Knockdown of YAP/TAZ sensitizes tamoxifen-resistant MCF7 breast cancer cells.

Although endocrine therapy with tamoxifen has improved survival in breast cancer patients, resistance to this therapy remains one of the major causes of breast cancer mortality. In the present study, we found that the expression level of YAP/TAZ in tamoxifen-resistant MCF7 (MCF7-TR) breast cancer cells was significantly increased compared with that in MCF7 cells. Knockdown of YAP/TAZ with siRNA sensitized MCF7-TR cells to tamoxifen. Furthermore, siRNA targeting PSAT1, a downstream effector of YAP/TAZ, enhanced sensitivity to tamoxifen in MCF7-TR cells. Additionally, mTORC1 activity and survivin expression were significantly decreased during cell death induced by combination treatment with YAP/TAZ or PSAT1 siRNA and tamoxifen. In conclusion, targeting the YAP/TAZ-PSAT1 axis could sensitize tamoxifen-resistant MCF7 breast cancer cells by modulating the mTORC1-survivin axis.

Axillary Nodal Burden Assessed with Pretreatment Breast MRI Is Associated with Failed Sentinel Lymph Node Identification after Neoadjuvant Chemotherapy for Breast Cancer.

Background After publication of the findings of the American College of Surgeons Oncology Group Z1071 trial, sentinel lymph node biopsy (SLNB) has been increasingly performed in patients with breast cancer after neoadjuvant chemotherapy (NAC). Purpose To investigate the pretreatment breast MRI and clinical-pathologic characteristics associated with failed sentinel node identification after NAC in patients with breast cancer. Materials and Methods Patients who underwent SLNB after NAC between January 2015 and January 2019 were retrospectively identified. Two radiologists independently reviewed the characteristics of axillary nodes (number, perinodal infiltration, cortical thickness, and maximal diameter) at pretreatment breast MRI. The associations of the clinical-pathologic and imaging characteristics of the axillary nodes with sentinel node identification were assessed by using the χ2 test and/or the χ2 test for trend and multivariable logistic regression with odds ratio (OR) calculation. Results A total of 276 women (mean age ± standard deviation, 48 years ± 9; range, 27-68 years) were included. Sentinel nodes were identified in 252 of the 276 patients (91%). Multivariable analysis showed that higher (stage 3 or 4) clinical T stages (OR = 5.2, P = .004 for radiologist 1; OR = 4.6, P = .01 for radiologist 2), use of a single tracer (OR = 4.3, P = .04 for radiologist 1; OR = 3.9, P = .046 for radiologist 2), a greater number (10 or more) of suspicious axillary nodes (OR = 11.5, P = .002 for radiologist 1; OR = 8.3, P = .01 for radiologist 2), and the presence of perinodal infiltration (OR = 7.0, P = .002 for radiologist 1; OR = 7.5, P = .003 for radiologist 2) were associated with failed sentinel node identification. Conclusion A greater number of suspicious axillary nodes and the presence of perinodal infiltration at pretreatment MRI, higher clinical T stages, and use of a single tracer were independently associated with failed sentinel node identification after neoadjuvant chemotherapy in patients with breast cancer. © RSNA, 2020 See also the editorial by Imbriaco in this issue.

Efficacy of breast MRI for surgical decision in patients with breast cancer: ductal carcinoma in situ versus invasive ductal carcinoma.

