Tailored radiation dose according to margin width for patients with ductal carcinoma in situ after breast-conserving surgery.

A 2 mm resection margin is considered adequate for ductal carcinoma in situ (DCIS). We assessed the effectiveness of a tailored radiation dose for margins < 2 mm and the appropriate margin width for high-risk DCIS. We retrospectively evaluated 137 patients who received adjuvant radiotherapy after breast-conserving surgery for DCIS between 2013 and 2019. The patients were divided into three- positive, close (< 2 mm), and negative (≥ 2 mm) margin groups. Radiation dose to the tumor bed in equivalent dose in 2 Gy fractions were a median of 66.25 Gy, 61.81 Gy, and 59.75 Gy for positive, close, and negative margin groups, respectively. During a median follow-up of 58 months, the crude rates of local recurrence were 15.0%, 6.7%, and 4.6% in the positive, close, and negative margin groups, respectively. The positive margin group had a significantly lower 5-year local recurrence-free survival (LRFS) rate compared to the close and negative margin groups in propensity-weighted log-rank analysis (84.82%, 93.27%, and 93.20%, respectively; p = 0.008). The difference in 5-year LRFS between patients with the high- and non-high-grade tumors decreased as the margin width increased (80.4% vs. 100.0% for margin ≥ 2 mm, p < 0.001; 92.3% vs. 100.0% for margin ≥ 6 mm, p = 0.123). With the radiation dose tailored for margin widths, positive margins were associated with poorer local control than negative margins, whereas close margins were not. Widely clear margins (≥ 2 mm) were related to favorable local control for high-grade DCIS.

Oncologic efficacy of gonadotropin-releasing hormone agonist in hormone receptor-positive very young breast cancer patients treated with neoadjuvant chemotherapy.

BACKGROUND: Breast cancer in young women has been shown to have an aggressive behavior and poor prognosis. AIM: To evaluate the outcomes of young hormone receptor (HR)-positive patients with breast cancer treated with neoadjuvant chemotherapy (NAC), and the oncologic efficacy of gonadotropin-releasing hormone (GnRH) agonists. METHODS: This retrospective study involved a prospectively enrolled cohort. We included patients diagnosed with invasive breast cancer who were treated with NAC followed by curative surgery at the Samsung Medical Center and Samsung Changwon Hospital between January 2006 and December 2017. Among patients with HR-positive and human epidermal grow factor 2 (HER2)-negative breast cancer, we analyzed the characteristics and oncology outcomes between the patients equal to or younger than 35 years and the patients older than 35 years. RESULTS: Among 431 patients with NAC and HR-positive/HER2-negative breast cancer, 78 were 35 years old or younger, and 353 patients were older than 35 years. The median follow-up was 71.0 months. There was no statistically significant difference in disease free survival (DFS, P = 0.565) and overall survival (P = 0.820) between the patients equal to or younger than 35 years and the patients older than 35 years. The two groups differed in that the GnRH agonist was used more frequently in the group of patients equal to or younger than 35 years than in the other group (52.4% vs 11.2%, P < 0.001). Interestingly, for the DFS according to the GnRH agonist in the group of patients equal to or younger than 35 years, patients treated with the GnRH agonist had better DFS (P = 0.037). CONCLUSION: Administration of GnRH agonists might improve the DFS rate of HR-positive/HER2-negative breast cancer in the equal to or younger than 35 years group of patients with NAC.

Effect of high-dose radiation therapy on positive margins after breast-conserving surgery for invasive breast cancer.

