Adriamycin And Cyclophosphamide Research Articles

Comparison of neoadjuvant chemotherapy (NACT) with 5-flurouracil, epirubicin (100mg), cyclophosphamide (FEC100) followed by docetaxel (D) (75mg) versus adriamycin and cyclophosphamide (AC) followed by docetaxel (100mg) in locally advanced breast cancer (LABC): A randomized clinical study.

e12002 Background: NACT in LABC improves the rate of breast conservation and pathological complete response (pCR), which could be a surrogate marker for chemo responsiveness and survival. In this s...

Abstract S3-02: NSABP B-36: A randomized phase III trial comparing six cycles of 5-fluorouracil (5-FU), epirubicin, and cyclophosphamide (FEC) to four cycles of adriamycin and cyclophosphamide (AC) in patients (pts) with node-negative breast cancer

Abstract Background NSABP B-36 was originally designed as a 2X2 factorial randomized study to compare 6 cycles of FEC-100 with 4 cycles of standard AC with or without celecoxib in pts with node-negative breast cancer. The rationale for the trial was based on observations from other adjuvant trials suggesting that longer duration of anthracycline-based therapy may result in improved outcomes and also on accumulating evidence that prostaglandins may contribute to the malignant phenotype in breast cancer. The trial opened in May 2004 but random assignment to celecoxib v placebo was terminated in December 2004 (after 327 pts were enrolled) because of concerns for increased risk of cardiovascular disease with the use of COX-2 inhibitors. The trial continued as a two-arm study and completed accrual in July 2008. The primary endpoint of disease-free survival (DFS), and secondary endpoints of overall survival (OS), recurrence-free interval (RFI), distant recurrence-free interval (DRFI), and adverse events comparing FEC-100 and AC are reported here. Analyses of quality of life indicators will be reported separately. Methods 2,722 pts with T1-3, pN0 breast cancer were randomly assigned to either adriamycin 60 mg/m2 and cyclophosphamide 600mg/m2 every 21 days for 4 cycles (n=1361) or 5-FU 500mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 every 21 days for 6 cycles (n=1361). Hormone- receptor positive pts were to receive physician's choice of hormonal therapy for a minimum of 5 yrs. Trastuzumab for HER2-positive pts was at investigator's discretion but was not to begin for >3 weeks after the last dose of chemotherapy. All women treated with lumpectomy were to receive breast radiotherapy; post-mastectomy chest wall radiotherapy was at physician's discretion. The differences in DFS (OS, RFI, and DRFI) between two treatment arms were assessed by log-rank test stratified by hormone receptor status and type of surgery. Results Median follow-up is 82.8 months. Pt and tumor characteristics were equally distributed between the two groups (<50 years old: 40%, lumpectomy: 68%, and hormone positivity: 65 %). Overall, Grade 3 and 4 expected toxicities were more frequent in the FEC arm. Combined Grade 3/4 toxicities reaching statistical significance with a difference of 3% or more between AC and FEC arms included fatigue 3.55% v 8.45%, febrile neutropenia 3.70% v 9.42%, and thrombocytopenia 0.74% v 4.41%, respectively. While on treatment, Grade 3 left ventricular systolic dysfunction occurred in one pt in each arm. There were 2 toxicity deaths on AC and 5 on the FEC arm. Primary and secondary endpoint analyses at 8 ys did not reveal any significant differences in DFS, OS, RFI, or DRFI. EndpointAC (%)FEC (%)HRCIp-valueDFS83.082.81.040.85,1.260.70OS91.292.00.940.71,1.240.65RFI90.090.40.970.76,1.260.84DRFI92.393.00.890.66,1.200.43 Conclusions Six cycles of the FEC-100 regimen did not result in any efficacy advantage over 4 cycles of standard AC in node-negative breast cancer pts. As anticipated, the FEC-100 regimen resulted in greater toxicity. Support NCI: U10-CA-12027, -37377, -69974, -69651, -44066-26; Pharmacia & Upjohn Co. Citation Format: Jacobs A Samuel, John W Wilson, Hanna Bandos, Richard M Elledge, André Robidoux, Louis Fehrenbacher, Patrick J Ward, Johnathan Polikoff, Adam M Brufsky, Louise Provencher, Alexander HG Paterson, John T Hamm, Robert L Carolla, Luis Baez-Diaz, Priya Rastogi, Thomas B Julian, D Lawrence Wickerham, Sandra M Swain, Charles E Geyer Jr, Eleftherios P Mamounas, Norman Wolmark. NSABP B-36: A randomized phase III trial comparing six cycles of 5-fluorouracil (5-FU), epirubicin, and cyclophosphamide (FEC) to four cycles of adriamycin and cyclophosphamide (AC) in patients (pts) with node-negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S3-02.

