Surveillance for Distant Metastasis in Breast Cancer Patients Who Underwent Contemporary Management: A Report from the Korean Breast Cancer Society Survivor Research Group.

BACKGROUND: Current guidelines recommend against the use of routine imaging tests to detect distant metastasis in asymptomatic breast cancer patients. However, recent advancements in effective therapeutics and diagnostic accuracy have raised the need to reassess the clinical efficacy of intensive metastasis surveillance. We report the results of a multicenter retrospective study to investigate the association between intensive imaging studies and survival outcomes. PATIENTS AND METHODS: We retrospectively reviewed the data of 4130 patients who underwent surgery from 11 hospitals in Korea between January 2010 and December 2011. Patients were divided into two groups on the basis of the intensity of metastasis imaging studies during their disease-free period. The types and intervals of the imaging studies were based on each physician's decisions. RESULTS: High-intensive screening showed a shorter distant metastasis-free survival [p < 0.001, hazard ratio (HR) 1.62; 95% confidence interval (CI) 1.29-2.04], especially for patients in whom bone or lung was the first site of metastasis. With a median follow-up period of 110.0 months, the 5-year breast cancer-specific survival (BCSS) rate was 96.5%. The high-intensity screening group showed significantly poorer BCSS compared with the low-intensity screening group (p < 0.001, HR 3.13; 95% CI 2.32-4.21). However, both multivariable analysis and propensity score matching analysis showed no significant association between the screening intensity and BCSS. CONCLUSIONS: Frequent imaging studies to detect distant metastasis were associated with earlier detection of distant metastasis, especially for lung and bone metastasis. However, intensive surveillance showed no apparent association with BCSS despite the use of currently available treatments.

Characteristics and chronologically changing patterns of late-onset breast cancer in Korean women of age ≥ 70 years: A hospital based-registry study.

BACKGROUND: Women from Asian and western countries have vastly different ages of onset of breast cancer, with the disease tending to occur at an older age in the West. Through an investigation of the patterns of old-onset breast cancer (OBC) in Korean women, we aimed to identify the characteristics of Korean OBC and evaluate whether these patterns are changing in relation to increasing westernization. METHODS: This study retrospectively evaluated 102,379 patients who underwent surgical treatment of primary breast cancer between January 1, 2000 and December 31, 2013 in Korea. We used hospital -based breast cancer registry and analyzed data from these patients using multiple linear regression analysis to compare the characteristics and chronologically changing patterns between OBC (70 years of age or older) and non-OBC (40-69 years of age) patients in Korea. RESULTS: A total of 6% of the 102,379 patients had OBC. Overall, OBC had more favorable biological features, such as a higher incidence of luminal A subtype, than did non-OBC, except for a higher incidence rate of triple-negative breast cancer (TNBC). However, OBC also presented with a higher overall disease stage, including higher T and M stages. Although the incidence rates of both OBC and non-OBC have increased overtime, the relative proportion of OBC patients has slightly increased, whereas that of non-OBC has slightly decreased. The increase in the incidence of both OBC and non-OBC was primarily due to the luminal A subtype. CONCLUSIONS: Based on a hospital-based registry, overall, Korean OBC had favorable biological features but showed a higher rate of TNBC and advanced cancer stages. The incidence trend of breast cancer in Korea is slowly shifting toward an older age at onset, largely due to the luminal A subtype. Our results may provide novel insights into OBC in Asia, and aid in the development of optimal management of the disease in Asia. TRIAL REGISTRATION: Retrospectively registered.

Long-term risk of congestive heart failure in younger breast cancer survivors: A nationwide study by the SMARTSHIP group.