BACKGROUND: Preoperative breast magnetic resonance imaging (MRI) provides more information than mammography and ultrasonography for determining the surgical plan for patients with breast cancer. This study aimed to determine whether breast MRI is more useful for patients with ductal carcinoma in situ (DCIS) lesions than for those with invasive ductal carcinoma (IDC). METHODS: A total of 1113 patients with breast cancer underwent mammography, ultrasonography, and additional breast MRI before surgery. The patients were divided into 2 groups: DCIS (n = 199) and IDC (n = 914), and their clinicopathological characteristics and oncological outcomes were compared. Breast surgery was classified as follows: conventional breast-conserving surgery (Group 1), partial mastectomy with volume displacement (Group 2), partial mastectomy with volume replacement (Group 3), and total mastectomy with or without reconstruction (Group 4). The initial surgical plan (based on routine mammography and ultrasonography) and final surgical plan (after additional breast MRI) were compared between the 2 groups. The change in surgical plan was defined as group shifting between the initial and final surgical plans. RESULTS: Changes (both increasing and decreasing) in surgical plans were more common in the DCIS group than in the IDC group (P <  0.001). These changes may be attributed to the increased extent of suspicious lesions on breast MRI, detection of additional daughter nodules, multifocality or multicentricity, and suspicious findings on mammography or ultrasonography but benign findings on breast MRI. Furthermore, the positive margin incidence in frozen biopsy was not different (P = 0.138). CONCLUSIONS: Preoperative breast MRI may provide more information for determining the surgical plan for patients with DCIS than for those with IDC.

Endoscopy-assisted muscle-sparing Latissimus Dorsi muscle flap harvesting for partial breast reconstruction.

BACKGROUND: Using the Latissimus dorsi (LD) muscle flap is one of the popular surgical technique for breast reconstruction. However, usually, long postoperative scar was remained on donor site which does not have disease. The authors applied the endoscopy-assisted surgery to harvest the LD muscle flap for breast reconstruction. METHODS: From July 2018 to July 2019, five consecutive patients with breast cancer underwent partial mastectomy with endoscopy-assisted LD muscle flap reconstruction. The clinic-pathologic factors were analyzed and the cosmetic outcomes were assessed with breast shape, scarring of breast and back. A 4-6 cm of lateral incision (donor site scar) was designed and LD muscle was harvested under endoscopic surgery without gas inflation. And the harvested LD muscle was inserted for partial breast reconstruction after the cancer surgery was done. RESULTS: Mean operative time was 116.4 min (range, 92-134) and there was no major postoperative complication. The satisfactory degree of cosmetic outcomes were shown better in patient's survey than that of surgeon's. CONCLUSIONS: The endoscopy-assisted LD muscle flap harvesting would be useful technique to eliminate a large donor site incision in partial breast reconstruction.

Can chemotherapy be omitted for patients with N0 or N1 endocrine-sensitive breast cancer treated with gonadotropin-releasing hormone agonist and tamoxifen?

Purpose: Whether administering chemotherapy followed by tamoxifen plus a gonadotropin-releasing hormone (GnRH) agonist to treat patients with lower-risk hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer provides a greater benefit than administering tamoxifen plus GnRH agonist alone remains unclear. This study aimed to compare the outcomes of propensity score-matched (PSM) patients who underwent these 2 types of treatment plans. Methods: This retrospective study included patients treated at our institution between 2009 and 2019. Eligible patients had HR-positive, HER2-negative, invasive breast cancer who had undergone surgery. There were 579 patients with HR-positive, HER2-negative breast cancer who were treated with a GnRH agonist and tamoxifen; patients with pathologic N2 and those who received neoadjuvant chemotherapy were excluded. After 1:1 PSM of patients who underwent GnRH agonist treatment and tamoxifen with versus without chemotherapy, 122 patients from these 2 groups were analyzed. Survival rates were calculated using the Kaplan-Meier method and compared via the log-rank test. Results: After PSM, there were no significant differences in several baseline characteristics between the 2 groups. After a median follow-up of 62.8 months, the patients in both groups demonstrated similar outcomes with no significant difference in disease-free survival (P = 0.596). Conclusion: Patients derived no significant survival benefit from undergoing a chemotherapy regimen before receiving tamoxifen and GnRH agonist therapy compared to forgoing such chemotherapy.

Breast Cancer Statistics in Korea, 2019.

