Birgit Carly

HER2-positive circulating tumor cells in breast cancer.

Purpose Circulating Tumor Cells (CTCs) detection and phenotyping are currently evaluated in Breast Cancer (BC). Tumor cell dissemination has been suggested to occur early in BC progression. To interrogate dissemination in BC, we studied CTCs and HER2 expression on CTCs across the spectrum of BC staging. Methods Spiking experiments with 6 BC cell lines were performed and blood samples from healthy women and women with BC were analyzed for HER2-positive CTCs using the CellSearch®. Results Based on BC cell lines experiments, HER2-positive CTCs were defined as CTCs with HER2 immunofluoresence intensity that was at least 2.5 times higher than the background. No HER2-positive CTC was detected in 42 women without BC (95% confidence interval (CI) 0–8.4%) whereas 4.1% (95%CI 1.4–11.4%) of 73 patients with ductal/lobular carcinoma in situ (DCIS/LCIS) had 1 HER2-positive CTC/22.5 mL, 7.9%, (95%CI 4.1–14.9%) of 101 women with non metastatic (M0) BC had ≥1 HER2-positive CTC/22.5 mL (median 1 cell, range 1–3 cells) and 35.9% (95%CI 22.7–51.9%) of 39 patients with metastatic BC had ≥1 HER2-positive CTC/7.5 mL (median 1.5 cells, range 1–42 cells). In CTC-positive women with DCIS/LCIS or M0 BC, HER2-positive CTCs were more commonly detected in HER2-positive (5 of 5 women) than HER2-negative BC (5 of 12 women) (p = 0.03). Conclusion HER2-positive CTCs were detected in DCIS/LCIS or M0 BC irrespective of the primary tumor HER2 status. Nevertheless, their presence was more common in women with HER2-positive disease. Monitoring of HER2 expression on CTCs might be useful in trials with anti-HER2 therapies.

Breast cancer seeding associated with core needle biopsies: a systematic review.

BACKGROUND Preoperative diagnosis has become the standard in breast cancer (BC) management. Recently, ultrasound guided core needle biopsy (CNB) and stereotactic needle core biopsy have replaced fine needle aspiration cytology. Epithelial cell displacement (DE) occurs frequently after core needle biopsy (CNB) for breast cancer diagnosis. AIM Systematically review (between 1900 and 2008) the clinical significance of DE after CNB in BC patients, and associated risk factors (delay between biopsy and surgery, needle passes, duration of the procedure, tumor size, histological type, tumor grade, margins, type of surgery, and of adjuvant treatment). MATERIALS AND METHODS We selected 15 studies: 9 assessed the rate of DE after CNB and 6 the impact of CNB on outcome endpoints. RESULTS We found 3 prospective and 12 retrospective studies. However these had numerous biases such as insufficient power, confounding factors, selection of cases and controls, surrogate endpoints, heterogeneity of measured displacement. Malignant DE on surgical specimens occurred in 22% of the patients. A short interval between CNB and surgical excision increased the risk of detecting displaced cells. No increase in local recurrence was reported after CNB. Contradictory results were found in terms of sentinel node metastases. Only one study evaluated overall survival data and reported no worse survival in patients with preoperative CNB. CONCLUSION Although data are limited, no increased morbidity has been associated with iatrogenic seeding after CNB.

Safety of alternative treatments for menopausal symptoms after breast cancer: a qualitative systematic review

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.

A survey among breast cancer survivors: treatment of the climacteric after breast cancer

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.

Improving quality of life after breast cancer: prevention of other diseases

Many women with breast cancer will be diagnosed at an early stage through screening programmes. Furthermore, most women affected by breast cancer will not die from it but from other diseases, owing to recent improvements in treatment. This article assesses whether breast cancer survivors suffer more frequently from other diseases. Specifically, it examines whether they have a higher incidence of other cancers, cardiovascular events and osteoporotic fractures. Women with breast cancer and three or more co-morbid conditions have a 20-fold higher rate of mortality from causes other than breast cancer and a 4-fold higher rate of all-cause mortality when compared with patients who have none. Breast cancer survivors are at increased risk of other cancers, such as stomach, colorectal and lung. Radiotherapy, trastuzumab and aromatase inhibitors increase the risk of cardiovascular disease. However, tamoxifen does not, although it is associated with an increased risk of venous thromboembolism. Aromatase inhibitors, but not tamoxifen, increase the risk of osteoporotoic fracture and bisphosphonate therapy should be considered.

Effect of preventive hormonal therapy on breast density: a systematic qualitative review.

