breast carcinoma (MBC) is a rare type of breast cancer. Although patients with MBC may have a better prognosis than that of patients with invasive ductal carcinoma, many clinicians administer adjuvant chemotherapy regimens similar to those for other breast tumors. Using data from a nationwide clinical database, this study evaluated the significance of adjuvant systemic chemotherapy and whether it can be omitted in MBC patients.METHODS: We included 3,076 patients with a diagnosis of MBC recorded in the Korean Breast Cancer Registry between January 1990 and August 2016. We used the Kaplan-Meier method to analyze breast cancer-specific survival (BCCS) and overall survival (OS). Multivariate analysis was performed using a Cox proportional hazard ratio (HR) model to estimate the adjusted HR for each prognostic factor.RESULTS: A total of 2,988 MBC patients were enrolled and followed-up for a median of 100 months (range, 2–324 months). Multivariate analysis revealed that axillary lymph node (ALN) metastasis and estrogen receptor (ER) negativity were significant prognostic factors for BCSS. Meanwhile, old age, pathologic tumor stage, and ALN metastasis were significant prognostic factors for OS. Subgroup analysis of ER-positive MBC showed that ALN metastasis was a significant prognostic factor for BCSS. Additionally, old age, pathologic tumor stage, and ALN metastasis were prognostic factors for OS. Ultimately, ALN metastasis was the most statistically significant prognostic factor for MBC. However, chemotherapy had no significant effect on BCSS and OS. The Kaplan-Meier curves of BCSS and OS based on pathologic tumor and nodal stages and age revealed that chemotherapy did not statistically significantly improve prognosis, except for the N3 stage.CONCLUSION: Our large retrospective analysis revealed that adjuvant chemotherapy provided little benefit to improve the prognosis of most ER-positive MBC patients. Therefore, chemotherapy can be omitted in the treatment of most ER-positive MBC.]]>
Adenocarcinoma, Mucinous ; Breast Neoplasms ; Breast ; Carcinoma, Ductal ; Chemotherapy, Adjuvant ; Diagnosis ; Drug Therapy ; Estrogens ; Humans ; Lymph Nodes ; Methods ; Mucins ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies

PURPOSE: Although it is widely accepted that hormone receptor (HR) status is associated with later post-diagnostic periods, a debate exists as to whether the association is independent of age. The aim of our study was to confirm the impact of HR status on later period breast cancer-specific death (LP-BCSD) and later period non-breast cancer-specific death (LP-non-BCSD) in different age subgroups. METHODS: Surveillance, Epidemiology, and End Results databases were utilized to identify 181,108 breast cancer patients with > 5 years survival. The cumulative incidence of LP-BCSD and LP-non-BCSD was calculated using the Gray method. The subdistribution hazard ratio (SHR) of variables was estimated via the Fine and Gray proportional hazard regression model. Subgroup analyses for LP-BCSD and LP-non-BCSD were performed according to the HR status. RESULTS: The risk of LP-BCSD was exceeded by that of LP-non-BCSD at > 5 years since the diagnosis, particularly in old women. The competing risk regression model indicated that hormone receptor-positive (HR+) was an independent factor for more LP-BCSD (hazard ratio, 1.54; 95% confidence interval, 1.44–1.54; p < 0.001). However, stratified analysis indicated that HR+ was only associated with more LP-BCSD in the young women subgroup. Although HR+ was associated with more LP-non-BCSD, the predictive value of HR+ for LP-non-BCSD was eliminated after adjusting for age. CONCLUSIONS: HR+ was related to LP-BCSD in the premenopausal population. LP-BCSD should be an optimal endpoint in future trials designed to evaluate the role of extended adjuvant endocrine therapy.
Breast Neoplasms ; Breast ; Diagnosis ; Drug Therapy ; Epidemiology ; Female ; Humans ; Incidence ; Methods ; Prognosis ; Receptors, Estrogen

