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Although the term of lobular neoplasia was first proposed in 1978 and the term Lobular In situ Neoplasia (LIN) has been incorporated in the current World Health Organisation (WHO) classification to cover both atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), the clinical significance and the natural history of lobular neoplasia is far from being fully understood. Furthermore problems and confusion still remain surrounding (1) the most appropriate terminology and classification for these lesions, (2) the best course of long-term management after diagnosis.This article summarizes the opinions on LCIS management of a group of Belgian experts.

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AIM: To evaluate the prevalence and type of menopausal treatments used by breast cancer survivors. To assess factors that impaired the quality of life of these patients. MATERIAL AND METHODS: A questionnaire assessing quality of life was sent to 325 breast cancer patients. A 66% valid response rate was obtained. Among these responses, 169 women were postmenopausal. The following results concern these patients only. RESULTS: Forty-five women were using some treatment to alleviate certain menopausal symptoms (26.6%). More than half of the patients used no therapy to alleviate menopausal symptoms, either because they had no symptoms (n = 43; 25.4%), they feared breast cancer recurrence (n = 24; 14.2%), they were advised not to use a treatment (n = 27; 16%), it had been shown to be inefficient (n = 5; 3%), or because of contraindication (n = 3; 1.8%). In this survey, 62.3% of postmenopausal women affected by breast cancer suffered from hot flushes (n = 94), of which half were severe (n = 46). Among women suffering from hot flushes, a third used various products to alleviate their symptoms (n = 30). Younger women suffered more often from vasomotor symptoms than did older women (p < 0.000). Current users of aromatase inhibitors suffered more from sexual disorders than did non-users (p < 0.001). They had more often an unsatisfactory sexual life (p < 0.01), more vaginal dryness (p = 0.01) and a decreased libido (p < 0.02) compared to non-users. CONCLUSION: More than 50% of postmenopausal women suffered from climacteric symptoms such as hot flushes, but few were taking a treatment to alleviate these symptoms.

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Premature menopause occurs frequently in breast cancer patients (BC), but there are no specific data about its management. Although hormone therapy (HT) is very efficient in relieving menopausal symptoms, the prescription of this type of drug is still not indicated for BC patients, since in one randomized study (of two existing) an increased rate of new breast cancer (BC) occurrence in HT users was reported. The efficacy of other medications, such as serotonin re-uptake inhibitors, clonidine, veralipride, gabapentin, is much lower than that of HT. The efficacy of black cohosh and phyto-oestrogens remains to be proven. The safety of medications other than HT has not been established either in BC patients. There is a need for randomised trials assessing the safety of these drugs. In the meantime, patients should be informed about the absence of safety data. Prevention and treatment of urogenital atrophy is achieved by using vaginal moistures and weak oestrogen topical preparations. Prevention and treatment of osteoporosis is achieved by a healthy life style, adequate calcium and vitamin D intake and if necessary biphosphonate therapy.

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AIM: This qualitative review analyzes systematically the safety of drugs used to alleviate menopausal symptoms, other than hormone replacement therapy, in breast cancer patients. METHODS: We searched systematically studies using tibolone, serotonin reuptake inhibitors, clonidine, veralipride, gabapentin, black cohosh and phytoestrogens in breast cancer patients. We selected five studies for which we evaluated the methodology, characteristics of the studied populations, outcomes in terms of mortality and recurrence rates. RESULTS: Four trials were conducted using tibolone in breast cancer patients: one double-blind, randomized trial, one prospective controlled study, and two uncontrolled studies. They considerably lack power to detect any difference in breast cancer recurrence or mortality between the treated and control patients. Similar conclusions have to be drawn from the only controlled retrospective study analyzing the safety of antidepressants and antihistamines. We were unable to find studies reporting the safety of the other drugs in breast cancer patients. CONCLUSIONS: There are no valuable data indicating the absence of a harmful effect of drugs used to alleviate climacteric symptoms in breast cancer patients. There is a need for randomized trials to assess the safety of these drugs. In the meantime, patients should be informed about the absence of safety data.

