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Parviz Ghadirian, André Robidoux,
Edgard Nassif,
Ginette Martin,
Claude Potvin,
Erica Patocskai,
Rami Younan,
Nicole Larouche,
Annie Venne,
Shiyu Zhang,
Robert Royer,
Steven A Narod
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ABSTRACT: OBJECTIVE: To estimate the prevalence of BRCA mutations among early-onset and familial French-Canadian breast cancer patients in a single institution. METHODS: Study subjects were French-Canadian women with DCIS or invasive breast cancer (incident or prevalent) who were treated and followed at a single breast cancer clinic affiliated with the Research Center of University of Montreal (CRCHUM), who were either aged less than 50 years at diagnosis or who were 50 years or older and with at least two affected first- or second-degree relatives. Subjects were tested for six founder mutations (three in BRCA1 and three in BRCA2). RESULTS: 1,093 eligible cases were tested. Of these, 56 women (5.1%) were mutation carriers, including 43 BRCA2 carriers and 13 BRCA1 carriers. The prevalence of mutations was 5.3% for unselected women aged 50 and less and was 4.6% for familial cases over age 50. The prevalence of mutations was 3.3% for women with DCIS and was 5.3% for women with invasive cancer. CONCLUSIONS: It is rational to offer genetic testing to all French-Canadian women diagnosed recently or in the past with either DCIS or invasive breast cancer before age 50 or with familial breast cancer above age 50.
Clinical Genetics 04/2013; · 3.13 Impact Factor
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ABSTRACT: Background
We lack comprehensive information about the extent of out-of-pocket costs after diagnosis of early breast cancer and their effects on the family's financial situation.Methods
This longitudinal study assessed out-of-pocket costs and wage losses during the first year after diagnosis of early breast cancer among Canadian women and spouses. Out-of-pocket costs for treatments and follow-up, consultations with other practitioners, home help, clothing, and natural health products were estimated, with information collected from telephone interviews. Generalized linear models were used to identify women at risk of having higher costs and the effects of out-of-pocket costs on perceptions of the family's financial situation.ResultsOverall, 829 women (participation, 86.2%) and 391 spouses participated. Women's median net out-of-pocket costs during the year after diagnosis were $1002 (2003 Canadian dollars; mean = $1365; SD = $1238), and 74.4% of these costs resulted from treatments and follow-up. Spouses' median costs were $111 (mean = $234; SD = $320), or 9% of couples' total expenses. In multivariable analyses, the percentage of women with out-of-pocket costs of $1773 or more (upper quartile) was statistically significantly associated with higher education, working at diagnosis, living more than 50 km from the hospital where surgery was performed, and having two and three different types of adjuvant treatment (all 2-sided P values ≤ .01). However, when considered simultaneously with wage losses, out-of-pocket costs were not associated with perceived deterioration in the family's financial situation; rather, wage losses were the driving factor.Conclusions
Overall, out-of-pocket costs from breast cancer for the year after diagnosis are probably not unmanageable for most women. However, some women were at higher risk of experiencing financial burden resulting from these costs.
CancerSpectrum Knowledge Environment 01/2013; · 14.07 Impact Factor
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Alexander H G Paterson,
Stewart J Anderson,
Barry C Lembersky,
Louis Fehrenbacher,
Carla I Falkson,
Karen M King,
Lorna M Weir,
Adam M Brufsky,
Shaker Dakhil,
Thomas Lad,
Luis Baez-Diaz,
Julie R Gralow, André Robidoux,
Edith A Perez,
Ping Zheng,
Charles E Geyer,
Sandra M Swain,
Joseph P Costantino,
Eleftherios P Mamounas,
Norman Wolmark
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ABSTRACT: Bisphosphonates are thought to act through the osteoclast by changing bone microenvironment. Previous findings of adjuvant clodronate trials in different populations with operable breast cancer have been mixed. The National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-34 aims to ascertain whether oral clodronate can improve outcomes in women with primary breast cancer.
NSABP B-34 is a multicentre, randomised, double-blind, placebo-controlled study in 3323 women with stage 1-3 breast cancer. After surgery to remove the tumour, patients were stratified by age, axillary nodes, and oestrogen and progesterone receptor status and randomly assigned in a 1:1 ratio to either oral clodronate 1600 mg daily for 3 years (n=1662) or placebo (1661). The primary endpoint was disease-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00009945.