PURPOSE: Positive margins after breast-conserving surgery are associated with poor oncological outcomes and warrant additional surgery. This study aimed to evaluate the effectiveness of high-dose radiation therapy for positive margins by comparing local recurrence between patients with positive and negative margins. METHODS: We retrospectively evaluated 550 patients treated with adjuvant radiation therapy after breast-conserving surgery for invasive breast cancer between 2013 and 2019. The total equivalent dose in 2 Gy fractions (EQD2) to the tumor bed ranged from 65.81 to 66.25 Gy for positive margins and 59.31-61.81 Gy for negative margins. The differences in local recurrence between the positive and negative margin groups were analyzed. RESULTS: After a median follow-up of 58 months, the crude local recurrence rate was 7.3% in the positive margin group (n = 55) and 2.4% in the negative margin group (n = 495). Positive margins were associated with higher local recurrence without statistical significance in the entire cohort (p = 0.062). Among patients aged <60 years, those with positive margins had a significantly lower 5-year local recurrence-free survival rate than those with negative margins (89.16% vs. 97.57%, respectively; p = 0.005). In contrast, there was no significant difference in the 5-year local recurrence-free survival rate between patients with positive and negative margins among those aged ≥60 years (100.00% vs. 94.38%, respectively; p = 0.426). CONCLUSION: In this study, positive margins were not associated with poor local control in older patients after a high-dose boosts. Further prospective studies are needed to verify our findings.

Male metaplastic breast cancer with poor prognosis: A case report.

BACKGROUND: Metaplastic breast cancer (MBC) is a rare subtype of breast cancer. They constitute less than 1% of breast cancer cases and are much rarer in males. There are few reports of MBC because of its rarity. MBC, an aggressive type of cancer, is refractory to common treatment modalities of breast cancer and has a poor prognosis. CASE SUMMARY: We report a case of MBC in a 78-year-old man. He visited our clinic with a palpable mass on the left breast with no masses in the axillary areas. He had previously undergone robot-assisted laparoscopic radical prostatectomy for prostate cancer, but there was no family history of malignancy. The breast mass was visible on ultrasonography, mammography, and magnetic resonance imaging, and chest computed tomography revealed a lung mass in the posterior basal segment of the right lower lobe. The patient was diagnosed with metaplastic carcinoma on core needle biopsy with lung metastasis. Total mastectomy with sentinel lymph node biopsy and video-assisted segmentectomy of the right lung was performed. However, multiple metastases appeared 3 mo after surgery in the brain, chest, and abdomen, and the patient died 5 mo after the initial diagnosis. CONCLUSION: MBC is an aggressive and extremely rare breast cancer type. Further case reports are needed to determine the optimal treatment.

Factors Affecting Pathologic Complete Remission in Patients with Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy.

INTRODUCTION: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with improvement in survival outcomes. This study evaluated the pCR in patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer after NAC. METHODS: We evaluated 417 patients who were diagnosed with invasive breast cancer and treated with NAC followed by curative surgery between January 2007 and December 2020 and analyzed the pCR for HR-positive and HER2-negative breast cancer. RESULTS: The median age at the time of surgery was 45.4 years, and 9.1% of patients (38 of 417) with HR-positive/HER2-negative status had pCR. Among patients with HR-positive/HER2-negative breast cancer, patients with single HR-positivity had a 20.2% pCR rate, and patients with double HR-positivity had a 4.4% pCR rate. Patients with a high Ki-67 index exhibited a higher pCR rate than those with a lower Ki-67 index (14.5% vs. 3.2%). Patients with single HR-positive and high Ki-67 values exhibited a significantly higher pCR rate than those with double HR-positive and low Ki-67 values (27.8% vs. 2.1%; p < 0.001). CONCLUSION: NAC could improve prognosis in patients with HR-positive/HER2-negative breast cancer with a single HR-positive and high Ki-67 values.

Comparison of mutational profiles between triple-negative and hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancers in T2N0-1M0 stage: Implications of TP53 and PIK3CA mutations in Korean early-stage breast cancers.

