Breast Neoplasms: Whelan TJ

Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, Julian TB, Marks LB, Todor DA, Vicini FA, Whelan TJ, White J, Wo JY, Harris JR. · Radiation Oncology Flight, Wilford Hall Medical Center, Lackland AFB, TX, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #19545784 No free full text.

Abstract: PURPOSE: To present guidance for patients and physicians regarding the use of accelerated partial-breast irradiation (APBI), based on current published evidence complemented by expert opinion. METHODS AND MATERIALS: A systematic search of the National Library of Medicine's PubMed database yielded 645 candidate original research articles potentially applicable to APBI. Of these, 4 randomized trials and 38 prospective single-arm studies were identified. A Task Force composed of all authors synthesized the published evidence and, through a series of meetings, reached consensus regarding the recommendations contained herein. RESULTS: The Task Force proposed three patient groups: (1) a "suitable" group, for whom APBI outside of a clinical trial is acceptable, (2) a "cautionary" group, for whom caution and concern should be applied when considering APBI outside of a clinical trial, and (3) an "unsuitable" group, for whom APBI outside of a clinical trial is not generally considered warranted. Patients who choose treatment with APBI should be informed that whole-breast irradiation (WBI) is an established treatment with a much longer track record that has documented long-term effectiveness and safety. CONCLUSION: Accelerated partial-breast irradiation is a new technology that may ultimately demonstrate long-term effectiveness and safety comparable to that of WBI for selected patients with early breast cancer. This consensus statement is intended to provide guidance regarding the use of APBI outside of a clinical trial and to serve as a framework to promote additional clinical investigations into the optimal role of APBI in the treatment of breast cancer.

Truong PT, Olivotto IA, Whelan TJ, Levine M, Anonymous00110. · BC Cancer Agency-Vancouver Island Centre. · CMAJ. · Pubmed #15078851 links to  free full text

Abstract: OBJECTIVE: To provide information and recommendations to assist women with breast cancer and their physicians in making decisions regarding the use of locoregional post-mastectomy radiotherapy (PMRT). OUTCOMES: Locoregional control, disease-free survival, overall survival and treatment-related toxicities. EVIDENCE: This guideline is based on a review of all meta-analyses, consensus statements and other guidelines published between 1966 and November 2002. Searches of MEDLINE and CANCERLIT for English-language randomized controlled trials published between 1995 and November 2002 were also conducted to supplement the literature previously reviewed by the American Society of Clinical Oncology (ASCO) Health Services Research Committee panel in its published guideline. A nonsystematic review of the literature was continued through June 2003. RECOMMENDATIONS: Locoregional PMRT is recommended for women with an advanced primary tumour (tumour size 5 cm or greater, or tumour invasion of the skin, pectoral muscle or chest wall). Locoregional PMRT is recommended for women with 4 or more positive axillary lymph nodes. The role of PMRT in women with 1 to 3 positive axillary lymph nodes is unclear. These women should be offered the opportunity to participate in clinical trials of PMRT. Locoregional PMRT is generally not recommended for women who have tumours that are less than 5 cm in diameter and who have negative axillary nodes. Other patient, tumour and treatment characteristics, including age, histologic grade, lymphovascular invasion, hormone receptor status, number of axillary nodes removed, axillary extracapsular extension and surgical margin status, may affect locoregional control, but their use in specifying additional indications for PMRT is currently unclear. PMRT should encompass the chest wall and the supraclavicular, infraclavicular and axillary apical lymph node areas. To reduce the risk of lymphedema, radiation of the entire axilla should not be used routinely after complete axillary dissection of level I and II lymph nodes. A definite recommendation regarding the inclusion of the internal mammary lymph nodes in PMRT cannot be made because of limited and inconsistent data. The use of modern techniques in radiotherapy planning is recommended to minimize excessive normal tissue exposure, particularly to the cardiac and pulmonary structures. Common short-term side effects of PMRT, including fatigue and skin erythema, are generally tolerable and not dose-limiting. Severe long-term side effects, including lymphedema, cardiac and pulmonary toxicities, brachial plexopathy, rib fractures and secondary neoplasms, are relatively rare. The optimal sequencing of PMRT and systemic therapy is currently unclear. Regimens containing anthracyclines or taxanes should not be administered concurrently with radiotherapy because of the potential for increased toxicity. VALIDATION: The authors' original text was submitted for review, revision and approval by the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Subsequently, feedback was provided by 11 oncologists from across Canada. The final document was approved by the steering committee. SPONSOR: The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer was convened by Health Canada. COMPLETION DATE: November 2003.

