Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy.

PURPOSE: Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study we analyzed whether changes in local antitumor immunity take place after neoadjuvant paclitaxel therapy and if they correlate with response to treatment. EXPERIMENTAL DESIGN: Neoadjuvant chemotherapy (paclitaxel, 200 mg/m2 q2w, 4 treatments) was followed by definitive surgical management. Histological sections from the pre- and post-treatment surgical specimens of 25 patients were analyzed for the extent of lymphocytic infiltration and presence of tumor infiltrating lymphocytes (TILs). The cumulative apoptotic response in the tumor after the first dose of paclitaxel was also studied in 10 of 25 patients. RESULTS: Pretreatment lymphocytic infiltrate in the tumor was minimal in the majority of patients and showed no relationship with clinical response. In the patients without TILs before treatment, development of TILs after treatment was noted in 0/3 (0%) patients with stable disease, 3/12 (25%) patients with clinical partial response, and 4/6 (67%) patients with clinical complete response and pathological residual disease. These correlated with the tumor cell apoptotic response to the first dose of paclitaxel. CONCLUSIONS: These results suggest that development of TILs after treatment correlates with clinical response to neoadjuvant paclitaxel therapy. The possible mechanism(s) whereby neoadjuvant chemotherapy may lead to induction of antitumor T cells is discussed. Immunological processes may influence the response of breast cancer patients to neoadjuvant treatment.

Paclitaxel-induced apoptosis and mitotic arrest assessed by serial fine-needle aspiration: implications for early prediction of breast cancer response to neoadjuvant treatment.

The extent of tumor reduction from neoadjuvant chemotherapy for breast cancer correlates with outcome. We investigated whether the initial cellular responses to paclitaxel are related to the extent of tumor reduction. Eleven women with breast cancer received paclitaxel (every 2 weeks for 4 cycles) as neoadjuvant treatment. Serial fine-needle aspirations (FNA; 25-gauge, 1 pass) were obtained before treatment and at 24, 48, 72, and 96 h after the first paclitaxel dose. Microscopic counts of apoptotic and mitotic indices were performed. The change in cancer volume from treatment was determined using radiological measurements with allowance for change in the histopathological amount of cancer. Apoptotic and mitotic responses usually subsided within 4 days. The duration of the initial apoptotic response was different for women with different treatment results. Cumulative apoptotic response for the first 4 days inversely correlated with the proportion of residual cancer after neoadjuvant treatment. FNA is a versatile clinical method to obtain breast cancer cells for therapy response studies. Apoptotic response to the first dose of paclitaxel is almost complete within 4 days, implying that more frequent (weekly) paclitaxel dosing might be beneficial. The apoptotic response to the first dose of paclitaxel appeared to predict the amount of cancer reduction from this treatment. This is a promising start toward the development of an early chemopredictive assay for paclitaxel treatment of breast cancer.

Pituitary adenoma and bilateral male breast cancer: an unusual association.

An unusual case is presented of bilateral breast cancer in a male patient with a long history of endocrine dysfunction due to a prolactinoma. The role of abnormal endocrine function in the development of male breast cancer is reviewed. The strongest association between aberrant endocrine function and male breast cancer occurs in patients with Klinefelter's syndrome, who have an approximate 3% lifetime risk of developing breast cancer. Retrospective case-control studies indicate that both estrogen excess and androgen deficiency may be involved in male breast cancer. Clinical studies of estrogen, androgen, and prolactin levels in male breast cancer patients have yielded conflicting results, and the precise nature of the hormonal mechanisms involved in the development of male breast cancer remains to be defined.

Non-AIDS-defining malignancies in patients with HIV infection.

HIV-infected individuals are at an increased risk for development of cancers other than the three AIDS-defining malignancies. Two non-AIDS-defining cancers, germ cell tumors and Hodgkin's disease, have been reported in the setting of HIV infection with increased frequency compared with their incidence in the general population. Other non-AIDS-defining malignancies frequently reported in the setting of HIV infection include lung cancer, squamous and basal cell carcinomas of the skin, anal carcinoma, and pediatric leiomyosarcomas.

Treatment strategies for epidemic Kaposi's sarcoma.

As the AIDS epidemic progresses, Kaposi's sarcoma continues to contribute substantially to the morbidity suffered by AIDS patients. Advances in our understanding of the pathogenesis of Kaposi's sarcoma have resulted in treatment strategies that are being investigated in the laboratory and clinic. Agents that affect the abnormal cytokines associated with Kaposi's sarcoma or inhibit angiogenesis are in early clinical trials. The recent discovery of a putative Kaposi's sarcoma virus may lead to new preventive or therapeutic strategies. Interferon, usually in combination with an antiretroviral nucleoside analogue, remains an important therapeutic option for patients with relatively intact immune function. For patients with more advanced immune suppression, chemotherapy is usually given, although there is no standard treatment regimen. New chemotherapeutic agents, including the use of liposomal encapsulated anthracyclines and topoisomerase-1 inhibitors, are being evaluated.

Developments in the treatment of acute leukemia in adults.

Since 1977, when it was first demonstrated that a small number of patients with refractory leukemia could be cured by bone marrow transplantation, there has been an international effort to increase the proportion of patients cured. This article reviews recent developments in the treatment of adult leukemia with particular emphasis on reports published during the past year. Several new preparative regimens for transplantation are discussed. New chemotherapeutic strategies reported during the past year have included modulating the activity of cytarabine, the most active agent in autologous myelogenous leukemia, using other agents such as etoposide, mitoxantrone, and carboplatin, and attempting to overcome the multidrug resistance phenomenon. There has been further experience in the use of autologous marrow for transplantation, with several centers reporting excellent results for patients so treated. Biologic-based strategies are an exciting area of exploration. The implications of the landmark discovery of all-trans retinoic acid as a treatment for acute promyelocytic leukemia continue to be investigated. Reports of the use of targeted monoclonal antibodies, cytokines, and other immunotherapies have generated the hope that these strategies might prove to be non-cross-resistant therapies and thus effective against residual disease following conventional chemotherapy.