Breast (Edinburgh, Scotland)

Published by Elsevier
Online ISSN: 0960-9776
Publications
Survival curves by hospital volume.
Demographic and tumor characteristic of breast cancer women diagnosed between 2004 and 2006, by annual volume hospital.
Results of Cox PH model: Determinants of survival after breast cancer.
Article
To compare processes of care and survival for breast cancer by hospital volume in Belgium, based on 11 validated process quality indicators. Three databases were linked at the patient level: the Cancer Registry, the population and the claims databases. All women with a diagnosis of invasive breast cancer between 2004 and 2006 were selected. Hospitals were classified according to their annual volume of treated patients: <50 (very low), 50-99 (low), 100-149 (medium) and ≥ 150 patients (high). Cox and logistic regression models were used to test differences in 5-year survival and in achievement of process indicators across volume categories, adjusting for age, tumor grade and stage. A total of 25178 women with invasive breast cancer were treated in 111 hospitals. Half of the hospitals (N=57) treated <50 patients per year. Six of eleven process indicators showed higher rates in high-volume hospitals: multidisciplinary team meeting, cytological and/or histological assessment before surgery, use of neoadjuvant chemotherapy, breast-conserving surgery rate, adjuvant radiotherapy after breast-conserving surgery, and follow-up mammography. Higher volume was also associated with improved survival. The 5-year observed survival rates were 74.9%, 78.8%, 79.8% and 83.9% for patients treated in very-low-, low-, medium- and high-volume hospitals respectively. After case-mix adjustment, patients treated in very-low- or low-volume hospitals had a hazard ratio for death of 1.26 (95% CI 1.12, 1.42) and 1.15 (95% CI 1.01, 1.30) respectively compared with high-volume hospitals. Survival benefits reported in high-volume hospitals suggest a better application of recommended processes of care, justifying the centralization of breast cancer care in such hospitals.
 
Article
Introduction: The publication of the American College of Surgeons Oncology Group (ACOSOG) Z-0011 Trial concluded that axillary lymph node clearance is no longer necessary for women having breast conserving treatment with 1-2 positive axillary sentinel lymph glands. The current study was designed to investigate the clinical impact of the Z-0011 Trial in breast surgical practice. Materials and methods: The BreastSurgANZ National Breast Cancer Audit database was interrogated for women treated between 2005 and 2010 who would have met the entry criteria for the Z-0011 Trial. This group was then calculated as a proportion of the total breast cancer episodes treated during this period. Results: A total of 64,883 cases of breast cancer were eligible for analysis. 22,731 underwent breast conserving surgery and sentinel node biopsy for invasive breast cancer. A total of 4482 cases (6.9%) fulfilled the criteria for Z-11 Trial. Conclusion: Although the ACOSOG Z-0011 Trial has important implications for sentinel node positive cases undergoing breast conserving treatment, the overall impact of the Trial in breast clinical practice is small. It cannot be described as "practice changing". Women who fulfil the entry criteria for the Z-0011 Trial should be informed of the clinical relevance of the trial and be permitted to participate in informed discussions with members of the multidisciplinary team regarding their treatment options.
 
Article
Background: The aim of this study was to evaluate the significance of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for speculating the malignant level and prognostic value of operable breast cancers. Methods: Of 578 consecutive patients with primary invasive breast cancer who underwent curative surgery between 2005 and 2010, 311 patients (53.8%) who received FDG-PET/CT before initial therapy were examined. Results: Receiver operating characteristics (ROC) curve analysis showed the cutoff value of the maximum standardized uptake value (SUVmax) to predict cancer recurrence was 3.8 in all patients and 8.6 in patients with the triple-negative subtype, respectively. In all patients, 3-year DFS rates were 98.8% for patients with a tumor of SUVmax ≤ 3.8 and 91.6% for patients with a tumor of SUVmax > 3.8 (p < 0.001). High value of SUVmax was significantly associated with large tumor size (p < 0.001), lymph node metastasis (p = 0.040), high nuclear grade (p < 0.001), lymphovascular invasion (p = 0.032), negative hormone receptor status (p < 0.001), and positive HER2 status (p = 0.014). Based on the results of multivariate Cox analysis in all patients, high SUVmax (p = 0.001) and negative hormone receptor status (p = 0.005) were significantly associated with poor prognosis. In patients with triple-negative subtype, 3-year DFS rates were 90.9% for patients with a tumor of SUVmax ≤ 8.6 and 42.9% for patients with a tumor of SUVmax > 8.6 (p = 0.002), and high SUVmax was the only significant independent prognostic factor (p = 0.047). Conclusion: FDG-PET/CT is useful for predicting malignant behavior and prognosis in patients with operable breast cancer, especially the triple-negative subtype.
 
Article
Purpose: This study aims to determine the utility of ultrasonography (US)-guided direct dye-marking of sentinel lymph nodes (SLNs) by real-time virtual sonography (RVS) constructed with three-dimensional (3D) computed tomography (CT)-lymphography (LG). Patients and methods: We identified SLNs in 258 clinically node-negative breast cancer patients using an RVS system to display in real time a virtual multiplanar reconstruction CT image obtained from CT volume data corresponding to the same cross-sectional image from US. CT volume data were obtained using our original 3D CT-LG, which accurately detects SLNs in breast cancer. We then perform US-guided dye-marking close to SLNs using indocyanine green (ICG). Subsequently, indigo carmine blue dye was injected into the subareolar and peritumoral areas around each primary tumor. All patients underwent SLN biopsy and SLN metastases were examined pathologically. Results: In all 258 patients, we were able to detect the same SLNs visualized on 3D CT-LG, using the RVS system. We detected ICG close to SLNs in 257 of 258 patients (99.6%) during SLN biopsy. In 25 patients (9%), we failed to follow the blue lymphatic route stained by indigo carmine and SLNs were not stained by indigo carmine, but easily detected SLNs by ICG marking. Conclusion: US-guided direct ICG dye-marking of SLNs using this RVS system seems useful for the detection of SLNs, allowing easy detection of SLNs even when the stained lymphatic route is not followed.
 