Recht A, Edge SB, Solin LJ, Robinson DS, Estabrook A, Fine RE, Fleming GF, Formenti S, Hudis C, Kirshner JJ, Krause DA, Kuske RR, Langer AS, Sledge GW, Whelan TJ, Pfister DG, Anonymous00352. · Beth Israel Deaconess Medical Center, Boston, MA, USA. · J Clin Oncol. · Pubmed #11230499 No free full text.

Abstract: OBJECTIVE: To determine indications for the use of postmastectomy radiotherapy (PMRT) for patients with invasive breast cancer with involved axillary lymph nodes or locally advanced disease who receive systemic therapy. These guidelines are intended for use in the care of patients outside of clinical trials. POTENTIAL INTERVENTION: The benefits and risks of PMRT in such patients, as well as subgroups of these patients, were considered. The details of the PMRT technique were also evaluated. OUTCOMES: The outcomes considered included freedom from local-regional recurrence, survival (disease-free and overall), and long-term toxicity. EVIDENCE: An expert multidisciplinary panel reviewed pertinent information from the published literature through July 2000; certain investigators were contacted for more recent and, in some cases, unpublished information. A computerized search was performed of MEDLINE data; directed searches based on the bibliographies of primary articles were also performed. VALUES: Levels of evidence and guideline grades were assigned by the Panel using standard criteria. A "recommendation" was made when level I or II evidence was available and there was consensus as to its meaning. A "suggestion" was made based on level III, IV, or V evidence and there was consensus as to its meaning. Areas of clinical importance were pointed out where guidelines could not be formulated due to insufficient evidence or lack of consensus. RECOMMENDATIONS: The recommendations, suggestions, and expert opinions of the Panel are described in this article. VALIDATION: Seven outside reviewers, the American Society of Clinical Oncology (ASCO) Health Services Research Committee members, and the ASCO Board of Directors reviewed this document.

Goss PE, Muss HB, Ingle JN, Whelan TJ, Wu M. · Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. · Clin Breast Cancer. · Pubmed #18952554 No free full text.

Abstract: Women with hormone receptor-positive breast cancer have traditionally been treated with 5 years of adjuvant tamoxifen to reduce their risk of subsequent recurrent disease. Among those who experience subsequent disease recurrence, the majority do so after 5 years, suggesting that longer durations of endocrine therapy might be beneficial. Two options tested include longer tamoxifen and, in postmenopausal women, a switch to an aromatase inhibitor (AI). In the National Cancer Institute of Canada Cooperative Trials Group MA.17 trial, we tested the AI letrozole given to postmenopausal women for 5 years after tamoxifen as extended adjuvant therapy because of its efficacy in patients with advanced breast cancer in progression on previous tamoxifen. The first interim analysis (median, 2.4 patient years) showed substantial benefits from letrozole, and all patients were unblinded and offered the option of letrozole. Despite two thirds of the patients crossing over to letrozole, an intent-to-treat analysis at 54 months' follow-up continued to demonstrate the strong beneficial effect of extended adjuvant letrozole. Furthermore, significant benefit was demonstrated among patients who had been randomized to placebo but elected to take letrozole after a prolonged washout from previous tamoxifen (late extended adjuvant therapy). A trial examining the merits of > 5 years of treatment with an AI, MA.17R, is ongoing, as are a number of other trials of duration of therapy. This article reviews results from MA.17 and the design of these trials of duration.

Whelan TJ, Pritchard KI. · McMaster University, Hamilton, Ontario, Canada. · Clin Cancer Res. · Pubmed #16467124 links to  free full text

Abstract: PURPOSE: To review the health-related quality of life (QOL) of women treated with adjuvant hormonal therapy. EXPERIMENTAL DESIGN: To review the limited QOL data from randomized trials of tamoxifen versus placebo and ovarian ablation versus none. To discuss QOL results from randomized trials of aromatase inhibitors compared with tamoxifen or placebo for adjuvant therapy of postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive breast cancer. RESULTS: QOL is generally good in up to 3 years of follow-up with either tamoxifen or aromatase inhibitors. Vasomotor and sexual complaints remain problematic, however, in only a small proportion of women. There are fewer data regarding the QOL effects of ovarian ablation, which may nonetheless be more substantial. CONCLUSION: Tamoxifen and aromatase inhibitors cause specific vasomotor or gynecologic symptoms, which may affect sexual function. However, clinical benefits of these agents are generally achieved without major detrimental effect on overall QOL.

