Wire guided localisation for targeted axillary node dissection is accurate in axillary staging in node positive breast cancer following neoadjuvant chemotherapy.

AIM: This study investigated whether wire localisation of the histologically proven positive, clipped axillary lymph node (ALN) with subsequent targeted axillary dissection (TAD) following neoadjuvant chemotherapy (NACT) improves axillary staging in breast cancer. MATERIALS AND METHODS: We performed a retrospective review of patients with primary breast cancer and core biopsy proven metastatic ALNs, that had an excellent nodal radiological response following NACT, treated at our centre between January 2016 and December 2018. The initial cohort of patients (Group 1) underwent sentinel lymph node biopsy (SLNB), with a minimum of three nodes were sampled. The subsequent cohort (Group 2) had a marker clip inserted in the metastatic ALN prior to NACT. This cohort underwent wire guided excision of the clipped node in addition to SLNB, with a minimum of three nodes sampled. RESULTS: A total of 47 patients were identified. Group 1 comprised 22 patients with a sentinel lymph node (SLN) identification rate (IR) of 95%. 25 patients (Group 2) underwent wire guided clip location and the SLN IR was 100% with a 92% clipped node IR. Evidence of pathological complete response (pCR) in the clipped node was associated with pCR in other nodes. CONCLUSION: Targeted axillary dissection is a feasible technique following excellent response to NACT in selected patients with limited volume ALN metastasis, at diagnosis. The identification of the positive ALN during surgery is vital and the IR can be improved by clipping the node prior to NACT and wire guided localisation at the time of surgery.

Prognostic role of inflammatory biomarkers in metastatic breast cancer.

PURPOSE: The effects of inflammation on the prognosis, life expectancy and several parameters such as response to treatment of breast cancer have been previously studied. The purpose of this study was to investigate the effect of inflammatory markers on prognosis in patients with metastatic breast cancer. METHODS: This study was conducted on 81 patients with metastatic breast cancer who have been followed up at the Department of Medical Oncology, Hacettepe University Institute of Oncology, between December, 2009 and March, 2014. For all studied parameters Kaplan-Meier survival estimates and p values computed by log-rank test were calculated. A p value < 0.05 was considered statistically significant. RESULTS: Median follow-up time was 26 months. There were 38 deaths due to disease progression during the follow up. The levels of serum albumin, and erythrocyte sedimentation rate (ESR) were not associated with a significant effect on overall survival (OS). Among patients with a higher serum C-reactive protein (CRP), the estimated mean survival was 84±36 months, compared to 278±113 months among patients with a normal serum CRP (p=0.032). When patients with higher and normal lactate dehydrogenase (LDH) levels were compared, their 2-year OS survival rates were 68.2 and 87.7%, respectively (p=0.034). Among patients with higher serum ferritin levels, the estimated mean survival was 29±10 months, compared to 212±113 months for normal serum ferritin (p=0.01). Among patients with higher serum beta-2 microglobulin (ß2-M), the estimated mean OS survival was 28±8 months, compared to 84±57 months for those with normal levels (p<0.01). CONCLUSION: Serum CRP, ferritin and ß2-M can be useful prognostic factors for OS in patients with metastatic breast cancer.

Comparative study of receptor discordance between primary and corresponding metastatic lesions in breast cancer.

