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Donald Berry

Publications and source records attributed to Donald Berry.

14 recordsLinked to original sources
PubMed2006

Development and validation of nomograms for predicting residual tumor size and the probability of successful conservative surgery with neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) increases the likelihood that breast conservation therapy for breast cancer patients will be successful. There is no available nomogram to predict breast conservation after NACT. The aim of the current study was to develop and validate nomograms for predicting residual tumor size and probability of a patient becoming eligible for breast conservation surgery after NACT. METHODS: A total of 1147 patients treated at M. D. Anderson Cancer Center (Houston, TX) and the Institut Gustave Roussy (Villejuif, France) who received anthracycline with or without paclitaxel NACT were included in the analysis. Clinicopathologic data from 1 series were used to construct logistic regression models for breast conservation and residual tumor size < 3 cm after NACT and were validated on an independent series. RESULTS: The discrimination and the calibration of the nomogram for predicting the probability of residual tumor size < 3 cm after anthracycline-based NACT were good when applied to the validation set (concordance index = 0.79; U-index = 10(-3)). The discrimination of the nomogram for predicting eligibility for breast conservation therapy was also good (concordance index = 0.67). However, the calibration had to be adjusted to take into account global rates of breast conservation surgery. A second nomogram adapted to preoperative chemotherapy regimens containing paclitaxel was established. The concordance index of the nomogram for predicting breast conservation was 0.71 (P < 10(-6)) for the independent dataset and the calibration was also good. The confrontation of both nomograms showed that predictions were highly correlated (r = 0.97), suggesting that eligibility for breast conservation therapy was independent of the preoperative chemotherapy regimen used. CONCLUSIONS: Nomograms were developed for breast cancer patients who received NACT to predict residual tumor size and whether the patient would thus become eligible for breast conservation therapy. These tools may be useful when counseling patients about treatment options, and a web-based interface is now available to help guide patients and physicians in these decisions.

Anthracyclines↗
PubMed2006

Interleukin-6, multidrug resistance protein-1 expression and response to paclitaxel in women with metastatic breast cancer: results of cancer and leukemia group B trial 159806.

Several reports have suggested that breast cancer patients with elevated serum levels of interleukin-6 (IL-6) have a worse prognosis than patients with lower levels. We have studied IL-6 in breast cancer cell lines and have shown that autocrine production of IL-6 can confer multi-drug resistance in vitro by inducing multidrug resistance gene-1 transcription with subsequent overexpression of P-glycoprotein (PGP). Both IL-6 and PGP expression can be measured in malignant cells using immunohistochemical (IHC) techniques. We hypothesized that patients whose tumors expressed higher amounts of IL-6 or PGP would be less likely to respond to paclitaxel, an agent affected by the PGP pathway. If so, then IL-6 could serve as a predictive factor for paclitaxel sensitivity. Both IL-6 and PGP expression were measured in patients treated in a randomized trial that compared three doses of single agent paclitaxel (175, 210, and 250 mg/m(2) over 3 h every 3 weeks) in 469 women with metastatic breast cancer (CALGB 9342). No difference in complete and partial response was found among the three treatment arms. Tissue blocks in this trial were analyzed for IL-6 (154 patients) and PGP (149 patients) in paraffin-embedded sections from tumor samples; clinical characteristics of these patients were similar to the total sample of 469 patients. There were no significant differences among IL-6 or PGP scores whether measured as continuous or dichotomous variables, or by other scoring, and response to paclitaxel. In multivariate analysis neither IL-6 nor PGP was a significant predictor of time to progression or overall survival. IHC expression of IL-6 and PGP levels in tumor cells is not a predictive marker for response to paclitaxel in women with metastatic breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342.

INTRODUCTION: The response to paclitaxel varies widely in metastatic breast cancer. We analyzed data from CALGB 9342, which tested three doses of paclitaxel in women with advanced disease, to determine whether response and outcomes differed according to HER2, hormone receptor, and p53 status. METHODS: Among 474 women randomly assigned to paclitaxel at a dose of 175, 210, or 250 mg/m2, adequate primary tumor tissue was available from 175. Immunohistochemistry with two antibodies and fluorescence in situ hybridization were performed to evaluate HER2 status; p53 status was determined by immunohistochemistry and sequencing. Hormone receptor status was obtained from pathology reports. RESULTS: Objective response rate was not associated with HER2 or p53 status. There was a trend toward a shorter median time to treatment failure among women with HER2-positive tumors (2.3 versus 4.2 months; P = 0.067). HER2 status was not related to overall survival (OS). Hormone receptor expression was not associated with differences in response but was associated with longer OS (P = 0.003). In contrast, women with p53 over-expression had significantly shorter OS than those without p53 over-expression (11.5 versus 14.4 months; P = 0.002). In addition, triple negative tumors were more frequent in African-American than in Caucasian patients, and were associated with a significant reduction in OS (8.7 versus 12.9 months; P = 0.008). CONCLUSION: None of the biomarkers was predictive of treatment response in women with metastatic breast cancer; however, survival differed according to hormone receptor and p53 status. Triple negative tumors were more frequent in African-American patients and were associated with a shorter survival.