BACKGROUND: There is a controversy about late-onset congestive heart failure (CHF) among breast cancer survivors. This study investigated the incidence rate and risk factors of late-onset CHF more than 2 years after the breast cancer diagnosis. METHODS: A nationwide, retrospective study was conducted with the National Health Information Database. With 1:3 age- and sex-matched noncancer controls, Cox proportional hazard regression models were used to analyze the incidence and risk factors of late CHF. The cumulative incidence rate of late CHF was evaluated with a Kaplan-Meier analysis and a log-rank test. RESULTS: A total of 91,227 cases (286,480 person-years) and 273,681 controls (884,349 person-years) were evaluated between January 2007 and December 2013. The risks of late CHF were higher in cases than controls (hazard ratio [HR], 1.396; 95% confidence interval [CI], 1.268-1.538). Younger survivors (age ≤ 50 years) showed a higher risk of late CHF than their younger counterparts (HR, 2.903; 95% CI, 2.425-3.474). Although older age was a risk factor for late CHF, older survivors (age ≥ 66 years) showed no difference in the risk of late CHF in comparison with their counterparts (HR, 0.906; 95% CI, 0.757-1.084). Anthracyclines and taxanes were risk factors for late CHF, although trastuzumab, radiation, and endocrine therapy were not. CONCLUSIONS: Young breast cancer survivors have a greater risk of late CHF than the young population without cancer. More attention should be paid to young breast cancer survivors who receive taxane- or anthracycline-based regimens over the long term.

Isoflavone intake on the risk of overall breast cancer and molecular subtypes in women at high risk for hereditary breast cancer.

PURPOSE: We investigated the association between isoflavone (ISF) intake and hereditary breast cancer (BC) risk, particularly by molecular subtype, in East-Asian BRCA1/2 mutation carriers and non-carriers at a high risk of hereditary breast cancer (i.e., family history of BC (FHBC) and early-onset BC [EOBC, age < 40 years]). METHODS: The association between ISF intake and BC risk by molecular subtypes was assessed in 1709 participants (407 BRCA1/2 carriers, 585 FHBC non-carriers, 586 EOBC non-carriers, and 131 unaffected non-carriers) from the Korean Hereditary Breast Cancer Study using hazard ratios (HRs) and 95% confidence intervals (CIs) in weighted Cox regression models. Daily ISF intake was assessed using a validated food frequency questionnaire. We evaluated gene-environment interactions between BRCA1/2 mutation and ISF intake in 1604 BC cases by calculating the case-only odds ratios (CORs) and 95% CIs in logistic regression models. RESULTS: ISF intake was inversely associated with luminal A BC risk in BRCA2 mutation carriers and FHBC non-carriers (HR = 0.14, 95% CI = 0.04-0.50 for high intake [ISF intake ≥ 15.50 mg/day]; HR = 0.27, 95% CI = 0.11-0.69 for high intake, respectively). We observed a reduced risk of triple negative BC (TNBC) in BRCA1 carriers and FHBC non-carriers (HR = 0.09, 95% CI = 0.02-0.40 for high intake; HR = 0.19, 95% CI = 0.05-0.69 for high intake, respectively). In the case-only design, an interaction between BRCA1 mutation carrier status and ISF intake emerged in TNBC patients (COR = 0.39, 95% CI = 0.16-0.95). CONCLUSIONS: This study suggests that ISF intake is inversely associated with BC risk in women at high risk of hereditary BC and that the effect could differ by molecular subtypes.

Different prognosis of young breast cancer patients in their 20s and 30s depending on subtype: a nationwide study from the Korean Breast Cancer Society.

