Hormonal therapy in postmenopausal women with breast cancer

The treatment of postmenopausal women with breast cancer presents a number of challenges. Tamoxifen has had a substantial impact on mortality in women with early-stage, estrogen-receptor-positive tumors. Despite the improvement in the treatment of breast cancer, many patients will ultimately experience a recurrence. Present treatment approaches can provide effective palliation in the advanced disease setting, but, at best, there has been a modest impact on survival. Numerous options are now available to provide effective palliation for patients with advanced disease. These options include antiestrogens, pure antiestrogens, aromatase inhibitors and progestins and LHRH agonists. Recently, several studies have reviewed the efficacy of aromatase inhibitors as first-line agents in postmenopausal women. Anastrozole and letrozole have recently been approved as first-line agents in women with metastatic breast cancer. In addition to their role in metastatic breast, trials investigating the potential of aromatase inhibitors in the early breast cancer, both in the adjuvant and neoadjuvant setting are underway.     

Estrogen profiles of premenopausal women with breast cancer

Population surveys have demonstrated an inverse relationship between breast cancer incidence rates and the urine "estriol ratio," the concentration of estriol relative to the sum of the concentrations of estrone and estradiol. In this study, the urine estriol ratio was evaluated in premenopausal breast cancer patients and control women from Boston and San Francisco. Although at least 2 years had passed since last use of oral contraceptives, women with a history or oral contraceptive use for 19 months or longer excreted estrogen in low concentrations compared to nonusers and so were excluded. Among the remaining 73 cases and 55 controls, the cases had lower estriol ratios and higher estrone and estradiol levels than did controls. However, these differences, which averaged about 10%, were not statistically significant. Thus the hypothesis that a low estriol ratio is a cause of breast cancer is given only minimal support. Among women in their 40's, the excretion of estrogens is subject to many influences and is difficult to study. The many determinants of estrogen excretion, including age and oral contraceptive use, should be accommodated in the design of future studies of the estriol ratio.     

Hormonal profiles and estrogen receptors in Egyptian female breast cancer patients

AIMS AND BACKGROUND: Hormones are considered to be an important factor in the etiology of breast cancer. Serum hormonal profiles of premenopausal and postmenopausal breast cancer patients as well as estrogen receptor (ER) concentrations in breast cancer tissues were examined in an attempt to establish a possible association between hormones and breast cancer risk and to elucidate the biological features of the disease among Egyptian female patients. METHODS: Levels of estradiol (E2), testosterone (T), progesterone (P), LH, FSH, prolactin, T3, T4 and TSH were measured by highly specific radioimmunoassays in the sera of women with breast cancer and compared to those of control subjects. ER concentrations in breast tumor tissues were measured using 125I-radioreceptor assay. RESULTS: Levels of T and prolactin showed a significant increase in both premenopausal and postmenopausal patients. E2 and P levels were significantly increased in follicular premenopausal and postmenopausal patients. Luteal E2 showed non-significant changes, whereas the luteal P level was significantly decreased. No significant alterations were found in the levels of serum LH, FSH, T3, T4 and TSH either in premenopausal or postmenopausal patients. Higher levels of ER were found in the tumors of postmenopausal than in those of premenopausal patients. A positive correlation was found between levels of ER and age of the patients (r = 0.35), whereas a negative correlation was observed between ER and serum E2 (r = -0.26). CONCLUSIONS: This study provides evidence of an association between high levels of serum E2 and T and increased risk of breast cancer in postmenopausal women. Abnormalities in serum P and prolactin are probably associated with a breast cancer risk and ER may be considered as a biochemical marker for breast cancer development.     

Pharmacological breast cancer therapy (review)

Breast cancer ranks as the second most common cause of cancer death among women in the United States. Anticancer agents are an important component of breast cancer therapy. Drugs frequently used to treat breast cancer include methotrexate, 5-fluorouracil (5-FU), cyclophosphamide, anthracyclines, taxanes, trastuzumab, tamoxifen, and aromatase inhibitors. These agents inhibit breast cancer progression by a variety of different mechanisms. This review describes each of these drugs and the varying effects each of them have upon breast cancer cells.     

Breast cancer risk in women treated with augmentation mammoplasty (review)

Surgical implantation of breast prostheses has become increasingly popular while the incidence of breast cancer is increasing each year. There has been no definitive consensus regarding the casual relationship between augmentation mammoplasty and breast cancer incidence, detection, treatment, mortality and survival. This review summarizes the published evidence, including epidemiological studies and case reports. All studies examined state that there is no breast cancer risk in prior augmented women. Moreover, there is also no significant difference in frequency, stage or mean tumor size between augmented and non-augmented women.     

Circulating tumor markers in breast cancer (review)

The clinical application of circulating tumor markers remains a controversial subject in terms of useful methods and correct interpretation of findings. In particular and despite numerous investigations in the field, we do not have as yet specific or highly sensitive biological markers in breast cancer. Nevertheless, many oncologists often utilize circulating tumor markers in various phases of this malignancy to obtain additional information about disease extent and clinical course. For this reason, we have reviewed the present status of the most widely used serum tumor markers in this neoplasm. Both CEA and TPA are well known, but their organ specificity is not related to breast. Among novel biological markers identified by monoclonal antibodies, special attention has been devoted to circulating agents that are recognized by immunoreagents and that were obtained by immunization with breast-derived products. Both CA 15.3 and MCA are now being validated at the clinical level. From the present review it is clear that today we are still far from being able to make the diagnosis of breast cancer on the sole basis of laboratory findings. On the contrary, some of the available markers can be utilized as prognostic indicators of disease extent and treatment response. Their value greatly increases when combined with conventional diagnostic methods that can be prescribed on the basis of abnormal laboratory findings to confirm or rule out disease recurrence.     