Toxicity and quality of life of Korean breast cancer patients treated with docetaxel-containing chemotherapy without primary G-CSF prophylaxis

The aim of this study was to evaluate the toxicity and quality of life (QoL) of breast cancer patients treated with a docetaxel-containing chemotherapeutic regimen and to compare adriamycin and cyclophosphamide (AC) for four cycles followed by docetaxel (D) for four cycles with docetaxel, adriamycin, and cyclophosphamide (TAC) for six cycles without primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. Node-positive breast cancer patients who received surgery from three hospitals were included. Subjects received docetaxel-containing chemotherapy and completed a questionnaire on QoL (EORTC QLQ-C30 and QLQ-BR23) at each cycle. Toxicity was assessed using the National Cancer Institute Common Toxicity Criteria. All 78 eligible subjects and 542 cycles were analyzed. The incidence of dose reduction and grade 3 edema was higher in the AC-D group. The incidence of febrile neutropenia was significantly increased in the TAC group (63.4 %) compared to the AC-D group (29.7 %). Grade 3 or 4 anemia was higher in the TAC group, and grade 3 or 4 arthralgia was higher in the AC-D group. There were no significant differences in severe nausea and vomiting, fatigue, neuropathy, and peripheral edema. Baseline quality of life showed no difference between the two groups. The global health status decreased during chemotherapy and recovered to baseline level 3 months after chemotherapy. Although the incidence of febrile neutropenia was high without primary G-CSF prophylaxis and was more severe in the TAC group, QoL revealed comparable results in both regimens; therefore, it could be one of the considerations in the choice of treatment strategy.

Do Leucopenia Rates Change After Widespread Folic Acid Fortification in Randomized Controlled Trials of Breast Cancer Chemotherapy?

Abstract 4741 IntroductionFolate is an essential nutrient functioning in a variety of one-carbon transfer reactions, is necessary for red blood cell formation and growth, and deficiency is known to cause megaloblastic anemia. The role of folate in prevention of neural tube defects has been the driving force in public health measures leading to large-scale food fortification in the United States starting in 1996. It is not known if folate fortification has an impact on hematologic toxicities of patients undergoing chemotherapy. The goal of this study is to compare rates of leucopenia reported in pre and post folic acid fortification randomized clinical trials of Adriamycin and Cyclophosphamide (AC) chemotherapy in breast cancer. MethodsRandomized trials of breast cancer chemotherapy with AC conducted in the United States were searched for in the Medline database, bibliographies, and using Google Scholar. Studies were included if AC was used alone in any arm of study, at standard dosing. Only studies that included disease free survival (DFS), overall survival (OS), and rates of grade III/IV leucopenia for the AC group were included. Studies were eliminated if they included patients with known metastatic disease, “dose dense” or nonstandard AC regimens, or included growth factor support. Rates of phase III/IV leucopenia were grouped in pre and post 1996 folate fortification groups, and meta-analyzed in a random effects model using MIX, a comprehensive free software for meta-analysis of causal research data. ResultsSeven studies involving 14,386 patients were identified using the defined search methodology. There was no significant difference in phase III/IV leucopenia rates between prefolate (4.36% 95%CI 2.31-6.42%) and postfolate studies (7.07% 95%CI 5.41-8.73%). ConclusionsThis review disclosed no statistically significant difference in the rates of leucopenia in patients given AC for breast cancer before or after 1996. Postfolate studies did have 46% more leucopenia than those prior to folate fortification. The confidence intervals of the leucopenia rates overlapped but approached significance. This is contradictory to our theory that increased dietary folate might mitigate hematologic toxicities of chemotherapy. Further studies using individual patient data from institutions administering AC pre and post fortification would further elucidate the role of dietary folate in hematologic toxicities. Disclosures:No relevant conflicts of interest to declare.

