Psychosocial Support for Women with Advanced Breast Cancer

Women with advanced breast cancer frequently experience psychologic distress as a result of their illness and its treatment. This distress may be manifest as depression, anxiety, symptoms of the stress-response syndrome, difficulty coping and social isolation. Six randomized trials of psychosocial interventions have been conducted in metastatic breast cancer. Five of these evaluated group psychosocial support – supportive-expressive therapy in three studies, cognitive-behavioral in one, and a combination of cognitive-behavioral and supportive therapy in another. All of these studies identified psychological benefits, notably improvement in mood, pain control and coping, although benefits were small in one study that provided the control group with a home cognitive-behavioral study program. One study identified an unexpected survival benefit associated with a group intervention – three subsequent studies have failed to replicate this result. Survival results of one additional ongoing study are pending.Studies in early breast cancer, and in patients with a spectrum of other cancers, have demonstrated benefits of individual psychological interventions, educational interventions and relaxation/self-hypnosis/imagery interventions, however, these have not been adequately evaluated in metastatic breast cancer.Based on these results, it is recommended that psychosocial support be offered to women with advanced breast cancer. Current research does not provide sufficient information to determine the optimal type of intervention to be used, or the optimal timing and duration of such interventions. Furthermore, it is not clear which patients benefit the most from psychosocial intervention and whether there are some patients who do not require psychosocial intervention. Research to address these issues is recommended.     

KTP Laser and Neutral Red Phototherapy of Human Squamous Cell Carcinoma

Neutral red (NR) is a cationic, nontoxic vital dye employed as a histologic stain for proliferating cells; it has been used clinically for photodynamic treatment of herpes simplex virus lesions. NR is selectively taken up and concentrated by mitotic cells, an important characteristic for more effective antineoplastic agents. In the present study, UCLA-SO-P3 human squamous carcinoma cells displayed minimal toxicity when incubated with up to 50 μg/ml NR in the absence of light. However, cells incubated with greater than 0.5μg/ml NR followed by exposure to KTP laser light at 532 nm exhibited nearly 100% tumor cell death. The degree of cell toxicity was proportional to NR dose and laser light fluence. This study demonstrates that NR is an excellent cancer cell photosensitizer in vitro, and, after adding additional in vivo preclinical testing, may prove to be a useful agent in photodynamic destruction of head and neck tumors.     

Determinants of tissue estradiol levels and biologic responsiveness in breast tumors

Estradiol stimulates the growth of breast tumor cells in both pre- and post menopausal women. Following the menopause, the levels of estradiol in breast tumor tissues are similar to those from tumors obtained prior to cessation of ovarian function, even though plasma estrogen levels are 10–50 fold lower in post- than in premenopausal women. These observations suggested the possibility of enhanced estradiol uptake from plasma or in situ synthesis in post-menopausal women. We systematically studied these possibilities in a series of model systems. Initially we demonstrated a very high affinity estradiol binding site in tissues from castrated rats. Enhanced uptake occurred under conditions of low plasma estrogen levels when compared to animals with higher estradiol levels. In situ synthesis also occurred both through the sulfatase and aromatase pathways. In further studies, we compared uptake from plasma with in situ synthesis via aromatase in a nude mouse model. Under the conditions utilized, in situ synthesis resulted in much higher tissue estradiol levels and tumor growth rates than did uptake from plasma. During these studies we demonstrated that tumors deprived of estradiol developed mechanisms rendering them more sensitive to estrogen. This involved the ability of cells to adapt to estradiol deprivation to allow them to be responsive to four log lower amounts of estrogen than when studied under wild type conditions. In addition, cells adapted by increasing their level of aromatase and thus developing the capability to become more sensitive to estrogen precursors. Taken together, these studies demonstrate that breast cancer tissue is highly plastic and can adapt to conditions of estrogen deprivation via a variety of mechanisms.