Hormone Receptor Subtype in Ductal Carcinoma in Situ: Prognostic and Predictive Roles of the Progesterone Receptor.

BACKGROUND: We investigated the prognostic and predictive roles of the hormone receptor (HRc) subtype in patients with ductal carcinoma in situ (DCIS). We focused on identifying the roles of the progesterone receptor (PR) independent of estrogen receptor (ER) status. METHODS: Nationwide data of 12,508 female patients diagnosed with DCIS with a mean follow-up period of 60.7 months were analyzed. HRc subtypes were classified as ER-/PR-, ER-/PR+, ER+/PR-, and ER+/PR+ based on ER and PR statuses. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The ER+/PR+ group showed better prognoses than the ER+/PR- and ER-/PR- groups in the patients who received tamoxifen therapy (p = .001 and p = .031, respectively). HRc subtype was an independent prognostic factor (p = .028). The tamoxifen therapy group showed better survival than the patients who did not receive tamoxifen, but only in the ER+/PR+ subgroup (p = .002). Tamoxifen therapy was an independent prognostic factor (HR, 0.619; 95% CI, 0.423 - 0.907; p = .014). PR status was a favorable prognostic factor in patients with DCIS who received tamoxifen therapy (p < .001), and it remained a prognostic factor independent of ER status (HR, 0.576; 95% CI, 0.349 - 0.951; p = .031). CONCLUSION: The HRc subtype can be used as both a prognostic and predictive marker in patients with newly diagnosed DCIS. Tamoxifen therapy can improve overall survival in the ER+/PR+ subtype. PR status has significant prognostic and predictive roles independent of ER status. Testing for the PR status in addition to the ER status is routinely recommended in patients with DCIS to determine the HRc subtype in clinical settings. IMPLICATIONS FOR PRACTICE: The hormone receptor (HRc) subtype was an independent prognostic factor, and the estrogen receptor (ER)+/progesterone receptor (PR) + subtype showed a better survival in patients with ductal carcinoma in situ (DCIS) who received tamoxifen therapy. PR was an independent prognostic factor independent of ER, and PR was a favorable prognostic factor in patients with DCIS who received tamoxifen therapy. The HRc subtype could be used as both a prognostic and predictive marker in patients with newly diagnosed DCIS. Testing of PR status in addition to ER status is routinely recommended for patients with DCIS to determine the HRc subtype in clinical settings.

The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress.

BACKGROUND: Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. METHODS: Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. DISCUSSION: This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00912548 . Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005 . Registered October 26 2009.

Comparison of swallowing disorder following gasless transaxillary endoscopic thyroidectomy versus conventional open thyroidectomy.

BACKGROUND: In conventional open thyroidectomy, it is necessary to create a sub-platysma muscle flap in front of the strap muscle to provide working space. Adhesion between the flap and the strap muscle can occur after the operation, disrupting strap muscle movement and causing a swallowing disorder. Gasless transaxillary endoscopic thyroidectomy approaches the thyroid through the posterior of the strap muscle and does not require a sub-platysma muscle flap. The present study compared flap/muscle adhesion and occurrence of swallowing disorder following gasless transaxillary endoscopic thyroidectomy versus conventional open thyroidectomy. METHODS: Patients (N = 47) receiving thyroidectomy at the Kangbuk Samsung Medical Center, Seoul, Korea, were divided into two groups: group O (24 patients) underwent conventional open thyroidectomy, and group E (23 patients) underwent gasless transaxillary endoscopic thyroidectomy. The subjective Swallowing Impairment Index (SIS)-6 was used to evaluate the degree of post-operative swallowing disorder. Video recordings of swallowing movement were used to determine the contraction/relaxation (CR) ratio and evaluate adhesion, pre-operation, 3 days post-operation, and 1 month post-operation. Barium videofluoroscopy was used to measure movement of the hyoid bone and strap muscle. RESULTS: Group O had significantly higher post-operative SIS-6 scores than group E (p < 0.027), indicating greater swallowing disorder. The CR ratio increased in group O after the operation and continued to increase during 1 month post-operation, but decreased in group E (p < 0.001). Videofluoroscopy showed that hyoid bone movement in group O decreased by 55.46 and 56.75% at 3 days and 1 month post-operation, respectively, while the corresponding decreases in group E were 84.04 and 83.69%. CONCLUSIONS: Conventional open thyroidectomy allowed adhesion of the strap muscle and sub-platysma muscle flap, resulting in non-specific dysphagia. These complications did not occur following gasless transaxillary endoscopic thyroidectomy.