Short term results from GHRH analogue use in pre-menopausal breast cancer in Korea

Background Hormone receptor-positive, pre-menopausal breast cancer patients can be treated by chemotherapy and/or ovarian suppression therapy. We reported our experience of gonadotropin-releasing hormone analogue plus tamoxifen (GnRHa + T) or adriamycin and cyclophosphamide (AC) followed by tamoxifen (AC → T) in pre-menopausal women with hormone-response, node-negative breast cancer. Methods We retrospectively reviewed the records of 587 pre-menopausal women with hormone-responsive, node-negative breast cancer. Of these, 269 were treated with adriamycin and cyclophosphamide (AC) followed by tamoxifen (AC → T), and 318 were treated with gonadotropin-releasing hormone analogue plus tamoxifen (GnRHa + T). Among them, 151 patients were treated by goserelin acetate 3.6 mg/kg and 125 patients were treated by leuprorelin acetate 3.75 mg/kg every 28 days subcutaneously. Findings At a median follow-up time of 30 months, eight patients had relapsed and three had died. DFS did not differ between the AC → T and GnRHa + T groups. Of the three deaths, two were not related to breast cancer. The third patient, in the AC → T group, died because of brain metastasis. GnRHa + T treatment had no effect on blood profile and did not cause the development of detrimental symptoms but decreased bone mineral density. The efficacy of leuprorelin was similar to that of goserelin. Interpretation GnRHa + T treatment can be an alternative treatment option in pre-menopausal women with endocrine-responsive, node-negative, breast cancer patients. The efficacy and tolerability of leuprorelin were similar to that of goserelin.

Adriamycin and cyclophosphamide followed by tamoxifen, versus the combination of gonadotropin-releasing hormone analog and tamoxifen, in the treatment of premenopausal endocrine-responsive node-negative breast cancer.

Abstract Abstract #1151 Purpose
 To compare the efficacy of adriamycin and cyclophosphamide (AC) followed by tamoxifen (AC->T) with gonadotropin-releasing hormone analog plus tamoxifen (GnRHa+T) in premenopausal women with hormone-response, node-negative breast cancer.
 Patients and Methods 
 We retrospectively reviewed the records of 587 premenopausal women with hormone- responsive, node-negative breast cancer. Of these, 269 were treated with AC->T, and 318 were treated with GnRHa (goserelin acetate 3.6 mg/kg or leuprorelin acetate 3.75 mg/kg every 28 days subcutaneously)+T. The main study outcome was disease-free survival (DFS).
 Results
 At a median follow-up time of 30 months, eight patients had relapsed and three had died. DFS did not differ between the AC->T and GnRHa+T groups. Of the three deaths, two were not related to breast cancer. The third patient, in the AC ->T group, died because of brain metastasis. GnRHa+T treatment had no effect on blood profile and did not cause the development of detrimental symptoms but decreased bone mineral density. The efficacy of leuprorelin was similar to that of goserelin.
 Conclusion 
 GnRHa +T and AC->T had comparable efficacy after 30 months of follow-up. The efficacy and tolerability of leuprorelin acetate was similar to that of goserelin. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1151.