PURPOSE: Numerous studies have demonstrated that breast cancer in young women (BCY) has unfavorable prognostic features and more unfavorable subtypes. However, few studies have evaluated the effect of subtype disparities on breast cancer prognosis by age, especially for BCY. We analyzed breast cancer mortality stratified by tumor subtype according to age among patients younger than 50 years. METHODS: Data from the Korean Breast Cancer Society Registry for patients diagnosed with invasive breast cancer when aged less than 50 years between 2003 and 2010 were reviewed retrospectively. RESULTS: We identified 30,793 patients with breast cancer who were eligible for analysis. Of these, 793 (2.6%) were aged 20-29 and 8926 (28.8%) were aged 30-39. Median follow-up duration was 84 months. Mean age was 42.4 years. Patients in their 20s were more likely to have cancer of advanced stage and higher nuclear grade, present with lymphovascular invasion, and have unfavorable subtypes. Patients in the 20s group showed worse prognosis. In multivariate analysis for overall survival (OS), the hazard ratio (HR) for patients in the 20s group was higher than that for the 30s and 40s groups, and patients with triple-negative breast cancer (TNBC) showed higher HR than patients with HER-2 or luminal subtype (all p < 0.0001). When stratified by subtype, luminal subtype showed significantly worse prognosis in the 20s group than the 30s and 40s groups, whereas HER-2 and TNBC subtypes showed no significant difference. CONCLUSION: Patients in their 20s with breast cancer had unfavorable characteristics and worse prognosis than patients in their 30s and 40s. When stratified by tumor subtype, patients in their 20s with luminal subtype of breast cancer showed worse prognosis than older patients, whereas HER-2 and TNBC subtypes showed no significant differences.

Effects of compensatory cognitive training intervention for breast cancer patients undergoing chemotherapy: a pilot study.

PURPOSE: Numerous breast cancer patients experience cognitive changes during and after chemotherapy. Chemotherapy-related cognitive impairment can significantly affect quality of life. This pilot study attempted to determine the effects of a compensatory cognitive training on the objective and subjective cognitive functioning of breast cancer patients receiving adjuvant chemotherapy. METHODS: Fifty-four patients were assigned to either a compensatory cognitive training or waitlist condition. They were assessed at baseline (T1), the completion of the 12-week intervention (T2), and 6 months after intervention completion (T3). Outcomes were assessed using the standardized neuropsychological tests and the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), version 3. Raw data were converted to T-scores based on baseline scores, and a repeated-measures ANCOVA, adjusting for age, intelligence, depression, and treatment, was used for analysis. The effect sizes for differences in means were calculated. RESULTS: The intervention group improved significantly over time compared to the waitlist group on objective cognitive function. Among ten individual neuropsychological measures, immediate memory, delayed memory, verbal fluency in category, and verbal fluency in letter showed significant group × time interaction. In subjective cognitive function, scores of the waitlist group significantly decrease over time on perceived cognitive impairments, in contrast to those of the intervention group. CONCLUSION: The 12-week compensatory cognitive training significantly improved the objective and subjective cognitive functioning of breast cancer patients. Because this was a pilot study, further research using a larger sample and longer follow-up durations is necessary.

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR).

BACKGROUND: Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. METHODS/DESIGN: Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. DISCUSSION: This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01589367.

Is there any correlation between model-based perfusion parameters and model-free parameters of time-signal intensity curve on dynamic contrast enhanced MRI in breast cancer patients?

OBJECTIVE: To find out any correlation between dynamic contrast-enhanced (DCE) model-based parameters and model-free parameters, and evaluate correlations between perfusion parameters with histologic prognostic factors. METHODS: Model-based parameters (Ktrans, Kep and Ve) of 102 invasive ductal carcinomas were obtained using DCE-MRI and post-processing software. Correlations between model-based and model-free parameters and between perfusion parameters and histologic prognostic factors were analysed. RESULTS: Mean Kep was significantly higher in cancers showing initial rapid enhancement (P = 0.002) and a delayed washout pattern (P = 0.001). Ve was significantly lower in cancers showing a delayed washout pattern (P = 0.015). Kep significantly correlated with time to peak enhancement (TTP) (ρ = -0.33, P < 0.001) and washout slope (ρ = 0.39, P = 0.002). Ve was significantly correlated with TTP (ρ = 0.33, P = 0.002). Mean Kep was higher in tumours with high nuclear grade (P = 0.017). Mean Ve was lower in tumours with high histologic grade (P = 0.005) and in tumours with negative oestrogen receptor status (P = 0.047). TTP was shorter in tumours with negative oestrogen receptor status (P = 0.037). CONCLUSIONS: We could acquire general information about the tumour vascular physiology, interstitial space volume and pathologic prognostic factors by analyzing time-signal intensity curve without a complicated acquisition process for the model-based parameters. KEY POINTS: • Kep mainly affected the initial and delayed curve pattern in time-signal intensity curve. • There is significant correlation between model-based and model-free parameters. • We acquired information about tumour vascular physiology, interstitial space volume and prognostic factors.

