We evaluated the response and toxicity of rituximab in the setting of progressive intermediate grade non-Hodgkin's lymphoma (NHL) after autologous peripheral stem cell transplantation (PSCT). Seven ...patients with a median age of 59 years (45-62), ECOG performance status 0-1, and CD20-positive diffuse large cell lymphoma with progression after PSCT were treated. All patients initially received 4-weekly infusions of rituximab (375 mg/m2). The maximum response was three CR and four PR. Median progression-free survival was 197 days (range 60-282). With a median follow-up of 204 (115-299) days, the patients' disease status is classified as two CR, one PR, and four PD. Four of five patients with ECOG performance status of 1 prior to treatment showed improvement to status 0 after treatment with rituximab. While follow-up is short, these results suggest that rituximab has significant activity in intermediate-grade non-Hodgkin's lymphoma that has relapsed after PSCT.
Resistance to anti-HER2 (human epithelial growth factor receptor 2) trastuzumab therapy occurs commonly in HER2-positive breast cancer and involves overactivation of HER2 and/or AKT1. Using the model ...of trastuzumab-sensitive or trastuzumab-resistant HER2-positive cells with wild-type PTEN, negative regulator of AKT1, we explore the involvement of cysteine protease calpain in mechanisms of trastuzumab resistance. Overexpression of calpain1 or activation of endogenous calpain during adhesion or trastuzumab treatment of trastuzumab-sensitive cells induces cleavage of cytoplasmic domains of HER2/phospho-HER2; cleavage occurs in HER2-positive tumors. Expression of the catalytically inactive mutant of calpain1 reduces the cleavage to enhance the activity of HER2, inactivates PTEN to enhance the activation of AKT1, induces desensitization to trastuzumab and promotes survival of trastuzumab-sensitive cells. In the model of trastuzumab resistance, constitutive overactivation of HER2 and AKT1 correlates with reduced activation of calpain. Moreover, inhibitors of the catalytic site of calpain reduce the increase in constitutive activity of AKT1 and survival of trastuzumab-resistant cells selectively. Together, by regulating the activation of HER2 and PTEN/AKT1, calpain regulates trastuzumab sensitivity and survival, and the deregulation of the activation of calpain promotes trastuzumab resistance. Trastuzumab-resistant cells activate AKT1 in a mechanism dependent on the residual calpain activity, inhibition of which restores trastuzumab sensitivity and rescues resistance. These data identify calpain as a new therapeutic target in HER2-positive breast cancer.
Background: Sexual morbidity after chemotherapy and hormonal therapy for breast cancer can seriously affect patients' quality of life. Bupropion is an antidepressant that has been reported to ...increase libido. Objective: To investigate the improvement of sexual function in female breast cancer patients using bupropion. Patients and methods: We performed an 8-week open trial using bupropion in women diagnosed with breast cancer who had received chemotherapy and were currently receiving adjunctive hormonal therapy. The Arizona Sexual Experience Scale (ASEX) was used. The ASEX scale includes five questions that evaluate sexual function in the following areas: libido, excitability and ability to reach orgasm. Women received oral Bupropion 150 mg/daily for 8 weeks and were evaluated prior to the initiation of the study and again during Weeks 4 and 8. Results: Twenty patients were included in the study. At the beginning of the study, the mean ASEX score was 23.45 21.67–25.24 95% CI. After 4 weeks of treatment, we observed a reduction in the mean ASEX score that persisted until the end of the study, at eight weeks: 18.45 16.59–20.31 95% CI (P = 0.0003) and 18.95 16.60–21.30 95% CI (P = 0.0024), respectively. Conclusion: In this non-controlled open trial bupropion 150 mg/daily was associated with improved sexual function in women receiving adjuvant systemic treatment for breast cancer.
Breast cancer and pregnancy Moore, H C; Foster, Jr, R S
Seminars in oncology,
12/2000, Letnik:
27, Številka:
6
Journal Article
Recenzirano
A diagnosis of breast cancer during pregnancy or the postpartum period is an unfortunate occurrence. Hormonal factors appear to play an important role early on in the development of breast cancer; ...however, pregnancy itself does not clearly influence the outcome of an established breast cancer. Diagnosis can be challenging in a pregnant woman and delays in diagnosis are common. Treatment decisions must take into consideration not only toxicity to the mother, but short- and long-term consequences for the fetus as well. Other special considerations with pregnancy-associated breast cancer include the timing of delivery, the potential for nursing, and concerns for future fertility. In general, management of pregnancy associated breast cancer follows the same principals as in non-pregnant patients of similar age. With thoughtful application of available therapies, outcome can be optimized for both the mother and her child.