Article
This randomized, open-label phase II study compared the efficacy of sunitinib monotherapy with that of single-agent standard-of-care (SOC) chemotherapy in patients with previously treated advanced triple-negative breast cancer (TNBC). Patients with advanced TNBC, relapsed after anthracycline- and taxane-based chemotherapy, were randomized to receive either sunitinib (37.5 mg/day) or the investigator's choice of SOC therapy. Progression-free survival was the primary endpoint. Median progression-free survival was 2.0 months with sunitinib and 2.7 months with SOC chemotherapy (one-sided P = 0.888). Median overall survival was not prolonged with sunitinib (9.4 months) compared with SOC chemotherapy (10.5 months; one-sided P = 0.839). The objective response rate was 3% with sunitinib and 7% with SOC chemotherapy (one-sided P = 0.962). Sunitinib monotherapy did not improve efficacy compared with SOC chemotherapy in patients with previously treated advanced TNBC, for which identification of effective treatments and therapeutic targets remains an urgent need. NCT00246571.
 
Article
For young women with breast cancer mothers might either be a source of support or of increased stress, depending on the premorbid relationship and on the psychological effect of the daughter's diagnosis on her mother. To examine the effects of a breast cancer diagnosis on young women's relationships with their mothers and the possible support needs of these mothers from the daughters' perspective. We developed and pre-tested a self-administered questionnaire on 10 survivors of breast cancer diagnosed ≤ age 40. Then, consecutive recurrence-free young women diagnosed with breast cancer were asked to complete the modified questionnaire. Of 110 daughters approached from July/11 to May/12, 90 (82%) participated. In 11 cases (13%), the daughters had turned to their mothers before approaching anyone else. Of the 83 daughters who disclosed their diagnosis to their mothers, 76 (92%) stated their mothers had been emotionally and/or practically supportive, and 43 (54%) reported that the breast cancer diagnosis had a favorable impact on their relationship with their mothers. Of the 35 employed mothers, 26 had taken time off from work to support their daughters. Nineteen mothers, eight of whom had been living in a different country, had slept over or moved in with daughters during their treatment. Twenty-two daughters believed their mothers felt responsible to some extent for their developing breast cancer. Fifty-nine daughters indicated that health care professionals could help mothers by providing information pamphlets, education sessions, and linking to support groups. Mothers are an important source of support for young daughters with breast cancer, with the mother-daughter relationship frequently becoming closer after the diagnosis. However, the practical and emotional burden on mothers appears to be high. Future studies should address the effects of a breast cancer diagnosis in young daughters from the mothers' perspective, and the benefit of formal supports for these mothers.
 
Article
Background: Acquisition of additional breast tissue has become integral to breast oncology research. This questionnaire study examines patient willingness to undergo research-dedicated breast biopsies either at time of diagnostic biopsy (T1) or after carcinoma diagnosis has been confirmed and eligibility for a specific study established (T2), and influencing factors thereof. Methods: Prior to consultation, patients attending breast clinics were recruited to complete a questionnaire examining willingness to undergo an extra fine needle aspirate (FNA) and/or core needle biopsy (CNB) for research either at T1 or T2. Descriptions of FNA and CNB procedures were supplied to those with no prior experience. Patient perspectives towards donating surplus tissue remaining from a diagnostic procedure and/or surgery for future research were also explored. Findings: A total of 100 patients were recruited, 42% with prior history of breast carcinoma (BC), 22% with family history of BC (FHBC) and 65%/42% with previous experience of CNB/FNA respectively. Overall, 57% were willing to undergo additional biopsy at one or both time points. Willingness to undergo additional biopsy was greater for T1 than T2, but equivalent for CNB and FNA (willingness CNB T1, 50% vs T2, 26%, willingness FNA T1 50% vs T2 29%). A statistically significant increase in willingness to undergo CNB and/or FNA at T1 and/or T2 was seen in association with prior diagnosis of BC, FHBC, previous visit to breast clinic and prior experience of breast biopsy. 83% of patients expressed a willingness to allow surplus tissue to be stored in a biobank for future research. Interpretation: Where possible patients should be approached to undergo baseline research biopsies at time of diagnostic process rather than subsequently. Patients do not find FNA more acceptable than core biopsy. Prior exposure to the biopsy procedure increases willingness to undergo research-dedicated biopsies.
 
Distribution of body mass index (BMI). This figure shows the distribution of patients according to baseline BMI. a) Whole patients with information of BMI (n ¼ 109). BMI ranged from 17.4 to 38.8 kg/m 2 (median, 23.7 kg/m 2 ). b) Patients included in the multivariate analysis (n ¼ 81). BMI ranged from 17.4 to 38.8 kg/m 2 (median, 23.9 kg/m 2 ). The distribution of BMI between the two dataset was not significantly different (p ¼ 0.58, Wilcoxon rank-sum test).
Correlation between pathological response and tumor reduction rate (n ¼ 80). a) No significant correlation was found in tumor reduction rate by uni-dimensional measurements at 24 weeks based on the pathological response. b) Tumor reduction rate using bi-dimensional measurements. Pathological responders showed a significantly larger reduction rated by bi-dimensional measurements compared to pathological non-responders (p ¼ 0.04, Wilcoxon rank-sum test).
Correlation between body mass index (BMI) and clinical response (WHO criteria) (n ¼ 81). This graph shows the objective response rate (ORR: CR þ PR in WHO criteria) according to BMI group. The ORR in the low BMI group was 21.7%, 56.0% in the intermediate BMI group and 60.6% in the high BMI group (p ¼ 0.01, chi-square test).
Baseline patient and tumor characteristics by Body Mass Index (BMI) category.
Article
Some studies have shown that high body mass index (BMI) is associated with inferior outcome after adjuvant therapy with anastrozole in breast cancer patients. We aimed to investigate predictive effect of BMI on clinical response to neoadjuvant therapy with exemestane in postmenopausal patients with primary breast cancer. The study group consisted of 109 patients from the JFMC 34-0601 neoadjuvant endocrine therapy trial. Patients were categorized into three groups according to BMI: low (BMI < 22 kg/m(2)), intermediate (22 ≤ BMI < 25 kg/m(2)) and high (BMI ≥ 25 kg/m(2)). Statistical analyses were performed to explore the predictive effect of BMI on clinical response. Higher BMI correlated with positive progesterone receptor status (p < 0.01) and low Ki-67 index (p = 0.03). Objective response rates (ORR) were 21.7% in low BMI, 56.0% in intermediate BMI and 60.6% in high BMI, respectively (p = 0.01). In a multivariate analysis, low BMI was an independent negative predictor of clinical response. Low BMI was associated with a decreased ORR to neoadjuvant endocrine therapy with exemestane. Our results may suggest that the predictive effect of BMI varies according to the type of aromatase inhibitor and objective outcome.
 