Utility of MRI and PET/CT after neoadjuvant chemotherapy in breast cancer patients: correlation with pathological response grading system based on tumor cellularity.

BACKGROUND: MRI and PET/CT are useful for assessing breast cancer patients after neoadjuvant chemotherapy (NAC). PURPOSE: To investigate the utility of MRI and PET/CT in the prediction of pathologic response to neoadjuvant chemotherapy using Miller-Payne grading system in patients with breast cancer. MATERIAL AND METHODS: From January 2008 to December 2010, 59 consecutive patients with pathologically proven breast cancer, who underwent neoadjuvant chemotherapy followed by surgery were retrospectively enrolled. The maximal diameter decrease rate and volume reduction rate by three-dimensional (3D) MRI and standardized uptake value (SUV) reduction rate by PET/CT were calculated and correlated with the Miller-Payne grading system using the Spearman rank correlation test. Patients with Miller-Payne grades 1 or 2 were classified into the non-responder group and patients with grades 3, 4, and 5 were in the responder group. To differentiate between responders and non-responders, receiver-operating characteristic (ROC) analysis was performed. RESULTS: The volume reduction rate was 64.87 ± 46.95, diameter decrease rate was 48.09 ± 35.02, and SUV decrease rate was 62.10 ± 32.17. Among three parameters, the volume reduction rate was most correlated with histopathologic grades of regression (ρ = 0.755, P < .0001) followed by diameter decrease rate (ρ = 0.660, P < 0.0001), and SUV decrease rate of primary breast mass (ρ = 0.561, P = 0.0002). The area under the ROC curve (Az) value was largest in the volume reduction rate (Az = 0.9), followed by SUV decrease rate (Az = 0.875), and diameter decrease rate (Az = 0.849). The best cut-offs for differentiating responders from non-responders in the ROC curve analysis were a 50% decrease in diameter, 68.9% decrease in volume, and 60.1% decrease in SUV after NAC. CONCLUSION: Volumetric measurement using 3D MRI combined with conventional diameter measurement may be more accurate to evaluate pathologic response after NAC.

Omission of Breast Surgery in Predicted Pathologic Complete Response after Neoadjuvant Systemic Therapy: A Multicenter, Single-Arm, Non-inferiority Trial.

PURPOSE: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. METHODS: The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuum-assisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years. DISCUSSION: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05505357. Registered on August 17, 2022. Clinical Research Information Service Identifier: KCT0007638. Registered on July 25, 2022.

Impact of local surgical treatment on survival in young women with T1 breast cancer: long-term results of a population-based cohort.

The aim of this study was to analyze the effect of the type of local surgical treatment on survival in young women aged less than 40 years with T1 breast cancer. We analyzed data from 3,512 patients aged ≤40 years old who were diagnosed with T1 breast cancer from the Korean Breast Cancer Registry database between January 1988 and December 2006 and underwent either breast-conserving therapy (BCT) or mastectomy. The overall survival (OS) and breast-cancer-specific survival (BCSS) were compared between BCT and mastectomy. Of the 3,512 patients analyzed, 1,951 (55.6 %) underwent BCT, and 1,561 (44.4 %) underwent mastectomy. The median follow-up period was 111.0 (79.0-131.5) months. Overall, the 10-year OS rates for BCT and mastectomy were 95 and 92.1 %, respectively (p = 00004), and the 10-year BCSS rates for BCT and mastectomy patients were 96.9 and 94.9 %, respectively (p = 0.12). In node-negative patients, no significant difference was observed in either the OS (adjusted hazard ratio [HR] 1.072; 95 % CI, 0.750-1.5332, p = 0.704) or BCSS (adjusted HR 0.988; 95 % CI, 0.620-1.574, p = 0.960) rate between the BCT and mastectomy groups. In node-positive patients, no significant difference was observed in the OS (adjusted HR 1.634; 95 % CI, 0.982-2.272, p = 0.59) and BCSS (adjusted HR 1.410; 95 % CI, 0.755-2.633, p = 0.281) rates between the BCT and mastectomy groups. In this large, population-based analysis of young women with T1 breast cancer, the OS and BCSS were not different between BCT and mastectomy.