Median follow-up was 90·7 months (IQR 82·7-100·0) and 3311 patients had data for this period. Disease-free survival did not differ between groups (286 events in the clodronate group vs 312 in the placebo group; hazard ratio 0·91, 95% CI 0·78-1·07; p=0·27). Moreover, no differences were recorded for overall survival (0·84, 0·67-1·05; p=0·13), recurrence-free interval (0·83, 0·67-1·04; p=0·10), or bone metastasis-free interval (0·77, 0·55-1·07; p=0·12). Non-bone metastasis-free interval was slightly increased with clodronate (0·74, 0·55-1·00; p=0·047). Analyses in women age 50 years or older on study entry showed benefits of clodronate for recurrence-free interval (0·75, 0·57-0·99; p=0·045), bone metastasis-free interval (0·62, 0·40-0·95; p=0·027), and non-bone metastasis-free interval (0·63, 0·43-0·91; p=0·014), but not for overall survival (0·80, 0·61-1·04, p=0·094). Adherence to treatment at 3 years was 56% for the clodronate group and 60% for the placebo group. Grade 3 or higher liver dysfunction was noted in 23 of 1612 patients in the clodronate group and 12 of 1623 patients in the placebo group; grade 3-4 diarrhoea was noted in 28 patients in the clodronate group and in ten in the placebo group. There was one possible case of osteonecrosis of the jaw in the clodronate group.
Findings of NSABP B-34 suggest that bisphosphonates might have anticancer benefits for older postmenopausal women. A meta-analysis of adjuvant bisphosphonate trials is suggested before recommendations for use in non-osteoporotic postmenopausal women with primary breast cancer are made.
National Cancer Institute, Bayer Oy (formerly Schering Oy).
The lancet oncology 06/2012; 13(7):734-42. · 14.47 Impact Factor
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John R Mackey,
Robert S Kerbel,
Karen A Gelmon,
Deanna M McLeod,
Stephen K Chia,
Daniel Rayson,
Sunil Verma,
Loretta L Collins,
Alexander H G Paterson, André Robidoux,
Kathleen I Pritchard
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ABSTRACT: Angiogenesis is critical for tumor growth and a promising therapeutic target. This review will summarize and analyze data from clinical trials of anti-angiogenic agents in the treatment of breast cancer (BC).
A systematic search of PubMed and conference databases was performed to identify reports of randomized clinical trials investigating specific anti-angiogenic agents in the treatment of BC.
Phase III trials in advanced BC have demonstrated a reduction in the risk of disease progression (22-52%), improved response rates and net improvements in progression-free survival of 1.2 to 5.5 months, but no significant improvements in overall survival with the addition of bevacizumab to chemotherapy. Results of phase III trials in early breast cancer have been inconsistent. Bevacizumab-containing regimens have also been associated with higher overall adverse event rates compared to chemotherapy alone. Phase III trials of the tyrosine kinase inhibitor sunitinib were negative, while randomized phase II trials of sorafenib and pazopanib have improved some outcomes when combined with chemotherapy or targeted therapy compared to controls. In addition to expected vascular class safety signals, tyrosine kinase inhibitors show "off-target" side effects. Ongoing clinical trials evaluating combinatorial strategies based on biological synergies and translational studies identifying biological predictors of response will be crucial to establish meaningful clinical benefits in selected BC populations.
Most trials of anti-angiogenic agents in BC have reported improved response rate and progression-free survival but no increase in overall survival compared to chemotherapy alone. Optimizing the therapeutic indices of these agents is a focus of ongoing research and will be critical to their future development.
Cancer treatment reviews 02/2012; 38(6):673-88. · 5.30 Impact Factor
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Harry D Bear,
Gong Tang,
Priya Rastogi,
Charles E Geyer, André Robidoux,
James N Atkins,
Luis Baez-Diaz,
Adam M Brufsky,
Rita S Mehta,
Louis Fehrenbacher,
James A Young,
Francis M Senecal,
Rakesh Gaur,
Richard G Margolese,
Paul T Adams,
Howard M Gross,
Joseph P Costantino,
Sandra M Swain,
Eleftherios P Mamounas,
Norman Wolmark
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ABSTRACT: Bevacizumab and the antimetabolites capecitabine and gemcitabine have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer. The primary aims of this trial were to determine whether the addition of capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel, followed by doxorubicin plus cyclophosphamide, would increase the rates of pathological complete response in the breast in women with operable, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and whether adding bevacizumab to these chemotherapy regimens would increase the rates of pathological complete response.
We randomly assigned 1206 patients to receive neoadjuvant therapy consisting of docetaxel (100 mg per square meter of body-surface area on day 1), docetaxel (75 mg per square meter on day 1) plus capecitabine (825 mg per square meter twice a day on days 1 to 14), or docetaxel (75 mg per square meter on day 1) plus gemcitabine (1000 mg per square meter on days 1 and 8) for four cycles, with all regimens followed by treatment with doxorubicin-cyclophosphamide for four cycles. Patients were also randomly assigned to receive or not to receive bevacizumab (15 mg per kilogram of body weight) for the first six cycles of chemotherapy.
