Results of a Phase Ib Study Investigating Durvalumab in Combination with Eribulin in Patients with HER2-Negative Metastatic Breast Cancer and Recurrent Ovarian Cancer.

INTRODUCTION: The release of tumor-associated antigens with cytotoxic chemotherapy treatment may enhance the response to immune checkpoint blockade. Eribulin is a microtubule inhibitor with proven overall survival (OS) benefit in metastatic breast cancer (MBC), which may also enhance intratumoral vascular remodeling. Durvalumab, a humanized monoclonal antibody, targets the programmed cell death ligand-1 (PD-L1) receptor. This study sought to determine the maximum tolerated dose and recommended phase II dose (RP2D) of eribulin in combination with durvalumab, as well as the safety and preliminary antitumor activity of the combination in patients with previously treated HER2-negative (HER2-) MBC and recurrent ovarian cancer (ROC). METHODS: Cohorts of 3-6 patients with HER2- MBC and ROC were treated in a modified 3+3 design. Eligible patients received escalating doses of eribulin (1.1 mg/m2 or 1.4 mg/m2 IV on day 1 and day 8) with durvalumab (1.12 g IV on day 1) in 21-day cycles until dose-limiting toxicity (DLT), intolerable adverse events (AEs), disease progression, or other reasons for withdrawal. PRIMARY ENDPOINT: the rate of DLTs during cycles 1 and 2 of therapy. Secondary endpoints: AE rate, objective response rate (ORR), progression-free survival (PFS), and OS. RESULTS: Nine patients with a median of 4 prior therapies for advanced disease were treated: 5 patients with HER2- MBC (1 with triple-negative disease and 4 with hormone-positive disease) and 4 patients with ROC. The RP2D of eribulin was 1.4 mg/m2 in combination with durvalumab. There were no DLTs experienced during the first two cycles of therapy. The most common treatment-related AEs (>50%) were fatigue, neutropenia, decreased white blood cell count, anemia, AST and alkaline phosphatase elevation, hyperglycemia, and nausea; most were grade 1 or 2. There was one immune-related AE of grade 3 (hepatitis) after 5 cycles of treatment, for which patient came off study. Two other patients discontinued study drug related to toxicity (neutropenia [n = 1], hepatic toxicity [n = 1]). ORR was 55%, and 4 additional patients experienced stable disease. All MBC patients exhibited a response to therapy. Median PFS was 6.2 months. Median OS was 15.0 months. CONCLUSION: The combination of eribulin at a dose of 1.4 mg/m2 with standard dose durvalumab had a favorable AE profile in patients with previously treated HER2- MBC and ROC. The early antitumor activity observed in all MBC patients enrolled in the study suggests that further investigation of this combination is warranted.

An emerging generation of endocrine therapies in breast cancer: a clinical perspective.

Anti-estrogen therapy is a key component of the treatment of both early and advanced-stage hormone receptor (HR)-positive breast cancer. This review discusses the recent emergence of several anti-estrogen therapies, some of which were designed to overcome common mechanisms of endocrine resistance. The new generation of drugs includes selective estrogen receptor modulators (SERMs), orally administered selective estrogen receptor degraders (SERDs), as well as more unique agents such as complete estrogen receptor antagonists (CERANs), proteolysis targeting chimeric (PROTACs), and selective estrogen receptor covalent antagonists (SERCAs). These drugs are at various stages of development and are being evaluated in both early and metastatic settings. We discuss the efficacy, toxicity profile, and completed and ongoing clinical trials for each drug and highlight key differences in their activity and study population that have ultimately influenced their advancement.

Fibromixoma acral superficial envolvendo quirodáctilo: um relato de caso / Superficial acral fibromyxoma involving the fingers: a case report

O fibromixoma acral superficial é um tumor mesenquimal raro e benigno. Acomete principalmente homens de meia-idade; entretanto, pode ocorrer em qualquer sexo e faixa etária. Apresenta crescimento lento, com predileção por áreas ungueais e periungueais.

Superficial acral fibromyxoma is a rare and benign mesenchymal tumor. It mainly affects middle-aged men; however, it can occur in any gender and age group. It has a slow growth, with a preference for nail and periungual areas

Genomic comparison of paired primary breast carcinomas and lymph node macrometastases using the Oncotype DX Breast Recurrence Score® test.