The prognostic relevance of psammoma bodies and ultrasonographic intratumoral calcifications in papillary thyroid carcinoma.

BACKGROUND: Although psammoma bodies (PB) are found in up to 50 % of papillary thyroid carcinomas (PTC), their clinicopathological significance remains uncertain. The aim of the present study was to determine the clinicopathological significance of PB and the correlation between PB and ultrasonographic intratumoral calcification in PTC. METHODS: The clinicopathological parameters, ultrasonographic calcifications, and the presence of PB were evaluated in 258 surgically resected conventional PTC. RESULTS: Psammoma bodies were found in 141 of 258 PTC (54.7 %). The presence of PB was significantly correlated with tumor multifocality, extrathyroidal extension, and lymph node metastasis (P = 0.009, P = 0.004, and P < 0.001, respectively), but not with the BRAF(V600E) mutation. Higher incidences of both intratumoral and extratumoral PB were found in overt PTC (>1 cm) than in papillary microcarcinomas (≤1 cm) (P < 0.001 and P = 0.015, respectively). Extratumoral PB were only identified in 48.9 % of 141 PTC with PB, and PTC with extratumoral PB showed higher incidences of tumor multifocality, extrathyroidal extension, and nodal metastasis compared to PTC with intratumoral PB (P = 0.014, P = 0.005 and P = 0.001, respectively). Ultrasonographic intratumoral calcification corresponded to clusters of intratumoral PB (P < 0.001) and was associated with nodal metastasis (P = 0.026). CONCLUSIONS: The findings of the present study suggest that the presence of PB may be a useful prognostic indicator of aggressive PTC behaviors. In addition, confirmation of ultrasonographic intratumoral calcification would be a useful decision-making criterion when determining the need for preoperative or intraoperative surveillance of nodal metastasis.

Adding Ovarian Suppression to Tamoxifen for Premenopausal Breast Cancer: A Randomized Phase III Trial.

PURPOSE: The addition of ovarian function suppression (OFS) for 5 years to tamoxifen (TAM) for treatment of premenopausal patients with breast cancer after completion of chemotherapy has beneficial effects on disease-free survival (DFS). This study evaluated the efficacy of adding 2 years of OFS to TAM in patients with hormone receptor-positive breast cancer who remain in a premenopausal state or resume ovarian function after chemotherapy. PATIENTS AND METHODS: We enrolled 1,483 premenopausal women (age ≤ 45 years) with estrogen receptor-positive breast cancer treated with definitive surgery after completing adjuvant or neoadjuvant chemotherapy. Ovarian function was assessed every 6 months for 2 years since enrollment on the basis of follicular-stimulating hormone levels and vaginal bleeding history. If ovarian function was confirmed to be premenopausal at each visit, the patient was randomly assigned to complete 5 years of TAM alone (TAM-only) group or 5 years of TAM with OFS for 2 years that involved monthly goserelin administration (TAM + OFS) group. DFS was defined from the time of enrollment to the time of the first event. RESULTS: A total of 1,293 patients were randomly assigned, and 1,282 patients were eligible for analysis. The estimated 5-year DFS rate was 91.1% in the TAM + OFS group and 87.5% in the TAM-only group (hazard ratio, 0.69; 95% CI, 0.48 to 0.97; P = .033). The estimated 5-year overall survival rate was 99.4% in the TAM + OFS group and 97.8% in the TAM-only group (hazard ratio, 0.31; 95% CI, 0.10 to 0.94; P = .029). CONCLUSION: The addition of 2 years of OFS to TAM significantly improved DFS compared with TAM alone in patients who remained premenopausal or resumed ovarian function after chemotherapy.

Parity Differently Affects the Breast Cancer Specific Survival from Ductal Carcinoma In Situ to Invasive Cancer: A Registry-Based Retrospective Study from Korea.

