Breast density reduction as a predictor for prognosis in premenopausal women with estrogen receptor-positive breast cancer: an exploratory analysis of the updated ASTRRA study.

BACKGROUND: While the relationship between mammographic breast density reduction (MDR) and endocrine therapy efficacy has been reported in estrogen receptor (ER)-positive breast cancer, it is still unclear in premenopausal women, especially in the case of adding ovarian function suppression (OFS) to antihormone therapy. The authors investigated the impact of MDR on prognosis stratified by treatment based on the updated results of the ASTRRA trial. MATERIALS AND METHODS: The ASTRRA trial, a randomized phase III study, showed that adding OFS to tamoxifen (TAM) improved survival in premenopausal women with estrogen receptor-positive breast cancer after chemotherapy. The authors updated survival outcomes and assessed mammography before treatment and the annual follow-up mammography for up to 5 years after treatment initiation. Mammographic density (MD) was classified into four categories based on the Breast Imaging-Reporting and Data System. MDR-positivity was defined as a downgrade in MD grade on follow-up mammography up to 2 years after randomization, with pretreatment MD grade as a reference. RESULTS: The authors evaluated MDR in 944 of the 1282 patients from the trial, and 813 (86.2%) had grade III or IV MD. There was no difference in the MDR-positivity rate between the two treatment groups [TAM-only group (106/476 (22.3%)) vs. TAM+OFS group (89/468 (19.0%)); P =0.217). MDR-positivity was significantly associated with better disease-free survival (DFS) in the TAM+OFS group (estimated 8-year DFS: 93.1% in MDR-positive vs. 82.0% in MDR-negative patients; HR: 0.37; 95% CI: 0.16-0.85; P =0.019), but not in the TAM-only group ( Pinteraction =0.039). MDR-positive patients who received TAM+OFS had a favorable DFS compared to MDR-negative patients who received only TAM (HR: 0.30; 95% CI: 0.13-0.70; P =0.005). CONCLUSION: Although the proportion of MDR-positive patients was comparable between both treatment groups, MDR-positivity was independently associated with favorable outcomes only in the TAM+OFS group.

Adding Ovarian Suppression to Tamoxifen for Premenopausal Women With Hormone Receptor-Positive Breast Cancer After Chemotherapy: An 8-Year Follow-Up of the ASTRRA Trial.

PURPOSE: To determine the updated long-term outcomes of the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy (ASTRRA) trial. PATIENTS AND METHODS: This study is a post-trial follow-up of the ASTRRA trial, involving 1,483 premenopausal women younger than 45 years treated with definitive surgery after completing adjuvant or neoadjuvant chemotherapy for estrogen receptor-positive breast cancer. Patients were randomly assigned in a 1:1 ratio to complete 5 years of tamoxifen (TAM) alone (TAM-only) or 5 years of TAM with ovarian function suppression (OFS) for 2 years (TAM + OFS). The primary end point was disease-free survival (DFS), and the secondary end point was overall survival (OS). RESULTS: At 106.4 months of median follow-up, there was a continuous significant reduction in the DFS event rate in the TAM + OFS group. The 8-year DFS rate was 85.4% in the TAM + OFS group and 80.2% in the TAM-only group (hazard ratio [HR], 0.67; 95% CI, 0.51 to 0.87). There were no significant differences in OS between the two groups. The OS rate was 96.5% in the TAM + OFS group and 95.3% in the TAM-only group (HR, 0.78; 95% CI, 0.49 to 1.25). CONCLUSION: Adding OFS for 2 years to adjuvant TAM with a longer follow-up resulted in consistent DFS benefits, suggesting that adding OFS to TAM should be considered for patients who remain in a premenopausal state or resume ovarian function after chemotherapy.

Survival Outcomes of Patients With Breast Cancer Diagnosed Using Vacuum-Assisted Biopsy: A Nationwide Study From the Korean Breast Cancer Society.