PURPOSE: Adjuvant therapy decisions may in part be based on results of Oncotype DX Breast Recurrence Score® (RS) testing of primary tumors. When necessary, lymph node metastases may be considered as a surrogate. Here we evaluate the concordance in gene expression between primary breast cancers and synchronous lymph node metastases, based on results from quantitative RT-PCR-based RS testing between matched primary tumors and synchronous nodal metastases. METHODS: This retrospective, exploratory study included patients (≥ 18 years old) treated at our center (2005-2009) who had ER+ , HER2-negative invasive breast cancer and synchronous nodal metastases with available tumor blocks from both sites. Paired tissue blocks underwent RS testing, and RS and single-gene results for ER, PR, and HER2 were explored between paired samples. RESULTS: A wide distribution of RS results in tumors and in synchronous nodal metastases were modestly correlated between 84 paired samples analyzed (Pearson correlation 0.69 [95% CI 0.55-0.78]). Overall concordance in RS group classification between samples was 63%. ER, PR, and HER2 by RT-PCR between the primary tumor and lymph node were also modestly correlated (Pearson correlation [95% CI] 0.64 [0.50-0.75], 0.64 [0.49-0.75], and 0.51 [0.33-0.65], respectively). Categorical concordance (positive or negative) was 100% for ER, 77% for PR, and 100% for HER2. CONCLUSIONS: There is modest correlation in continuous gene expression, as measured by the RS and single-gene results for ER, PR, and HER2 between paired primary tumors and synchronous nodal metastases. RS testing for ER+ breast cancer should continue to be based on analysis of primary tumors.

Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102.

Purpose The mammalian target of rapamycin inhibitor everolimus targets aberrant signaling through the PI3K/AKT/mammalian target of rapamycin pathway, a mechanism of resistance to anti-estrogen therapy in estrogen receptor (ER)-positive breast cancer. We hypothesized that everolimus plus the selective ER downregulator fulvestrant would be more efficacious than fulvestrant alone in ER-positive metastatic breast cancer resistant to aromatase inhibitor (AI) therapy. Patients and Methods This randomized, double-blind, placebo-controlled, phase II study included 131 postmenopausal women with ER-positive, human epidermal growth factor receptor 2-negative, AI-resistant metastatic breast cancer randomly assigned to fulvestrant (500 mg days 1 and 15 of cycle 1, then day 1 of cycles 2 and beyond) plus everolimus or placebo. The study was designed to have 90% power to detect a 70% improvement in median progression-free survival from 5.4 months to 9.2 months. Secondary end points included objective response and clinical benefit rate (response or stable disease for at least 24 weeks). Prophylactic corticosteroid mouth rinses were not used. Results The addition of everolimus to fulvestrant improved the median progression-free survival from 5.1 to 10.3 months (hazard ratio, 0.61 [95% CI, 0.40 to 0.92]; stratified log-rank P = .02), indicating that the primary trial end point was met. Objective response rates were similar (18.2% v 12.3%; P = .47), but the clinical benefit rate was significantly higher in the everolimus arm (63.6% v 41.5%; P = .01). Adverse events of all grades occurred more often in the everolimus arm, including oral mucositis (53% v 12%), fatigue (42% v 22%), rash (38% v 5%), anemia (31% v. 6%), diarrhea (23% v 8%), hyperglycemia (19% v 5%), hypertriglyceridemia (17% v 3%), and pneumonitis (17% v 0%), although grade 3 to 4 events were uncommon. Conclusion Everolimus enhances the efficacy of fulvestrant in AI-resistant, ER-positive metastatic breast cancer.

A Phase I/II study of suberoylanilide hydroxamic acid (SAHA) in combination with trastuzumab (Herceptin) in patients with advanced metastatic and/or local chest wall recurrent HER2-amplified breast cancer: a trial of the ECOG-ACRIN Cancer Research Group (E1104).

