements in survival time. Therefore, when estimating survival time, HER2 positive MBC now needs to be considered as a separate entity to HER2 negative MBC. Using data from trials of HER2 targeted therapies for HER2 positive MBC, we aimed to estimate worst-case, typical, and best-case scenarios for survival time to provide oncologists with a simple method to estimate and explain survival time to their patients in this situation. Method We sought randomised trials of HER2 targeted therapies in MBC published from 2001 to 2014. We recorded median progression free survival (PFS), median overall survival (OS), and extracted the following percentiles (represented scenario) from each OS curve: 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case). We also estimated these scenarios for each OS curve by multiplying its median by four simple multiples: 0...
Background: Progression Free Survival (PFS) is a common if controversial clinical trial endpoint.... more Background: Progression Free Survival (PFS) is a common if controversial clinical trial endpoint. There are concerns that drugs shown to improve PFS may not improve overall survival (OS) or produce discernable clinical benefits for patients (pts). Trials do not address directly how worthwhile disease control is to pts or routinely include Patient Reported Outcomes (PROs) to capture any improvements in well-being or QoL. PFS might excite clinical scientists but there are few prospective data showing a causal relationship between PFS and improved PROs such as arrest of the worst symptoms of disease or tolerable treatment side-effects. Nor do we know if pts' knowledge of their PFS status affects anxiety. Such issues are currently being explored in the Assessing the VALue to Pts of PFS (AVALPROFS) study. We report here what pts understood about the meaning of PFS, the therapeutic aims of treatment and the most important likely benefits for them. Methods: Experienced researchers conducted semi-structured interviews with pts prior to starting treatment with novel therapies shown to improve PFS. Pts had metastatic lung, breast, renal, gynaecological, head and neck cancers or malignant melanoma. Results: 74 pts (39 female, 35 male), mean age 66 yrs (range 32−85) participated. The most common tumour sites were lung 27(36.5%), breast 15(20.3%) and melanoma 15(20.3%). The majority of pts 46/74(62.2%) were currently symptomatic. Only 3(4%) recalled explicit use of the term PFS by their oncologist. Most 46(62.2%) had no idea what PFS meant, 20(27%) thought it was about 'controlling cancer' and 8(10.8%) 'length of survival'. When asked what they understood were the primary aims of treatment, although 68(91.9%) said 'to slow or stop the cancer', 36(48.6%) thought that this also meant 'living longer' and 25(33.8%) 'to help them feel better'. 31(41.9%) said that 'to live longer' was the most important aim and a majority 48(65%) were confident that these therapeutic aims would be realised. The primary personal treatment benefits they expected would be 'keeping cancer under control' 65(87.8%), 'providing hope' 44(59.5%), 'feeling better' 36(48.6%) and 'doing something' 31(41.9%). Additionally 30(40.5%) expected that with treatment they would 'live longer'. Conclusions: PFS is an alien concept for most pts; the word survival implies that the primary therapeutic aim and likely benefit will be to extend life. Not all drugs tested in clinical trials that show PFS benefits go on to produce OS gains, although controlling the cancer may still be worthwhile provided that the toxicities are manageable and/or pts gain symptomatic relief. Progression free interval may be a less confusing term to use when pts make decisions about further treatment. Conflict of interest: Other Substantive Relationships: The project is funded by Boehringer-Ingelheim via an unrestricted educational grant.
Purpose This study aimed to explore differences in physical activity and fitness between women wi... more Purpose This study aimed to explore differences in physical activity and fitness between women with metastatic breast cancer compared to healthy controls and factors associated with their physical activity levels. Methods Seventy-one women with metastatic breast cancer, aged (mean (SD)) 57.7 (9.5) and 2.9 (3.1)years after the onset of metastatic disease, and 71 healthy controls aged 55.0 (9.4) years participated. Of those with metastatic disease, 27 % had bone-only metastases, 35 % visceral-only metastases and 38 % bone and visceral metastases. Patient-reported outcomes and physical measures of muscle strength and aerobic fitness assessments were obtained. Participants wore a SenseWear® physical activity monitor over 7 days, and the average steps/ day and the time spent in moderate-to-vigorous intensity physical activity were determined. Results Women with metastases were significantly (i) less aerobically fit than the control group (25.3 (5.4) vs. 31.9 (6.1)mL•kg −1 •min −1 ; P<0.001); (ii) weaker (e.g. lower limb strength for the metastatic and control groups was 53.5 (23.7) vs. 76.0 (27.4)kg, respectively; P<0.001); (iii) less active, with the metastatic group attaining only 56 % of the mean daily step counts of the healthy women; and (iv) more symptomatic, reporting higher levels of fatigue and dyspnoea (P<0.001). Conclusion Women living in the community with metastatic breast cancer possessed lower aerobic fitness, reduced muscular strength and less daily physical activity compared to healthy counterparts. They also experienced poorer functioning and higher symptom burden. Implications for Cancer Survivors Women living with metastatic breast cancer may benefit from a physical activity programme to address their physical impairments.
