Tumor size, node status, grading, HER2 and estrogen receptor status still retain a strong value in patients with operable breast cancer diagnosed in recent years.

Breast cancer prognosis has improved greatly in recent years. Consequently, a thorough search for sensitive prognostic factors, able to help clinicians offer appropriate therapy, has become a priority in this area. In this study, we considered all new cases of invasive breast cancer diagnosed in the Province of Modena, Italy, between 1997 and 2007, registered by the Modena Cancer Registry. The principal endpoint of this study was relapse-free survival (RFS). A set of 11 clinic and pathological parameters was investigated. After a median follow-up of 73 months, 494 relapses were recorded. Tumor size, node status, grading, HER2 and estrogen receptor status were retained as independent factors in a multivariate analysis. Using these variables, a prognostic model was devised to identify three groups at different risk. In the training sample, the 5-year RFS rates resulted 96.0%, 82.9% and 63.7% in patients at low, intermediate and high risk, respectively (p < 0.0001). In the validation sample, the 5-year RFS was 96.2%, 85.4% and 66.9%, respectively. To conclude our study demonstrates that a very simple prognostic index based on easily available clinical data may represent a useful tool for the identification of patients at different risk of relapse and may be a notable device to predict who truly benefits from medical treatment

Clinical and Pathological Features of Breast Cancer in Systemic Sclerosis: Results from the Sclero-Breast Study

Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients

CLINICAL AND PATHOLOGICAL FEATURES OF BREAST CANCER IN PATIENTS WITH SYSTEMIC SCLEROSIS: PRELIMINARY DATA FROM THE SCLERO-BREAST STUDY

Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients

STRATEGIES TO PREDICT TREATMENT RESPONSE AND SELECT THERAPIES IN METASTATIC BREAST CANCER PATIENTS USING A NEXT GENERATION SEQUENCING MULTI-GENE PANEL

The standard of care for many patients with advanced breast cancer (BC )is gradually evolving from empirical treatment based on clinicalpathological characteristics to the use of targeted approaches based on the molecular profile of the tumor. In the last decade, an increasing number of molecularly targeted drugs have been developed for the treatment of metastatic BC. These drugs target specific molecular abnormalities that confer to cancer cells a survival advantage. Interestingly, the ability to perform multigene testing for a range of molecular alterations may provide an opportunity to clarify the mechanisms of treatment response, to find the strategies to overcome treatment resistance and thus, to identify patients who are more likely to develop relapse and who may be candidates for matched targeted therapies. The main aim of this study is to find prognostic and predictive molecular biomarkers for the management of metastatic BC patients in clinical practice

STRATEGIES TO PREDICT TREATMENT RESPONSE AND SELECT THERAPIES IN METASTATIC BREAST CANCER PATIENTS USING A NEXT GENERATION SEQUENCING (NGS) MULTI-GENE PANEL