The addition of capecitabine or gemcitabine to docetaxel therapy, as compared with docetaxel therapy alone, did not significantly increase the rate of pathological complete response (29.7% and 31.8%, respectively, vs. 32.7%; P=0.69). Both capecitabine and gemcitabine were associated with increased toxic effects--specifically, the hand-foot syndrome, mucositis, and neutropenia. The addition of bevacizumab significantly increased the rate of pathological complete response (28.2% without bevacizumab vs. 34.5% with bevacizumab, P=0.02). The effect of bevacizumab on the rate of pathological complete response was not the same in the hormone-receptor-positive and hormone-receptor-negative subgroups. The addition of bevacizumab increased the rates of hypertension, left ventricular systolic dysfunction, the hand-foot syndrome, and mucositis.
The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response, which was the primary end point of this study. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00408408.).
New England Journal of Medicine 01/2012; 366(4):310-20. · 53.30 Impact Factor
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Eva Grunfeld,
Jim A Julian,
Gregory Pond,
Elizabeth Maunsell,
Douglas Coyle,
Amy Folkes,
Anil A Joy,
Louise Provencher,
Daniel Rayson,
Dorianne E Rheaume,
Geoffrey A Porter,
Lawrence F Paszat,
Kathleen I Pritchard, André Robidoux,
Sally Smith,
Jonathan Sussman,
Susan Dent,
Jeffrey Sisler,
Jennifer Wiernikowski,
Mark N Levine
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ABSTRACT: An Institute of Medicine report recommends that patients with cancer receive a survivorship care plan (SCP). The trial objective was to determine if an SCP for breast cancer survivors improves patient-reported outcomes.
Women with early-stage breast cancer who completed primary treatment at least 3 months previously were eligible. Consenting patients were allocated within two strata: less than 24 months and ≥ 24 months since diagnosis. All patients were transferred to their own primary care physician (PCP) for follow-up. In addition to a discharge visit, the intervention group received an SCP, which was reviewed during a 30-minute educational session with a nurse, and their PCP received the SCP and guideline on follow-up. The primary outcome was cancer-related distress at 12 months, assessed by the Impact of Event Scale (IES). Secondary outcomes included quality of life, patient satisfaction, continuity/coordination of care, and health service measures.
Overall, 408 survivors were enrolled through nine tertiary cancer centers. There were no differences between groups on cancer-related distress or on any of the patient-reported secondary outcomes, and there were no differences when the two strata were analyzed separately. More patients in the intervention than control group correctly identify their PCP as primarily responsible for follow-up (98.7% v 89.1%; difference, 9.6%; 95% CI, 3.9 to 15.9; P = .005).
The results do not support the hypothesis that SCPs are beneficial for improving patient-reported outcomes. Transferring follow-up to PCPs is considered an important strategy to meet the demand for scarce oncology resources. SCPs were no better than a standard discharge visit with the oncologist to facilitate transfer.
Journal of Clinical Oncology 12/2011; 29(36):4755-62. · 18.37 Impact Factor
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ABSTRACT: Patients with breast cancer incur out-of-pocket costs when they receive adjuvant radiation. These treatments are administered in dedicated centers on a daily basis over 4 to 5 weeks. We assessed the extent of out-of-pocket costs to access radiotherapy and identified women at risk of experiencing higher costs.
This prospective study was conducted among 800 women from eight Quebec hospitals (participation, 86%), of whom 693 women received adjuvant radiotherapy. Costs to access treatment (transportation, parking, lodging, and meals) were estimated on the basis of information collected by telephone interviews. Generalized linear models were used to identify women at risk of having higher costs.
Mean and median total costs (including financial aid received) to access radiotherapy were 445 Canadian dollars (Can$; standard deviation, Can$407) and Can$311, respectively. Women who lived at home but far from the radiotherapy center had the highest risk of experiencing weekly costs of at least Can$122 (highest quartile; prevalence ratio [PR], 5.8; 95% CI, 4.7 to 7.1) followed by women who lived away from home and farther from the center (PR, 4.5; 95% CI, 3.4 to 6.0) and by women who lived away from home and closer to the center (PR, 2.14; 95% CI, 1.3 to 3.5). When women stayed at a cancer lodge during treatment, costs were reduced by 80%.
Considered in and of themselves, out-of-pocket costs for access to radiotherapy appeared relatively modest. Financial assistance initiatives for women who lived away from home during treatments contributed to a substantial reduction of access costs. These efforts should be maintained, but financial assistance should also target patients with cancer who live at home during treatments but have to travel relatively long distances on a daily basis.