PURPOSE: Suberoylanilide hydroxamic acid (SAHA; vorinostat), a small molecule inhibitor of histone deacetylase, attenuates signaling pathways known to confer trastuzumab resistance. A combination of SAHA and trastuzumab may be a promising strategy to improve the efficacy of trastuzumab against breast cancer. In this Phase I/II study, we evaluated the toxicity and response rate after treatment with SAHA and trastuzumab in patients with HER2-overexpressing metastatic breast cancer with trastuzumab-resistant progressive disease. METHODS: In Phase I, the SAHA dose was modified in cohorts of 3-6 patients to find the dose level at which 0 or 1 patients experienced a dose-limiting toxicity (DLT) during the first cycle of therapy. In the Phase II study, response to the recommended dose identified in Phase I was based on the response evaluation criteria in solid tumors. Overall survival and time to progression were also evaluated. RESULTS: The recommended dose was determined to be 200 mg twice a day on days 1-14 and IV trastuzumab 6 mg/kg on day 1 of a 21-day cycle (n = 6). The Phase II study (n = 10) was terminated when the pre-planned efficacy evaluation found that none of the patients in the primary analysis set responded to combination SAHA and trastuzumab treatment. CONCLUSIONS: In patients with HER2-positive metastatic breast cancer who had relapsed or progressed during trastuzumab therapy, we observed no DLTs with SAHA 200 mg twice daily combined with trastuzumab; however, there was insufficient statistical evidence that adding SAHA reversed trastuzumab resistance in these patients.

Association Between Use of a Scalp Cooling Device and Alopecia After Chemotherapy for Breast Cancer.

Importance: Chemotherapy-induced alopecia is a common and distressing adverse effect. In previous studies of scalp cooling to prevent chemotherapy-induced alopecia, conclusions have been limited. Objectives: To evaluate whether use of a scalp cooling system is associated with a lower amount of hair loss among women receiving specific chemotherapy regimens for early-stage breast cancer and to assess related changes in quality of life. Design, Setting, and Participants: A prospective cohort study conducted at 5 US medical centers of women with stage I or II breast cancer receiving adjuvant or neoadjuvant chemotherapy regimens excluding sequential or combination anthracycline and taxane (106 patients in the scalp cooling group and 16 in the control group; 14 matched by both age and chemotherapy regimen). The study was conducted between August 2013 and October 2014 with ongoing annual follow-up for 5 years. Exposures: Use of a scalp cooling system. Scalp cooling was initiated 30 minutes prior to each chemotherapy cycle, with scalp temperature maintained at 3°C (37°F) throughout chemotherapy and for 90 minutes to 120 minutes afterward. Main Outcomes and Measures: Self-estimated hair loss using the Dean scale was assessed 4 weeks after the last dose of chemotherapy by unblinded patient review of 5 photographs. A Dean scale score of 0 to 2 (≤50% hair loss) was defined as treatment success. A positive association between scalp cooling and reduced risk of hair loss would be demonstrated if 50% or more of patients in the scalp cooling group achieved treatment success, with the lower bound of the 95% CI greater than 40% of the success proportion. Quality of life was assessed at baseline, at the start of the last chemotherapy cycle, and 1 month later. Median follow-up was 29.5 months. Results: Among the 122 patients in the study, the mean age was 53 years (range, 28-77 years); 77.0% were white, 9.0% were black, and 10.7% were Asian; and the mean duration of chemotherapy was 2.3 months (median, 2.1 months). No participants in the scalp cooling group received anthracyclines. Hair loss of 50% or less (Dean score of 0-2) was seen in 67 of 101 patients (66.3%; 95% CI, 56.2%-75.4%) evaluable for alopecia in the scalp cooling group vs 0 of 16 patients (0%) in the control group (P < .001). Three of 5 quality-of-life measures were significantly better 1 month after the end of chemotherapy in the scalp cooling group. Of patients who underwent scalp cooling, 27.3% (95% CI, 18.0%-36.6%) reported feeling less physically attractive compared with 56.3% (95% CI, 31.9%-80.6%) of patients in the control group (P = .02). Of the 106 patients in the scalp cooling group, 4 (3.8%) experienced the adverse event of mild headache and 3 (2.8%) discontinued scalp cooling due to feeling cold. Conclusions and Relevance: Among women undergoing non-anthracycline-based adjuvant chemotherapy for early-stage breast cancer, the use of scalp cooling vs no scalp cooling was associated with less hair loss at 4 weeks after the last dose of chemotherapy. Further research is needed to assess outcomes after patients receive anthracycline regimens, longer-term measures of alopecia, and adverse effects. Trial Registration: clinicaltrials.gov Identifier: NCT01831024.

Randomized phase II trial of fulvestrant alone or in combination with bortezomib in hormone receptor-positive metastatic breast cancer resistant to aromatase inhibitors: a New York Cancer Consortium trial.