Breast density (BD) is recognized as one of the strongest independent risk factors of breast cancer (BC). Unlike most other risk factors, BD can be modified, suggesting that it may be a biomarker for preventive interventions. We conducted a qualitative systematic review to address the effect of preventive hormonal therapy on BD. Among the 26 relevant studies, 10 assessed the effect of tamoxifen on BD (TAM: n = 2 877), 9 that of raloxifene (RLX: n = 1 544), and 7 that of aromatase inhibitors (AI: n = 416). The studies were characterized by a large heterogeneity in designs and in methods of BD measurement. BD could be reduced by TAM (10 studies/10). However, the effect of RLX and AI on BD remains unclear due to conflicting results between studies. Consequently, it is crucial to develop practical, accurate, and reproducible methods of measurement in order to be able to compare the effect of preventive hormonal agents on BD and to determine whether change in BD can be used as a predictor of response to therapy.

Treatment of Premature Menopause in Breast Cancer Patients

Abstract 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.

What information do public organizations provide to Belgian women on primary prevention of breast cancer

Women need to be adequately informed about risk factors and risk reduction strategies for breast cancer to seek optimal primary prevention care. The aim of this study was to determine the amount and content of written information published by Belgian health services and related to primary prevention of breast cancer. We collected all available French language brochures and leaflets related to breast cancer primary prevention and analyzed which risk factors and risk reduction strategies were mentioned. Risk factors and prevention strategies were seldom mentioned. Among the 21 selected leaflets, pertinent to the patient, alcohol was mentioned in eight leaflets; age and genetic predisposition in five; overweight/obesity, personal history of breast cancer, and exercise in four; hormonal treatment in three; family history in two; earlier high-risk benign lesions in one, and ethnicity, breast density, and earlier chest radiation therapy in none. Lifestyle modifications were described in nine, but not one mentioned chemoprevention and risk reduction surgeries. As breast cancer risk reduction now represents an achievable medical objective for women, available written information to women must be improved to help them make an informed choice regarding risk reduction strategies.

Risks of osteoporosis associated with breast cancer treatment: the need to access to preventive treatment.

The results of available clinical studies suggest that breast cancer treatment significantly affect bone turnover, BMD and fracture risk. This is for instance the case for all third-generation aromatase inhibitors. For these reasons it is recommended that breast cancer patients exercise regularly and take daily calcium (1500 mg) and vitamin D (800UI) supplements. Most experts recommend that all women starting medical castration or aromatase inhibitor therapy should be assessed for their risk of osteoporosis and undergo bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DEXA). Patients with pre-existing osteopenia and osteoporosis should be evaluated for conditions which worsen skeletal health, such as vitamin D deficiency, hyperparathyroidism, hyperthyroidism and hyper-calcuria. If these patients have a BMD score of -2.5 or lower, a low BMD (T-score between -1 and -2.5) and additional risk factors for osteoporosis or fragility fractures, bisphosphonate therapy should be considered. The optimal duration of bisphosphonate therapy is unknown. It should probably be given for as long as aromatase inhibitor therapy is continued. In addition, bisphosphonate therapy may also reduce the risk of bone metastases. This approach seems to be cost effective based on an economic evaluation model.

Breast Cancer Prevention in BRCA1/2 Mutation Carriers: A Qualitative Review

To the Editor: We recently qualitatively reviewed the literature on primary prevention strategies in BRCA 1 ⁄2 mutation carriers for chemoprevention and risk reduction surgery. The trials had to provide information on the effectiveness of primary prevention (bilateral mastectomy, bilateral salpingo-oophorectomy or tamoxifen) in terms of breast cancer risk reduction in BRCA 1 or 2 mutation carriers. This review focused on breast cancer incidence, total mortality and specific breast cancer mortality. The data from each study was descriptively summarized; a quantitative meta-analysis was not feasible in the absence of randomized controlled trials and with such heterogeneous study designs and insufficient data. Ten studies were retained. Six multi-center cohort studies evaluate the efficacy of bilateral prophylactic salpingo-oophorectomy (1‐6). They report a reduction of approximately 50% in the incidence of breast cancer and one trial reveals a mortality reduction after bilateral salpingo-oophorectomy. Three cohort studies evaluate the incidence of breast cancer after bilateral prophylactic mastectomy (7‐9). All of these studies report a significant reduction of more than 95% of the incidence of breast cancer in the BPM group. However these trials are of insufficient methodological quality and the data on the effectiveness of BPM on mortality is not available at present. One study evaluates the effectiveness of tamoxifen in healthy BRCA mutation carriers (10). This analysis shows a nonsignificant reduction of the incidence of breast cancer in BRCA 2 mutation carriers (RR: 0.38, 95% CI: 0.06‐1.56). However, this study did not highlight a reduction of the incidence of breast cancer in BRCA 1 mutation carriers (RR: 1.67, 95% CI: 0.32‐10.70). It is difficult to draw conclusions concerning the effectiveness of tamoxifen in BRCA mutation carriers given that the only study available is a (post hoc) analysis including too few cases. Primary prevention is a promising approach in the fight against breast cancer, especially for women at very high risk carrying BRCA mutations. More studies are necessary, especially to evaluate the effect of prevention on mortality.