A Nomogram for Predicting the Oncotype DX Recurrence Score in Women with T1-3N0-1miM0 Hormone Receptor‒Positive, Human Epidermal Growth Factor 2 (HER2)‒Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This preliminary study was conducted to evaluate the association between Oncotype DX (ODX) recurrence score and traditional prognostic factors. We also developed a nomogram to predict subgroups with low ODX recurrence scores (less than 25) and to avoid additional chemotherapy treatments for those patients. MATERIALS AND METHODS: Clinicopathological and immunohistochemical variables were retrospectively retrieved and analyzed from a series of 485 T1-3N0-1miM0 hormone receptor-positive, human epidermal growth factor 2‒negative breast cancer patients with available ODX test results at Asan Medical Center from 2010 to 2016. One hundred twenty-seven patients (26%) had positive axillary lymph node micrometastases, and 408 (84%) had ODX recurrence scores of ≤25. Logistic regression was performed to build a nomogram for predicting a low-risk subgroup of the ODX assay. RESULTS: Multivariate analysis revealed that estrogen receptor (ER) score, progesterone receptor (PR) score, histologic grade, lymphovascular invasion (LVI), and Ki-67 had a statistically significant association with the low-risk subgroup. With these variables, we developed a nomogram to predict the low-risk subgroup with ODX recurrence scores of ≤25. The area under the receiver operating characteristic curve was 0.90 (95% confidence interval [CI], 0.85 to 0.96). When applied to the validation group the nomogram was accurate with an area under the curve = 0.88 (95% CI, 0.83 to 0.95). CONCLUSION: The low ODX recurrence score subgroup can be predicted by a nomogram incorporating five traditional prognostic factors: ER, PR, histologic grade, LVI, and Ki-67. Our nomogram, which predicts a low-risk ODX recurrence score, will be a useful tool to help select patients who may or may not need additional ODX testing.

No Association of Positive Superficial and/or Deep Margins with Local Recurrence in Invasive Breast Cancer Treated with Breast-Conserving Surgery / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the effect of positive superficial and/or deep margin status on local recurrence (LR) in invasive breast cancer treated with breast-conserving surgery (BCS) followed by radiotherapy. MATERIALS AND METHODS: In total, 3,403 stage 1 and 2 invasive breast cancer patients treated with BCS followed by radiotherapy from January 2000 to December 2008 were included in this study. These patients were divided into three groups according to margin status: clear resection margin status for all sections (group 1, n=3,195); positive margin status in superficial and/or deep sections (group 2, n=121); and positive peripheral parenchymal margin regardless of superficial and/or deep margin involvement (group 3, n=87). The LR-free survival between these three groups was compared and the prognostic role of margin status was analyzed. RESULTS: Across all groups, age, tumor size, nodal status, and human epidermal growth factor receptor 2 status did not significantly differ. High grade, positive extensive intraductal component, hormone receptor positivity, hormone therapy received, and chemotherapy not received were more prevalent in groups 2 and 3 than in group 1. Five-year LR rates in groups 1, 2, and 3 were 1.9%, 1.7%, and 7.7%, respectively. Multivariate analysis revealed that group 3 was a significant predictor for LR (hazard ratio [HR], 4.78; p < 0.001), but that positive superficial and/or deep margin was not (HR, 0.66; p=0.57). CONCLUSION: Superficial and/or deep margin involvement following BCS is not an important predictor for LR.

Predicting Successful Conservative Surgery after Neoadjuvant Chemotherapy in Hormone Receptor-Positive, HER2-Negative Breast Cancer

PURPOSE: This study aimed to determine whether clinicopathological factors are potentially associated with successful breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) and develop a nomogram for predicting successful BCS candidates, focusing on those who are diagnosed with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors during the pre-NAC period. METHODS: The training cohort included 239 patients with an HR-positive, HER2-negative tumor (≥3 cm), and all of these patients had received NAC. Patients were excluded if they met any of the following criteria: diffuse, suspicious, malignant microcalcification (extent >4 cm); multicentric or multifocal breast cancer; inflammatory breast cancer; distant metastases at the time of diagnosis; excisional biopsy prior to NAC; and bilateral breast cancer. Multivariate logistic regression analysis was conducted to evaluate the possible predictors of BCS eligibility after NAC, and the regression model was used to develop the predicting nomogram. This nomogram was built using the training cohort (n=239) and was later validated with an independent validation cohort (n=123). RESULTS: Small tumor size (p < 0.001) at initial diagnosis, long distance from the nipple (p=0.002), high body mass index (p=0.001), and weak positivity for progesterone receptor (p=0.037) were found to be four independent predictors of an increased probability of BCS after NAC; further, these variables were used as covariates in developing the nomogram. For the training and validation cohorts, the areas under the receiver operating characteristic curve were 0.833 and 0.786, respectively; these values demonstrate the potential predictive power of this nomogram. CONCLUSION: This study established a new nomogram to predict successful BCS in patients with HR-positive, HER2-negative breast cancer. Given that chemotherapy is an option with unreliable outcomes for this subtype, this nomogram may be used to select patients for NAC followed by successful BCS.