PURPOSE: Breast cancer is mainly diagnosed using core needle biopsy (CNB), although other biopsy methods, including vacuum-assisted biopsy (VAB), may also be used. We compared differences in clinical characteristics and prognoses of patients with breast cancer according to biopsy methods used for diagnosis. METHODS: A total of 98,457 patients who underwent various biopsy methods (CNB, fine-needle aspiration [FNA], VAB, and excisional biopsy) for diagnosing breast cancer were recruited. Using CNB as a reference, related clinicopathological factors and prognostic differences between biopsy methods were analyzed retrospectively using large-scale data from the Korean Breast Cancer Society Registration System. The associations between biopsy methods and clinicopathological factors were compared using multinomial logistic regression analysis, and the prognoses of patients undergoing the different biopsy methods, as breast cancer-specific survival (BCSS) and overall survival (OS), were compared using the Kaplan-Meier method and Cox proportional hazard model. RESULTS: Univariate and multivariate analyses showed that unlike FNA, both VAB and excisional biopsy were significantly associated with tumor size, palpability, tumor stage, and histologic grade as relatively good prognostic factors compared to CNB. In particular, VAB showed lower odds ratios for these factors than excisional biopsy. In the univariate analysis, the prognosis of patients undergoing VAB was better than that of those undergoing CNB with respect to BCSS (hazard ratio [HR], 0.188, p < 0.001) and OS (HR, 0.359; p < 0.001). However, in the multivariate analysis, there were no significant prognostic differences from CNB in both BCSS and OS; differences were only evident for FNA. CONCLUSION: In this study, we showed that the characteristics of breast cancer differed according to various biopsy methods. Although VAB is not a standard method for breast cancer diagnosis, it showed no prognostic differences to CNB.

Axillary Lymph Node Dissection Rates and Prognosis From Phase III Neoadjuvant Systemic Trial Comparing Neoadjuvant Chemotherapy With Neoadjuvant Endocrine Therapy in Pre-Menopausal Patients With Estrogen Receptor-Positive and HER2-Negative, Lymph Node-Positive Breast Cancer.

In this study, we aimed to evaluate axillary lymph node dissection (ALND) rates and prognosis in neoadjuvant chemotherapy (NCT) compare with neoadjuvant endocrine therapy (NET) in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-), lymph node (LN)-positive, premenopausal breast cancer patients (NCT01622361). The multicenter, phase 3, randomized clinical trial enrolled 187 women from July 5, 2012, to May 30, 2017. The patients were randomly assigned (1:1) to either 24 weeks of NCT including adriamycin plus cyclophosphamide followed by intravenous docetaxel, or NET involving goserelin acetate and daily tamoxifen. ALND was performed based on the surgeon's decision. The primary endpoint was ALND rate and surgical outcome after preoperative treatment. The secondary endpoint was long-term survival. Among the 187 randomized patients, pre- and post- neoadjuvant systemic therapy (NST) assessments were available for 170 patients. After NST, 49.4% of NCT patients and 55.4% of NET patients underwent mastectomy after treatment completion. The rate of ALND was significantly lower in the NCT group than in the NET group (55.2% vs. 69.9%, P=.046). Following surgery, the NET group showed a significantly higher mean number of removed LNs (14.96 vs. 11.74, P=.003) and positive LNs (4.84 vs. 2.92, P=.000) than the NCT group. The axillary pathologic complete response (pCR) rate was significantly higher in the NCT group (13.8% vs. 4.8%, P=.045) than in the NET group. During a median follow-up of 67.3 months, 19 patients in the NCT group and 12 patients in the NET group reported recurrence. The 5-year ARFS (97.5%vs. 100%, P=.077), DFS (77.2% vs. 84.8%, P=.166), and OS (97.5% vs. 94.7%, P=.304) rates did not differ significantly between the groups. In conclusion, although survival did not differ significantly, more NCT patients might able to avoid ALND, with fewer LNs removed with lower LN positivity. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01622361, identifier NCT01622361.

Patient-Reported Outcomes From Phase III Neoadjuvant Systemic Trial Comparing Neoadjuvant Chemotherapy With Neoadjuvant Endocrine Therapy in Pre-Menopausal Patients With Estrogen Receptor-Positive and HER2-Negative, Lymph Node-Positive Breast Cancer.

