Adjuvant treatment recommendations for patients with ER-positive/HER2-negative early breast cancer by Swiss tumor boards using the 21-gene recurrence score (SAKK 26/10).

BACKGROUND: To evaluate the effect of Recurrence Score® results (RS; Oncotype DX® multigene assay ODX) on treatment recommendations by Swiss multidisciplinary tumor boards (TB). METHODS: SAKK 26/10 is a multicenter, prospective cohort study of early breast cancer patients: Eligibility: R0-resection, ≥10% ER+ malignant cells, HER2-, pN0/pN1a. Patients were stratified into low-risk (LR) and non-low-risk (NLR) groups based on involved nodes (0 vs 1-3) and five additional predefined risk factors. Recommendations were classified as hormonal therapy (HT) or chemotherapy plus HT (CT + HT). Investigators were blinded to the statistical analysis plan. A 5%/10% rate of recommendation change in LR/NLR groups, respectively, was assumed independently of RS (null hypotheses). RESULTS: Two hundred twenty two evaluable patients from 18 centers had TB recommendations before and after consideration of the RS result. A recommendation change occurred in 45 patients (23/154 (15%, 95% CI 10-22%) in the LR group and 22/68 (32%, 95% CI 22-45%) in the NLR group). In both groups the null hypothesis could be rejected (both p < 0.001). Specifically, in the LR group, only 5/113 (4%, 95% CI 1-10%) with HT had a recommendation change to CT + HT after consideration of the RS, while 18/41 (44%, 95% CI 28-60%) of patients initially recommended CT + HT were subsequently recommended only HT. In the NLR group, 3/19 (16%, 95% CI 3-40%) patients were changed from HT to CT + HT, while 19/48 (40%, 95% CI 26-55%) were changed from CT + HT to HT. CONCLUSION: There was a significant impact of using the RS in the LR and the NLR group but only 4% of LR patients initially considered for HT had a recommendation change (RC); therefore these patients could forgo ODX testing. A RC was more likely for NLR patients considered for HT. Patients considered for HT + CT have the highest likelihood of a RC based on RS.

Tomosynthesis-guided vacuum-assisted breast biopsy: A feasibility study.

PURPOSE: Evaluation of feasibility and clinical performance of a tomosynthesis-guided vacuum-assisted breast biopsy (TVAB) system compared to Stereotaxy (SVAB). MATERIALS AND METHODS: All biopsies were performed on consecutive patients: 148 TVAB biopsies and 86 biopsies on different patients using SVAB. Evaluation criteria for each biopsy were technical feasibility, histopathology, procedure time, and complications. RESULTS: All 148 TVAB biopsies were technically successful, and gained the targeted groups of microcalcifications (100 %). In 1 of 86 SVAB procedures, it was not possible to gain the targeted microcalcifications (1 %), in 3 of 86 the needle had to be adjusted (4 %). All TVAB biopsies were performed without clinically relevant complications. Distortions were biopsied exclusively by TVAB, mean size 0.9 cm, p < 0.0001. Of the 24 distortions, 13 were cancer, 11 Radial Scars/ CSL. The mean procedure time for TVAB was 15.4 minutes (range 7-28 min), for SVAB 23 minutes (range 11-46 min), p < 0.0001. CONCLUSIONS: TVAB is able to biopsy small architectural distortions with high accuracy. TVAB is easily feasible and appears to have the same degree of clinical performance for diagnosing microcalcifications. The increased number of biopsied distortions by TVAB is presumably due to increased use of tomosynthesis and its diagnostic potential. KEY POINTS: • TVAB is easily feasible. • TVAB is able to target architectural distortions with high accuracy. • TVAB diagnoses microcalcifications with the same clinical performance as SVAB.

Mutation Profiling of Lung Cancers with Long-Term Response to Gefitinib Therapy.