This article provides an annual update of Korean breast cancer statistics, including the incidence, tumor stage, type of surgical treatment, and mortality. The data was collected from the Korean Breast Cancer Society registry system and Korean Central Cancer Registry. In 2019, 29,729 women were newly diagnosed with breast cancer. Breast cancer has continued to increase in incidence since 2002 and been the most common cancer in Korean women since 2019. Of the newly diagnosed cases in 2019, 24,820 (83.5%) were of invasive carcinomas, and 4,909 (16.5%) were of carcinoma in situ. The median age of women with breast cancer was 52.8 years, and breast cancer was most commonly diagnosed in the age group of 40-49 years. The number of patients who have undergone breast conserving surgery has continued to increase since 2016, with 68.6% of patients undergoing breast conserving surgery in 2019. The incidence of early-stage breast cancer continues to increase, with stage 0 or I breast cancer accounting for 61.6% of cases. The most common subtype of breast cancer is the hormone receptor-positive human epidermal growth factor receptor 2-negative subtype (63.1%). The 5-year relative survival rate of patients with breast cancer from 2015 to 2019 was 93.6%, with an increase of 14.3% compared to that from 1993 to 1995. This report improves our understanding of breast cancer characteristics in South Korea.

Survival analysis of breast cancer patients after diagnosis of second primary malignancies, focusing on the second primary hematologic malignancy.

Purpose: Although the overall survival (OS) of breast cancer patients is increasing with improved detection and therapies, so is the risk of breast cancer patients developing subsequent malignancies. We investigated the OS of breast cancer survivors according to sites of second primary malignancies (SPM). The OS of the second primary hematologic malignancy (SPHM) was then compared with that of metastatic breast cancer (MBC). Methods: We retrospectively analyzed patients diagnosed with primary breast cancer between 1998 and 2019. Only those with SPM were eligible for analysis. First, the OS of patients with SPM diagnosed as the first event after the diagnosis of breast cancer was analyzed. Next, the OS of patients with SPHM, with or without breast cancer relapse, was compared with that of patients with MBC, matched using the propensity score. Results: Patients diagnosed with SPM without breast cancer relapse as the first event had a significantly better OS than did patients with MBC, but the OS of those with SPHM as the first event did not differ significantly from that of patients with MBC (hazard ratio [HR], 1.558; 95% confidence interval [CI], 0.856-2.839; P = 0.147). The OS of patients with SPHM with or without breast cancer relapse was worse than that of the MBC group after propensity score matching (HR, 1.954; 95% CI, 1.045-3.654; P = 0.036). Conclusion: Prognosis of SPM diagnosed as the first event was statistically better than that of MBC, except in case of SPHM. Patients with SPHM, with or without MBC, showed poor OS before and after propensity score matching.

Nebivolol Sensitizes BT-474 Breast Cancer Cells to FGFR Inhibitors.

BACKGROUND/AIM: The fibroblast growth factor receptor (FGFR) signaling pathway is abnormally activated in human cancers, including breast cancer. Therefore, targeting the FGFR signaling pathway is a potent strategy to treat breast cancer. The purpose of this study was to find drugs that could increase sensitivity to FGFR inhibitor effects in BT-474 breast cancer cells, and to investigate the combined effects and underlying mechanisms of these combinations for BT-474 breast cancer cell survival. MATERIALS AND METHODS: Cell viability was measured by MTT assay. Protein expression was determined by western blot analysis. mRNA expression was detected by Real-time PCR. Drug synergy effect was determined by isobologram analysis. RESULTS: Nebivolol, a third generation ß1-blocker, synergistically increased the sensitivity of BT-474 breast cancer cells to the potent and selective FGFR inhibitors erdafitinib (JNJ-42756493) and AZD4547. A combination of nebivolol and erdafitinib markedly reduced AKT activation. Suppression of AKT activation using specific siRNA and a selective inhibitor further enhanced cell sensitivity to combined treatment with nebivolol and erdafitinib, whereas SC79, a potent activator of AKT, reduced cell sensitivity to nebivolol and erdafitinib. CONCLUSION: Enhanced sensitivity of BT-474 breast cancer cells to nebivolol and erdafitinib was probably associated with down-regulation of AKT activation. Combined treatment with nebivolol and erdafitinib is a promising strategy for breast cancer treatment.

The Significance of p-AKT1 as a Prognostic Marker and Therapeutic Target in Patients With Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor-2-Positive Early Breast Cancer.

