Clinicopathological predictors of postoperative upstaging to invasive ductal carcinoma (IDC) in patients preoperatively diagnosed with ductal carcinoma in situ (DCIS): a multi-institutional retrospective cohort study.

BACKGROUND: We conducted a prospective study with the intention to omit surgery for patients with ductal carcinoma in situ (DCIS) of the breast. We aimed to identify clinicopathological predictors of postoperative upstaging to invasive ductal carcinoma (IDC) in patients preoperatively diagnosed with DCIS. PATIENTS AND METHODS: We retrospectively analyzed patients with DCIS diagnosed through biopsy between April 1, 2010 and December 31, 2014, from 16 institutions. Clinical, radiological, and histological variables were collected from medical records. RESULTS: We identified 2,293 patients diagnosed with DCIS through biopsy, including 1,663 DCIS (72.5%) cases and 630 IDC (27.5%) cases. In multivariate analysis, the presence of a palpable mass (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.2-2.6), mammography findings (≥ category 4; OR 1.8; 95% CI 1.2-2.6), mass formations on ultrasonography (OR 1.8; 95% CI 1.2-2.5), and tumor size on MRI (> 20 mm; OR 1.7; 95% CI 1.2-2.4) were independent predictors of IDC. Among patients with a tumor size on MRI of ≤ 20 mm, the possibility of postoperative upstaging to IDC was 22.1%. Among the 258 patients with non-palpable mass, nuclear grade 1/2, and positive for estrogen receptor, the possibility was 18.1%, even if the upper limit of the tumor size on MRI was raised to ≤ 40 mm. CONCLUSION: We identified four independent predictive factors of upstaging to IDC after surgery among patients with DCIS diagnosed by biopsy. The combined use of various predictors of IDC reduces the possibility of postoperative upstaging to IDC, even if the tumor size on MRI is larger than 20 mm.

Phase II study of S-1 in combination with trastuzumab for HER2-positive metastatic breast cancer.

AIM: We undertook a prospective phase II study to evaluate the efficacy of S-1 plus trastuzumab combination regimen for human epidermal-growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: HER2-positive MBC patients received oral administration of S-1 (80 mg/m2/day, days 1 to 28, every 6 weeks) and intravenous weekly trastuzumab (2 mg/kg), according to the results of a prior Phase I trial of our group. RESULTS: A total of 28 patients were enrolled and received a median of 3.5 (range 1-10) cycles of treatment. Overall response rate and clinical benefit rate were 53.6% and 75.0%, respectively. Progression-free survival was 30 weeks. With regard to grade 3 and 4 adverse effects, leucopenia, neutropenia, increase in serum alanine aminotransferase, and diarrhea were observed. CONCLUSION: Combination of S-1 and trastuzumab was tolerable and had excellent efficacy with good response and disease control in this trial.

A pilot study of wider use of accelerated partial breast irradiation: intraoperative margin-directed re-excision combined with sole high-dose-rate interstitial brachytherapy.

BACKGROUND: Accelerated partial breast irradiation (APBI) is generally limited to patients at extremely low risk of local recurrence. The significance of the risk factors, however, depends on the extent of surgery, radiation, and systemic therapy. In Japan, wide excision is generally supplemented by intraoperative margin-directed re-excision if the frozen section examination yields positive results. This approach combined with conventional radiotherapy achieved an excellent 10-year local control rate of 93%, and young age and ductal carcinoma in situ were not risk factors for local recurrence. To reduce the treatment duration, high-dose-rate interstitial brachytherapy (HDRIB) was employed. The first APBI phase I / II trial in Japan was conducted to determine if wider indications for early breast cancer patients were appropriate. METHODS: The subjects comprised 20 patients including those with extensive intraductal component (n=7), ductal carcinoma in situ (n=2), positive final margins (n=3), and of younger age (< or = 45 years; n=5). Breast-conserving surgery using an intraoperative re-excision approach was followed by intraoperative implantation of applicators. Sole HDRIB of a 36-42 Gy in 6-7 fractions was delivered postoperatively over 3-4 days. Tumors were staged as follows: cT1 (n=12), cT2 (n=8), cN0 (n=20). Systemic therapy was used in 16 patients (80%). The median follow-up period was 52 months (range, 26-86 months). RESULTS: Te five-year crude local, distant control, and Kaplan-Meier cause-specific survival rates were 95%, 95%, and 89%, respectively. Fat necrosis developed in 1 patient. CONCLUSIONS: Sole HDRIB with intraoperative margin-directed re-excision was feasible under wider indications compared to other contemporary APBI series, and achieved acceptable and similar results to these series in terms of the local control rate and complications.