Late toxicities of adjuvant chemotherapy and side effects of endocrine therapy may cause long-term quality-of-life impairments for some individuals who have been treated for breast cancer. ...Chemotherapy has been associated with durable effects on cognitive function and fatigue and with the induction of menopause. Endocrine therapies can increase menopausal and sexual symptoms and can contribute to weight gain. Overall, however, quality of life is good for the majority of breast cancer survivors who have received adjuvant systemic therapy. Behavioral interventions that target fatigue and sleep disturbance may further enhance quality of life.
To assess the effect of menopausal hormone therapy (HT) on reoccurrence, cancer-related mortality, and overall mortality after a diagnosis of breast cancer.
We performed a quantitative review of all ...studies reporting experience with menopausal HT for symptomatic use after a diagnosis of breast cancer. Rates of reoccurrence, cancer-related mortality, and overall mortality were calculated in this entire group. A subgroup analysis was performed in studies using a control population to assess the odds ratio of cancer reoccurrence and mortality in hormone users versus non-users.
Fifteen studies encompassing 1416 breast cancer survivors using HT were identified. Seven studies included a control group comprised of 1998 patients. Among the 1416 HT users, reoccurrence was noted in 10.0% (95% CI: 8.4–11.6%). Cancer-related mortality occurred at a rate of 2.6% (95% CI: 1.8–3.7%), while overall mortality was 4.5% (95% CI: 3.4–5.8%). Compared to non-users, patients using HT had a decreased chance of reoccurrence and cancer-related mortality with combined odds ratio of 0.5 (95% CI: 0.2–0.7) and 0.3 (95% CI: 0.0–0.6), respectively.
In our review, menopausal HT use in breast cancer survivors was not associated with increased cancer reoccurrence, cancer-related mortality or total mortality. Despite conflicting opinions on this issue, it is important for primary care physicians to feel comfortable medically managing the increasing number of breast cancer survivors. In the subset of women with severe menopausal symptoms, HT options should be reviewed if non-hormonal methods are ineffective. Future trials should focus on better ways to identify breast cancer survivors who may safely benefit from HT versus those who have a substantial risk of reoccurrence with HT use.
Colon cancer is an important cause of cancer-related mortality. A series of clinical trials of adjuvant systemic therapy have been performed in attempt to establish means to improve outcome in this ...disease. By the early 1990s, a role for 5-fluorouracil (5-FU)-based chemotherapy in stage III colon cancer had been firmly established. The precise role for chemotherapy in stage II disease remains under investigation. Progress continues toward optimizing the schedule and duration of systemic therapy, allowing for maximal efficacy with a minimum of toxicity. It appears that approximately 6 months of 5-FU and leucovorin are as effective as more prolonged regimens. Levamisole does not appear to add to the benefit of 5-FU and leucovorin. Several newer agents such as the oral fluorinated pyrimidines, irinotecan (CPT-11) and oxaliplatin have demonstrated activity in metastatic colon cancer and hold promise as potentially effective drugs to be tested in the adjuvant setting.
Many women now survive breast cancer, but find themselves at increased risk of menopausal complications. How to manage menopause after breast cancer is a complex issue, given that estrogen has a role ...in the development of breast cancer and valid concerns exist about estrogen replacement therapy in patients who have had breast cancer. This article explores the relationship between estrogens and breast cancer and discusses management options for a variety of menopausal complications in breast cancer survivors.
Although the results of the Women's Health Initiative showed an increased risk of breast cancer in women taking hormone replacement therapy (HRT), the absolute risk is very low. We discuss ...limitations of the study, questions that remain, and how to discuss the study with women at average risk and high risk for breast cancer.
Background: High-dose chemotherapy with autologous stem-cell transplantation is used increasingly in the treatment of poor-prognosis primary breast cancer. Because these patients may be cured with ...standard multimodality therapy, it is important to address both the efficacy of transplantation, and its effect on the delivery of standard treatments including local radiation therapy. Patients and methods: Patients with high risk primary breast cancer were treated with high-dose cyclophosphamide and thiotepa and stem-cell transplant following surgery and conventional-dose adjuvant chemotherapy. Outcome, including sites of failure and delivery of local radiation therapy, was assessed for 103 patients. Results: Overall and disease-free survival rates at 18 months were 83% (±4%) and 77% (±4%) respectively. Twenty patients (19.4%) received radiation therapy prior to transplant. Of the remaining 83, 77 received radiation therapy after transplant. Overall, 5 (19.2%) of 26 first sites of recurrence were local alone. For patients receiving radiation prior to transplant, 3 of 7 (43%, 95% CI: 6%–80%) sites of first recurrence were local, while 2 of 19 (10.5%, 95% CI: 0%–24.5%) sites of first recurrence were local alone in patients receiving post-transplant radiation or no radiation. Conclusion: Transplantation does not appear to significantly compromise the delivery or outcome of local radiation therapy for primary breast cancer.
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