Whelan TJ. · Department of Medicine, McMaster University, Hamilton, Ontario, Candada. · J Clin Oncol. · Pubmed #15755980 No free full text.

This publication has no abstract.

Whelan TJ, Loprinzi C. · Juravinski Cancer Centre, 699 Concession St, Room 3-62, Hamilton, Ontario, L8V 5C2 Canada. · J Clin Oncol. · Pubmed #15755969 No free full text.

This publication has no abstract.

Winer EP, Hudis C, Burstein HJ, Wolff AC, Pritchard KI, Ingle JN, Chlebowski RT, Gelber R, Edge SB, Gralow J, Cobleigh MA, Mamounas EP, Goldstein LJ, Whelan TJ, Powles TJ, Bryant J, Perkins C, Perotti J, Braun S, Langer AS, Browman GP, Somerfield MR. · Dana-Farber Cancer Institute, 44 Binney St, D1210, Boston, MA 02115, USA. · J Clin Oncol. · Pubmed #15545664 No free full text.

Abstract: PURPOSE: To update the 2003 American Society of Clinical Oncology technology assessment on adjuvant use of aromatase inhibitors. RECOMMENDATIONS: Based on results from multiple large randomized trials, adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer should include an aromatase inhibitor in order to lower the risk of tumor recurrence. Neither the optimal timing nor duration of aromatase inhibitor therapy is established. Aromatase inhibitors are appropriate as initial treatment for women with contraindications to tamoxifen. For all other postmenopausal women, treatment options include 5 years of aromatase inhibitors treatment or sequential therapy consisting of tamoxifen (for either 2 to 3 years or 5 years) followed by aromatase inhibitors for 2 to 3, or 5 years. Patients intolerant of aromatase inhibitors should receive tamoxifen. There are no data on the use of tamoxifen after an aromatase inhibitor in the adjuvant setting. Women with hormone receptor-negative tumors should not receive adjuvant endocrine therapy. The role of other biomarkers such as progesterone receptor and HER2 status in selecting optimal endocrine therapy remains controversial. Aromatase inhibitors are contraindicated in premenopausal women; there are limited data concerning their role in women with treatment-related amenorrhea. The side effect profiles of tamoxifen and aromatase inhibitors differ. The late consequences of aromatase inhibitor therapy, including osteoporosis, are not well characterized. CONCLUSION: The Panel believes that optimal adjuvant hormonal therapy for a postmenopausal woman with receptor-positive breast cancer includes an aromatase inhibitor as initial therapy or after treatment with tamoxifen. Women with breast cancer and their physicians must weigh the risks and benefits of all therapeutic options.

Winer EP, Hudis C, Burstein HJ, Chlebowski RT, Ingle JN, Edge SB, Mamounas EP, Gralow J, Goldstein LJ, Pritchard KI, Braun S, Cobleigh MA, Langer AS, Perotti J, Powles TJ, Whelan TJ, Browman GP. · Health Services Research Department, American Society of Clinical Oncology, 1900 Duke Street, Suite 200, Alexandria, VA 22314, USA. · J Clin Oncol. · Pubmed #12149306 No free full text.

Abstract: OBJECTIVE: To conduct an evidence-based technology assessment to determine whether the routine use of anastrozole or any of the aromatase inhibitors in the adjuvant breast cancer setting is appropriate for broad-based conventional use in clinical practice. POTENTIAL INTERVENTIONS: Anastrozole, letrozole, and exemestane. OUTCOMES: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefit. EVIDENCE: A comprehensive, formal literature review was conducted for relevant topics and is detailed in the text. Testimony was collected from invited experts and interested parties. The American Society of Clinical Oncology (ASCO)-prescribed technology assessment procedure was followed. BENEFITS/HARMS: The ASCO panel recognizes that a woman and her physician's decision regarding adjuvant hormonal therapy is complex and will depend on the importance and weight attributed to information regarding both cancer and non-cancer-related risks and benefits. CONCLUSION: The panel was influenced by the compelling, extensive, and long-term data available on tamoxifen. Overall, the panel considers the results of the Arimidex (anastrozole) or Tamoxifen Alone or in Combination (ATAC) trial and the extensive supporting data to be very promising but insufficient to change the standard practice at this time (May 2002). A 5-year course of adjuvant tamoxifen remains the standard therapy for women with hormone receptor-positive breast cancer. The panel recommends that physicians discuss the available information with patients, and, in making a decision, acknowledge that treatment approaches can change over time. Individual health care providers and their patients will need to come to their own conclusions, with careful consideration of all of the available data. (Specific questions addressed by the panel are summarized in Appendix 3.) VALIDATION: The conclusions of the panel were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors.