Article
Sentinel lymph node biopsy (SLNB) is a staging technique with a significant impact on patients’ quality of life: the oncological effectiveness in a large number of patients affected by breast carcinoma has been already demonstrated, and the clinical research is now focusing on new indication for the biopsy and widespread adoption of the technique. At the European Institute of Oncology we are applying SLNB under local anesthesia: our aim is to improve the management of the disease with low costs for the structure and patients, and to improve patients’ acceptance of breast cancer treatments. We are now discussing the impact of the SLNB under local anesthesia on the activity of a breast surgery department. We also present an update of our experience.
 
Article
The aim of this randomized phase II study was to evaluate the anti-tumor activity and safety of capecitabine and vinorelbine in patients with metastatic breast cancer pretreated with taxanes and anthracyclines. We planned to randomize 72 patients to capecitabine 1250 mg/m(2) orally bid days 1-14 or vinorelbine 30 mg/m(2) i.v. days 1 and 8, both given every 3 weeks. The study was stopped due to poor accrual with 47 patients enrolled. Responses were seen in 2/23 patients treated with capecitabine (8.7%; 95% CI 1.1-29.0) and 3/24 patients treated with vinorelbine (12.5%; 95% CI 2.7-32.4). Median progression-free survival was 2.8 and 2.6 months, and median overall survival was 9.3 and 11.0 months, in the capecitabine and vinorelbine arms, respectively. There was more hematologic toxicity, neurotoxicity, and nausea/vomiting with vinorelbine and more diarrhea and hand-foot syndrome with capecitabine. The anti-tumor activity of capecitabine and vinorelbine seems to be comparable, but the toxicity profiles are different.
 
Article
Vascular endothelial growth factor (VEGF) is used to evaluate the angiogenic activity in breast carcinoma. Nitric oxide (NO) and insulin-like growth factor-I (IGF-I) are also implicated in breast tumorigenesis, including angiogenesis. We measured serum VEGF, IGF-I and nitrate+nitrite levels in 38 patients with metastatic and 23 with nonmetastatic breast cancer and in 16 controls. Serum VEGF and IGF-I levels were higher in patients with metastatic disease than in those with nonmetastatic disease or in controls (P<0.001). Serum nitrate+nitrite levels were higher in patients with metastatic and nonmetastatic disease than in controls (P<0.001). Patients with visceral metastasis and local metastasis had higher serum VEGF and nitrate+nitrite levels than patients with bone metastasis (P<0.05). In the metastatic disease group, there was a positive correlation between serum VEGF levels and nitrate+nitrite levels (r=0.436, P<0.05). Within the group with nonmetastatic disease, premenopausal patients had higher serum IGF-I levels than did postmenopausal patients (P<0.001). NO may involve an angiogenic process that is stimulated by VEGF in breast carcinoma. Larger studies are required to clarify these suggestions.
 
Article
The incidence of malignancy in excision biopsies performed for atypical ductal hyperplasia (ADH) diagnosed on needle biopsies has decreased since the advent of larger tissue sampling and improved accuracy using vacuum-assisted Mammotome biopsy. We undertook a retrospective study to identify predictive factors for understaging of ADH diagnosed on 11-gauge Mammotome biopsy, to determine whether it was possible to avoid surgical excision in women where mammographically visible calcifications had been completely removed. Sixty-one biopsy diagnosed ADH lesions were correlated with surgical excision findings that revealed DCIS in 14 (23%). The mammographic and biopsy features were statistically analyzed using Fisher's exact test. There was no association between morphology, extent of calcifications, number of cores sampled with underestimation of malignancy (P=0.503, 0.709, 0.551 respectively). In the absence of residual calcifications, the frequency of underestimation of carcinoma still occurred in 17%.
 
Article
Researchers from eleven countries (i.e. Austria, England, Estonia, Finland, France, Germany, Ireland, Netherlands, Poland, Spain, and Sweden) compared how their DRG systems deal with breast cancer surgery patients. DRG algorithms and indicators of resource consumption were assessed for those DRGs that individually contain at least 1% of all breast cancer surgery patients. Six standardised case vignettes were defined and quasi prices according to national DRG-based hospital payment systems were ascertained. European DRG systems classify breast cancer surgery patients according to different sets of classification variables into three to seven DRGs. Quasi prices for an index case treated with partial mastectomy range from €577 in Poland to €5780 in the Netherlands. Countries award their highest payments for very different kinds of patients. Breast cancer specialists and national DRG authorities should consider how other countries' DRG systems classify breast cancer patients in order to identify potential scope for improvement and to ensure fair and appropriate reimbursement.
 
Article
The successful translation of the scientific principles of targeting the breast tumour oestrogen receptor (ER) with the nonsteroidal anti-oestrogen tamoxifen and using extended durations (at least 5 years) of adjuvant therapy, dramatically increased patient survivorship and significantly enhanced a drop in national mortality rates from breast cancer. The principles are the same for the validation of aromatase inhibitors to treat post-menopausal patients but tamoxifen remains a cheap, life-saving medicine for the pre-menopausal patient. Results from the Oxford Overview Analysis illustrate the scientific principle of "longer is better" for adjuvant therapy in pre-menopausal patients. One year of adjuvant therapy is ineffective at preventing disease recurrence or reducing mortality, whereas five years of adjuvant tamoxifen reduces recurrence by 50% which is maintained for a further ten years after treatment stops. Mortality is reduced but the magnitude continues to increase to 30% over a 15-year period. With this clinical database, it is now possible to implement simple solutions to enhance survivorship. Compliance with long-term anti-hormone adjuvant therapy is critical. In this regard, the use of selective serotonin reuptake inhibitors (SSRIs) to reduce severe menopausal side effects may be inappropriate. It is known that SSRIs block the CYP2D6 enzyme that metabolically activates tamoxifen to its potent anti-oestrogenic metabolite, endoxifen. The selective norepinephrine reuptake inhibitor, venlafaxine, does not block CYP2D6, and may be a better choice. Nevertheless, even with perfect compliance, the relentless drive of the breast cancer cell to acquire resistance to therapy persists. The clinical application of long-term anti-hormonal therapy for the early treatment and prevention of breast cancer, focused laboratory research on the discovery of mechanisms involved in acquired anti-hormone resistance. Decades of laboratory study to reproduce clinical experience described not only the unique mechanism of selective ER modulator (SERM)-stimulated breast cancer growth, but also a new apoptotic biology of oestradiol action in breast cancer, following 5 years of anti-hormonal treatment. Oestradiol-induced apoptotic therapy is currently shown to be successful for the short-term treatment of metastatic ER positive breast cancer following exhaustive treatment with anti-hormones. The "oestrogen purge" concept is now being integrated into trials of long-term adjuvant anti-hormone therapy. The Study of Letrazole Extension (SOLE) trial employs "anti-hormonal drug holidays" so that a woman's own oestrogen may periodically purge and kill the nascent sensitized breast cancer cells that are developing. This is the translation of an idea first proposed at the 1992 St. Gallen Conference. Although tamoxifen is the first successful targeted therapy in cancer, the pioneering medicine is more than that. A study of the pharmacology of tamoxifen opened the door for a pioneering application in cancer chemoprevention and created a new drug group: the SERMs, with group members (raloxifene and lasofoxifene) approved for the treatment and prevention of osteoporosis with a simultaneous reduction of breast cancer risk. Thus, the combined strategies of long-term anti-hormone adjuvant therapy, targeted to the breast tumour ER, coupled with the expanding use of SERMs to prevent osteoporosis and prevent breast cancer as a beneficial side effect, have advanced patient survivorship significantly and promise to reduce breast cancer incidence.
 