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BACKGROUND: This qualitative review systematically analyses the safety of hormone therapy (HT) in breast cancer (BC) patients. METHODS: We systematically searched studies reporting the use of HT in BC patients. We selected 20 studies in which we evaluated the methodology, characteristics of the studied populations and outcomes in terms of mortality and recurrence rates (RRs). RESULTS: Many studies evaluating HT were uncontrolled and retrospective. Ten prospective and two randomized studies were found. These were characterized by heterogeneity in populations, tumour characteristics, prognostic factors and treatments. Two studies reported a reduced RR, and two reported lowered BC mortality rates in HT users. One randomized study reported an increased rate of new BC events in HT users. CONCLUSIONS: There are currently no reassuring data indicating the absence of a harmful effect of HT. Further studies should analyse whether some regimens are safer than others. There is a need for randomized trials assessing the safety of these regimens. In the meantime, patients should be informed about the absence of safety data.

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PURPOSE: To compare a full-dose epirubicin-cyclophosphamide (HEC) regimen with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen (EC) in the adjuvant therapy of node-positive breast cancer. PATIENTS AND METHODS: Node-positive breast cancer patients who were aged 70 years or younger were randomly allocated to one of the following treatments: CMF for six cycles (oral cyclophosphamide); EC for eight cycles (epirubicin 60 mg/m(2), cyclophosphamide 500 mg/m(2); day 1 every 3 weeks); and HEC for eight cycles (epirubicin 100 mg/m(2), cyclophosphamide 830 mg/m(2); day 1 every 3 weeks). RESULTS: Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Patient characteristics were well balanced among the three arms. One and three cases of congestive heart failure were reported in the EC and HEC arms, respectively. Three cases of acute myeloid leukemia were reported in the HEC arm. After 4 years of median follow-up, no statistically significant differences were observed between HEC and CMF (event-free survival [EFS]: hazards ratio [HR] = 0.96, 95% confidence interval [CI], 0.70 to 1.31, P =.80; distant-EFS: HR = 0.97, 95% CI, 0.70 to 1.34, P =.87; overall survival [OS]: HR = 0.97, 95% CI, 0.65 to 1.44, P =.87). HEC is more effective than EC (EFS: HR = 0.73, 95% CI, 0.54 to 0.99, P =.04; distant-EFS: HR = 0.75, 95% CI, 0.55 to 1.02, P =.06; OS HR = 0.69, 95% CI, 0.47 to 1.00, P =.05). CONCLUSION: This three-arm study does not show an advantage in favor of an adequately dosed epirubicin-based regimen over classical CMF in the adjuvant therapy of node-positive pre- and postmenopausal women with breast cancer. Moreover, this study confirms that there is a dose-response curve for epirubicin in breast cancer adjuvant therapy.

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Breast cancer metastasizes to bone more frequently than to any other organ, and over 80% of advanced breast cancer patients develop bone metastases. Our recent demonstration that human breast cancer cells express bone sialoprotein (BSP), a bone matrix protein, provides a possible clue for the selective affinity of breast cancer cells for bone. We tested the hypothesis that detection of BSP in primary human breast cancer could be a potential indicator of the ability of breast cancer cells to metastasize to bone. BSP expression was evaluated in the primary breast cancers of 39 patients using immunoperoxidase and two specific anti-BSP antibodies. None of these patients presented clinically or scintigraphically detectable bone metastases at the time of surgery. In the course of their disease, 22 patients developed clinically diagnosed bone metastases. Expression of BSP in breast cancer cells from patients who developed bone metastases was significantly higher (p = 0.008, according to the Mann-Whitney test) than in patients with no bone involvement. No association was found between BSP expression in the primary breast lesions and axillary lymph node metastases. BSP expression was significantly increased in infiltrating ductal carcinoma compared with infiltrating lobular carcinoma (p = 0.0023). No correlation was found between immunoreactivity to BSP antibodies and estrogen receptor (ER) status, progesterone receptor (PR) status, or age. Our data suggest that BSP could help to identity which women will develop bone metastases and provide new bases for the understanding of the molecular mechanism(s) responsible for breast cancer cells osteotropism.