Muss HB, Tu D, Ingle JN, Martino S, Robert NJ, Pater JL, Whelan TJ, Palmer MJ, Piccart MJ, Shepherd LE, Pritchard KI, He Z, Goss PE. · University of Vermont College of Medicine, 1 South Prospect St, Saint Joseph 3400, Burlington, VT 05401, USA. · J Clin Oncol. · Pubmed #18332474 No free full text.

Abstract: PURPOSE: National Cancer Institute of Canada Clinical Trials Group trial MA.17 randomly assigned 5,187 postmenopausal, hormone-receptor-positive patients with early breast cancer who completed 5 years of tamoxifen to receive either letrozole or placebo. At 30 months median follow-up, letrozole significantly improved disease-free survival (DFS) in all patients and overall survival (OS) in node-positive patients. Breast cancer incidence increases with age and more than 1,300 women age 70 years or older were enrolled onto MA.17, making it ideal to explore the benefits, toxicities, and quality of life (QOL) impact of letrozole on older women. PATIENTS AND METHODS: In this study, 5,169 randomly assigned patients were divided into three age groups: younger than 60 years (n = 2,152), 60 to 69 years (n = 1,694), and >or= 70 years (n = 1,323). Log-rank test was used to compare differences in DFS, distant-disease-free survival, and OS between age and treatment groups, and Cox models were used to estimate hazard ratios and associated 95% CIs. QOL was measured using the Medical Outcomes Short Form-36 and the Menopause-Specific Quality-of-Life questionnaire. RESULTS: At 4 years, DFS demonstrated statistically significant differences favoring letrozole only in patients age younger than 60 years (hazard ratio = 0.46; P = .0004); there was no interaction between age and treatment, indicating a similar effect of letrozole among all age groups. There was no difference in toxicity or QOL at 24 months among letrozole- and placebo-treated patients age >or= 70 years. CONCLUSION: Healthy patients age 70 years and older completing 5 years of tamoxifen should be considered for extended adjuvant therapy with letrozole.

Whelan TJ, Goss PE, Ingle JN, Pater JL, Tu D, Pritchard K, Liu S, Shepherd LE, Palmer M, Robert NJ, Martino S, Muss HB. · McMaster University, Hamilton, Canada. · J Clin Oncol. · Pubmed #16157934 No free full text.

Abstract: PURPOSE: To evaluate the impact of letrozole compared with placebo after adjuvant tamoxifen on quality of life (QOL) in the MA.17 trial. METHODS: Patients completed the Short Form 36-item Health Survey (SF-36) and the Menopause Specific Quality of Life Questionnaire (MENQOL) at baseline, 6 months, and annually. Mean change scores from baseline were compared between groups for summary measures and domains. A response analysis compared the proportion of patients who demonstrated an important change in QOL. RESULTS: Of 5,187 randomly assigned women in the trial, 3,612 (69.9%) participated in the QOL substudy: 1,799 were allocated to placebo and 1,813 were allocated to letrozole. No differences were seen between groups in mean change scores from baseline for the SF-36 physical and mental component summary scores at 6, 12, 24, and 36 months. Small (< 0.2 standard deviations) but statistically significant differences in mean change scores from baseline were seen for the SF-36 domains of physical functioning (12 months), bodily pain (6 months) and vitality (6 and 12 months), and the MENQOL vasomotor (6, 12, and 24 months) and sexual domains (12 and 24 months). On the response analysis, a significant difference was seen between groups for the bodily pain domain (percentage of patients reporting a worsening of QOL, 47% placebo v 51% letrozole; P = .009) and the vasomotor domain (22% placebo v 29% letrozole; P = .001). CONCLUSION: Letrozole did not have an adverse impact on overall QOL. Small effects were seen in some domains consistent with a minority of patients experiencing changes in QOL compatible with a reduction in estrogen synthesis.