The proteasome inhibitor bortezomib enhances the effect of the selective estrogen receptor (ER) downregulator (SERD) fulvestrant by causing accumulation of cytoplasmic ER aggregates in preclinical models. The purpose of this trial was to determine whether bortezomib enhanced the effectiveness of fulvestrant. One hundred eighteen postmenopausal women with ER-positive metastatic breast cancer resistant to aromatase inhibitors (AIs) were randomized to fulvestrant alone (Arm A-500 mg intramuscular (i.m.) day -14, 1, 15 in cycle 1, and day 1 of additional cycles) or in combination with bortezomib (Arm B-1.6 mg/m2 intravenous (i.v.) on days 1, 8, 15 of each cycle). The study was powered to show an improvement in median progression-free survival (PFS) from 5.4 to 9.0 months and compare PFS rates at 6 and 12 months (α=0.10, ß=0.10). Patients with progression on fulvestrant could cross over to the combination (arm C). Although there was no difference in median PFS (2.7 months in both arms), the hazard ratio for PFS in Arm B versus Arm A (referent) was 0.73 (95% confidence interval (CI)=0.49, 1.09, P=0.06, 1-sided log-rank test, significant at the prespecified 1-sided 0.10 α level). At 12 months, the PFS proportion in Arm A and Arm B was 13.6% and 28.1% (P=0.03, 1-sided χ2-test; 95% CI for difference (14.5%)=-0.06, 29.1%). Of 27 patients on arm A who crossed over to the combination (arm C), 5 (18%) were progression-free for at least 24 weeks. Bortezomib likely enhances the effectiveness of fulvestrant in AI-resistant, ER-positive metastatic breast cancer by reducing acquired resistance, supporting additional evaluation of proteasome inhibitors in combination with SERDs.

Avaliação da migração de neutrófilos e da frequência relativa de linfócitos CD4+/CD8+ em crianças com síndrome de Down e controles / Evaluation of both neutrophil migration and the relative frequency of CD4+/CD8+ limphocytes in children with Down syndrome and controls

Objetivos: Avaliar a migração de neutrófilos e a frequência relativa de linfócitos CD4+/CD8+ em crianças com síndrome de Down e controles saudáveis.Métodos: Este foi um estudo de caso-controle realizado no Instituto de Pesquisas Biomédicas, no Hospital São Lucas da PUCRS. Os pacientes do grupo de estudo foram selecionados por uma amostragem de conveniência, representando todas as crianças com síndrome de Down e idade entre três e 13 anos, que frequentavam os ambulatórios de Pediatria e de Otorrinolaringologia do Hospital São Lucas da PUCRS e do Kinder - Centro de Integração da Criança Especial, em Porto Alegre, Rio Grande do Sul, nos meses de janeiro e dezembro de 2012. Para o grupo controle foram recrutadas crianças saudáveis e sem síndrome de Down, participantes de outro estudo em andamento no Instituto de Pesquisas Biomédicas. Foram selecionados os pacientes com maior volume de células armazenadas em criotubos. Para avaliar os parâmetros da resposta imune, foram realizados ensaio de quimiotaxia de neutrófilos e imunofenotipagem de células T CD4+ e CD8+. Associações foram avaliadas pelo teste do qui-quadrado, t de Student ou Mann-Whitney. Todos os testes foram bidirecionais e as diferenças foram consideradas significativas quando p menor que 0,05.Resultados: Foram incluídos 19 pacientes (13 com síndrome de Down e seis controles), com médias de idade de 8,13 e 9,83 anos, respectivamente. Não foram observadas alterações significativas no grupo com síndrome de Down em relação à capacidade de migração dos neutrófilos. Houve uma tendência a valores percentuais menores de células T CD4+ e maiores de CD8+ para o grupo com síndrome de Down. Houve diferença significativa na relação CD4+/CD8+ entre os dois grupos, sendo a mesma menor no grupo com síndrome de Down.Conclusões: Este estudo sugere que os pacientes com síndrome de Down apresentam uma taxa CD4+/CD8+ diminuída, o que pode contribuir para as infecções frequentes e recorrentes nessas crianças.