The standard of care for many patients with advanced breast cancer (BC )is gradually evolving from empirical treatment based on clinicalpathological characteristics to the use of targeted approaches based on the molecular profile of the tumor. In the last decade, an increasing number of molecularly targeted drugs have been developed for the treatment of metastatic BC. These drugs target specific molecular abnormalities that confer to cancer cells a survival advantage [1]. Interestingly, the ability to perform multigene testing for a range of molecular alterations may provide an opportunity to clarify the mechanisms of treatment response, to find the strategies to overcome treatment resistance and thus, to identify patients who are more likely to develop relapse and who may be candidates for matched targeted therapies [2-3]. The main aim of this study is to find prognostic and predictive molecular biomarkers for the management of metastatic BC patients in clinical practice. MATERIALS AND METHODS The amplicon-sequencing analyses took advantage of the Ion AmpliSeq™ technology (Thermo Fisher, Waltham, MA, USA). A custom panel was designed with the help of the Designer online tool (www.ampliseq.com), which was employed to generate optimized primers encompassing the coding DNA sequences (with 100bp of exon padding and the UTRs regions) of 25 genes in the Human Reference Genome (hg19); these genes were selected searching and screening scientific literature for treatments resistance in BC and are reported in Table 1. Primer pairs were divided into two pools to optimize multiplex PCR conditions and the coverage, that assessed to 89.02%. The customized Ion AmpliSeq panel was employed on samples from 7 primary BC samples and matched metastatic sites (3 skin, 3 lymph node and 1 lung metastases). They were all processed using the Ion AmpliSeq Library Kit 2.0, starting from 15 nanograms of FFPE extracted DNA/pool. Samples were barcoded with the Ion Express Kit to optimize matched patients pooling on the same 318 Chip v2 sequencing chip. The template-positive Ion Sphere Particles were sequenced on a Personal Genome Machine (Thermo Fisher, Waltham, MA, USA). RESULTS The mutation profiles of paired primary and secondary tumors of the seven patients enrolled in this study are presented in Table 2. Ten different genes (PTEN, PIK3CA, mTOR, ERBB2, ERBB3, MET, INPP4B, MAP2K1, CDK6, KRAS) in 6 different patients showed possible damaging variants as shown in Table 2. • Four patients (number 1, 3, 5 and 6) showed no additional or different mutations in secondary tumors if compared to primary samples. • In patient number 2, the metastatic site presented new mutations if compared to the primary tumor. • Finally in patient number 4 and 7 we did not detect in metastases some of the mutations found in the primary tumor. DISCUSSION In 5 patients (71,4%) the mutational status of primary tumor could explain treatment resistance and thus predict relapse, in one patient the mutational status of the new subclones could be relevant for guiding differently the subsequent treatment choices. In 2 patients (28,5%) we were not able to detect in metastases some of the mutations found in the primary tumor. This could be explained by considering the clonal evolution of metastases. These preliminary data suggest that the multi-gene panel analysis of primary and secondary tumors may help clinicians: • in discriminating BC patients HR+ and/or HER2+ with mutations predicting an increased risk of adjuvant treatment resistance and thus relapse • in guiding treatment selection strategies in the metastatic setting. The study is still open and we are currently recruiting other patients.The main aim of this study is to find prognostic and predictive molecular biomarkers for the management of metastatic BC patients in clinical practice. The preliminary data suggest that the multi-gene panel analysis of primary and secondary tumors may help clinicians: • in discriminating BC patients HR+ and/or HER2+ with mutations predicting an increased risk of adjuvant treatment resistance and thus relapse • in guiding treatment selection strategies in the metastatic setting. The study is still open and we are currently recruiting other patients

Racial differences in the outcome of patients with urothelial carcinoma of the upper urinary tract: an international study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86897/1/j.1464-410X.2011.10188.x.pd

KI67 AS A PREDICTOR OF RESPONSE AND LONG TERM SURVIVAL IN HORMONE RECEPTOR POSITIVE/HER2 NEGATIVE BREAST CANCER PATIENTS TREATED WITH PREOPERATIVE CHEMOTHERAPY

