Incidence and Predictors of Low Dose-Intensity in Adjuvant Breast Cancer Chemotherapy: A Nationwide Study of Community Practices

Purpose: This retrospective study was undertaken to assess practice patterns in adjuvant chemotherapy for early-stage breast cancer (ESBC) and to define the incidence and predictive factors of reduced relative dose-intensity (RDI). Patients and Methods: A nationwide survey of 1,243 community oncology practices was conducted, with data extracted from records of 20,799 ESBC patients treated with adjuvant chemotherapy. Assessments included demographic and clinical characteristics, chemotherapy dose modifications, incidence of febrile neutropenia, and patterns of use of colony-stimulating factor (CSF). Dose-intensity was compared with published reference standard regimens. Results: Dose reductions ≥15% occurred in 36.5% of patients, and there were treatment delays ≥7 days in 24.9% of patients, resulting in 55.5% of patients receiving RDI less than 85%. Nearly two thirds of patients received RDI less than 85% when adjusted for differences in regimen dose-intensity. Multivariate analysis identified several independent predictors for reduced RDI, including increased age; chemotherapy with cyclophosphamide, methotrexate, and fluorouracil, or cyclophosphamide, doxorubicin, and fluorouracil; a 28-day schedule; body-surface area greater than 2 m 2 ; and no primary CSF prophylaxis. CSF was often initiated late in the chemotherapy cycle. Conclusion: Patients with ESBC are at substantial risk for reduced RDI when treated with adjuvant chemotherapy. Patients at greatest risk include older patients, overweight patients, and those receiving three-drug combinations or 28-day schedules. Predictive models based on such risk factors should enable the selective application of supportive measures in an effort to deliver full dose-intensity chemotherapy.

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Chemotherapy for Early-Stage Breast Cancer: A Paradigm in Flux

Journal of Pharmacy Practice ◽

10.1177/0897190008314777 ◽

2008 ◽

Vol 21 (1) ◽

pp. 46-56

Author(s):

Lan-Phuong P. Tran ◽

Jodi L. Grabinski

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Chemotherapy ◽

Early Stage ◽

Breast Cancer Mortality ◽

The United States ◽

Early Stage Breast Cancer ◽

Breast Cancer Chemotherapy ◽

Therapeutic Decisions ◽

Adjuvant Breast Cancer

Breast cancer is the most common malignancy among women in the United States. A reduction in breast cancer mortality has been observed over recent years and is in part attributable to general use of adjuvant chemotherapy and trastuzumab. Besides the addition of specific therapeutic agents, the therapy of early-stage breast cancer has benefited from dose-dense approaches, identification of molecular markers, and translational research innovations such as prognostic gene expression assays. Treatment recommendations for adjuvant breast cancer chemotherapy are traditionally guided by results from clinical studies reflecting a general population; however, molecular and genomic information can potentially enable clinicians to formulate more refined therapeutic decisions. These advances also generate further questions regarding situations where application of therapy is necessary to optimize efficacy and circumstances where sparing therapy is appropriate. Taken together, the advances made through early-stage breast cancer chemotherapy positions us closer to fulfilling the promise of personalized medicine. This article reviews the recent progress of adjuvant chemotherapy and trastuzumab in breast cancer.

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Abstract P3-12-07: Dose delays, dose reductions, and relative dose intensity in early stage breast cancer patients receiving (neo)adjuvant chemotherapy in community oncology practices

10.1158/0008-5472.sabcs13-p3-12-07 ◽

2013 ◽

Author(s):

AM Favret ◽

X Li ◽

N Denduluri ◽

PK Morrow ◽

M Bhor ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

Early Stage ◽

Dose Intensity ◽

Early Stage Breast Cancer ◽

Breast Cancer Patients ◽

Community Oncology ◽

Neo Adjuvant Chemotherapy ◽

Dose Reductions

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Relative dose intensity in early stage breast cancer chemotherapy: A retrospective analysis of incidence, risk factors and outcomes at a south-west Sydney cancer clinic

Asia-Pacific Journal of Clinical Oncology ◽

10.1111/ajco.12093 ◽

2013 ◽

Vol 9 (4) ◽

pp. 365-372 ◽

Cited By ~ 8

Author(s):

Jessica Sandy ◽

Stephen Della-Fiorentina

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Retrospective Analysis ◽

Cancer Chemotherapy ◽

Early Stage ◽

Dose Intensity ◽

Breast Cancer Chemotherapy ◽

South West ◽

Incidence Risk ◽

Cancer Clinic

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Risk of Marrow Neoplasms After Adjuvant Breast Cancer Therapy: The National Comprehensive Cancer Network Experience

Journal of Clinical Oncology ◽

10.1200/jco.2013.54.6119 ◽

2015 ◽

Vol 33 (4) ◽

pp. 340-348 ◽

Cited By ~ 57

Author(s):

