Mature results of a randomized phase II multicenter study of exemestane versus tamoxifen as first-line hormone therapy for postmenopausal women with metastatic breast cancer.

BACKGROUND: Women with hormone-responsive metastatic breast cancer (MBC) may respond to or have stable disease with a number of hormone therapies. We explored the efficacy and safety of the steroidal aromatase inactivator exemestane as first-line hormonal therapy in MBC in postmenopausal women. PATIENTS AND METHODS: Patients with measurable disease were eligible if they had received no prior hormone therapy for metastatic disease and had hormone receptor positive disease or hormone receptor unknown disease with a long disease-free interval from adjuvant therapy. They were randomized to tamoxifen 20 mg/day or exemestane 25 mg/day in this open-label study. RESULTS: Blinded independently reviewed response rates for exemestane and tamoxifen were 41% and 17%, respectively. Fifty-seven per cent of exemestane- and 42% of tamoxifen-treated patients experienced clinical benefit, defined as complete or partial response, or disease stabilization lasting at least 6 months. There was a low incidence of severe flushing, sweating, nausea and edema in women who received exemestane. One exemestane-treated patient had a pulmonary embolism with grade 4 dyspnea. CONCLUSIONS: Exemestane is well tolerated and active in the first-line treatment of hormone-responsive MBC. An ongoing EORTC phase III trial is comparing the efficacy, measuring time-to-disease progression, of exemestane and tamoxifen.     

Ein Beitrag zur pathologischen Anatomie der Landry'schen Paralyse

Ohne ZusammenfassungZum Schlusse spreche ich Herrn Prof. Dr. Schmidt für die Ueberlassung des Falles meinen verbindlichsten Dank aus.     

Highlights from the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, USA, 12-15 May 2001

Key issues discussed at the breast cancer sessions of the 37th American Society of Clinical Oncology (ASCO) meeting, 2001, included the following: breast cancer in the elderly; toxicity; updates on HER2 and use of trastuzumab (anti-HER2) in metastatic disease; and several early reports on novel therapeutic strategies. As was stated by numerous speakers both at this and other meetings, and as demonstrated by several abstracts, the use of predictive factors appears to be the most effective way to enhance the efficacy of numerous therapies, both target specific and nonspecific.     

Decrease in the number of SE-rosettes by means of sera containing immune complexes

The number of peripheral blood lymphocytes (PBL) rosetting with sheep erythrocytes (SE-rosettes) was significantly decreased by preincubation with both sera containing immune complexes (IC) and prepared antigen-antibody complexes. However, this effect of decrease in rosetting ability of PBL could be completely reversed by a second incubation of the cells for 30 minutes at 37 degrees C in IC-free medium. The immune complexes and antigen-antibody complexes respectively could bind reversibly to T cells via Fc-receptors and subsequently interfere with the T cell receptors for SE by steric hindrance.     

HER2/neu as a predictive factor in breast cancer

One of the current trends in breast cancer research is to identify markers that can predict response to specific anticancer therapies; intense laboratory research and therapeutic trials are exploiting this strategy. The combination of cytotoxic drugs directed at the tumor population with the highest probability of being sensitive to them with molecules targeted at intracellular signaling and cell cycle control pathways, which may be deregulated as part of the malignant process, represents our best hope for improved survival in both early and advanced disease. The transmembrane tyrosine kinase receptor, HER2/neu, has been the subject of much investigation with respect to its prognostic value, predictive value, and as a target of antibody-mediated therapy. Retrospective evidence strongly suggests that HER2 overexpression is associated with decreased disease-free and overall survival in node-positive, and possibly also node-negative, breast cancer. Prospective trials have demonstrated that antibodies to HER2 can produce tumor responses in women with advanced disease that overexpresses this molecule. Moreover, the combination of such antibodies with cytotoxic drugs has been one of the few recent strategies to improve survival duration in metastatic breast cancer. The evidence supporting the role of HER2 as a factor predictive of response to hormone therapy and cytotoxic drugs is more ambiguous and requires prospective assessment. The available literature is reviewed herein, with a focus on the predictive value of HER2, potential mechanisms of resistance and sensitivity to various drugs, and future research directions involving this important molecule.     

Landmark adjuvant randomized clinical trials of systemic therapy in early breast cancer

In this era of evidence-based medicine, it is generally recognized that level 1 evidence is important before a new drug or strategy can be universally accepted and consequently change the standard of care. This level of evidence requires the existence of either several well-designed randomized phase III trials or a meta-analysis of multiple well-designed controlled studies. Some of these randomized phase III trials can be considered milestones in the history of adjuvant systemic breast cancer therapy, playing a crucial role in changing clinical practice and establishing new standards of care. In this article, the authors analyze in detail some of these landmark studies of adjuvant endocrine and cytotoxic therapy, emphasizing their strengths and weaknesses.     

Long-term effects of a cancer awareness program for community pharmacists.

A continuing education program resulted in a 52% improvement in the specified professional behaviors of community pharmacists within one month. However, surveyed effects were not permanent and decreased significantly within 18 months. Following a simple mailing of specially designed literature, desired behaviors again underwent significant improvement comparable to that attributed to the original continuing education program. A better understanding of professional behaviors as functions of time and different educational modes would be invaluable to educators in both academic and postgraduate programs.     

ASO Visual Abstract: Sentinel Node Biopsy Should Not Be Routine in Older Patients with ER-Positive HER2-Negative Breast Cancer Who Are Willing and Able to Take Hormone Therapy

Annals of Surgical Oncology -     

Lifetime moderate-to-vigorous physical activity and ER/PR/HER-defined post-menopausal breast cancer risk

Purpose

Squamous cell carcinoma of breast accounts for less than 0.1% of all breast cancers. The purpose of this study is to describe the epidemiology and survival of this rare malignancy.

Methods

Data were extracted from the National Cancer Institute’s Surveillance, Epidemiology and End Results Registry to identify women diagnosed with squamous cell carcinoma of breast between 1998 and 2013. SEER*Stat 8.3.1 was used to calculate age-adjusted incidence, age-wise distribution, and annual percentage change in incidence. Kaplan–Meier curves were plotted for survival analysis. Univariate and multivariate Cox proportional hazard regression model was used to determine predictors of survival.

Results

A total of 445 cases of squamous cell carcinoma of breast were diagnosed during the study period. The median age of diagnosis was 67 years. The overall age-adjusted incidence between 1998 and 2013 was 0.62 per 1,000,000 per year, and the incidence has been on a decline. Approximately half of the tumors were poorly differentiated. Stage II was the most common stage at presentation. Majority of the cases were negative for expression of estrogen and progesterone receptor. One-third of the cases underwent breast conservation surgery while more than half of the cases underwent mastectomy (unilateral or bilateral). Approximately one-third of cases received radiation treatment. The 1-year and 5-year cause-specific survival was 81.6 and 63.5%, respectively. Excluding patient with metastasis or unknown stage at presentation, in multivariate Cox proportional hazard model, older age at diagnosis and higher tumor stage (T3 or T4) or nodal stage at presentation were significant predictors of poor survival.

Conclusions

Our study describes the unique characteristics of squamous cell carcinoma of breast and demonstrates that it is an aggressive tumor with a poor survival. Older age and higher tumor or nodal stages at presentation were independent predictors of poor survival for loco-regional stages.