Magnetic resonance imaging enhancement features before and after neoadjuvant chemotherapy in patients with breast cancer: a predictive value for responders.

PURPOSE: This study examined the ability of magnetic resonance imaging (MRI) enhancement features to predict the response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. METHODS: This retrospective study included 107 patients with breast cancer. All patients underwent a baseline breast MRI before NAC and follow-up MRI a mean of 3.7 months later. Breast MRI scans were evaluated using the Breast Imaging Reporting and Data System MRI lexicon. In addition, whole-breast vascularity (WBV) in the cancer-bearing breast was graded according to increased vessel number in comparison with the contralateral breast. Histopathologic tumor regression was graded semiquantitatively based on the Miller-Payne grading system. The ability of each MRI feature to predict the response was evaluated using a logistic regression analysis. Correlations between changes in MRI features and response were also evaluated using the Spearman rank correlation test. RESULTS: There were 73 responders (68%), including 59 partial and 14 complete responders. No significant difference in baseline MRI features was found between the responders and nonresponders, except for tumor size (P = 0.044). No dynamic enhancement feature on baseline MRI was useful for the early prediction of a response. In addition, an increased WBV did not predict a response, and the WBV change on the follow-up MRI was not correlated with the response. However, the change in the initial enhancement pattern (P = 0.007) and kinetic curve type (P = 0.003) were significantly correlated with response. CONCLUSIONS: No baseline MRI feature described using the Breast Imaging Reporting and Data System MRI lexicon was useful for early prediction of the response to NAC.

Effects of Post Traumatic Growth on Successful Aging in Breast Cancer Survivors in South Korea: The Mediating Effect of Resilience and Intolerance of Uncertainty.

This study aimed to identify post-traumatic growth and successful aging and the mediating effects of resilience and intolerance of uncertainty in breast cancer survivors. This study employed a descriptive survey approach. Data were collected from 143 breast cancer survivors between 27 January and 10 December 2021, at a cancer center in Gyeongsangnam-do, South Korea. SPSS/WIN 25.0 and PROCESS Macro version 3.5 were used for data analysis. Descriptive statistics were analyzed with SPSS. PROCESS was used to conduct a mediation analysis and the significance of the mediating effect was evaluated using 95% confidence intervals. Successful aging was significantly associated with post-traumatic growth, resilience, and the intolerance of uncertainty. The impact of post-traumatic growth on successful aging was mediated by resilience in breast cancer survivors. Resilience should be considered when developing nursing interventions to enhance post-traumatic growth and promote successful aging in breast cancer survivors.

Prognostic significance of TP53 and PIK3CA mutations analyzed by next-generation sequencing in breast cancer.