Chronological Improvement in Survival of Patients with Breast Cancer: A Large-Scale, Single-Center Study / 한국유방암학회지

PURPOSE: This study aimed to chronologically evaluate survival of patients with breast cancer in Korea and investigate the observed changes during the last 20 years. We also sought to determine factors that may influence outcomes and changes in the duration of survival over time. METHODS: We retrospectively analyzed a total of 10,988 patients with breast cancer who were treated at our institution between January 1993 and December 2008. We divided the study period into three periods (P1, 1993–1997; P2, 1998–2002; and P3, 2003–2008). We retrospectively reviewed the collected data from the Asan database, including age at diagnosis, clinical manifestations, pathology report, surgical methods, types of adjuvant treatment modalities, type of recurrence, and follow-up period. RESULTS: At a median follow-up of 8.2 years, we observed that survival outcomes have improved recently. The 5-year breast cancer-specific survival (BCSS) rate also increased from 82.8% in P1 to 92.6% in P3 (p < 0.001). The survival rate in patients with tumors at each stage increased in similar patterns in all patients, and, remarkably, there was a significant survival improvement in patients with stage III breast cancer (P1 vs. P3: 5-year BCSS, 57.4% vs. 80.0%, p < 0.001). The time period was a significant prognostic factor in multivariate analysis (P1 vs. P2: hazard ratio [HR], 0.83, p=0.035; P1 vs. P3: HR, 0.75, p=0.015). CONCLUSION: The study results suggest an improvement in breast cancer survival in Korea, which is consistent with the development of treatments and early detection.

Clinicopathologic Characteristics of Pregnancy-Associated Breast Cancer: Results of Analysis of a Nationwide Breast Cancer Registry Database / 한국유방암학회지

PURPOSE: This study aimed to evaluate the clinicopathological characteristics of pregnancy-associated breast cancer (PABC) in comparison with non-pregnancy associated breast cancer (non-PABC). METHODS: A total of 344 eligible patients with PABC were identified in the Korean Breast Cancer Society Registry database. PABC was defined as ductal carcinoma in situ, invasive ductal carcinoma, or invasive lobular carcinoma diagnosed during pregnancy or within 1 year after the birth of a child. Patients with non-PABC were selected from the same database using a 1:2 matching method. The matching variables were operation, age, and initial stage. RESULTS: Patients with PABC had significantly lower survival rates than patient with non-PABC (10-year survival rate: PABC, 76.4%; non-PABC, 85.1%; p=0.011). PABC patients had higher histologic grade and were more frequently hormone receptor negative than non-PABC patients. Being overweight (body mass index [BMI], ≥23 kg/m²), early menarche (≤13 years), late age at first childbirth (≥30 years), and a family history of breast cancer were more common in the PABC group than in the non-PABC group. Multivariate analysis showed the following factors to be significantly associated with PABC (vs. non-PABC): early menarche (odds ratio [OR], 2.165; 95% confidence interval [CI], 1.566–2.994; p<0.001), late age at first childbirth (OR, 2.446; 95% CI, 1.722–3.473; p<0.001), and being overweight (OR, 1.389; 95% CI, 1.007–1.917; p=0.045). CONCLUSION: Early menarche, late age at first childbirth, and BMI ≥23 kg/m² were more associated with PABC than non-PABC.

