Risk factors for breast cancer-related lymphedema: correlation with docetaxel administration.

BACKGROUND: Upper-limb lymphedema is a well-known complication of breast cancer and its treatment. This retrospective cohort study aims to determine what risk factors affect breast cancer-related lymphedema in patients with breast cancer. METHODS: This retrospective study comprised patients diagnosed with breast cancer and who underwent surgery at Wakayama Medical University Hospital between January 1, 2012 and December 31, 2018. Assessed factors using univariate and multivariate analyses were patient-related factors (age, gender, and BMI), breast cancer-related factors (tumor size, nodal status, histology, tumor location, and intrinsic subtype), and treatment-related factors (type of surgery, application, timing and regimen of chemotherapy, and application of radiotherapy). RESULTS: This study included 1041 patients. BMI did not affect the onset of breast cancer-related lymphedema. There were only six sentinel lymph node biopsy cases in the breast cancer-related lymphedema group (6.6%). In cases of axillary lymph node dissection, adjuvant chemotherapy was marginally associated with increased risk of breast cancer-related lymphedema compared to no chemotherapy (HR 2.566; 95% CI 0.955-6.892; p = 0.0616). Among anti-cancer agents, docetaxel (HR 3.790; 95% CI 1.413-10.167; p = 0.0081) and anti-HER2 therapy (HR 2.507; 95% CI 1.083-5.803; p = 0.0318) were associated with increased risk of lymphedema according to multivariate analysis. Neo-adjuvant chemotherapy did not affect the onset of breast cancer-related lymphedema. Radiotherapy (HR 2.525; 95% CI 1.364-4.676; p = 0.0032) was an important risk factor for breast cancer-related lymphedema. CONCLUSIONS: Axillary lymph node dissection, radiotherapy and adjuvant chemotherapy, especially docetaxel, were risk factors for breast cancer-related lymphedema, but BMI and neo-adjuvant chemotherapy were not.

Quantitative Evaluation of Hormesis in Breast Cancer Using Histoculture Drug Response Assay.

PURPOSE: Hormesis is a phenomenon of growth stimulation at low doses and inhibition at higher doses. In cancer treatment, little is known about how hormesis affects cancer cell proliferation. We evaluated the hormetic dose-response relationship of paclitaxel using surgically resected breast cancer specimens on the basis of histoculture drug response assay (HDRA). METHODS: We used surgically resected fresh tumor specimens from 22 patients with breast cancer: 17 invasive ductal, 3 mucinous, and 2 other "special-type" cancers. All patients were female, ranging in age between 40 and 86 (median 60) years. Small pieces of viable cancer tissue were placed on collagen gel and cultured for 7 days with paclitaxel. Inhibition rates of paclitaxel at several concentrations were measured and fitted to a sigmoid dose-response curve. RESULTS: Hormesis was observed in 9 of the 22 cases; ED50 of cytotoxic effect was significantly higher (P = .0036) in hormesis (H) group (44.6 ± 4.2 µg/mL) than in nonhormesis (N) group (26.7 ± 3.5 µg/mL). CONCLUSION: We evaluated hormesis in breast cancer tissue using HDRA for the first time although previously confirmed in cultured cells. Hormesis seems to occur in patients undergoing treatment with anticancer agents, especially in a metastatic setting. Meanwhile, tumor growth may be stimulated in patients who are resistant to paclitaxel.

[Application of Bevacizumab beyond Progressive Disease in Patients with Lung Cancer Recurrence after Surgery].

BACKGROUND: The benefits of continuing bevacizumab (BEV) beyond progressive disease (PD) in patients with non-small cell lung cancer (NSCLC) remain unclear. We present our experience of continuing chemotherapy with BEV in patients with recurrent NSCLC after surgery. PATIENTS: From January 2010 to December 2016, chemotherapy with BEV was continued beyond PD in 20 patients. These patients included 10 men and 10 women, and their mean age at surgery was 71±10 years. Recurrence was observed at 630±460 days after surgery. RESULTS: The average number of protocols with BEV was 3±1 (1-6). The presented side effects were acceptable. Eight patients died of cancer. The 5-year survival rates after surgery, recurrence, and initiation of BEV were 78.8%, 50.1%, and 34.3%, respectively, and the median survival times were 2,465, 2,017, and 1,120 days, respectively. CONCLUSION: The majority of patients with operable NSCLC had a good performance status. We could detect recurrence early on, before the symptoms appeared, by regular examination. Therefore, these patients had an advantage in that more chemotherapeutic regimens could be administered to them and their prognosis could be improved by the continuation of BEV beyond over PD.

Class III Beta-tubulin Expression in Non-small Cell Lung Cancer: A Predictive Factor for Paclitaxel Response.

AIM: In order to clarify whether class III beta-tubulin (TUBB3) is a predictive marker for paclitaxel (PTX) chemotherapy, chemosensitivity was examined using an in vitro drug sensitivity assay. PATIENTS AND METHODS: Twelve specimens from non-small cell lung cancer (NSCLC) patients were obtained for dose-response curve analysis and measurement of the half-maximal effective dose (ED50) of PTX using the histoculture drug response assay (HDRA). Forty-one specimens were evaluated using the HDRA and the inhibition ratio (IR) at a concentration of 25 µg/ml PTX (IR25) was measured. TUBB3 expression was evaluated by H-score in immunohistochemical staining. RESULTS: The ED50 of PTX was 24.5 ± 8.06 µg/ml. The median H-score was significantly higher (p=0.0076) in the high effective dose (HE)-group (ED50 >25 µg/ml) than in the low effective (LE)-group (ED50 ≤ 25 µg/ml). The mean IR25 was 53.8 ± 26.6%. The median H-score for the high-inhibition ratio (HI)-group (IR25 >50%) was significantly higher (p=0.0337) than the low-inhibition ratio (LI)-group (IR25 ≤ 50%). CONCLUSION: High TUBB3 expression in NSCLC appeared to correlate with lower PTX sensitivity.