The areola is a rare location for squamous cell carcinoma (SCC) because sunlight exposure, the main risk factor for SCC, is unusual on it. Acantholytic SCC (ASCC) is a rare histologic variant of SCC, characterized by pseudoglandular appearance with acantholytic tumor cells. A 59-year-old male presented a painful erythematous papule on his right areola. He had a history of psoralen ultraviolet A phototherapy for psoriasis in his 20s. Biopsy revealed an epithelial tumor and pseudoglandular structures with acantholytic tumor cells. In immunohistochemistry, cytokeratin 5/6, epithelial membrane antigen, and p63 were positive, while cytokeratin 7, carcinoembryonic antigen, S-100, and estrogen and progesterone receptors were negative. Periodic acid-Schiff stain was negative. Ki-67 labeling index was 79.7%. The final diagnosis was ASCC of the areola. After wide local excision, recurrence have not been reported. Here, we report a case of ASCC on the areola, focusing on its rare histologic variant and uncommon location.

Purpose: The luminal subtype of breast cancer has heterogeneous biological characteristics with respect to the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (HER2), and Ki-67. We analyzed luminal B breast cancer subcategorized by PR expression and identified clinically relevant prognostic factors. Methods: We collected the clinical and pathologic data of 247 breast cancer patients (stage 1-4) who were diagnosed with luminal B subtype, defined as ER- and/or PR-positive and/or HER2-positive and with a high Ki-67 proliferation index (>14%). We classified them into PR intact and PR low groups according to PR expression pattern. We also analyzed the clinical and pathological data of each group, including age at diagnosis, tumor size, node metastasis, breast and axillary operative method, margin involvement, tumor-node-metastasis (TNM) stage, histological grade, nuclear grade, number of tumors, and expression of ER, PR, Ki-67, and Bcl-2; evaluated recurrence or metastatic characteristics; and analyzed disease-free survival (DFS) and overall survival (OS) in both groups. Results: Among the 247 luminal B breast cancer patients (stage 1-4), 141 were classified into the PR intact group (57.1%) and 106 into the PR low group (42.9%). The PR low group was associated with age >50 years (p=0.001), low Bcl-2 expression (p<0.001), and high proportion of mastectomies (p<0.001). DFS and OS were significantly lower in the PR low group (p=0.025 and 0.024, respectively). Conclusion This study showed that decreased in PR expression (PR low group) in luminal B breast cancer was related to poor prognosis compared to normal PR expression (PR intact group).

Purpose: The biggest concern related to ductal carcinoma in situ (DCIS) is local recurrence and recurrence patterns. The purpose of this study was to investigate the relationship between clinicopathological factors and relapse in patients treated with DCIS. Methods: We reviewed medical records of 104 patients who were diagnosed as DCIS between January 1999 and December 2015 at a single institute. We compared and analyzed clinicopathological factors such as age at diagnosis, preoperative lesions on ultrasonography, preoperative tumor markers, operation methods in the breast, histological grade, nuclear grade, resection margin, comedonecrosis, estrogen receptor/ progesterone receptor expression, human epidermal factor receptor 2eu expression, Ki-67, postoperative implementation of adjuvant hormonal therapy, and radiotherapy by dividing them into recurrent and non-recurrent groups. Results: Seventeen patients (16.3%) of 104 patients relapsed in the ipsilateral or contralateral breast. The median follow-up period of non-relapsed group was 4.9 years (range, 0.5–19.15) and the median follow-up period of relapsed group was 3.5 years (range, 1.4–14.13). Clinicopathological factors that were significantly related to relapse were nuclear grade (p=0.022) and Ki-67 (p=0.025) based on the results of chi-square or Fisher’s exact analysis. In multivariate analysis using logistic regression, Ki-67 (p=0.021) was significantly associated with DCIS relapse. Conclusion This study suggested that the higher Ki-67 over 14% was strongly associated with DCIS relapse.

Purpose: Adjuvant chemotherapy (AC) is recommended for patients with stage II colorectal cancer with adverse features. However, the effect of adjuvant treatment in elderly patients with high-risk stage II colorectal cancer remains controversial. This study aimed to investigate the oncologic outcomes in elderly high-risk stage II colorectal cancer patients who underwent curative resection with or without AC. Methods: Patients aged over 70 years having stage II colorectal adenocarcinoma with at least 1 adverse feature who underwent radical surgery between 2008 and 2017 at a single center were included. We compared recurrence-free survival (RFS) and overall survival (OS) between patients who received more than 80% of the planned AC cycle (the AC+ group) and those who did not receive it (the AC− group). Results: The AC+ and AC– group contained 46 patients and 50 patients, respectively. The log-rank test revealed no significant intergroup differences in RFS (P = 0.083) and OS (P = 0.122). In the subgroup of 27 patients with more than 2 adverse features, the AC+ group (n = 16) showed better RFS (P = 0.006) and OS (P = 0.025) than the AC− group. In this subgroup, AC was the only significant factor affecting RFS in the multivariate analysis (P = 0.023). AC was significantly associated with OS (P = 0.033) in the univariate analysis, but not in the multivariate analysis (P = 0.332). Conclusion Among elderly patients with stage II high-risk colorectal cancer, the AC+ group did not show better RFS or OS than the AC− group. However, selected patients with more than 2 adverse features might benefit from AC.