We aimed to evaluate the patient-reported outcomes (PROs) in a prospective phase III clinical trial, comparing neoadjuvant endocrine therapy (NET) with conventional neoadjuvant chemotherapy (NCT) in patients with hormone status positive, lymph node-positive premenopausal breast cancer (NCT01622361). The patients were randomized prospectively to either 24 weeks of NCT with adriamycin plus cyclophosphamide followed by taxane or NET with gonadotropin-releasing hormone agonist and tamoxifen. The patients were examined at the surgery unit of a large tertiary care hospital with a comprehensive cancer center. PROs were assessed on the first day of the trial (day 1, baseline) and at the end of treatment, using the breast cancer module of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 23 (EORTC QLQ BR23). One hundred and eighty-seven patients were randomly assigned to chemotherapy (n=95) or endocrine therapy (n=92), and 174 patients completed 24 weeks of the neoadjuvant treatment period (n=87, in each group). Baseline scores were similar between the groups. After treatment, there were no statistically significant differences in the function scales, including body image, sexual functioning, and sexual enjoyment between the groups, although the endocrine treatment group showed a significant improvement in the future perspective (hazard ratio, 8.3; 95% confidence interval, 1.72-18.38; P = 0.021). Similarly, there were no statistically significant differences in the symptom scales between the groups, including adverse effects of systemic therapy, breast symptoms, arm symptoms, and upset about hair loss. In conclusion, overall PROs were similar in both treatment groups, except for "future perspective," which was significantly better in the NET group than in the NCT group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.Gov, identifier NCT01622361.

Local Recurrence in Young Women with Breast Cancer: Breast Conserving Therapy vs. Mastectomy Alone.

We compared the cumulative incidence of local recurrence in young patients (≤40 years) with breast cancer between breast conserving therapy (BCT) and mastectomy alone. Among 428 women with early-stage breast cancer who were treated between 2001 and 2012, 311 underwent BCT and 117 underwent mastectomy alone. Adjuvant systemic treatments were administered to 409 patients (95.6%). We compared the cumulative incidence of LR and survival rates between two groups. During a median follow-up period of 91 months, the 10-year cumulative incidence of LR was 9.3% (median interval of 36.5 months from surgery). Patients treated with BCT tended to have a higher risk for local recurrence (11.1% for BCT vs. 4.1% for mastectomy alone, p = 0.078). All patients with isolated LR after BCT (n = 23) underwent salvage mastectomy followed by systemic treatments. The 5-year distant metastasis-free survival and overall survival of patients with isolated LR after BCT were 44.2% and 82.2%, respectively. The BCT group exhibited an approximately 2.5-fold higher risk of LR than mastectomy alone group. Patients with isolated LR after BCT showed poor prognosis despite undergoing aggressive salvage treatments. The development of novel treatments should be investigated to reduce LR for improving prognosis and preserving cosmetic outcomes in young women.

Clinical Outcomes Following Letrozole Treatment according to Estrogen Receptor Expression in Postmenopausal Women: LETTER Study (KBCSG-006).

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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01069211.

Prognostic Value of Skeletal Muscle Depletion Measured on Computed Tomography for Overall Survival in Patients with Non-Metastatic Breast Cancer.

