A Rare Case of Thoracic SMARCA4-Deficient Undifferentiated Tumor With Diffuse Brain Metastasis.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described rare and aggressive malignancy characterized by undifferentiated cell morphology and the loss of the Brahma-related gene 1 (BRG1) protein. Its pathogenesis involves mutational loss of SMARCA4 gene expression, which encodes the BRG1 protein that serves as one of the catalytic subunits of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. This malignancy of the thorax predominantly affects middle-aged male smokers and commonly metastasizes to lymph nodes, bones, adrenal glands, liver, gastrointestinal tract, central nervous system, and kidney. Cases of brain metastasis have been reported but are less common. We report a case of this tumor initially presenting with diffuse brain metastasis in a 55-year-old male with a significant smoking history. We reviewed the current literature on the diagnostic and therapeutic challenges posed by this highly aggressive thoracic tumor.

Breast cancer and racial disparity between Caucasian and African American women, part 1 (BRCA-1).

Breast cancer is a commonly diagnosed malignancy and the second leading cause of cancer-related death among American women today. Despite the lower incidence of breast cancer among African American women, they are more likely to die from the disease each year than their white counterparts. We present a retrospective cohort study of the tumor registry data from electronic medical records of patients diagnosed with breast cancer at the University of Florida Health, Jacksonville from 2000 to 2005. A total of 907 patients were diagnosed with breast cancer; 445 patients with invasive breast cancer had complete medical records and were selected for this review. Much like previously published research, we found that African American patients presented with a more advanced stage and aggressive subtype of breast cancer than white patients, and were less likely to have health insurance. However, we have yet to determine if universal health care insurance can lead to improved health care access, better breast cancer awareness, and an enhanced attitude toward breast cancer screenings. Such factors would ultimately lead to an earlier diagnosis and better outcomes in both African American and white patients. We plan to investigate this critical issue in a follow-up study (BRCA-2; Breast Cancer and Racial Disparity Between Caucasian and African American Women, Part 2), which will begin a few years after the complete implementation of the universal health care law enacted by President Obama in 2010. The higher frequency of aggressive tumor subtypes in African American women warrants more attention. We suggest further research to determine whether decreasing the initial age for screening or increasing the frequency of mammograms in African American women would improve breast cancer outcomes. This study underscores the importance of identifying and preventing obstacles in routine breast cancer screening, as well as increasing breast cancer awareness.

Efficacy of neoadjuvant cisplatin and oral capecitabine in triple-negative breast cancers: a pilot study.

Due to the lack of molecular targets, triple-negative breast cancers (TNBCs) typically represent a worse prognosis compared to their hormone-positive counterparts. While neoadjuvant chemotherapy has been used for breast cancers for a long time, there is no standard chemotherapy regimen for TNBCs. Cisplatin has generally been regarded as an effective chemotherapy agent against TNBCs. However, here we present a pilot study involving the use of cisplatin in combination with oral capecitabine in the neoadjuvant setting in 16 patients with TNBC. Twelve patients were African American and 4 patients were white. Six patients completed all 4 cycles of chemotherapy, 6 patients completed 3 cycles, and 4 patients completed 2 cycles. A complete clinical response was observed in 2 patients, and 10 patients achieved partial clinical response. One patient had progressive disease, and 3 patients were lost to follow-up or taken off study. Following chemotherapy, 12 patients underwent surgery (7 patients had breast conservation, and 5 patients had a mastectomy). Ten of the 12 patients who had surgery achieved a partial pathologic response and the other 2 patients had complete pathologic response. Grade 3 nausea, vomiting, and diarrhea occurred in 7 patients; 1 patient experienced dehydration and renal failure; and 5 patients had grade 1/2 hand-foot syndrome. There were no grade 4 or 5 toxicities. The response to cisplatin-capecitabine combination chemotherapy in the neoadjuvant setting was suboptimal compared to that with single-agent cisplatin in prior studies. The toxicity profile with this combination was also worse than that of cisplatin alone. Based on our findings, we do not recommend this combination regimen in the neoadjuvant setting for TNBCs. However, future studies analyzing the use of cisplatin with other combinations are warranted.

Plasmablastic lymphoma of the stomach: an unusual presentation.

Plasmablastic lymphoma (PBL) is listed in the World Health Organization (WHO) classification as a subtype of diffuse large B-cell lymphoma (DLBCL). Some morphologic features of PBL are similar to DLBCL; however, PBL has minimal or no expression of CD20 and leukocyte common antigen. Instead, PBL has been characterized by the plasmablastic morphology of the cancer cells, with high mitotic figures. It is believed to be an aggressive lymphoma. We describe a case of a patient who seemed to pose a diagnostic dilemma, and who was later found to have PBL.

Breast cancer and HIV in the era of highly active antiretroviral therapy: two case reports and review of the literature.