Protocol for male breast lump/gynaecomastia. N.B. the difference in policy between males and females reflects the lower risk for men (1:200 female breast cancers) coupled with the lower cancer rates in younger patients in general.
Patient age and protocol scores for MBCs presenting during the 9 year study period.
Article
Triple assessment in men varies, possibly in response to currently published non-specific guidance. The study aims to assess the efficacy of triple assessment as part of an age related protocol currently used in the clinical setting. 1141 referrals between 01.01.01 and 31.12.09 were evaluated. Patient age ranged from 29 to 89 years. Mammography (M) was performed in men ≥35years. Sensitivity for clinical examination (CE) was 64.0%, M 77.8%, US 92.0%. 25 cancers were diagnosed, 24 aged >40years, 1 aged 29. 2 presented with nipple discharge. The cancer <40years was diagnosed with CE and US, all others had suspicious CE and/or M necessitating US and biopsy. We suggest a protocol incorporating mammography in men ≥40years would capture all cancers. Combined specificities approaching 100% suggest men >40 years scored benign after CE and M warrant no further assessment. Bloody nipple discharge is a suspicious sign and the reassurance of non-bloody discharge should be treated with caution.
 
Article
Background: The comparative safety of breast reconstruction in obese patients remains to be clearly defined. This study utilized multi-institutional data to characterize the effect of body mass index (BMI) on breast reconstruction outcomes. Methods: Utilizing Current Procedural Terminology (CPT) codes, patients undergoing tissue expander, pedicled transverse rectus abdominis myocutaneous (TRAM) flap, latissimus dorsi flap, and free flap breast reconstruction were identified in the National Surgical Quality Improvement Program (NSQIP) database. Patients were stratified as obese (BMI ≥ 30) and non-obese (BMI < 30). Overall postoperative morbidity, flap complications, non-flap complications, and reoperation rates were compared among the groups. Results: Of 12,986 patients who underwent breast reconstruction, 3636 (28.0%) were obese. Overall morbidity was significantly elevated in obese patients across all forms of reconstruction (p < 0.05). BMI was correlated with increased surgical complications for tissue expander, pedicled TRAM, and free flap reconstructions (OR = 1.09, OR = 1.05, OR = 1.10, respectively; p < 0.05). Medical complications were higher in obese patients undergoing tissue expander and pedicled TRAM reconstructions (p = 0.001 and p < 0.001), but no significant difference was observed in latissimus and free flap reconstruction patients. Compared with obese tissue expander recipients, obese patients reconstructed using autologous tissue had higher rates of reoperations (12.8% versus 9.1%), overall morbidity (18.0% versus 9.5%), surgical (12.7% versus 8.3%), and medical complications (9.0% versus 2.2%). Conclusions: The NSQIP database allows for evaluation and comparison of reconstructive outcomes in the obese population. Increased BMI was associated with higher morbidity in autologous reconstruction than tissue expander reconstruction. Among autologous procedures, latissimus flaps experienced the lowest captured 30 day morbidity.
 
Article
The modulation of Bmi-1 is observed in several tumor tissues, and its heightened protein level is suspected to be involved in tumorigenesis by acting as a transcriptional repressor in the INK4a/ARF locus. To elucidate the modulation of Bmi-1 in invasive ductal breast cancers, we examined its transcript and protein levels. The bmi-1 mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) showed that it was significantly up-regulated in 28 specimens out of 33 breast carcinoma tissues compared with those of non-neoplastic tissues just adjusted to tested specimens. Immunohistochemical staining for Bmi-1 also showed that 44 specimens out of 71 breast carcinoma tissues (62%) had strong positive signals with a more intense staining pattern in the invading fronts than in the central portions of primary invasive breast cancers. Univariate and multivariate analyses showed that a high level of Bmi-1 expression was significantly correlated with axillary lymph node metastases and positive estrogen receptor status. These findings suggested that Bmi-1 might be involved in the tumor progression and metastasis of invasive ductal breast cancer.
 
Article
Phyllodes tumours are rare neoplasms of the female breast, especially among adolescent women. We present the case of a 17-year old female patient with a large benign phyllodes tumour. The patient was treated by one-stage excision with reduction mammaplasty. Symmetry of breast contour and nipple-areola complex position could be restored. At follow-up after 13 years good cosmetic result was maintained and there was no evidence of local recurrence. Standard plastic surgical techniques like reduction mammaplasty might be applied in treating large benign tumours compromising the aesthetic aspect of the breast.
 
Article
A woman's build, the risk of breast cancer and its subsequent prognosis seem to be related. In most but not all case-control and prospective cohort studies, an inverse relationship has been found between weight and breast cancer among premenopausal women. However, most large epidemiological studies have found that overweight or obese women are at increased risk of developing postmenopausal breast cancer. It is suggested that higher body mass index is associated with a more advanced stage of breast cancer at diagnosis in terms of tumour size but data on lymph node status is not so consistent. All treatment modalities for breast cancer such as surgery, radiotherapy, chemotherapy and hormonal treatment may be adversely affected by the presence of obesity. The overall and disease-free survival is worse in most but not all studies of prognosis of obese pre- and postmenopausal women with breast cancer.
 