Breast cancer is one of the most prevalent malignant tumors affecting women globally. It is a heterogeneous disease characterized by mutations in several genes. Several gene panels have been applied to assess the risk of breast cancer and determine the appropriate treatment. As a powerful tool, Next-generation sequencing (NGS) has been widely utilized in cancer research due to its advantages, including high speed, high throughput, and high accuracy. In this study, we aim to analyze the correlation between somatic mutations in breast cancer, analyzed using NGS, and the prognosis of patients. Between May 2018 and May 2019, a total of 313 patients with breast cancer underwent surgical treatment, which included total mastectomy and breast-conserving surgery. Among these patients, 265 were diagnosed with invasive ductal carcinoma. In this study, we analyzed the NGS results, clinicopathological characteristics, and their correlation with prognosis. Using a gene panel, we examined 143 somatic mutations in solid cancers. Notably, the study population included patients who had received neoadjuvant chemotherapy. The mean age of the patients was 53.1 (±10.28) years, and the median follow-up time was 48 months (range, 8-54). Among the 265 patients, 68 had received prior systemic therapy. Of these, 203 underwent breast-conserving surgery, and 62 underwent a mastectomy. Various somatic mutations were observed in NGS, with the most frequent mutation being PIK3CA mutations, which accounted for 44% of all mutations. TP53 mutations were the second most frequent, and ERBB2 mutations were the third most frequent. TP53 mutations were associated with poor disease-free survival (P = .027), while PIK3CA mutations were associated with better disease-free survival (P = .035) than PIK3CA wild-type. In our study, we identified various somatic mutations in breast cancer. Particularly, we found that TP53 and PIK3CA mutations are potentially associated with the prognosis of breast cancer. These findings suggest that the presence of specific mutations may have implications for predicting the prognosis of breast cancer. Further research and validation are needed to gain a deeper understanding of the role of these mutations and their mechanisms in prognosis prediction.

Characteristics of double heterozygosity for BRCA1 and BRCA2 germline mutations in Korean breast cancer patients.

To investigate clinical, pathological, and familial characteristics of Korean patients with double heterozygosity for BRCA1 and BRCA2 mutations, six breast tumors of five patients who carried deleterious mutations in both of the genes were included. Medical records of the patients were reviewed and genetic testing by direct sequencing was undertaken to detect mutations in BRCA1 and BRCA2. Seven frameshift and three nonsense mutations were identified, and four mutations are novel in the Breast Cancer Information Core. There were no Ashkenazi founder mutations detected. The mean age at diagnosis for breast cancer was 33 years. All six tumors were infiltrating ductal carcinoma and poorly differentiated. Pathologic stage was I or II, and immunohistochemistry showed negative immunoreactivity for estrogen receptor and Her-2/neu in all tumors. Positive immunoreactivity for progesterone receptor was found only in one tumor. Three patients had familial history of breast, ovarian or other cancers. One patient who was diagnosed for breast cancer at the age of 26 had two maternal family members of metachronous bilateral breast cancer. Another patient who experienced metachronous bilateral breast cancer had maternal history of ovarian and esophageal cancer. In summary, Korean patients with double heterozygosity for BRCA1 and BRCA2 were young at diagnosis of breast cancer. Tumors were early stage, high grade, and almost triple-negative phenotype. All familial history of breast, ovary or other cancer was maternal. Close surveillance and accurate risk assessment should be provided for the patients with mutations in the both of the genes.

Prevalence of BRCA1 and BRCA2 mutations in non-familial breast cancer patients with high risks in Korea: the Korean Hereditary Breast Cancer (KOHBRA) Study.

Prevalence and phenotype of BRCA mutation can vary by race. The purpose of this study is to evaluate the prevalence of BRCA1/2 mutations in non-familial breast cancer patients with high risks in Korea. A subset of 758 patients was selected for this study from the KOHBRA nationwide multicenter prospective cohort study. Mutations in BRCA1/2 genes were tested using fluorescent-conformation sensitive gel electrophoresis, denaturing high performance liquid chromatography or direct sequencing. Mutation of BRCA1/2 genes were identified in 65 (8.6%) patients among total 758 patients [BRCA1 mutation: 25 (3.3%), BRCA2 mutation: 40 (5.3%)]. According to risk groups, mutation of BRCA1/2 genes were identified in 53 (8.5%) of 625 early onset patients (age ≤ 40), in 22 (17.7%) of 124 bilateral breast cancer patients, in 3 (50.0%) of 6 breast and ovarian cancer patients, in one (5.9%) of 17 male breast cancer patients, in 5 cases (7.6%) of 66 multiple organ cancer patients. The most common mutation was 509C>A for BRCA1 and 7708C>T for BRCA2. The prevalence of BRCA1/2 mutations by age in early onset patients was significantly different (age <35 vs age ≥35; 10.0 vs 2.9%, p = 0.0007). BRCA1/2 mutations for non-familial Korean breast cancer patients were detected at a high rate, particularly, in patients with early onset of less than 35 years of age, bilateral breast cancer, and breast and ovarian cancer. Individualized genetic counseling should be offered for non-familial breast cancer patients with these risk factors.

