Excision Can Be Delayed until Size Grows in Small Papillary Lesions of the Breast

Purpose@#The management of intraductal papilloma (IDP) without atypia remains controversial. This study evaluated the manifestations and incidence of malignancy during observation without surgery in patients diagnosed with IDP by core needle biopsy (CNB), to confirm whether close follow-up instead of surgical treatment is the preferred treatment option in selected patients. @*Methods@#We retrospectively reviewed the data of 589 patients diagnosed with IDP by CNB between January 2009 to December 2018. The data of the 102 IDP lesions from 90 women who did not undergo immediate excision were analyzed. Of these, 84 patients received imaging follow-up without excision, while 18 patients underwent delayed excision during follow-up. @*Results@#During the median follow-up period of 18.6 months, the mean change in tumor size and mean percent change in tumor size were −0.06 cm and −0.22%, respectively. Delayed excision was performed in 18 patients (17.6%). In the delayed excision group, three (16.7%) patients and one (5.6%) patient were diagnosed with atypical papilloma and intraductal papillary carcinoma, respectively, based on the final pathological findings. The upstaged group (atypia and malignancy; four patients) showed a 62.0% increase in the tumor size, which is higher than the benign group that showed a 10.4% increase in tumor size. However, the difference was not statistically significant (p=0.185). @*Conclusion@#Observation without excision is possible for small IDP without atypia, because of the minimal changes in tumor size and low incidence of malignancy after excision. However, to avoid a missed diagnosis of malignancy, excision should be considered if the lesion increases in size during follow-up.

Nomogram for accurate prediction of breast and axillary pathologic response after neoadjuvant chemotherapy in node positive patients with breast cancer

PURPOSE: Many patients with cytology proven node-positive breast cancer receive a neoadjuvant chemotherapy (NAC) treatment. We developed a nomogram to predict the breast and axillary pathologic complete responses (pCR) in patients with a cytologically proven axillary node positive breast cancer with NAC. METHODS: We selected 995 patients who were diagnosed with an invasive breast cancer and axillary lymph nodes metastasis, and who were treated with NAC followed by a curative surgery at the Samsung Medical Center between January 2007 and December 2014. The baseline patient and tumor characteristics, chemotherapy regimen, and tumor and nodal responses were thoroughly analyzed and reviewed. A nomogram was developed using a binary logistic regression model with a cross validation. RESULTS: Axillary pCR was achieved in 47.3% and breast pCR was achieved in 24.3% of the patients after NAC. In this case, the both pCR was associated with an initial clinical tumor stage, negative progesterone receptor status, positive human epidermal growth factor receptor 2 status, and clinical radiologic nodal responses. A nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (area under the curve [AUC], 0.868; 95% confidence interval, 0.84–0.89) and calibration fit as noted in that case. The cross validation had an average AUC 0.853 (0.837–0.869). CONCLUSION: Our nomogram might help to predict breast and axillary pCRs after NAC in patients with an initially node-positive breast cancer. Minimal surgery might be acceptable in patients for whom the nomogram indicates a high probability of achieving pCRs.

Use of Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Patients with Axillary Node-Positive Breast Cancer in Diagnosis / 한국유방암학회지

PURPOSE: This study aimed to evaluate the effects of sentinel lymph node biopsy (SLNB) on recurrence and survival after neoadjuvant chemotherapy (NAC) in breast cancer patients with cytology-proven axillary node metastasis. METHODS: We selected patients who were diagnosed with invasive breast cancer and axillary lymph node metastasis and were treated with NAC followed by curative surgery between January 2007 and December 2014. We classified patients into three groups: group A, negative sentinel lymph node (SLN) status and no further dissection; group B, negative SLN status with backup axillary lymph node dissection (ALND); and group C, no residual axillary metastasis on pathology with standard ALND. RESULTS: The median follow-up time was 51 months (range, 3–122 months) and the median number of retrieved SLNs was 5 (range, 2–9). The SLN identification rate was 98.3% (234/238 patients), and the false negative rate of SLNB after NAC was 7.5%. There was no significant difference in axillary recurrence-free survival (p=0.118), disease-free survival (DFS; p=0.578) or overall survival (OS; p=0.149) among groups A, B, and C. In the subgroup analysis of breast pathologic complete response (pCR) status, there was no significant difference in DFS (p=0.271, p=0.892) or OS (p=0.207, p=0.300) in the breast pCR and non-pCR patients. CONCLUSION: These results suggest that SLNB can be feasible and oncologically safe after NAC for cytology-determined axillary node metastasis patients and could help reduce arm morbidity and lymphedema by avoiding ALND in SLN-negative patients.

