Risk Factors, Patterns, and Distribution of Bone Metastases and Skeletal-Related Events in High-Risk Breast Cancer Patients.

BACKGROUND: More than a quarter of breast cancer patients are at risk to develop recurrent metastases to the bone. OBJECTIVE: This study was designed to identify risk factors and predilections of bone metastasis and skeletal-related events (SRE) in a population of breast cancer survivors initially diagnosed in advanced stages and with high-risks of relapse. METHODS: Associated risk factors, distribution, and attainable treatment of bone metastasis and SRE were analyzed in a cohort of 1,329 breast cancer patients. The association with dependent variables was subsequently analyzed using multivariable logistic regression. Sociodemographic and adverse clinical characteristics were included as covariates of progression into bone metastasis and SREs. RESULTS: Of 1329 breast cancer patients, 246 patients (18.5%) were diagnosed as metastatic breast cancer in which 232 of them (94.3%) had bone metastases. Spines were the most common sites of bone metastases (25.6%). In multivariable analysis, advanced stage at diagnosis (OR=1.840, 95%CI:1.198-2.826, P=0.005), luminal subtype (OR=1.788, 95%CI:1.206-2.652, P=0.045), lobular histology (OR=1.795, 95%CI:1.012-3/184, P=0.046), positive axillary lymph node (OR=1.771, 95%CI:1.087-2.886, P=0.022), multiple metabolic comorbidities (OR=2.193, 95%CI:1.371-3.508, P=0.001), early menopause (OR=2.136, 95%CI:1.116-4.464, P=0.046) were significantly associated with risk of recurrent bone metastases. SREs occurred in 89 (68.5%) patients. Several risk factors for SREs were early menopausal age (OR=2.342, P=0.024), advanced stages (OR=1.404, P=0.039), lobular histology (OR=2.279, P=0.007), and having multiple metabolic comorbidities (OR=1.728, P=0.039). CONCLUSION: Bone metastases and SREs are relatively high in breast cancer patients diagnosed in advanced stages. Luminal subtypes, having multiple metabolic comorbidities, and lobular histology are associated with higher risks of recurrent bone metastases. Living in rural areas and advanced stage at diagnosis as a risk factors for bone metastases might represent a social gradient of care delivery.

Hemi-mandibulectomy without bony reconstruction: A case report of mandibular metastasis from a silent differentiated papillary thyroid cancer.

INTRODUCTION: Distant spread to the jaw is a rare metastatic manifestation from papillary thyroid cancer. Complete resection of tumor extension in the facial and oral regions requires consideration to compromise mastication functioning and facial aesthetics. Current advances in the microvascular surgery have facilitated excellent restoration of patient's functioning. Inadequate expertise, facility, longer surgery time and inpatient care, and healthcare insurance disbursement are common challenges in developing countries to perform microvascular surgery. CASE PRESENTATION: A 54-year female presented in an oncology clinic with a rapid progressive lump in the jaw without inflammatory signs. CT-scan revealed a 5.9x5.3 × 5cm lesion with osteo-destruction in the left mandible body. Biopsy was performed indicating a papillary adenocarcinoma invasion. Neck sonography showed hypoechoic nodule with regular border in the thyroid lobes. Fine-needle aspiration biopsy revealed benign follicular cells with Bethesda class II. Total thyroidectomy with frozen section and left hemi-mandibulectomy without bony reconstruction were then performed. Histopathological examination showed papillary thyroid cancer with follicular variant in the thyroid and mandible lesion. Thyroid ablation, TSH suppression, and chewing rehabilitation programs were accomplished by the patient. DISCUSSION: Partial mandibulectomy without bony reconstruction might be an option for selected patients with careful consideration from multidisciplinary team members in which extensive surgery with immediate bony reconstruction is not possible.

Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors.