PURPOSE: It is well-known that tumor phenotype may change during the progression of breast cancer (BC). The purpose in this study was to compare the discordance in estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) between primary and recurrent/metastatic lesions (RML) and also to evaluate the prognostic significance of change in tumor phenotype on survival in patients with metastatic BC. METHODS: The medical records of 6638 patients with BC from two breast centers treated between 1992 and 2015 were retrospectively analyzed. Of the 6638 patients, 549 cases in whom recurrence was histologically proven by biopsy or by surgical resection were enrolled into this study. RESULTS: Our presentation 13.5% of the patients had metastatic disease. Biopsy on recurrence was obtained from distant metastasis sites in 250 (63.6%) patients or from locoregional soft tissues/lymph-nodes in 143 (36.4%). Receptor discordance in ER, PgR and HER2 expressions between primary and RML were 27.2% (p=0.32), 38.6% (p<0.001) and 14.4% (p=0.007), respectively. Subsequent gain of ER and PgR showed significantly higher overall survival (OS) and post-recurrence survival (PRS) compared to the corresponding concordant-negative patients (119 vs 57 months, p=0.001 and 56 vs 31 months, p=0.03 for ER, 148 vs 58 months, p=0.003 and 64 vs 31 months, p=0.01 for PgR, respectively), hormone receptor (HR) loss was associated with worse OS. Similarly, HER2-loss cases experienced poorer PRS and OS outcomes, compared with those having stable HER2 expression (median 26 vs 60 months, p=0.009 for PRS and median 60 vs 111 months, p=0.06 for OS, respectively). CONCLUSION: This study confirmed the receptor discordance in ER/PgR and HER2 receptor expressions between primary and RML in patients with metastatic BC. As the loss of receptor expression is the most responsible factor for the discordance, treatments of recurrent/metastatic tumors should be individualized on the basis of molecular and genomic properties.

Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients.

PURPOSE: The relation between higher body mass index (BMI) and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is a controversial issue according to the data of Western and Asian patients. The aim of this study is to evaluate BMI and pCR to NAC and discuss the importance of pCR outcomes in Turkish BC patients as a bridging country between Europe and Asia. PATIENTS AND METHODS: Of the 4423 BC patients diagnosed between the years 1994 and 2015 in Hacettepe University Cancer Institute, 295 female patients with stage II and III BC were enrolled in the study. Three different group divisions were done according to patients' BMI as normal or underweight (N/U) patients (BMI <25 kg/m2), overweight (OW) patients (BMI = 25-29.9 kg/m2) and obese (OB) patients (BMI ≥30 kg/m2). BC subtypes were defined as luminal-like (ER/PR-positive and HER2-negative), HER2/luminal (ER/PR-positive and HER2-positive), HER2-type (ER/PR-negative and HER2-positive), and triple-negative (TNBC; ER/PR- and HER2-negative). The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed according to Kaplan-Meier method. The Log-rank test was used to compare the subgroup analysis and logistic regression analysis to determine the independent prognostic factors. RESULTS: In this study, a total number of 93 (31.5%) patients were N/U, 107 (36.3%) patients were OW and 95 (32.2%) patients were OB. Among groups, except for the age, no baseline clinicopathological differences were found. In 70 (23.7%) patients, pCR was achieved. pCR rates in N/U, OW and OB were 31.2%, 22.4%, and 17.9% respectively, showing a considerable trend towards significance (P = 0.09 in chi-square test). In the multivariate logistic regression analysis, obesity was an independent adverse prognostic feature on pCR to NAC compared to N/U patients (OR, 0.34; 95% CI, 0.13 to 0.85, P = 0.02). The recurrence rates were slightly increased with the increase of BMI (N/U = 24.7%, OW = 29.0% and OB = 40%; P = 0.06 respectively). Median RFS was significantly higher in N/U group compared to OB patients (150 vs. 76 months respectively, P = 0.03) and was also higher in pCR group compared to non-pCR patients (151 vs. 77 months P = 0.004). Median OS was significantly higher in N/U patients compared to OB patients (N/U = not reached, OW = 211 and OB = 114 months; P = 0.01) and was also higher in pCR group compared to non-pCR patients (not reached vs. 211 months P = 0.04). In Cox regression analysis; pCR, histopathological grade and TNBC were found as independent prognostic factors on OS (HR, 0.29; 95% CI, 0.11 to 0.79, P = 0.015, HR, 2.09; 95% CI, 1.14 to 3.83, P = 0.017, HR, 1.95; 95% CI, 1.01 to 3.77, P = 0.046, respectively). CONCLUSION: It was observed that obesity was an important independent prognostic factor which has an adverse effect on pCR. Moreover it causes decreasing RFS and OS in BC patients who had received NAC. The probability of inefficient treatment in obese patients should be considered.

The association between body mass index and immunohistochemical subtypes in breast cancer.