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The major variations in the pattern and level of cancer throughout the world reflect for the most part differences in the environment. It is generally agreed that carcinogenesis may arise as a result of chemical, physical, biologic, and genetic insults to cells. In addition, specific external factors may initiate and/or support malignant transformation, such as smoking, occupational and environmental chemicals, radiation, dietary factors, and specific viruses. Furthermore, endogenous compounds, such as steroid sex hormones, may be promoters for carcinogenesis of hormone-dependent tissue. Although some cancers seem to be related to inherited traits, research generally does not support the notion of group or inherited differences in cancer statistics. The leading causes of cancer death in females in 1991 in the United states were lung cancer (52,068), breast cancer (43,583), and colorectal cancer (29,017). According to the American Cancer Society, this year 182,000 women will be diagnosed with breast cancer, 73,900 with lung cancer, and 66,000 with colorectal cancer. Even with our knowledge about the influence of life style and environmental causes of cancer, little progress has been made. In breast cancer, only 25 to 30% can be attributed to known risk factors. Lung cancer in females, on the other hand, once a rare disease, turns out to be the leading cause of cancer death among women in industrialized countries, mostly due to smoking.

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In case of invasive breast cancer, the pathologic assessment of axillary lymph nodes status gives information on staging, prognosis and on the use of systemic adjuvant therapy. Removing at least ten axillary lymph nodes seems to prevent complications arising from uncontrolled tumor growth in the axilla. An axillary dissection is not justified in ductal carcinoma in situ (DCIS). To assess new techniques of axillary dissection will probably help to decrease the complications of the classical approach with oncological safety. Liposuction and endoscopic biopsies seem to give good results in preliminary studies.

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Hormone replacement therapy (HRT) after menopause can effectively reduce climacteric-related symptoms and therefore increase quality of life. A large number of studies have also demonstrated that with a sufficient dosage bone loss can be prevented and fracture frequency reduced. Epidemiological and experimental studies also suggest a decrease in cardiovascular mortality and morbidity among HRT users compared to nonusers. From an epidemiological perspective, in order to obtain optimal prevention of osteoporosis and of cardiovascular diseases, a high proportion of postmenopausal women should be treated using long-term therapy. Surveys generally show that only a small proportion of postmenopausal women use hormone replacement therapy (in Belgium, around 14%) and that the long-term compliance to treatment, which is mandatory in the prevention due to low compliance remains unknown. The reasons why patients patients do not pursue their treatment in the long run remain unclear. Fear of cancer and drug-related side effects, such as unacceptable bleeding, have been among the most frequently mentioned causes. Thus, individual information on patients regarding HRT seems to be crucial issue. A few recent studies have suggested a favorable role of osteoporosis prevention and bone mass measurements to increase compliance, but this is not well established and will depend on the physician's attitude toward HTR and osteoporosis prevention. At present, very little is known about the physician's decision to treat postmenopausal women with HRT. Sometimes, the physician's attitude has been reported was very negative toward HRT-apparently, many physicians think HRT increases cardiovascular risk, even though most data suggest a reduction of cardiovascular risk among HRT users. Very little research has actually been performed on how to improve compliance. Education and behavioral strategies may be of use. Improved communication between patients and physicians, establishing a confidential relationship with patients, and the involvement of nursing counseling are all strategies which may improve compliance. The use of easy-to-take medication that induces no bleeding, supported by calendar devices or reminders, may facilitate chronic use of medication. Future research needs to investigate the physician's and patient's decision-making processes and the reasons for those decisions.

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