Antitumour antibiotic containing regimens for metastatic breast cancer
Protocols, 2001
ABSTRACT Antitumour antibiotics are used in the management of metastatic breast cancer. Some of t... more ABSTRACT Antitumour antibiotics are used in the management of metastatic breast cancer. Some of these agents have demonstrated higher tumour response rates than non-antitumour antibiotic regimens, however a survival benefit has not been established in this setting. To identify and review the randomised evidence comparing anti-tumour antibiotic containing chemotherapy regimens with regimens not containing an anti-tumour antibiotic in the management of women with metastatic breast cancer. The specialised register maintained by the Editorial Base of the Cochrane Breast Cancer Group was searched on 2nd May, 2003 using the codes for &quot;advanced breast cancer&quot; and &quot;chemotherapy&quot;. Details of the search strategy and coding applied by the Group to create the register are described in the Group&#39;s module on The Cochrane Library. Randomised trials comparing anti-tumour antibiotic containing regimens with regimens not containing anti-tumour antibiotics in women with metastatic breast cancer. Data were collected from published trials. Studies were assessed for eligibility and quality, and data were extracted by two independent reviewers. Hazard ratios (HRs) were derived from time-to-event outcomes where possible, and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Quality of life and toxicity data were extracted where present. A primary analysis was conducted for all trials and by class of antitumour antibiotic. Thirty-three trials reporting on 45 treatment comparisons were identified. All trials published results for tumour response and 26 trials published time-to-event data for overall survival. The observed 4084 deaths in 5284 randomised women did not demonstrate a statistically significant difference in survival between regimens that contained antitumour antibiotics and those that did not (HR 0.97, 95% CI 0.91 to 1.03, P = 0.35) and no significant heterogeneity. Antitumour antibiotic regimens were favourably associated with time-to-progression (HR 0.84, 95% CI 0.77 to 0.91) and tumour response rates (odds ratio (OR) 1.34, 95% CI 1.21 to 1.48) although statistically significant heterogeneity was observed for these outcomes. These associations were consistent when the analysis was restricted to the 29 trials that reported on anthracyclines. Patients receiving anthracycline-containing regimens were also more likely to experience toxic events compared to patients receiving non-antitumour antibiotic regimens. No statistically significant difference was observed in any outcome between mitoxantrone-containing and non-antitumour antibiotic-containing regimens. Compared to regimens without antitumour antibiotics, regimens that contained these agents showed a statistically significant advantage for tumour response and time to progression in women with metastatic breast cancer but were not associated with an improvement in overall survival. The favourable effect on tumour response and time to progression observed in anthracycline-containing regimens was also associated with greater toxicity.
