Alternative therapy and abnormal liver function during adjuvant chemotherapy in breast cancer patients

Although hepatotoxicity has been rarely reported during adjuvant chemotherapy in breast cancer patients, we observed a high frequency in our patients who were also taking alternative agents. We therefore sought to determine the association between hepatotoxicity and alternative agents during adjuvant chemotherapy in breast cancer patients. All breast cancer patients were treated with the same chemotherapeutic regimen and had normal baseline liver function test (LFT). LFT was checked repeatedly during each cycle of chemotherapy. Patients showing LFT abnormalities were asked about use of alternative agents, and, after the end of chemotherapy, a questionnaire was administered to each patient on their use of alternative agents. Of 178 patients, 65 (36.5%) admitted using alternative therapy, and significantly more patients in this group developed LFT abnormalities (37/65, 56.9%) than those who denied taking alternative therapy (25/113, 22.1%, p=0.001). Although LFT abnormalities were mild to moderate and normalized in most patients after cessation of alternative agents, it remained a serious problem in one patient. In conclusion, alternative therapy may be one of the etiologies for abnormal LFT in breast cancer patients receiving adjuvant chemotherapy.     

Psychological factors in women choosing radiation therapy for breast cancer

A relatively new non-disfiguring radiotherapeutic treatment for early breast cancer appears to be as effective as mastectomy. Fifty-one women who chose this alternative were studied. The vast majority were more concerned about insult to their personal body image than they were about how they would appear to others, and most believed that they would have a great deal of difficulty adjusting emotionally to a mastectomy. In patients with suicidal ideation directly related to fears of mastectomy, these thoughts disappeared or diminished when they learned about the alternative treatment.     

The susceptibility to amphotericin B-induced hemolysis of erythrocytes from women with breast cancer before and during therapy

The kinetics of hemolysis induced by amphotericin B in erythrocytes obtained from women with breast cancer before and during therapy (surgical operation, chemotherapy) was investigated. The changes in absorbance of erythrocyte suspension were monitored by absorption spectrophotometric methods at λ=590 nm. The kinetics of hemolysis induced by amphotericin B in erythrocytes of patients before operation or chemotherapy is the permeability type and is not changed during therapy. The process is similar to that observed in erythrocytes from healthy women. There is no statistical difference between the resistance to amphotericin B of erythrocytes obtained from women with breast cancer before treatment and the resistance obtained for healthy women. The resistance is independent of the cancer stage. Significant increase in the resistance to amphotericin B is found after surgical operation (P<0.01). The increase in resistance to amphotericin B is correlated with the decrease of erythrocyte number, hemoglobin content, and hematocrit. Chemotherapy does not change the resistance of erythrocytes to amphotericin B. The osmotic fragility of patient erythrocytes does not show any significant difference to that obtained for healthy women. No correlation between the osmotic fragility and the resistance of erythrocytes to amphotericin B was found. This indicates that erythrocyte resistance to amphotericin B is not determined by volume and membrane surface area.     

The effect of short intermittent light exposures on the melatonin circadian rhythm and NMU-induced breast cancer in female F344/N rats

We investigated the effects of altered endogenous nighttime melatonin concentrations on mammary tumor production in an N-nitroso-N-methylurea (NMU)-induced breast cancer model in female Fischer 344 (F344)/N rats. Experiments were designed 1) to evaluate whether short-duration intermittent exposures to light at night would affect the nocturnal rise of melatonin, resulting in a decrease in nighttime serum melatonin concentrations, 2) to evaluate whether any suppression of nighttime serum melatonin concentrations could be maintained for a period of weeks, and 3) to determine the effects of suppressed serum melatonin concentrations on the incidence and progression of NMU-induced breast cancer. In vivo studies were used to assess serum melatonin concentrations after 1 day and 2 and 10 weeks of nightly administration of short-duration intermittent light exposure at night and incidence of NMU-induced tumors. Five 1-minute exposures to incandescent light every 2 hours after the start of the dark phase of the light: dark cycle decreased the magnitude of the nocturnal rise of serum melatonin concentrations in rats by approximately 65%. After 2 weeks of nightly intermittent light exposures, an average decrease of the peak nighttime serum melatonin concentrations of approximately 35% occurred. The amelioration continued and, at 10 weeks, peak nighttime serum melatonin concentrations were still decreased, by approximately 25%. Because peak endogenous nighttime serum melatonin values could be moderately suppressed for at least 10 weeks, a 26-week NMU mammary tumor study was conducted. Serum melatonin concentrations and incidence, multiplicity, and weight of NMU-induced mammary tumors were assessed. A group of pinealectomized (Px) animals was also included in the tumor study. No effect on the development of mammary tumors in an NMU-induced tumor model in rats occurred when endogenous nighttime serum melatonin concentrations were moderately suppressed by short-duration intermittent light exposures at night. At necropsy, there were no alterations in mammary tumor incidence (28/40 NMU controls, 28/40 NMU + light, 31/40 NMU + Px), multiplicity (2.18 tumors/tumor-bearing NMU control, 1.89 NMU + light, 2.39 NMU + Px), or average tumor weight (1.20 g NMU control, 1.19 g NMU + light, 0.74 g NMU + Px). Tumor burden had no effect on the serum melatonin cycle. At 26 weeks, however, animals exposed to intermittent light at night exhibited approximately 3-fold higher serum melatonin concentrations as compared with controls. Additionally, rats that had been pinealectomized at 4 weeks of age had serum melatonin concentrations that were markedly higher than the expected baseline concentrations for pinealectomized rats (<15 pg/ml), suggesting the reestablishment of a melatonin cycle. This finding was unexpected and suggests that melatonin can be produced by an organ or tissue other than the pineal gland.     