Olivotto IA, Chua B, Elliott EA, Parda DS, Pierce LJ, Shepherd L, Vallow LA, White JR, Whelan TJ. · Radiation Oncology, British Columbia Cancer Agency and University of British Columbia, Vancouver Island Centre, 2410 Lee Avenue, Victoria, BC V8R 6V5, Canada. · Clin Breast Cancer. · Pubmed #14715112 links to  free full text

This publication has no abstract.

Whelan TJ, Levine M, Julian J, Kirkbride P, Skingley P. · Department of Medicine, McMaster University, Cancer Care Ontario, Hamilton Regional Cancer Centre, Canada. · Cancer. · Pubmed #10820347 links to  free full text

Abstract: BACKGROUND: The purpose of this study was to evaluate the effect of breast irradiation on quality of life, including cosmetic outcome, for patients enrolled in a clinical trial. METHODS: Between 1984 and 1989, a randomized trial was conducted in Ontario, Canada, in which women with lymph node negative breast carcinoma who had undergone lumpectomy and axillary lymph node dissection were randomized to either breast irradiation or no further treatment. A modified version of the Breast Cancer Chemotherapy Questionnaire (BCQ) was administered to women at baseline, 1 month (4 weeks), and 2 months (8 weeks) after randomization. Irritation of the skin of the breast, breast pain, and appearance of the breast to the patient were also assessed every 3 months for the first 2 years of the study. RESULTS: Of 837 patients, 416 were randomly allocated to radiation therapy and 421 to no further treatment. The mean change in quality of life from baseline to 2 months was -0.05 for the radiation group and +0.30 for the control group. The difference between groups was statistically significant (P = 0.0001). Longer term radiation therapy increased the proportion of patients who were troubled by irritation of the skin of the breast and breast pain. Radiation therapy did not increase the proportion of patients at 2 years who were troubled by the appearance of the treated breast; 4.8% in irradiated and nonirradiated patients (P = 0.62). CONCLUSIONS: Breast irradiation therapy had an effect on quality of life during treatment. After treatment, irradiated patients reported increased breast symptoms compared with controls. However, no difference was detected between groups at 2 years in the rates of skin irritation, breast pain, and being upset by the appearance of the breast.

O'Brien MA, Whelan TJ, Charles C, Ellis PM, Gafni A, Lovrics P, Hasler A, Dimitry S. · Supportive Cancer Care Research Unit, Juravinski Cancer Centre and McMaster University, Hamilton, ON, Canada. · Patient Educ Couns. · Pubmed #18755565 No free full text.

Abstract: OBJECTIVE: There is limited understanding about what treatment decision making (TDM) means to patients. The study objective was to identify any processes or stages of TDM as perceived by women with early stage breast cancer (ESBC). METHODS: Initial consultations with a surgeon or medical oncologist were videotaped. Subsequently, women viewed their consultation using a qualitative approach with video-stimulated recall (VSR) interviews. Interviews were taped, transcribed, and analyzed. RESULTS: There were 6 surgical and 15 medical oncology (MO) consultations. Most women described TDM as beginning soon after diagnosis and involving several processes including gathering information from informal and formal networks and identifying preferred treatment options before the specialist consultation. Many women wanted more information from their surgeon so they could engage in subsequent TDM with their medical oncologist. CONCLUSION: In this study, women with ESBC began TDM soon after diagnosis and used several iterative processes to arrive at a decision about their cancer treatment. VSR interviews can be useful to investigate TDM occurring during the consultation. PRACTICE IMPLICATIONS: Women with ESBC rely on information provided by their surgeons and family physicians to make treatment decisions about surgery and also to prepare them for subsequent discussions with medical oncologists about chemotherapy.

Whelan TJ, Kim DH, Sussman J. · Department of Oncology, McMaster University, Hamilton, Ontario, Canada; Juravinski Cancer Centre, Hamilton, Ontario, Canada. · Semin Radiat Oncol. · Pubmed #18725113 No free full text.

