David B. Geffen

The impact of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in early-stage estrogen-receptor-positive breast cancer in an oncology practice with a unified treatment policy

BACKGROUND The 21-gene recurrence score (RS) assay has been validated in retrospective studies as prognostic of distant disease recurrence and predictive of the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). There is limited published data on the impact of the assay on clinical practice, particularly in the context of a single practice with a unified treatment policy. PATIENTS AND METHODS Between 2006 and 2009, RS was obtained on 135 patients in a single practice with a uniform treatment policy. Treatment recommendations before and after RS result were analyzed retrospectively. Pre-RS treatment recommendations were based on clinicopathological features and Adjuvant! Online (AO) calculated survival advantage. RS and AO survival advantage for adding chemotherapy were compared for each patient. RESULTS The distribution by risk group of RS was low- 49.6%, intermediate-37.8%, and high-12.6%. In 34 patients (25.2%, 95% confidence interval 17.9% to 32.5%), recommendation for chemotherapy was changed after obtaining assay result. Most changes (70.6%) were from chemotherapy to no chemotherapy. The RS correlated poorly with AO predictions. CONCLUSION The 21-gene assay, when applied in a consistent manner in early-stage BC, changes treatment recommendations in one-quarter of patients tested.

Post-traumatic stress disorder and quality of life in long-term survivors of Hodgkin's disease and non-Hodgkin's lymphoma in Israel.

Post-traumatic stress disorder (PTSD) has not been examined systematically in long-term survivors of lymphoma. In this study, PTSD and health related quality of life (HRQoL) were assessed in 44 patients with Hodgkins disease <formula>(<italic>n</italic>=8)</formula> or non-Hodgkins lymphoma <formula>(<italic>n</italic>=36).</formula> Forty-four individuals who had experienced traumatic events as defined by the Diagnostic and Statistical Manual-IV (DSM-IV) as possible triggers for PTSD served as controls. The study participants were administered two questionnaires--the PTSD inventory scale and the Short Form-36 (SF-36) HRQoL instrument measuring physical and mental HRQoL. Full PTSD was defined as meeting the DSM-IV criteria for the diagnosis in all three symptom groups measured on the PTSD inventory scale-intrusion, avoidance and hyper-arousal and partial PTSD as meeting the diagnostic criteria in two of the symptom groups. There was a significant increase in the hyper-arousal scale in the lymphoma survivor group (F 5, <formula><italic>P</italic><0.05</formula>). Overall, full or partial PTSD was found in 14 lymphoma survivors (32%) and in 11 individuals (25%) in the control group (difference not significant). Survivors whose disease had started at an earlier age suffered significantly more intensive intrusion and avoidance symptoms. The lymphoma survivor group had a significantly lower physical HRQoL than the control group independent of PTSD symptoms. In both groups, the presence of PTSD symptoms correlated with a lower HRQoL. These results suggest that lymphoma is a trauma similar to other more accepted definitions of trauma which can lead to PTSD, and is associated with more severe hyper-arousal symptoms. Psychological interventions in the early stages of treatment or follow-up may help reduce the morbidity from PTSD and improve quality of life.

Combined Multimodal Approach to the Treatment of Metastatic Anal Carcinoma: Report of a Case and Review of the Literature

Background: We report on a patient with squamous cell anal carcinoma and liver metastases, who underwent multimodal treatment for cure, consisting of repeated partial hepatectomy in combination with chemoradiotherapy. Patients and Methods: A 54-year-old woman presented with squamous cell anal carcinoma and liver metastases. She was treated with a combination of chemoradiotherapy for the primary tumor and then underwent surgery for liver metastases. 2 and 5 years after presentation, the patient underwent repeated partial hepatectomies for recurrent liver disease. At present, 5 months after completing therapy and 71 months after the initial diagnosis, she is in good health with no evidence of disease. Results: Repeated partial hepatectomy led to prolonged survival in a patient with squamous cell anal carcinoma metastatic to the liver. Conclusions: This is the first report of aggressive partial hepatectomy for recurrent liver metastases resulting from anal cancer. Based on our experience, we suggest that in selected patients repeated hepatectomy should be part of an aggressive multimodal treatment program with curative intent.

Renal involvement in diffuse aggressive lymphomas: results of treatment with combination chemotherapy.

Nine (5.1%) of 175 patients with advanced disseminated diffuse aggressive non-Hodgkins lymphoma presented with renal involvement and were initially treated with combination chemotherapy alone. These patients were classified as having renal involvement based on histologic and radiographic criteria. Five of the nine patients presented with a serum creatinine level greater than 2.5 mg/dL. Four patients achieved a complete remission of all systemic disease. Eight patients had complete resolution of renal involvement. Two patients later had recurrent renal disease associated with other sites of recurrence. All five patients who presented with an elevated serum creatinine level recovered normal renal function; in fact, four patients had normal renal function by the end of the first cycle of therapy. No patient required hemodialysis. Only one patient remains alive and free of disease at 55 months; five patients have died with disseminated disease; two patients have died without evidence of disease; and one patient was lost to follow-up while in remission. Initial local control of renal involvement including normalization of renal function in diffuse aggressive lymphoma can be rapidly achieved by combination chemotherapy alone.

Rituximab in a Patient with Acute Renal Failure due to B-cell Lymphomatous Infiltration of the Kidneys

Renal failure is known to occur in lymphoproliferative disorders because of ureteral obstruction or parenchymal infiltration by disease. Rituximab is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B-lymphocytes. The pharmacokinetics and metabolism of rituximab is not well established. The extent of renal clearance is not fully known, with little experience reported on the use of rituximab in patients with renal failure. We present a case where rituximab was administered to a patient with acute renal failure due to bilateral kidney infiltration by non-Hodgkins lymphoma (NHL). The patients renal function improved on therapy, with no need for hemodialysis and there were no significant toxicities. Rituximab may be used as a treatment option for NHL patients with impaired renal function.