Black or African American↗
PubMed2005

Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer.

CONTEXT: Adjuvant chemotherapy improves survival for patients with local-regional breast cancer, but healthy older patients at high risk of recurrence are frequently not offered adjuvant chemotherapy, and the benefit of adjuvant chemotherapy in older patients is uncertain. OBJECTIVE: To compare the benefits and toxic effects of adjuvant chemotherapy among breast cancer patients in age groups of 50 years or younger, 51 to 64 years, and 65 years or older. DESIGN AND SETTING: Retrospective review of data from 4 randomized trials that accrued patients from academic and community medical centers between 1975 and 1999. Median follow-up for all patients was 9.6 years. All trials randomized patients to different regimens, doses, schedules, and durations of chemotherapy and all had a treatment arm with doses or schedules that were regarded to be "high" and potentially more toxic. PATIENTS: A total of 6487 women with lymph node-positive breast cancer; 542 (8%) patients were 65 years or older and 159 (2%) were 70 years or older. MAIN OUTCOME MEASURE: Comparison of disease-free survival, overall survival, and treatment-related mortality among different age groups. RESULTS: Multivariate analysis showed that smaller tumor size, fewer positive lymph nodes, more chemotherapy, and tamoxifen use were all significantly (P<.001) related to longer disease-free and overall survival. There was no association between age and disease-free survival. Overall survival was significantly (P<.001) worse for patients aged 65 or older because of death from causes other than breast cancer. Thirty-three deaths (0.5% of all patients) were attributed to treatment, and older women had higher treatment-related mortality. Older women and younger women derived similar reductions in breast cancer mortality and recurrence from regimens containing more chemotherapy. CONCLUSION: Age alone should not be a contraindication to the use of optimal chemotherapy regimens in older women who are in good general health.

Age Factors↗
PubMed2005

Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer.

PURPOSE: The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2) -positive disease. PATIENTS AND METHODS: Forty-two patients with HER2-positive disease with operable breast cancer were randomly assigned to either four cycles of paclitaxel followed by four cycles of fluorouracil, epirubicin, and cyclophosphamide or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks. The primary objective was to demonstrate a 20% improvement in pCR (assumed 21% to 41%) with the addition of trastuzumab to chemotherapy. The planned sample size was 164 patients. RESULTS: Prognostic factors were similar in the two groups. After 34 patients had completed therapy, the trial's Data Monitoring Committee stopped the trial because of superiority of trastuzumab plus chemotherapy. pCR rates were 25% and 66.7% for chemotherapy (n = 16) and trastuzumab plus chemotherapy (n = 18), respectively (P = .02). The decision was based on the calculation that, if study continued to 164 patients, there was a 95% probability that trastuzumab plus chemotherapy would be superior. Of the 42 randomized patients, 26% in the chemotherapy arm achieved pCR compared with 65.2% in the trastuzumab plus chemotherapy arm (P = .016). The safety of this approach is not established, although no clinical congestive heart failure was observed. A more than 10% decrease in the cardiac ejection fraction was observed in five and seven patients in the chemotherapy and trastuzumab plus chemotherapy arms, respectively. CONCLUSION: Despite the small sample size, these data indicate that adding trastuzumab to chemotherapy, as used in this trial, significantly increased pCR without clinical congestive heart failure.

Adult↗
PubMed2004

Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer.

BACKGROUND: In women 70 years of age or older who have early breast cancer, it is unclear whether lumpectomy plus tamoxifen is as effective as lumpectomy followed by tamoxifen plus radiation therapy. METHODS: Between July 1994 and February 1999, we randomly assigned 636 women who were 70 years of age or older and who had clinical stage I (T1N0M0 according to the tumor-node-metastasis classification), estrogen-receptor-positive breast carcinoma treated by lumpectomy to receive tamoxifen plus radiation therapy (317 women) or tamoxifen alone (319 women). Primary end points were the time to local or regional recurrence, the frequency of mastectomy for recurrence, breast-cancer-specific survival, the time to distant metastasis, and overall survival. RESULTS: The only significant difference between the two groups was in the rate of local or regional recurrence at five years (1 percent in the group given tamoxifen plus irradiation and 4 percent in the group given tamoxifen alone, P<0.001). There were no significant differences between the two groups with regard to the rates of mastectomy for local recurrence, distant metastases, or five-year rates of overall survival (87 percent in the group given tamoxifen plus irradiation and 86 percent in the tamoxifen group, P=0.94). Assessment by physicians and patients of cosmetic results and adverse events uniformly rated tamoxifen plus irradiation inferior to tamoxifen alone. CONCLUSIONS: Lumpectomy plus adjuvant therapy with tamoxifen alone is a realistic choice for the treatment of women 70 years of age or older who have early, estrogen-receptor-positive breast cancer.

