Isaac Kim

Adjuvant endocrine therapy alone in patients with node-positive, luminal A type breast cancer

Abstract Luminal A breast cancer has a much better prognosis than other subtypes, with a low risk of local or regional recurrence. However, there is controversy around under- versus overtreatment with regard to adjuvant treatment of node-positive, luminal A breast cancer. The purpose of this study was to identify whether adjuvant systemic chemotherapy has any benefit in node-positive, luminal A breast cancer and to evaluate feasibility of endocrine therapy without chemotherapy in this group. This was a retrospective study of 11,025 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between January 2004 and December 2013. Luminal A subtype was defined as ER+, HER2-, and Ki-67 < 14%. We compared AC based (AC: doxorubicin or epirubicin, plus cyclophosphamide) adjuvant chemotherapy versus endocrine therapy without chemotherapy in patients with node-positive, luminal A breast cancer. We performed 1: n matching, with a maximum n of 8 on endocrine therapy group (n = 50) to chemotherapy group (n = 642). The median age of the patients in each group at the time of surgery was 58.3 ± 9.5 years in the chemotherapy group and 58.7 ± 11.7 in the endocrine therapy only group. The median follow-up time was 51.9 months (range, 1–125 months). In multivariable analysis, omission of adjuvant chemotherapy in luminal A cancer had no influence on OS and DFS. Axillary lymph node metastasis and progesterone receptor (PR) status were significantly different between the endocrine therapy alone group and the chemotherapy group in terms of OS. Nuclear grade, PR status, and adjuvant radiotherapy were significantly different between the endocrine therapy alone group and the chemotherapy group with regard to DFS. In survival analysis, there were no differences in OS (P = .137) and DFS (P = .225) between the 2 groups. Adjuvant chemotherapy could provide little benefit to postmenopausal patients with luminal A, node-positive breast cancer, and endocrine therapy alone may help reduce morbidity. Future studies with a large number of patients and longer follow-up time are necessary to determine whether chemotherapy might be avoided in this patient population.

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

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.

Oncologic Safety of Immediate Breast Reconstruction in Breast Cancer Patients Who Underwent Neoadjuvant Chemotherapy: Short-Term Outcomes of a Matched Case–Control Study

Introduction: Although the indication for immediate breast reconstruction (IBR) after skin‐sparing mastectomy (SSM) or nipple‐sparing mastectomy (NSM) has been expanded, IBR after neoadjuvant chemotherapy (NACT) is still controversial. We conducted retrospective matched case–control study to analyze oncologic outcomes between patients who underwent TM only and those who underwent IBR after SSM or NSM after NACT. Patients and Methods: A retrospective review of breast cancer patients who underwent IBR after SSM or NSM after NACT between 2008 and 2015 at a single center was conducted. These cases were maximally matched by 1:5 to patients who underwent total mastectomy (TM) alone after NACT. Matching variables included age, clinical T and N stage before NACT, response to NACT, and pathologic stage after NACT. Pathologic stage followed the 7th edition of the American Joint Committee on Cancer (AJCC) classification. Results: Overall, 31 patients were enrolled onto the IBR after SSM or NSM group (study group) and matched to 85 patients (control group). In the study group, 13 patients (41.9%) underwent NSM and 18 (58.1%) underwent SSM. Median follow‐up duration was 29.2 (range, 7–31) and 38.8 (range, 11–85) months for the study and control groups (P = .012), respectively, and median age was 37.0 (range, 26–57) and 40.0 (range, 24–56) years (P = .890), respectively. Overall survival (P = .971), disease‐free survival (P = .520), distant metastasis‐free survival (P = .795), and local recurrence‐free survival (P = .628) did not differ significantly between the 2 groups. Conclusion: IBR after SSM or NSM might be a feasible surgical treatment option even in breast cancer patients who underwent NACT. Micro‐Abstract: We analyzed oncologic outcome by matching variables including age and clinical T and N stage before immediate breast reconstruction (IBR) after neoadjuvant chemotherapy (NACT), response to NACT, and pathologic stage after NACT. IBR after skin‐sparing mastectomy or nipple‐sparing mastectomy may be a feasible surgical treatment option even in breast cancer patients who underwent NACT.

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

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.

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

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

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.