BACKGROUND: Body mass index (BMI) is defined as a poor prognostic factor in patients with breast cancer (BC). However, there are controversial results regarding the various effects of BMI on BC, hence the exact pathophysiology of the relation between obesity and BC is still under debate, and remains unclear. This paper aims to investigate the association between BMI at presentation and BC subtypes defined according to the immunohistochemical classification in both premenopausal and postmenopausal patients with BC. PATIENTS AND METHODS: This study is a retrospective and explorative analysis of the 3767 female BC patients from a single center. All patients' BMI at the time of initial diagnosis and tumor demographics were recorded. BMI was stratified into 3 groups as normal-weighted (BMI <25 kg/m2), over-weighted (BMI = 25-29.9 kg/m2), and obese (BMI ≥30 kg/m2). Immunohistochemical classification of the tumors was categorized into 4 groups as follows; luminal-like, HER2/luminal-like, HER2-like, and triple-negative according to the ER/PR and HER2 status. Distribution of Immunohistochemical subtypes, tumor characteristics, and overall survival (OS) analysis were evaluated according to the BMI groups in both premenopausal and postmenopausal patients. RESULTS: Median BMI of premenopausal and postmenopausal patients was 25.5 (kg/m2) and 28.8 (kg/m2), respectively (P < 0.001). In parallel with the increasing age, patients were more obese at diagnosis in both premenopausal (P < 0.001) and postmenopausal period (P < 0.001). Triple-negative subtype was significantly more frequent in premenopausal patients with BMI ≥30 kg/m2 compared to BMI <30 kg/m2 (P = 0.007). Additionally, premenopausal patients with BMI ≥30 kg/m2 had less common luminal-like subtype (P = 0.033) and more frequently presented with higher tumor stage (P = 0.012) and tumor grade (P = 0.004) compared to patients with BMI <25 kg/m2. On the other hand, premenopausal patients with BMI <25 kg/m2 had significantly more ER-positive tumors (P < 0.001) and lower stages of disease (P = 0.01) compared to their counterparts with BMI ≥25 kg/m2. Premenopausal obese patients with triple-negative (P = 0.001) and luminal-like subtype (P = 0.002) had significantly shorter OS duration compared to overweight counterparts. HER2/luminal-like subtype was found to be significantly greater in postmenopausal overweight patients (P = 0.005). However, BMI had no any other significant effect on survival and immunohistochemical subtypes in postmenopausal patients. Multivariate analysis revealed that triple-negative subtype, grade III tumor, BMI ≥30 kg/m2, T3-4 (P < 0.001), nodal involvement, metastatic disease, and lymphovascular involvement were significantly associated with poorer OS. CONCLUSION: Our data indicated that BMI was an independent factor in patients with BC, with an association indicating a decreased incidence for luminal-like subtype and increased incidence for triple-negative subtype among premenopausal patients. However, this significance was not found in postmenopausal patients. Accordingly, a plausible etiological heterogeneity in BC might play a role among immunohistochemical subtypes in every life stage of women.

Trastuzumab 1-year vs 9-week in early-stage HER2-positive, lymph node negative breast cancer patients.

PURPOSE: Optimal duration of adjuvant trastuzumab therapy in early-stage HER2-positive, lymph node-negative breast cancer is unknown. To establish this, we compared 1-year and 9-week trastuzumab regimens in HER2-positive, lymph node-negative early-stage breast cancer patients. METHODS: We retrospectively analyzed 4374 breast cancer patients. There were 181 early-stage, lymph node-negative breast cancer patients who were treated with adjuvant trastuzumab for either 9-week or 1-year schedule. A total of 101 patients received trastuzumab for 9 weeks and the remaining 80 patients received this adjuvant therapy for 1 year. Disease free survival (DFS) and overall survival (OS) rates of both groups were calculated. RESULTS: There was no difference between groups according to OS. Five-year OS rates were 95.5% in the 9-week group and 93.3% in the 1-year group (p=0.78). DFS was affected by age, having tamoxifen therapy and disease stage. Nine-week trastuzumab group was superior to 1-year group and 5-year DFS rates were 91% in 9-week group and 81.2% in 1-year group (p=0.02). However, the 1-year group had more stage II patients than the 9-week group. We did not find any difference between groups regarding developing congestive heart failure. CONCLUSION: It appeared that 9-week trastuzumab treatment was not inferior to 1-year trastuzumab treatment in early-stage, lymph node-negative breast cancer patients.

