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Background: Use of anthracycline-based chemotherapy in patients with early breast cancer (EBC) has been well-established but is often associated with cardiotoxicity. Based on data suggesting a limited benefit of anthracyclines in human epidermal growth factor receptor 2 (HER2)-negative patients, the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS) C study randomized patients to either anthracycline-containing or anthracycline-free chemotherapy. Given the proven prognostic value of circulating tumor cells (CTCs) in EBC, we compared the prevalence of CTCs after chemotherapy between both treatment arms for a preliminary efficacy assessment., Methods: The SUCCESS C trial (NCT00847444) is an open-label, phase III study randomizing 3547 patients with HER2-negative EBC to either 3 cycles of epirubicin, 5-fluorouracil, and cyclophosphamide followed by 3 cycles of docetaxel (FEC-DOC) or 6 cycles of docetaxel and cyclophosphamide (DOC-C). CTC status was prospectively evaluated in hormone receptor-positive patients at the time of last chemotherapy cycle using the US Food and Drug Administration-approved CellSearch System (Janssen Diagnostics)., Results: Data on CTC status were available for 1766 patients. Overall, CTCs were found in 221 (12.5%) patients. Univariate analyses revealed that presence of CTCs at time of last chemotherapy cycle was not significantly associated with tumor or patient characteristics (all P > .1). There was no significant difference with respect to presence of CTCs between patients randomized to FEC-DOC or DOC-C (11.5% vs. 13.6%; P = .18)., Conclusions: The comparable prevalence of CTCs at the time of last chemotherapy cycle may indicate that anthracycline-free chemotherapy is equally effective to anthracycline-containing chemotherapy in HER2-negative, hormone receptor-positive EBC. However, efficacy data from the final survival analysis of SUCCESS C have to be awaited to confirm these preliminary findings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response., Material and Methods: We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer., Results: After neoadjuvant chemotherapy, 82.4% of patients showed pathologic partial response, with only 9.8% showing pathologic complete response. In multivariate analysis, MYC immunoreactivity and high MYC gain defined as MYC/nucleus ≥ 5 were significant predictor factors for pathologic partial response. Using the receiver operating characteristic curve analysis, the ratio of 2.5 MYC/CEP8 (sensitivity of 80% and specificity of 89.1%) or 7 MYC/nuclei copies (sensitivity of 80% and specificity of 73.9%) as the best cutoff in predicting a pathologic complete response was identified. Thus, MYC may have a role in chemosensitivity to AC and/or docetaxel drugs. Additionally, MYC amplification may be a predictor factor of pathologic response to the AC+T regimen in patients with breast cancer. Moreover, patients with an increased number of MYC copies showed pathologic complete response to this neoadjuvant treatment more frequently., Conclusion: The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Neoadjuvant chemotherapy (NCT) is a standard of care for locally advanced and initially inoperable breast cancer. NCT can test chemotherapy efficacy and can be followed by breast-conserving surgery. Considering taxanes as one of the most effective agents, we analyzed the efficacy of a neoadjuvant schedule without anthracyclines and based only on taxanes and carboplatin, trying to avoid cardiotoxicity, which is the most serious side effect correlated with anthracyclines., Patients and Methods: We enrolled 61 patients with breast cancer, belonging to 4 subgroups, according to molecular phenotypes: 24 triple-negative/basal-like, 13 HER2-like, 20 luminal B, and 4 luminal A. All patients underwent weekly chemotherapy with carboplatin AUC2, paclitaxel 80 mg/m 2 , with trastuzumab (in case of HER2 positivity) 2 mg/kg, except for luminal A patients, who underwent only hormonal therapy. Among 61 patients, 26 (43%) received modified radical mastectomy and 35 (57%) received breast-conserving surgery., Results: The patients obtaining pathologic complete response (pCR) were 20 (83%) of 24 triple-negative/basal-like, 10 (76%) of 13 HER2-like, 6 (30%) of 20 luminal B, and 3 (75%) of 4 luminal A. All the patients were evaluated for toxicity: no grade 4 was detected, 5 patients experienced grade 3 neuropathy, then reverted to G2 after chemotherapy discontinuation. At a minimum follow-up of 5 years, median overall survival was 48 months., Conclusion: