Comparison of Combination Chemotherapy Regimens in Treating Older Women Who Have Undergone Surgery for Breast Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different ways after surgery may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective in treating older women with breast cancer. PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to see how well they work in treating older women who have undergone surgery for breast cancer.

Sex

Female

Minimum age

65 Years

1. Patients with operable, histologically confirmed adenocarcinoma of the female breast.
2. TNM Stage per AJCC Cancer Staging Manual 6th edition:

   * T1-4 (Tumor size \> 1 cm), N0, M0 or T1-4, N1-3, M0
   * Patients with bilateral, synchronous breast cancer are eligible as long as one primary tumor meets the criteria above.
3. Patients with HER2/neu positive, negative or unknown disease are eligible for this trial.

   Patients whose tumors are HER2 positive by either immunohistochemistry 3+ staining or demonstrate gene amplification by FISH will be eligible to receive trastuzumab, as outlined in the protocol.
4. Age 65 years or older
5. Performance status 0-2 (Common Toxicity Criteria).
6. Prior treatment:

   * Surgical resection -

     * All tumor should be removed by either a modified radical mastectomy or a lumpectomy. Patients must be registered ≤ 84 days from mastectomy or within 84 days of axillary dissection if patient's most extensive breast surgery was a breast sparing procedure.
     * Node dissection: Axillary node dissection is not required. Management of the axilla is at the discretion of the treating physician. There is no restriction on eligibility based on the number of nodes removed.
     * Mastectomy: There should be no evidence of gross or microscopic invasive tumor at the surgical resection margins noted in the final surgery or pathology reports for patients who have had a modified radical mastectomy. Patients with close margins (tumor \< 1 mm from margin) are eligible.
     * Segmental mastectomy (lumpectomy): Although clear margins are preferable, DCIS or LCIS at the surgical resection margin will not render a patient who has undergone a segmental mastectomy ineligible for this study. Invasive tumor at the final resection margin will render a patient ineligible.
   * No prior chemotherapy for this malignancy.
   * Patients with a history of hypersensitivity to 5-FU or known dihydropyrimidine dehydrogenase (DPD) deficiency are not eligible to participate.
   * Patients may receive up to four weeks of tamoxifen therapy for this malignancy and still be eligible for study entry. Patients who received tamoxifen or raloxifene for purposes of chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (including previous breast cancer) are eligible. Tamoxifen or raloxifene therapy should be discontinued before the patient is enrolled on this study.
7. Required Initial Laboratory Data:

   * Granulocytes \> 1,500/µl
   * Platelet count ≥100,000/µl
   * Calculated Creatinine Clearance \> 30 mL/min
   * Total bilirubin ≤ ULN

• BACKGROUNDPal SK, Mortimer J. Adjuvant chemotherapy for older adults with breast cancer: making the standard a standard. Womens Health (Lond). 2009 Sep;5(5):481-4. doi: 10.2217/whe.09.43. PMID 19702447
• RESULTPartridge AH, Archer L, Kornblith AB, Gralow J, Grenier D, Perez E, Wolff AC, Wang X, Kastrissios H, Berry D, Hudis C, Winer E, Muss H. Adherence and persistence with oral adjuvant chemotherapy in older women with early-stage breast cancer in CALGB 49907: adherence companion study 60104. J Clin Oncol. 2010 May 10;28(14):2418-22. doi: 10.1200/JCO.2009.26.4671. Epub 2010 Apr 5. PMID 20368559
• RESULTKornblith AB, Archer L, Lan L, et al.: Quality of life of early stage breast cancer patients 65 years old or older randomized to standard chemotherapy or capecitabine: A Cancer and Leukemia Group B Study (CALGB 49907). [Abstract] 32nd Annual San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, Texas. A-5035, 2009.
• RESULTMuss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Becker HP, Kartcheske PA, Wheeler JD, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Magrinat G, Parker BA, Hart RD, Grenier D, Norton L, Hudis CA, Winer EP; CALGB Investigators. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009 May 14;360(20):2055-65. doi: 10.1056/NEJMoa0810266. PMID 19439741
• RESULTMuss HB, Berry DL, Cirrincione C, et al.: Standard chemotherapy (CMF or AC) versus capecitabine in early-stage breast cancer (BC) patients aged 65 and older: results of CALGB/CTSU 49907. [Abstract] J Clin Oncol 26 (Suppl 15): A-507, 2008.
• RESULTPartridge AH, Archer LE, Kornblith AB, et al.: CALGB 60104: adherence with adjuvant capecitabine among women age 65 and older with early stage breast cancer treated on CALGB 49907. [Abstract] J Clin Oncol 26 (Suppl 15): A-6542, 2008.
• DERIVEDHoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.