Effects of Less than 60 Days Delay in Surgery on Tumor Progression and Survival Outcomes in Invasive Breast Cancer Patients

PURPOSE: The effect of delays in surgical treatment on survival outcomes in patients with breast cancer remains uncertain, but it is an issue of importance to both patients and clinicians. The purpose of this study was to determine the impact of delayed surgical treatment on survival and tumor progression such as changes in tumor size and lymph node metastasis. METHODS: Among 1,219 patients who underwent breast cancer surgery at Asan Medical Center between January 2008 and December 2008, 1,074 patients were finally included in the study following the application of inclusion and exclusion criteria. Patients were divided into two groups based on the interval between diagnosis and surgery: ≤30 days (group 1) and >30 days (group 2). We retrospectively analyzed clinical characteristics, changes in tumor size and axillary lymph-node status, and overall survival (OS) and disease-free survival (DFS) rates. RESULTS: Between group 1 and group 2, there were no differences in clinical characteristics or in changes in tumor size between findings based on ultrasonography (USG) with biopsy at diagnosis and pathologic results (p=0.134). Furthermore, changes in tumor size and lymph-node status between USG results at Asan Medical Center and pathologic results also showed no differences (p=0.249 and p=0.233, respectively). There were also no significant differences in DFS (p=0.395) or OS (p=0.813). CONCLUSION: Our study showed that short-term delays of ≤2 months between diagnosis and surgery for breast cancer do not negatively affect cancer progression or survival rates.

Survival Outcome of Combined GnRH Agonist and Tamoxifen Is Comparable to That of Sequential Adriamycin and Cyclophosphamide Chemotherapy Plus Tamoxifen in Premenopausal Patients with Lymph-Node–Negative, Hormone-Responsive, HER2-Negative, T1-T2 Breast C / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to compare treatment outcomes between combined gonadotropin-releasing hormone agonist and tamoxifen (GnRHa+T) and sequential adriamycin and cyclophosphamide chemotherapy and tamoxifen (AC->T) in premenopausal patients with hormone-responsive, lymph-node–negative breast cancer. MATERIALS AND METHODS: In total, 994 premenopausal women with T1-T2, lymph-node–negative, hormone-receptor-positive, HER2-negative breast cancer between January 2003 and December 2008 were included in this retrospective cohort study. GnRHa+T and AC->T were administered to 608 patients (61.2%) and 386 patients (38.8%), respectively. Propensity score matching and inverse probability weighting were applied to the original cohort, and 260 patients for each treatment arm were included in the final analysis. Recurrence-free, cancer-specific, and overall survival was compared between the two treatment groups. RESULTS: A total of 994 patients were followed up for a median of 7.4 years (range, 0.5 to 11.4 years). The 5-year follow-up rate was 98.7%, and 13 patients were lost to follow-up. In propensity-matched cohorts (n=520), there was no difference in recurrence-free, cancer-specific, and overall survival rates between the two treatment groups (p=0.306, p=0.212, and p=0.102, respectively), and this was maintained after applying inverse probability weighting. CONCLUSION: GnRHa+T is a reasonable alternative to AC->T in patients with premenopausal, hormone-responsive, HER2-negative, lymph-node–negative, T1-T2 breast cancer.

Measurement of Depression in Breast Cancer Patients by Using a Mobile Application : A Feasibility and Reliability Study / 신경정신의학

OBJECTIVES: This study examined feasibility and reliability of a mobile application to measure depression in breast cancer patients. METHODS: Forty-two breast cancer patients from the Department of Surgery at Asan Medical Center were included in the study. The Beck Depression Inventory (BDI), EuroQol Five Dimensional Questionnaire, and EuroQol Visual Analogue Scale were assessed at baseline and twice after surgery at regular intervals. The Patient Health Questionnaire-9 (PHQ-9) was delivered by as a push notification via mobile application every two weeks for 12 months. Feasibility was calculated using number of respondents and total number of PHQ-9 completed. Reliability was calculated from the relationship between PHQ-9 and BDI scores obtained within each two week period. Agreement between PHQ-9 and BDI scores in the diagnosis of depression was evaluated by kappa statistic and McNemar's test. RESULTS: One thousand and ninety-two notifications for PHQ-9 were sent, and 622 responses were reported (compliance rate=57%). The compliance rate was not related to demographic factors except for the date of the first use of the application. Pearson's r between PHQ-9 and BDI scores was 0.599 (p<0.001), and kappa analysis demonstrated moderate level of agreement in diagnosis of depression (κ=0.431). CONCLUSION: The compliance rate for patients reporting their symptoms by mobile application is high and the scores of PHQ-9 and BDI are correlated, which suggests that the mobile data measuring depression is reliable. However, this is a preliminary study and further study is needed to determine other factors that influence compliance rate.

