Carol Sawka

Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence

Purpose: To compare the clinical features, natural history, and outcomes for women with “triple-negative” breast cancer with women with other types of breast cancer. Experimental Design: We studied a cohort of 1,601 patients with breast cancer, diagnosed between January 1987 and December 1997 at Womens College Hospital in Toronto. Triple-negative breast cancers were defined as those that were estrogen receptor negative, progesterone receptor negative, and HER2neu negative. The prognostic significance of triple-negative breast cancer was explored. Results: The median follow-up time of the 1,601 women was 8.1 years. One hundred and eighty of 1,601 patients (11.2%) had triple-negative breast cancer. Compared with other women with breast cancer, those with triple-negative breast cancer had an increased likelihood of distant recurrence (hazard ratio, 2.6; 95% confidence interval, 2.0-3.5; P < 0.0001) and death (hazard ratio, 3.2; 95% confidence interval, 2.3-4.5; P < 0.001) within 5 years of diagnosis but not thereafter. The pattern of recurrence was also qualitatively different; among the triple-negative group, the risk of distant recurrence peaked at ∼3 years and declined rapidly thereafter. Among the “other” group, the recurrence risk seemed to be constant over the period of follow-up. Conclusions: Triple-negative breast cancers have a more aggressive clinical course than other forms of breast cancer, but the adverse effect is transient.

Randomized Trial of Long-Term Follow-Up for Early-Stage Breast Cancer: A Comparison of Family Physician Versus Specialist Care

PURPOSE Most women with breast cancer are diagnosed at an early stage and more than 80% will be long-term survivors. Routine follow-up marks the transition from intensive treatment to survivorship. It is usual practice for routine follow-up to take place in specialist clinics. This study tested the hypothesis that follow-up by the patients family physician is a safe and acceptable alternative to specialist follow-up. PATIENTS AND METHODS A multicenter, randomized, controlled trial was conducted involving 968 patients with early-stage breast cancer who had completed adjuvant treatment, were disease free, and were between 9 and 15 months after diagnosis. Patients may have continued receiving adjuvant hormonal therapy. Patients were randomly allocated to follow-up in the cancer center according to usual practice (CC group) or follow-up from their own family physician (FP group). The primary outcome was the rate of recurrence-related serious clinical events (SCEs). The secondary outcome was health-related quality of life (HRQL). RESULTS In the FP group, there were 54 recurrences (11.2%) and 29 deaths (6.0%). In the CC group, there were 64 recurrences (13.2%) and 30 deaths (6.2%). In the FP group, 17 patients (3.5%) compared with 18 patients (3.7%) in the CC group experienced an SCE (0.19% difference; 95% CI, -2.26% to 2.65%). No statistically significant differences (P < .05) were detected between groups on any of the HRQL questionnaires. CONCLUSION Breast cancer patients can be offered follow-up by their family physician without concern that important recurrence-related SCEs will occur more frequently or that HRQL will be negatively affected.

Use of Complementary/Alternative Medicine by Breast Cancer Survivors in Ontario: Prevalence and Perceptions

PURPOSE To determine the prevalence of use of complementary/alternative medicine (CAM) by breast cancer survivors in Ontario, Canada, and to compare the characteristics of CAM users and CAM nonusers. PATIENTS AND METHODS A questionnaire was mailed to a random sample of Ontario women diagnosed with breast cancer in 1994 or 1995. RESULTS The response rate was 76.3%. Overall, 66.7% of the respondents reported using CAM, most often in an attempt to boost the immune system. CAM practitioners (most commonly chiropractors, herbalists, acupuncturists, traditional Chinese medicine practitioners, and/or naturopathic practitioners) were visited by 39.4% of the respondents. In addition, 62.0% reported use of CAM products (most frequently vitamins/minerals, herbal medicines, green tea, special foods, and essiac). Almost one half of the respondents informed their physicians of their use of CAM. Multiple logistic regression analysis determined that support group attendance was the only factor significantly associated with CAM use. CONCLUSION CAM use is common among Canadian breast cancer survivors, many of whom are discussing CAM therapy options with their physicians. Knowledge of CAM therapies is necessary for physicians and other health care practitioners to help patients make informed choices. CAM use may play a role in the positive benefits associated with support group attendance.

Randomized trial of a patient decision aid for choice of surgical treatment for breast cancer.