Aims: To evaluate neutrophil migration and the relative frequency of CD4+/CD8+ lymphocytes in children with Down syndrome and in healthy controls.Methods: This was a case-control study carried out at the Institute of Biomedical Research, affiliated with São Lucas Hospital of the Pontifical Catholic University of Rio Grande do Sul (PUCRS). Patients with Down syndrome were selected by convenience sampling, including all children with Down syndrome aged 3 to 13 years treated at the Pediatric and Otolaryngology Outpatient Clinics of São Lucas Hospital and at Kinder - Center for Children with Special Needs, in Porto Alegre, State of Rio Grande do Sul, Brazil, between January and December 2012. Healthy children without Down syndrome, participants in another ongoing study conducted by Institute of Biomedical Research, were recruited to the control group. Those patients with the largest volume of cells stored in cryotubes were selected. A neutrophil chemotaxis assay and immunophenotyping of CD4+ and CD8+ T cells were performed to evaluate the functionality of the immune response. Associations were assessed by the chi-squared test, Student's t test, or Mann-Whitney's test. All tests were bidirectional, and p values less than 0.05 were regarded as statistically significant.Results: This study included 19 patients (13 with Down syndrome and six controls), with a mean age of 8.13 and 9.83 years, respectively. No significant changes concerning neutrophil migration were observed in the Down syndrome group. However, patients with Down syndrome tended to have a lower rate of CD4+ T cells and a higher rate of CD8+ T cells. The CD4+/CD8+ ratio revealed significant difference between the groups, being lower in patients with Down syndrome.Conclusions: This study suggests that patients with Down syndrome show a decreased CD4+/CD8+ ratio, which may contribute to the frequent and recurrent infections in these children.

Manejo da asma em crianças na sala de emergência / Asthma management in children at emergency room

As crises de asma são episódicas, mas a inflamação da via aérea é cronicamente presente. Estas são normalmente reversíveis, espontaneamente ou com tratamento, mas podem ser graves e fatais. Devem ser classificadas segundo sua gravidade e o tratamento instituído o mais precocemente possível, pois uma falha ou atraso no seu reconhecimento para adoção de medidas terapêuticas efetivas pode colocar em risco a vida do paciente pediátrico.

The acute exacerbations are episodic, but airway inflammation is chronically present. These are usually reversible, either spontaneously or with treatment, but can be serious and fatal. Asthma attacks are classified according to their severity and treatment implemented as soon as possible, because a failure in their recognition or a delay in the adoption of effective therapeutic interventions may threat the life of pediatric patients.

Melanoma: diagnóstico e manejo / Melanoma: what to do after diagnosis?

O melanoma maligno é o tipo mais fatal de câncer de pele, e o seu diagnóstico precoce oferece um prognóstico melhor. Para isso, são necessários a correta suspeição e o diagnóstico o mais brevemente possível. Esse capítulo abordará os passos a serem seguidos a partir de uma lesão suspeita.

The melanoma of the skin is the most commonly fatal form of skin cancer, and the soon diagnosis offers a better prognostic. Because of that, the suspicion and correct diagnosis have to occur briefly. This chapter will approach the steps from de suspicion until treatment.

Impact of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on childhood pneumonia hospitalizations in Brazil two years after introduction.

INTRODUCTION: Pneumococcal disease is a major public health problem worldwide. From March to September of 2010, 10-valent pneumococcal non-typeable Haemophilus influenzae protein conjugate vaccine (PHiD-CV) was introduced in the Brazilian childhood National Immunization Program (NIP) in all 27 Brazilian states. The aim of the present study is to report national time-trends in incidence of hospital admissions for childhood pneumonia in Brazil before and after two years of introduction of this new pneumococcal conjugate vaccine. METHODS: Analysis of hospitalization data of children aged 0-4 years in Brazilian public health system with an admission diagnosis of pneumonia from 2002 to 2012 was performed comparing pre (2002-2009) and post-vaccination periods (2011-2012). Hospital number of admission due to pneumonia and all non-respiratory diseases were obtained from DATASUS, the Brazilian government open-access public health database system. Incidence of pneumonia hospitalization was compared to incidence of all non-respiratory admissions. RESULTS: Admission rates for pneumonia decreased steadily from 2010 to 2012. In children aged less than four years, incidence of pneumonia hospitalizations decreased 12.65% when pre (2002-2009) and post-vaccination introduction periods (2011-2012) were compared and adjusted for seasonality and secular-trend (p<0.001). On the other hand, non-respiratory admission rates remained stable comparing both periods (p=0.39). CONCLUSION: Childhood pneumonia hospitalization rates were fluctuating prior to 2010 and decreased significantly in the two years after PHiD-CV introduction. Conversely, rate of non-respiratory admissions has shown no decrease. These data are an evidence of the effectiveness and public health impact of this new pneumococcal vaccine.