BACKGROUND: Obesity and other metabolic comorbidities affect over 10% of patients with breast cancer and are closely related with adverse outcomes. Although metabolic comorbidities among breast cancer patients in low- and middle-income countries are suggested to be lower, only a few studies are currently available. Effective management of metabolic comorbidities in cancer patients has been associated with better outcomes. METHODS: Non-metastatic breast cancer patients (N = 1081) treated in our department (2014-2018) were monitored for the presence of high Body Mass Index (BMI), diabetes or glucose intolerance, dyslipidemia, and hypertension and the development of recurrent metastatic diseases during a median follow-up of 3.9 years. RESULTS: Glucose intolerance, hypertension, dyslipidemia, and BMI ≥ 27.7 kg/m2 considered at risk for metabolic comorbidities were found in 26.5, 42.6, 27.7, and 23.3% of breast cancer patients, respectively. Diabetes or glucose intolerance and having both glucose intolerance and dyslipidemia were associated with the risk of recurrent metastatic disease (OR = 1.442, 95%CI = 1.071-1.943, p = 0.016 and OR = 1.495, 95%CI = 1.090-2.049, p = 0.010; respectively). Having three or more metabolic comorbidities was significantly associated with the risk of recurrent metastatic disease (OR = 1.647, 95%CI = 1.139-2.382, p = 0.008) compared to patients without any comorbidity. The metabolic comorbidities were distributed unevenly among breast cancer subtypes. A significant association with recurrent metastatic disease was found in the Luminal B-like subtype. In post-menopausal patients, having more than three comorbidities was associated with a higher risk of recurrent metastatic disease compared to those without any comorbidity (OR = 2.000, 95%CI = 1.035-3.067, p = 0.001). The risks of having three or more metabolic comorbidities were significantly higher in breast cancer survivors who were obese, lived in an urban area, and received hormonal therapy of aromatase inhibitors. CONCLUSION: Metabolic comorbidities were frequently found in breast cancer patients and were associated with higher risks to develop recurrent metastatic disease, particularly in post-menopausal women. Subsequent larger studies are needed to better understand the association of metabolic comorbidities with patients' quality of life and prognosis, and to explore the potential combination of clinical intervention and lifestyle modification in breast cancer survivors to treat as well as reduce their impact.

Concurrent manifestations of Horner's syndrome and esophageal metastasis of breast cancer: case report of a young woman after a period of non-adherence to treatment: a case report.

BACKGROUND: Esophageal involvement and Horner's syndrome are rare manifestations of breast cancer distant metastases that can pose a significant challenge in diagnosis and treatment. In addition to the more aggressive behavior of breast cancer diagnosed in young women, non-adherence to treatment is associated with increased risk of distant metastasis. CASE PRESENTATION: A 36-year-old Javanese woman presented to our institution with dysphagia, hoarseness, and frequent hiccups. In the 6 weeks prior to the current admission, the patient also reported tingling in the neck and shoulder, anhidrosis in the left hemifacial region, and drooping of the upper left eyelid. She was previously managed as tuberculoid laryngitis. Plain X-rays showed burst fractures of the cervical vertebrae and slight pleural effusion. Laryngoscopy revealed bowing of the vocal cords and liquid residue in the vallecula that was reduced upon chin tuck. Esophageal metastasis was confirmed with endoscopy showing thickening of the wall and positive cytology swab with ductal malignant cells. The patient had a history of breast cancer with a period of loss to follow-up of 4 years. CONCLUSIONS: Physicians should consider potential distant metastasis of breast cancer to the esophagus and sympathetic nervous system of the neck particularly in a high-risk woman with presentation of dysphagia and manifestations of Horner's syndrome.

Pre-treatment neutrophil-lymphocyte and platelet-lymphocyte ratios as additional markers for breast cancer progression: A retrospective cohort study.

BACKGROUND: Breast cancer is the most prevalent cancer that causes significant morbidity and loss of productivity. Around a third of all breast cancer patients are potentially develop distant metastases albeit the current implementation of multidisciplinary treatment. A simple but effective marker to predict the risks of cancer progression is very important for clinicians to improve treatment and surveillance. METHODS: We recruited 1083 non-metastatic patients and analyzed the ratios of neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) in relation to progression-free survivals (PFS) and risks of distant metastases. RESULTS: Baseline clinicopathological variables were not significantly different in the pretreatment NLR and PLRs. Using maximum points of sensitivity and specificity of the Receiver Operating Characteristic (ROC) curve, cut-off values were determined 2.8 for NLR and 170 for PLR. Higher NLR was associated with skin and chest wall cancer infiltration (T4, P = 0.0001). Elevated PLR was associated with more advanced stages at diagnosis (P = 0.03). High NLR values were significantly associated with risks of disease progression (OR 1.555, 95% CI: 1.206-2.005, P = 0.001). Patients with high NLR had shorter PFS (34.9 vs 53.5 months, Log-rank test = 0.001) and shorter time to develop recurrent distant metastatic disease (66.6 vs 104.6 months, Log-rank test = 0.027). CONCLUSION: High NLR is significantly associated with higher risk of disease progression and shorter time to develop metastases particularly among breast cancer patients diagnosed in the advanced stages.

