Determinants of physical,affective, and cognitive fatigue during breast cancer therapy and 12 months follow‐up

Fatigue is common in cancer survivors but often insufficiently treated. Due to its complexity a one‐size‐fits‐all treatment seems not appropriate. To gain more information on influencing factors and sub‐dimensions of fatigue we investigated potential determinants and correlates of physical, affective, and cognitive fatigue in breast cancer survivors during and after adjuvant therapy. Within the follow‐up of two randomized controlled trials physical, affective, and cognitive fatigue were repeatedly assessed during and up to 12 months after cancer therapy with the 20‐item Fatigue Assessment Questionnaire in 255 breast cancer survivors. Determinants of the different fatigue dimensions over time were explored with linear mixed models. Chemotherapy appeared as significant precipitating factor for physical fatigue. However, type of cancer therapy had no impact on fatigue one year post‐treatment. Obesity was significantly associated with increased physical fatigue throughout all time points (Δ=15.5 at 12 months) whereas exercise appeared to be beneficial (Δ = ?6.3). In contrast, affective fatigue was significantly associated with poor social support and worries about the future. In addition, poor sleep quality and previous use of psychopharmaceuticals were significantly associated with physical, affective, as well as cognitive fatigue. Further, hot flashes were associated with increased physical and cognitive fatigue. In conclusion, the broad diagnosis ‘fatigue’ in cancer survivors needs to be recognized as a diversity of symptoms determined by specific characteristics and likely different etiologies. Taking potential influencing factors such as obesity, physical inactivity, sleep problems, hot flashes, lack of social support, or psychological disorders into consideration might enable a better, individually‐tailored fatigue treatment.     

Patients' preferences for adjuvant chemotherapy in early-stage breast cancer: is treatment worthwhile?

When making decisions about adjuvant chemotherapy for early-stage breast cancer, costs and benefits of treatment should be carefully weighed. In this process, patients' preferences are of major importance. The objectives of the present study were: (1) to determine the minimum benefits that patients need to find chemotherapy acceptable, and (2) to explore potential preference determinants, namely: positive experience of the treatment, reconciliation with the treatment decision, and demographic variables. Preferences were elicited from patients scheduled for adjuvant chemotherapy (chemotherapy group: n = 38) before (T(1)), during (T(2)), and 1 month after chemotherapy (T(3)), and were compared to responses from patients not scheduled for chemotherapy (no-chemotherapy group: n = 38). The patients were asked, for a hypothetical situation, to indicate the minimum benefit (in terms of improved 5-year disease-free survival) to find adjuvant chemotherapy acceptable. In the chemotherapy group, the median benefit was 1% at all 3 measurement points. In the no-chemotherapy group the attitude towards chemotherapy became more negative over time, although not statistically significantly so (T(1): 12%, T(2): 15%, T(3): 15%; P = 0.10). At all measurement points, the patients in the chemotherapy group indicated that they would accept chemotherapy for significantly (P< 0.01) less benefit than the patients in the no-chemotherapy group. Of the demographic variables, age was related to preferences, but only at T(2)and only in the no-chemotherapy group. The more positive attitude towards chemotherapy and the stability of preferences in the chemotherapy group indicated that reconciliation with the treatment decision was a more important determinant of patients' preferences than positive experience of the treatment.     

Cognitive function after systemic therapy for breast cancer

An underinvestigated area of breast cancer survivorship involves the possible impairment of cognitive function following adjuvant chemohormonal therapy. Numerous reports of disturbing and disruptive changes in short- and long-term memory, attention span, concentration, and language skills have been made by breast cancer patients who have received chemotherapy. This article reviews the four published studies that have documented cognitive dysfunction following adjuvant chemohormonal therapies commonly used in breast cancer. The studies describe a subset of approximately one-third of participants who experienced long-term cognitive impairment. Patient- and treatment-related factors that may influence cognitive function are outlined. The impact of these cognitive impairments on the individual breast cancer survivor's quality of life is discussed, as is the potential overall impact of this research on future adjuvant therapy. The need for a prospective longitudinal study documenting the neuropsychological sequelae of adjuvant chemohormonal therapy is emphasized.     

Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer.

PURPOSE: The prospective applicability of new biologic tumor information to personalize adjuvant treatment of women with operable breast cancer remains to be demonstrated. The aim of the present study was to investigate whether patients with fast-proliferating, node-negative breast cancer could benefit from adjuvant chemotherapy with fluorouracil, epirubicin, and cyclophosphamide (FEC). PATIENTS AND METHODS: Beginning in November 1989, we analyzed the proliferative activity of primary tumors in a consecutive series of women with node-negative breast cancer to identify subgroups of patients with a worse prognosis and who were therefore suitable candidates for adjuvant systemic therapy. Proliferative activity was determined by means of the [3H]-thymidine incorporation assay using an autoradiographic technique. Women with fast-proliferating breast cancer ([3H]-thymidine labeling index, > 2.3%) were randomized to receive either six cycles of adjuvant FEC or no adjuvant therapy until disease progression. RESULTS: One-hundred twenty-five and 123 patients treated with radical surgery for pT1 to T2, N0, M0 breast cancer were randomized to the FEC and control arms, respectively. After a median follow-up of 70 months, 27 events (21.6%) were observed in the FEC arm and 39 (32.2%) in the control arm, with a significantly lower number of locoregional relapses in the FEC group. Five-year disease-free survival (DFS) was 81% in the FEC group and 69% in the control group (P <.02 by log-rank test). Cox multivariate analysis described the impact of adjuvant therapy with FEC on DFS as independent of the patients' main clinical-pathologic characteristics. CONCLUSION: FEC adjuvant polychemotherapy seems able to significantly improve the clinical outcome of patients with fast-proliferating, node-negative breast cancer.     

Secondary acute myelocytic leukemia after adjuvant therapy for early-stage breast carcinoma. A new complication of cyclophosphamide, methotrexate, and 5-fluorouracil therapy

The occurrence of treatment-related hematologic malignancies after adjuvant therapy with alkylating agents for gastrointestinal cancers, ovarian carcinoma, and breast cancer and after treatment for Hodgkin's disease, non-Hodgkin's lymphoma, germ-cell tumors, and multiple myeloma has been well documented. Adjuvant chemotherapy is frequently used for the treatment of early stage breast cancer, and to date there has been no increase in the incidence of secondary myelodysplastic syndromes or acute leukemia after cyclophosphamide-based regimens when compared with surgical controls. This report describes two patients who developed acute myelocytic leukemia only after exposure to cyclophosphamide, methotrexate, and 5-fluorouracil adjuvant therapy. These two cases of acute leukemia, which developed 3 years after diagnosis of breast cancer and initiation of chemotherapy, were characterized by trilineage dysplasia and pancytopenia, and had abnormalities of chromosomes 5 and 7: characteristics consistent with treatment-related leukemia. Many women are diagnosed with early stage breast cancer each year who are potential candidates for adjuvant therapy. Although certain subgroups of patients have been shown to benefit from adjuvant therapy, continued efforts must be directed at identifying responders so that others will not be exposed to the additional risks of chemotherapy.     

Patients’ preferences for surgical and adjuvant systemic treatment in early breast cancer: A systematic review

Purpose

Treatment decisions in early breast cancer can revolve around type of surgery and whether or not to have adjuvant systemic therapy. This systematic review aims to give an overview of patient self-reported factors affecting preferences for breast conserving surgery (BCS) versus mastectomy (MAST), the minimal benefit patients require from adjuvant chemotherapy (aCT) and/or adjuvant hormonal therapy (aHT) to consider it worthwhile, and factors influencing this minimally-required benefit.

Methods

PubMed and EMBASE were searched for relevant articles. Two reviewers independently selected articles and extracted data.