Journal of Clinical Oncology 09/2011; 29(30):4007-13. · 18.37 Impact Factor
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Karen A Gelmon,
Marc Tischkowitz,
Helen Mackay,
Kenneth Swenerton, André Robidoux,
Katia Tonkin,
Hal Hirte,
David Huntsman,
Mark Clemons,
Blake Gilks,
Rinat Yerushalmi,
Euan Macpherson,
James Carmichael,
Amit Oza
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ABSTRACT: Olaparib (AZD2281) is a small-molecule, potent oral poly(ADP-ribose) polymerase (PARP) inhibitor. We aimed to assess the safety and tolerability of this drug in patients without BRCA1 or BRCA2 mutations with advanced triple-negative breast cancer or high-grade serous and/or undifferentiated ovarian cancer.
In this phase 2, multicentre, open-label, non-randomised study, women with advanced high-grade serous and/or undifferentiated ovarian carcinoma or triple-negative breast cancer were enrolled and received olaparib 400 mg twice a day. Patients were stratified according to whether they had a BRCA1 or BRCA2 mutation or not. The primary endpoint was objective response rate by Response Evaluation Criteria In Solid Tumors (RECIST). All patients who received treatment were included in the analysis of toxic effects, and patients who had measurable lesions at baseline were included in the primary efficacy analysis. This trial is registered at ClinicalTrials.gov, number NCT00679783.
91 patients were enrolled (65 with ovarian cancer and 26 breast cancer) and 90 were treated between July 8, 2008, and Sept 24, 2009. In the ovarian cancer cohorts, 64 patients received treatment. 63 patients had target lesions and therefore were evaluable for objective response as per RECIST. In these patients, confirmed objective responses were seen in seven (41%; 95% CI 22-64) of 17 patients with BRCA1 or BRCA2 mutations and 11 (24%; 14-38) of 46 without mutations. No confirmed objective responses were reported in patients with breast cancer. The most common adverse events were fatigue (45 [70%] of patients with ovarian cancer, 13 [50%] of patients with breast cancer), nausea (42 [66%] and 16 [62%]), vomiting (25 [39%] and nine [35%]), and decreased appetite (23 [36%] and seven [27%]).
Our study suggests that olaparib is a promising treatment for women with ovarian cancer and further assessment of the drug in clinical trials is needed.
AstraZeneca.
The lancet oncology 08/2011; 12(9):852-61. · 14.47 Impact Factor
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Priya Rastogi,
Marc E Buyse,
Sandra M Swain,
Samuel A Jacobs, André Robidoux,
Marcia K Liepman,
Eduardo R Pajon,
Philip A Dy,
Juan G Posada,
Marianne K Melnik,
Fanny Piette,
Charles E Geyer,
Elfetherios P Mamounas,
Norman Wolmark
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ABSTRACT: Bevacizumab with chemotherapy improves outcomes in patients with metastatic breast cancer (MBC). The purpose of this trial was to determine the activity and safety profile of neoadjuvant bevacizumab with chemotherapy in women with locally advanced breast cancer (LABC).
Between November 2006 and August 2007, 45 women with HER2(-) LABC began preoperative standard AC (doxorubicin [Adriamycin], cyclophosphamide) × 4 cycles followed by docetaxel 75 mg/m(2) intravenously (I.V.) on day 1 and capecitabine 825 mg/m(2) twice daily on days 1-14 (TX, docetaxel [Taxotere] and capecitabine [Xeloda]) every 21 days for 4 cycles. Bevacizumab 15 mg/kg I.V. was given concurrently with chemotherapy every 21 days for a total of 6 preoperative doses. Postoperatively bevacizumab was resumed for a total of 10 doses. The primary endpoint was pathologic complete response (pCR) in the breast.
Thirty patients (66.7%) had stage IIIA disease, 12 (26.7%) patients had stage IIIB, and 3 patients (6.7%) had stage IIIC. Of these, 10 (22%) had inflammatory breast cancer (IBC), and 27 (60%) had estrogen receptor (ER)(+) disease. A pCR in the breast with negative axillary nodes was documented in 4 (9%) of 45 patients. Toxicities that were seen with AC and bevacizumab included fatigue (grade 2/3; 31% and 9%, respectively), mucositis (grade 2/3; 29% and 2%, respectively), and headache (grade 2/3; 16% and 7%, respectively). Toxicities seen with TX and bevacizumab included mucositis (grade 2/3; 48% and 25%, respectively), fatigue (grade 2/3; 43% and 18%, respectively), and hand-foot syndrome (grade 2/3; 34% and 23%, respectively).
This regimen demonstrated only modest activity with substantial toxicity and does not appear to warrant further evaluation.