PURPOSE: The purpose of this study was to evaluate the prognostic value of skeletal muscle depletion measured on computed tomography (CT) in patients with non-metastatic invasive breast cancer. METHODS: This retrospective study included 577 consecutive women (mean age ± standard deviation: 48.9 ± 10.2 years with breast cancer who underwent a preoperative positron-emission tomography (PET)/CT scan and curative surgery between January 2012 and August 2014. The total abdominal muscle area (TAMA), subcutaneous fat area (SFA), and visceral fat area (VFA) were measured on CT images at the L3 vertebral level. Univariate and multivariate Cox proportional-hazard regression analyses were performed to evaluate whether there was an association between sarcopenia and overall survival (OS) outcome. RESULTS: Of the 577 women, 49 (8.5%) died after a mean of 46 months. The best TAMA threshold for predicting OS was 83.7 cm2. The multivariate Cox proportional-hazard analysis revealed that sarcopenia (TAMA ≤ 83.70 cm2) was a strong prognostic biomarker (hazard ratio [HR], 1.951; 95% confidence interval [CI], 1.061-3.586), along with large tumor size, axillary lymph node metastasis, high nuclear grade, estrogen receptor status, and adjuvant radiation therapy. In the subgroup analysis of patients aged ≥ 50 years, TAMA (≤ 77.14 cm2) was a significant independent factor (HR, 2.856; 95% CI, 1.218-6.695). CONCLUSION: Skeletal muscle depletion measured on CT was associated with worse OS outcome in patients with non-metastatic breast cancer.

Correlations of female hormone levels with background parenchymal enhancement and apparent diffusion coefficient values in premenopausal breast cancer patients: Effects on cancer visibility.

PURPOSE: To evaluate the relationships between female hormone levels and background parenchymal enhancement (BPE) or apparent diffusion coefficient (ADC) values of breast parenchyma, as well as the effects of BPE and ADC values on cancer visibility. METHODS: This prospective study was performed in 164 consecutive premenopausal patients who were diagnosed with invasive breast cancer from November 2016 to December 2018. Two radiologists analyzed the qualitative, quantitative BPE and ADC values of normal contralateral breast parenchyma. We also analyzed the cancer visibility using a three-point scale (0: no visibility, 1: slight visibility, 2: excellent visibility). RESULTS: The progesterone level was significantly correlated with qualitative BPE grade and quantitative values of the BPE, as well as with the mean ADC. On contrast enhanced image (CEI), the visibility score was significantly associated with tumor size, qualitative and quantitative BPE. On diffusion weighted image (DWI), tumor size was significantly associated with the visibility score, whereas the ADC value was not. Of four lesions with a score of 0 on CEI, three had a score of 2 and one a score of 1 on DWI. Regarding the visibility score on DWI, tumor size and histologic type were significantly different among the three groups. CONCLUSIONS: Qualitative or quantitative BPE of breast parenchyma was positively correlated with the progesterone level and the mean ADC was negatively correlated. The cancer visibility was affected by BPE on CEI, but not by ADC on DWI. Small-sized cancer and invasive lobular cancer could be the causes of false-negative diagnoses on DWI.

Clinicopathological and Molecular Analysis of 45 Cases of Pure Mucinous Breast Cancer.

Pure mucinous breast carcinoma (PMBC) is characterized by clusters of tumor cells floating in abundant extracellular mucin and can be classified into paucicellular (Type A) and hypercellular (Type B) subtypes. However, the clinicopathological and genomic differences between these two subtypes have not been well characterized. We retrospectively investigated the clinicopathologic features of 45 cases of surgically removed PMBC (31 Type A and 14 Type B). We also performed whole-exome sequencing (WES) in eight cases of PMBC. We found that Type B PMBC occurs at an older age and shows more aggressive clinical behavior than Type A. WES analysis revealed that HYDIN was the most frequently mutated gene in both types of PMBC. Although Type B PMBC showed a tendency toward more frequent genetic alterations, there were no statistically significant differences between the two subtypes in single nucleotide variants or insertions or deletions of bases associated with moderate or high effects. Our results provide additional evidence that PMBCs are clinicopathologically and genetically heterogeneous and lack pathognomonic genetic alterations. Further, Type B PMBC is more frequently associated with lymph node metastasis than Type A.

Relationship between sex hormones levels and 18F-FDG uptake by the ovaries in premenopausal woman.