The reality in the follow-up of breast cancer survivors: survey of Korean Breast Cancer Society

PURPOSE: Follow-up after primary treatment for breast cancer is an important component of survivor care and various international guidelines exist for the surveillance. However, little is known about current actual practice patterns of physicians whether they adhere to or deviate from recommended guidelines. The aim of this study was to determine how physicians follow-up their patients after primary treatment for breast cancer in Korea. METHODS: A questionnaire survey with 34 questions in 4 categories was e-mailed to the members of Korean Breast Cancer Society from November to December 2013. Respondents were asked how they use follow-up modalities after primary treatment of breast cancer and we compared the survey results with present guidelines. RESULTS: Of the 129 respondents, 123 (95.3%) were breast surgeons. The most important consideration in follow-up was tumor stage. History taking, physical examinations, and mammography were conducted in similar frequency recommended by other guidelines while breast ultrasonography was performed more often. The advanced imaging studies such as CT, MRI, and bone scan, which had been recommended to be conducted only if necessary, were also examined more frequently. Regular screenings for secondary malignancy were performed in 38 respondents (29.5%). Five years later after primary treatment, almost the whole respondents (94.6%) themselves monitored their patients. CONCLUSION: A majority of respondents have been performed more intensive follow-up modalities in comparison with present guidelines and less frequently screenings for secondary malignancy. For optimal follow-up of breast cancer survivors, tailored delivery system should be considered.

Concurrent Gonadotropin-Releasing Hormone Agonist Administration with Chemotherapy Improves Neoadjuvant Chemotherapy Responses in Young Premenopausal Breast Cancer Patients / 한국유방암학회지

PURPOSE: This study aimed to determine the oncologic efficacy of gonadotropin-releasing hormone (GnRH) agonist treatment concurrent with chemotherapy in a neoadjuvant setting. METHODS: A retrospective analysis was performed on 332 cases of invasive breast cancer in patients who were <40 years old at diagnosis and received GnRH agonists concurrent with neoadjuvant chemotherapy (GnRH agonist group) or neoadjuvant chemotherapy alone (neochemotherapy-alone group) from December 2010 to September 2014. Pathologic complete response rates (pCR) and Ki-67 changes were evaluated between the two groups. RESULTS: Median age was 32+/-3.9 and 36+/-3.0 years in the GnRH agonist group and neochemotherapy-alone group, respectively (p<0.001). After adjustment for tumor size, grade, lymph node metastasis, hormone receptor (HR) status, and chemotherapy regimen, the GnRH agonist group exhibited a higher pCR rate with an odds ratio (OR) of 2.98 (95% confidence interval [CI], 1.37-6.34) and a greater decrease in Ki-67 expression after treatment (p=0.05) than the neochemotherapy-alone group. For HR-negative tumors, the GnRH agonist group showed a higher pCR rate (multivariate OR, 3.50; 95% CI, 1.37-8.95) and a greater decrease in Ki-67 expression (p=0.047). For HR-positive breast cancer, the pCR rate, change in Ki-67 index, and clinical response were higher, and preoperative endocrine prognostic index scores were lower, in the GnRH agonist group, but these did not reach statistical significance. CONCLUSION: Concurrent administration of GnRH agonists during neoadjuvant chemotherapy improved pCR rates and suppressed Ki-67 expression, especially in HR-negative tumors.

Reliability of the Percent Density in Digital Mammography with a Semi-Automated Thresholding Method / 한국유방암학회지

PURPOSE: The reliability of the quantitative measurement of breast density with a semi-automated thresholding method (Cumulus(TM)) has mainly been investigated with film mammograms. This study aimed to evaluate the intrarater reproducibility of percent density (PD) by Cumulus(TM) with digital mammograms. METHODS: This study included 1,496 craniocaudal digital mammograms from the unaffected breast of breast cancer patients. One rater reviewed each mammogram and estimated the PD using the Cumulus(TM) method. All images were reassessed by the same rater 1 month later without reference to the previously assigned values. The repeatability of the PD was evaluated by an intraclass correlation coefficient (ICC). All patients were grouped based on their body mass index (BMI), age, family history of breast cancer, breastfeeding history and breast area (calculated with Cumulus(TM)), and subgroup analysis for the ICC of each group was performed. All patients were categorized by their Breast Imaging Reporting and Data System (BI-RADS) density pattern, and the mean and standard deviation of the PD by each BI-RADS categories were compared. RESULTS: The ICC for the PD was 0.94, indicating excellent repeatability. The discrepancy between the paired PD values ranged from 0 to 23.93, with an average of 3.90 (standard deviation=3.39). The subgroup ICCs for the PD ranged from 0.88 to 0.96, indicating excellent reliability in all subgroups regardless of patient variables. The ICCs of the PD for the high-risk (BI-RADS 3 and 4) and low-risk (BI-RADS 1 and 2) groups were 0.90 and 0.88, respectively. CONCLUSION: This study suggests that PD calculated with digital mammograms has an acceptable reliability regardless of patient age, BMI, family history of breast cancer, breastfeeding history, breast size, and BI-RADS density pattern.