Clinical Breast Cancer 05/2011; 11(4):228-34. · 2.38 Impact Factor
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ABSTRACT: Many agents are being studied for the treatment of metastatic breast cancer (MBC), yet few studies have demonstrated longer overall survival (OS), the primary measure of clinical benefit in MBC. This paper examines the key endpoints in clinical trials and U.S. Food and Drug Administration (FDA) approvals of drugs for MBC. PubMed was searched (1980 to October 2009) for reports of phase III trials investigating chemotherapy and/or targeted therapy agents in MBC. FDA approval histories (1996-2009) for cytotoxic and biological agents indicated for MBC were reviewed. Of the 73 phase III MBC trials reviewed, a strikingly small proportion of trials demonstrated a gain in OS duration (12%, n = 9). OS gains were less frequently noted in first-line trials (8%) than in trials of second-line plus other lines of therapy (22%). Few trials were designed with the capacity to detect OS effects. Among 37 phase III trials conducted in the last 15 years, only three systemic therapies were approved for first-line use and nine were approved for use as second-line or other lines of therapy. Of these, only four were supported by results showing longer survival times. There is substantial discordance among the design and conduct of clinical trials, FDA drug approval, and the current view of OS as the ultimate measure of clinical benefit. There is an urgent need to reassess standards for clinical benefit in MBC and to establish guidelines for study design and conduct and drug approval. In the end, what matters most is ensuring rapid access to safe and effective oncology treatments.
The Oncologist 01/2011; 16(1):25-35. · 3.91 Impact Factor
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David N Krag,
Stewart J Anderson,
Thomas B Julian,
Ann M Brown,
Seth P Harlow,
Joseph P Costantino,
Takamaru Ashikaga,
Donald L Weaver,
Eleftherios P Mamounas,
Lynne M Jalovec,
Thomas G Frazier,
R Dirk Noyes, André Robidoux,
Hugh Mc Scarth,
Norman Wolmark
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ABSTRACT: Sentinel-lymph-node (SLN) surgery was designed to minimise the side-effects of lymph-node surgery but still offer outcomes equivalent to axillary-lymph-node dissection (ALND). The aims of National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-32 were to establish whether SLN resection in patients with breast cancer achieves the same survival and regional control as ALND, but with fewer side-effects.
NSABP B-32 was a randomised controlled phase 3 trial done at 80 centres in Canada and the USA between May 1, 1999, and Feb 29, 2004. Women with invasive breast cancer were randomly assigned to either SLN resection plus ALND (group 1) or to SLN resection alone with ALND only if the SLNs were positive (group 2). Random assignment was done at the NSABP Biostatistical Center (Pittsburgh, PA, USA) with a biased coin minimisation approach in an allocation ratio of 1:1. Stratification variables were age at entry (≤ 49 years, ≥ 50 years), clinical tumour size (≤ 2·0 cm, 2·1-4·0 cm, ≥ 4·1 cm), and surgical plan (lumpectomy, mastectomy). SLN resection was done with a blue dye and radioactive tracer. Outcome analyses were done in patients who were assessed as having pathologically negative sentinel nodes and for whom follow-up data were available. The primary endpoint was overall survival. Analyses were done on an intention-to-treat basis. All deaths, irrespective of cause, were included. The mean time on study for the SLN-negative patients with follow-up information was 95·6 months (range 70·1-126·7). This study is registered with ClinicalTrials.gov, number NCT00003830.
5611 women were randomly assigned to the treatment groups, 3989 had pathologically negative SLN. 309 deaths were reported in the 3986 SLN-negative patients with follow-up information: 140 of 1975 patients in group 1 and 169 of 2011 in group 2. Log-rank comparison of overall survival in groups 1 and 2 yielded an unadjusted hazard ratio (HR) of 1·20 (95% CI 0·96-1·50; p=0·12). 8-year Kaplan-Meier estimates for overall survival were 91·8% (95% CI 90·4-93·3) in group 1 and 90·3% (88·8-91·8) in group 2. Treatment comparisons for disease-free survival yielded an unadjusted HR of 1·05 (95% CI 0·90-1·22; p=0·54). 8-year Kaplan-Meier estimates for disease-free survival were 82·4% (80·5-84·4) in group 1 and 81·5% (79·6-83·4) in group 2. There were eight regional-node recurrences as first events in group 1 and 14 in group 2 (p=0·22). Patients are continuing follow-up for longer-term assessment of survival and regional control. The most common adverse events were allergic reactions, mostly related to the administration of the blue dye.
Overall survival, disease-free survival, and regional control were statistically equivalent between groups. When the SLN is negative, SLN surgery alone with no further ALND is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes.
US Public Health Service, National Cancer Institute, and Department of Health and Human Services.