Regional lymph node infiltration and thick lesions are associated with poor prognosis in high-risk resected melanomas: A retrospective cohort study.

BACKGROUND: Acral lentiginous and mucosal melanoma that represent lesions without cumulative sun-induced damages account for 65% of melanomas among Asians but constitute only 5% in Caucasians. The distinct clinical manifestations might influence the clinical course, response to treatment, and outcomes. Factors associated with the prognosis of high-risk resected melanoma in Asians are still rarely reported. METHODS: Clinical, histological determinants of non-distant metastatic melanoma patients who underwent complete resection in 2014-9 were analyzed. RESULTS: Mucosal melanoma, nodular melanoma, and acral lentiginous melanoma accounted for 45.1%, 40.2%, and 14.2% of total melanoma cases (N = 82), respectively. Among cutaneous melanomas, all patients were diagnosed with Breslow's depth more than 4 mm (T4), 51% with ulceration, 95.6% with diameter more than 6 mm, 59% with lympho-vascular invasion, and 74% with regional lymph node infiltration. In mucosal melanomas, 78.3% were diagnosed in advanced stages, 14.5% with regional spread to lymph nodes and 77% with regional infiltration beyond mucosa. Lesions with ulceration were associated with higher risk of distant metastasis (OR 3.003, 95%CI:1.01-9.09). Infiltration into regional lymph node was associated with shorter overall survival (median survivals were 17 vs 23.4 months, Mantel-Cox test P = 0.049). Patients diagnosed at Breslow T4 were also associated with poorer overall survival than T1-3 (median survivals were 23 vs 32 months, Mantel-Cox test P = 0.047). CONCLUSION: The majority of melanoma patients in our population were diagnosed in advanced stages with a higher risk for recurrence and progression into distant metastasis. Regional lymph node involvement and thicker tumor (T4) were associated with poor prognosis.

Complete diaphysis resorption of the femur: A case report in a metastatic papillary thyroid cancer.

INTRODUCTION: Although differentiated thyroid cancers generally have a good prognosis, a small proportion of patients will have recurrent or progressive disease. Bone resorption due to thyroid cancer can cause significant challenges in the clinical management and rehabilitation. PRESENTED CASE: Nearly total femur resorption was found as a first presentation in a patient with thyroid cancer. The patient complained about chronic pain in her left thigh that had progressed into an inability to walk. She was treated by a traditional healer for six years before she was persuaded by a social worker to seek medical help. X-rays showed pathological loss of the right diaphyseal femur. Neck CT-scan showed a left thyroid mass with tracheal deviation, with multiple lytic lesions in the sternum and 5th rib. Needle biopsy of the thyroid mass resulted in an inconclusive follicular neoplasm. Total thyroidectomy and neck dissection revealed a classical type of papillary thyroid carcinoma. After thyroid ablation, she opted for palliative radiotherapy and bisphosphonate treatment for the bone metastases. DISCUSSION: Bone metastases are rarely detected at the time of thyroid cancer diagnosis. In the presence of bone metastasis, median survival of well-differentiated thyroid cancer decreases into only 4 years. Bone metastases are often neglected and less studied than regional lymph node and lung metastases. CONCLUSION: Although well differentiated thyroid cancer is usually indolent, a neglected bone metastasis at an initial diagnosis might adversely affect patient's quality of life and prognosis.

Clinical characteristics and the associated risk factors of the development of bilateral breast cancers: A case-control study.