Article
The purpose of this clinical cohort study was to examine long-term survival in groups of screen-detected and symptomatic breast cancer patients attending a specialist breast unit, and to determine the factors affecting this survival. A total of 3239 breast cancer cases (1252 screen-detected and 1987 symptomatic) diagnosed between 1989 and 2002 were followed up until the end of 2002, and breast cancer-specific survival was examined in the screened and symptomatic groups, in relation to patient age, tumour size, nodal status and histological grade. Long-term survival in this clinical cohort was high. Relative survival values in the symptomatic group were similar to population-based estimates for southeast England derived from data held at the Thames Cancer Registry, whilst survival values in the screening group were 11-12 percentage points higher at 4 years after diagnosis and onwards. Ten-year relative survival estimates were 88% in the screening group and 77% in symptomatic cases. In groups of comparable age, the difference in breast cancer-specific survival at 10 years was 19 percentage points. Survival was significantly related to tumour characteristics (size, nodal status and grade), but not to morphological tumour type or deprivation score of the subject. After adjustment for other factors, the difference in survival between the two groups was much attenuated and became statistically non-significant. The higher survival seen in the screening group can be almost entirely accounted for in terms of the detection of early stage and lower grade tumours which screening provides.
 
Article
The proto-oncogene pituitary tumor-transforming gene (PTTG) is described as abundantly overexpressed in a variety of neoplasms and cancer cell lines. We analyzed PTTG mRNA expression in 72 tumor samples derived from primary tumors of patients suffering from breast cancer and in unaffected breast epithelium, checking for correlations between expression levels and standard clinico-pathological parameters over a 5-year observation period. We found a direct correlation between PTTG mRNA overexpression and lymph node infiltration. Furthermore, overexpression of this gene in tumors correlated with a higher degree of tumor recurrence within the subsequent observation period. Taken together, these results demonstrate that determination of PTTG expression in primary tumors of the breast is a powerful tool for the assessment of potential tumor aggressiveness.
 
Patient survival (breast cancer deaths as end-point) according to vascular proliferation index (VPI) (KaplaneMeier method, log rank test for difference).
Microvessel proliferation (MVP) by nestin staining of immature endothelium (red) co-expressed with Ki-67 positive nucleus (blue). Ki-67 negative nucleus (no staining) and Ki-67 positive nucleus (blue) in nestin positive endothelial cells (red) are indicated by arrows. Ki-67 positive tumour cell nucleus (blue) and Ki-67 negative tumour cell nucleus (no staining) are indicated by arrowheads (Â400).
Nestin negative vessel (no staining) and nestin positive vessel (red) are indicated by arrows. Ki-67 positive tumour cell nucleus (blue) and Ki-67 negative tumour cell nucleus (no staining) are indicated by arrowheads (Â630).
Vascular proliferation index (VPI) and associations with clinico-pathological and molecular characteristics in breast cancer.
Article
Background: To quantify tumour angiogenesis, microvessel density (MVD) has been widely used. We here present a novel angiogenesis marker, microvessel proliferation (MVP), based on dual immunohistochemical staining of nestin and Ki-67. Immature endothelial cells express nestin, and when co-expressed with the proliferation marker Ki-67, the number of proliferating immature blood vessels can be measured. Materials and methods: Microvessel proliferation was evaluated in 178 breast cancer samples and estimated by vascular proliferation index (VPI), the ratio between the number of vessels containing proliferating endothelial cells and the total number of immature vessels. Results: High VPI was strongly associated with several markers of aggressive breast cancer, such as negative oestrogen receptor (ER) status (p = 0.003), high tumour cell proliferation by Ki-67 (p = 0.004), high p53 expression (p = 0.001), and five profiles for the basal-like phenotype (odds ratios (OR); range 3.4-6.3). Also, high VPI was significantly associated with interval detected breast cancer compared with screening detected lesions (p < 0.0005), and adverse outcome in univariate and multivariate survival analysis (p = 0.034 and p = 0.022, respectively). Conclusion: Microvessel proliferation is a novel marker of ongoing angiogenesis and was associated with aggressive tumour features, basal-like phenotypes, interval presentation, and prognosis in this series of breast cancer.
 
Radial scar without associated atypical epithelial proliferation: 14-G NCB showing a central area of fibroelastosis containing entrapped benign tubules; central sclerotic zone is surrounded by radiating ducts and lobules that show varying degrees of adenosis, usual ductal hyperplasia and cysts.
Ultrasound longitudinal scanning of RS, with morphological features similar to breast carcinoma: hypoechoic mass, with irregular margins.
Article
The purpose of this study was to evaluate the reliability of image-guided 14-gauge needle core biopsy in the diagnosis of radial scar without associated atypical epithelial proliferation, by comparison with definitive histological diagnosis on surgical excision. The records of 8792 consecutive image-guided 14-gauge needle core biopsy of the breast performed from January 1996 to December 2009 were reviewed. Forty-nine cases of radial scar without associated atypical epithelial proliferation were identified and compared with definitive histological diagnosis on surgical excision. The definitive histological diagnosis on surgical excision confirmed the results of image-guided 14-gauge needle core biopsy in 36 of 49 cases (73.5%), in 9 cases (18.3%) radial scar was associated with atypical epithelial proliferation, while 4 cases out of 49 cases were upgraded to carcinoma (3 cases of ductal carcinoma in situ and one case of invasive lobular carcinoma), with an underestimation rate of 8.2%. A diagnosis of radial scar without associated atypical epithelial proliferation on image-guided 14-gauge needle core biopsy does not exclude a malignancy on surgical excision; consequently during the multidisciplinary discussion further assessment by surgical excision or vacuum-assisted excision, as recently reported, needs to be considered to obtain a definitive histological diagnosis.
 
Re-excision rate and "extra" tissue volume for different clear margin width definitions.
Article
The goal in breast conserving surgery (BCS) of ductal carcinoma in situ (DCIS) is removal of the tumor with a clear surgical margin. However, re-excision rates are regrettably high. To date, there are no adequate procedures for intraoperative margin assessment of DCIS. A multicenter, single arm study was conducted to evaluate the benefit of a novel device (MarginProbe(®)) in intraoperative margin assessment during BCS of DCIS, the associated reduction of re-excisions and the cosmetic outcome of the treated patients. We present results of 42 patients enrolled in 3 German institutions. The device was used as an adjunctive tool to standard of care. The device use was associated with a reduction in re-excision rates by 56%, from 39% to 17% (p = 0.018).
 