Patterns of sore mouth in outpatients with cancer receiving chemotherapy

The aims of this secondary data analysis were to (a) categorize patterns in the development, duration, intensity, and resolution of sore mouth (which can be considered a proxy for oral mucositis) severity and distress over two cycles of chemotherapy in cancer outpatients and (b) examine the relationship of demographic (age, gender, marital status, and educational level) and disease characteristics (type of cancer and type of chemotherapy) to specific patterns of sore mouth (SM). Visual graphical analysis (VGA) was applied to identify individual patterns of SM severity and distress in 51 outpatients receiving chemotherapy who provided daily reports of sore mouth using a computerized interactive voice response system. The majority were female (n = 41, 8%) with a mean age of 53 (SD = 8.35). Most had breast cancer (68%), and one third received chemotherapy with adriamycin and cyclophosphamide (AC). VGA is a technique in which graphs of individual patients' symptoms are coded for specific individual or group profiles. Seven distinct patterns were identified based on variability in onset, duration, and intensity (degree of severity or distress). Chemotherapy agents were significantly associated with patterns of SM. The AC regimen was significantly associated with late onset; however, the intensity did not last long. In contrast, patients receiving R-CHOP were significantly more likely to experience duration intensity (SM after day 15 and a score equal to or greater than a 5 on a 1-10 scale). VGA revealed symptom patterns often hidden in traditional analysis. Understanding individual variability is important to the design and implementation of future intervention research and clinical care.

Impact of a Reduced Dose Intensity of Adjuvant Anthracycline Based Chemotherapy in a Population-Based Cohort of Stage I-II Breast Cancers

Background:Reductions in the dose intensity (DI) of adjuvant anthracycline-based chemotherapy in early stage breast cancer are frequently required due to treatment toxicity or poor tolerance, but the implications of a minimal reduction in DI on clinical outcome remain uncertain.Patients and methods:Women with stage I–II breast cancer treated with adjuvant adriamycin and cyclophosphamide (AC) from 1990–95 were identified in a provincial breast cancer database. Cases were classified into four cohorts: (1) all cycles delivered at full dose and on time; (2) one single dose reduction or dose delay; (3) >1 dose reduction or dose delay; (4) <2 cycles of chemotherapy delivered.Results:484 eligible cases were identified (cohort (1): n = 268; (2): n= 88; (3): n= 89; (4) n= 39). Slight imbalances in lymph node status (p=0.05) and adjuvant hormonal therapy (p=0.05) were observed between the cohorts. Fifty-five per cent (267/484) of the patients had node-positive disease and 33% (158/484) were ER+. 45% of cases had a reduction in DI. With a median follow-up of 9.6 years, there were no significant differences in relapse-free survival (p=0.94), breast cancer-specific survival (p=0.87) or overall survival (p=0.86) between the four cohorts. Outcomes were independent of hormone receptor status.Conclusions:Although toxicity related reductions in the DI of adjuvant AC chemotherapy for early stage breast cancer are common, they did not appear to significantly impact on clinical outcomes in this population-based cohort of women with stage I–II breast cancers.

A New Model of Patient Tumor-Derived Breast Cancer Xenografts for Preclinical Assays

To establish a panel of human breast cancer (HBC) xenografts in immunodeficient mice suitable for pharmacologic preclinical assays. 200 samples of HBCs were grafted into Swiss nude mice. Twenty-five transplantable xenografts were established (12.5%). Their characterization included histology, p53 status, genetic analysis by array comparative genomic hybridization, gene expression by Western blotting, and quantitative reverse transcription-PCR. Biological profiles of nine xenografts were compared with those of the corresponding patient's tumor. Chemosensitivities of 17 xenografts to a combination of Adriamycin and cyclophosphamide (AC), docetaxel, trastuzumab, and Degarelix were evaluated. Almost all patient tumors established as xenografts displayed an aggressive phenotype, i.e., high-grade, triple-negative status. The histology of the xenografts recapitulated the features of the original tumors. Mutation of p53 and inactivation of Rb and PTEN proteins were found in 83%, 30%, and 42% of HBC xenografts, respectively. Two HBCx had an ERBB2 (HER2) amplification. Large variations were observed in the expression of HER family receptors and in genomic profiles. Genomic alterations were close to those of original samples in paired tumors. Three xenografts formed lung metastases. A total of 15 of the 17 HBCx (88%) responded to AC, and 8 (47%) responded to docetaxel. One ERBB2-amplified xenograft responded to trastuzumab, whereas the other did not. The drug response of HBC xenografts was concordant with that of the patient's tumor in five of seven analyzable cases. This panel of breast cancer xenografts includes 15 triple-negative, one ER positive and 2 ERBB2 positive. This panel represents a useful preclinical tool for testing new agents and protocols and for further exploration of the biological basis of drug responses.