PURPOSE: Phosphorylated AKT1 (p-AKT1) at Ser473 is a functional isoform of AKT and a key component of the PI3K/mTOR/AKT pathway. This study aimed to evaluate the prognostic significance of p-AKT1 (Ser473) based on the molecular subtypes of breast cancer. METHODS: To investigate the prognostic value of p-AKT1 (Ser473), we performed a retrospective chart review of patients with breast cancer. Data on p-AKT1 (Ser473) positivity, hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) expression status, and other clinicopathological factors were obtained. Furthermore, the therapeutic effect of blocking p-AKT1 (Ser473) in breast cancer cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis assay, apoptosis protein array, and western blot analysis. RESULTS: A total of 3,044 patients were evaluated, and the median follow-up time was 43 (range: 0-125) months. In patients with HR-positive and HER2-positive disease, the p-AKT1 (Ser473)-positive group had worse disease-free survival (DFS) than the p-AKT1 (Ser473)-negative group (hazard ratio, 1.9; 95% confidence interval, 1.1-3.5; p = 0.024). In the multivariate analysis, p-AKT1 (Ser473) remained a significantly worse prognostic factor in patients with HR-positive/HER2-positive breast cancer (p = 0.03). There was no difference in DFS according to p-AKT1 (Ser473) status among patients with other breast cancer subgroups. In vitro analysis showed that blocking p-AKT1 (Ser473) levels enhanced trastuzumab-induced cell death in HR-positive/HER2-positive and p-AKT1 (Ser473)-positive breast cancer cells. CONCLUSION: p-AKT1 (Ser473) is a prognostic marker for poor outcomes in patients with HR-positive/HER2-positive breast cancer and may have a potential value as a therapeutic target.

Sonographic findings in Nicolau syndrome following intramuscular diclofenac injection: a case report.

Nicolau syndrome (also known as embolia cutis medicamentosa and livedoid dermatitis) is a rare but severe localized adverse drug reaction of intramuscular injection of various drugs. The typical presentation is pain around the injection site soon after injection, followed by erythema, livedoid patch, hemorrhagic patch, and finally necrosis of skin, subcutaneous fat, and muscle tissue. We report a case that occurred in a 34-year-old woman after intramuscular injection of diclofenac sodium. Sonography showed diffuse thickening with increased echogenicity of the skin and subcutaneous fat layer, while MRI revealed extensive edema involving gluteal and piriformis muscles and deep fascia, and fluid collection.

Aesthetic Scar-Less Mastectomy and Breast Reconstruction.

Surgical approaches in breast cancer have been changing to ensure both oncologic safety and cosmetic results. Although the concept of "oncoplastic breast surgery" has been accepted for decades, breast and plastic surgeons have been striving to develop more advanced surgical skills that ensure non-inferior oncologic outcomes with better cosmetic outcomes. Endoscopic or robotic devices, which are currently available only for chest or abdominal surgeries, could be used for breast surgery to ensure better cosmetic outcomes. The authors refer to this surgical concept as "aesthetic scar-less breast surgery and reconstruction," a term that encompasses the consequential concepts rather than naming it with simple technical words such as endoscopy-assisted or robot-assisted surgery. The "scar-less" term simply means leaving less of a scar, and better results can be expected by designing incisions on invisible areas. Herein, we summarize our experiences with various techniques of "aesthetic scar-less" surgery and review the existing literature on this topic.

miR-3188 Enhances Sensitivity of Breast Cancer Cells to Ionizing Radiation by Down-regulating Rictor.

BACKGROUND/AIM: Rictor is an adaptor protein essential for mTORC2, which regulates cell growth and survival. The aim of this study was to identify microRNAs (miR) that down-regulate Rictor and investigate their function on breast cancer cell survival. MATERIALS AND METHODS: Trypan blue assay, MTT assay, polymerase chain reaction analysis, luciferase reporter assay and western blot analysis were carried out in breast cancer cell lines HCC1954, MDA-MB-231, SK-BR-3, and BT474. RESULTS: miR-3188 overexpression suppressed the expression of Rictor and inhibited cell viability in HCC1954 and MDA-MB-231, highly Rictor-expressing breast cancer cells. In addition, miR-3188 overexpression decreased the protein level of p-AKT at Ser473, a substrate of mTORC2. Moreover, miRNA-3188 overexpression sensitized breast cancer cells to ionizing radiation (IR) by down-regulating Rictor and p-AKT. CONCLUSION: miR-3188 enhances IR sensitivity by affecting the mTORC2/AKT signalling pathway by altering the expression of Rictor, which could be a promising therapeutic strategy for the future treatment of breast cancer.