Coping with chemotherapy for breast cancer

Relations among coping, physical symptoms, and affect were investigated in 43 women undergoing adjuvant chemotherapy for breast cancer. Patients were assessed at the same point in their treatment so that the time for which coping was reported would be equivalent across individuals. Patients were asked how they coped specifically with chemotherapy, rather than how they coped with cancer in general, to make the domain specific. Positive and negative affect were assessed separately, using a scale free of somatic content. Relations between coping and affect were consistent with prior studies that have employed a general approach to assessing coping. Coping correlates of positive and negative mood differed. When the relations between physical symptoms and affect were examined, physical symptoms were related to negative affect but not to positive affect. Findings are discussed in terms of their implications for coping with cancer as well as their implications for the general coping literature.     

Neoadjuvant chemotherapy modifies serum angiotensinase activities in women with breast cancer

Purpose

The aim of this study was to investigate the putative changes in serum angiotensinase activities (aminopeptidase N, APN; aminopeptidase B, APB; aminopeptidase A, APA; aspartyl aminopeptidase, ASAP) involved in the renin–angiotensin system (RAS) in women with breast cancer treated or not with a neoadjuvant therapy of paclitaxel and anthracycline and in healthy women volunteers.

Methods

We fluorometrically analysed serum APN, APB, APA and ASAP activities using their corresponding aminoacyl-β-naphthylamides as substrates in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline.

Results

When compared with healthy controls, women with breast cancer not treated with neoadjuvant chemotherapy, showed a decrease in angiotensinase activity, which support the putative increase of angiotensin II (Ang II) levels, indicating that the tumour process would favour the development of the disease. Also, an increase in APN and APB activities was observed, which support a role for angiotensin IV (Ang IV). In women treated with a neoadjuvant therapy, we described an increase in ASAP and APA activities, supporting the idea that this treatment increases Ang II catabolism. The resulting decrease in Ang II level could lead to an inhibition of the tumour growth.

Conclusion

Present results show changes in serum angiotensinase activities in women with breast cancer and in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline. Therefore, considerable attention should be focused on the development of RAS blockade therapy as a new strategy for breast cancer treatment.     

Specific response expectancies predict anticipatory nausea during chemotherapy for breast cancer.

Clinical research has demonstrated that large numbers of chemotherapy patients continue to experience nausea in the clinic prior to infusions. A better understanding of the mechanisms responsible for such anticipatory nausea (AN) is likely to provide critical information for identifying intervention targets. In the present study the authors investigated the contribution of expectancy, history of nausea, and distress to AN in 60 women with Stage I or II breast cancer receiving standard adjuvant chemotherapy. The predictors were each independently associated with AN (p < .05). However, only expectations significantly predicted AN in simultaneous regression analyses. Results suggest that interventions to reduce AN during chemotherapy should target patients' expectations.     

Efficacy of cognitive-behavioral therapy for insomnia in women treated for nonmetastatic breast cancer

This study investigated the efficacy of a multimodal cognitive-behavioral intervention for women who had been treated for nonmetastatic breast cancer. Ten participants were enrolled in the treatment protocol in a multiple-baseline design. Intervention time series analyses of daily sleep diary data revealed significant improvements of sleep efficiency and total wake time. These results were corroborated by polysomnographic data. In addition, insomnia treatment was associated with significant improvements of mood, general and physical fatigue, and global and cognitive dimensions of quality of life. These findings suggest that cognitive-behavioral therapy, previously found effective for primary insomnia, is also of clinical benefit for insomnia secondary to cancer.     