The lancet oncology 10/2010; 11(10):927-33. · 14.47 Impact Factor
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Victor G Vogel,
Joseph P Costantino,
D Lawrence Wickerham,
Walter M Cronin,
Reena S Cecchini,
James N Atkins,
Therese B Bevers,
Louis Fehrenbacher,
Eduardo R Pajon,
James L Wade, André Robidoux,
Richard G Margolese,
Joan James,
Carolyn D Runowicz,
Patricia A Ganz,
Steven E Reis,
Worta McCaskill-Stevens,
Leslie G Ford,
V Craig Jordan,
Norman Wolmark
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ABSTRACT: The selective estrogen-receptor modulator (SERM) tamoxifen became the first U.S. Food and Drug Administration (FDA)-approved agent for reducing breast cancer risk but did not gain wide acceptance for prevention, largely because it increased endometrial cancer and thromboembolic events. The FDA approved the SERM raloxifene for breast cancer risk reduction following its demonstrated effectiveness in preventing invasive breast cancer in the Study of Tamoxifen and Raloxifene (STAR). Raloxifene caused less toxicity (versus tamoxifen), including reduced thromboembolic events and endometrial cancer. In this report, we present an updated analysis with an 81-month median follow-up. STAR women were randomly assigned to receive either tamoxifen (20 mg/d) or raloxifene (60 mg/d) for 5 years. The risk ratio (RR; raloxifene:tamoxifen) for invasive breast cancer was 1.24 (95% confidence interval [CI], 1.05-1.47) and for noninvasive disease, 1.22 (95% CI, 0.95-1.59). Compared with initial results, the RRs widened for invasive and narrowed for noninvasive breast cancer. Toxicity RRs (raloxifene:tamoxifen) were 0.55 (95% CI, 0.36-0.83; P = 0.003) for endometrial cancer (this difference was not significant in the initial results), 0.19 (95% CI, 0.12-0.29) for uterine hyperplasia, and 0.75 (95% CI, 0.60-0.93) for thromboembolic events. There were no significant mortality differences. Long-term raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive disease and grew closer over time to tamoxifen in preventing noninvasive disease, with far less toxicity (e.g., highly significantly less endometrial cancer). These results have important public health implications and clarify that both raloxifene and tamoxifen are good preventive choices for postmenopausal women with elevated risk for breast cancer.
Cancer Prevention Research 06/2010; 3(6):696-706. · 4.91 Impact Factor
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André Robidoux,
Aman U Buzdar,
Emmanuel Quinaux,
Samuel Jacobs,
Priya Rastogi,
Virginie Fourchotte,
Rami J Younan,
Eduardo R Pajon,
Ibrahim A Shalaby,
Ajit M Desai,
Louis Fehrenbacher,
Charles E Geyer,
Eleftherios P Mamounas,
Norman Wolmark
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ABSTRACT: Background: Neoadjuvant chemotherapy has become standard treatment for women with locally advanced breast cancer (LABC). Various regimens have explored the addition of newer agents to determine safety and efficacy. The aim of this phase II study was to incorporate albumin-bound paclitaxel with sequential anthracycline-based therapy. Patients and Methods: Sixty-six women with LABC but without prior treatment and regardless of hormone receptor or HER2 status were enrolled. All patients were to receive albumin-bound paclitaxel weekly for 12 weeks followed by 5-fluorouracil/ epirubicin/cyclophosphamide (FEC) every 3 weeks for 4 cycles. Trastuzumab was allowed in HER2-positive (HER2+) patients. Primary endpoint was pathologic complete response (pCR; CR) in breast. Secondary endpoints included pCR in breast and nodes, clinical CR, 2-year progression-free survival, and overall survival. Results: Sixty-five patients received at least 1 dose of chemotherapy and were included in this analysis. Sixty-three patients completed 4 cycles of albumin-bound paclitaxel. Sixty-two patients received at least 1 dose of FEC, and 58 completed 4 cycles. Seventeen of 19 HER2+ women received trastuzumab. The pCR in breast was 29% (19 of 65). For the HER2+ subset, the pCR was 58% (11 of 19). Both albumin-bound paclitaxel and FEC were well tolerated. The most significant toxicities were grade 2/3 neuropathy (16%) with albumin-bound paclitaxel and grade 3/4 febrile neutropenia (7%) with FEC. Conclusion: Albumin-bound paclitaxel given over 12 weeks is well tolerated. Albumin-bound paclitaxel should be further evaluated in a randomized setting in both adjuvant and neoadjuvant trials.
Clinical Breast Cancer 02/2010; 10(1):81-6. · 2.38 Impact Factor
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Rowan Chlebowski,
Jack Cuzick,
Dereck Amakye,
Ingo Bauerfeind,
Aman Buzdar,
Stephen Chia,
Bruno Cutuli,
Rick Linforth,
Nicolaì Maass,
Shinzaburo Noguchi, André Robidoux,
Sunil Verma,
Peyman Hadji
Breast (Edinburgh, Scotland) 09/2009; 18 Suppl 2:S1-11. · 2.09 Impact Factor
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ABSTRACT: We describe the frequency of, satisfaction with, and characteristics associated with confidant use among patients and their spouse in the year after diagnosis of non-metastatic breast cancer.