Value of accurate diagnosis for metastatic supraclavicular lymph nodes in breast cancer: assessment with neck US, CT, and 18F-FDG PET/CT.

PURPOSE: Neck ultrasonography (US), computed tomography (CT), and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are all known to be useful imaging modalities for detecting supraclavicular lymph node (SCN) metastasis in breast cancer. The authors compared the diagnostic values of neck US, CT, and PET/CT in the detection of SCN metastasis in breast cancer. METHODS: SCN metastases identified in neck US, CT, or PET/CT during follow-up visits of patients with breast cancer were pathologically confirmed with the use of US-guided fine-needle aspiration cytology. The clinicopathological factors of the patients were analyzed, and the statistical parameters including sensitivity, specificity, positive and negative predictive values, false-positive and false-negative rates, and accuracy of neck US, CT, and PET/CT were compared. RESULTS: Among 32 cases of suspicious SCNs, 24 were pathologically confirmed as metastasis of breast cancer. The sensitivity of US + CT was 91.7%, which was the same as that of PET/CT, while the sensitivity rates of US alone and CT alone were 87.5% and 83.3%, respectively. Accuracy was 99.8% in PET/CT alone and 98.1% in US + CT. The false-negative rate was 0.1% in US + PET/CT, while it was 0.2% in PET/CT and US + CT, 0.3% in US alone and 0.4% in CT alone. CONCLUSION: PET/CT can be the first choice for detecting SCN metastases in breast cancer. However, if PET/CT is unavailable for any reason, US + CT could be a good second option to avoid false-negative results.

Peritumoral edema in breast cancer at preoperative MRI: an interpretative study with histopathological review toward understanding tumor microenvironment.

Peritumoral edema (PE) of breast cancer at T2-weighted MR images is considered a poor prognostic sign and may represent the microenvironment surrounding the tumor; however, its histopathological mechanism remains unclear. The purpose of the study was to identify and describe detailed histopathological characteristics associated with PE at preoperative breast MRI in breast cancer patients. This retrospective study included breast cancer patients who had undergone preoperative MRI and surgery between January 2011 and December 2012. Two radiologists determined the presence of PE in consensus based on the signal intensity surrounding the tumor at T2-weighted images. The following detailed histopathological characteristics were reviewed by two breast pathologists using four-tiered grades; lymphovascular invasion, vessel ectasia, stromal fibrosis, growth pattern, and tumor budding. Tumor necrosis and tumor infiltrating lymphocytes were assessed using a percent scale. Baseline clinicopathological characteristics, including age and histologic grade, were collected. The associations between detailed histopathologic characteristics and PE were examined using multivariable logistic regression with odds ratio (OR) calculation. A total of 136 women (median age, 49 ± 9 years) were assessed; among them 34 (25.0%) had PE. After adjustment of baseline clinicopathological characteristics that were significantly associated with PE (age, T stage, N stage, histologic grade, and subtype, all Ps < 0.05), lymphovascular invasion (P = 0.009), vessel ectasia (P = 0.021), stromal fibrosis (P = 0.024), growth pattern (P = 0.036), and tumor necrosis (P < 0.001) were also associated with PE. In comparison with patients without PE, patients with PE were more likely to have a higher degree of lymphovascular invasion (OR, 2.9), vessel ectasia (OR, 3.3), stromal fibrosis (OR, 2.5), lesser degree of infiltrative growth pattern (OR, 0.4), and higher portion of tumor necrosis (OR, 1.4). PE of breast cancer at MRI is associated with detailed histopathological characteristics of lymphovascular invasion, vessel ectasia, stromal fibrosis, growth pattern, and tumor necrosis, suggesting a relevance for tumor microenvironment.