Taxane/carboplatin-based/anthracycline-free NCT is the best treatment for inoperable breast cancer in terms of efficacy and toxicity, because this approach avoids cardiotoxicity and obtains an optimal rate (64%) of pCR, with an important impact on survival., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The effect of body mass index (BMI) and chemotherapy dose reduction on pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for locoregional breast cancer remains unclear. Contemporary studies have reported largely on trial populations and used dose-capping., Patients and Methods: Patient registries at the University of Iowa were queried to identify patients with operable breast cancer who received NAC. Dose reductions were calculated for taxanes (T), anthracyclines (A) and non-A-T chemotherapy. Clinical-pathologic characteristics, chemotherapy dose reductions, and adverse events were compared between normal (BMI <25) and overweight/obese patients (BMI ≥25). Additionally, the synergistic effect of BMI and chemotherapy dose reduction on pCR was assessed., Results: Of 171 eligible patients, 112 were overweight/obese. Chemotherapy dosing was capped in 2 patients; all others initiated full weight-based treatment. Overweight/obese patients required more frequent taxane (44.6% vs. 25.4%; P = .01) and any chemotherapy dose reductions (50.9% vs. 33.9%; P = .03). pCR was attained in 29.2% of patients. In a multivariable model, the interaction term for BMI as a continuous variable and any chemotherapy dose reduction was significant independent of the clinical stage and tumor receptor status (P = .04). For obese patients, any chemotherapy dose reduction was significantly associated with increased odds of not attaining pCR., Conclusion: During NAC, overweight/obese patients more often have chemotherapy dose reductions. Chemotherapy dose reduction in obese patients was a powerful predictor of not attaining pCR. This was not seen for normal or overweight patients. Opportunities might exist to improve pCR rates in this higher-risk group., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Metastatic breast cancer (MBC) is treated with cytotoxic drugs or endocrine agents according to the site and extent of the disease, biology, previous treatments, and the patient's condition, comorbidities, and wishes. In MBC, vinorelbine (VRB) and capecitabine (X; VRB + X) are chemotherapy drugs that hold activity as first or later lines of therapy. We conducted a systematic literature review and meta-analysis to quantify the efficacy of the VRB + X combination in HER2-negative (HER2 - ) MBC. We searched PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library, and CINAHL for phase II/III clinical trials that assessed VRB + X for patients with HER2 - MBC. Pooled estimates of the overall response rate (RR), median progression-free survival (PFS), and overall survival (OS) were computed using random or fixed effects models. Twenty-seven studies were included in the analysis, encompassing a total of 1356 MBC patients. All were phase II (n = 21) or prospective/pilot (n = 5) trials, except for 1 that was a phase III controlled trial. The pooled estimate for the RR in first-line therapy (n = 16 trials) was 52.9% (95% confidence interval [CI], 46.5%-59.2%). For second-line trials, data were available in n = 9 studies and the overall RR was 41% (95% CI, 31.2%-51.6%). The pooled estimates for median PFS and OS in first-line therapy were 7.3 (95% CI, 6.2-8.3) and 22.3 (95% CI, 20-24.5) months, respectively. Vinorelbine + X, with the dose and schedules currently used in clinical practice, appears to be an effective and feasible chemotherapy for MBC, for first- and also for second-line therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to evaluate predictive factors and the clinical characteristics of durable responders to capecitabine monotherapy in heavily-treated patients with metastatic breast cancer (MBC)., Patients and Methods: Between December 2000 and May 2012, a total of 236 evaluable patients with MBC who had been treated with second- or greater-line palliative capecitabine monotherapy after a previous treatment regimen with anthracycline and taxane were included. Capecitabine (1250 mg/m(2) twice daily) was administered for 2 weeks followed by a 1-week rest period., Results: The response rate was 23.3% and median progression-free survival (PFS) was 4.7 months (95% confidence interval, 4.0-5.5). Among 236 patients, 33 patients (14.0%) showed durable response (>12 months) to capecitabine monotherapy. Patients with durable response showed