Patterns of Axillary Lymph Node Metastasis in Breast Cancer: A Prospective Single-Center Study / 한국유방암학회지

PURPOSE: The recent trend in breast cancer treatment is to minimize axillary dissection. However, no pattern of axillary metastasis has been precisely established. The purpose of this study was to evaluate the metastatic lymphatic pattern using near-infrared fluorescence imaging with indocyanine green (ICG) in breast cancer with cytologically proven axillary metastasis. METHODS: This was a prospective single-center study. We evaluated 147 patients with breast cancer involving cytologically proven axillary metastasis, and compared physiological and nonphysiological lymphatic metastasis. RESULTS: We performed lymphatic mapping for 64 patients who exhibited level II lymphatic flow on near-infrared fluorescence imaging with ICG, and found that all had axillary metastasis: 51 patients who did not receive neoadjuvant chemotherapy (NAC) and 13 patients post-NAC. Of patients who did not receive NAC, 32 had physiological lymphatic metastasis and 19 had nonphysiological lymphatic metastasis. The risk factors for nonphysiological lymphatic metastasis were age ≥55 years, high Ki-67 index (>20%), and perinodal extension in both univariate and multivariate analysis (p < 0.05). CONCLUSION: Patients with identified risk factors in cytologically-proven axillary metastasis who did not receive NAC may have nonphysiological lymphatic metastasis.

Erratum: Development of a Nomogram to Predict N2 or N3 Stage in T1-2 Invasive Breast Cancer Patients with No Palpable Lymphadenopathy / 한국유방암학회지

This article was initially published on the Journal of Breast Cancer with a misspelled the name of third author.

Necessity of In Situ Hybridization Test of Human Epidermal Growth Factor Receptor 2 (HER2) Status in Breast Cancer Patients with Equivocal HER2 Immunohistochemistry Results

PURPOSE: Accurate human epidermal growth factor receptor 2 (HER2) status is important in predicting prognosis and providing treatment for HER2-positive breast cancer patients. However, performing in situ hybridization (ISH) can be an economic burden on developing countries. This study aimed to find an alternative to the ISH test by predicting the HER2 status in patients with equivocal immunohistochemistry (IHC) results. METHODS: We retrospectively reviewed the clinical data of 15,535 patients who underwent curative surgery for invasive breast cancer between February 2005 and April 2015 at the Samsung Medical Center. Equivocal HER2 IHC results were obtained for 461 patients. Logistic regression analysis using stepwise selection was performed to identify the clinicopathological factors related to silver in situ hybridization (SISH) status. We analyzed the data by dividing the estrogen receptor and progesterone receptor (PR) into three groups according to Allred score. RESULTS: Multivariable analysis identified poorly differentiated histological grade, lower PR score, higher expression of Ki-67 and p53, and lower expression of cytokeratin 5/6 and epidermal growth factor receptor as predictors of SISH-positive results. The area under the curve for the receiver-operating characteristic curve was 0.74. CONCLUSION: We identified factors related to a positive HER2 status by SISH. However, there was insufficient power in the prediction model for diagnosis and evaluation. Therefore, the SISH test is essential in determining the HER2 status of breast cancer patients when the IHC result is equivocal.

Prognostic Validation of the American Joint Committee on Cancer 8th Staging System in 24,014 Korean Patients with Breast Cancer / 한국유방암학회지