Patterns of Delaying Surgery for Breast Cancer During the COVID-19 Outbreak in Daegu, South Korea.

Background: The coronavirus disease 2019 (COVID-19) outbreak in South Korea has affected the diagnosis, treatment, and follow-up protocols of various cancers. This study investigated the patterns of delaying surgery for breast cancer during the COVID-19 outbreak in South Korea and evaluated factors that may have affected the decision to delay surgery. Methods: From February 18 to April 18, 2020, which was the critical period for COVID-19 in South Korea, patients with breast cancer who were scheduled for surgery were evaluated in terms of their decision in delaying the procedure. The patients were divided into two groups: delaying and non-delaying surgery groups. The association between personal and clinicopathological factors and delaying surgery was evaluated. Results: In patients belonging to the delaying surgery group, the mean delay period was 15.9 (standard deviation [SD], ±10.9) days. Patients in the non-delaying surgery group were relatively younger (p = 0.003), single (p = 0.038), had planned mastectomy (p = 0.041), received needle biopsy for diagnosis (p = 0.021), and had a higher clinical N stage (p = 0.049) and multifocal lesions of breast cancer (p = 0.020). However, there were no significant differences in terms of the pathological T and N stages between the two groups. Conclusion: During the COVID-19 outbreak, there was no occurrence of nosocomial infection in the non-delaying surgery group and no statistical difference in pathological stage between the delaying and non-delaying surgery groups. Although patients in the delaying surgery group tended to be relatively older and married and had planned small-scale surgery with a good prognosis of breast cancer, the prognosis did not appear to have changed whether delaying or proceeding with surgery for breast cancer during the COVID-19 outbreak.

Real Scarless Transoral Robotic Thyroidectomy Using Three Ports Without Axillary Incision.

Introduction: Conventional transoral robotic thyroidectomy (TORT) requires an axillary incision and additional flap dissection. This study aimed to outline the first ever experiences with TORT using three ports without axillary incision and compare the results between three-port and four-port TORT. Materials and Methods: A total of 100 consecutive patients were enrolled. The study sample comprised 47 patients who underwent four-port TORT from November 2016 to June 2017, and 53 patients who underwent three-port TORT from September 2018 to June 2019. The indication of the three-port TORT was the anterior/posterior length of the thyroid <1.8 cm and mass size <1.5 cm. Results: Operative time (minutes) was shorter in the three-port group (166.3 ± 35.4 versus 138.5 ± 34.4, P = .005). Hospital stay (days) was also shorter in the three-port group (3.8 ± 0.4 versus 2.4 ± 0.6, P = .003). TORT using three ports yielded a higher cosmetic satisfaction (3.68 ± 0.52 versus 3.89 ± 0.30, P = .002). Postoperative complications, level of calcium, parathyroid hormone, and pain were not significantly different between the groups. Conclusions: Our study showed that three-port TORT was associated with a shorter operative time, hospital stay, and excellent cosmesis than the conventional four-port option. In conclusion, TORT using three ports is a comparable and an effective operation method as a real scarless operation.

Predicting the Benefit of Adjuvant Aromatase Inhibitor Therapy in Postmenopausal Breast Cancer Patients with Phosphorylated S6K1 Expression Status.