Background The study was conducted to evaluate the effect of sex hormones on F-18 fluorodeoxyglucose (18F-FDG) uptake by normal ovaries. Patients and methods A total of 197 premenopausal women were included in this study. Based on 18F-FDG positron emission tomography/computed tomography (PET/CT) images obtained from these subjects, the association of ovarian 18F-FDG uptake with levels of sex hormones, including estradiol, progesterone, testosterone, follicle-stimulating hormone, and luteinizing hormone was investigated. We also analysed the relationship between the menstrual cycle and ovarian 18F-FDG uptake. Results The highest ovarian 18F-FDG uptake occurred at 2 weeks after the onset of menstruation (median maximum standardized uptake value [SUVmax] = 3.40, median mean SUV [SUVmean] = 2.20), and the lowest ovarian 18F-FDG uptake was observed during the first week of the menstrual cycle (median SUVmax = 1.60, median SUVmean = 1.20). Ovarian 18F-FDG uptake was weakly positively correlated with progesterone levels (rho = 0.28, p < 0.001 for SUVmax, rho = 0.30, p < 0.001 for SUVmean), and this pattern was consistently observed in subjects in the follicular-phase group (rho = 0.29, p = 0.003 for both SUVmax and SUVmean) but not in subjects in the luteal-phase group. Conclusions Based on PET images, ovarian glucose metabolism in premenopausal women tended to increase slightly with increasing progesterone concentration.

The effect of sex hormones on normal breast tissue metabolism: Evaluation by FDG PET/CT.

This study investigated the effect of sex hormones on F-fluorodeoxyglucose (FDG) uptake in normal breast tissue.The retrospective study included 249 premenopausal women (median age, 45 years) who were diagnosed with unilateral breast cancer and underwent FDG positron emission tomography/computed tomography and hormone tests. The volume of interest was within the contralateral normal breast and the standardized uptake values (SUVs) were measured. The correlations of sex hormones (including estrogen, progesterone, testosterone, follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) with the SUVs of the normal breast were analyzed.There was a weak negative correlation between age and breast FDG uptake (P = .012, Spearman coefficient = -.16 for the maximum standardized uptake values [SUVmax]), especially in the luteal phase group (P = .005, Spearman coefficient = -.27 for SUVmax). The SUVs of normal breast tissue were increased when progesterone levels were higher (P = .043, Spearman coefficient = .13 for SUVmax). In the irregular menstrual cycle group, FDG uptake in the breast decreased as FSH (P = .027, Spearman coefficient = -.42 for SUVmax) and LH (P = .048, Spearman coefficient = -.44 for SUVmax) increased.Glucose metabolism of normal breast tissue decreases with age, and progesterone weakly affects breast FDG uptake. Gonadotropins may affect breast FDG uptake in premenopausal women with irregular menstrual cycles.

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.

Intraoperative Specimen Mammography for Margin Assessment in Breast-Conserving Surgery.

The purpose of this study aimed to determine whether intraoperative specimen mammography is an effective margin assessment method in Asian women. Thus, 182 patients who underwent breast-conserving surgery (BCS) were evaluated. After wide excision, intraoperative specimen mammography was used to assess margin adequacy. The control group comprised 84 patients who underwent BCS and were evaluated for margin of frozen section during surgery. 61.6% patients had dense breasts and 85.7% of dense breasts could margin assess by intraoperative specimen mammography. There were no significant differences in the incidence of extremely close margins (p = 0.421) and second operation (p = 0.252) between both groups. Significant correlations were found between radiological and histological margins (R2 = 0.222, p < 0.05). The frozen section analysis group had longer operative time than the specimen mammography group. The study results show that intraoperative specimen mammography of breast lesions in BCS is useful in identifying margin clearance.

Change in microcalcifications on mammography after neoadjuvant chemotherapy in breast cancer patients: correlation with tumor response grade and comparison with lesion extent.

