A Phase II Trial Exploring the Success of Cryoablation Therapy in the Treatment of Invasive Breast Carcinoma: Results from ACOSOG (Alliance) Z1072.

BACKGROUND: Cryoablation is a well-established technique to treat fibroadenomas. Pilot studies suggest this could be an effective non-surgical treatment for breast cancer. American College of Surgeons Oncology Group Z1072 is a phase II trial exploring the effectiveness of cryoablation in the treatment of breast cancers. METHODS: The primary endpoint of Z1072 was the rate of complete tumor ablation, defined as no remaining invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) on pathologic examination of the targeted lesion. A secondary objective was to evaluate the negative predictive value of magnetic resonance imaging (MRI) to determine residual IBC or DCIS. Eligible patients included those with unifocal invasive ductal breast cancer ≤2 cm, with <25 % intraductal component and tumor enhancement on MRI. A total of 19 centers contributed 99 patients, of which 86 patients (87 breast cancers) were evaluable for data analysis. RESULTS: Final pathology results, regardless of whether residual IBC/DCIS was in the targeted ablation zone or elsewhere in the breast, showed successful ablation in 66/87 (75.9 %) cancers. The 90 % confidence interval for the estimate of successful cryoablation was 67.1-83.2, with the one-sided lower-sided 90 % CI of 69.0. The negative predictive value of MRI was 81.2 % (90 % CI 71.4-88.8). When multifocal disease outside of the targeted cryoablation zone was not defined as an ablation failure, 80/87 (92 %) of the treated cancers had a successful cryoablation. CONCLUSION: Further studies with modifications on the Z1072 protocol could be considered to evaluate the role for cryoablation as a non-surgical treatment of early-stage breast cancer.

Screening for psychological distress in surgical breast cancer patients.

BACKGROUND: This pilot study assessed the levels of patient emotional distress and impact on clinic throughput time. METHODS: From April through August 2012, 149 breast cancer patients at the Penn State Hershey Breast Center were screened with the emotions thermometer (ET), a patient-rated visual 0-10 scale that measures distress, anxiety, depression, anger, burden, and need for help. Also, patients indicated their most pressing cancer-related concerns. Clinic visit time was computed and compared with a control group. RESULTS: Using a previously validated cut point ≥4 for any thermometer, we found emotional difficulty in the following proportions: distress 22 %, anxiety 28 %, depression 18 %, anger 14 %, burden 16 %, and need for help 10 %; 35 % scored above the cut point on at least 1 thermometer. We found higher levels of distress in all domains associated with younger age at diagnosis. More extensive surgery (bilateral mastectomy vs unilateral mastectomy vs. lumpectomy) was correlated with higher levels of psychosocial distress. Most often cited concerns, experienced by >20 %, included eating/weight, worry about cancer, sleep problems, fatigue, anxiety, and pain. Mean clinic visit time for evaluable patients screened using the ET (n = 109) was 43.9 min (SD 18.6), compared with 42.6 min (SD 16.2) for the control group (n = 50). CONCLUSIONS: Utilizing the ET, more than one-third of women screened met criteria for psychological distress. Younger age at diagnosis and more extensive surgery were risk factors. The ET is a simple validated screening tool that identifies patients in need of further psychological evaluation without impacting clinic throughput time.

Role of c-Src and focal adhesion kinase in progression and metastasis of estrogen receptor-positive breast cancer.

The non-receptor tyrosine kinases c-Src and focal adhesion kinase (Fak) mediate signal transduction pathways that regulate cell proliferation, survival, invasion, and metastasis. Here, we investigated whether c-Src and Fak are activated during progression of hormone-dependent breast cancer. Maximally active c-Src was overexpressed in a subset of tamoxifen-resistant variants and in metastases of recurrent hormone-treated breast cancer. Active Fak was also frequently observed in these tumors. We also show that estrogen receptor (ER) can bind to Fak and that estrogen can modulate Fak autophosphorylation supporting a cross-talk between these two pathways. Inhibition of c-Src activity blocked proliferation of all tamoxifen-resistant variants, suggesting that inhibitors of c-Src-Fak activity may delay or prevent progression and metastasis of ER-positive tumors. These studies also raise the possibility that fully active forms of c-Src and Fak in breast tumors may be biomarkers to predict tamoxifen resistance and/or risk of recurrence in ER-positive breast cancer.