Correlation of educational status and clinicopathological characteristics of breast cancer: a single center experience.

PURPOSE: Educational status may be an important parameter in assessing breast cancer risk and prognosis. The purpose of this study was to investigate the correlation between the level of education and clinicopathological characteristics of breast cancer, including tumor grade, HER-2 and estrogen receptor (ER) status, tumor size, axillary lymph node involvement and metastasis. METHODS: The study included 1800 women who were diagnosed with invasive breast cancer during 2005-2013 at Hacettepe University Cancer Institute. Patients were divided into three groups according to their educational status at the time of diagnosis as follows: low (illiterate and elementary school, 5 years or less of education), medium (secondary school and upper secondary school, 6-12 years of education) and high (university level, more than 12 years of education). The associations between educational status and clinicopathologic features of breast cancer at the time of diagnosis were evaluated. RESULTS: In all patient, a significant relationship was found between educational status and T stages (p<0.0001). Patients with higher educational levels were reported to have smaller tumor size regardless to their age and were less likely to have axillary lymph node involvement (p=0.001) or metastasis (p=0.001). A significant correlation was found between educational status and ER positivity in patients over 50 years of age (p=0.03). When the patients of all ages were evaluated, no statistically significant correlation was shown (p=0.27) between educational status and ER positivity. A significant relationship was found between educational status and HER-2 status (p=0.003), regardless of the patients' age. HER-2 positivity increased in patients with low educational status, however this significance was lost in patients over the age of 50 (p=0.1). CONCLUSION: The relationship between educational status and biological factors in breast cancer are not conclusive as yet, but this particular study revealed that educational status played a major influence in each of the five breast cancer prognostic factors: ER status, HER-2 status, tumor size, lymph node status and metastasis.

Left laterality is an independent prognostic factor for metastasis in N3 stage breast cancer.

PURPOSE: Development of metastasis in patients with breast cancer (BC) is the most important negative prognostic factor and this process mainly begins with lymphatic involvement. Therefore, axillary, subclavicular, internal mammary or supraclavicular nodal involvement is a crucial step before metastasis. Anatomical differences between the right and left lymphatic drainages of the breasts may significantly affect the rate, site and time to development of distant metastasis. The purpose of this study was to investigate if laterality is an independent prognostic factor for metastasis in N3 breast cancer patients. METHODS: From a total of 4215 BC patients diagnosed between 1994 and 2015 in our center, 305 non-metastatic women with pathological N3 (pN3) nodal status at presentation were enrolled in this study. Patients were divided into two groups: left and right BC. Analysis of overall survival (OS) and time to first metastasis (TTM) was performed according to Kaplan-Meier method with log-rank test. RESULTS: The median number of lymph node involvement and lymph node ratio (number of positive lymph nodes / total number of excised lymph nodes) between the two groups was equal (14 and 0,66 respectively). Recurrence was observed in 123 patients [53 (35%) right vs 70 (44%) left group]. Patients with left BC had significantly higher rate of axial bone metastases compared with the right BC group (55.7 vs 35.8%, p<0.02, respectively). TTM was significantly shorter in the left BC group [49.1 months (95% CI 36.5-61.8) vs 103.6 months (95% CI 47.0-160); p7equals;0.03, respectively]. Median OS did not differ between the groups, however, there was a trend towards lower OS in patients with left BC (p=0.68). CONCLUSION: Left laterality in patients with pN3 non-metastatic BC is an independent prognostic factor associated with shorter TTM, increased risk of distant metastases and axial bone involvement compared with right laterality.

Handedness and breast cancer characteristics.

