Dose-dense Chemotherapy In Breast Cancer Research Articles

The relevance of macrocytosis induction during neoadjuvant dose-dense chemotherapy in breast cancer patients.

The aim of this study was to explore the red blood cell changes that occur during neoadjuvant dose-dense chemotherapy (NAC) of breast cancer. Also, we investigated the role of macrocytosis as a predictive biomarker for pathological complete response and disease-free survival (DFS) in these patients. A retrospective analysis of 82 breast cancer patients' data treated with anthracycline-cyclophosphamide-paclitaxel (AC-T) NAC in three oncology institutions in south Croatia from 2013 to 2020 was carried out. During chemotherapy mean corpuscular volume increased with time, with a median increase of 7.25 fl. Macrocytosis was induced in 38% of patients overall. Development of macrocytosis did not correlate with DFS [hazard ratio = 0.525; 95% confidence interval (CI), 0.074-3.768; P = 0.525]. Higher percentage of patients in macrocytosis group achieved PCR, 39% vs. 29% in no macrocytosis group, but this difference was not statistically significant. The relevance of macrocytosis induction during dose-dense neoadjuvant chemotherapy in breast cancer should be further explored.

Adjuvant dose-dense chemotherapy in breast cancer: a systematic review and meta-analysis of randomized trials.

Dose-dense (DD) chemotherapy (CT) aimed at achieving a higher rate of cancer cell destruction has been adopted as an adjuvant therapy in high-risk breast cancer (BC), with the goal being to improve outcomes. We performed an updated systematic review and meta-analysis of the existing data from randomized phase III trials regarding the efficacy and toxicity of this adjuvant DD-CT strategy in early BC. Randomized-controlled trials that compared a DD with a standard adjuvant CT schedule in adult women with resected BC were identified by searching the databases of Pubmed, the Cochrane Cancer Register of Controlled Trials, SCOPUS, EMBASE, and the Web of Science up to March 2015. Hazard ratios (HRs) of death and recurrence, and the relative risks of adverse events, were estimated and pooled. A total of 8 phase III trials encompassing 17,188 randomized patients met the inclusion criteria. The patients who received DD-CT had better overall survival (OS: HR 0.86, 95 % confidence interval [CI] 0.79-0.93, P = 0.0001) and disease-free survival (DFS: HR 0.84, 95 % CI 0.77-0.91, P < 0.0001) than those on the conventional schedule. A statistically significant OS benefit was observed in patients with hormone receptor-negative (ER-) tumors (HR 0.8, P = 0.002), but not in those with ER-positive BC (HR 0.93, 95 % CI 0.82-1.05; P = 0.25). DD-CT leads to better OS and DFS, particularly in women with ER- early BC. These results suggest that the DD strategy should be the standard care offered to high-risk ER- BC patients.

Maternal and Neonatal Outcomes of Dose-Dense Chemotherapy for Breast Cancer in Pregnancy

To estimate the effect of dose-dense chemotherapy during pregnancy on maternal and neonatal outcomes. This is a retrospective cohort study in which women were identified from the international Cancer and Pregnancy Registry at Cooper Medical School at Rowan University in Camden, New Jersey. A chart analysis was completed and Fisher's exact test and independent t test were used in comparing patient outcomes. Ten women received dose-dense chemotherapy, received every 2 weeks, and 99 women received conventional chemotherapy, received with at least 3-week intervals, for breast cancer during pregnancy. Birth weight, gestational age at delivery, rate of growth restriction, congenital anomalies, and incidence of maternal and neonatal neutropenia were not statistically different between the two groups. In the small cohort of women in our registry, dose-dense chemotherapy does not appear to increase the risk of fetal or maternal complications.

Dose-Dense Chemotherapy for Breast Cancer: What Does the Future Hold?