significantly greater incidence of estrogen receptor (ER) positivity (81.8% vs. 59.1%; P = .012), single-organ metastasis (51.5% vs. 32.0%; P = .047), and absence of lymph node metastasis (75.8% vs. 54.2%; P = .023), compared with patients without durable response. In multivariate analysis, ER positivity and single-organ metastasis retained a significant association with better PFS to capecitabine monotherapy (hazard ratio [HR], 0.51; P < .001 and HR, 0.62; P = .004)., Conclusion: Our data suggest that ER positivity and single-organ metastasis can be useful predictive markers for better PFS to second- or greater-line palliative capecitabine monotherapy in anthracycline- and taxane-pretreated MBC patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to assess the efficacy and safety of trabectedin for advanced breast cancer., Patients and Methods: In an open-label, phase II, multicenter study, women with advanced breast cancer previously treated with ≤ 2 lines of chemotherapy for advanced disease, including both anthracyclines and taxanes, were randomized (1:1) to 3-hour infusions of trabectedin 1.3 mg/m(2) once every 3 weeks (1/3 treatment arm) or 0.58 mg/m(2) every week for 3 of 4 weeks (3/4 treatment arm). The primary end point was objective response. Secondary end points included time to progression (TTP), progression-free survival (PFS), and overall survival (OS)., Results: Fifty-two women (median age, 50 years; median chemotherapy agents, 4) were enrolled. Relative trabectedin dose intensities were 81% and 76% in the 1/3 and 3/4 treatment arms, respectively. Objective response rates were 12% (3 of 25) and 4% (1 of 27), respectively. Stable disease was observed in 14 (56%) and 11 (41%) patients in the 1/3 and 3/4 treatment arms, respectively, with median durations of 3.5 and 3.7 months. Median TTP and PFS were higher in the 1/3 treatment arm (3.1 months each) than in the 3/4 treatment arm (2.0 months each). At a median follow-up of 7 months in both treatment arms, median OS was not reached in the 1/3 treatment arm and was 9.4 months in the 3/4 treatment arm. The most frequent drug-related adverse events in the 1/3 and 3/4 treatment arms, respectively, were alanine aminotransferase (ALT) level increases (68% vs. 63%), nausea (56% vs. 59%), and asthenia (56% vs. 48%). Neutropenia and increases in ALT levels were the most frequent grade 3/4 events. Both types of events were usually transient and reversible., Conclusion: In the population studied, trabectedin showed a manageable safety profile for both regimens analyzed. There were higher objective response rates and a longer PFS in the 1/3 treatment arm compared with the 3/4 treatment arm., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Angiogenesis is an established target for the treatment of MBC. Aflibercept (VEGF-Trap) is a humanized fusion protein, which binds VEGF-A, VEGF-B, and PIGF-1 and -2., Patients and Methods: A 2-stage phase II study with primary end points of confirmed tumor response and 6-month progression-free survival (PFS). If either end point was promising after the initial 21 patients, an additional 20 patients would be enrolled. Measurable disease, <2 previous chemotherapy treatments, previous anthracycline or taxane therapy, and Eastern Cooperative Oncology Group performance status of 0 or 1 were required. Aflibercept was given at a dose of 4 mg/kg intravenous every 14 days., Results: Twenty-one patients were enrolled; 71% had visceral disease, 57% were estrogen receptor negative, 19% had HER2(+) disease with previous trastuzumab treatment, and 33% had 2 previous chemotherapy regimens. Partial response rate was 4.8% (95% confidence interval [CI], 0.1%-23.8%) and 6-month PFS was 9.5% (95% CI, 1.2%-30.4%). Neither primary end point met efficacy goals and the study was terminated. A median of 3 cycles was given. Median PFS was 2.4 months. Common grade 3 or 4 adverse events were hypertension (33%), fatigue (19%), dyspnea (14%), and headache (14%). Two cases of severe left ventricular dysfunction were noted., Conclusions: Aflibercept did not meet efficacy goals in patients previously treated with MBC. Toxicity was as expected for anti-VEGF therapy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Resistance to chemotherapy is a complex and very frequent problem in the treatment of breast cancer. It is associated with a poor prognosis and short overall survival. We report a patient with advanced breast cancer without response to anthracyclines or taxanes but who controlled the disease for 15 months with the combination of ixabepilone and capecitabine.

