now that he is in hospital, could either of the following be considered palliative care--trying to relieve the pressure on his brain to alleve his pain and paranoia and help him say what he wants to to you and others? Palliative care does not mean doing nothing...it just means concentrating on being comfortable rather than trying to cure
(1)fulvestrant (an injection)
case report
A 64-year-old man was diagnosed with breast cancer and underwent surgery in October 2000, when a radical mastectomy and axillary node dissection were carried out. Pathological examination revealed a 3 x 2 cm2 well-differentiated, invasive, ductal breast carcinoma (stage IIb), involving 1 of the 12 nodes that were tested. The tumour was found to be positive for both estrogen receptor (ER present in 40% of the tumoral cells) and progesterone receptor (in the 90% of the cells) and was HER-2/neu negative. The patientreceived six cycles of adjuvant chemotherapy (FEC75 regimen) followed by chest wall irradiation and tamoxifen 20 mg/day p.o. for 5 years.
In June 2005, the patient presented moderate/mild dyspnoea on exertion. Chest X-ray and thoracic computed tomography (CT) scan revealed pleuropulmonary metastatic disease. Four courses of 4-epirubicin chemotherapy (75 mg/m2 i.v., every 3 weeks) were administered, followed by four courses of docetaxel (75 mg/m2 i.v., every 3 weeks). In the evaluation after the fourth cycle, we found a pulmonary progression. Then, he received four cycles of capecitabine treatment (1250 mg/m2 b.i.d. p.o. on days 1–14, every 3 weeks). At the next evaluation, there was an increase in the number and size of lung lesions (Figure 1). As he did not respond to chemotherapy, it was decided to initiatetreatment with fulvestrant (loading-dose regimen: 500 mg i.m. on day 1, 250 mg i.m. on days 14 and 28, and followed by 250 mg i.m. monthly thereafter).
After 4 months of fulvestrant treatment, the patient reported an improvement in his dyspnoea and a new chest CT scan showed a partial response (partial reduction of the pulmonary lesions and pleural effusion), with a decrease in the size and number of the pulmonary nodules and pleural effusion (Figure 2).
discussion
Male breast cancer is rare in comparison to female breast cancer and represents 1% of all diagnosed breast cancers [1]. The low incidence of male breast cancer precludes the development and completion of large clinical trials to assess the efficacy of breast cancer treatments in this population and, therefore, it is recommended that its management follows the same general principles as for female breast cancer [2]. Although male breast cancer shares many similarities with breast cancer in women, there are also important differences, mainly in relation to its hormone dependency and responsiveness to endocrine therapy [3]. In females, 60%–70% of breast cancers are ER positiveand/or PgR positive. In contrast, 90% of male breast tumours express ER and >80% express PgR, showing a greater expression of ER-beta [4] and being probably produced by low estrogen levels in growing tumour microenvironment. The lower rate of HER-2/neu and p53 expression and a higher rate of Bcl-2 overexpressionhave been reported in male breast cancer [5]. Physiological mechanisms of hormonal production and conversion together with metabolic aberrations may also play an important role in the development of resistance to the hormonal manipulation. This should be considered during the design of a male breast cancer treatment plan. Consequently, it may be inappropriate to extrapolate the treatment principles established for female breast cancer to the management of male breast cancer.
In male breast cancer treatment, best responses have been observed with hormonal therapy. Among the different endocrine options available, tamoxifen is the best established [6]. However, additional hormonal treatment options are required. The use of aromatase inhibitors can be ineffective due to the high proportion of circulating estrogens in men that are independent of aromatase activity [6, 7]. Taking into account the experiences showed in the hormonal treatment of prostate cancer [8], different activity between steroid and nonsteroid aromatase inhibitors in male breast cancer should be considered.
Fulvestrant is an additional therapeutic option that has confirmed efficacy in women previously treated with tamoxifen. To date, there have only been limited data on the use of fulvestrant in male breast cancer. Its novel mechanism of action, along with the available in vitro data [9], indicates that fulvestrant may be a useful treatment option for these patients. The activity in this case report supports further evaluation of fulvestrant in the male breast cancer setting.