Triple-negative breast cancer (TNBC) has higher loco-regional recurrence and visceral metastasis compared to other breast cancer subtypes; however, little is known about the molecular pathogenesis of TNBC. Therefore, we compared the mutation profiles of early TNBC with those of hormone receptor-positive (HR+) and/or human epidermal growth factor receptor 2-negative (HER2-) breast cancer using a customized next-generation sequencing capture panel. DNA was obtained from the primary tumor tissues of 34 patients diagnosed with pT2N0-1M0 HR+/HER2- breast cancer or TNBC. Using SureSelectXT kit (Agilent), next-generation sequencing for 48 breast cancer-associated genes was performed on HiSeq platform (Illumina) with germline confirmation. Also, plasma was collected from 24 patients before surgery, cell-free nucleic acids were extracted, and performed therascreen PIK3CA RGQ PCR assay. Significant mutations were found in TP53, PIK3CA, AR, BRCA1, PTEN, BRCA2, BRIP2, KIT, MET, AKT1, ALK, BARD1, BRAF, CD274, ERBB2, FGFR1, IDH2, NOTCH1, RET, and STK11 (in descending order of occurrence). TP53 mutations were identified in the TNBC group more frequently than in the HR+/HER2- group (P = 0.003). The presence of TP53 mutations was associated with a higher tumor grade (P = 0.008), p53 positivity (P < 0.0001), and a higher Ki-67 index (P = 0.004). PIK3CA was the most frequently mutated gene in HR+/HER2- breast cancer (8/22, 36.4%), but not in TNBC (1/12, 8.3%). The TP53 mutation is associated with higher tumor grade and Ki-67 expression in both groups, and with larger tumor size in TNBC, but not in HR+/HER2- breast cancer. In the foundation of TP53 mutation, concomitant mutation numbers are proportional to tumor size, reflecting clonal progression.

Prognostic value of SUVmax in breast cancer and comparative analyses of molecular subtypes: A systematic review and meta-analysis.

BACKGROUND: To assess the prognostic capability of the maximum standardized uptake values (SUVmax) measured in the primary tumor and axillary lymph nodes (ALNs) by pretreatment fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography and analyze outcomes according to the molecular breast cancer subtypes. METHODS: The databases were systematically searched using keywords for breast cancer, positron emission tomography/computed tomography, and SUVmax; the extracted studies reported at least 1 form of survival data, event-free survival (EFS) and overall survival. Comparative analyses of the pooled hazard ratios (HRs) for EFS and overall survival were performed to assess their correlations with SUVmax. The pooled HR was estimated using random-effects model according to the results of heterogeneity. RESULTS: Thirteen eligible studies comprising 3040 patients with breast cancer were included. The pooled HRs of high SUVmax in the primary tumor and ALN were 3.01 (95% CI 1.83-4.97, P < .00001; I2 = 82%) and 3.72 (95% CI 1.15-12.01; I2 = 92%; P = .03), respectively. Patients with higher SUVmax demonstrated a poorer survival prognosis. Furthermore, comparative analyses according to the molecular subtypes demonstrated that the SUVmax in the primary tumor or ALN can be a predictive parameter in patients with the luminal subtype disease. Subtype analysis results indicated a significant association of the luminal group, with a HR of 2.65 (95% CI 1.31-5.37; I2 = 27%; P = .007). CONCLUSIONS: SUVmax from pretreatment is a significant prognostic factor for EFS in patients with breast cancer. Despite several limitations, correlation with molecular subtype (luminal type) was demonstrated. Further large-scale studies are required to investigate the precise prognostic capability of SUVmax.

Metastasis to breast from ovarian cancer and primary ovarian cancer concurrently diagnosis.