Results

We identified 15 studies on surgical and six on adjuvant systemic treatment decision-making. Factors affecting patient preference for BCS most frequently related to body image (44%), while factors influencing preference for MAST most often related to survival/recurrence (46%). To make adjuvant systemic therapy worthwhile, the median required absolute increase in survival rate was 0.1–10% and the median required additional life expectancy was 1 day to 5 years. The range of individual preferences was wide within studies. Participants in the aHT studies required larger median benefits than those in the aCT studies. Factors associated with judging smaller benefits sufficient most often (44%) related to quality of life (e.g., less treatment toxicity).

Conclusion

Decisive factors in patients’ preferences for surgery type commonly relate to body image and survival/recurrence. Most participants judged small to moderate benefits sufficient to consider adjuvant systemic therapy worthwhile, but individual preferences varied widely. Clinicians should therefore consider the patient’s preferences to tailor their treatment recommendations accordingly.     

Adjuvant therapy in colon cancer: current status and future directions

The role of adjuvant chemotherapy in patients with stage III colon cancer is now well established and 5-FU/LV should be the reference regimen to which new drugs are tested against in the adjuvant setting. In stage II colon cancer, because the risk of recurrence is lower, any absolute benefit of chemotherapy is likely to be less than in stage III disease. The studies performed so far have been generally underpowered to detect what might be a clinically significant effect on survival. Molecular profiling of tumours may identify individuals more likely to benefit from adjuvant therapy and tailor individual treatment in the future. After potential curative treatment for localised colon cancer, about two out of five patients will experience disease recurrence, but the most effective strategies for follow-up remain to be established. New drugs such as irinotecan, oxaliplatin and oral fluoropyrimidines may offer improved efficacy or patients' convenience in the adjuvant setting and their impact on survival will be evaluated in the recently closed large randomised studies. This review summarises the current status of adjuvant therapy in colon cancer and describes the future directions for research.     

Psychosocial factors in adjuvant hormone therapy for breast cancer: an emerging context for adherence research

Purpose

For patients with hormone receptor positive breast cancer, survivorship entails prolonged self-management of adjuvant treatment in the form of daily hormone therapy. Although sustained daily adherence across the 5-year course of therapy is associated with improved recurrence-free survival outcomes, adherence is suboptimal and many women discontinue hormone therapy prematurely. Factors associated with breast cancer survivors’ nonadherence and nonpersistence are not comprehensively understood. Furthermore, psychosocial variables have only received limited research attention, despite their documented relationships with adherence in other chronic illness populations.

Methods

A systematic literature review identified 14 studies that analyzed relationships between psychosocial factors and breast cancer survivors’ adherence and/or persistence with adjuvant hormone therapy.

Results

Although identified relationships were complex and at times inconsistent, salient conclusions emerged. Interpersonal factors, in the form of positive social support and patient-centered interactions with medical providers, as well as intrapersonal factors, such as anxiety and beliefs about the relative benefits of medication use, were reliably associated with better adherence and persistence. Depression did not demonstrate the negative impact on adherence that has been observed in other medical populations. No relationships between quality of life and adherence were identified.

Conclusions

Adjuvant hormone therapy appears to be a unique context for medication adherence, which warrants further attention and more rigorous analysis in future research.

Implications for Cancer Survivors

Individual patients’ psychosocial characteristics and health care preferences should be considered when striving to optimize medication adherence.     

Stability of decisional role preference over the course of cancer therapy

Cancer patients vary in their preferred level of involvement in medical decision making, and responding to patients' desired level of involvement is a key element of good medical care. While the literature has clearly demonstrated heterogeneity among cancer patients' preferences, less is known about how the preferences of any given patient may change over time. This longitudinal study compared cancer patients' preferences for involvement in medical decision making from the time of diagnosis to the time of completion of therapy. Data from 729 cancer patients with mixed diagnoses were analyzed. Most patients reported a change in preferred level of involvement over time, and multivariate analysis demonstrated that patients tend to prefer a decreasing level of involvement over time (p<0.0001). Stability of patients' preferences was also associated with type of cancer, but not with other sociodemographic characteristics. The results from this study highlight the importance of reevaluating patients' preferences for involvement in medical decision making throughout the course of cancer therapy, as such preferences are likely to change.     