Within the last several decades adjuvant polychemotherapy for breast cancer has evolved with the development of anthracyclines and taxanes. Parallel to these developments, granulocyte-colony stimulating factor support has permitted the safe delivery of chemotherapy at shorter ('dose-dense') intertreatment intervals, which, as predicted by preclinical models, has further improved survival. Recently, insights into tumor biology have led the development of targeted therapies, such as trastuzumab for HER2-positive disease, and this has now been successfully incorporated into dose-dense therapy. Newer targeted agents may be similarly incorporated into dose-dense regimens to further improve patient outcomes. This article reviews dose-dense therapy and discusses its role as a chemotherapy foundation for additional targeted agents.

Biological Effects of Pegfilgrastim on Circulating Neutrophils in Breast Cancer Patients Undergoing Dose-Dense Chemotherapy

Pegfilgrastim is a covalent conjugate of filgrastim and polyethylene glycol that has proved to be effective in supporting myelopoiesis during chemotherapy. Since very limited information is available on the biological effects of pegfilgrastim on neutrophils exposed to chemotherapy, we analyzed the following parameters in neutrophils of patients undergoing dose-dense chemotherapy for breast cancer: apoptosis, by a TUNEL technique; actin polymerization, using FITC-labeled phalloidin, and alkaline phosphatase activity by cytochemistry. Peripheral blood buffy coat smears were obtained before starting treatment and immediately before each chemotherapy course. After pegfilgrastim stimulation we observed the following: (1) stability of the absolute neutrophil count for the whole duration of treatment and no infectious events; (2) a reduction in the neutrophil constitutive apoptosis rate in comparison with that observed in control patients treated with standard chemotherapy courses with no growth factor support; (3) persistent abnormalities of actin assembly in neutrophils, indicative of changes in cytoskeletal organization, and (4) a significant increase in the activity of leukocyte alkaline phosphatase, a sensitive marker of the later stages of neutrophil maturation. In conclusion, these results suggest that pegfilgrastim improves the neutrophil functions in patients exposed to chemotherapy by inhibition of constitutive apoptosis, thereby prolonging the survival of these cells.

Lymphopenia Associated with Adjuvant Anthracycline/Taxane Regimens

Background We observed 2 cases of Pneumocystis carinii pneumonia (PCP) occurring in HIV-negative patients during treatment with dose-dense chemotherapy with doxorubicin/cyclophosphamide (AC) followed by paclitaxel (T). These represent the first case reports of PCP occurring during dose-dense chemotherapy for breast cancer. Because lymphocyte depletion is thought to predispose patients to PCP, we explored whether the shortened intervals between cycles during dose-dense chemotherapy might place patients at risk for lymphocyte depletion and thereby a potentially increased risk of opportunistic infection. Patients and Methods Three cohorts of patients were analyzed. Cohort 1 involved 135 patients receiving dose-dense AC → T on a phase II study. Cohort 2 included 64 patients who received treatment with dose-dense AC → albumin-bound paclitaxel on a phase II clinical trial. Cohort 3 consisted of 59 patients who received AC → T given every 3 weeks who were identified from the Clinical Research Information System database at Dana-Farber Cancer Institute. For cohorts 1 and 3, the electronic medical record was reviewed to determine absolute lymphocyte counts (ALCs) and absolute neutrophil counts (ANCs) for day 1 of each of the 8 cycles of treatment. For cohort 2, data was prospectively collected and entered into an electronic database. The lowest ALC obtained by each patient on day 1 of any cycle was termed the nadir. Results Patients experienced grade 3 (ALC < 500 cells/mm 3) or grade 4 (ALC < 200 cells/mm 3) lymphopenia in all 3 cohorts: 63% with dose-dense AC →T, 23.4% in dosedense AC → albumin-bound paclitaxel, and 69% with dose-dense AC → T every 3 weeks. Patients experienced their lowest median ALC count at cycle 5 of treatment in all 3 cohorts, with a median nadir of 400 cells/mm 3 in cohort 1, 690 cells/mm 3 in cohort 2, and 400 cells/mm 3 in cohort 3. Conclusion The majority of patients receiving AC → T every 2 or 3 weeks experience grade 3/4 lymphopenia. Median lymphocyte counts appear to be lowest around cycle 5, the point at which we observed 2 cases of PCP. Lymphocyte counts appear to be reaching a low enough level to place patients at risk for opportunistic infection during treatment with dosedense AC → T and with AC → T given every 3 weeks.