BACKGROUND: After neoadjuvant chemotherapy (NAC), persistent microcalcifications are often observed in spite of a decrease in the primary tumor size. PURPOSE: To analyze the changes in microcalcifications after NAC and to evaluate the accuracy of residual microcalcifications in predicting the extent of residual cancer. MATERIAL AND METHODS: Eighty patients who received NAC and underwent both mammography and magnetic resonance imaging (MRI) before and after the completion of NAC were included. The location of microcalcifications was classified into two types: inside the mass and outside the mass. RESULTS: The extent of the residual calcifications was larger than the pathologic residual lesion in 14 (74%) of 19 patients with complete response (CR) on MRI, but the discrepancy was <1 cm in eight (42%) patients. The median value of the discrepancy was significantly higher in patients showing CR with outside calcifications compared to CR with inside calcifications (2.0 cm vs. 0.7 cm, P = 0.008). After NAC, the decrease of calcifications was more frequently observed in cancers showing CR on MRI or Miller-Payne grade 5 and the increase of calcifications more frequently occurred in cancers showing progress disease on MRI or Miller-Payne grade 1 ( P < 0.001 and P = 0.044). CONCLUSION: The change in microcalcifications after NAC was correlated with the tumor response to NAC. The discrepancy was highest in the group showing CR on MRI with outside calcifications. In tumors with inside calcifications, the discrepancy was relatively low within an acceptable range.

The feasibility of synthetic MRI in breast cancer patients: comparison of T2 relaxation time with multiecho spin echo T2 mapping method.

OBJECTIVE:: To compare the T2 relaxation times acquired with synthetic MRI to those of multi-echo spin-echo sequences and to evaluate the usefulness of synthetic MRI in the clinical setting. METHODS:: From January 2017 to May 2017, we included 51 patients with newly diagnosed breast cancer, who underwent additional synthetic MRI and multiecho spin echo (MESE) T2 mapping sequences. Synthetic MRI technique uses a multiecho and multidelay acquisition method for the simultaneous quantification of physical properties such as T1 and T2 relaxation times and proton density image map. A radiologist with 9 years of experience in breast imaging drew region of interests manually along the tumor margins on two consecutive axial sections including the center of tumor mass and in the fat tissue of contralateral breast on both synthetic T2 map and MESE T2 map images. RESULTS:: The mean T2 relaxation time of the cancer was 84.75 ms (± 15.54) by synthetic MRI and 90.35 ms (± 19.22) by MESE T2 mapping. The mean T2 relaxation time of the fat was 129.22 ms (± 9.53) and 102.11 ms (± 13.9), respectively. Bland-Altman analysis showed mean difference of 8.4 ms for the breast cancer and a larger mean difference of 27.8 ms for the fat tissue. Spearman's correlation test showed that there was significant positive correlation between synthetic MRI and MESE sequences for the cancer (r = 0.713, p < 0.001) and for the fat (r = 0.551, p < 0.001). The positive estrogen receptor and low histologic grade were associated with little differences between two methods (p = 0.02 and = 0.043, respectively). CONCLUSION:: T2 relaxation times of breast cancer acquired with synthetic MRI showed positive correlation with those of MESE T2 mapping. Synthetic MRI could be useful for the evaluation of tissue characteristics by simultaneous acquisition of several quantitative physical properties. ADVANCES IN KNOWLEDGE:: Synthetic MRI is useful for the evaluation of T2 relaxation times of the breast cancers.

Differences in prognosis and efficacy of chemotherapy by p53 expression in triple-negative breast cancer.

PURPOSE: TP53 mutation is the most common mutation in breast cancer, and it is considered a target marker of triple-negative breast cancer (TNBC). We investigated whether expression of p53 detected by immunochemical staining predicts the chemotherapy response of TNBC. METHODS: A total of 11,393 TNBC patients who had between stage I and stage III enrolled in the Korean Breast Cancer Society Registry database from January 1, 2000 to December 31, 2015. There were 6,331 'p53-positive (+) TNBC' patients and 5062 'p53-negative (-) TNBC' patients. RESULTS: In univariate analysis, p53(+) TNBC had a worse prognosis than p53(-) TNBC in patients not receiving chemotherapy (P = 0.003). However, there was no difference in prognosis between p53(+) TNBC and p53(-) TNBC for patients receiving chemotherapy. In multivariate analysis adjusted for age and stage, the risk of p53(+) TNBC was 1.84 times higher than that of p53(-) TNBC in the non-chemotherapy group. However, there was no difference between p53(+) TNBC and p53(-) TNBC in patients receiving chemotherapy. In p53(+) TNBC, the risk was 0.6-fold lower when chemotherapy was administered than when chemotherapy was not administered. However, in p53(-) TNBC, there was no risk reduction effect by chemotherapy. CONCLUSION: The prognosis of p53(+) TNBC has worse than p53(-) TNBC, but the risk for survival was significantly reduced with chemotherapy. It suggests that p53(+) TNBC would be more sensitive to chemotherapy than p53(-) TNBC.

Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients Receiving Letrozole as an Early Adjuvant Treatment.

PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from -0.39 at baseline to -0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.

Quantitative analysis of background parenchymal enhancement in whole breast on MRI: Influence of menstrual cycle and comparison with a qualitative analysis.

OBJECTIVE: We quantitatively analyzed background parenchymal enhancement (BPE) in whole breast according to menstrual cycle and compared it with a qualitative analysis method. MATERIALS AND METHODS: A data set of breast magnetic resonance imaging (MRI) from 273 breast cancer patients was used. For quantitative analysis, we used semiautomated in-house software with MATLAB. From each voxel of whole breast, the software calculated BPE using following equation: [(signal intensity [SI] at 1 min 30 s after contrast injection - baseline SI)/baseline SI] × 100%. RESULTS: In total, 53 patients had minimal, 108 mild, 87 moderate, and 25 marked BPE. On quantitative analysis, mean BPE values were 33.1% in the minimal, 42.1% in the mild, 59.1% in the moderate, and 81.9% in the marked BPE group showing significant difference (p = .009 for minimal vs. mild, p < 0.001 for other comparisons). Spearman's correlation test showed that there was strong significant correlation between qualitative and quantitative BPE (r = 0.63, p < 0.001). The mean BPE value was 48.7% for patients in the first week of the menstrual cycle, 43.5% in the second week, 49% in the third week, and 49.4% for those in the fourth week. The difference between the second and fourth weeks was significant (p = .005). Median, 90th percentile, and 10th percentile values were also significantly different between the second and fourth weeks but not different in other comparisons (first vs. second, first vs. third, first vs. fourth, second vs. third, or third vs. fourth). CONCLUSION: Quantitative analysis of BPE correlated well with the qualitative BPE grade. Quantitative BPE values were lowest in the second week and highest in the fourth week.

Clinical Characteristics and Prognosis Associated with Multiple Primary Cancers in Breast Cancer Patients.

PURPOSE: Breast cancer is one of the most common malignancies worldwide and the second most common cancer among Korean women. The prognosis of breast cancer is poor in patients with other primary cancers. However, there have been few clinical studies regarding this issue. Therefore, we analyzed the characteristics and prognosis of patients with breast cancer with multiple primary cancers (MPCs). METHODS: Data from the Korean Breast Cancer Society Registry were analyzed. Data from enrolled patients who underwent surgery for breast cancer were analyzed for differences in prognosis dependent on the presence of MPCs, and which MPC characteristics affected their prognosis. RESULTS: Among the 41,841 patients analyzed, 913 patients were found to have MPCs, accounting for 950 total MPCs. There was a significant difference in survival rates between the breast cancer only group and the MPC group. The 5-year survival rates were 93.6% and 86.7% and the 10-year survival rates were 87.5% and 70.4%, respectively. Among the 913 patients with MPCs, patients with two or more MPCs had significantly worse prognoses than patients with a single MPC. With respect to the time interval between breast cancer and MPC occurrence, patients with a 5-year or greater interval had significantly better prognoses than patients with less than 1 year between occurrences. Among MPCs, thyroid cancer was the most common primary cancer. However, this type was not related to the prognosis of breast cancer. Gynecologic cancer, colorectal cancer, upper gastrointestinal cancer, and lung cancer were related to breast cancer prognosis. CONCLUSION: MPCs were a poor prognostic factor for patients with breast cancer. Two or more MPCs and a shorter time interval between occurrences were worse prognostic factors. Although MPCs were a poor prognostic factor, thyroid cancer did not affect the prognosis of patients with breast cancer.