Despite major advances in the adjuvant treatment of breast cancer, many women will develop metastatic disease, either de novo or following optimal adjuvant therapy. Further effective therapeutic options are needed for women who progress following anthracycline- and taxane-containing regimens. Capecitabine is approved by the US Food and Drug Administration as monotherapy in this setting. Other agents such as gemcitabine or vinorelbine might be considered based on multiple phase II studies. Combination therapies generally increase response rates but with a concomitant increase in toxicity. Other agents that have been studied in this setting include etoposide, irinotecan, and pemetrexed. Novel agents undergoing testing include the fluorinated vinca alkaloid vinflunine and the halichondrin B analogue eribulin. Responses have been seen in taxane-pretreated patients with the use of another conventional taxane, novel formulations, or alternative schedules. Pegylated liposomal doxorubicin might be considered in some patients for whom there is a concern regarding cardiac toxicity with the conventional preparation. The epothilones are a novel group of microtubule-stabilizing agents. Ixabepilone is a member of this class that has been approved as monotherapy in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine. It is also approved with capecitabine in patients whose cancer is resistant to treatment with anthracyclines and taxanes. Decision-making regarding treatment selection must take into account multiple patient and tumor factors. The therapeutic indices of the available treatments should be considered in the context of the individual patient.

Purpose: Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer. No randomized controlled trial or systematic review with an IBC-only cohort that evaluates interventions has been published. We conducted a systematic review of the literature to characterize the reporting of clinical criteria and response to neoadjuvant therapy for IBC., Patients and Methods: We searched MEDLINE and other sources for the following: previously untreated patients with IBC without metastasis in cohort studies; utilized chemotherapy; and reported clinical outcomes. The following 4 groups were analyzed: no anthracycline induction, low-dose anthracycline induction, moderate-dose anthracycline induction, and high-dose chemotherapy requiring stem cell support. Weighted averages for the overall response rates were calculated using a random effects model., Results: Twenty-seven studies met all criteria, totaling 1232 patients. Clinical description of IBC eligibility criteria and reported response assessments varied significantly among studies. The response rates and 3- and 5-year overall survival for all 27 studies ranged from 14% to 100%, 22% to 84%, and 32% to 75%, respectively. Pathologic complete response rates after no anthracycline induction, low-dose anthracycline induction, moderate-dose anthracycline induction, and neoadjuvant high-dose chemotherapy subgroups were 4% (95% confidence interval [CI], 1%-18%), 11% (95% CI, 7%-17%), 14% (95% CI, 8%-22%), and 32% (95% CI, 24%-41%), respectively., Conclusion: The criteria and reporting of IBC and treatment response was notably variable, with significant potential for subject heterogeneity. Pathologic complete response rates appear to be related to intensity of neoadjuvant treatment; however, this analysis is not based on randomized data. Future clinical trials should define and report the criteria for IBC diagnosis and response assessment to enhance interstudy comparisons.