Article
We have been studying the molecular and cellular basis of chronic low-dose, frequently administered, metronomic chemotherapy regimens for the treatment of cancer in a variety of preclinical models, including human breast cancer xenografts. The advantages of metronomic-maintenance-type chemotherapy regimens include significantly reduced host toxicity, potentially reduced costs, increased convenience for patients when oral chemotherapy drugs are used, and the possibility of adopting chronic combination therapies involving conventional chemotherapy drugs and cytostatic molecularly targeted therapies. However, a disadvantage is the empiricism associated with determining the optimal biologic dose (OBD). Recently, we have developed a surrogate biomarker approach involving measurement of circulating endothelial progenitor cells (CEPs) in peripheral blood to help determine the OBD of anti-angiogenic drugs or treatments, including metronomic chemotherapy. Using this approach we determined the OBD for different metronomic chemotherapy regimens and then tested the effect of such drugs for the treatment of established, advanced (high volume) and widespread human breast cancer metastases in immunodeficient mice. This treatment strategy, which was maintained for over 6 months, with no breaks, resulted in marked prolongation of survival and was devoid of overt toxicity. These results suggest the possibility of using metronomic chemotherapy regimens as an adjuvant therapy for early-stage disease, including breast cancer, as was demonstrated recently using long-term daily low-dose UFT for the treatment of early-stage resected non-small cell lung cancer or UFT in combination for early stage breast cancer combined with tamoxifen.
 
Article
The tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised ‘kits’, there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2.
 
Summary of histologic findings at core biopsy and surgical excision.
Article
The assessment of papillary lesions continues to be a challenging area in breast radiology and pathology. The management of intraductal papillomas without atypia of the breast remains controversial. The purpose of the present study was to determine diagnostic accuracy of radiographical diagnosis, core biopsy, and surgical excision in papillary breast lesions. By using files from 1995 to 2010, 151 cases of intraductal papilloma with or without atypia were identified. Patients were stratified as follows: core biopsy followed by surgical excision (n = 61), core biopsy alone (n = 19), and surgical excision alone (n = 71). The upstage rate of intraductal papillomas without atypia on core biopsy to atypia or malignancy on excision was 8.9%. Excision specimens revealed intraductal papillomas without atypia in 68 out of 71 cases, and atypical papillomas in 3 cases. Our findings suggest that radiographic and histopathological diagnosis of intraductal papillomas show high accuracy and good concordance. In cases where the radiographic diagnosis reveals suspicious lesions core biopsy represents the first choice.
 
Article
This previously unreported Renaissance painting depicts a young woman with locally advanced breast cancer reaching out towards a healing potion in the church of Santa Maria della Grazia in Milan, that houses Leonardo da Vinci's Last supper. Today's potion may well contain neoadjuvant systemic therapy including trastuzumab that may allow breast conserving surgery and targeted intraoperative radiotherapy.
 
Article
The use of Breast Conserving Surgery (BCS) followed by radiotherapy (BSC-RT) in pT1 (2cm) and pT2-tumours (2-5cm) was investigated in the Netherlands from 1990 to 2001. From the Netherlands Cancer Registry, patients were selected with invasive tumours <5.0cm. Trends were determined and explanatory factors were determined by multivariate logistic regression. Over the period 52,937 pT1-tumours and 36,285 pT2-tumours were diagnosed. The percentage BCS and BCS-RT in patients 80 years or older remained lowest. Multivariate logistic regression revealed that older age (70+), tumour size >2cm, positive clinical nodes and medium hospital size decreased the chance of BCS. For BCS-RT the same factors and negative pathological nodes decreased the chance of BCS-RT. Between regions large differences were seen. Cancer registry data are useful to monitor the guideline implementation strategies. Multidisciplinary treatment planning, surgeon and patient education could increase the use of BCS combined with RT in all age groups.
 
Article
There are controversial data on the meaning of viral induction of breast cancer. The aim of this study was to investigate the presence of human papillomavirus (HPV) DNA in patients with breast carcinoma and the correlation of viral infection with disease outcome. Paraffin-embedded sections from 81 patients with breast cancer were analyzed for HPV DNA by polymerase chain reaction (PCR) using the SPF1/2 primers covering about 40 different low-, intermediate- and high-risk types. We found all samples were negative for HPV DNA. Our analysis could not support a role of HPV in breast carcinoma. Controversial published data indicate a need for further, larger epidemiologic studies.
 
Article
The aim of this study was to evaluate if re-biopsy with 10-gauge vacuum-assisted biopsy (VAB) could get definitive diagnosis for breast lesions with ultrasound (US) imaging-histologic discordance at 16-gauge core needle biopsy (CNB). From January 2007 to June 2008, a consecutive biopsy was performed on 1069 lesions with US-guided 16-gauge CNB. A total of 28 lesions were considered to be US imaging-histologic discordant and all of them underwent subsequent 10-gauge VAB. All malignant lesions located at VAB were treated with subsequent surgery and all benign lesions at VAB were followed up for at least 1 year. Six of the 28 lesions (21.4%) had pathologic upgrade after VAB. In them, one case upgraded from adenosis to ductal carcinoma in situ (DCIS); one case upgraded from adenosis to infiltrating ductal carcinoma (IDC); one case upgraded from atypical ductal hyperplasia to IDC; two cases upgraded from intraductal papilloma to DCIS; and one case upgraded from sclerosing adenosis to invasive lobular carcinoma (ILC). The subsequent surgery further demonstrated the diagnosis of VAB for all the lesions with histologic upgrade. Re-biopsy could improve diagnostic accuracy in patients with breast lesions showing imaging-histologic discordance during CNB, and 10-gauge VAB was a valuable method to deal with re-biopsy.
 