BACKGROUND: The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and unknown EGFR mutation status has recently been questioned. PATIENTS AND METHODS: We conducted a retrospective study of patients with unknown EGFR mutation status and long-term response (LTR) to gefitinib in the Swiss Iressa expanded access program (EAP). We assessed patient characteristics, and performed Sanger sequencing and next generation sequencing on archived tumor tissue. We hypothesized that EGFR mutations are prevalent in patients with LTR. RESULTS: Of 430 patients in the EAP, 18 (4%) fulfilled our definition of LTR, and 16 of them had archived tumor tissue. Patient characteristics were as expected for age, sex, and smoking history. Median duration of therapy was 38 months (range 24-142 months). Sanger sequencing revealed EGFR exon 18-21 mutations in 6 (38%) of the tumors. Next generation sequencing revealed no further EGFR-mutated cases, but reported in 15 (94%) of the tumors mutations in other genes (ALK, BRAF, DDR2, KEAP1, MET, PTEN, STK11) previously associated with NSCLC. CONCLUSION: Larger studies are needed to define the prognostic values of different driver mutations in patients with NSCLC.

Value of one-view breast tomosynthesis versus two-view mammography in diagnostic workup of women with clinical signs and symptoms and in women recalled from screening.

OBJECTIVE: The purpose of this study is to compare the diagnostic value of one-view digital breast tomosynthesis versus two-view full-field digital mammography (FFDM) alone, and versus a combined reading of both modalities. MATERIALS AND METHODS: The datasets of one-view digital breast tomosynthesis and two-view FFDM of abnormal mammograms in 144 consecutive women admitted for diagnostic workup with clinical signs and symptoms (n = 78) or recalled from screening (n = 66) were read alone and in a combined setting. The malignant or benign nature of the lesions was established by histologic analysis of biopsied lesions or by 12-16-month follow-up. RESULTS: Eighty-six of the 144 patients were found to have breast cancer. The BI-RADS categories for one-view digital breast tomosynthesis were significantly better than those for two-view FFDM (p < 0.001) and were equal to those of the combined reading in both women admitted for diagnostic workup and women recalled from screening. The sensitivity and negative predictive values of digital breast tomosynthesis were superior to those of FFDM in fatty and dense breasts overall and in women admitted for diagnostic workup and in women recalled from screening. Only 11% of digital breast tomosynthesis examinations required additional imaging, compared with 23% of FFDMs. CONCLUSION: In patients with abnormal mammograms, one-view digital breast tomosynthesis had better sensitivity and negative predictive value than did FFDM in patients with fatty and dense breasts. They also suggest that digital breast tomosynthesis would likely increase the predictive values if incorporated in routine screening.

Long-term follow-up of concurrent radiotherapy and chemotherapy for locally advanced cervical cancer: 12-Year survival after radiochemotherapy.

Recently randomized trials show an overall survival advantage of 30% for cisplatin-based chemotherapy given concurrently with radiation therapy. Current data do not allow to conclude which drugs could be best combined with cisplatin. Here we report the very long-term results of a prospective phase II trial of concurrent radiochemotherapy in advanced cancer of the cervix. Psychological impact has been evaluated with long-term survivors. Patient with squamous cell carcinoma of the cervix FIGO stage IIB, III or IVA received a concomitant chemotherapy with cisplatin, fluorouracil and mitomycin C and radiotherapy. From June 1988 to September 1990, 22 of 23 patients were eligible. The overall response rate was 82%. All 22 patients treated showed acute hematological toxicity and two patients developed severe late bowel toxicity. Ten patients (45%) were alive after a median observation time of 145.5 months. Intolerance to certain food and vaginal changes due to radiotherapy remain problematic. The lack of improvement compared to cisplatin alone and late bowel toxicity do not support the use of mitomycin C in the combination of the concurrent treatment of chemoradiation. The psychological impact of this treatment should not be minimized. Most problems tend to diminish with time with the exception of intestinal side effects and vaginal changes.