Platinum containing regimens for metastatic breast cancer
Protocols, 2001
Studies have reported high tumour response rates for platinum-containing regimens in the treatmen... more Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. To identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer. The specialised register maintained by the editorial base of the Cochrane Breast Cancer Group was searched on 2nd May 2003 using the codes for &quot;advanced breast cancer&quot;, &quot;chemotherapy&quot;. Details of the search strategy applied to create the register, and the procedure used to code references, are described in the Cochrane Breast Cancer Group module on The Cochrane Library. Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with metastatic breast cancer. Studies were assessed for eligibility and quality, and data (from published trials) were extracted by two independent reviewers. Hazard ratios were derived for time-to-event outcomes, where possible, and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data (not available) were extracted where present. Thirteen eligible trials were identified, of which 12 had published time-to-event data. The quality of randomisation was generally not described.Data, based on an estimated 987 deaths in 1377 women, was unable to show a statistically significant difference in favour of platinum-containing regimens. The hazard ratio (HR) for overall survival was 1.00 (95% confidence interval (CI) 0.88 to 1.15, p=0.96), with minor heterogeneity. Results were similar when the analysis was limited to trials in women receiving first line chemotherapy. There was no statistically significant difference in favour of platinum-containing regimens for time to progression (overall HR of 1.06 (95% CI 0.95 to 1.19, p=0.31) although there was marked evidence of heterogeneity (p&lt; 0.0001). There was a statistically significant difference in overall response in favour of platinum-containing regimens (OR 1.47; 95% CI 1.23 to 1.76, p=0.0001). However, there was strong statistical evidence of heterogeneity (p &lt; 0.00010) probably reflecting the varying efficacy of the comparator regimens used in the trials. Heterogeneity may also reflect the differences, and difficulties, in assessing response. Women receiving platinum-containing regimens experienced statistically significant greater toxicity levels for leukopenia, hair loss, nausea and vomiting and anaemia compared with those receiving non-platinum regimens. In view of the significant excess toxicity, lack of progression or survival benefit and the availability of less toxic active agents it is difficult to justify the use of platinum-containing regimens, particularly as first line treatment for women with metastatic breast cancer in routine clinical practice. Ongoing trials are examining the possibility of synergy between platins and trastuzamab, a monoclonal antibody treatment. No randomised trials containing oxalplatin were identified for the present review.
Neoadjuvant chemotherapy with sequential anthracycline–docetaxel with gemcitabine for large operable or locally advanced breast cancer: ANZ 0502 (NeoGem)
The Breast, 2014
Neoadjuvant chemotherapy has a sound rationale for use in women with large operable breast cancer... more Neoadjuvant chemotherapy has a sound rationale for use in women with large operable breast cancer, and achievement of pathological complete response (pCR) is prognostic. Epirubicin and cyclophosphamide followed by docetaxel is a standard chemotherapy regimen for early breast cancer. In metastatic breast cancer the combination of gemcitabine and a taxane has shown promising results. This phase II study investigated the efficacy and safety of incorporating gemcitabine into neoadjuvant therapy. Female patients with operable breast cancer that was clinically T2 (≥3 cm) or T3-4, N0-1, M0 were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin and cyclophosphamide followed by docetaxel and gemcitabine, plus trastuzumab if HER2-positive. The primary endpoint was the pathological complete response (pCR) rate in the breast in separate HER2-negative and HER2-positive cohorts. Secondary endpoints included pCR in both the breast and axillary lymph nodes, clinical and radiological response rates, disease free survival and safety. 81 patients were enrolled: 63 HER2-negative and 18 HER2-positive. 67 (84%) completed all cycles of chemotherapy, and 78 (96%) proceeded to surgery. pCR was achieved by 12 (20%) patients with HER2-negative, and 9 (53%) with HER2-positive disease. At the first interim analysis, addition of prophylactic G-CSF was recommended due to excess neutropenia. The HER2-negative cohort was closed to accrual because it did not meet the pre-specified target for pCR, and the HER2-positive cohort was closed due to slow accrual. At a median follow-up of 24 months, 12 of 81 (15%) patients had experienced a relapse of their breast cancer. Neoadjuvant gemcitabine, when added to docetaxel, after epirubicin and cyclophosphamide, did not reach the pre-specified expectations for pCR rate in HER2-negative tumours. Excess neutropenia was observed, requiring growth factor support. Addition of gemcitabine to docetaxel in this schedule cannot be recommended. Australia and New Zealand Clinical Trials Registry (www.anzctr.org.au) registration number ACTRN12606000191594.
