Changes in volume and incidence of lymphedema during and after treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) in patients with breast cancer

Janine T. Hidding & Carien H. G. Beurskens & Philip J. van der Wees & Wilmy C. A. M. Bos & Maria W. G. Nijhuis-van der Sanden & Hanneke W. M. van Laarhoven. Support Care Cancer November 2017

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Changes in volume and incidence of lymphedema during and after treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC) in patients with breast cancer

Janine T. Hidding & Carien H. G. Beurskens & Philip J. van der Wees & Wilmy C. A. M. Bos & Maria W. G. Nijhuis-van der Sanden & Hanneke W. M. van Laarhoven. Support Care Cancer November

Purposes The purposes of this study were to investigate the incidence of lymphedema in patients with breast cancer during and after adjuvant treatment with docetaxel, doxorubicin, and cyclophosphamide (TAC), to identify predictors for development of lymphedema, and to describe consequences in daily life in relation to lymphedema.

Methods This is a prospective study with measurements before chemotherapy (T0), during chemotherapy before cycle 2 (T1), cycle 4 (T2), and 1 month after completion of treatment (T3). Volume change was monitored using tape measurements. Lymphedema was defined as ≥ 10% volume difference. Linear mixed-effect models were estimated to analyze differences in arm volume and consequences in daily life (total score and domain scores of the Lymph-International Classification of Functioning (ICF) questionnaire) over time and to identify treatment and patient characteristics as predictors for changes in volume.

Results Forty-eight patients completed all measurements. Volume did not change during TAC treatment. One month after treatment, volume was significantly increased compared to T0-T2, and 12 patients (25%) had developed lymphedema. Axillary lymph node dissection was associated with lymphedema (ES 2.9, 95% CI 0.02–5.7; p < 0.05). In patients with and without lymphedema, 1 month after completion (T3), the Lymph-ICF questionnaire showed significant limitations in physical function compared to T0-T2. Inpatients with lymphedema at T3, a significant association between volume and total score on the Lymph-ICF questionnaire on physical function and mobility activities was observed.

Conclusions One month after treatment in 12 patients (25%), volume difference increased over 10%. Axillary lymph node dissection was predictive for development of lymphedema. All patients, but more patients with lymphedema, perceived difficulties in activities in daily life after treatment.

Main findings

  • Docetaxel (75 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) were administered intravenously on day 1 of a three-weekly cycle for a total of six courses. Dexamethasone was administered 8 mg orally twice daily for 3 days, starting the day before start of TAC during all cycles.
  • Patients were measured at four time points: at baseline before cycle1 (T0), during chemotherapy before cycle2 (T1) and cycle4 (T2), and 1 month after the 6th cycle (T3). Three months after completion, the Lymph ICF questionnaire was sent to the patients.
  • Weight was registered before the first and after the last cycle to determine body mass index (BMI) and weight changes. Volume of both arms was measured by tape measurement, and impairments in functions and limitations in activities in daily life were measured by the Lymph ICF questionnaire. Measurements were performed by three physiotherapists.
  • All patients with a volume difference ≥ 10%, at any time point, were referred for treatment.
  • Mean volume did not change during treatment but increased significantly from 2.3% at T0 to 5.1% at 1 month after completion of TAC. During cytotoxic treatment with TAC, they observed no significant changes in volume between upper extremities in the total study population. However, 1month after completion of TAC, volume was increased significantly, and 25% of the patients had developed a volume difference over 10%, defined as lymphedema.
  • As no measurements were performed between cycles 4 and 6, the exact time point of onset of lymphedema cannot be determined. A longer follow-up would have enabled the distinction between transient swelling from persistent lymphedema.
  • Arm volume increased significantly 1month after treatment with TAC and in 12 out of 48 patients (25%) relative volume difference increased over 10%.