Prognostic role of MRI enhancement features in patients with breast cancer: value of adjacent vessel sign and increased ipsilateral whole-breast vascularity.

OBJECTIVE: The purpose of this study was to compare adjacent vessel sign, increased ipsilateral whole-breast vascularity, and various MRI features as described in the American College of Radiology BI-RADS MRI lexicon with histopathologic predictors in patients with unilateral breast cancer. MATERIALS AND METHODS: We retrospectively evaluated breast MRI examinations of 249 patients with histologically confirmed breast cancer. In addition to the BI-RADS MRI lexicon, the adjacent vessel sign and increased ipsilateral whole-breast vascularity of the cancer-bearing breast were evaluated by two independent observers. MRI features were then correlated with histopathologic prognostic factors. RESULTS: The adjacent vessel sign was significantly (p=0.023 to p<0.001) associated with tumor size, lymph node metastasis, distant metastasis, nuclear grade, and expression of estrogen and progesterone receptors. Increased ipsilateral whole-breast vascularity was significantly associated with all histopathologic predictors (p=0.017 to p<0.001). In multivariate analysis, the significant and independent predictors were a spiculated margin and rim enhancement for negative estrogen and progesterone receptors, a kinetic curve type for higher histologic grade, and an increased ipsilateral whole-breast vascularity for larger tumor size, lymph node metastasis, distant metastasis, higher nuclear grade, and higher histologic grade. CONCLUSION: In conjunction with the standard BI-RADS MRI lexicon, the adjacent vessel sign and increased ipsilateral whole-breast vascularity may serve as additional predictors of a poor prognosis.

Magnetic resonance imaging patterns of tumor regression after neoadjuvant chemotherapy in breast cancer patients: correlation with pathological response grading system based on tumor cellularity.

PURPOSE: The objectives of the study were to analyze the tumor shrinkage pattern on magnetic resonance imaging (MRI) after neoadjuvant chemotherapy and to evaluate whether there is any difference in shrinkage pattern between pathological responder and nonresponder groups. In addition, we wanted to compare tumor diameter obtained from MRI with histological diameter according to the tumor shrinkage pattern. METHODS: Between July 2008 and December 2010, 55 consecutive patients (56 lesions) with pathologically proven breast cancer who underwent neoadjuvant chemotherapy followed by surgery were retrospectively enrolled. The shrinkage pattern was classified into 4 categories: I (concentric shrinkage without surrounding lesion), II (concentric shrinkage with surrounding lesions), III (shrinkage with residual multinodular lesions, and IV (diffuse contrast enhancement in whole quadrants). Histological regression was scored on a 5-point scale regarding tumor cellularity reduction (Miller-Payne grading system). Patients with Miller-Payne grade 1 or 2 were classified into the nonresponder group, and patients with grade 3, 4, or 5 were in the responder group. RESULTS: Of 56 lesions, pattern I was seen in 29 lesions, pattern II in 13 lesions, pattern III in 5 lesions, and pattern IV in 4 lesions. Three lesions were not visualized on MRI after neoadjuvant chemotherapy, and 2 lesions were increased in size. There was a statistically significant difference in the tumor shrinkage pattern between responder and nonresponder groups (P = 0.017). All 5 lesions with type III shrinkage pattern were found in the responder group, and all 4 lesions with pattern IV were in the nonresponder group. Magnetic resonance imaging diameter of lesions with types I, II, and IV patterns showed significant correlation with the histological diameter. Among them, the correlation factor was highest in pattern IV (ρ = 0.94, P < 0.001) followed by pattern I (ρ = 0.67, P < 0.01) and pattern II (ρ = 0.502, P = 0.08). However, in type III shrinkage pattern, tumor size measured on MRI was not significantly correlated with histological size (P = 0.87). CONCLUSIONS: Types III and I shrinkage patterns were more frequently observed in the pathological responder group, and type IV was more frequently noted in the nonresponder group. Tumor diameter measured on MRI showed strong correlation with histological diameter in lesions with types I and IV shrinkage patterns, whereas lesions with type III did not show significant correlation. Type II pattern showed similar frequencies between the 2 groups and moderate correlation between sizes obtained from MRI and histology.