Aged↗
PubMed2004

Her2/neu-positive disease does not increase risk of locoregional recurrence for patients treated with neoadjuvant doxorubicin-based chemotherapy, mastectomy, and radiotherapy.

PURPOSE: Preclinical data suggest that overexpression of Her2/neu confers cellular radioresistance. We retrospectively studied whether Her2/neu-positive disease was associated with locoregional recurrence (LRR) after postmastectomy radiotherapy (RT) for breast cancer. METHODS AND MATERIALS: Data from 337 patients treated in four institutional prospective clinical trials neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT were reviewed. The trials were conducted between 1989 and 2000. Of the 337 patients, 108 (32%) had tumors that were tested for Her2/neu, with positivity defined by 3+ immunohistochemistry staining or gene amplification detected by fluorescence in situ hybridization. RT was delivered to the chest wall and draining lymphatics (median dose, 50 Gy) followed by a chest wall boost (median dose, 10 Gy). RESULTS: Thirty-two patients had Her2/neu-positive disease and 76 patients had Her2/neu-negative disease. The Her2/neu-positive tumors were associated with a greater rate of estrogen receptor-negative disease (p = 0.03), the presence of supraclavicular disease at diagnosis (p = 0.027), and a greater number of positive lymph nodes after chemotherapy (p = 0.026). Despite these adverse features, the actuarial overall LRR rate was roughly equivalent for the patients with Her2/neu-positive tumors vs. those with Her2/neu-negative tumors (5-year rate 17.5% vs. 13.9%, respectively; 10-year rate 17.5% vs. 18.9%, respectively; p = 0.757). On Cox regression analysis of LRR adjusted for N stage and estrogen receptor status, the hazard ratio for Her2/neu positivity was 0.89 (95% confidence interval, 0.31-2.59; p = 0.83). CONCLUSION: Her2/neu overexpression does not appear to predispose to LRR after neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT.

Adult↗
PubMed2003

Staging system for breast cancer: revisions for the 6th edition of the AJCC Cancer Staging Manual.

Since its inception, the AJCC staging system for breast cancer has been in an almost constant state of evolution, striving with each revision to reflect the most up-to-date clinical research as well as the widespread consensus among physicians about appropriate diagnostic and treatment standards. To date, these revisions have essentially represented a "fine-tuning" of the initial judgment that tumor size, lymph node status, and presence of distant metastases are the most significant prognostic factors for breast cancer. With the problems of standardization and reproducibility being resolved, it is likely that histologic grade will join this group of independent markers and be incorporated into the AJCC staging system in the near future. Over the last 15 years. considerable attention has been focused on the discovery of new markers visualized with immunohistochemistry and RT-PCR that may be validated as independent prognostic indicators (reviewed by Mirza et al). To date, the usefulness of many of these markers has been limited by lack of standardization in measurement techniques, but several show great promise for the future. By increasing the number of prognostic markers that can give independent information about patient outcome, physicians will be better able to determine optimal treatment approaches for individual patients.

Advisory Committees↗
PubMed2002

Revision of the American Joint Committee on Cancer staging system for breast cancer.

PURPOSE: To revise the American Joint Committee on Cancer staging system for breast carcinoma. MATERIALS AND METHODS: A Breast Task Force submitted recommended changes and additions to the existing staging system that were (1) evidence-based and/or consistent with widespread clinical consensus about appropriate diagnostic and treatment standards and (2) useful for the uniform accrual of outcome information in national databases. RESULTS: Major changes included the following: size-based discrimination between micrometastases and isolated tumor cells; identifiers to indicate usage of innovative technical approaches; classification of lymph node status by number of involved axillary lymph nodes; and new classifications for metastasis to the infraclavicular, internal mammary, and supraclavicular lymph nodes. CONCLUSION: This revised staging system will be officially adopted for use in tumor registries in January 2003.

Breast Neoplasms↗
PubMed2002

Pre-counseling education materials for BRCA testing: does tailoring make a difference?

