Folate receptor alpha (FOLR1) has been identified as a potential prognostic and therapeutic target in a number of cancers. A correlation has been shown between intense overexpression of FOLR1 in breast tumors and poor prognosis, yet there is limited examination of the distribution of FOLR1 across clinically relevant breast cancer subtypes. To explore this further, we used RNA-seq data from multiple patient cohorts to analyze the distribution of FOLR1 mRNA across breast cancer subtypes comprised of estrogen receptor positive (ER+), human epidermal growth factor receptor positive (HER2+), and triple negative (TNBC) tumors. FOLR1 expression varied within breast tumor subtypes; triple negative/basal tumors were significantly associated with increased expression of FOLR1 mRNA, compared to ER+ and HER2+ tumors. However, subsets of high level FOLR1 expressing tumors were observed in all clinical subtypes. These observations were supported by immunohistochemical analysis of tissue microarrays, with the largest number of 3+ positive tumors and highest H-scores of any subtype represented by triple negatives, and lowest by ER+ tumors. FOLR1 expression did not correlate to common clinicopathological parameters such as tumor stage and nodal status. To delineate the importance of FOLR1 overexpression in triple negative cancers, RNA-interference was used to deplete FOLR1 in overexpressing triple negative cell breast lines. Loss of FOLR1 resulted in growth inhibition, whereas FOLR1 overexpression promoted folate uptake and growth advantage in low folate conditions. Taken together, our data suggests patients with triple negative cancers expressing high FOLR1 expression represent an important population of patients that may benefit from targeted anti-FOLR1 therapy. This may prove particularly helpful for a large number of patients who would typically be classified as triple negative and who to this point have been left without any targeted treatment options.

Background Data suggest that weight, and specifically BMI, plays a role in breast cancer development and outcome. We hypothesized there would be a correlation between BMI and clinical outcome in patients with early stage HER2-positive breast cancer enrolled in the N9831 adjuvant trial. Methods Patients were grouped according to baseline BMI: normal, BMI < 25; overweight, 25 ≤ BMI < 30; and obese, BMI ≥30. Disease-free survival (DFS) was estimated by the Kaplan-Meier method. Comparisons between treatment arms A, B, and C (chemotherapy +/− trastuzumab) were performed using a stratified Cox proportional hazards model. Results Analysis was completed on 3017 eligible patients. Obese patients were more likely to be older and postmenopausal (p<0.0001 for both), have larger tumors (p=0.002) and positive lymph nodes (p=0.004). In the pooled analysis cohort, differences in DFS among the BMI groups were statistically significant (5-year DFS rates were 82.5%, 78.6%, and 78.5% for normal weight, overweight and obese women, respectively; logrank p-value = 0.02). The adjusted HR comparing the DFS of overweight to normal women was 1.30 (95% CI: 1.06 to 1.61) and obese to normal women was 1.31 (95% CI: 1.07 to 1.59). There were no statistically significant differences in DFS by weight group for women within any trial arm. Conclusion Patients with early stage HER2 positive breast cancer and normal BMI had a better 5-year DFS compared with overweight and obese women. Adjuvant trastuzumab improves clinical outcome regardless of BMI.

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Breast cancer continues to be one of the leading causes of cancer mortality in the world. The treatment generally involves multiple modalities including surgery, radiation and/or chemotherapy. Anthracyclines, one of the first chemotherapeutic agents introduced in the 1960s, has been the backbone for the last 30 years and has been used extensively so far. However, the cardiac toxicity and the concern for secondary hematological malignancy has always been a challenge. A better understanding of the tumor biology, role of Her2 expression and the discovery of trastuzumab and other anti-Her 2 agents along with other effective novel therapeutic options, have revolutionized the treatment for breast cancer. The role of anthracyclines has come under close scrutiny, especially in the adjuvant setting for patients with early stage breast cancer and those with low or intermediate risk of disease recurrence. Recent studies have highlighted such a shift in the use of anthracyclines in both the academic and community clinical practice. However, in patients with a high risk of relapse, anthracyclines still hold promise. Ongoing clinical trials are underway to further define the role of anthracyclines in such a patient population. This review highlights the development, clinical utility, limitations and potential future use of anthracyclines in the adjuvant setting for patients with breast cancer. We consulted PubMed, Scopus, MEDLINE, ASCO annual symposium abstracts, and http://clinicaltrials.gov/ for the purpose of this review. Crozier JA, Swaika A, Moreno-Aspitia A. Adjuvant chemotherapy in breast cancer: To use or not to use, the anthracyclines.