A Review of Breast Cancer Survivorship Issues from Survivors' Perspectives / 한국유방암학회지

Despite the fact that more breast cancer survivors are currently enjoying longer lifespans, there remains limited knowledge about the factors and issues that are of greatest significance for these survivors, particularly from their perspectives. This review was based on the concept that the topics addressed should focus on the perspectives of current survivors and should be extended to future modalities, which physicians will be able to use to gain a better understanding of the hidden needs of these patients. We intended to choose and review dimensions other than the pathology and the disease process that could have been overlooked during treatment. The eight topics upon which we focused included: delay of treatment and survival outcome; sexual well-being; concerns about childbearing; tailored follow-up; presence of a family history of breast cancer; diet and physical activity for survivors and their families; qualitative approach toward understanding of breast cancer survivorship, and; mobile health care for breast cancer survivors. Through this review, we aimed to examine the present clinical basis of the central issues noted from the survivors' perspectives and suggest a direction for future survivorship-related research.

Survival Outcomes of Different Treatment Methods for the Ipsilateral Breast of Occult Breast Cancer Patients with Axillary Lymph Node Metastasis: A Single Center Experience / 한국유방암학회지

PURPOSE: This study compared the survival outcomes of different treatment methods for the ipsilateral breast of occult breast cancer (OBC) patients with axillary lymph node metastasis. METHODS: A retrospective study was conducted in which forty OBC patients with axillary lymph node metastasis were identified out of 15,029 patients who had been diagnosed with a primary breast cancer at between 1992 and 2010. The patients were categorized into three treatment groups based on ipsilateral breast management: breast-conserving surgery (BCS) (n=17), mastectomy (n=12), and nonsurgical intervention with or without radiation therapy (No surgery with or without radiation therapy [No Op+/-RT]) (n=11). All patients underwent axillary lymph node dissection. Cases were evaluated based on treatment and potential prognostic factors with respect to overall survival (OS) and disease-free survival (DFS). RESULTS: During the follow-up period (median follow-up of 71.5 months), the overall OS and DFS were 76.9% and 74.9%, respectively. The 5-year treatment-specific OS was 72.0% for the BCS group, 74.0% for the mastectomy group, and 87.5% for the No Op+/-RT group (log-rank p=0.49). The 5-year DFS was 70.6% for the BCS group, 66.7% for the mastectomy group, and 90.9% for the No Op+/-RT group (log-rank p=0.36). Recurrence rates for the BCS and No Op+/-RT groups were 5.9% and 18.2%, respectively. Histologic grade and lymph node status were inversely correlated with DFS (log-rank p=0.04 and p<0.01, respectively). CONCLUSION: There was no difference in survival outcomes between the three treatment methods for the ipsilateral breast (mastectomy, BCS, and No Op+/-RT) of OBC patients with axillary lymph node metastasis. A large-scale multicenter study is needed to validate the results from this small retrospective study.

Surgical Outcomes after Total Colectomy with Ileorectal Anastomosis in Patients with Medically Intractable Slow Transit Constipation

PURPOSE: The aim of this study was to evaluate outcomes of a total colectomy with ileorectal anastomosis in patients with slow transit constipation. METHODS: A retrospective review of 37 consecutive patients with slow transit constipation who underwent a total colectomy between 1994 and 2008 was undertaken. Preoperative and postoperative Wexner's constipation scores were collected and used to evaluate the outcomes after surgical treatment. Also patients' postoperative satisfaction scores were collected using a 4-point scale. RESULTS: The 37 patients consisted of 31 women and 6 men, with a median age of 41 years (range, 17 to 71 years). Pre- and post-operative Wexner's scores were collected from 33 patients (89.1%), and the mean preoperative Wexner's score was 19.3 (range, 11 to 24), which decreased to an average post-operative score of 2.3 (range, 0 to 8). Neither intraoperative complications nor postoperative mortalities were noted. Five patients (13.5%) had early postoperative complications, and the most common complication was postoperative ileus (10.8%). Seven patients (18.9%) had late postoperative complications, and postoperative ileus (10.8%) was also the most common. Twenty seven of 33 patients were satisfied with their surgical outcome (81.8%). CONCLUSION: A total colectomy with ileorectal anastomosis might be an effective surgical procedure with acceptable morbidity to treat medically intractable slow transit constipation.