The incidence of human immunodeficiency virus (HIV) infection is rising in US women; however its impact on breast cancer incidence, stage at presentation, response and treatment toxicity remains unknown. To address the impact of HIV infection and use of highly active antiretroviral therapy (HAART) on the natural history of breast cancer we present two cases of breast cancer in HIV-infected women and also review the literature. A literature search was done on Medline using the key words HIV/AIDS, breast cancer, and HAART therapy, restricted to English language. There were mostly case reports and one large series of 20 cases reported by Hurley et al. Data concerning the impact of HIV infection and HAART therapy regarding pathogenesis, stage at presentation, tumor type, response, and toxicity associated with treatment were reviewed. The literature review shows that the breast cancer incidence is either same or less in HIV-infected patients compared to the general population. However, the patients with HIV infection present with more advanced stage and aggressive disease, and they also have poor chemotherapy tolerance. The impact of HAART on breast cancer incidence in HIV-infected patients is still unclear.

An unusual case of primary small cell neuroendocrine carcinoma of the breast.

Primary small cell neuroendocrine carcinoma of breast is a rare entity, with only case reports in literature. Histologically, these tumors are similar to small cell carcinoma of the lung with some evidence of ductal carcinoma-in-situ with areas of ductal, lobular, or papillary differentiation. Immunoreactivity for neuroendocrine markers is present in two thirds of cases, while 33-50% are positive for estrogen receptor or progesterone receptor. Her2/neu expression has not been reported in small cell carcinoma of the breast. Here we are presenting 53-year-old women with locally advanced primary small cell neuroendocrine carcinoma of breast. We will discuss clinicopathological findings, treatment options, prognosis and review of the literature on primary small cell carcinoma of breast.

Consolidative involved-node proton therapy for Stage IA-IIIB mediastinal Hodgkin lymphoma: preliminary dosimetric outcomes from a Phase II study.

PURPOSE: To compare the dose reduction to organs at risk (OARs) with proton therapy (PT) versus three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) in patients with mediastinal Hodgkin lymphoma (HL) enrolled on a Phase II study of involved-node radiotherapy (INRT). METHODS AND MATERIALS: Between June 2009 and October 2010, 10 patients were enrolled on a University of Florida institutional review board-approved protocol for de novo "classical" Stage IA-IIIB HL with mediastinal (bulky or nonbulky) involvement after chemotherapy. INRT was planned per European Organization for Research and Treatment of Cancer guidelines. Three separate optimized plans were developed for each patient: 3D-CRT, IMRT, and PT. The primary end point was a 50% reduction in the body V4 with PT compared with 3D-CRT or IMRT. RESULTS: The median relative reduction with PT in the primary end point, body V4, was 51% compared with 3D-CRT (p = 0.0098) and 59% compared with IMRT (p = 0.0020), thus all patients were offered treatment with PT. PT provided the lowest mean dose to the heart, lungs, and breasts for all 10 patients compared with either 3D-CRT or IMRT. The median difference in the OAR mean dose reduction with PT compared with 3D-CRT were 10.4 Gy/CGE for heart; 5.5 Gy/CGE for lung; 0.9 Gy/CGE for breast; 8.3 Gy/CGE for esophagus; and 4.1 Gy/CGE for thyroid. The median differences for mean OAR dose reduction for PT compared with IMRT were 4.3 Gy/CGE for heart, 3.1 Gy/CGE for lung, 1.4 Gy/CGE for breast, 2.8 Gy/CGE for esophagus, and 2.7 Gy/CGE for thyroid. CONCLUSIONS: All 10 patients benefitted from dose reductions to OARs with PT compared with either 3D-CRT or IMRT. It is anticipated that these reductions in dose to OAR will translate into lower rates of late complications, but long-term follow-up on this Phase II INRT study is needed.

Effective dose reduction to cardiac structures using protons compared with 3DCRT and IMRT in mediastinal Hodgkin lymphoma.

PURPOSE: We investigated the dosimetric impact of proton therapy (PT) on various cardiac subunits in patients with Hodgkin lymphoma (HL). METHODS AND MATERIALS: From June 2009 through December 2010, 13 patients were enrolled on an institutional review board-approved protocol for consolidative involved-node radiotherapy (INRT) for HL. Three separate treatment plans were developed prospectively by using three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and PT. Cardiac subunits were retrospectively contoured on the 11 patients with intravenous-contrast simulation scans, and the doses were calculated for all treatment plans. A Wilcoxon paired test was performed to evaluate the statistical significance (p < 0.05) of 3DCRT and IMRT compared with PT. RESULTS: The mean heart doses were 21 Gy, 12 Gy, and 8 Gy (relative biologic effectiveness [RBE]) with 3DCRT, IMRT, and PT, respectively. Compared with 3DCRT and IMRT, PT reduced the mean doses to the left and right atria; the left and right ventricles; the aortic, mitral, and tricuspid valves; and the left anterior descending, left circumflex, and right circumflex coronary arteries. CONCLUSIONS: Compared with 3DCRT and IMRT, PT reduced the radiation doses to all major cardiac subunits. Limiting the doses to these structures should translate into lower rates of cardiac toxicities.