American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer.

PURPOSE: To address whether all medically fit patients with curatively resected stage II colon cancer should be offered adjuvant chemotherapy as part of routine clinical practice, to identify patients with poor prognosis characteristics, and to describe strategies for oncologists to use to discuss adjuvant chemotherapy in practice. METHODS: An American Society of Clinical Oncology Panel, in collaboration with the Cancer Care Ontario Practice Guideline Initiative, reviewed pertinent information from the literature through May 2003. RESULTS: A literature-based meta-analysis found no evidence of a statistically significant survival benefit of adjuvant chemotherapy for stage II patients. Recommendations The routine use of adjuvant chemotherapy for medically fit patients with stage II colon cancer is not recommended. However, there are populations of patients with stage II disease that could be considered for adjuvant therapy, including patients with inadequately sampled nodes, T4 lesions, perforation, or poorly differentiated histology. CONCLUSION: Direct evidence from randomized controlled trials does not support the routine use of adjuvant chemotherapy for patients with stage II colon cancer. Patients and oncologists who accept the relative benefit in stage III disease as adequate indirect evidence of benefit for stage II disease are justified in considering the use of adjuvant chemotherapy, particularly for those patients with high-risk stage II disease. The ultimate clinical decision should be based on discussions with the patient about the nature of the evidence supporting treatment, the anticipated morbidity of treatment, the presence of high-risk prognostic features on individual prognosis, and patient preferences. Patients with stage II disease should be encouraged to participate in randomized trials.     

The impact of adjuvant therapy for breast cancer on cognitive function: current evidence and directions for research

Available evidence supports the hypothesis that adjuvant chemotherapy for breast cancer can produce cognitive deficits, and that these deficits may have a significant impact on patients' quality of life. Studies have generally compared the results of a variety of cognitive measures performed following treatment to standardized population-based norms or to cancer patients who received local therapy, rather than to the individual's baseline level of functioning. Several longitudinal studies are in progress or in the planning stages to better quantify and understand the incidence and impact of cognitive effects of adjuvant chemotherapy, and to identify possible susceptibility factors in subgroups. Although the neurocognitive changes appear to be subtle, there may be enough data to consider discussing the possibility of cognitive dysfunction as an adverse effect when assessing the risks and benefits of adjuvant chemotherapy. Likewise, as the aromatase inhibitors are increasingly given to larger numbers of women in the adjuvant setting, it will be important to understand the cognitive impact of estrogen deprivation. Finally, there is interest in examining supportive pharmacologic or behavioral measures that might prevent or decrease cognitive effects in this setting. Herein, the data on cognitive changes associated with chemotherapy for breast cancer, current and future research directions, as well as possible treatments are reviewed.     

Adjuvant breast cancer treatment and cognitive function: current knowledge and research directions

Evidence is mounting that potentially curative systemic adjuvant therapy for early-stage breast cancer may result in cognitive impairment. Five published studies have investigated cognitive function in this setting, and the consistent results of all five studies suggest an adverse effect of adjuvant chemotherapy. These studies are reviewed with particular attention to their methodologic limitations. For example, all five studies used cross-sectional designs, none controlled for possible confounding hormonal factors, and three examined patients who had not received a uniform chemotherapy regimen. The potential roles of chemotherapy-induced menopause and of adjuvant hormonal therapy in cognitive impairment are also discussed. Priorities for future research include confirmation of an effect of adjuvant chemotherapy in a study with a longitudinal design, closer examination of the potential contribution of hormonal factors, and similar studies on the effect of adjuvant therapy on cognitive function in other cancer types. If an effect of systemic adjuvant therapy on cognitive function is confirmed, such an effect will have implications for informed consent. It may also result in incorporation of objective measures of cognition in clinical trials of adjuvant therapy and in the investigation of preventive interventions that might minimize the impact of cognitive dysfunction after cancer treatment.     

Outcomes of high-dose chemotherapy and autologous stem-cell transplantation in stage IIIB inflammatory breast cancer.