Molecular subtypes a) according to immunoexpression of ER/PR, HER2 and Ki67 and b) chromosome 17 gene alterations of the study group.
Article
Male breast cancer (MBC) is a rare disease. To date, therapy is mainly based on studies and clinical experiences with breast cancer in women. Only little is known about molecular typing of MBC, particularly with regard to potential biological predictors for adjuvant therapy. In female breast cancer tumors with chromosome 17 centromere (CEP17) duplication, HER2 and/or Topoisomerase II alpha (Topo II-α) gene alterations have been suggested to be associated with poor prognosis and increased sensitivity to anthracycline-containing regimens. In a well characterized cohort of 96 primary invasive MBC, we studied CEP17, HER2 and Topo II-α alterations by fluorescence in-situ hybridization (FISH), and expression of hormone receptors (HR), HER2 and Ki67 by immunohistochemistry to define molecular subtypes. Tumor characteristics and follow-up data were available and correlated with molecular findings. HER2 amplification and Topo II-α amplification/deletion were exceptionally rare in MBC (6.3% and 3.1%, respectively). CEP17 polysomy were found in 9.4% of tumors. HER2, Topo II-α and CEP17 gene alterations were not correlated to patients outcome. 96.9% of our cases were HR positive. Triple negative tumors were found in only 3.1% of the cases. In nodal negative tumors luminal A subtypes were significantly associated with better overall survival. Our results provide evidence for a predominant male breast cancer phenotype, characterized by HR expression and a lack of HER2/Topo II-α alterations and CEP17 duplicates. Therefore, the impact of anthracycline sensitivity linked to HER2/Topo II-α alterations as found in female breast cancer has low clinical significance for this specific male breast cancer phenotype.
 
Agents administered concomitantly with trastuzumab
Article
Though preclinical evidence supports the protracted use of trastuzumab to reach sustained anti-tumor activity, the activity of trastuzumab beyond disease progression remains controversial in HER-2 over-expressing (HER-2+) metastatic breast cancer (MBC) patients. We retrospectively evaluated a total of 59 patients with HER-2 + MBC treated at our institution with trastuzumab-based therapies. Our results were added to those obtained in similar observational studies and summary estimates for overall response (OR) and clinical benefit (CB) to first and second trastuzumab-based lines were calculated. In our series of patients we observed an OR of 59.3% and 27% for first and second trastuzumab-based lines, respectively, with a corresponding CB of 83% and 62.2%, respectively. Time to first and second progression were 9.5 months and 6.7 months, respectively. The combined analysis showed an OR of 50% for first trastuzumab-based regimen and 21.2% for second trastuzumab-based line. The corresponding values for CB were 77.6% and 42.6%, respectively. A second trastuzumab-containing regimen beyond progression yields a considerable rate of OR and CB in HER-2 + MBC patients. Randomized trials are warranted.
 
Changed cases between core and resection in cases with and without Neoad- juvant chemotherapy
Rates of PR changes in cases with neoadjuvant chemotherapy (173 patients) and controls without neoadjuvant chemotherapy (117 patients)
ER and PR changed (neg/pos and pos/neg) cases and response for neoad- juvant chemotherapy
Article
Neoadjuvant chemotherapy (NAC) is now a relatively standard treatment for breast carcinoma. However, some tumors are known to develop resistance to chemotherapies. We investigated whether the status of estrogen receptor (ER), progesterone receptor (PR) and Her-2 expressions in breast cancer cases prior to NAC could be changed after NAC. We used immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. No differences were found in ER or Her-2 status, but a significant difference was found in PR status. Changes in Her-2 status were suspected in four specimens after NAC (3+ to 1+ for 3 patients, and 1+ to 3+ for one patient) according to the IHC results. However, in all four of these cases, FISH of the resections showed no change. When IHC indicates a change in Her-2 expression after NAC, FISH is recommended.
 
Article
The Seventh Milan Breast Cancer Conference (MBCC), Innovation in Care and Research, held in Milan, Italy from 15 to 17 June 2005 was attended by more of 1100 physicians from 62 countries. This meeting report summarizes the highlights of the 12 sessions.
 
Article
Based upon the results of the NCIC CTG MA.17 trial, letrozole has become the only approved aromatase inhibitor (AI) in the extended adjuvant treatment setting following 5 years of tamoxifen therapy. In this trial, the AI letrozole decreased the overall risk of breast cancer recurrence by 42% compared with placebo in postmenopausal women completing 5 years of tamoxifen. The benefit of letrozole exceeded the expected difference after median follow-up of more than 2 years and led to the unblinding of the trial. The 30-month updated analyses found a 4.8%, 4-year disease-free survival improvement overall, an improvement in distant disease-free recurrence in both node-negative and node-positive patients, and a survival benefit for node-positive patients. Generally well tolerated, letrozole caused some adverse events including arthralgias and osteoporosis. However, results from the Zometa-Femara adjuvant synergy trial (Z-FAST) suggest that zoledronic acid, when used concomitantly with letrozole, is able to manage bone loss in postmenopausal women with early breast cancer.
 
Article
From 1981 to 1995, 1755 patients aged 70 years or over who had nonmetastatic unilateral breast carcinoma received curative local or regional treatment in our institute. Median follow-up was 8 years. The median age of these patients was 75 years (range: 70-94), and 86% were under 81 years of age. Tumors were classed as T3-4 in 24% of them; 18% had N1b/N2 tumors, and in 12% grade 3 disease was present. Only 19% were both ER and PR negative. The S phase fraction was <5% in 79% of patients. In 1046 patients (60%) modified radical mastectomy was performed, while 20% underwent lumpectomy and in 20% radiotherapy was the only treatment administered. Adjuvant endocrine therapy was given in 463 (26%) cases, and only 3% of patients received chemotherapy. The median overall survival time was 121 months. The overall cancer-related death rate was 49%. The 10-year disease-free survival (DFS) rate was 64%, and the 10-year local relapse rate was 14%. Prognostic factors determined on univariate analysis were tumor size, clinical nodal status (ER and PR), and grade. No significant difference in outcome was observed between mastectomy and conservative treatment. Parameters for which correlations with DFS were found on multivariate analysis were clinical nodal status (P < 0.0001), tumor size (P < 0.0001), ER (P < 0.0001), and PR (P = 0.04). Breast cancer in elderly women is frequently hormone-dependent (81%) with a low proliferation index. Prognostic factors are the same as in younger postmenopausal patients. More than 50% of these patients died from a cause other than their breast cancer.
 