Abstract: Hypofractionation is attractive for whole- or partial-breast irradiation because it permits treatment to be given with fewer fractions in a shorter period of time and at less cost. A number of cohort studies suggest that hypofractionation may be given to the whole breast safely and with good local control. Recent randomized trials have confirmed that hypofractioned whole-breast irradiation is equivalent to more conventional whole-breast irradiation with respect to local recurrence and cosmetic outcome. Recently, there has been a renewed interest in hypofractionation for the delivery of partial-breast irradiation using a number of techniques including high-dose rate brachytherapy, 3-dimensional conformal radiation using external-beam techniques, and intraoperative therapy. Early cohort studies report good local control and acceptable morbidity. Randomized trials are now underway to compare this approach to conventional whole-breast irradiation.

Dayes IS, Levine MN, Julian JA, Pritchard KI, D'Souza DP, Kligman L, Reise D, Wiernikowski JA, Bonilla L, Whelan TJ. · Department of Oncology, McMaster University, Hamilton, Ontario, Canada. · Breast Cancer Res Treat. · Pubmed #17851756 No free full text.

Abstract: INTRODUCTION: Accrual rates for a randomized trial of decongestive therapy in breast cancer patients with lymphedema were lower than anticipated. In two centres, patients presenting to lymphedema clinic were screened for eligibility to understand the accrual process and help define the patient population. MATERIALS AND METHODS: All breast cancer patients presenting to two lymphedema clinics in regional cancer centres were screened for study entry. Circumferential arm measurements were taken and volumes calculated. Patients were then screened for trial eligibility. All report forms were sent to the trial coordinating centre. RESULTS: A total of 408 patients were screened. Median arm volume excess was 239 ml (9.5%). One third of patients had little or no excess volume. Only 28.3% of patients had sufficient excess volume for trial eligibility. Of these, a significant number of patients were excluded because of active malignancy or previous decongestive therapy. CONCLUSIONS: The finding of moderate to severe lymphedema observed in clinics screening for trial eligibility was less than expected. The natural history of lymphedema in breast cancer patients is potentially changing. Some patients may be presenting with sensory changes suggestive of lymphedema but due to other causes, such as nerve disruption following axillary dissection.

Moy B, Tu D, Pater JL, Ingle JN, Shepherd LE, Whelan TJ, Goss PE. · Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. · Ann Oncol. · Pubmed #16936184 links to  free full text

Abstract: BACKGROUND: Aromatase inhibitors are widely employed in the adjuvant treatment of early stage breast cancer. The impact of aromatase inhibitors has not been established in ethnic minority women. PATIENTS AND METHODS: The purpose of this study was to evaluate the impact of letrozole on minority women in MA.17, a placebo-controlled trial of letrozole following 5 years of tamoxifen in postmenopausal women with early stage breast cancer. Retrospective comparison of disease-free survival (DFS), side effects, and mean changes in quality of life (QOL) scores from baseline between Caucasian and minority women was performed. RESULTS: Minority (n = 352) and Caucasian (n = 4708) women were analyzed. There was no difference between these groups in DFS (91.6% versus 92.4% respectively for 4 year DFS). Letrozole, compared with placebo, significantly improved DFS for Caucasians (HR = 0.55; P < 0.0001) but not for minorities (HR = 1.39; P = 0.53). Among women who received letrozole, minorities had a significantly lower incidence of hot flashes (49% versus 58%; P = 0.02), fatigue (29% versus 39%; P = 0.005), and arthritis (2% versus 7%; P = 0.006) compared with Caucasians. Mean change in QOL scores for minority women who received letrozole demonstrated improved mental health at the 6-month assessment (P = 0.02) and less bodily pain at the 12-month assessment (P = 0.046). CONCLUSION: Letrozole improved DFS in Caucasians but a definite benefit in minority women has not yet been demonstrated. Minority women tolerated letrozole better than Caucasians in terms of toxicity. These results need confirmation in other trials of aromatase inhibitors.

Pierce LJ, Levin AM, Rebbeck TR, Ben-David MA, Friedman E, Solin LJ, Harris EE, Gaffney DK, Haffty BG, Dawson LA, Narod SA, Olivotto IA, Eisen A, Whelan TJ, Olopade OI, Isaacs C, Merajver SD, Wong JS, Garber JE, Weber BL. · Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, MI 48109-0010, USA. · J Clin Oncol. · Pubmed #16636335 No free full text.

Abstract: PURPOSE: We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls. METHODS: A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls. RESULTS: There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05). CONCLUSION: IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.