In a prospective study of 308 women diagnosed in 1996-97 in Quebec and their spouses, participants were interviewed about confidant use 2 weeks, 3 and 12 months after treatment start. Study completion among eligible individuals was high (patients, 86%; spouses, 84%).
Compared to before diagnosis when 55% of patients reported confiding in >or=1 individuals, 84% reported confiding since diagnosis when interviewed 2 weeks after treatment start (prevalence ratio (PR(2 weeks)) = 1.43, p < 0.0001). Spouses reported a greater increase in confiding (PR(2 weeks) = 1.97, p < 0.0001). Nonetheless, spouses were significantly less likely to report confidant use at any given time (PRs comparing spouses to patients: range 0.43-0.61). The primary confidant types with increases were nurses (both couple members) and physicians (patients). Most patients and spouses (84% to 93%) were satisfied with their confidant situation. At 3 months, the woman's having >or=2 types of adjuvant therapy predicted greater confidant use in both partners.
Judging from the relative differences in confidant use, the effect of diagnosis of non-metastatic breast cancer on natural support-seeking behaviour over time is at least as strong among spouses as among their wives.
The majority of women and their spouses appear satisfied with their confidant situation, even in the first months after diagnosis when this type of support-seeking behaviour increased in both partners.
Journal of Cancer Survivorship 09/2009; 3(4):202-11. · 2.63 Impact Factor
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ABSTRACT: Ductal carcinoma in situ (DCIS) has an excellent prognosis, but its management can resemble that of early invasive breast cancer. We compared aspects of quality of life of women with DCIS to that of women with invasive disease during the first year after treatment initiation. Participants came from consecutive series of women with newly diagnosed, non-metastatic breast cancer treated in eight Quebec hospitals in 2003. Psychological distress and health-related quality of life were measured using the Psychiatric Symptom Index (PSI) and the SF-12 mental and physical component scales (MCS, PCS). Data were obtained 1, 6, and 12 months after the start of treatment. We used generalized linear models to compare mean scores and explored the possible clinical significance of between-group differences with effect size (ES). Participation and retention among eligible women were high, 86 and 97%, respectively. Among the 800 women who completed all interviews, 13.4% (n = 107) had DCIS and 86.6% (693) invasive disease. No statistically significant between-group differences were found at 1, 6, or 12 months in psychological state (PSI and MCS: P values from 0.065 to 0.904; ES from -0.01 to -0.21). Women with DCIS reported significantly higher levels of physical health, particularly when compared at 1 month to women with invasive disease who had chemotherapy (P value < 0.0001; ES = 0.82). Measured in symptoms of psychological distress, the better prognosis or less aggressive management of DCIS does not offset the general psychological effects of a cancer diagnosis to any great degree.
Breast Cancer Research and Treatment 08/2009; 120(3):685-91. · 4.43 Impact Factor
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ABSTRACT: It has been suggested that gene-environment interaction is related to the risk of cancer. To evaluate departure from multiplicative effects between BRCA mutations and diet diversity in breast cancer (BC), a case-only study was carried out in a French-Canadian population including 738 patients with incident primary BC comprising 38 BRCA mutation carriers. Diet diversity was assessed using a validated food frequency questionnaire. Unconditional logistic regression analysis was performed to assess case-only odds ratio (COR) and 95% confidence interval (CI) while adjusting for age, body mass index, smoking, hormonal replacement therapy, and total energy intake. Ours results reveal a strong and significant interaction between BRCA mutations and vegetable and fruit diversity (COR = 0.27; 95%CI = 0.10-0.80; P = 0.03) when comparing the upper to the lower quartiles. The estimates for departure from multiplicative effects between BRCA mutations and total or other food groups' diversity were not supportive of the idea of a gene-environment interaction. The results of this study suggest that the combination of BRCA mutations and vegetable and fruit diversity may be associated with a reduced risk of BC.