A decision aid for the surgical treatment of early breast cancer was evaluated in a randomized controlled trial. The decision aid, a tape and workbook, includes explicit presentation of probabilities, photographs and graphics, and a values clarification exercise. Community surgeons were randomized to use the decision aid or a control pamphlet. Patients completed a questionnaire prior to using the decision aid, after reviewing it but prior to surgery, and 6 months after enrollment. There was no difference in anxiety, knowledge, or decisional regret across the 2 groups. There was a nonsignificant trend toward lower decisional conflict in the decision aid group. A subgroup of women who were initially leaning toward mastectomy or were unsure had lower decisional conflict. Although the decision aid had minimal impact on the main study outcomes, a subgroup may have benefited. Such subgroups should be identified, and appropriate decision support interventions should be developed and evaluated.

Standardized synoptic cancer pathology reporting: a population-based approach.

Cancer pathology reports contain information which is critical for patient management and for cancer surveillance, resource planning, and quality purposes. The College of American Pathologists (CAP) has defined scientifically validated content of checklists that form the basis for synoptic cancer pathology reporting. We outline how the CAP standards were implemented in a large Canadian province over a 3‐year period resulting in improvements in rates of synoptic reporting and completeness of cancer pathology reporting. J. Surg. Oncol. 2009;99:517–524.

Decision aids: are they worth it? A systematic review.

Objectives: The field of consumer decision support interventions has grown rapidly in the last 20 years, particularly since the increased formalization of evidence-based decision-making in health care. However, little is known as yet about the effect these decision aids have on relevant outcomes. To identify outcomes influenced by consumer decision aids (CDAs) and the particular effects of CDAs on those outcomes. Method: Published reports of randomized controlled trials and other designs in English identified from searches of Medline, Cancerlit, CINAHL, PsycINFO, Social Science Abstracts, the Cochrane Library and Current Contents, and from ancestry searches, hand searches and consultation with key informants. Studies were included if consumers were the decision-makers, decisions were real and not hypothetical, the intervention met a strict definition of a CDA and decisions involved treatment or screening. Data on setting, subjects, decision types, decision aid features and outcomes were extracted. The validity of each study included was evaluated by two team members. Summative ratings were calculated and categorized as high, medium and low. Results: Over 500 titles were initially assessed; 96 study reports were obtained and screened for inclusion. Twenty-two reports representing 20 studies met the inclusion criteria. Eight studies with a low rating were excluded. Results were synthesized from the remaining 12 studies. Published studies of CDAs are increasing although still few in number. Outcomes such as knowledge and decision-making processes are influenced by CDAs but effects on treatment preferences, the actual decision or other outcomes have yet to be clearly established. Conclusions: Improved outcomes result from the use of CDA in some categories of outcome but insufficient evidence exists yet to support improved outcomes in all categories or to evaluate whether, given the considerable costs of many CDAs, funding for extensive ongoing development and testing can be sustained.

Development of a patient decision aid for choice of surgical treatment for breast cancer

Purpose A patient decision aid for the surgical treatment of early stage breast cancer was developed and evaluated. The rationale for its development was the knowledge that breast conserving therapy (lumpectomy followed by breast radiation) and mastectomy produce equivalent outcomes, and the current general agreement that the decision for the type of surgery should rest with the patient.

An individual patient-based meta-analysis of tamoxifen versus ovarian ablation as first line endocrine therapy for premenopausal women with metastatic breast cancer

We performed a meta-analysis of randomized trials comparing tamoxifen to ovarian ablation carried out either by surgery or irradiation as first-line hormonal therapy for pre-menopausal women with metastatic breast cancer. Patients in all trials included were required to have measurable disease and to be currently menstruating or within 1 year of cessation of menses, and to have estrogen receptor (ER) positive or unknown disease (ER negative women were admitted to one of the studies). Individual patient data were obtained from the four studies identified and the results updated to June 1992. A total of 220 eligible patients were enrolled in the four trials. There was no difference in overall response rate between tamoxifen and oophorectomy across the four trials (p = 0.94, Mantel-Haenszel test). The odds reduction for progression was 14% ± 12% and for mortality 6% ± 13% in favour of tamoxifen, results which were not statistically significant (p = 0.32 and 0.72, respectively). Although the design of all four studies included a cross-over to the other therapy, only 54/111 patients receiving ovarian ablation and 34/109 patients receiving tamoxifen as primary therapy actually crossed over to the other arm at the time of disease progression. Response to initial treatment with tamoxifen was predictive of subsequent response to ovarian ablation (p < 0.05), and response to initial therapy with ovarian ablation was predictive of subsequent response to tamoxifen (p < 0.05). Support curves based on log-likelihood ratios revealed that this meta-analysis provides moderate evidence rejecting a 14% advantage for ovarian ablation compared to tamoxifen in terms of odds of disease progression. A 25% advantage for ovarian ablation with respect to odds of death is also rejected with moderate evidence. We conclude that the efficacy of tamoxifen appears to be similar to that of ovarian ablation by surgery or irradiation as first-line therapy for premenopausal, ER positive metastatic breast cancer, and is unlikely to be substantially inferior.