PURPOSE: Around 10% of the population is left-handed (LH) and the new data suggests that there is genetic as well as environmental influence on the hand preference. The purpose of this study was to evaluate the relationship between breast cancer and hand preference. METHODS: Breast cancer patients diagnosed and treated at the Department of Medical Oncology, Hacettepe University, Institute of Oncology between March 2006 and May 2010 were included in the study. The preferred handedness was asked in all patients and recorded in the patients' medical database. RESULTS: A total of 898 patients with breast cancer were analyzed for handedness, basic characteristics and survival. The median age was 48 years (range 20-83) and all but one patient were female. Of all, 434 (48.3%) patients were pre, 61 (6.8%) were peri, and 399 patients (44.4%) were postmenopausal. Nearly all of the patients (n=869, 96.7%) were operated and modified radical mastectomy was the most frequent type of surgery (N=654, 72.8%). Invasive ductal carcinoma was observed in 659 (73.3%) and in 659 patients (73.1%)estrogen receptors (ER) were positive. Similarly 569 (63.4 %) patients were progesterone receptor (PR) positive and 181 (20.2%) had HER2 overexpression. Most of the patients had T2 (434; 48.3%), N0 (376; 41.9%) and M0 (830; 92.4%) tumors. Of all, 55 (6.1%) patients were LH and the remaining 843 (93.9%) were right-handed (RH). There was no statistically significant difference between the groups related to ER or PR status, TNM classification, tumor localization, menopausal status, HER2 or histological subtype. However the median age of diagnosis in right-handers was higher (48-46 years, p=0.02). There were 10 (1.1%) patients who had already passed away at the time of analysis. The mean overall survival (OS) for RH patients was 33 months (range 1-281) and for LH patients it was 35 months (range 1-182) (p=0.751). The disease disease-free survival (DFS) was 29 months for both groups (p=1.00). CONCLUSION: In our trial the onset of breast cancer was 2 years earlier in LH patients with similar disease characteristics compared to RH patients. As a consequence, it may be advocated that the screening of LH patients should start earlier.

Efficacy and safety of eribulin monotherapy in patients with heavily pretreated metastatic breast cancer.

PURPOSE: Eribulin is a non-taxane microtubule inhibitor, which can be used after anthracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of eribulin monotherapy in heavily pretreated MBC patients. METHODS: In this single-center trial, a total of 66 MBC patients who received eribulin monotherapy in Hacettepe University Cancer Institute between 2013 and 2015 were retrospectively analyzed. Kaplan-Meier survival analysis was carried out for progression free survival (PFS) and for overall survival (OS). Two-sided p values <0.05 were considered as statistically significant. RESULTS: Sixty-six patients who received at least one cycle of eribulin were registered. Most patients were heavily pretreated with a median of 4 (range 2-7) previous chemotherapy lines prior to eribulin. Median patient age was 50 years (range 28-67). Most patients were treated with eribulin at 4th or 5th line (33.3 and 27.3%, respectively). Brain metastases were present in 19 (28.8%) patients at the time of initial eribulin administration. Median PFS was 5 (95% CI 4.1-5.8) and median OS was 8 (95% CI 6-9.9) months. Fifteen patients (22.7%) responded to treatment with partial remission (PR) and 36 (54%) had stable disease (SD). No hypersensitivity reactions and no toxic deaths were observed. Three (5%) patients experienced grade 4 neurotoxicity. Fourteen (21.5%) patients developed grade 3-4 neutropenia. CONCLUSION: Eribulin monotherapy is an effective and safe regimen for MBC patients. Its low toxicity profile compared to other intravenous cytotoxic agents and the ease in its intravenous administration make this agent a preferable option for both physicians and patients.

Management of hair loss associated with endocrine therapy in patients with breast cancer: an overview.

Endocrine therapy-induced hair loss (ETIHL) associated with aromatase inhibitors and tamoxifen treatment is currently mostly reported but remained an unresolved therapeutic issue in patients with breast cancer (BC) since the number of studies regarding the management is limited in literature. Herein we investigated the possible causes of this clinical problem and its relation with endocrine therapies widely used for BC survivors and made some modest practical recommendations in light of the literature review in order to provide an optimal management. On the basis of literature findings, common causes of hair loss apart from endocrine therapies should be investigated with an initial evaluation workup and then should be corrected, if observed. Treatment with topical 5-alpha reductase inhibitors and supplementation of Vitamin C and omega-3 fatty acids are likely appeared to be the most appropriate treatment agents for ETIHL without causing an adverse effect on BC prognosis. However, more prospective, randomised, placebo-controlled studied are required in order to confirm our results and also identify the clinical effects of this problem on patients with BC.