Although tailored print materials (TPMs) have been assessed for a variety of behavioral targets, their effectiveness as decision aids for genetic testing had not been evaluated at the time this study began. We compared TPMs and non-tailored print material (NPMs) that included similar content about genetic testing for breast and ovarian cancer susceptibility. TPMs were prepared especially for an individual based on information from and about her. We mailed baseline surveys to 461 women referred by physicians or identified through a tumor registry. All had personal and family histories of breast and/or ovarian cancer and, on the basis of these histories, an estimated > or =10% probability of carrying a mutation in the breast/ovarian cancer genes BRCA1 or BRCA2. The 325 (70%) who responded were randomly assigned to receive TPM or NPM. Followup surveys, mailed 2 weeks following receipt of print materials, were returned by 262 women (81% of baseline responders). Participants were predominately white (94%) and well-educated (50% college graduates). The mean age was 49 years. At follow-up, TPM recipients exhibited significantly greater improvement in percent of correct responses for the 13-item true/false measure of knowledge (24% increase for TPM vs. 16% for NPM; p < 0.0001) and significantly less over-estimation of risk of being a mutation carrier (40% TPM group overestimated vs. 70% NPM; p < 0.0001). Anxiety did not differ significantly between groups. Reactions to materials differed on two items: "seemed to be prepared just for me" (76% TPM vs. 52% NPM; p < 0.001) and "told me what I wanted to know about BRCA1 and 2 testing" (98% TPM vs. 91% NPM; p < 0.05). TPMs showed an advantage in increasing knowledge and enhancing accuracy of perceived risk. Both are critical components of informed decision making.

Adult↗
PubMed2002

Association of high-dose cyclophosphamide, cisplatin, and carmustine pharmacokinetics with survival, toxicity, and dosing weight in patients with primary breast cancer.

This report investigates relationships between the pharmacokinetics and pharmacodynamics of high-dose alkylators used for the treatment of primary breast cancer. Eighty-five women with primary breast cancer involving >or=10 lymph nodes received four cycles of standard-dose chemotherapy followed by a high-dose regimen consisting of: cyclophosphamide (1875 mg/m(2) once daily x 3), cisplatin (165 mg/m(2) given over 72 h), carmustine (600 mg/m(2)), and stem cell transplantation. Dosages were attenuated in patients whose body weight exceeded their calculated ideal weight by >20%. Pharmacokinetics of the high-dose chemotherapeutic agents were evaluated in each patient by collection and analysis of serial blood samples. Area under the concentration time curve (AUC) for cyclophosphamide and carmustine was highly variable (>10-fold inter-patient range) with coefficients of variation > 50%, in contrast to cisplatin exposures (2-fold range; coefficient of variation 12%). The dosing method for overweight patients resulted in significantly lower systemic exposure to cisplatin (P = 0.035). The parent cyclophosphamide clearance on the 1st day of administration was significantly higher in patients who experienced acute cardiac toxicity (n = 5; P = 0.011), whereas carmustine disposition was not found to be different in those developing pulmonary toxicity (n = 25; P = 0.96). Kaplan-Meier analysis (median follow-up of 5.9 years) demonstrated that patients with lower cyclophosphamide AUC (faster parent drug clearance to potentially cytotoxic compounds) survived longer (P = 0.031). Inter-individual differences in the pharmacokinetic disposition of high-dose chemotherapy may explain variability in both response and toxicity. Prospective strategies, which attempt to individualize AUC, should be evaluated in this setting.

Adult↗
PubMed2002

Evaluation of paclitaxel in adjuvant chemotherapy for patients with operable breast cancer: preliminary data of a prospective randomized trial.

PURPOSE: Paclitaxel has significant antitumor activity in patients with metastaticbreast cancer who have been previously treated with or exposed to anthracycline-containing chemotherapy. In this prospective randomized trial, the role of paclitaxel was evaluated in an adjuvant setting to determine its impact on reducing the risk of recurrence in patients with operable breast cancer. EXPERIMENTAL DESIGN: Five hundred twenty-four patients were randomized to be treated either with 4 cycles of paclitaxel followed by 4 cycles of combination therapy with 5-fluorouracil, Adriamycin, and cyclophosphamide (Pac/FAC) or with 8 cycles of FAC alone. Patients with intact primary breast cancer received the initial 4 cycles of paclitaxel or 4 cycles of FAC in a neoadjuvant setting. Planned duration of therapy was the same in all patients. After completion of 8 cycles of chemotherapy, those patients who were > or =50 years and whose tumors were positive for estrogen receptors received tamoxifen for 5 years. RESULTS: Ninety-two patients have had a recurrence after a median follow-up of 60 months with a range of 5-89 months. Estimated disease-free survival at 48 months was 0.83 for FAC and 0.86 for Pac/FAC group. The difference between the two groups was not statistically significant (P = 0.09). The overall estimated hazard ratio for Pac/FAC compared with FAC derived by fitting the Cox regression model and incorporating terms for prognostic factors was 0.66. CONCLUSION: Preliminary results suggest that the addition of paclitaxel to a FAC regimen of adjuvant or neoadjuvant therapy may further reduce the risk of disease recurrence; however, differences were not statistically significant. At the time of this analysis, there have been 47 deaths. The survival data are too preliminary to permit meaningful evaluation of the impact of paclitaxel on mortality.

Antineoplastic Agents, Phytogenic↗