Randomized Phase III Study of Fludarabine Phosphate Versus Cyclophosphamide, Vincristine, and Prednisone in Patients With Recurrent Low-Grade Non-Hodgkin’s Lymphoma Previously Treated With an Alkylating Agent or Alkylator-Containing Regimen

PURPOSE To compare in a phase III study the safety and efficacy of fludarabine to that of cyclophosphamide, vincristine, and prednisone (CVP) in recurrent, low-grade, non-Hodgkins lymphoma after previous response to systemic treatment. PATIENTS AND METHODS Patients were randomized to fludarabine (25 mg/m(2) intravenously on days 1 to 5, every 28 days) or CVP (cyclophosphamide 750 mg/m(2) and vincristine 1.2 mg/m(2) both intravenously on day 1 and prednisone 40 mg/m(2) orally on days 1 to 5, every 21 days). The primary outcome assessed was progression-free survival (PFS); secondary outcomes included treatment-free survival (TFS), overall survival (OS), treatment-related toxicity, and quality of life (QoL) according to the European Organization for Research and Treatment of Cancers Quality of Life Questionnaire C-30 version 1.0 instrument. RESULTS Ninety-one patients were randomized, 47 to fludarabine and 44 to CVP. There was no difference in response rates, with 64% (complete response [CR], 9%) for fludarabine versus 52% (CR, 7%) for CVP (P =.72). With a median follow-up of 42 months, median PFS (11 months v 9.1 months; P =.03) and TFS (15 months v 11 months; P =.02) were superior in patients receiving fludarabine. No difference in median overall survival was detected (57 months for fludarabine v 44 months for CVP; P =.95). Three patients receiving fludarabine died of treatment-related toxicity compared with none of the patients receiving CVP. Peripheral neuropathy and alopecia were more common with CVP. Patients receiving fludarabine had higher scores for social function (P =.008); no other differences in QoL were detected. CONCLUSION In recurrent low-grade lymphoma, fludarabine improves PFS, TFS, and social function scores in comparison with CVP but does not improve OS.

Are medical oncologists biased in their treatment of the large woman with breast cancer

AbstractPurpose. Obesity and breast cancer are common conditions that often coexist. Concerns of relative overdosing of chemotherapy in the large cancer patient have led clinicians to apply empiric dose reductions, ‘cap’ the body surface area (BSA) at 2m2, or use ideal rather than actual body weight to calculate BSA. There are no data supporting or refuting these practices and their prevalence is unknown. We sought to determine the distribution of body size and prevalence of obesity in the breast cancer population of our cancer centre, and to determine clinician chemotherapy dosing practices in the era of modern adjuvant chemotherapy. Patients and methods. Women with invasive breast cancer receiving systemic therapy at our institution between 1980 and 1998 were identified and their recorded height and weight were used to calculate BSA and body mass index (BMI). We reviewed the first cycle adjuvant chemotherapy dosing practices from 1990–1998. The ideal dose of chemotherapy was calculated based on calculated BSA, and then contrasted with the actual dose received at cycle one. Discrepancies were recorded and categorized, using the largest single drug reduction if more than one drug was reduced. Results. Mean BMI in the systemic therapy population was 26.4±5.3kg/m2, 54% were overweight, 2% severely obese and 18% moderately so. Their mean BSA was 1.7±0.2m2 and only 5% had a BSA≥2m2. In the adjuvant chemotherapy subgroup, most patients received >85% of their ideal dose. The mean dose reduction was 5.3±11.3% versus 9.9±11.3% in the BSA <2 and >2m2 groups, respectively (p=0.02), and 4.3±8.2% versus 6.7±13.1% in the BMI <25 and ≥25kg/m2 groups, respectively (p=0.008). While only 24% of chemotherapy dose reductions of ≥15% were in the BSA ≥2m2 group, 76% were in the BMI ≥25kg/m2 group. Conclusions. Obesity is prevalent in this breast cancer population. BSA is not a sensitive index of large body size. We consistently detected more frequent empiric dose reductions at cycle one of adjuvant chemotherapy, with reductions of greater magnitude in the largest women (BSA ≥2m2) and those who were overweight (BMI ≥25kg/m2).