Purpose: Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. Methods This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness.Discussion: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy.We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety.

Purpose: It is known that as the T stage of a carcinoma progresses, the prognosis becomes poorer. However, there are few studies about factors that affect the prognosis of T4 advanced colon cancer. This study aimed to identify the prognostic factors associated with disease-free survival (DFS) and overall survival (OS) in T4 colon cancer. Methods: Patients diagnosed with stage T4 on histopathology after undergoing curative surgery for colon cancer between March 2009 and March 2018 were retrospectively analyzed for factors related to postoperative survival. Primary outcomes were DFS and OS. Results: Eighty-two patients were included in the study. DFS and OS of the pathologic (p) T4b group were not inferior to that of the pT4a group. Multivariate analysis showed that differentiation (hazard ratio [HR], 4.994; P = 0.005), and laparoscopic surgery (HR, 0.323; P = 0.008) were significant prognostic factors for DFS, while differentiation (HR, 7.904; P ≤ 0.001) and chemotherapy (HR, 0.344; P = 0.038) were significant prognostic factors for OS. Conclusion Tumor differentiation, laparoscopic surgery, and adjuvant chemotherapy were found to be significant prognostic factors in patients with T4 colon cancer. Adjuvant chemotherapy and curative resections by laparoscopy might improve the prognosis in these patients.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Purpose: To investigate the characteristics of HER2-positive breast cancer according to HER2 low (2+) or high (3+) classification using immunohistochemistry (IHC). Methods: Data were collected from 205 HER2-positive breast cancer patients in the final assay, regardless of IHC or in situ hybridization (ISH). We thus classified patients into two groups: HER2 2+/low and HER2 3+/high based on the IHC assay. We subsequently compared the clinical and pathological characteristics between groups. Results: The median patient age was 49 years in the HER2 2+/low group and 53 years in the HER2 3+/high group. We observed a significantly lower Allred score for estrogen receptor (ER) and progesterone receptor (PR) (0-6) (p<0.001), less lymphatic invasion (LI), (p=0.010), neural invasion (p=0.041), higher Ki-67 (p=0.001), and lower Bcl-2 (p<0.001) in the HER2 3+/high group than in the HER2 2+/low group. Lymph node recurrence was more frequently observed in the HER2 2+/low group than in HER2 3+/high group (p=0.005). Disease-free survival (DFS) was better in the HER2 3+/high group than in the HER2 2+/low group (p=0.028), but there were no significant differences in overall survival between the groups (p=0.233). Conclusion The HER2 3+/high group was associated with lower ER and PR expression, less LI, higher Ki-67, and lower Bcl-2 than that in HER2 2+/low group in HER2-positive breast cancer. Furthermore, compared to the HER2 2+/low group, the HER2 3+/high group had an improved DFS.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Purpose: To investigate the characteristics of HER2-positive breast cancer according to HER2 low (2+) or high (3+) classification using immunohistochemistry (IHC). Methods: Data were collected from 205 HER2-positive breast cancer patients in the final assay, regardless of IHC or in situ hybridization (ISH). We thus classified patients into two groups: HER2 2+/low and HER2 3+/high based on the IHC assay. We subsequently compared the clinical and pathological characteristics between groups. Results: The median patient age was 49 years in the HER2 2+/low group and 53 years in the HER2 3+/high group. We observed a significantly lower Allred score for estrogen receptor (ER) and progesterone receptor (PR) (0-6) (p<0.001), less lymphatic invasion (LI), (p=0.010), neural invasion (p=0.041), higher Ki-67 (p=0.001), and lower Bcl-2 (p<0.001) in the HER2 3+/high group than in the HER2 2+/low group. Lymph node recurrence was more frequently observed in the HER2 2+/low group than in HER2 3+/high group (p=0.005). Disease-free survival (DFS) was better in the HER2 3+/high group than in the HER2 2+/low group (p=0.028), but there were no significant differences in overall survival between the groups (p=0.233). Conclusion The HER2 3+/high group was associated with lower ER and PR expression, less LI, higher Ki-67, and lower Bcl-2 than that in HER2 2+/low group in HER2-positive breast cancer. Furthermore, compared to the HER2 2+/low group, the HER2 3+/high group had an improved DFS.