Combination Chemotherapy With or Without Fluorouracil and/or Pegfilgrastim in Treating Women With Node-Positive Breast Cancer

RATIONALE: Drugs used in chemotherapy, such as epirubicin, cyclophosphamide, paclitaxel, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Colony-stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving combination chemotherapy and pegfilgrastim after surgery may kill any tumor cells that remain after surgery. It is not yet known whether combination chemotherapy is more effective with or without fluorouracil and/or pegfilgrastim in treating breast cancer. PURPOSE: This randomized phase III trial is studying combination chemotherapy to compare how well it works when given with or without fluorouracil and/or pegfilgrastim in treating women with node-positive breast cancer.

Sex

Female

Minimum age

18 Years

Maximum age

70 Years

DISEASE CHARACTERISTICS:

* Histologically confirmed primary breast cancer

  * No histology other than carcinoma
* Node-positive disease

  * Must have at least 1 involved axillary node or internal mammary node
* Previously resected disease

  * Has undergone radical surgery (i.e., mastectomy or conservative surgery) with axillary node dissection within the past 7 weeks
* No inflammatory carcinoma
* No prior or concurrent ipsilateral or contralateral invasive breast carcinoma
* No metastatic disease, including metastasis in the ipsilateral supraclavicular lymph nodes
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* Female
* Menopausal status not specified
* ECOG performance status 0-1
* Absolute neutrophil count ≥ 1,500/mm³
* WBC ≥ 4,000/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 9 g/dL
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* Creatinine ≤ 1.5 times ULN
* AST and ALT ≤ 2.5 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No chronic liver or renal disease
* No other serious medical illness requiring medication
* No other malignancy except adequately treated, cone-biopsied in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin
* No symptomatic peripheral neuropathy \> grade 2
* No hypersensitivity to study drugs or their components
* No recent myocardial infarction, congestive heart failure, or serious arrhythmia

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior chemotherapy
* No prior cytotoxic regimens
* No prior radiation therapy, except for intraoperative radiation therapy

• DERIVEDMolinelli C, Delucchi V, Blondeaux E, Boni L, Poggio F, Soldato D, Antonj L, Arpino G, Nistico C, Fabi A, De Laurentiis M, Buono G, Puglisi F, Nader-Marta G, Fozza A, Pitto F, Boncore F, Cardinali B, Fregatti P, Lambertini M, Del Mastro L. Dose-dense adjuvant chemotherapy in HER2-low breast cancer: An exploratory analysis of the GIM2 trial. Breast. 2026 Aug;88:104848. doi: 10.1016/j.breast.2026.104848. Epub 2026 Jun 22. PMID 42364416
• DERIVEDDel Mastro L, Poggio F, Blondeaux E, De Placido S, Giuliano M, Forestieri V, De Laurentiis M, Gravina A, Bisagni G, Rimanti A, Turletti A, Nistico C, Vaccaro A, Cognetti F, Fabi A, Gasparro S, Garrone O, Alicicco MG, Urracci Y, Mansutti M, Poletti P, Correale P, Bighin C, Puglisi F, Montemurro F, Colantuoni G, Lambertini M, Boni L; Gruppo Italiano Mammella Investigators. Fluorouracil and dose-dense adjuvant chemotherapy in patients with early-stage breast cancer (GIM2): end-of-study results from a randomised, phase 3 trial. Lancet Oncol. 2022 Dec;23(12):1571-1582. doi: 10.1016/S1470-2045(22)00632-5. Epub 2022 Nov 10. PMID 36370716
• DERIVEDLambertini M, Bruzzi P, Poggio F, Pastorino S, Gardin G, Clavarezza M, Bighin C, Pronzato P, Del Mastro L. Pegfilgrastim administration after 24 or 72 or 96 h to allow dose-dense anthracycline- and taxane-based chemotherapy in breast cancer patients: a single-center experience within the GIM2 randomized phase III trial. Support Care Cancer. 2016 Mar;24(3):1285-94. doi: 10.1007/s00520-015-2907-2. Epub 2015 Aug 27. PMID 26306520
• DERIVEDDel Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, Durando A, Turletti A, Nistico C, Valle E, Garrone O, Puglisi F, Montemurro F, Barni S, Ardizzoni A, Gamucci T, Colantuoni G, Giuliano M, Gravina A, Papaldo P, Bighin C, Bisagni G, Forestieri V, Cognetti F; Gruppo Italiano Mammella (GIM) investigators. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 x 2 factorial, randomised phase 3 trial. Lancet. 2015 May 9;385(9980):1863-72. doi: 10.1016/S0140-6736(14)62048-1. Epub 2015 Mar 2. PMID 25740286