Antonio C. Wolff ◽

Amanda L. Blackford ◽

Kala Visvanathan ◽

Hope S. Rugo ◽

Beverly Moy ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Cumulative Incidence ◽

Early Stage ◽

Myelogenous Leukemia ◽

Early Stage Breast Cancer ◽

Individual Risk ◽

Breast Cancer Cohort ◽

Adjuvant Breast Cancer

Purpose Outcomes for early-stage breast cancer have improved. First-generation adjuvant chemotherapy trials reported a 0.27% 8-year cumulative incidence of myelodysplastic syndrome/acute myelogenous leukemia. Incomplete ascertainment and follow-up may have underestimated subsequent risk of treatment-associated marrow neoplasm (MN). Patients and Methods We examined the MN frequency in 20,063 patients with stage I to III breast cancer treated at US academic centers between 1998 and 2007. Time-to-event analyses were censored at first date of new cancer event, last contact date, or death and considered competing risks. Cumulative incidence, hazard ratios (HRs), and comparisons with Surveillance, Epidemiology, and End Results estimates were obtained. Marrow cytogenetics data were reviewed. Results Fifty patients developed MN (myeloid, n = 42; lymphoid, n = 8) after breast cancer (median follow-up, 5.1 years). Patients who developed MN had similar breast cancer stage distribution, race, and chemotherapy exposure but were older compared with patients who did not develop MN (median age, 59.1 v 53.9 years, respectively; P = .03). Two thirds of patients had complex MN cytogenetics. Risk of MN was significantly increased after surgery plus chemotherapy (HR, 6.8; 95% CI, 1.3 to 36.1) or after all modalities (surgery, chemotherapy, and radiation; HR, 7.6; 95% CI, 1.6 to 35.8), compared with no treatment with chemotherapy. MN rates per 1,000 person-years were 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), and 0.54 (all three modalities). Cumulative incidence of MN doubled between years 5 and 10 (0.24% to 0.48%); 9% of patients were alive at 10 years. Conclusion In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy.

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Adjuvant chemotherapy and survival outcome in node-negative breast cancer with a 21-gene recurrence score of 26–30

Future Oncology ◽

10.2217/fon-2020-1315 ◽

2021 ◽

Author(s):

Shi-Ping Yang ◽

Jia Yao ◽

Ping Zhou ◽

Chen-Lu Lian ◽

Jun Wang ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Early Stage ◽

Recurrence Score ◽

Tumor Grade ◽

Early Stage Breast Cancer ◽

Sensitivity Analyses ◽

Breast Cancer Patients ◽

Cancer Specific Survival ◽

Chemotherapy Patients

Aim: To investigate the benefit of chemotherapy among early-stage breast cancer patients with 21-gene recurrence scores of 26–30. Methods: We identified 3754 patients in the Surveillance, Epidemiology, and End Results database. Results: 57.6% of the patients received adjuvant chemotherapy. Patients with higher tumor grade, larger tumors and younger age were more likely to receive chemotherapy. The receipt of chemotherapy was independently associated with better breast cancer-specific survival than in patients without chemotherapy before (p = 0.016) and after (p = 0.043) propensity score matching. The sensitivity analyses showed that survival gain was pronounced in patients with poorly differentiated or undifferentiated disease. Conclusions: Adjuvant chemotherapy improves the outcome for early-stage breast cancer with 21-gene recurrence score of 26–30, especially for patients with high-grade tumors.

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Chemotherapy-Induced Activation of Hemostasis: Dalteparin Suppresses Both Thrombin and Interleukin-6 Expression in Breast Cancer Patients Receiving Adjuvant Chemotherapy.

Blood ◽

10.1182/blood.v104.11.3509.3509 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3509-3509

Author(s):