Size of BeckerÔ expanders used.
Time from implantation to removal for infection.
a. An example of capsular contracture. b. Following revisional surgery and symmetrisation.
Long-term outcome following reconstruction with BeckerÔ expanders.
Article
Background: Single-stage reconstruction using permanent expander implants is an established technique following mastectomy. Short and long-term outcome data following breast reconstruction using Becker tissue expanders is limited. Method: A retrospective case note review of patients undergoing expander-based procedures between 1989 and 2007 was undertaken. Data recorded included postoperative symptoms and complications, the use of radiotherapy, revisional surgery, and device failure. Results: Three hundred and thirteen expanders were used in 276 patients with a mean age of 48.3 (17-78) years, over the 18 year study period. The mean follow up period was 64.6 (1-199) months. 256 Becker expanders were used during 175 latissimus dorsi (LD) and 52 subpectoral (SP) reconstructions, 13 contralateral augmentations and 16 implant replacements. The postoperative infection rate was 5.8%, leading to an expander loss rate of 3.8%. The use of prophylactic antibiotics was associated with an increased postoperative infection rate (p = 0.046). Six haematomas (2.5%) and 12 cases of skin envelope necrosis (5.0%) required unscheduled intervention. Symptoms of pain, distortion and hardness were experienced by 21.3% of patients, and radiotherapy was associated with a significantly higher risk of adverse symptoms (p < 0.0001). No patient developed symptomatic implant rupture or silicone granuloma but 17.9% of reconstructions underwent revisional surgery, the rate being highest following SP reconstruction (p = 0.029). Nine patients developed injection port complications (3.8%), and the overall device failure rate was 1.3%. The original expander has been retained by 74.2% of women. Conclusion: The Becker permanent expander is a reliable implant associated with a low complication rate and a high retention rate when used during breast reconstruction.
 
Article
Although breast density is considered a strong predictor of breast cancer risk, its quantitative assessment is difficult. The aim of this study is to demonstrate that breast density assessment with a fully automated software is feasible and correlates with the semi-automated evaluation and the quantitative BI-RADS standards. A data set of 160 mammograms was evaluated by three blinded radiologists. Intra-observer (reader 1: k=0.71; reader 2: k=0.76; reader 3: k=0.62) and inter-observer (reader 1 vs reader 2: k=0.72; reader 2 vs reader 3: k=0.80; reader 3 vs reader 1: k=0.72) variability for the semi-automated software were good on a four-grade scale (D1/D2/D3/D4) and correlated with BI-RADS evaluation made by other two blinded radiologists (r=0.65, p<0.01). Inter-observer (reader 1 vs reader 2: k=0.85; reader 2 vs reader 3: k=0.91; reader 3 vs reader 1: k=0.85) variability for the semi-automated software was very good on a two-grade scale (D1-D2/D3-D4). The use of the fully automated software eliminated intra- and inter-observer differences, correlated with BI-RADS categories (r=0.62, p<0.01) and can replace the semi-automated one (Bland-Altman statistics). Our study demonstrates that automated estimation of breast density is feasible and eliminates subjectivity. Furthermore both the semi-automated and the fully automated density estimation are more accurate than BI-RADS quantitative evaluation and could also be used in the daily clinical practice.
 
Prognostic effect of SUVmax on disease-free survival in entire population and various risk groups. Risk group HR >4.7 vs. 4.7 (95% CI)
Article
Background: We retrospectively investigated (18)F-FDG uptake by the primary breast tumor as a predictor for relapse and survival. Patients and methods: We studied 203 patients with cT1-T3N0 breast cancer. Standardized uptake value (SUVmax), was measured on the primary tumor. After a median follow-up of 68 months (range 22-80), the relation between SUVmax and tumor factors, disease free-survival (DFS) and overall survival (OS) was investigated. Results: In the PET-positive patients, the median FDG uptake by the tumor was 4.7. FDG uptake was significantly related to tumor size, number of involved axillary nodes, grade, negative ER, high Ki-67 and HER2 overexpression. No distant metastases or deaths occurred in the PET-negative group. Five-year DFS was 97% and 83%, respectively in the PET-negative and PET-positive groups (P = 0.096). At univariate analysis, DFS was significantly lower in patients with SUVmax >4.7 compared to the patients with negative PET (P = 0.042), but not to the patients with SUVmax ≤4.7 (P = 0.106). At multivariable analysis, among PET-positive patients, SUVmax was not an independent prognostic factor for DFS (HR(>4.7 vs ≤4.7): 1.02 (95% CI 0.45-2.31)). Five-year OS was 100% and 93%, respectively, in the PET-negative and PET-positive groups (P = 0.126). Conclusion: FDG uptake by the primary lesion was significantly associated with several prognostic variables, but it was not an independent prognostic factor.
 
Article
Surgical treatment of non-palpable solitary invasive carcinoma consists of localization, tumorectomy and sentinel lymph node biopsy which can successfully be performed with the use of isotopes (SNOLL). The aim of our study was to find out the success rate of SNOLL and the factors that correlated with complete excision of invasive carcinoma. Solitary non-palpable carcinoma was preoperatively diagnosed in 181 cases. After peritumoral injection of nanocolloid labeled with 99mTc under mammographic (N=79) or ultrasound (N=102) guidance, tumorectomy and sentinel node biopsy were performed. Clear surgical margins were obtained in 82% of cases. Surgical margins were likely to be clear (p<0.05) if: (1) the patients were older than 50 years, (2) the weight of surgical specimens >50 g, (3) the tumor radiologic diameter was <or=20 mm, (4) invasive carcinoma was ductal rather than other types of invasive carcinomas. Only one surgical procedure was sufficient for surgical treatment of 75% of cases with non-palpable solitary invasive carcinoma.
 
Article
In the current study the long-term effects of a pilot service screening programme in the Swedish county of Gävleborg were studied. Women aged 40-64 years in 13 sub-areas were followed from start of screening between 1974 and 1979. Two control groups were used for comparison; the neighbouring counties and all of Sweden. A reference period prior to the study period was used to facilitate an adjustment for possible differences in baseline breast cancer mortality. Only deaths from breast cancer diagnosed after the first invitation to screening were analysed. Two outcome measures were used for breast cancer mortality; the underlying cause of death and excess mortality. Using the neighbouring counties as a control group, the relative risk, after 22 years of follow-up, of 10 years of screening was estimated at 0.84 (95% CI 0.71-1.00) using excess mortality. Due to lead time bias the relative risk was overestimated by 4%. Hence, a significant 20% reduction of breast cancer excess mortality was found.
 
Top-cited authors
Carolyn C Compton
  • Arizona State University
Paolo Veronesi
  • IEO - Istituto Europeo di Oncologia
Steven D Heys
  • University of Aberdeen
Mattia Intra
  • IEO - Istituto Europeo di Oncologia
Lesley Fallowfield
  • University of Sussex