PURPOSE: The American Joint Committee on Cancer (AJCC) recently released the breast cancer staging system, 8th edition, which included additional four biologic factors. However, there has been no external validation of the prognostic value of the new stages with different population-based databases. METHODS: To validate the prognostic value of the new staging system in the Asian population, with a focus on Korean patients with breast cancer, we performed a retrospective study with data from the Korean Breast Cancer Society that included 24,014 patients with invasive ductal or lobular carcinoma who underwent surgery between January 2009 and January 2012 in Korea. The proportional differences were evaluated between the anatomic staging system (AJCC 7th edition) and the prognostic staging system (AJCC 8th edition, December 2017 published version). Comparisons of overall survival (OS) and disease-free survival (DFS) with Kaplan-Meier graphs and hazard ratios were also performed. RESULTS: Our analysis included 24,014 patients (median age, 50 years; range, 20–91 years). Stage I, II, and III disease accounted for 47.6%, 43.5%, and 8.9%, respectively, of anatomic stages and 61.8%, 27.6%, and 10.8%, respectively, of clinical prognostic stages. A total of 6,272 cases (26.1%) were upstaged, 4,656 (19.4%) were downstaged, and 13,086 (54.5%) remained unchanged. OS and DFS decreased in the order from prognostic stages IA to IIIC but did not change among the anatomic stage groups. CONCLUSION: Our data suggests that the prognostic staging system provides superior prognostic value to the anatomic staging system in Korean patients with breast cancer.

Verification of a Western Nomogram for Predicting Oncotype DX™ Recurrence Scores in Korean Patients with Breast Cancer / 한국유방암학회지

A recent study conducted at the University of Tennessee Medical Center using a large dataset from the National Cancer Database (NCDB) reported the use of nomograms for predicting Oncotype DX™ (ODX) scores with clinicopathologic data. We reviewed the data of 218 patients who underwent the ODX test at a single institution in Korea to confirm that nomograms can accurately predict ODX score groups using our data, which differ from those of the NCDB in terms of ethnicity. The concordance index (c-index) of nomograms was much lower than that of the University of Tennessee Medical Center for high- and low-risk groups of commercial ODX and Trial Assigning Individualized Options for Treatment values. Although the nomogram for predicting ODX scores was based on a large dataset, it could not be generalized to patients in Asia. Further studies using large datasets of patients from different ethnicities should be performed to develop a nomogram applicable to patients worldwide.

Comparison of Core Needle Biopsy and Surgical Specimens in Determining Intrinsic Biological Subtypes of Breast Cancer with Immunohistochemistry / 한국유방암학회지

PURPOSE: We evaluated the concordance between core needle biopsy (CNB) and surgical specimens on examining intrinsic biological subtypes and receptor status, and determined the accuracy of CNB as a basic diagnostic method. METHODS: We analyzed breast cancer patients with paired CNB and surgical specimen samples during 2014. We used monoclonal antibodies for nuclear staining, and estrogen receptor (ER) and progesterone receptor (PR) status evaluation. A positive test was defined as staining greater than or equal to 1% of tumor cells. Human epidermal growth factor receptor 2 (HER2) was graded by immunohistochemistry and scored as 0 to 3+ according to the recommendations of the American Society of Clinical Oncology/College of American Pathologists. Ki-67 immunostaining was performed using the monoclonal antibody Ki-67, and the results were divided at 10% intervals. The cutoff value for high Ki-67 was defined as 20%. Concordance analysis of ER, PR, HER2, Ki-67, and five intrinsic biological subtypes was performed on CNB and surgical specimens. Statistical analysis for concordance was calculated using κ-tests. RESULTS: We found very good agreement for ER and PR with a concordance of 96.7% for ER (κ=0.903), and 94.3% for PR (κ=0.870). HER2 and Ki-67 showed concordance rates of 84.8% (κ=0.684) and 83.5% (κ=0.647), respectively, which were interpreted as good agreement. Five subgroups analysis showed 85.8% agreement and κ-value of 0.786, also indicating good agreement. CONCLUSION: CNB showed high diagnostic accuracy compared with surgical specimens, and good agreement for ER, PR, HER2, and Ki-67. Our findings reaffirmed the recommendation of CNB as an initial procedure for breast cancer diagnosis, and the assessment of receptor status and intrinsic biological subtypes to determine further treatment plans.

Fertility Rates in Young Korean Breast Cancer Patients Treated with Gonadotropin-Releasing Hormone and Chemotherapy / 한국유방암학회지