PURPOSE: Internal mammary lymph node (IMN) involvement is associated with poor prognosis in breast cancer. This study investigated the treatment outcomes of initial clinically IMN-positive breast cancer patients who received adjuvant radiotherapy (RT), including IMN irradiation, following primary breast surgery. MATERIALS AND METHODS: We retrospectively reviewed data of 95 breast cancer patients with clinically detected IMNs at diagnosis treated with surgery and RT between June 2009 and December 2015. Patients received adjuvant RT to the whole breast/chest wall and regional lymph node (axillary, internal mammary, and supraclavicular) areas. Twelve patients received an additional boost to the IMN area. RESULTS: The median follow-up was 43.2 months (range, 4.5 to 100.5 months). Among 77 patients who received neoadjuvant chemotherapy, 52 (67.5%) showed IMN normalization and 19 (24.6%) showed a partial response to IMN. There were 3 and 24 cases of IMN failure and any recurrence, respectively. The 5-year IMN failure-free survival, disease-free survival (DFS), and overall survival (OS) were 96%, 70%, and 84%, respectively. IMN failure-free survival was significantly affected by resection margin status (97.7% if negative, 87.5% for close or positive margins; p = 0.009). All three patients with IMN failure had initial IMN size ≥1 cm and did not receive IMN boost irradiation. The median age of the three patients was 31 years, and all had hormone receptor-negative tumors. CONCLUSION: RT provides excellent IMN control without the support of IMN surgery. Intensity-modulated radiotherapy, including IMN boost for breast cancer patients, is a safe and effective technique for regional lymph node irradiation.
Breast Neoplasms ; Breast ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Lymph Nodes ; Prognosis ; Radiotherapy ; Radiotherapy, Adjuvant ; Radiotherapy, Intensity-Modulated ; Recurrence ; Retrospective Studies

PURPOSE: Core needle biopsy (CNB) is a widely used procedure for breast cancer diagnosis and analyzing results of immunohistochemistry (IHC). Several studies have shown concordance or discordance in IHC results between CNB and surgical specimens (SS). A double-check (CNB and SS) is inefficient and costly to perform a double-check on all patients. Therefore, it is important to determine which patients would benefit from a double-check. METHODS: We collected the medical records of patients who underwent breast cancer surgery at Pusan National University Yangsan Hospital between April 2009 and June 2018 (n = 620). Molecular subtypes were classified as follows by hormone receptors (HR) and human epidermal growth factor receptor-2 (HER2): HR+/HER2+, HR+/HER2−, HR−/HER2+, HR−/HER2−. Clinicopathological factors including age, obesity, histological grade, preoperative CEA, CA15-3, T stage, N stage, and menopausal status were assessed to determine whether they were associated with subtype change. RESULTS: Increasing histological grade (P < 0.001; odds ratio [OR], 3.693; 95% confidence interval [CI], 1.941–7.025), preoperative CEA ≥ 5 ng/mL (P =0.042; OR, 2.399; 95% CI, 1.009–5.707) and higher T stage (P = 0.015; OR, 2.241; 95% CI, 1.152–4.357) were significantly associated with subtype change. On multivariable analyses, subtype changes were more common in high-grade breast cancer (P < 0.001; OR, 1.077; 95% CI, 1.031–1.113) and CEA ≥ 5 (P = 0.032; OR, 2.658; 95% CI, 1.088–6.490). CONCLUSION: Patients with moderate- to high-grade tumors or CEA ≥ 5 ng/mL are required a double-check to determine the molecular subtype of breast cancer.
Biopsy ; Biopsy, Large-Core Needle ; Breast Neoplasms ; Breast ; Busan ; Diagnosis ; Drug Therapy ; Epidermal Growth Factor ; Gyeongsangnam-do ; Humans ; Immunohistochemistry ; Medical Records ; Obesity ; Odds Ratio

PURPOSE: Tumor-infiltrating lymphocyte (TIL), programmed death-ligand 1 (PD-L1) expression and neutrophil-to-lymphocyte ratio (NLR) is associated to immunogenicity and prognosis of breast cancer. We analyzed baseline NLR, changes of NLR, TIL, and PD-L1 during neoadjuvant chemotherapy (NAC) and their clinical implication in triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Between January 2008 to December 2015, 358 TNBC patients were analyzed. Baseline NLR, 50 paired NLR (initial diagnosis, after completion of NAC) and 34 paired tissues (initial diagnosis, surgical specimen after completion of NAC) were collected. Changes of TIL, CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 expression were assessed with immunohistochemical stain. RESULTS: Low NLR (≤ 3.16) was associated to superior survival (overall survival: 41.83 months vs. 36.5 months, p=0.002; disease-free survival [DFS]: 37.85 months vs. 32.14 months, p=0.032). Modest NLR change after NAC (–30% < NLR change < 100%) showed prolonged DFS (38.37 months vs. 22.37 months, p=0.015). During NAC, negative or negative conversion of tumor PD-L1 expression was associated to poor DFS (34.77 months vs. 16.03 months, p=0.037), and same or increased TIL showed trends for superior DFS, but without statistical significance. Positive tumor PD-L1 expression (H-score ≥ 5) in baseline or post-NAC tissue was associated to superior DFS (57.6 months vs. 12.5 months, p=0.001 and 53.3 months vs. 18.9 months, p=0.040). Positive stromal PD-L1 expression in baseline was also associated to superior DFS (50.2 months vs. 20.4 months, p=0.002). CONCLUSION: In locally advanced TNBC, baseline NLR, changes of NLR during NAC was associated to survival. Baseline PD-L1 expression and changes of PD-L1 expression in tumor tissue during NAC also showed association to prognosis.
Breast Neoplasms ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Humans ; Lymphocytes, Tumor-Infiltrating ; Prognosis ; Triple Negative Breast Neoplasms