PURPOSE: To evaluate the disease-free survival (DFS) and overall survival (OS), prognostic factors, and treatment-related mortality of women with stage IIIB inflammatory breast cancer (IBC) treated with combined modality therapy (CMT) and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation. PATIENTS AND METHODS: Between 1989 and 1997, 47 consecutive patients with stage IIIB IBC were treated with CMT and HDCT and were the subject of this retrospective analysis. Chemotherapy was administered to all patients before and/or after definitive surgery. Neoadjuvant and adjuvant chemotherapy was administered to 33 and 34 patients, respectively, and 20 patients received both. All patients received HDCT with autologous stem-cell transplantation, and 41 patients received locoregional radiation therapy. Tamoxifen was prescribed to patients with estrogen receptor (ER)-positive cancer. RESULTS: The mean duration of follow-up from diagnosis was 30 months (range, 6 to 91 months) and from HDCT was 22 months (range, 0.5 to 82 months). At 30 months, the Kaplan-Meier estimates of DFS and OS from diagnosis were 57.7% and 59.1%, respectively. At 4 years, the Kaplan-Meier estimates of DFS and OS from diagnosis were 51.3% and 51.7%, respectively. In a multivariate analysis, the only factors associated with better survival were favorable response to neoadjuvant chemotherapy (P =.04) and receipt of tamoxifen (P =.06); however, the benefit of tamoxifen was only demonstrated in patients with ER-positive breast cancer. At last follow-up, 28 patients (59. 6%) were alive and disease-free. Seventeen patients (36.2%) developed recurrent breast cancer. Seventeen patients died: 15 from disease recurrence and two (4.2%) from treatment-related mortality due to HDCT. CONCLUSION: In this analysis, the early results of treatment with CMT and HDCT compare favorably with other series of patients with stage IIIB IBC treated with CMT alone. These outcomes must be confirmed with longer follow-up and controlled studies.     

Can we approach zero relapse in breast cancer?

Adjuvant hormonal therapy and adjuvant chemotherapy have contributed significantly to the falling rates of breast cancer mortality. The introduction of taxanes and aromatase inhibitors in the adjuvant setting represents recent important improvements. More recently, the demonstration of significant benefit in the adjuvant setting with novel molecular targeted therapies (such as trastuzumab [Herceptin; Genentech, Inc., South San Francisco, CA, http://www.gene.com]) is already beginning to have a substantial impact on the adjuvant treatment of patients with certain tumor characteristics (i.e., HER-2 positivity). Neoadjuvant treatment represents an approach that offers an intermediate end point (i.e., pathologic complete response) that can be used as a marker of therapeutic activity. Furthermore, the use of genomic profiling is starting to replace the traditional prognostic and predictive factors currently used to estimate risks for recurrence and response to particular adjuvant therapies. These recent developments have demonstrated that the notion of approaching zero relapse in breast cancer patients is now within our reach.     

Undertreatment strongly decreases prognosis of breast cancer in elderly women.

PURPOSE: No consensus exists on therapy of elderly cancer patients. Treatments are influenced by unclear standards and are usually less aggressive. This study aims to evaluate determinants and effect of treatment choice on breast cancer prognosis among elderly patients. PATIENTS AND METHODS: We reviewed clinical files of 407 breast cancer patients aged >/= 80 years recorded at the Geneva Cancer Registry between 1989 and 1999. Patient and tumor characteristics, general health status, comorbidity, treatment, and cause of death were considered. We evaluated determinants of treatment by logistic regression and effect of treatment on mortality by Cox model, accounting for prognostic factors. RESULTS: Age was independently linked to the type of treatment. Overall, 12% of women (n = 48) had no treatment, 32% (n = 132) received tamoxifen only, 7% (n = 28) had breast-conserving surgery only, 33% (n = 133) had mastectomy, 14% (n = 57) had breast-conserving surgery plus adjuvant therapy, and 2% (n = 9) received miscellaneous treatments. Five-year specific breast cancer survival was 46%, 51%, 82%, and 90% for women with no treatment, tamoxifen alone, mastectomy, and breast-conserving surgery plus adjuvant treatment, respectively. Compared with the nontreated group, the adjusted hazard ratio of breast cancer mortality was 0.4 (95% CI, 0.2 to 0.7) for tamoxifen alone, 0.4 (95% CI, 0.1 to 1.4) for breast-conserving surgery alone, 0.2 (95% CI, 0.1 to 0.7) for mastectomy, and 0.1 (95% CI, 0.03 to 0.4) for breast-conserving surgery plus adjuvant treatment. CONCLUSION: Half of elderly patients with breast cancer are undertreated, with strongly decreased specific survival as a consequence. Treatments need to be adapted to the patient's health status, but also should offer the best chance of cure.     