Only estrogen receptor “positive” is not enough to predict the prognosis of breast cancer

PurposeBeginning in 2018, biomarkers including estrogen receptor (ER) status were incorporated in the 8th AJCC staging system. ER expression levels were not considered in these changes. We hypothesized that the levels of ER expression could affect the prognosis of breast cancer.MethodsA retrospective review was conducted to identify all female patients with invasive breast cancer between 2003 and 2012. ER negative (group I), weakly ER-positive (group II), and strongly ER-positive (group III) were defined as Allred total scores of 0–2, 3–5, and 6–8, respectively. We examined a multigene panel, designated the BCT score, which is a newly developed prognostic model for predicting the risk of a distant metastasis.ResultsAmong the 4949 patients enrolled in this study, 1310 (26.5%), 361 (7.3%), and 3277 (66.2%) were categorized as group I, II, and III, respectively. Median F/U duration was 57.8 months. Compared to group III, patients in group II were younger, had larger tumors, and were also more likely to have PR-negative tumors, HER-2 amplification, high Ki-67, and high nuclear grade. Between group II and III, there was a significant difference in OS (P = 0.0764, 0.909, and 0.010, respectively). After adjusting for additional factors that may affect OS, the HR for OS showed higher in group II than in group III. The baseline median BCT score indicated that lower ER expression was associated with significantly higher BCT score (P < 0.0001) and significantly more likely to have high risk group (P < 0.0001) relative to higher levels of ER expression group.ConclusionER expression levels affect the prognosis of breast cancer. The risk for patients with weakly ER-positive breast cancer should not be underestimated.

Conditional disease-free survival among patients with breast cancer.

Abstract Conditional disease-free survival (CDFS) reflects changes over time. Because traditional disease-free survival (DFS) is estimated from the date of diagnosis, it is limited in the ability to predict risk of recurrence in patients who have been disease free. In this study, we determined CDFS of breast cancer patients and estimated the prognostic factors for DFS. We retrospectively reviewed clinical data of 7587 consecutive patients who underwent curative surgery for breast cancer between January 2004 and December 2013 at Samsung Medical Center. Univariate and multivariate analyses were performed to identify risk factors for DFS, which was computed using the Kaplan–Meier method. CDFS rates were based on cumulative DFS estimates. Median follow-up duration was 20.59 months. Three-year DFS was 93.46% at baseline. Three-year CDFS survival estimates for patients who had been disease free for 1, 2, 3, 4, and 5 years after treatment were calculated as 92.84%, 92.37%, 93.03%, 89.41%, and 79.64%, respectively. Three-year CDFS increased continuously each year after 1 year of DFS in hormone receptor (HR)-negative patients but decreased each year in HR-positive patients. In HR-positive patients who are disease free after 3 years, continuous care including surveillance and metastases workup should be considered, although this is not recommended in the current guidelines. On the other hand, the social costs may be reduced in HR-negative patients by extending the surveillance interval. Further studies are needed to identify indicators of DFS prognosis in breast cancer patients.

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

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.

Risk factors affecting breast cancer-related lymphedema: Serial body weight change during neoadjuvant anthracycline plus cyclophosphamide followed by taxane

Micro‐Abstract We investigated the serial change in body weight during neoadjuvant chemotherapy (NAC) and the presence and degree of lymphedema (LE) using a telephone questionnaire assessment of 406 in breast cancer. The increase in body weight during NAC was significant after the second cycle of taxane. The body weight change was more significant in the LE group. Introduction: The aim of our study was to analyze the risk of lymphedema (LE) according to the clinicopathologic factors and to investigate the serial change in body weight during neoadjuvant anthracycline plus cyclophosphamide followed by taxane and its correlation with the incidence of LE. Patients and Methods: We performed a retrospective 2‐center study of 406 patients who had undergone neoadjuvant chemotherapy (NAC) followed by surgery from 2007 to 2014. The regimen included 4 cycles of anthracycline plus cyclophosphamide, followed by 4 cycles of taxane. We investigated the presence and degree of LE using a telephone questionnaire assessment. Weight changes were calculated at each cycle of NAC, and the baseline and preoperative body weights were used to calculate the rate of change to account for the change in weight before and after NAC. Results: Of the 406 patients, 270 answered the questionnaires, of whom 97 (35.9%) experienced LE. The increase in body weight was significant during the 4 cycles of taxane, but the change in weight was not significant during the 4 cycles of anthracycline plus cyclophosphamide. The change in body weight was most significant just after the fourth cycle of taxane (P < .001). The body mass index (BMI) was an independent factor of LE occurrence on multivariate analysis. However, the change in body weight was not a significant factor for the incidence of LE. Conclusion: Because a BMI ≥ 25 kg/m2 was an independent factor of LE occurrence on multivariate analysis, patients with a preoperative BMI ≥ 25 kg/m2 should be closely monitored for LE given their increased risk, and monitoring and education should be initiated before surgery and continued throughout the course of NAC.