Due to advances in the treatment and diagnosis of cancer, many women survive long after treatment, and therefore express concerns about the impact of estrogen deficiency on their quality of life. Cancer treatment can induce menopause through surgical removal of the ovaries, chemotherapy, or radiation. Women who undergo induced menopause usually experience more sudden and severe menopausal symptoms, including vasomotor symptoms, psychological symptoms, genitourinary symptoms, cardiovascular disease, and osteoporosis. Menopausal hormone therapy (MHT) is especially important in women younger than 40. In this review, we consider the role of MHT after the diagnosis of breast, gynecologic, colorectal, stomach, liver, lung, and hematologic cancers. MHT is advantageous in endometrial cancer type I, cervical squamous cell carcinoma, colorectal cancer, hepatocellular carcinoma, and hematologic malignancies. However, MHT is not recommended for use in breast cancer, endometrial stromal sarcoma, hormone receptor–positive gastric cancer, and lung cancer survivors because it is linked to an increased risk of cancer recurrence. Depending on the type of cancer, clinicians should recommend that cancer survivors receive appropriate MHT in order to reduce vasomotor symptoms and to benefit from its positive effects on the cardiovascular and skeletal systems.
Breast ; Breast Neoplasms ; Carcinoma, Hepatocellular ; Carcinoma, Squamous Cell ; Cardiovascular Diseases ; Colorectal Neoplasms ; Diagnosis ; Drug Therapy ; Endometrial Neoplasms ; Estrogens ; Female ; Hematologic Neoplasms ; Humans ; Liver ; Lung ; Lung Neoplasms ; Menopause ; Osteoporosis ; Ovary ; Quality of Life ; Recurrence ; Sarcoma, Endometrial Stromal ; Stomach ; Stomach Neoplasms ; Survivors

PURPOSE: We investigated the changes in serum 25-hydroxyvitamin D (25[OH]D) levels before and after neoadjuvant chemotherapy (NCT) and the associations with pathologic complete response (pCR) and survival in patients with breast cancer. METHODS: Serum 25(OH)D concentrations were measured pre- and post-NCT in 374 patients between 2010 and 2013. Based on a cutoff of 20 ng/mL, patients were categorized into “either sufficient” or “both deficient” groups. The associations with clinicopathological data, including pCR and survival, were analyzed using multivariable analyses. RESULTS: Patients with either pre- or post-NCT sufficient 25(OH)D levels accounted for 23.8%, and the overall pCR rate was 25.9%. Most patients showed 25(OH)D deficiency at diagnosis and 65.8% showed decreased serum levels after NCT. Changes in 25(OH)D status were associated with postmenopause status, rural residence, baseline summer examination, and molecular phenotype, but not pCR. No association between survival and 25(OH)D status was found, including in the subgroup analyses based on molecular phenotypes. CONCLUSION: Most Korean patients with breast cancer showed vitamin D deficiency at diagnosis and a significant decrease in the serum concentration after NCT. No association with oncologic outcomes was found. Therefore, although optimal management for vitamin D deficiency is urgent for skeletal health, further research is warranted to clearly determine the prognostic role of vitamin D in patients with breast cancer who are candidates for NCT.
Breast Neoplasms* ; Breast* ; Diagnosis ; Drug Therapy* ; Humans ; Neoadjuvant Therapy ; Phenotype ; Polymerase Chain Reaction ; Postmenopause ; Treatment Outcome ; Vitamin D ; Vitamin D Deficiency