BACKGROUND: The clinical impacts of bilateralism on prognosis and clinical decision-making remain contradictory particularly in areas with low incidence and delayed diagnosis of primary breast cancer. Identification of women at risk of bilateral breast cancer is required to improve patient management and to design the appropriate surveillance. METHODS: A total of 1083 women were enrolled and analyzed for the presence of synchronous and metachronous bilateral breast cancer as cases and unilateral breast cancer as controls during the median follow-up of 4.8 years. RESULTS: The incidence of bilateral breast cancer was 7.5% (81 of 1083). In comparison with unilateral breast cancers, bilateral cases were significantly diagnosed in younger women (P = 0.037, mean age was 35.6 years) who had a larger tumor size (P = 0.012, mean tumor size was 8 cm in diameter). Histological type of lobular cancer was identified as one of the risk factors for the development of contralateral breast cancer (OR 5.564, 95% CI: 3.219-9.620) and synchronous bilateral breast cancer (OR 2.561, 95% CI: 1.182-5.550). Bilateral breast cancer had significantly shorter progression-free survival (Mean survival was 26.6 vs 52.5 months for bilateral and unilateral breast cancers, respectively; P = 0.001) and shorter time to develop distant metastasis (Mean survival was 41.7 vs 104 months for bilateral and unilateral breast cancers, respectively; P = 0.001). CONCLUSION: Patients with first primary breast tumors with lobular histological type and advanced stages were observed to have higher risks for the development of contralateral breast cancers.

Risk factors of distant metastasis after surgery among different breast cancer subtypes: a hospital-based study in Indonesia.

BACKGROUND: More than one third of breast cancer patients including those that are diagnosed in early stages will develop distant metastasis. Patterns of distant metastasis and the associated risks according to the molecular subtypes are not completely revealed particularly in populations of patients with delayed diagnosis and advanced stages. METHODS: Breast cancer patients (n = 1304) admitted to our institute (2014-2017) were evaluated to identify the metastatic patterns and the associated risks. Metastatic breast cancers at diagnosis were found in 245 patients (18.7%), and 1059 patients were then grouped into non-metastatic and metastatic groups after a median follow-up of 3.8 years. RESULTS: Infiltration of the tumor to the skin and chest wall prevailed as the most powerful predictor for distant metastasis (OR 2.115, 95% CI 1.544-2.898) particularly in the luminal A-like subtype (OR 2.685, 95% CI 1.649-4.371). Nodal involvement was also significantly associated with the risk of distant metastasis (OR 1.855, 95% CI 1.319-2.611), and the risk was higher in the Luminal A-like subtype (OR 2.572, 95% CI 1.547-4.278). Luminal A-like subtype had a significant higher risk of bone metastasis (OR 1.601, 95% CI 1.106-2.358). In respect to treatment, a combination of anthracyclines and taxanes-based chemotherapy was significantly associated with lower distant organ spread in comparison with anthracycline-based chemotherapy (OR 0.510, 95% CI 0.355-0.766) and the effect was stronger in Luminal A-like subtype (OR 0.417, 95% CI 0.226-0.769). Classification into Luminal and non-Luminal subtypes revealed significant higher risks of bone metastasis in the Luminal subtype (OR 1.793, 95% CI 1.209-2.660) and pulmonary metastasis in non-Luminal breast cancer (OR 1.445, 95% CI 1.003-2.083). CONCLUSION: In addition to guiding the treatment plan, a comprehensive analysis of clinicopathological variables including the molecular subtypes could assist in the determination of distant metastasis risks of breast cancer patients. Our study offers new perspectives concerning the risks of distant metastasis in breast cancer subtypes in order to plan intensive surveillance or escalation of treatment particularly in a setting where patients are predominantly diagnosed in late stages.

Aggressive behavior of Her-2 positive colloid breast carcinoma: A case report in a metastatic breast cancer.

INTRODUCTION: Colloid breast carcinoma is a rare form of invasive ductal cancer characterized by large amount of mucous deposition. It is considered as an indolent cancer that usually affects older women. Colloid breast carcinoma generally expresses estrogen and progesterone receptors but negative for Her-2. Recommended surgery and adjuvant treatment of colloid breast carcinoma is not well-established. PRESENTED CASE: A 46 years-old woman presented as an aggressive colloid breast carcinoma showing skin ulceration, enlargement of multiple axillary lymph nodes and a metastasis in the pleura at diagnosis. The primary tumor showed strong positive expression of estrogen, progesterone as well as Her-2 receptors. The patient was treated with 6 cycles of paclitaxel and carboplatin followed by mastectomy, radiotherapy, and hormonal therapy. Patient tolerated the treatment course and showed improvement both in the locoregional control and pleural metastasis. DISCUSSION: Colloid breast carcinoma with aggressive clinical course is rarely found. Nodal involvement as a sign of poor prognosis in colloid breast carcinoma ranges only between 12 and 19%. Therefore, axillary node clearance is usually excluded during the surgery of colloid breast carcinomas. However, in the presence of high-risk characteristics, mastectomy involving axillary lymph node dissection is still contentious. In patients with Her-2 overexpression, treatment using anti-Her2 (trastuzumab) is also still disputed in colloid breast carcinoma because of the higher resistance rates. CONCLUSION: Although clinically aggressive colloid breast carcinoma is rare, thorough clinical assessment and immediate treatment initiation will be beneficial for patients with high risk of relapse and metastatic spread.