J. R. de la Haba RodrĂ*guez*, I. Porras Quintela, G. Pulido Cortijo, M. Berciano Guerrero and E. Aranda
Department of Medical Oncology, Hospital Universitario Reina Sofia, Cordoba, Spain
* (E-mail:
juandelahaba@hotmail.com)
Endocrinology. 2008 Oct;149(10):5219-26. Epub 2008 Jul 3.
ICI 182,780 penetrates brain and hypothalamic tissue and has functional effects in the brain after systemic dosing.
Alfinito PD, Chen X, Atherton J, Cosmi S, Deecher DC.
Women's Health and Musculoskeletal Biology, Wyeth Research, RN 3164, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA.
Previous reports suggest the antiestrogen ICI 182,780 (ICI) does not cross the blood-brain barrier (BBB). However, this hypothesis has never been directly tested. In the present study, we tested whether ICI crosses the BBB, penetrates into brain and hypothalamic tissues, and affects known neuroendocrine functions in ovariectomized rats. Using HPLC with mass spectrometry, ICI (1.0 mg/kg.d, 3 d) was detected in plasma and brain and hypothalamic tissues for up to 24 h with maximum concentrations of 43.1 ng/ml, and 31.6 and 38.8 ng/g, respectively. To evaluate antiestrogenic effects of ICI in the brain after systemic dosing, we tested its ability to block the effect of 17 alpha-ethinyl estradiol (EE) (0.3 mg/kg, 8 d) on tail-skin temperature abatement in the morphine-dependent model of hot flush and on body weight change. In the morphine-dependent model, EE abated 64% of the naloxone-induced tail-skin temperature increase. ICI pretreatment (1.0, 3.0 mg/kg.d) dose dependently inhibited this effect. ICI (3.0 mg/kg.d) alone showed estrogenic-like actions, abating 30% the naloxone-induced flush. In body weight studies, EE-treated rats weighed 58.5 g less than vehicle-treated rats after 8 d dosing. This effect was partially blocked by ICI (3.0 mg/kg.d) pretreatment. Similar to EE treatment, rats receiving 1.0 or 3.0 mg/kg.d ICI alone showed little weight gain compared with vehicle-treated controls. Thus, ICI crosses the BBB, penetrates into brain and hypothalamic tissues, and has both antiestrogenic and estrogenic-like actions on neuroendocrine-related functions.
PMID: 18599545
(2)a tiny study but shows response, duration
Clin Breast Cancer. 2009 May;9(2):118-21. Links
Bevacizumab and paclitaxel for breast cancer patients with central nervous system metastases: a case series.
Labidi SI, Bachelot T, Ray-Coquard I, Mosbah K, Treilleux I, Fayette J, Favier B, Galy G, Blay JY, Guastalla JP.
Department of Medical Oncology, Centre Leon Berard, Laennec, France.
labidi@lyon.fnclcc.fr
Central nervous system (CNS) metastases are a major concern in patients with stage IV breast cancer. Recent studies have shown the efficacy of anti-vascular endothelial growth factor drugs on brain tumors, in particular glioblastoma, but none has explored their efficacy and tolerance in breast cancer patients with CNS metastases. We report 4 cases of patients with CNS metastases treated with bevacizumab and paclitaxel. All but 1 had previous whole-brain radiation therapy, performance status 0-2, and radiographic evidence of progressive CNS metastases. Patients received paclitaxel 80 mg/m2 on days 1, 8, and 15, and bevacizumab 10 mg/kg on days 1 and 15. Response was evaluated according to the World Health Organization criteria. Three patients had brain metastases, and 1 had meningeal lesions. Only 1 patient was chemotherapy-naive. Significant antitumor activity was observed, with 1 complete response and 3 partial responses in the CNS metastases. With a mean follow-up of 9 months, duration of response was 11, 10, 8, and 6 months. No patient had extra-CNS progression. This observed antitumor activity suggests efficiency of the combination of bevacizumab and paclitaxel and warrants further evaluation of this combination as an alternative option for the treatment of multiple CNS metastases in breast cancer.
PMID: 19433393