Research ne of the major concerns for women diagnosed with early breast cancer (BC) is their risk... more Research ne of the major concerns for women diagnosed with early breast cancer (BC) is their risk of developing metastatic cancer (MBC). 1 Information on the risk of and prognosis for patients with MBC is important to help patients make decisions about treatment and plan for the future. It is also important for health service planning and identifying research priorities. Currently, cancer registries do not routinely report this information. Consumer groups in Australia 2 and internationally 3 have urged for improved data collection on cancer recurrence and reporting. Over the past 20 years, cancer registries have documented continued improvements in survival among patients with BC. 4 These survival gains have been attributed to advances in treatment, particularly systemic adjuvant therapies after pivotal trials, and to a lesser extent, BC screening programs. 5,6 However, the gains for women with early BC in terms of their risk of developing MBC have not been well documented. Earlier studies may no longer be relevant to contemporary populations. At present, clinicians generally rely on published clinical trials for information on these outcomes, but the extent to which trial data can be applied to the general population of women with BC is not known. We aimed to report Australian population-based estimates of the incidence of MBC for women initially diagnosed with non-metastatic BC. We were particularly interested in the experiences of women aged 70 years and older, and of women from regional and remote areas, two populations not well represented in clinical trials. Methods All women aged 18 years and older diagnosed with invasive (not intraductal) localised or regional BC between 1 January 2001 and 31 December 2002 and recorded on the New South Wales Central Cancer Registry (CCR) were included. Patients were excluded if the extent of disease spread at diagnosis was recorded as distant or unknown, or if they had no hospital care recorded on the NSW Admitted Patient Data Collection (APDC). Data sources Incidence of metastatic breast cancer in an Australian population-based cohort of women with non-metastatic breast cancer at diagnosis O Research Objectives: To estimate the incidence of metastatic breast cancer (MBC) in Australian women with an initial diagnosis of non-metastatic breast cancer. Design, setting and participants: A population-based cohort study of all women with non-metastatic breast cancer registered on the New South Wales Central Cancer Register (CCR) in 2001 and 2002 who received care in a NSW hospital. Main outcome measures: 5-year cumulative incidence of MBC; prognostic factors for MBC. Results: MBC was recorded within 5 years in 218 of 4137 women with localised node-negative disease (5-year cumulative incidence, 5.3%; 95% CI, 4.6%-6.0%); and 455 of 2507 women with regional disease (5-year cumulative incidence, 18.1%; 95% CI, 16.7%-19.7%). The hazard rate for developing MBC was highest in the second year after the initial diagnosis of breast cancer. Determinants of increased risk of MBC were regional disease at diagnosis, age less than 50 years and living in an area of lower socioeconomic status. Conclusions: Our Australian population-based estimates are valuable when communicating average MBC risks to patients and planning clinical services and trials. Women with node-negative disease have a low risk of developing MBC, consistent with outcomes of adjuvant clinical trials. Regional disease at diagnosis remains an important prognostic factor.
... Periodic funny turns. ... A 48-year-old woman with no previous history of ill health had a te... more ... Periodic funny turns. ... A 48-year-old woman with no previous history of ill health had a temporary loss of consciousness (syncopal episode) while playing tennis. She became flushed in the face, felt light-headed, and believed she was going to collapse. ...
Background Trastuzumab-a humanised monoclonal antibody against HER2-has been shown to improve dis... more Background Trastuzumab-a humanised monoclonal antibody against HER2-has been shown to improve diseasefree survival after chemotherapy in women with HER2-positive early breast cancer. We investigated the drug's eff ect on overall survival after a median follow-up of 2 years in the Herceptin Adjuvant (HERA) study. Methods HERA is an international multicentre randomised trial that compared 1 or 2 years of trastuzumab treatment with observation alone after standard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node positive or high-risk node negative breast cancer. 5102 women participated in the trial; we analysed data from 1703 women who had been randomised for treatment with trastuzumab for 1 year and 1698 women from the control group, with median follow-up of 23•5 months (range 0-48 months). The primary endpoint of the trial was diseasefree survival. Here, we assess overall survival, a secondary endpoint. Analyses were done on an intent-to-treat basis. This trial is registered with the European Clinical Trials Database, number 2005-002385-11. Findings 97 (5•7%) patients randomised to observation alone and 58 (3•4%) patients randomised to 1 year of treatment with trastuzumab were lost to follow-up. 172 women stopped trastuzumab prematurely. 59 deaths were reported for trastuzumab and 90 in the control group. The unadjusted hazard ratio (HR) for the risk of death with trastuzumab compared with observation alone was 0•66 (95% CI 0•47-0•91; p=0•0115). 218 disease-free survival events were reported with trastuzumab compared with 321 in the control group. The unadjusted HR for the risk of an event with trastuzumab compared with observation alone was 0•64 (0•54-0•76; p<0•0001). Interpretation Our results show that 1 year of treatment with trastuzumab after adjuvant chemotherapy has a signifi cant overall survival benefi t after a median follow-up of 2 years. The emergence of this benefi t after only 2 years reinforces the importance of trastuzumab in the treatment of women with HER2-positive early breast cancer.
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Papers by N. Wilcken