Breast Cancer Research and Treatment 02/2009; 117(2):417-22. · 4.43 Impact Factor
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ABSTRACT: Several lifestyle factors play a significant role in determining an individual's risk of breast cancer. Many of them could be modified to protect against the malignancy. A nested case-control study was conducted to examine the association between selected lifestyle factors and non-BRCA-related breast cancer risk among French-Canadian women. Some 280 women with breast cancer and who were nongene carriers of mutated BRCA gene were recruited as cases. Another 280 women, without any cancer and nongene carriers of mutated BRCA gene served as controls. A tested lifestyle questionnaire was interviewer administered to incident cases to obtain information on weight history, smoking, physical activity, and other lifestyle risk factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in logistic regression models. Comparing cases to controls, breast cancer risk was higher among subjects who reached their maximum body mass index (BMI) at an older age (>50 years) (OR = 2.83; 95% CI: 2.34-2.91). A positive association was noted between breast cancer risk and weight gain of >34 lbs compared to weight gain of </=15 lbs, since the age of 20 (OR = 1.68; 95% CI: 1.10-2.58). Weight gain of >24 lbs compared to weight gain of </=9 lbs, since the age of 30 also resulted in the same relationship (OR = 1.96; 95% CI: 1.46-3.06). Similarly, since the age of 40, weight gain of >12 lbs compared to weight gain of </=1 lb was associated with increased breast cancer risk (OR = 1.91; 95% CI: 1.53-2.66). Women who smoked >9 pack-years of cigarettes had a 59% higher breast cancer risk (P = .05). Subjects who engaged in >24.8 metabolic-equivalent- (MET-) hours per week compared to </=10.7 MET-hours per week of moderate physical activity had a 52% (P = .01) decreased risk and total physical activity between 16.2 and 33.2 MET-hours per week compared to </=16.2 MET-hours per week, resulted in a 43% (P = .05) lower risk of breast cancer. In conclusion, weight history did affect breast cancer risk. Moreover, smoking appeared to raise the risk, whereas moderate physical activity had a protective effect.
Journal of Cancer Epidemiology 01/2009; 2009:748367.
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ABSTRACT: The utility of chemotherapy for women who experience a locoregional recurrence after primary treatment of early breast cancer remains an open question. An international collaborative trial is being conducted by the Breast International Group (BIG), the International Breast Cancer Study Group (IBCSG), and the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine the effectiveness of cytotoxic therapy for these patients, either alone or in addition to selective use of hormonal therapy and trastuzumab.
The trial population includes women who have had a previous diagnosis of invasive breast cancer treated by mastectomy or breast-conserving surgery, but subsequently develop an isolated local and/or regional ipsilateral invasive recurrence. Excision of all macroscopic tumor without evidence of systemic disease is required for study entry. Patients are randomized to receive chemotherapy or no chemotherapy; type of chemotherapy is not protocol-specified. Radiation, hormonal therapy, and trastuzumab are given as appropriate. The primary endpoint is disease-free survival (DFS). Quality-of-life measurements are collected at baseline, and then at 9 and 12 months. The accrual goal is 977 patients.
This report describes the characteristics of the first 99 patients. Sites of recurrence at study entry were: breast (56%), mastectomy scar/chest wall (35%), and regional lymph nodes (9%). Two-thirds of patients have estrogen-receptor-positive recurrences.
This is the only trial actively investigating the question of "adjuvant" chemotherapy in locally recurrent breast cancer. The case mix of accrual to date indicates a broad representation of this patient population.
Annals of Surgical Oncology 10/2008; 15(11):3227-31. · 4.17 Impact Factor
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John T Hamm,
John W Wilson,
Priya Rastogi,
Barry C Lembersky,
George C Tseng,
Young K Song,
Wanseop Kim, André Robidoux,
Jane M Raymond,
Carl G Kardinal,
Ibrahim A Shalaby,
Rafat Ansari,
Soonmyung Paik,
Charles E Geyer,
Norman Wolmark
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ABSTRACT: This phase II protocol of neoadjuvant chemotherapy with gemcitabine/epirubicin/paclitaxel (GET) was designed to determine the pathologic complete response (pCR) rate in the breast, clinical response rate, disease-free survival, and overall survival at 2 years as well as toxicity in patients with locally advanced breast cancer. This trial also evaluated the feasibility of tissue collection for gene-expression profiling.
Seventy-six women with stage IIB, IIIA, and IIIB breast cancer were entered into this trial. Patients received a maximum of 6 cycles of neoadjuvant GET chemotherapy every 21 days (gemcitabine 1000 mg/m2 intravenously [i.v.] on days 1 and 4, epirubicin 90 mg/m2 i.v. bolus on day 1, and paclitaxel 175 mg/m2 i.v. on day 1). After chemotherapy, patients underwent surgery and were assessed for pathologic response.
The pCR rate among the 74 patients evaluable for efficacy was 23% (95% CI, 14%-34.2%). Adverse events among the 76 patients evaluable for toxicity included anemia requiring transfusion (14.5%), infection with grade 3/4 neutropenia (10.5%), febrile neutropenia (7.9%), and platelet transfusion (6.6%). Infectious complications occurred in 24 patients (31.6%), of whom 18.4% were in the setting of neutropenia. High-quality RNA and successful probe synthesis were obtained from all pretreatment core biopsy specimens that contained tumor cells (n=66; 88%).
Neoadjuvant GET chemotherapy is an active regimen but with substantial toxicity. Tissue collection for gene-expression profiling is feasible in a multi-institutional setting.
Clinical Breast Cancer 06/2008; 8(3):257-63. · 2.38 Impact Factor