PURPOSE: Multiparity might increase general mortality for women, but has inconclusive in patients with breast cancer. Here, we aim to discover their effect in terms of the breast cancer development hypothesis: from ductal carcinoma in situ to invasive carcinoma. METHODS: We included 37 947 patients from the web-based breast cancer registration program of the Korean Breast Cancer Society and analyzed survivals using multivariate Cox regression analysis and whether the associations of these factors displayed linear trends. They were divided into the following groups: (1) pure ductal carcinoma in situ (DCIS), (2) invasive ductal carcinoma (IDC) mixed with intraductal component (DCIS-IDC), and (3) node negative pure IDC. RESULTS: The mean age was 48.9 ± 9.9 years including premenopausal women was 61.8%. Although patients with parities of 1-3 had better prognosis compared with patients with nulliparous women, high parity (⩾4) increased the hazard ratio (HR) of overall survival (OS) (DCIS: HR, 1.52; 95% confidence interval [CI] 0.62-3.78; IDC: HR, 1.43, 95% CI 0.89-2.31; and DCIS-IDC: HR, 1.44, 95% CI 0.45-4.59) during 84.2 (±10.7) months. For breast cancer specific survival (BCSS), the HR of the IDC group (P-value for trend = .04) increased along with increasing parity and was worse than nulliparous patients, and the HR of the DCIS-IDC group increased but was better than nulliparous patients (P-value for trend = .02). Compared with nulliparous patients, any age at first birth (AFB) decreased HR of OS in the DCIS and IDC groups (DCIS: P = .01; IDC: P = .04). CONCLUSIONS: Parity show dual effects on OS of women with all ductal typed breast cancer but show different effects on BCSS in Korea.

Magnetic resonance imaging and clinicopathological factors for the detection of occult nipple involvement in breast cancer patients.

PURPOSE: Nipple sparing mastectomy provides good cosmetic results and low local recurrence rates for breast cancer patients. However, there is a potential risk of leaving an occult tumor within the nipple, which could lead to cancer relapse and poor prognosis for the patient. The objective of this study was to investigate the occult nipple involvement rate in mastectomy specimens, and to identify preoperative magnetic resonance imaging (MRI) findings and the clinicopathological characteristics of the primary tumor that may correlate with nipple invasion. METHODS: Four hundred sixty-six consecutive mastectomy samples with grossly unremarkable nipples were evaluated. Demographic and clinicopathological data were collected. Nipple involvement was evaluated using serial histological sections. The tumor size and tumor-nipple distance were measured using preoperative MRI images. RESULTS: Thirty-six of the 466 therapeutic mastectomy specimens (7.7%) were found to have occult nipple involvement. In univariate analysis, tumor size, tumor-nipple distance, lymph node status, p53 mutation, and lymphovascular invasion (LVI) were found to influence the likelihood of nipple involvement. Multivariate logistic regression analysis, adjusted by lymph node status, p53 mutation, and LVI, showed that tumor size and tumor-nipple distance were predictive factors indicating nipple involvement. With regard to tumor location, only tumors in the central area of the breast showed a significant association with nipple involvement. CONCLUSION: In this study, a statistically significant association was found between occult nipple involvement and tumor size, tumor-nipple distance, axillary lymph node status, LVI, and p53 mutation. A cutoff point of 2.2 cm for tumor size and 2 cm for tumor-nipple distance could be used as parameters to predict occult nipple involvement.

Activation of nuclear factor-κB contributes to growth and aggressiveness of papillary thyroid carcinoma.

Nuclear factor-κB (NF-κB) is involved in proliferation, angiogenesis, and metastasis in various malignancies; however, the role of NF-κB in papillary thyroid carcinoma (PTC) has not been fully elucidated. The purpose of this study was to elucidate the role and clinicopathological significance of the NF-κB signaling pathway in PTC. We investigated NF-κB RelA expression in 122 patients with conventional PTC by immunohistochemistry, and evaluated the correlation between RelA expression and clinicopathological parameters, including BRAF(V600E) mutation. Nuclear expression of NF-κB RelA, regardless of cytoplasmic expression, was identified in 91 of 122 PTCs (74.6%), and was more frequent in PTCs larger than 1cm (overt PTC) (P=0.001). There were significant differences in clinicopathological parameters, such as extrathyroidal extension (P=0.031), nodal metastasis (P=0.021) and BRAF(V600E) mutation (P=0.039), between NF-κB-positive and negative PTCs. Proliferation index was strongly associated with NF-κB activation (P=0.045) but not with BRAF(V600E) mutation (P=0.141). Taken together, our results suggest that NF-κB RelA activation contributes, at least in part, to tumor growth and aggressiveness of PTC after tumor transformation. The expression pattern of NF-κB may serve as a prognostic marker and a potential therapeutic target.