Purpose: This study was designed to evaluate the efficacy and safety of single-agent gemcitabine for the treatment of patients with anthracycline- and taxane-pretreated metastatic breast cancer (MBC). Eligible patients were required to have bidimensionally measurable MBC that had been treated with 2-4 prior chemotherapy regimens that included an anthracycline and a taxane. Gemcitabine was delivered at a dose of 800 mg/m2 on days 1, 8, and 15 of a 28-day cycle until evidence of disease progression., Patients and Methods: Twenty-two patients were enrolled and included in the safety analysis; 18 patients were evaluable for response. The median age of patients was 54 years (range, 36-70 years). The mean number of prior chemotherapy regimens for metastatic disease was 2.3, and the mean dose of gemcitabine delivered was 911 mg/m2 (range, 600-1600 mg/m2)., Results: Overall, gemcitabine was well tolerated with minimal grade 3 toxicities; the only grade 4 toxicity was 1 case of pulmonary embolus. Three patients had evidence of partial tumor regression (17%; 95% CI, 4%-41%), and 1 patient had a 41% decrease in tumor volume, including liver metastasis., Conclusions: Gemcitabine is active and well tolerated as monotherapy given in heavily pretreated patients with MBC after anthracyclines and taxanes. The activity and safety reported in this trial are consistent with previous reports in similar patients.

Thirty-five patients with metastatic breast cancer (MBC) entered a phase II study of pegylated liposomal doxorubicin 35 mg/m2 intravenously (i.v.) on day 1 plus vinorelbine 30 mg/m2 i.v. on day 1 every 4 weeks. Patients were required to have measurable disease, previous chemotherapy with an anthracycline-containing regimen, and a normal left ventricular ejection fraction (LVEF). Thirty-four patients were assessable for response and toxicity. The overall response rate (on an intent-to-treat basis) was 35% (12 of 34; 95% CI, 20%-54%). One complete response and 11 partial responses were noted. In addition, 14 patients (41%) had stable disease of > 4 months duration, and 7 patients (20.5%) had disease progression. The response rates to the combination when it was used as first- and second-line chemotherapy were 31% (4 of 13) and 38% (8 of 21), respectively. Median time to disease progression was 7 months (range, 1-35 months) and median overall survival was 13 months (range, 2 to > 62 months). Neutropenia was the most frequent toxicity (grade 4 in 44% of patients and 19% of cycles), but neutropenic fever was seen in only 3 cases. No septic deaths occurred. Nonhematologic grade 3 side effects included skin toxicity (palmar-plantar erythrodysesthesia syndrome, 6%) and mucositis (15%). Late alopecia was seen in 53% of patients (grade 1 in 41%, and grade 2 in 12%). The median LVEFs were 64% (range, 50%-81%) at baseline and 62% (range, 37%-70%) after treatment. Three patients presented an LVEF decrease to < 50%; however, no clinical heart failure was noted, and 2 of these patients recovered normal values after cessation of therapy. The combination of pegylated liposomal doxorubicin and vinorelbine can be safely administered to patients with anthracycline-pretreated MBC and is active in this population.

The addition of capecitabine to docetaxel on a 3-week schedule resulted in superior response rate, increased time to progression (TTP), and improved overall survival in patients with anthracycline-pretreated metastatic breast cancer (MBC). Because the toxicity profile of weekly docetaxel differs from the standard 21-day docetaxel schedule, we performed a phase I/II trial to test the efficacy and safety of weekly docetaxel in combination with capecitabine given for 14 days every 21 days. The phase I study identified the doses of docetaxel (30 mg/m2 weekly) and capecitabine (900 mg/m2 twice daily on days 1-14 every 21 days) used in phase II. Twenty female patients with measurable or assessable MBC were enrolled. Eighteen patients had previously received anthracyclines; 2 had contraindications to anthracyclines. Patients remained on study for a maximum of eight 3-week cycles or until tumor progression or unacceptable toxicity occurred; response assessments were scheduled after cycle 2, 5, and 8. Seventeen patients were assessed after cycle 2; 3 subjects (18%) had a partial response (PR), 9 had stable disease (53%; SD), and 5 patients (29%) had progressive disease (PD). Ten patients were assessable after cycle 5. Two patients (20%) had a PR, 5 patients (50%) had SD, and 3 patients (30%) had PD. The most common grade 3 toxicities were nail loss (45%), asthenia (30%), and hand-foot syndrome (30%), and toxicities led to study discontinuation in 10 patients. The median time to treatment failure was 10 weeks and median TTP was 26 weeks. The median duration of response was 9 weeks and the median duration of SD was 16 weeks. The median overall survival was 82 weeks. This schedule of weekly docetaxel in combination with day 1-14 capecitabine has activity; however, toxicity discourages the use of this schedule in lieu of the standard docetaxel/capecitabine regimen.