Predictive gene expression patterns of response to adriamycin and cyclophosphamide (AC) in human breast cancers

527 Background: Adriamycin and cyclophosphamide (AC) and docetaxel (D) are widely used in the treatment of breast cancer. We conducted a prospective, randomized, multicenter trial to discover predictive markers of AC and D and hypothesized that gene expression profiles can select appropriate patients who may respond to AC, and that these patterns are different from our published docetaxel (D) profiles Methods: One hundred and twenty patients were randomized to either 4 cycles of AC (60/600 mg/m2) or D (100mg/m2) prior to surgery. Core biopsies from 60 patients were obtained before treatment with neoadjuvant AC. Pathologic responses were assessed after AC. Gene expression patterns were determined using Affymetrix U133A GeneChips. Differential genes for AC response were then validated by QRT-PCR in an independent cohort of 33 patients treated with AC. Results: The median age was 48 yrs (range 30–72), clinical response rates were 57% (34/60), and pathological complete response (pCR) or near pCR (npCR) was observed in 22% (12/60) in AC arm. Differential expression between sensitive and resistant tumors with a low false discovery rate (FDR 5–10%) was obtained. Of these 82 differentially expressed genes, pathways up-regulated in sensitive tumors included TOP2A, metabolism (LYZ), survival (CFLAR, CASP3), cell cycle (MKI67), cytokines and other inflammatory genes. This molecular portrait for AC was not predictive of docetaxel response. By QRT-PCR of 4 genes (LYZ, CFLAR, MKI67 and TOP2A) in the independent tumor set, LYZ was predictive of AC pathologic complete response. Additional genes will be validated in the second cohort. Conclusions: The molecular profile for AC is different from the docetaxel expression profile. This potential predictive test may allow selection of the most appropriate chemotherapy schedule for women with breast cancer. No significant financial relationships to disclose.

National Surgical Adjuvant Breast and Bowel Project (NSABP)

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by National Surgical Adjuvant Breast and Bowel Project (NSABP). Clinical trials include: NSABP B-35 – A clinical trial comparing anastrozole with tamoxifen in postmenopausal patients with ductal carcinoma in situ (DCIS) undergoing lumpectomy with radiation therapy.NSABP B-36 – A clinical trial of adjuvant therapy comparing six cycles of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) to four cycles of adriamycin and cyclophosphamide (AC) in patients with node-negative breast cancer.NSABP B-38 – A phase III, adjuvant trial comparing three chemotherapy regimens in women with node-positive breast cancer: docetaxel/doxorubicin/cyclophosphamide (TAC); dose-dense (DD) doxorubicin/cyclophosphamide followed by DD paclitaxel (DD AC→P): DD AC followed by DD paclitaxel plus gemcitabine (DD AC→PG).NSABP B-39 – A randomized phase III study of conventional whole breast irradiation (WBI) versus partial breast irradiation (PBI) for women with stage 0, I, or II breast cancer.

P-166: Chemotherapy-related amenorrhea in premenopausal women with breast cancer: The effect of paclitaxel, dose density and trastuzumab

The effect of the addition of paclitaxel (T) to adriamycin and cyclophosphamide (AC), use of a dose dense (DD, q2wk) regimen, or use of trastuzumab/herceptin (H) on menstrual functioning in premenopausal women with early breast cancer remains uncertain. No previous studies have evaluated the effects of DD and H on the menstrual cycle.