PURPOSE: Phosphorylated ribosomal S6 kinase 1 (pS6K1) is a major downstream regulator of the mammalian target of rapamycin (mTOR) pathway. Recent studies have addressed the role of S6K1 in adipogenesis. pS6K1 may affect the outcome of estrogen depletion therapy in patients with hormone-sensitive breast cancer due to its association with adipogenesis and increased local estrogen levels. This study aimed to investigate the potential of pS6K1 as a predictive marker of adjuvant aromatase inhibitor (AI) therapy outcome in postmenopausal or ovarian function-suppressed patients with hormone-sensitive breast cancer. METHODS: Medical records were retrospectively reviewed in postmenopausal or ovarian function-suppressed patients with estrogen receptor-positive and node-positive primary breast cancer. pS6K1 expression status was scored on a scale from 0 (negative) to 3+ (positive) based on immunohistochemical analysis. RESULTS: A total of 428 patients were eligible. The median follow-up duration was 44 months (range, 1-90). In patients with positive pS6K1 expression, AIs significantly improved disease-free survival (DFS) compared to selective estrogen receptor modulators (SERMs) (5 year-DFS: 83.5% vs. 50.7%, p = 0.016). However, there was no benefit of AIs on DFS in the pS6K1 negative group (5 year-DFS 87.6% vs. 91.4%, p = 0.630). On multivariate analysis, AI therapy remained a significant predictor for DFS in the pS6K1 positive group (hazard ratio, 0.39; 95% confidence interval, 0.16-0.96; p = 0.041). pS6K1 was more effective in predicting the benefit of AI therapy in patients with ages < 50 (p = 0.021) compared to those with ages ≥ 50 (p = 0.188). CONCLUSION: pS6K1 expression may predict AI therapy outcomes and serve as a potential predictive marker for adjuvant endocrine therapy in postmenopausal and ovarian function-suppressed patients with hormone-sensitive breast cancer. AIs may be more effective in patients with pS6K1 positive tumors, while SERM could be considered an alternative option for patients with pS6K1 negative tumors.

Comparison of clinical features and oncologic outcomes between familial non-hereditary and hereditary breast cancer in Korean female patients.

BACKGROUND: The authors compared the clinical features between familial (non-hereditary) and hereditary breast cancer. And we also analyzed their oncologic outcomes to establish appropriate surveillance protocol for familial (non-hereditary) and hereditary breast cancer. METHODS: Among 232 patients with breast cancer who were performed BRCA gene evaluation, twenty-eight patients were diagnosed as hereditary breast cancer with BRCA gene mutation and one-hundred and seventy-six patients were familial (non-hereditary) breast cancer. The clinical characteristics and oncologic outcomes were compared between two groups. RESULTS: While the incidence of multifocality was higher in familial (non-hereditary) breast cancer group (p < 0.001), the bilaterality was higher in hereditary breast cancer group (p < 0.001). And the rate of pathologic complete remission was also significantly higher in hereditary breast cancer group (p = 0.030). The characteristics of tumor were different between familial (non-hereditary) breast cancer and hereditary breast cancer. The oncologic outcome was better in familial (non-hereditary) breast cancer group than hereditary breast cancer group except death. CONCLUSION: The clinical characteristics of familial (non-hereditary) breast cancer were different from those of hereditary breast cancer but similar to those of sporadic breast cancer. The prognosis of the familial (non-hereditary) breast cancer was significantly better than hereditary breast cancer.

Predicting Radiation Resistance in Breast Cancer with Expression Status of Phosphorylated S6K1.

Emerging evidence suggests that the mammalian target of rapamcyin (mTOR) pathway is associated with radio-resistance in cancer treatment. We hypothesised that phosphorylated ribosomal S6 kinase 1 (p-S6K1), a major downstream regulator of the mTOR pathway, may play a role in predicting radio-resistance. Therefore, we evaluated the association of p-S6K1 expression with radio-resistance in breast cancer cell lines and patients. During median follow-up of 33 (range, 0.1-111) months for 1770 primary breast cancer patients who underwent surgery, patients expressing p-S6K1 showed worse 10-year loco-regional recurrence-free survival (LRFS) compared to that of p-S6K1-negative patients after radiotherapy (93.4% vs. 97.7%, p = 0.015). Multivariate analysis revealed p-S6K1 expression as a predictor of radio-resistance (hazard ratio 7.9, 95% confidence interval 1.1-58.5, p = 0.04). In vitro, CD44high/CD24low MCF7 cells with a radioresistant phenotype expressed higher levels of p-S6K1 than control MCF7 cells. Furthermore, the combination of radiation with treatment of everolimus, an mTOR-S6K1 pathway inhibitor, sensitised CD44high/CD24low MCF7 cells to a greater extent than MCF7 cells. This study provides in vivo and in vitro evidence for p-S6K1 expression status as an important marker for predicting the resistance to radiotherapy and as a possible target for radio-sensitization in breast cancer patients.