Trastuzumab improves time to disease progression (TTP) and survival when added to chemotherapy for HER-positive metastatic breast cancer (MBC), but it is associated with infrequent cardiac dysfunction (CD). We analyzed data from a previous pivotal randomized trial of 469 women with HER2-overexpressing MBC. The aim was to determine the benefit of adding trastuzumab to chemotherapy in terms of TTP that was free of CD, including all CD, moderate or severe (New York Heart Association class III/IV) CD only, or moderate or severe CD that did not improve with cardiac therapy. We also assessed moderate or severe CD-free survival. We assessed the impact of trastuzumab for these indices on the entire cohort and on specific chemotherapy subsets. Median TTP or any CD improved when trastuzumab was added to all chemotherapy (4.6 months vs. 6.6 months with trastuzumab, P = 0.0001), an anthracycline (doxorubicin or epirubicin) plus cyclophosphamide (AC; 6.0 months vs. 6.6 months, P = 0.24), and paclitaxel (2.8 months vs. 6.6 months, P = 0.0001). When defined as time to moderate or severe CD, median TTP improved when trastuzumab was added to all chemotherapy (4.6 months vs. 7.0 months, P = 0.0001), AC (6.0 months vs. 7.2 months, P = 0.02), and paclitaxel (2.8 months vs. 6.9 months, P = 0.0001). There was no statistical difference between moderate and severe CD-free survival with trastuzumab added to chemotherapy. Outcomes improved with trastuzumab despite CD. In particular, the benefit from trastuzumab/paclitaxel outweighed the potential risk of CD in patients with MBC. These types of analyses will be critical for trials assessing trastuzumab as adjuvant therapy.

This phase II study was designed to evaluate the response rate (RR) and toxicity of gemcitabine/vinorelbine in patients with metastatic breast cancer. All patients had previously received anthracyclines. Treatment consisted of gemcitabine 1200 mg/m2 and vinorelbine 30 mg/m2 on days 1 and 8, every 3 weeks. Twenty-five patients were enrolled. Median age was 59 years (range, 33-73 years). Ten patients had received only adjuvant therapy with anthracyclines. The remaining 15 patients had received chemotherapy for metastatic disease, including taxanes in 11 cases. Four patients could not be evaluated for response. By intent-to-treat analysis, the overall RR was 44% (95% CI, 24.4%-65%). Median duration of response and median time to treatment failure were 21 and 17 weeks, respectively. The main toxicity was hematologic, with grade 3/4 neutropenia occurring in 13 patients and 1 patient developing febrile neutropenia. Two deaths from pneumonia occurred. These results reveal an encouraging activity with a reasonable toxicity profile in a patient population with an unfavorable prognosis. Our group is conducting a randomized study to compare this combination with vinorelbine alone in patients with metastatic breast cancer after failure to respond to anthracyclines and taxanes

Gemcitabine has demonstrated single-agent efficacy in the treatment of advanced breast cancer, with response rates of up to 42%. The agent is well tolerated, with relatively mild side effects, and has limited overlapping toxicities with other drugs used in combination chemotherapy for breast cancer. It is, therefore, a good candidate for inclusion in multidrug regimens for the treatment of this disease. This article reviews results of gemcitabine/anthracycline-containing double- and triple-drug combinations used to treat patients with early-stage and advanced breast cancer. Results from phase I and II trials were promising, with good tolerability and overall response rates ranging from 33%-89% in advanced disease and up to 95% in the neoadjuvant treatment of early-stage disease. A phase III trial is currently comparing gemcitabine/epirubicin/paclitaxel and 5-fluorouracil/epirubicin/cyclophosphamide in patients with advanced breast cancer. Preliminary toxicity data on 78 patients show that both regimens were well tolerated, with similar incidences of treatment-related effects. Additional comparative studies of gemcitabine-containing drug regimens in breast cancer are warranted.