Here we describe the first reported case of Nocardia beijingensis infection in the United States, made rarer by its presence in an immunocompetent patient. CASE REPORTA 48-year-old Caucasian male presented to an outside facility with a 1-month history of nonproductive hacking cough, low-grade fevers, drenching night sweats, and weight loss, which prompted further investigation. His medical history was unremarkable. His social history was remarkable for his work as a cotton farmer and no tobacco or alcohol use. He had traveled to Eastern Europe 1 year earlier. Computed tomography (CT) of the chest, abdomen, and pelvis showed a 5-cm ill-defined mass in the right hilum, causing narrowing of the branches of the upper-lobe bronchus and peripheral lung collapse. Also noted was lymphadenopathy in the hilar, periaortic, and aorticopulmonary window. Findings on the CT scan were concerning for possible carcinoma, lymphoma, or thymoma. A mediastinoscopy with lymph node biopsy was performed, but it was nondiagnostic.The patient was referred to the Mayo Clinic Florida for further evaluation. Physical examination revealed decreased breath sounds in the left apical lung. There was no lymphadenopathy noted in the cervical, supraclavicular, or axillary region. A complete blood count demonstrated mild anemia, neutrophil-predominant leukocytosis of 20,000 cells/l, and thrombocytosis of 935,000/l. The lactate dehydrogenase level was normal at 219 U/liter. C-reactive protein was elevated at 209 mg/liter. Testing for human immunodeficiency virus (HIV) and hepatitis B and C viruses was negative. A positron emission tomography (PET) scan revealed a 9.9-by 5.1-by 6.9-cm left paramediastinal mass extending to the left superhilar region with a maximum standardized uptake value (SUV) of 29.6 ( Fig. 1 and Fig. 2). Compared to the results of the CT scans done previously, a new hypermetabolic 1.4-cm suprasternal notch nodule that was suspicious for an abnormal lymph node was found. A PET scan also revealed a diffusely hyperstimulated bone marrow. A bone marrow biopsy specimen showed myeloid and megakaryocytic hyperplasia, and the findings were consistent with reactive marrow changes.The patient subsequently underwent a Chamberlain-McNeil left thoracotomy, during which a solid lung that was extremely vascular was encountered and biopsy specimens of the left lung and thymus were obtained. Further surgical dissection revealed a round hard lymph node that was noted on imaging and that was palpated and excised. Pathology showed lung tissue with acute and chronic changes of granulomatous inflammation and organizing pneumonia. Thymic tissue had an atrophic appearance and was negative for any neoplasm. Flow cytometry was negative for abnormal T-or B-cell populations. Gram staining and Grocott's methenamine silver staining of the thymic tissue were negative.Mediastinal lymph nodes showed reactive hyperplasia. Interestingly, on the Gram stain, Gram-positive bacilli with a beaded filamentous appearance were identified. The sputum, lung, and lymph node b...