Contralateral enhancing lesions on magnetic resonance imaging in patients with breast cancer: role of second-look sonography and imaging findings of synchronous contralateral cancer.

OBJECTIVES: The purposes of this study were to assess the clinical utility of sonography for evaluation of contralateral suspicious lesions detected on magnetic resonance imaging (MRI) in patients with breast cancer and to compare imaging findings of the index and synchronous contralateral cancers. METHODS: We performed breast MRI on 853 consecutive patients with histologically confirmed breast cancer between January 2006 and December 2009. All patients underwent mammography and whole-breast sonography before MRI. We included 126 contralateral enhancing lesions in 98 patients who underwent second-look sonography. Lesions with sonographic correlation were biopsied using sonographic guidance, and lesions without sonographic correlation were biopsied using computed tomographic guidance or followed with imaging modalities. RESULTS: Of 126 suspicious lesions, 81 (64%) were correlated on sonography, and 45 (36%) were not. Of 81 correlated lesions, 16 (20%) were malignant, and 65 (80%) were benign. Of 45 lesions that were not correlated on sonography, only 1 (2%) was malignant. Of 17 contralateral cancers, 11 were detected on initial sonography and 5 on second-look sonography. The index and contralateral cancers showed statistically significant differences in the sonographic boundary (P = .003) and posterior echogenicity (P = .013). The contralateral cancers detected on initial or second-look sonography showed significant differences in the echo pattern (P = .001). CONCLUSIONS: Magnetic resonance imaging is a reliable tool for detection of occult contralateral breast cancer. With second-look sonography, we can find additional contralateral cancer. When enhancing lesions on MRI are not correlated on sonography, MRI- or computed tomography-guided biopsy or short-term imaging follow-up should be done.

Prognosis of pregnancy after breast cancer diagnosis according to the type of treatment: A population-based study in Korea by the SMARTSHIP group.

BACKGROUNDS: In this study, we evaluated the incidence and outcomes of pregnancy after breast cancer was diagnosed in women of childbearing age. Additionally, we evaluated the prognosis of patients who became pregnant after breast cancer, according to the treatment. METHODS: This was a retrospective cohort study of women aged 20-45 years who were surgically treated for breast cancer between 2004 and 2014 using the Korean National Health Insurance database. The patients were classified into six groups according to the treatment. Propensity score matching was applied to the cohort to analyze the risk of breast cancer-associated mortality after pregnancy and childbirth. RESULTS: Of the 45,765 patients who had been newly diagnosed with breast cancer, 1826 (4%) became pregnant after breast cancer diagnosis. Among the pregnant group, the HR of the risk of death was 0.15 (95% CI, 0.06 to 0.36) for patients who became pregnant ≥49 months after the diagnosis. In patients who received endocrine therapy and chemotherapy, the pregnant group had better prognosis than the non-pregnant group. There was no significant difference between the pregnant group and the non-pregnant group in patients who received chemotherapy and trastuzumab with or without endocrine therapy. CONCLUSION: The risk of death was low in women who became pregnant ≥49 months after the diagnosis of breast cancer. The prognosis of pregnant women was non-inferior to that of non-pregnant women, even in women who received trastuzumab. These findings provide reassurance to patients with HER2-positive cancer who are considering future pregnancy.