Impact of taxanes on weight gain during neoadjuvant chemotherapy (Ctx) for breast cancer (BC)

10606 Background: Weight gain after the diagnosis of BC has been associated with increased risk of recurrence and mortality. Previous studies have documented weight gain after cyclophosphamide, methotrexate, and 5-fluoruracil (CMF) and adriamycin and cyclophosphamide (AC) chemotherapy, but the impact of taxane chemotherapy has not been described. Methods: We reviewed the charts of 119 patients (pts) who completed neoadjuvant Ctx between 1997–2005. Age, baseline body mass index (BMI), tumor size, nodal status, hormone receptor status, menopausal status, co-morbid illnesses and anti-depressant use were collected. Weight was recorded at each Ctx visit and at follow-up visits for two years. Results: 22 pts received AC only. 97 pts received AC followed by a taxane - 58 docetaxel (D), 39 paclitaxel (P). Median f/u time was 26.3 months. 66/119 (55%) of pts gained weight during Ctx, with a median change of + 1 pound (range -28 to +19.5 pounds) at the end of Ctx. 49/119 (41%) of pts gained weight during AC and 76/97 (78%) of pts gained weight during the taxane. Mean weight change after AC was -1.8 pounds compared to +3.2 pounds after the taxane (p &lt; 0.001). Age, baseline BMI, and menopausal status prior to Ctx did not predict weight gain. There was no difference in weight gain between pts who received D vs. P (p = 0.19). 8/22 (36%) patients who received AC alone recurred, and 13/95 (14%) who received both AC and T recurred; however this was not statistically significant (p = 0.23). Total weight change during neoadjuvant Ctx did not predict recurrence; however weight gain during the AC portion was associated with a higher risk of recurrence when adjusted for weight gain during taxane Ctx (p = 0.035, Cox regression). Each one pound gained was associated with an 11% increase in risk of recurrence. Conclusions: Weight gain is common during neoadjuvant Ctx for BC, particulary during treatment with taxanes. Further follow up is required to establish if weight gain is maintained over time and to determine the impact of weight change on BC outcomes and health. No significant financial relationships to disclose.

Chemotherapy-related amenorrhea in women with early breast cancer: The effect of paclitaxel or dose density

10506 Background: The effect of the addition of paclitaxel (T) to adriamycin and cyclophosphamide (AC), or dose density (DD, q2wk) on menstrual functioning in women with early breast cancer remains uncertain. Methods: We reviewed data from premenopausal women treated at Dana-Farber Cancer Institute and Brigham and Women’s Hospital who received adjuvant chemotherapy with either AC or AC-T from 1997–2005 for whom pre- and post-treatment menstrual data were available. A multivariable logistic regression model evaluating amenorrhea at 6 months or greater follow-up was conducted. Results: Of the 403 patients eligible for analysis, average age at diagnosis was 41 years (range 25–50); average weight was 67kg; 10% were smokers, 53% had never smoked; 24% were nulliparous. 60% of women received AC, 40% AC-T; 20% of women received DD therapy (either AC or AC-T); 72% received tamoxifen. The multivariable model adjusting for age, weight, gravity, parity, smoking, alcohol use, and tamoxifen use, revealed that risk of amenorrhea was not statistically different in patients receiving AC-T versus AC (OR = 1.45, 95% CI 0.78–2.69) or in patients receiving DD therapy versus standard (OR = 1.61, 95% CI 0.74–3.49). However, a planned future analysis including data from an additional 200+ patients may yield significant differences. Age directly correlated with risk of amenorrhea, OR = 1.40, 95% CI 1.30–1.50) for every year increase in age, and women receiving tamoxifen were more likely to be amenorrheic (OR = 1.99, 95% CI 1.05–3.79). Conclusions: The addition of T to AC or use of DD therapy does not appear to increase the likelihood of amenorrhea in follow-up. These findings may assist premenopausal women with breast cancer when making decisions at diagnosis and in follow-up. No significant financial relationships to disclose.

The effect of the stromal component of breast tumours on prediction of clinical outcome using gene expression microarray analysis