Effect of body mass index on the efficacy of adjuvant tamoxifen in premenopausal patients with hormone receptor-positive breast cancer.

PURPOSE: Obesity has been confirmed to be an adverse prognostic factor in patients who were treated with aromatase inhibitors; however, such relationship has never been thoroughly investigated in patients treated with tamoxifen. The purpose of this study was to examine the effect of body mass index (BMI) on the efficacy of adjuvant tamoxifen in premenopausal patients with hormone receptor-positive breast cancer. METHODS: Newly diagnosed premenopausal and non-metastatic hormone receptor-positive breast cancer patients were enrolled in the study. Patients with BMI ranging between 18.5 and 24.9 kg/m(2) were considered as normal weight patients (Arm A, n = 408), and/patients with a BMI ≥ 25 kg/m(2) were considered as overweight and obese patients (Arm B, n = 418). RESULTS: In both normal weight and overweight patients, the baseline clinicopathologic properties and the treatment history with radiotherapy and chemotherapy were similar and no statistical significant difference could be detected. Tamoxifen in combination with luteinizing hormone-releasing hormone (LHRH) agonist was used in 33% (136/408) of the patients in Arm A and in 22% (91/418) of patients in Arm B (p<0.001). Three-year disease free survival (DFS) rates were 89% and 87% in arm A and arm B, respectively (p=0.39). Three-year overall survival (OS) rates were 99% in arm A and 94% in arm B which appeared to be of significance (p=0.028). In univariate analysis no statistical significant effect of LHRH agonist usage on DFS (p=0.58) and OS (p=0.96) was found. CONCLUSION: Although BMI had no negative effect on recurrence risk, poor OS was observed in overweight and obese premenopausal breast cancer patients with hormone-receptor positive tumors who were treated with tamoxifen.

Current management of aromatase inhibitor-induced arthralgia.

Aromatase inhibitors (AIs) are standard of care in the adjuvant setting of postmenopausal women with hormone receptor positive breast cancer. Despite their beneficial effects on survival outcomes in breast cancer, AIs-induced arthralgia (AIA) is a common side effect which may lead to drug discontinuation and decreased AIs adherence among patients. So far, the exact pathophysiology of AIA is still an unclarified condition that explains why the optimal treatment in its management has not yet been established. Moreover, studies regarding the alternative treatment options for AIA are limited due to small sample size. Herein, we report a summary of current treatment options and their effectiveness in AIA with a practical algorithm in light of the relevant literature.

Patients' understanding of treatment goals and disease course and their relationship with optimism, hope, and quality of life: a preliminary study among advanced breast cancer outpatients before receiving palliative treatment.

PURPOSE: The aims of this study were to explore advanced breast cancer patients' knowledge of treatment intent and expectation of illness course and to evaluate their relationship with optimism, hope, and quality of life (QoL). METHODS: Patients with advanced breast cancer (n = 55) who were treated in the ambulatory clinic of the University of Hacettepe were included in the study. They completed Life Orientation Scale, The Hope Scale, and the European Organization for Research and Treatment of Cancer Quality of Life questionnaires. The data regarding the knowledge of illness progression and the perceptions of therapy intent were assessed using self-administered open-ended questionnaires that were answered by the patients. RESULTS: The data revealed that 58.2 % of the patients had an inaccurate perception of treatment intent, believing the aim of treatment was cure, whereas only 38.2 % of the patients had a realistic expectation that their disease may remain stable or may progress over a year. In addition, the awareness of disease progression and perception of goals of treatment was significantly related to hope and optimism scores but not to QoL. CONCLUSIONS: A large proportion of patients diagnosed with advanced breast cancer believed that their treatment was "curative", and they would improve within a year. Findings of our study suggest that patients with inaccurate perception of treatment intent and unrealistic expectation of prognosis have higher hope and optimism scores than those who do not, but there were no significant differences in terms of global health status.