The cognitive sequelae of standard-dose adjuvant chemotherapy in women with breast carcinoma: results of a prospective, randomized, longitudinal trial

BACKGROUND: Retrospective trials have reported that chemotherapy-induced cognitive dysfunction was experienced by a subset of patients with breast carcinoma. However, recent evidence indicated that a subset also exhibited impaired cognitive function at baseline, before the start of chemotherapy. A prospective, longitudinal trial that incorporates baseline neuropsychologic evaluations is necessary to determine to what extent cognitive dysfunction is attributable to chemotherapy in this population. METHODS: Eighteen women with breast carcinoma underwent a comprehensive neuropsychologic evaluation before treatment and at short-term and long-term intervals after chemotherapy. The incidence, nature, severity, and chronicity of cognitive dysfunction developing in patients with breast carcinoma treated with a standard dose of adjuvant chemotherapy were assessed. RESULTS: Before the start of systemic therapy, 33% of women in the current cohort exhibited cognitive impairment. At the short-term postchemotherapy time point, 61% of the cohort exhibited a decline relative to baseline in 1 or more domains of cognitive functioning and reported greater difficulty in maintaining their ability to work. The most common domains of cognitive dysfunction were related to attention, learning, and processing speed. At the long-term postchemotherapy time point, approximately 50% of patients who experienced declines in cognitive function demonstrated improvement, whereas 50% remained stable. Self-reported ability to perform work-related activities also improved over this interval. Neither impairment at baseline nor subsequent treatment-related cognitive decline exhibited any statistically significant correlation with affective well-being or with demographic or clinical characteristics. CONCLUSIONS: The current study is the first longitudinal trial to report evidence of an association between cognitive dysfunction and chemotherapy in a subgroup of women with nonmetastatic breast carcinoma. The importance of using prospective research designs, appropriate cognitive measures, and statistical methods to evaluate subgroup effects was discussed. Identification of mechanisms associated with cognitive dysfunction and of risk factors contributing to subgroup vulnerability is necessary.     

Perspectives, preferences, care practices, and outcomes among older and middle-aged patients with late-stage cancer.

PURPOSE: To evaluate relationships among physician and cancer patient survival estimates, patients' perceived quality of life, care preferences, and outcomes, and how they vary across middle-aged and older patient groups. PATIENTS AND METHODS: Subjects were from the Study to Understand Prognoses and Preferences for Risks of Treatments (SUPPORT) prospective cohort studied in five US teaching hospitals (from 1989 to 1994), and included 720 middle-aged (45 to 64 years) and 696 older (> or = 65 years) patients receiving care for advanced cancer. Perspectives were assessed in physician and patient/surrogate interviews; care practices and outcomes were determined from hospital records and the National Death Index. General linear models were used within age groups to obtain adjusted estimates. RESULTS: Although most patients had treatment goals to relieve pain, treatment preferences and care practices were linked only in the older group. For older patients, preference for life-extending treatment was associated with more therapeutic interventions and more documented discussions; cardiopulmonary resuscitation (CPR) preference was linked to more therapeutic interventions and longer survival. For middle-aged patients, better perceived quality of life was associated with preferring CPR. In both groups, patients' higher survival estimates were associated with preferences for life-prolonging treatment and CPR; physicians' higher survival estimates were associated with patients' preferences for CPR, fewer documented treatment limitation discussions about care, and actual 6-month survival. More discussions were associated with readmissions and earlier death. More aggressive care was not related to outcomes. CONCLUSION: Fewer older patients preferred CPR or life-prolonging treatments. Although older patients' goals for aggressive treatment were related to care, this was not so for middle-aged patients. Aggressive care was not related to prolonged life in either group.     