An emergency case of small bowel obstruction due to multiple gallstones in a limited resource setting.

INTRODUCTION: Gallstone ileus is an uncommon intestinal obstruction caused by impaction of gallstones passing through the cholecysto-intestinal fistula. Diagnosis of gallstone ileus remains a major challenge because the symptoms and signs are unspecific and the recommended laboratory examinations are not always available particularly in limited health resource settings including in Indonesia. In addition, treatment of choice is still debatable involving enterolithotomy only with or without additional cholecystectomy and fistula repair in one or two-stage surgery. PRESENTED CASE: A 49 years old overweight Javanese woman presented in the emergency room with nausea, frequent vomiting, abdominal distension, and absence of defecation in the past 3 days before admission. Previous abdominal surgery and history of biliary disease were not reported during anamnesis. Plain abdominal X-rays revealed small bowel obstruction. Upon emergency laparotomy, the mechanical bowel obstruction was caused by multiple gallstones in the terminal ileum. DISCUSSION: Although the incidence of gallstone ileus is 5% of all intestinal obstruction cases, the mortality rate is around 25%. Diagnosis is often difficult and half of the cases are diagnosed intraoperatively. Surgical management is still controversial involving enterolithotomy with or without cholecystectomy and fistula repair in one or two stage procedure. CONCLUSIONS: Although the incidence is rare, elaborating thorough anamnesis, physical and basic laboratory examinations in gastrointestinal obstruction should consider gallstone ileus as a potential differential diagnosis particularly in a patient with any risk factors of the biliary disease. Enterolithotomy only might be acceptable for any emergency case due to the equivalent clinical outcomes and relatively low complications.

Pathological profiles and clinical management challenges of breast cancer emerging in young women in Indonesia: a hospital-based study.

BACKGROUND: Breast cancer diagnosed at a young age is often associated with aggressive biology, advanced stage, and unfavorable prognosis. The median age of breast cancer diagnosis in Indonesia is younger (48 vs. 68 years-old in Europe) with a relatively higher proportion of patients younger than 40 years old. Although prognosis and outcome of young breast cancer are well studied in developed nations, research evaluating biological characteristics, delivered treatment, and clinical outcomes is very limited in Indonesia. METHODS: We analyzed all breast cancer patients who underwent surgery at Dr. Sardjito Hospital, Indonesia, in 2012-2017. Details of pathology profiles, treatment administrated, and outcomes, as well as reproductive factors among patients younger than 40 years old, were collected and analyzed. Kaplan-Meier curve was used to assess conditional survival based on baseline characteristics. RESULTS: From the total of 1259 breast cancer patients (median age 51 years), 144 (11.4%) were younger than 40 years old (median age 37 years). Of these young patients, 19 (13.2%) were bilateral and 92 (64%) were diagnosed in advanced stages (stages IIIA-C and IV). Median tumor diameter was 5.5 cm and nodal infiltration was present in 73%. Distant metastasis was found in 16% at the time of diagnosis. Moderate and poor differentiation of tumor were 20.8 and 78.5%, respectively, and lymphovascular invasion was found in 90.3%. Around 40% were hormone receptor-positive, 30.6% human epidermal growth factor receptor 2 positive, and 38.2% triple negative. Patients underwent radical surgery in 121 cases (84%) and breast conserving surgery in 7 cases (4.9%). Adjuvant chemotherapy was administrated in 68% and hormonal therapy in 34%. Progression-free survival was significantly shorter in patients with advanced stage, skin and chest wall involvement (T4), positive lymph node infiltration, positive hormonal receptor, and triple negative subtype (log-rank Mantel-Cox tests, p < 0.05). CONCLUSION: We found a high frequency of young breast cancer with biologically more aggressive tumors, late diagnosis, frequent relapse, and poor prognosis. Further actions to improve clinical management and meet psychosocial needs in young breast cancer patients are warranted.