Metastasis to breast from ovarian cancer is very rare, and it is very difficult to distinguish the primary breast cancer from the secondary one. In our case, a 61-year-old woman presented to the hospital with complaints of lower abdominal pain and distention. Abdominal-pelvic computed tomography (CT) imaging revealed a solid ovarian cystic tumor with numerable ascites in the abdominal cavity and disseminated peritoneal carcinomatosis. To confirm the presence of metastasis in other organs, a preoperative imaging studies including chest CT was performed. Chest CT imaging revealed an enlargement of both the axillary lymph nodes (r/o metastatic lymphadenopathy) and breast imaging studies (breast sonography and mammography) revealed masses penetrated the pectoralis major muscle in the left breast and metastatic lymphadenopathy in Lt axilla. The core needle biopsy result of breast lesion showed unknown origin carcinoma with micropapillary features and no psammoma bodies. So, we could not distinguish primary breast cancer and breast metastasis from ovarian cancer because breast metastasis from ovary could be contained psammoma bodies, generally. Although the possibility of primary breast cancer could not be ruled out absolutely, the neoadjuvant chemotherapy included Paclitaxel and Carboplatin is known to be effective for both breast and ovarian cancer. So after neoadjuvant chemotherapy, mastectomy concurrently with ovarian cancer surgery was performed. The histopathologic features of the ovaries and breast were similar and psammoma bodies also could be observed, which were not detected in previous core needle biopsied specimen. And lymph nodes from the breast and the ovaries also showed consistent findings. Combined with histopathologic report and medical records, the final diagnosis confirmed as a metastasis of ovarian cancer to breast. After surgery, the patient has continued with metastatic ovarian cancer specific treatment. Breast metastatic tumors must be distinguished from primary breast tumors to avoid any unnecessary surgery. It might be difficult to diagnosis precisely by using only core needle biopsy because of inadequate specimen volume. Although surgical resection may be effective for both diagnosis and palliative treatment, further studies focused on less invasive biopsy are needed for exact histopathological diagnosis.

Clinicopathological Features of BRCA1/2 Mutation-Positive Breast Cancer.

PURPOSE: The BRCA1/2 gene is the most well-known and studied gene associated with hereditary breast cancer. BRCA1/2 genetic testing is widely performed in high-risk patients of hereditary breast cancer in Korea. This study aimed to investigate the clinicopathological characteristics of BRCA1/2 mutation-positive breast cancer patients. METHODS: The clinical data of 188 Korean breast cancer patients who underwent genetic testing of BRCA1/2 mutation between March 2015 and February 2020 at Pusan National University Yangsan Hospital were retrospectively reviewed. The characteristics of breast cancer according to the expression of BRCA1 and BRCA2 mutations were analyzed using the Health Insurance Review and Assessment Service guideline criteria and other clinicopathological factors. RESULTS: The factor associated with BRCA1/2 gene expression was cancer stage, and mutation expression was significantly decreased in stage I compared to stage 0 (p = 0.033; odds ratio [OR], 0.169; 95% confidence interval [CI], 0.033-0.867), and there was a tendency to increase in stage II (p = 0.780; OR, 1.150; 95% CI, 0.432-3.064). BRCA1 was significantly associated with triple-negative breast cancer (TNBC) (p = 0.004; OR, 5.887; 95% CI, 1.778-19.498). Gene expression of BRCA2 was significantly reduced under 40 years of age (p = 0.040; OR, 0.198; 95% CI, 0.042-0.930). There was no difference in disease-free survival (p = 0.900) and overall survival (p = 0.733) between the BRCA1/2 mutation-positive and -negative groups. CONCLUSION: In this study, the clinicopathological characteristics of breast cancer patients with BRCA1/2 gene mutations were identified. BRCA1 gene expression was highly correlated with TNBC. BRCA1/2 mutation did not have a poor prognosis regarding recurrence and death.

A comparative study of the clinical characteristics and outcomes of HR-positive HER2-negative breast cancer patients over and under 65 years old.