Clinical significance of HER2-positive and triple-negative status in small (≤ 1 cm) node-negative breast cancer.

BACKGROUND: Data regarding the clinical significance of HER2(+) and TN status in patients with small node-negative tumors are limited and conflicting. It remains unclear who, among those with small lesions, might benefit from more aggressive adjuvant therapy. PATIENTS AND METHODS: We identified all node-negative breast cancer patients with tumor size ≤ 1 cm diagnosed between January 1, 1995 and December 31, 2008 using our institutional breast service database. Patients were classified according to their receptor status into 3 groups: (1) hormone receptor (HR)-positive (estrogen receptor [ER]- or progesterone receptor [PR]-positive, HER2(-)); (2) HER2(+) (immunohistochemistry 3(+) or fluorescence in situ hybridization amplification ≥ 2); and (3) TN (ER(-), PR(-), and HER2(-)). RFS was calculated using Kaplan-Meier methods. RESULTS: Among 656 patients with tumors ≤ 1 cm, 494 (75%) of the patients were HR(+), 107 (16%) were HER2(+), and 55 (9%) were TN. Median age was 59 years (range, 27-92 years). Median follow-up was 3.5 years. The 5-year RFS rates were 98.2%, 97.1%, and 83.5% in patients with HR(+), HER2(+), and TN tumors, respectively (P < .001). In multivariate analysis, TN status was associated with worse RFS (hazard ratio, 6.70; 95% confidence interval [CI], 3.02-14.86), and HER2(+) was not (hazard ratio, 1.64; 95% CI, 0.73-3.69). CONCLUSION: TN, but not HER2(+) status, was associated with worse RFS in patients with T1abN0 tumors, and adjuvant chemotherapy might be considered in patients with TN breast cancer.

Cediranib in combination with fulvestrant in hormone-sensitive metastatic breast cancer: a randomized Phase II study.

Hormone receptor-positive breast cancer is treated with estrogen inhibitors. Fulvestrant (FASLODEX™), an estrogen receptor (ER) antagonist with no known agonist effects, competitively binds, blocks and degrades the ER. Vascular endothelial growth factor (VEGF) may mediate resistance to ER antagonists. Cediranib is a highly potent VEGF signaling inhibitor with activity against all three VEGF receptors. This randomized Phase II study evaluated cediranib plus fulvestrant. Postmenopausal women with hormone-sensitive metastatic breast cancer were eligible. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), duration of response, clinical benefit rate (CBR), safety/tolerability and pharmacokinetics (PK). Patients received cediranib 45 mg/day (n=31) or placebo (n=31) both plus fulvestrant. Demographic/baseline characteristics were well balanced. Patients treated with cediranib had a numerical advantage in PFS (hazard ratio=0.867, P=0.669; median 223 vs. 112 days, respectively) and ORR (22 vs. 8 %, respectively) vs. placebo, although not statistically significant. CBR was 42 % in both arms. The most common adverse events (AEs) in the cediranib arm were diarrhea (68 %), fatigue (61 %) and hypertension (55 %). The incidence of grade ≥ 3 AEs (68 % vs. 32 %), serious AEs (48 % vs. 13 %), discontinuation AEs (39 % vs. 10 %), and cediranib dose reductions/interruptions (74 % vs. 32 %) were higher in the cediranib arm. There was no evidence of a clinically relevant effect of cediranib on fulvestrant PK. Cediranib plus fulvestrant may demonstrate clinical activity in this population, but cediranib 45 mg was not sufficiently well tolerated. Investigation of lower doses of cediranib plus hormonal/chemotherapy could be considered.

Effects of adjuvant chemotherapy in HER2-positive or triple-negative pT1ab breast cancers: a multi-institutional retrospective study.