Background Irinotecan has a 20-25% response rate (RR) in patients with previously treated metastatic breast cancer (MBC). Epidermal growth factor receptor (EGFR) is overexpressed in some MBC, especially in triple-negative breast cancer (TNBC). Cetuximab is a monoclonal antibody against EGFR with additive activity preclinical to irinotecan. Materials and Methods We report a one-stage phase II study on MBC, measurable disease, and prior anthracycline and/or taxane therapy. Patients received cetuximab 400 mg/m2 on day 1 cycle 1 then 250 mg/m2 weekly thereafter and irinotecan 80 mg/m2 on days 1 and 8 of each 21-day cycle. Primary endpoint was overall response rate (ORR) by RECIST criteria. Results 19 eligible patients enrolled from February to September 2006; 74% had visceral disease, 37% were hormone receptor positive, 11% HER2+, and 58% triple negative. Patients received a median of 2 cycles (range: 1-37). Confirmed ORR was 11% (95% CI: 1-33%), with 1 PR and 1 CR. One patient had stable disease (SD) for 8 months. RR for TNBC vs non-TNBC was 18% vs 0% (p=0.49). Median time to progression was 1.4 mo (95% CI: 1.0-2.2) and median overall survival was 9.4 mo (95% CI: 2.8-16.1). 12 patients progressed on therapy within 2 cycles. Due to low response rate and rapid progression, the study leadership decided to close the trial early. Conclusion The tolerability of the combination of cetuximab and irinotecan is acceptable but demonstrated low overall activity. Potentially promising results were noted in patients with TNBC and further studies of these patients may be considered.

These results are the first to elicit outcomes in a broad classification of ethnic minorities and underscore the urgency for development of novel therapeutics, especially in T-cell NHL. In addition, in-depth studies of disease biology and health care utilization are required for better triage of health care resources, especially for ethnic minorities.

Background Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer associated with poor survival, in which adjuvant systemic treatments are limited to chemotherapy. Due to competing mortality risks and comorbidities, older patients with TNBC are often undertreated with adjuvant chemotherapy, and clinical trials on this problem are scarce, despite a growing patient population. This study aimed to assess outcomes for patients aged 70 years and older with TNBC with or without chemotherapy in a national population-based registry, to provide information that can assist in treatment decisions for these patients.Methods In this population-based registry study, data on all patients aged 70 years and older diagnosed with primary early TNBC (larger than 5 mm in diameter and without distant metastasis) and surgically treated between Jan 1, 2009, and Dec 31, 2016, were retrieved from the Swedish National Breast Cancer Register, the Swedish Patient Register, and the Swedish Cause of Death Register. Patients with incomplete data (on oestrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 status, surgical procedure in the breast, or information about chemotherapy) were excluded. A propensity score-matched (PSM) model was used to examine the outcomes of adjuvant chemotherapy on 5-year breast cancer-specific survival (BCSS) and 5-year overall survival (OS), adjusted for age, tumour size, tumour grade, nodal status, and comorbidities. FindingsOf 1130 women eligible for analysis, 368 (32•6%) received adjuvant chemotherapy, 45 (4•0%) received neoadjuvant treatment, and 717 (63•5%) did not receive chemotherapy. 5-year BCSS was significantly improved in patients who received adjuvant chemotherapy (85% [95% CI 81-89]) compared with patients who did not receive chemotherapy (68% [64-72]; p<0•0001). A similar benefit was observed in 5-year OS (79% [95% CI 75-84] vs 49% [45-53]; p<0•0001). In our PSM analysis, 5-year BCSS in patients treated with adjuvant chemotherapy was 83% (95% CI 78-89), versus 73% (67-80; p=0•014) in patients not treated with chemotherapy. 5-year OS in patients treated with adjuvant chemotherapy was 75% (95% CI 69-82), versus 63% (57-71; p=0•029) in patients who did not receive chemotherapy.Interpretation In this PSM registry analysis of surgically treated female patients aged 70 years and older with TNBC without distant metastasis, we identified a significant benefit both in 5-year BCSS and 5-year OS with adjuvant chemotherapy versus no chemotherapy, which persisted when adjusting for age and comorbidities. These results underline the importance of considering adjuvant chemotherapy in older patients.