Adjuvant Chemotherapy for Rectal Cancer After Neoadjuvant Treatment: FOLFOX, 5-FU,or Observation

A multimodality approach incorporating concurrent chemotherapy with radiotherapy prior to surgery has become the standardized approach in the management of localized rectal cancer. However, it is unknown whether any further therapy after surgery may be beneficial in improving patient outcomes. Previous completed randomized clinical trials have not added any clarity in this regard, whether adjuvant chemotherapy or intensified chemotherapy regimens improve patient outcomes in those who have previously received neoadjuvant therapy. Despite the lack of evidence, based off the survival data in stage III colon cancer, adjuvant chemotherapy has become a standardized practice in the management of resected rectal cancer. Furthermore, recommendations include the consideration of added oxaliplatin to adjuvant therapy in this disease. While it is unclear whether all patients should receive adjuvant chemotherapy, a subset of patients, including those who achieve a pathologic response may benefit from further treatment. Ongoing studies utilizing an individualized, stepwise multimodality approach may define the role of adjuvant therapy and the appropriate regimen in patients with resected rectal cancer.     

Manganese superoxide dismutase polymorphism, treatment-related toxicity and disease-free survival in SWOG 8897 clinical trial for breast cancer

To date, the few studies of associations between a functional polymorphism in the oxidative stress-related gene manganese superoxide dismutase (SOD2) and breast cancer survival have been inconsistent. In a homogeneous patient population from a large cooperative group trial Southwest Oncology Group (SWOG) 8897, we evaluated this polymorphism in relation to both treatment-related toxicity and disease-free survival (DFS). Among 458 women who received cyclophosphamide-containing adjuvant chemotherapy, those with variant C alleles, related to higher antioxidant activity, experienced less grade 3–4 neutropenia (OR = 0.52, 95% CI = 0.29–0.92) but had worse DFS (HR = 1.59, 95% CI = 0.99–2.55) than women with TT genotypes. No associations were observed among 874 women who were followed without adjuvant therapy. Our results are consistent with the hypothesis that women with higher SOD2 antioxidant activity may experience less treatment-related toxicity but shorter time to disease recurrence or death after breast cancer adjuvant chemotherapy, supporting the modifying effects of oxidative stress-related enzymes on cancer treatment toxicity and efficacy.     

Patient preferences for adjuvant chemotherapy of early breast cancer: how much benefit is needed?

Adjuvant chemotherapy for early-stage breast cancer has been shown to delay recurrence and improve survival. However, the benefits are modest and must be balanced against the adverse treatment effects. We assessed the size of the survival benefit needed to justify the toxicity of chemotherapy, based on the preferences of women who had previously received adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). We also attempted to identify circumstances in which larger survival gains would be needed. In semistructured interviews, 104 women who had received adjuvant CMF chemotherapy were asked to rate the survival benefit that would justify 6 months of such treatment, using a series of hypothetical trade-offs between shorter survival without treatment and longer survival with treatment. Similar preferences were sought for a greater probability of 5-year survival. Most patients considered 6 months of adjuvant CMF chemotherapy worthwhile for relatively modest survival gains: 77% considered an increase of from 5 to 6 years worthwhile, 74% thought an increase of from 15 to 17 years worthwhile, and more than 70% considered such treatment justified for a 5% greater chance of living 5 or more years. Smaller survival benefits were needed for women who had experienced less toxicity (P =.01), had not received initial radiotherapy (P =.01), had better social support (P =.02), and had others at home dependent on their support (P =.0001). Modest survival benefits are sufficient to justify adjuvant cytotoxic chemotherapy for most women with early-stage breast cancer. Individual preferences are important when weighing trade-offs between survival and adverse treatment effects.