PURPOSE: Gonadotropin-releasing hormone (GnRH) agonists have been used with adjuvant chemotherapy to protect ovarian function. However, there are no data on the actual pregnancy rates among young breast cancer patients receiving GnRH agonists and concurrent chemotherapy in Korea. METHODS: Among patients who underwent surgery from January 2002 to April 2012, premenopausal patients aged between 20 and 40 years were included in the analysis. We retrospectively reviewed clinicopathologic features (e.g., age, obstetric and menstruation history), recurrence, and survival status. The rate of resumption of menstruation was calculated in all patients. In the married group, pregnancy and delivery rates were also recorded. RESULTS: Among 101 patients, 19 were lost to follow-up and 82 were eligible for the analysis. Among them, 31 were married, 10 of 51 got married, and 41 remained unmarried through the follow-up period. Among the married patients, 15 became pregnant and gave birth to 19 babies, whereas 26 did not become pregnant. The pregnancy rate in the married group was 50.0% (15/30). Three of 15 pregnancies (20.0%) were multiparous. Most of the delivered babies were healthy and 80.0% of patients had no problems breastfeeding (12/15). More than half the patients in all groups recovered menstrual status within 12 months. CONCLUSION: Fifty percent of young breast cancer patients who attempted pregnancy succeeded in pregnancy after adjuvant chemotherapy and GnRH agonists. Further studies that include control groups are required to confirm whether the use of GnRH agonists improves pregnancy.

Development of a Nomogram to Predict N2 or N3 Stage in T1–2 Invasive Breast Cancer Patients with No Palpable Lymphadenopathy / 한국유방암학회지

PURPOSE: Subsequent to the American College of Surgeons Oncology Group (ACOSOG) Z0011 and After Mapping of the Axilla: Radiotherapy or Surgery (AMAROS) trials, complete axillary lymph node dissection is not routinely performed, even in cases where metastatic sentinel lymph nodes are detected. We investigated the percentage of N2 or N3 stages in T1–2 invasive breast cancer patients with no lymphadenopathy and developed a nomogram to predict the possibility of N2 or N3 stages in these patients. METHODS: We retrospectively reviewed the charts of invasive breast cancer patients who were clinically N0 stage, but had a positive sentinel or non-sentinel lymph node detected on sentinel lymph node biopsy. The association of potential risk factors with known outcomes (N2 or N3 stages) was tested using logistic regression analysis. Variables with p<0.05 in the multivariate analysis were included in the nomogram. Internal performance validation was carried out using a 5-fold cross validation method. RESULTS: Among a total of 1,437 patients, 1,355 patients had stage N1 disease (94.3%), while 82 had stage N2 or N3 disease (5.7%). Multivariate stepwise logistic regression analysis revealed lymphovascular invasion (p=0.008), T2 stage (p=0.026), metastatic lymph node ratio (p<0.001), and perinodal extension (p<0.001) as independent predictors of N2 or N3 stages. A nomogram was developed based on these factors. The area under the curve estimated from the receiver operating characteristic graph was 0.8050 in the model set and 0.8246 in the test set. CONCLUSION: Our nomogram can be employed for the prediction of N2 or N3 stage among cases fulfilling the ACOSOG Z0011 or AMAROS criteria.

Comparison of Prognosis according to Tumor Size in Small Breast Cancer with Lymph Node Involvement

PURPOSE: Larger tumor size and more extensive lymph node (LN) involvement have been considered independent factors for poor prognosis of breast cancer. We evaluated whether smaller tumor size may be a factor of worse prognosis compared with larger tumor size in small-sized breast cancer with LN involvement. METHODS: A retrospective analysis was conducted at a single center for 1,400 patients with small-sized (≤2 cm) and LN involved (N1–N3) breast cancer who underwent radical surgery, had no distant metastases, and were diagnosed between 2004 and 2014. We subdivided their tumor size into four subgroups (T1mi, T1a, T1b, T1c) graded using the 7th American Joint Committee on Cancer staging and two subgroups (T1ab [≤1 cm] and T1c [>1 cm]) divided by tumor size. The relationship between tumor size, prognosis and specific features were analyzed using the Chi-square test, Kaplan-Meier method, and Cox regression analysis. RESULTS: There were significant differences in estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2) and HER2 amplified type among the four subgroups in all patients. Especially, HER2-amplified type also appeared in distribution significantly between the two subgroups in all patients (T1ab [13.0%] vs. T1c [8.0%], p=0.008). The overall survival of the T1N1 staged patients in the smaller-sized tumor group (T1ab) was lower than that of those in the larger-sized group (T1c) (p=0.005). In the multivariate Cox regression analysis of all patients, the T1ab group showed a higher mortality risk compared with the T1c group (adjusted hazard ratio, 2.540; 95% confidence interval, 1.195–5.397; p=0.015). CONCLUSION: Smaller-sized tumors with LN involvement indicated worse prognosis compared with larger-sized tumors.