Purpose: The purpose of this study was to compare the clinical characteristics and outcomes of hormone receptor-positive (HR+) human epidermal growth factor 2-negative (HER2-) breast cancer among elderly patients (over 65 years old) and younger patients. Methods: This was a retrospective cohort study of 328 patients who were treated for breast cancer at Pusan National University Yangsan Hospital between January 2009 and December 2014. Tumor characteristics, surgical methods, and survival outcomes were compared between the two age groups (<65 and ≥65 years old). Kaplan-Meier curves for disease-free survival (DFS) and overall survival (OS) were also constructed according to the age groups. Results: Among the 328 patients with HR+ HER2- breast cancer, 184 (56.1%) were <65 years old and 144 (43.9%) were ≥65 years old. Breast cancer stages were similar between the two age groups, but the older patients were treated less often with chemotherapy (81% vs. 66%, P=0.002). During the follow-up period, 17 deaths and 36 cases of recurrence or metastasis were reported. There was no difference in DFS between the two groups (P=0.840); however, the OS of the older age group was significantly lower than that of the younger age group (P=0.015). Conclusion: This study suggested that HR+ HER2- breast cancer patients belonging to the two age groups had no significant difference in DFS. However, older age is an independent factor affecting OS rate. Therefore, even if patients are old, but their physical condition is satisfactory, standard and active treatment may be necessary, similar to that given to younger patients.

Utility of sentinel lymph node biopsy in papillary thyroid microcarcinoma.

Purpose: There are many studies on sentinel lymph node (SLN) biopsy in thyroid carcinoma but SLN biopsy (SLNB) in papillary thyroid carcinoma (PTC) remains open to debate. Therefore in this retrospective study, the usefulness of SLNB in thyroid carcinoma patients who had micro-PTC without cervical lymphadenopathy was assessed. Methods: SLNB was performed in 114 patients who were diagnosed with micro-PTC in a single lobe without palpable or ultrasound-detected lymph node at the tertiary center between January 2012 and December 2013. After SLNB, all patients underwent total thyroidectomy and central neck dissection or thyroid lobectomy and central neck dissection of the single side. Results: SLNs were identified in 112 of 114 patients with 41 positive SLNs and 71 negative SLNs on intraoperative frozen sections. However, eight negative patients were found to be positive in the final pathology. Sentinel node identification rate and false negative value of SLNB were 98.2% and 11.3%, respectively. In the univariate analysis, higher lymph node metastasis was detected in men than in women. Higher detection number of SLN showed higher probability of lymph node metastasis. Conclusion: SLNB may be helpful in papillary thyroid cancer, especially in male patients. Also, it is useful for the staging of nodal status and clearance of persistent disease.

What predicts better prognosis in elderly breast cancer patients?

Purpose: As we enter an aging society, the number of elderly patients with breast cancer is increasing. We assessed the prognostic factors for breast cancer recurrence or metastasis in patients over the age of 65 years by analyzing tumor characteristics and long-term clinical outcomes. Methods: In this retrospective study, the data of 286 breast cancer patients aged 65 years and older, who underwent treatment at the Pusan National University Hospital and Pusan National University Yangsan Hospital from 2008 to 2014, were analyzed. The patients were divided into two groups: those with recurrence or metastasis and those without. Cox-regression model was used to analyze the risk factors for recurrence or metastasis. Kaplan-Meier method was used to analyze survival rates by the log-rank test. Results: Among the 286 patients with invasive breast cancer, 43 patients (15.0%) had recurrence or distant metastasis during a median follow-up period of 61 months. Advanced stages of breast cancer and patients who are not adapted to endocrine therapy were associated with poor prognosis. Conclusion: In this study, advanced stages of breast cancer and endocrine therapy were the prognostic factors for breast cancer recurrences or metastases. Early detection of elderly breast cancer generally increases the possibility of diagnosis at an earlier stage, which can lead to a better prognosis. Moreover, endocrine therapy should be administered to elderly patients who manifest favorable intrinsic subtypes of breast cancer.

Thyrotropin suppression therapy for papillary thyroid carcinoma with a huge recurred neck lymph node.

Differentiated thyroid cancer (DTC) originating from thyroid tissue is affected by thyrotropin (TSH). TSH suppression therapy is usually recommended after thyroidectomy in cases of DTC. A 57-year-old woman who harbored a very huge recurred lymph node underwent TSH suppression therapy because of the risk of surgical complications. After TSH suppression, the huge neck lymph node exhibited a response and decreased in size. She had been followed up for 144 months. TSH suppression therapy could be considered as an alternative treatment option in a recurred DTC patient with a high perioperative risk.