Ilene Ceil Weitz ◽

Howard A. Liebman

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Thrombin Generation ◽

Systemic Chemotherapy ◽

Early Stage ◽

Optimal Dose ◽

Cytokine Expression ◽

Breast Cancer Patients ◽

Chemotherapeutic Regimen ◽

Chemotherapy Patients

Thrombotic events are well documented in patients with cancer and have frequently been described in the setting of systemic chemotherapy. We have previously reported (Thromb Haemost2002; 88:213–220) that patients treated for breast and lung cancer demonstrate significant hemostatic activation, as documented by increases in thrombin-antithrombin (TAT) complexes and D-dimers, within 1 hour of receiving chemotherapy. The hemostatic effects appear to be cumulative with baseline pretreatment levels of TAT increasing with progressive cycles of chemotherapy. In the same study, we demonstrated that a single injection of dalteparin, a LMW heparin, administered prior to therapy could suppress hemostatic activation. We proposed that the progressive increases in basal thrombin generation resulted from chemotherapy-induced increases in inflammatory cytokines. We measured plasma levels of Il-6 in the 10 women with early stage breast cancer from this study who were receiving cyclophosphamide-doxorubicin adjuvant chemotherapy. Patients had plasma samples drawn prior to each cycle of chemotherapy, and at 1 hour, 24 and 48 hours after treatment. Prior to 2nd cycle of chemotherapy the patients received 2500 U dalteparin, prior to the 4th cycle of treatment, the patients received 5000 U dalteparin. No LMW heparin was given with the 1st and 3rd cycles. There were statistically significant increases in plasma TAT and D-dimers after chemotherapy in cycles 1 and 3. There was a significant increase in basal thrombin generation as measured over the four cycles of treatment unrelated to the presence of active cancer. Both pretreatment doses of dalteparin effectively prevented increases in markers of hemostatic activation after receiving chemotherapy. With each cyle of chemotherapy the 1 hour Il-6 levels were slightly lower than the pretreatment levels, but this was not statistically significant and could reflect a direct effect of the chemotherapeutic regimen on cytokine production. However, in cycle 1 and 3 the Il-6 levels increased to greater than pretreatment levels by 48 hours. There was a statistically significant increase in plasma Il-6 levels measured prior to the 4th cycle of chemotherapy when compared to the plasma Il-6 measured prior to the 1st cycle (4.976pg/ml± 1.620 vs 3.30 pg/ml±1.005 ; P<0.05). There was a trend for the pretreatment Il-6 levels measured prior to the 3rd cycle and 21 days after receiving 2500 U dalteparin to be lower than the levels measured prior to cycle 2, although not statistically significant (4.032±2.415 vs. 6.203±3.862; p=0.072). A 21 day sample was not obtained following the fourth cycle in which 5000U dalteparin was given and therefore the effect of this dose on basal thrombin generation and Il-6 expression could not be determined. We conclude; 1) the progressively increasing basal generation of thrombin associated with systemic chemotherapy in patients with breast cancer is associated with increases in the inflammatory cytokine, Il-6. 2) The increased expression of Il-6 and possibly other cytokines may be responsible for the progressive increases in hemostatic activation with repeated cycles of chemotherapy. In our study, there is a suggestion that a LMW heparin, dalteparin, not only prevented chemotherapy-induced hemostatic activation, but may also suppress chemotherapy-related cytokine expression. However, the optimal dose of dalteparin necessary for suppression of chemotherapy-induced cytokine expression is unknown and may vary with different malignancies and chemotherapy agents.

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Feasibility and toxicity of docetaxel before or after fluorouracil, epirubicin, and cyclophosphamide as adjuvant chemotherapy for early-stage breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.604 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 604-604

Author(s):

H. Abe ◽

T. Umeda ◽

Y. Kawai ◽

M. Tanaka ◽

T. Shimizu ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Febrile Neutropenia ◽

Adverse Events ◽

Early Stage ◽

Dose Intensity ◽

Completion Rate ◽

Early Stage Breast Cancer ◽

Hematological Toxicity ◽

Grade 3

604 Background: As adjuvant chemotherapy for breast cancer, the addition of docetaxel to regimens containing anthracyline has been shown to be effective. However, tolerance and safety associated with the administration order of the two drugs have not been evaluated. Methods: Breast cancer patients with node-positive or high-risk patients with node-negative were eligible. The treatment completion rate and toxicity were evaluated in 2 arms who underwent a total of 6 courses of the following regimens: Arm A: 3 courses of fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 (FEC100: q3w) followed by 3 courses of docetaxel (DOC100: 100 mg/m2, q3w); and Arm B: 3 courses of DOC100 (q3w) followed by 3 courses of FEC100 (q3w). Results: June 2006 to April 2008, 42 patients were registered. To the present, analysis has been completed in 21 patients in arm A and 21 in arm B. The mean age of patients was 49.1 years and 53.8 years, respectively. In arm A, the stage of cancer was 1 in 4 patients, 2a in 10, and 2b in 7, in arm B, the stage of cancer was 1 in 3 patients, 2a in 9, and 2b in 9. The adjuvant chemotherapy completion rate was 100 % for arm A and 95.2 % for arm B. The relative dose intensity (RDI) was 94.2 % for FEC100 and 97.8 % for DOC100 in arm A, and 98.9 % for DOC100 and 95.2 % for FEC100 in arm B. In arm A, grade 3 or higher hematological toxicity was observed in 9 patients, and febrile neutropenia developed in 3 patients with FEC100. In arm B, grade 3 or higher hematological toxicity was observed in 7 patients, but febrile neutropenia was not noted in any patients. Grade 3 or higher non-hematological toxicity was observed with FEC100 in 2 patients each in the two arms. Grade 1 or 2 edema developed in 11 patients with DOC100 in the two arms. Conclusions: In both arm A and B, adverse events associated with FEC100 were frequently observed but spontaneously recovered, or adequate management was possible by supportive therapy. Adverse events associated with DOC100 were mild. The regimens in both arms A and B were safe regarding adjuvant chemotherapy for early stage breast cancer. However, DOC100 followed by FEC100 may be more tolerable and effective. No significant financial relationships to disclose.

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