Predictive factors for invasive cancer in surgical specimens following an initial diagnosis of ductal carcinoma in situ after stereotactic vacuum-assisted breast biopsy in microcalcification-only lesions.

PURPOSE: The aim of this study was to determine the incidence of invasive breast carcinoma in patients with preoperative diagnosis of ductal carcinoma in situ (DCIS) by stereotactic vacuum-assisted biopsy (SVAB) performed for microcalcification-only lesions, and to identify the predictive factors of invasion. METHODS: From 2000 to 2010, the records of 353 DCIS patients presenting with microcalcification-only lesions who underwent SVAB were retrospectively reviewed. The mammographic size of microcalcification cluster, presence of microinvasion within the cores, the total number of calcium specks, and the number of calcium specks within the retrieved core biopsy specimen were recorded. Patients were grouped as those with or without invasion in the final pathologic report, and variables were compared between the two groups. RESULTS: The median age was 58 years (range, 34-88 years). At histopathologic examination of the surgical specimen, 63 of 353 patients (17.8%) were found to have an invasive component, although SVAB cores had only shown DCIS preoperatively. The rate of underestimation was significantly higher in patients with microcalcification covering an area of 40 mm or more, in the presence of microinvasion at biopsy, and in cases where less than 40% of the calcium specks were removed from the lesion. CONCLUSION: Invasion might be underestimated in DCIS cases diagnosed with SVAB performed for microcalcification-only lesions, especially when the mammographic size of calcification is equal to or more than 40 mm or if microinvasion is found within the biopsy specimen and less than 40% of the calcifications are removed. At least 40% of microcalcification specks should be removed from the lesion to decrease the rate of underestimation with SVAB.

A comprehensive review of denosumab for bone metastasis in patients with solid tumors.

BACKGROUND: Denosumab is fully human monoclonal antibody that specifically binds and inactivates receptor activator of NF-kB ligand (RANKL), an important ligand that regulates bone remodeling. In this review, we aimed to show the clinical data about denosumab treatment and discuss its advantages for the management of patients with solid tumors and bone metastasis. SCOPE: Denosumab showed positive results in clinical studies of solid tumors with bone metastasis. PubMed database and ASCO Symposium Meeting abstracts were searched until August 2015 by using the terms 'denosumab', 'RANKL inhibitor' and 'bone metastasis'. The last search was on 21 August 2015. All resulting studies were retrieved and were also checked for related publications. Clinical trials in this review fulfilled the following criterion: inclusion of sufficient data to allow estimation of the efficacy and safety of denosumab. FINDINGS: The effects of denosumab on skeletal-related events (SREs) were investigated in three large randomized trials: one in patients with breast cancer, one in patients with prostate cancer, and one in patients with multiple myeloma or solid tumors other than breast or prostate cancer. In the breast cancer and prostate cancer studies denosumab was non-inferior and also superior to zoledronic acid in terms of the primary outcome time to first on-study SRE. In the third study denosumab was non-inferior to zoledronic acid but was not superior to zoledronic acid in solid tumors excluding breast and prostate cancer with bone metastases. In the three studies median overall survival and disease progression rates were similar between zoledronic acid and denosumab. Denosumab has also been studied in bone loss associated with hormonal therapy in both breast and prostate cancer. Adjuvant denosumab significantly reduced the risk of clinical fracture risk by 50% in breast cancer patients and by 62% in non-metastatic prostate cancer patients treated with adjuvant aromatase inhibitors or androgen deprivation therapy. In addition, biochemical markers of bone turnover and fractures were significantly reduced in patients under denosumab treatment. CONCLUSION: The promising outcomes in the initial trials with denosumab have shown clinical activity and a favorable safety profile in patients with solid tumors and bone metastasis. Denosumab significantly reduced treatment-related osteoporosis associated with breast and prostate cancer and was superior to zoledronic acid in prevention or delaying of SRE.