IntroductionThe aim of this study was to examine the effect of the cellular composition of biopsies on the error rates of multigene predictors of response of breast tumours to neoadjuvant adriamycin and cyclophosphamide (AC) chemotherapy.Materials and methodsCore biopsies were taken from primary breast tumours of 43 patients prior to AC, and subsequent clinical response was recorded. Post-chemotherapy (day 21) samples were available for 16 of these samples. Frozen sections of each core were used to estimate the proportion of invasive cancer and other tissue components at three levels. Transcriptional profiling was performed using a cDNA array containing 4,600 elements.ResultsTwenty-three (53%) patients demonstrated a 'good' and 20 (47%) a 'poor' clinical response. The percentage invasive tumour in core biopsies collected from these patients varied markedly. Despite this, agglomerative clustering of sample expression profiles showed that almost all biopsies from the same tumour aggregated as nearest neighbours. SAM (significance analysis of microarrays) regression analysis identified 144 genes which distinguished high- and low-percentage invasive tumour biopsies at a false discovery rate of not more than 5%. The misclassification error of prediction of clinical response using microarray data from pre-treatment biopsies (on leave-one-out cross-validation) was 28%. When prediction was performed on subsets of samples which were more homogeneous in their proportions of malignant and stromal cells, the misclassification error was considerably lower (8%–13%, p < 0.05 on permutation).ConclusionThe non-tumour content of breast cancer samples has a significant effect on gene expression profiles. Consideration of this factor improves accuracy of response prediction by expression array profiling. Future gene expression array prediction studies should be planned taking this into account.

Energy Balance in Women With Breast During Adjuvant Treatment

Objective To compare weight, body composition, and major determinants of energy balance of women treated with adjuvant chemotherapy (n=8) using Adriamycin and cyclophosphamide (AC), or radiation therapy (n=10). Design The study used a nonrandomized prospective design. Pretreatment and posttreatment measurements, obtained at baseline and 12 weeks, respectively, included weight, body composition (determined using dual-energy x-ray absorptiometry), energy intake (determined using 3-day food records), resting energy expenditure (determined in indirect calorimetry), and physical activity (determined using 3-day physical activity records). Poststudy follow-up weights were obtained for 13 women. Subjects/setting Eighteen premenopausal women with breast cancer in the early stage, recruited from outpatient clinics, participated in and completed the study. Statistical analyses performed Unpaired Student t tests or χ 2 tests were used to test for differences in baseline subject characteristics, and repeated measures analysis of variance was used to compare groups before and after treatment. Results Body weight was unchanged in both treatment groups during the study, although poststudy follow-up weights (n=13) suggested a tendency for weight gain in both groups. Significant changes in body composition for both groups included a mean loss of 0.8 kg total lean body mass (LBM), a mean loss of 0.4 kg LBM in the leg region, and a mean 1.3% increase in percent body fat, from 40.0% to 41.3%. Overall, no between-group differences were observed in any factors associated with energy balance. Applications In this short-term study, AC chemotherapy using fewer antineoplastic agents and number of treatments than most chemotherapy protocols for breast cancer, did not result in weight gain during treatment. Regardless of weight gain, changes in body composition may occur in women with breast cancer during or after treatment. These potential changes have important implications for preventive nutrition counseling. J Am Diet Assoc. 1999;99:1222–1227.

Offering a choice between two adjuvant chemotherapy regimens: a pilot study to develop a decision aid for women with breast cancer

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 (≥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.

Randomized comparison of hexamethylmelamine, adriamycin, cyclophosphamide (hac) vs. cisplatin, adriamycin, cyclophosphamide (pac) in advanced ovarian cancer: long-term results

Since the late 1970s hexamethylmelamine (H) and cisplatin (P) have been added to several combination chemotherapies in the treatment of advanced ovarian cancer. The main reasons for their inclusion were the higher complete response rate produced by the Hexa-CAF regimen over that of single agent L-PAM (9) and by the 300/b objective response rate achieved with P in patients resistant to alkylating agents (8). In 1978, we tested the activity of H and P, each in combination with adriamycin and cyclophosphamide (AC), a regimen for which promising preliminary results were already available (4). The first analysis of the study, performed at a median follow-up time of 36 months, showed that the HAC regimen was as effective as PAC in terms of response, duration of remission and survival (6). The occurrence of late relapses after negative second-look laparotomy suggests that early survival data may be prognostically inadequate in ovarian cancer and that the impact of a treatment is betterjudged on the basis of long-term analysis (2, 7). The present report summarises the results of the HAC vs. PAC study at a median follow-up time of 10 years (range, 107-140 months).