Goffin JR, Savage C, Tu D, Shepherd L, Whelan TJ, Olivotto IA. · National Cancer Institute of Canada, Clinical Trials Group, Kingston, Ontario, Canada. · Ann Oncol. · Pubmed #15277269 links to  free full text

Abstract: 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.

Irwin E, Arnold A, Whelan TJ, Reyno LM, Cranton P. · McMaster University, School of Nursing, OCTRF Hamilton Regional Cancer Centre, Hamilton, Ontario, Canada. · Patient Educ Couns. · Pubmed #14528554 No free full text.

Abstract: BACKGROUND: The primary objective of this study was to develop a decision aid which would encourage and assist patients to become involved in treatment decision making, and help clinicians to objectively educate patients about the benefits and risks of adjuvant chemotherapy for breast cancer. A secondary objective was to investigate the factors influencing this treatment decision-making process for women when choosing between adriamycin and cyclophosphamide (AC) versus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy. METHODS: An educational visual instrument called a Decision Board was developed consisting of written and graphical material. The Decision Board displays general information about chemotherapy and detailed information about each chemotherapy regimen, including the schedule and side effects, and was presented to patients with a scripted standardized oral explanation. The instrument was evaluated in 46 premenopausal women newly diagnosed with node-positive breast cancer. Following presentation of the board, the patients were given a take home version to review and asked to return 1-2 weeks later with a decision. During the second visit each patient was asked to complete a questionnaire regarding demographics, learning and comprehension, treatment preference, and factors influencing their decision. RESULTS: Recall of information was acceptable (> or = 80%). The Decision Board was found helpful by all, but the level of difficulty with decision making was variable. Out of 46 women, 23 women chose AC, 21 chose CMF, and two chose no treatment. The major factors affecting treatment preference were related to the impact on quality of life, the length of therapy, and the side effects, in particular, vomiting and alopecia. CONCLUSIONS: The Decision Board appears to be a valuable educational tool that enables patients to become well-informed and directly involved in their treatment decisions.

Winer EP, Hudis C, Burstein HJ, Bryant J, Chlebowski RT, Ingle JN, Edge SB, Mamounas EP, Gelber R, Gralow J, Goldstein LJ, Pritchard KI, Braun S, Cobleigh MA, Langer AS, Perotti J, Powles TJ, Whelan TJ, Browman GP. · American Society of Clinical Oncology, Alexandria, VA 22314, USA. · J Clin Oncol. · Pubmed #12732612 No free full text.

This publication has no abstract.

Whelan TJ, Julian J, Wright J, Jadad AR, Levine ML. · Departments of Medicine, Clinical Epidemiology, and Biostatistics, McMaster University, and Cancer Care Ontario, Hamilton Regional Cancer Centre, Hamilton, ON, Canada. · J Clin Oncol. · Pubmed #10715291 No free full text.

Abstract: PURPOSE: Recent randomized trials in women with node-positive breast cancer who received systemic treatment report that locoregional radiation therapy improves survival. Previous trials failed to detect a difference in survival that results from its use. A systematic review of randomized trials that examine the effectiveness of locoregional radiation therapy in patients treated by definitive surgery and adjuvant systemic therapy was conducted. METHODS: Randomized trials published between 1967 and 1999 were identified through MEDLINE database, CancerLit database, and reference lists of relevant articles. Relevant data was abstracted. The results of randomized trials were pooled using meta-analyses to estimate the effect of treatment on any recurrence, locoregional recurrence, and mortality. RESULTS: Eighteen trials that involved a total of 6,367 patients were identified. Most trials included both pre- and postmenopausal women with node-positive breast cancer treated with modified radical mastectomy. The type of systemic therapy received, sites irradiated, techniques used, and doses of radiation delivered varied between trials. Data on toxicity were infrequently reported. Radiation was shown to reduce the risk of any recurrence (odds ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.83), local recurrence (odds ratio, 0.25; 95% CI, 0.19 to 0.34), and mortality (odds ratio, 0.83; 95% CI, 0.74 to 0.94). CONCLUSION: Locoregional radiation after surgery in patients treated with systemic therapy reduced mortality. Several questions remain on how these results should be translated into current-day clinical practice.

Olivotto IA, Whelan TJ. · No affiliation provided · Int J Radiat Oncol Biol Phys. · Pubmed #15001280 No free full text.

This publication has no abstract.