Associated morbidity in screened and diagnosed breast cancer patients: a retrospective study.

INTRODUCTION: Breast cancer (BC) screening has been associated with reduced mortality and morbidity. This study compares tumor characteristics and treatment morbidity in screened versus diagnosed women. MATERIALS AND METHODS: This retrospective study, conducted between 2010 and 2013, included 666 BC screened or diagnosed patients. We compared patients and tumors characteristics and received treatments. We also analyzed the results after excluding patients at risk of BC and conducted a multivariate analysis to assess odds ratios (OR). RESULTS: Screened women had smaller tumors (16,5 vs 22,6 mm, p < 0.001), of lower grade (p < 0.001) with a lower proliferation index (PI) (p < 0.001) than diagnosed women. Screened women were more frequently treated using conservative surgery (82.8% vs 59.7%, p < 0.001), needed less often axillary dissection (15.1% vs 35.4%, p < 0.001) and less often chemotherapy (20.8% vs 48.3% p < 0.001) than diagnosed women. In the multivariate analysis after adjustment for age and BC history, diagnosed women had increased (OR: 4.79, 95% IC: 3.19-7,18) risk to be administered chemotherapy and to undergo axillary dissection (OR: 4.18, 95% IC: 1.56-11.17) than screened women. CONCLUSION: Patients should be informed about the benefits in terms of morbidity that screening confers to them.

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.

Multifactorial approach to predicting resistance to anthracyclines.

PURPOSE: Validated biomarkers predictive of response/resistance to anthracyclines in breast cancer are currently lacking. The neoadjuvant Trial of Principle (TOP) study, in which patients with estrogen receptor (ER) -negative tumors were treated with anthracycline (epirubicin) monotherapy, was specifically designed to evaluate the predictive value of topoisomerase II-α (TOP2A) and develop a gene expression signature to identify those patients who do not benefit from anthracyclines. PATIENTS AND METHODS: The TOP trial included 149 patients, 139 of whom were evaluable for response prediction analyses. The primary end point was pathologic complete response (pCR). TOP2A and gene expression profiles were evaluated using pre-epirubicin biopsies. Gene expression data from ER-negative samples of the EORTC (European Organisation for Research and Treatment of Cancer) 10994/BIG (Breast International Group) 00-01 and MDACC (MD Anderson Cancer Center) 2003-0321 neoadjuvant trials were used for validation purposes. RESULTS: A pCR was obtained in 14% of the evaluable patients in the TOP trial. TOP2A amplification, but not protein overexpression, was significantly associated with pCR (P ≤ .001 v P ≤ .33). We developed an anthracycline-based score (A-Score) combining three signatures: a TOP2A gene signature and two previously published signatures related to tumor invasion and immune response. The A-Score was characterized by a high negative predictive value ([NPV]; NPV, 0.98; 95% CI, 0.90 to 1.00) overall and in the human epidermal growth factor receptor 2 (HER2) -negative and HER2-positive subpopulations. Its performance was independently confirmed in the anthracycline-based arms of the two validation trials (BIG 00-01: NPV, 0.83; 95% CI, 0.64 to 0.94 and MDACC 2003-0321: NPV, 1.00; 95% CI, 0.80 to 1.00). CONCLUSION: Given its high NPV, the A-Score could become, if further validated, a useful clinical tool to identify those patients who do not benefit from anthracyclines and could therefore be spared the non-negligible adverse effects.

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 immunofluorescence 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.

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 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.

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.

Management of BRCA1/2 associated breast cancer: a systematic qualitative review of the state of knowledge in 2006.

INTRODUCTION: The optimal clinical management of breast cancer (BC) arising in BRCA1/2 mutations carriers is a difficult issue complicated by the risk of subsequent malignancies and by the potential differences in response to local and systemic therapies. AIM: Systematically review the difference in outcome after breast conservation therapy (BCT) and uni-or bilateral mastectomy in BRCA1/2 related BC. MATERIAL AND METHODS: We selected 20 studies, for which we evaluated the methodology, the characteristics of the populations, biases, confounding risk factors and outcomes. RESULTS: All studies are retrospective, entailed by numerous biases. They varied with respect to patients' number, selection, and confounding factors. Hereditary BC patients carried an increased risk of ipsilateral recurrence in 5/17 studies, a worse survival in 4/14, an increased risk of contralateral BC in 14/16. CONCLUSION: Except for contralateral risk, the presence of a BRCA mutation does not seem to offer additional prognostic information. Large prospective trials, stratified for risk reduction strategies are warranted.

Influence of HRT on prognostic factors for breast cancer: a systematic review after the Women's Health Initiative trial.

INTRODUCTION: Mortality due to breast cancer has been reported to be the same or even lower in HRT users than in non-users. This has been attributed to earlier diagnosis and to better prognosis. Nevertheless, more advanced disease in HRT users was reported recently by the Women's Health Initiative (WHI) study. The objective of this study was to assess, using a systematic review of current literature, whether the data of the WHI study are in contradiction to observational data. METHODS: We selected 25 studies, for which we evaluated the methodology, the characteristics of the studied populations, confounding breast cancer risk factors and prognostic indicators. RESULTS: The WHI study, showing a worsening of some prognostic parameters, is in contradiction to most published observational studies. Most observational studies are retrospective, not well matched and did not consider most confounding factors. Their methodology and selection criteria varied considerably and the number of patients was often small. No differences in the distributions of histology, grade or steroid receptors were observed in the WHI trial, while this was the case in some of the observational studies. Other parameters (S phase, protein Neu, Bcl-2 gene, protein p53 and E-cadherin, cathepsin D) were not reported in the WHI trial. CONCLUSIONS: In view of these data, the current clinical message to patients should be changed: one can no longer declare that breast cancers developed while using HRT are of better prognosis.