Bisphosphonate therapy for women with breast cancer and at high risk for osteoporosis

Bisphosphonates are effective inhibitors of osteoclast activity and bone resorption, and are standard treatments for osteoporosis, hypercalcemia of malignancy, and metabolic bone disease. Bisphosphonates have also been established to effectively reduce skeletal-related events due to malignancy metastatic to bone. Bisphosphonates are now being incorporated into breast cancer treatment regimens in order to combat osteoporosis caused by ovarian suppression, chemotherapy treatment, aromatase inhibitors and the postmenopausal state itself. A large body of evidence suggests that African-American women are at higher risk for osteoporosis-related morbidity than their Caucasian counterparts. In this review, we highlight recommendations toward screening for osteoporosis in high-risk populations. We summarize the mechanisms of action of bisphosphonates in the treatment of osteoporosis and then summarize national recommendations toward incorporating the use of bisphosphonates as support for the bone health of breast cancer patients, as well as patients at high risk for osteoporosis.     

Nanotechnology for breast cancer therapy

Breast cancer is the field of medicine with the greatest presence of nanotechnological therapeutic agents in the clinic. A pegylated form of liposomally encapsulated doxorubicin is routinely used for treatment against metastatic cancer, and albumin nanoparticulate chaperones of paclitaxel were approved for locally recurrent and metastatic disease in 2005. These drugs have yielded substantial clinical benefit, and are steadily gathering greater beneficial impact. Clinical trials currently employing these drugs in combination with chemo and biological therapeutics exceed 150 worldwide. Despite these advancements, breast cancer morbidity and mortality is unacceptably high. Nanotechnology offers potential solutions to the historical challenge that has rendered breast cancer so difficult to contain and eradicate: the extreme biological diversity of the disease presentation in the patient population and in the evolutionary changes of any individual disease, the multiple pathways that drive disease progression, the onset of ‘resistance’ to established therapeutic cocktails, and the gravity of the side effects to treatment, which result from generally very poor distribution of the injected therapeutic agents in the body. A fundamental requirement for success in the development of new therapeutic strategies is that breast cancer specialists—in the clinic, the pharmaceutical and the basic biological laboratory—and nanotechnologists—engineers, physicists, chemists and mathematicians—optimize their ability to work in close collaboration. This further requires a mutual openness across cultural and language barriers, academic reward systems, and many other ‘environmental’ divides. This paper is respectfully submitted to the community to help foster the mutual interactions of the breast cancer world with micro- and nano-technology, and in particular to encourage the latter community to direct ever increasing attention to breast cancer, where an extraordinary beneficial impact may result. The paper initiates with an introductory overview of breast cancer, its current treatment modalities, and the current role of nanotechnology in the clinic. Our perspectives are then presented on what the greatest opportunities for nanotechnology are; this follows from an analysis of the role of biological barriers that adversely determine the biological distribution of intravascularly injected therapeutic agents. Different generations of nanotechnology tools for drug delivery are reviewed, and our current strategy for addressing the sequential bio-barriers is also presented, and is accompanied by an encouragement to the community to develop even more effective ones.     

A randomized trial of chemotherapy and hormonal therapy in advanced breast cancer

We randomized 81 postmenopausal women with advanced breast cancer, whose tumors were rich in estrogen receptors or of unknown estrogen-receptor status, to receive either estrogen therapy alone or estrogen therapy combined with chemotherapy. An additional 31 patients, whose tumors were poor in estrogen receptors, were randomized to receive either chemotherapy alone or estrogen combined with chemotherapy. The median duration of follow-up was 87 months. In the receptor-rich group, the survival of the 21 patients receiving combined therapy was significantly longer than that of 19 patients receiving estrogen as initial therapy (followed by chemotherapy after failure or relapse). The median survivals were 72 and 29 months, respectively (P = 0.05 by the generalized Wilcoxon method). Among 41 patients with tumors of unknown receptor status, a survival advantage from combined therapy over chemotherapy was seen in the first two years and then disappeared. The survival in 31 patients with receptor-poor tumors was uniformly short regardless of the therapeutic method. We conclude that combined therapy offers a survival advantage in postmenopausal patients with receptor-rich tumors.