Previous studies have reported higher recurrence rates in T1a/b N0 breast cancers characterized by high-risk biology (HER2+ or triple-negative), but the benefits of adjuvant chemotherapy in these patients have not been established. This study was designed to determine whether recurrence risk is reduced with chemotherapy and to define a group of patients most appropriate for treatment based on retrospective data. We pooled cases from two multi-institutional databases spanning the period of 1996-2010. A propensity score model adjusted unbalanced confounders between the groups treated or untreated with adjuvant chemotherapy and, in case of HER2-positive disease, with trastuzumab. Competing risk analysis was utilized to study effects of chemotherapy on cancer recurrences in the matched populations. Among the 318 patients identified, 41 % received adjuvant chemotherapy and 54 % of HER2+ patients received it with trastuzumab. The cumulative risk of recurrence at 5 years was 7.3 %. Age less than 35 years and triple-negative status were the only significant prognostic factors. Overall, administration of chemotherapy was not associated with a significant decrease in the risk of recurrence (HR 0.93, p = 0.91). The rate of recurrence in HER2+ patients who received trastuzumab was lower but not statistically significant (HR 0.50, p = 0.63). Clinical characteristics are of limited prognostic value for stratifying risk of recurrence in very small, node-negative HER2+, or triple-negative cancers. While limited by the small number of events, our analysis does not support the increasingly prevalent practice of administering adjuvant chemotherapy in this population without more accurate prognostic and predictive factors.

Internal mammary silicone lymphadenopathy diagnosed by robotic thoracoscopic lymphadenectomy.

Internal mammary lymphadenopathy can be caused by a variety of disease processes and is a difficult diagnostic dilemma. We report a case of internal mammary lymphadenopathy, in a patient with a significant history of malignancy, requiring a tissue diagnosis. Robotic thoracoscopic lymphadenectomy was used to facilitate excisional biopsy. Pathology was significant for silicone granulomatous lymphadenitis secondary to silicone breast implants inserted after mastectomy for breast cancer.

Paraneoplastic hypercalcemia in clear cell ovarian adenocarcinoma.

BACKGROUND: Hypercalcemia has been reported in association with a number of malignancies, but it is an unusual manifestation of ovarian cancer. This finding at presentation (possibly aggravated by oral calcium intake) led to discovery of a clear cell carcinoma of the ovary. The implications and pathophysiology of this association are reviewed. CASE REPORT: Following presentation with abdominal symptoms, this premenopausal woman was found to have bilateral adnexal masses and hypercalcemia. Her parathormone-related polypeptide was found to be elevated. After surgery and staging, she received adjuvant carboplatin and paclitaxel (later substituted by docetaxel). She has done well on her long-term follow-up. CONCLUSIONS: This rare paraneoplastic manifestation of ovarian cancer may be associated with long-term survival if discovered at an early stage. In this instance, further benefit may have been obtained from adjuvant platinum-based chemotherapy.

Vitamin D and breast cancer.

In addition to its role in calcium homeostasis and bone health, vitamin D has also been reported to have anticancer activities against many cancer types, including breast cancer. The discovery that breast epithelial cells possess the same enzymatic system as the kidney, allowing local manufacture of active vitamin D from circulating precursors, makes the effect of vitamin D in breast cancer biologically plausible. Preclinical and ecologic studies have suggested a role for vitamin D in breast cancer prevention. Inverse associations have also been shown between serum 25-hydroxyvitamin D level (25(OH)D) and breast cancer development, risk for breast cancer recurrence, and mortality in women with early-stage breast cancer. Clinical trials of vitamin D supplementation, however, have yielded inconsistent results. Regardless of whether or not vitamin D helps prevent breast cancer or its recurrence, vitamin D deficiency in the U.S. population is very common, and the adverse impact on bone health, a particular concern for breast cancer survivors, makes it important to understand vitamin D physiology and to recognize and treat vitamin D deficiency. In this review, we discuss vitamin D metabolism and its mechanism of action. We summarize the current evidence of the relationship between vitamin D and breast cancer, highlight ongoing research in this area, and discuss optimal dosing of vitamin D for breast cancer prevention.

Breast cancer in female-to-male transsexuals: two cases with a review of physiology and management.

Testosterone is important for the development of secondary sexual characteristics in female-to-male (FtM) transsexuals, but it may increase breast cancer risk. To date, only one breast cancer case has been reported in the literature in a FtM transsexual after 10 years of testosterone therapy. We describe 2 cases of breast cancers diagnosed in FtM transsexuals who have been treated with supraphysiological doses of testosterone. Our 2 cases demonstrate the unique issues that concern the management of FtM transsexuals with breast cancer and examine possible roles of testosterone in the development of breast cancer.