Weekly taxanes in metastatic breast cancer (review)

Metastatic breast cancer is still considered an incurable and difficult to treat disease, even if several classes of antineoplastic agents have shown various levels of activity in these patients. Taxanes are the most effective drugs in breast cancer, together with the anthracyclines, but they have several important side-effects with standard administration schedules. The weekly administration of both paclitaxel and docetaxel, respectively at 80-100 mg/m2/week and 35-40 mg/m2/week, is feasible and it has an efficacy level at least comparable with the standard 21-day administration. These schedules can also be administered at an increased dose-intensity with a better toxicity profile. Even if most of the data available today come from small phase I and/or II trials, the weekly schedules of taxanes administration are an attractive therapeutic chance, especially (but not only) in the elderly patients. Moreover the minimal side-effects make this approach very interesting for combination therapy with other drugs as well as with new biological agents such as anti-HER-2 and anti-EGF molecules. Ongoing phase III trials will clarify the efficacy of the weekly administration schedules and will define their role in the treatment of the metastatic breast cancer.     

Nordic walking for women with breast cancer: A systematic review

Nordic walking (NW) seems to be an interesting rehabilitation strategy for women with breast cancer (BC). No review article that has synthesised and summarised the existing scientific evidence about the effect of NW on BC survivors has been published so far. A systematic review was conducted aimed at identifying the characteristics and methodological quality of the studies that have analysed the effects of NW on women with BC. The critical appraisal of the randomised controlled trials (RCTs) was retrieved from the Physiotherapy Evidence Database (PEDro). The methodological quality of the uncontrolled studies was evaluated by means of the Quality Assessment Tool for Before–After Studies with No Control Group. Nine investigations (four RCTs and five quasi‐experimental studies) were included in the final analysis. The RCTs showed a fair methodological quality, while the quasi‐experimental studies obtained a score ranging from “fair” to “poor”. Judging from the findings of the analysed studies, NW had a significant and positive impact on a number of BC symptoms, including lymphedema, physical fitness, disability and morbid perceptions. No adverse effects were reported. However, due to the methodological limitations observed, further research is needed to confirm such findings.     

Osteoporosis in women with breast cancer

Osteoporosis is a disease that causes substantial morbidity and mortality for which preventive therapy is available. Women with breast cancer are at increased risk for osteoporosis for several reasons, including premature ovarian failure as a result of treatment, direct effects of chemotherapy, and effects of the breast cancer itself. As the incidence of breast cancer continues to increase and survival rates continue to improve, the importance of appropriate screening for and management of osteoporosis becomes more apparent. This article reviews the evidence supporting an increased risk for development of osteoporosis in women with breast cancer and summarizes strategies for prevention and treatment of osteoporosis in this population.     

New prognostic indicators in resectable breast cancer (review)

Despite advances in early diagnosis and primary treatment of breast cancer with surgery, radiation therapy or both modalities, more than one-third of newly diagnosed patients will develop recurrent or systemic disease and ultimately die. In recent years, systemic adjuvant treatment has shown positive results in high-risk women and tumor mortality has significantly decreased in patients entered clinical trials. This review outlines old and new prognostic indicators which will enable clinicians to improve the selection of patients who are real candidates to adjuvant chemotherapy and/or hormonal therapy.     

Hormonal therapy for advanced breast cancer

Hormonal therapy for advanced breast cancer has evolved significantly in the more than 100 years since the first publications documenting the effect of ovarian ablation on advanced breast cancer in premenopausal women. Since that time, not only have we developed the methods to measure estrogen and progesterone receptors in cancer cells, but more recently we have understood that expression of these receptors determines response to hormone therapy. The availability of more selective antiestrogen therapies has changed and significantly improved the treatment options for women who have advanced hormone-responsive breast cancer. Current research is focusing on reversing resistance to hormone therapy with the addition of targeted biologic agents to standard hormonal treatment.     

Stage at diagnosis and mortality in women with pregnancy-associated breast cancer (PABC)

Converging evidence indicates that women with pregnancy-associated breast cancer (PABC) have increased mortality compared to women with breast cancer not diagnosed near pregnancy (non-PABC). Our aim was to investigate if the stage distribution differs between PABC and non-PABC and if stage at diagnosis can explain the poorer prognosis observed among women with PABC. We identified 3,282 breast cancers in women aged 15–44 years at diagnosis for whom staging data (tumor size, nodal involvement, metastasis) were available in the Swedish Cancer Register between 2002 and 2009. Information on reproductive history and vital status was obtained from the Multi-Generation Register and the Cause of Death Register. PABC was defined as breast cancers diagnosed during pregnancy and up to 2 years after delivery (n = 317). Non-PABC was defined as cases diagnosed before pregnancy or more than 2 years postpartum. Stage distributions were compared between PABC and non-PABC, and mortality rates were modeled using Cox regression. Compared to women with non-PABC, the mortality was almost 50 % higher in women with PABC [unadjusted hazard ratio (HR) 1.47 (95 % CI 1.04–2.08)], a difference which was reduced after adjustment for age and calendar year of diagnosis [HR 1.27 (95 % CI 0.88–1.83)]. Although advanced stage of breast cancer at diagnosis was more common among PABC than among non-PABC, further adjustment for stage only slightly reduced the HR [1.22 (95 % CI 0.84–1.78)]. The difference in mortality between PABC and non-PABC was more pronounced among women above 35 years and among women with PABC diagnosed within 1 year postpartum. Age, rather than stage at diagnosis, appears to act as the principal driver of the increased mortality observed in women with PABC. However, these findings do not preclude an untoward influence on mortality by pregnancy-associated factors affecting tumor aggressiveness and progression.