Pneumocystis Carinii Pneumonia During Dose-Dense Chemotherapy for Breast Cancer

<i>Pneumocystis Carinii</i> Pneumonia During Dose-Dense Chemotherapy for Breast Cancer

Level of Fatigue in Women Receiving Dose-Dense Versus Standard Chemotherapy for Breast Cancer: A Pilot Study

To determine whether women receiving dose-dense chemotherapy for breast cancer experience different levels of fatigue than women receiving standard chemotherapy regimens for the disease. Quasi-experimental pilot study. Private physicians' offices in California. 15 women with stage I, II, or III breast cancer receiving dose-dense or standard chemotherapy. The average female participant was 48 years old (mean = 48.3), was married (80%), and had a college degree (73%). The revised Piper Fatigue Scale was completed by patients at three different times: pretreatment, three days after their cycle 1 chemotherapy dose, and three days after their cycle 2 chemotherapy dose. Patients returned completed surveys by mail. Fatigue levels associated with chemotherapy. Pretreatment total fatigue scores were not significantly different in the dose-dense and standard chemotherapy groups. Total fatigue scores were significantly higher in the dose-dense group at the cycle 1 and 2 time points. Fatigue scores were significantly higher in women who had undergone a mastectomy, were working, were HER2 positive, and had a tumor size larger than 2 cm. Dose-dense chemotherapy resulted in significantly greater fatigue. Nurses should educate women receiving dose-dense chemotherapy as part of informed consent and assist them in preparing and planning for fatigue. Information about which patients are more likely to experience significant fatigue allows nurses to judge the frequency with which they need to assess and manage fatigue to improve patient outcomes.

Current status of dose-dense chemotherapy for breast cancer

In an effort to improve the effectiveness of chemotherapy for breast cancer, examination of the impact of dose intensity, dose density, and treatment duration may have as much relevance as the specific antineoplastic agents utilized. After several years of pilot feasibility studies of dose-dense chemotherapy regimens, whose delivery has been made safe and feasible by the use of hematopoietic growth factor support (in particular, filgrastim), we now have phase III data demonstrating the advantages of this approach in the adjuvant treatment of breast cancer.

Dose-dense chemotherapy in breast cancer and lymphoma

Adjuvant combination chemotherapy reduces the risk of relapse and death for patients with invasive breast cancer and adds to the benefits obtained with hormonal treatment. Generally, anthracycline-containing regimens are superior to non-anthracycline regimens, treatments longer than 6 months are not advantageous and high-dose chemotherapy regimens, which require autologous hematopoietic stem cell support, have not proved consistently superior. The development and evaluation of the taxanes was highly anticipated as they have shown high levels of efficacy while appearing to be non-cross-resistant with partially non-overlapping toxicities. A role for taxanes in the adjuvant or neoadjuvant setting is now widely acknowledged, although they are not currently approved for treatment of early breast cancer in Europe. In patients with aggressive lymphoma who receive cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy, 40% to 70% of patients attain a complete remission, depending on risk factors such as age and extranodal involvement. Second- and third-generation regimens like m-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide), Pro-MACE-CytaBOM (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate), and MACOP-B (methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) have largely failed to improve treatment outcome. The use of monoclonal anti-CD20 antibodies or dose escalation have shown promising results in improving relapse-free and survival rates. In patients with breast cancer, the key Cancer and Leukemia Group B 9741 trial showed that dose-dense doxorubicin, cyclophosphamide, and paclitaxel chemotherapy with granulocyte colony-stimulating factor (G-CSF), repeated every 2 weeks, is superior to the same regimen administered at standard 3-weekly intervals. In lymphoma, dose-dense CHOP chemotherapy has shown superiority over standard CHOP regimens, particularly in elderly patients with aggressive non-Hodgkin’s lymphoma. G-CSF factor is essential to enable the administration of dose-dense chemotherapy and any reduction in its use leads to significant increases in infectious complications. Current evidence suggests that dose-dense chemotherapy, enabled by G-CSF, is an important breakthrough in the evolution of chemotherapy for breast cancer and lymphoma.