Stewart-Treves syndrome (STS) is a rare cutaneous angiosarcoma that develops in chronic lymphedema. The majority of STS is described in the upper extremity after aggressive locoregional therapy for breast cancer and is rarely reported in lower extremities. A 68-year-old woman presented with a 3-month history of multiple purpuric tumorous plaques and nodules on the right posterior thigh. She had a history of radical hysterectomy with lymph node dissection and postoperative radiotherapy due to uterine cervical cancer 16 years ago. She received right total hip replacement surgery due to hip joint avascular necrosis 14 years ago. She had suffered from chronic leg edema, especially on the right side. Skin biopsy on the right posterior thigh showed irregular vascular channels lined by atypical endothelial cells. Special stains showed positivity for CD31, CD34, factor VIII, and D2~40, which are pan-vascular or lymphatic markers. She showed a pelvic mass and pelvic bone metastasis on radiologic staging work-up. She refused all treatment, including surgery, radiotherapy, and chemotherapy, except for pain control. She died 2 months after diagnosis of this highly malignant tumor. The lymphedema on both lower extremities after uterine cervical cancer treatment was aggravated especially on the right lower extremity after right total hip replacement surgery. Increased weight of the right lower extremity resulted in 4 episodes of recurrent hip dislocation. We contend that these multiple factors (uterine cervical cancer treatment, total hip replacement surgery on the right side, and recurrent hip dislocations) attributed to development of Stewart-Treves syndrome. We herein report a case of Stewart-Treves syndrome of the lower extremity following chronic leg lymphedema after uterine cervical cancer treatment and hip surgery.
Aged ; Arthroplasty, Replacement, Hip* ; Biopsy ; Breast Neoplasms ; Coloring Agents ; Diagnosis ; Drug Therapy ; Edema ; Endothelial Cells ; Factor VIII ; Female ; Hemangiosarcoma ; Hip ; Hip Dislocation ; Hip Joint ; Humans ; Hysterectomy* ; Leg ; Lower Extremity* ; Lymph Node Excision ; Lymphedema ; Necrosis ; Neoplasm Metastasis ; Pelvic Bones ; Radiotherapy ; Skin ; Thigh ; Upper Extremity ; Uterine Cervical Neoplasms

PURPOSE: Sentinel lymph node biopsy (SLNB) can be performed when node-positive disease is converted to node-negative status after neoadjuvant chemotherapy (NCT). Tattooing nodes might improve accuracy but supportive data are limited. This study aimed to investigate the feasibility of charcoal tattooing metastatic axillary lymph node (ALN) at presentation followed by SLNB after NCT in breast cancers. MATERIALS AND METHODS: Twenty patientswith cytology-proven node metastases prospectively underwent charcoal tattooing at diagnosis. SLNB using dual tracers and axillary surgery after NCT were then performed. The detection rate of tattooed node and diagnostic performance of SLNB were analyzed. RESULTS: All patients underwent charcoal tattooingwithout significant morbidity. Sentinel and tattooed nodes could be detected during surgery after NCT. Nodal pathologic complete response was achieved in 10 patients. Overall sensitivity, false-negative rate (FNR), negative predictive value, and accuracy of hot/blue SLNB were 80.0%, 20.0%, 83.3%, and 90.0%, respectively. Retrieving more nodes and favorable nodal response were associated with improved performance. The best accuracy was observed when excised tattooed node was calculated together (FNR, 0.0%). Cold/non-blue tattooed nodes of five patients were removed during non-sentinel axillary surgery but clinicopathological parameters did not differ compared to patients with hot/blue tattooed node detected during SLNB, suggesting the importance of the tattooing procedure itself to improve performance. CONCLUSION: Charcoal tattooing of cytology-confirmed metastatic ALN at presentation is technically feasible and does not limit SLNB after NCT. The tattooing procedure without additional preoperative localization is advantageous for improving the diagnostic performance of SLNB in this setting.
Breast Neoplasms* ; Breast* ; Charcoal* ; Diagnosis* ; Drug Therapy* ; Humans ; Lymph Nodes* ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Prospective Studies ; Sentinel Lymph Node Biopsy* ; Tattooing*

Orbital metastasis is a rare event, and metastatic disease affecting the extraocular muscles is an even less frequent complication of solid tumors. Herein, we report an unusual case of ptosis as the initial presentation of an invasive breast cancer. A 68-year-old woman presented with III and VI partial nerve paresis, secondary to a compressive retrobulbar mass. Magnetic resonance imaging revealed an infiltrative lesion involving the extraocular muscles. Tissue biopsy yielded a result compatible with metastasis to the orbit, with immunohistochemistry analysis suggesting breast as the primary organ. Mammography identified an area of architectural distortion; stereotactic wire-guided biopsy confirmed the result of the previous orbital biopsy. A positron emission tomography scan demonstrated disseminated disease. Palliative chemotherapy with bone-modulating agents and subsequent hormonal therapy was proposed. Unfortunately, the patient did not respond to therapy and died 38 months after diagnosis.
Aged ; Biopsy ; Breast Neoplasms* ; Breast* ; Diagnosis ; Drug Therapy ; Female ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging ; Mammography ; Muscles* ; Neoplasm Metastasis ; Oculomotor Muscles ; Orbit ; Orbital Neoplasms ; Paresis ; Positron-Emission Tomography