Purpose: Breast cancer is a heterogeneous disease, and newer technologies have identified different molecular classes with distinct behaviour. In particular, hormone receptor positive tumors can be classified as luminal A or luminal B subtypes. Luminal A is a true endocrine dependent disease, generally characterized by high hormone receptor expression, low proliferation and HER2 negativity. Luminal B tumors show a more aggressive phenotype, expressed as a higher proliferation and/or HER2 positivity. It is known that hormone receptor positive tumors are less likely to achieve a pathologic complete response (pCR) after preoperative chemotherapy. Aim of the present analysis was to discriminate, on the basis of tumor proliferation as measured by Ki67, patients with hormone receptor positive/HER2 negative tumors with different probability of obtaining a pCR, and with different long term outcome. Patients and Methods: 274 consecutive stage II-III breast cancer patients treated with preoperative chemotherapy were evaluated. Patients were classified as having hormone receptor positive tumors in case of ER and/or PgR &gt;/= 10%. On the basis of immunohistochemical characteristic, patients were classified as follows: Luminal A, in case of hormone receptor positivity, HER2 negativity, and Ki67&lt;15% (16%); Ki67-Luminal B, in case of hormone receptor positivity, HER2 negativity and Ki67 &gt;/= 15% (37%); HER2-Luminal B in case of hormone receptor positivity and HER2 positivity (19%); HER2, in case of hormone receptor negativity and HER2 positivity (8%); triple negative, in case of hormone receptor negativity and HER2 negativity (20%) Results: Patients characteristics were as follows: median age 50 yrs (range: 27-76); clinical stage: IIA 35.7%, IIB 42.3%, III 22%. After a median of 4 courses of preoperative chemotherapy, 46% of the patients underwent conservative surgery. A pCR, as defined as absence of infiltrating tumor in both breast and axillary lymph-nodes, was observed in 28 patients (10.2%). All hormone receptor positive patients received adjuvant hormonal therapy for 5 years after surgery. The probability of obtaining a pCR was significantly lower in patients with hormone receptor positive tumors: 6.8% vs 17.5% in hormone receptor negative, p=0.010. No pCR was observed in the 40 patients classified as having Luminal A tumor; two pCRs only were observed among the 89 patients classified as having Ki67-Luminal B tumors. Patients in the Ki67-Luminal B group had significantly shorter disease-free survival (DFS) as compared with Luminal A patients (5-yr DFS 63% vs 86%, p= 0.0061). The 5-yr overall survival in Ki67-Luminal B group was 88% versus 93% in the Luminal A group. However, with 14 events only, this difference was not statistically significant. Conclusions: In this analysis, patients with Ki67-Luminal B have a worse DFS as compared to patients with Luminal A disease. Due to the limited number of events, no differences in the probability of obtaining a pCR were observed between Luminal A and Ki67-Luminal B tumors

Adenomyosis of the Extrapelvic Portion of the Round Ligament

Background: Adenomyosis is a disease of the uterus characterized by invasion of endometrial cells within the myometrium. Adenomyosis is typically confined to the uterus, with no distant localizations. This article reports on a case of adenomyosis of the distal extrapelvic portion of the round ligament. Case: The patient, a 49-year-old woman, had previously undergone surgery for pelvic endometriosis. This prior surgery included removal of uterus, fallopian tubes, and a portion of the sigmorectal intestine. She then presented with a nodule on the right side of her pubis. The nodule was close to the upper part of her right labia majora. She was experiencing cyclic pain, nodule enlargement, and edema on the right side of her pubis. The entire round ligament, from the internal inguinal canal to its distal end above the pubis, was removed. Histology testing revealed that the distal nodule was a myomalike neoformation containing endometrial tissue; this was definable as adenomyosis. Results: After the surgical procedure, the patient recovered quickly and after 6 months she was still free of symptoms. Conclusions: To the current authors' knowledge, this is the first case describing such a distant migration of endometrial cells up to the final extraperitoneal end of the round ligament to form a nodule of adenomyosis. A physical examination and imaging should be performed to rule out hernia, a cyst of the Nuck's duct, or lymph-node enlargement. Complete excision is curativeBackground: Adenomyosis is a disease of the uterus characterized by invasion of endometrial cells within the myometrium. Adenomyosis is typically confined to the uterus, with no distant localizations. This article reports on a case of adenomyosis of the distal extrapelvic portion of the round ligament. Case: The patient, a 49-year-old woman, had previously undergone surgery for pelvic endometriosis. This prior surgery included removal of uterus, fallopian tubes, and a portion of the sigmorectal intestine. She then presented with a nodule on the right side of her pubis. The nodule was close to the upper part of her right labia majora. She was experiencing cyclic pain, nodule enlargement, and edema on the right side of her pubis. The entire round ligament, from the internal inguinal canal to its distal end above the pubis, was removed. Histology testing revealed that the distal nodule was a myomalike neoformation containing endometrial tissue; this was definable as adenomyosis. Results: After the surgical procedure, the patient recovered quickly and after 6 months she was still free of symptoms. Conclusions: To the current authors' knowledge, this is the first case describing such a distant migration of endometrial cells up to the final extraperitoneal end of the round ligament to form a nodule of adenomyosis. A physical examination and imaging should be performed to rule out hernia, a cyst of the Nuck's duct, or lymph-node enlargement. Complete excision is curative. (J GYNECOL SURG 32:204