The 21-Gene Recurrence Score Assay (Oncotype DX™) in Estrogen Receptor-Positive Male Breast Cancer: Experience in an Israeli Cohort

Objective: The 21-gene recurrence score (RS) assay has been widely adopted for use in early estrogen receptor (ER)-positive breast cancer to assess the risk for distant recurrence and the potential benefit of adjuvant chemotherapy. The primary aim of this study was to assess RS distribution in Israeli male breast cancer (MBC) patients. Methods: The study population included 65 newly diagnosed Israeli MBC patients. Clinical and pathologic data were collected at the time of referral. Pathologic examinations were conducted at the pathology departments of the referring centers. The RS assay (Oncotype DX™) was performed on paraffin-embedded tumor samples at Genomic Health laboratories. Results: The mean age of the patients was 65.1 years (range 38-88 years). Low-risk (RS <18), intermediate-risk (RS 18-30) and high-risk (RS ≥31) scores were noted in 29 patients (44.6%), 27 patients (41.5%) and 9 patients (13.9%), respectively. The distribution of RS in male patients was similar to the distribution in 2,455 female patients from Israel referred during the same time period. Conclusion: Our data suggest that the distribution of Oncotype DX RS in ER-positive MBC patients is similar to that of female breast cancer patients.

Association between Bone Mineral Density and Incidence of Breast Cancer

Introduction Previous studies have suggested an inverse relationship between bone mineral density (BMD) and breast cancer incidence. The primary objective of this study was to assess whether BMD is associated with risk of subsequent breast cancer occurrence in the female population of southern Israel. Methods The electronic medical charts of women who underwent BMD at the Soroka Medical Center (SMC) between February 2003 and March 2011 were screened for subsequent breast cancer diagnoses. Women were divided by tertiles of BMD at 3 skeletal sites: lumbar spine (LS, L1–4), total hip (TH) and femoral neck (FN). The incidence of breast cancer was calculated. Results Of 15268 women who underwent BMD testing, 86 were subsequently diagnosed with breast cancer. Most women in the study were older than 50 years (94.2% and 92.7%, respectively; p = 0.597). Women who subsequently developed breast cancer had a higher mean body-mass index (BMI) (30.9±5.5 vs. 29.1±5.7 p = 0.004) and the mean BMD Z-score was significantly higher than in those without breast cancer for all 3 skeletal sites (LS: 0.36±1.58 vs. −0.12±1.42, p = 0.002; TH: 0.37±1.08 vs. 0.03±1.02, p = 0.002; FN: 0.04±0.99 vs. −0.18±0.94; p = 0.026). Women in the highest Z-score tertiles at the FN and TH had a higher chance of developing breast cancer compared to the lowest tertile; odds ratio of 2.15, 2.02, respectively (P = 0.004 and 0.01 respectively). No association was found between the BMD Z-score and the stage, histology, grade or survival from breast cancer. Conclusions This study provides additional support for an inverse association between BMD and the risk of breast cancer.

Primary Malignant Lymphoma of the Prostate – A Report of Three Cases

We report the clinical, morphological and immunohistochemical findings in 3 cases of primary non-Hodgkins malignant lymphoma of the prostate. After treatment with doxorubicin-based chemotherapy, two patients achieved a complete remission, and 1 died of infective endocarditis three months after diagnosis. Until a consensus has been reached regarding the optimal treatment of prostatic lymphoma, therapy should be determined by the histologic type diagnosed and stage of the lymphoma.

The protective effect of zoledronic acid on bone loss in postmenopausal women with early breast cancer treated with sequential tamoxifen and letrozole: a prospective, randomized, phase II trial.

Objective: This study reports the efficacy and safety of zoledronic acid (ZOL) in preventing bone loss in postmenopausal patients receiving an aromatase inhibitor (AI) following tamoxifen. Methods: Postmenopausal patients with stage I–III hormone receptor-positive breast cancer who received tamoxifen for 2.5–3 years were randomized to receive letrozole (2.5 mg/day) with (n = 47) or without (n = 43) ZOL (4 mg i.v. every 6 months) for 2 years. The primary endpoint was percent change from baseline in lumbar spine (LS) bone mineral density (BMD) up to 60 months. Results: Ninety patients (86 evaluable) with a median age of 59 years (42.9–83.6), 50/86 of whom had previously been treated with chemotherapy, were followed for a median time of 41.4 months. While the control group showed a significant decrease in LS T-score (p = 0.0005), the ZOL group presented an increase over time (p = 0.0143). Change over time in LS T-score was significantly different between groups, favoring ZOL (p < 0.0001 at 24 and 48 months). No fractures, renal dysfunction or osteonecrosis of the jaw were reported. The toxicity profile was similar to those previously reported for each drug. Conclusion: The addition of ZOL to letrozole was safe and efficacious in maintaining LS BMD in postmenopausal patients with hormone receptor-positive breast cancer and who were receiving letrozole following 2.5–3 years of tamoxifen.

Primary small noncleaved cell lymphoma of the liver : report of an adult case in complete remission after treatment with combination chemotherapy

Open liver biopsy in a 34-year-old woman with hepatosplenomegaly showed small noncleaved cell lymphoma. Except for an enlarged spleen, there was no evidence of other sites of involvement. She was treated with combination chemotherapy and is alive and free of disease > 5 years after diagnosis. We believe this to be the first reported case in an adult of primary hepatic or hepatosplenic lymphoma of the small cleaved cell type with long-term disease-free survival.