Search

Background: Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase inhibitors (MAP.3 and International Breast Cancer Intervention Study II [IBIS-II]). Here, we report blinded long-term follow-up results for the IBIS-II trial, which compared anastrozole with placebo, with the objective of determining the efficacy of anastrozole for preventing breast cancer (both invasive and ductal carcinoma in situ) in the post-treatment period., Methods: IBIS-II is an international, randomised, double-blind, placebo-controlled trial. Postmenopausal women at increased risk of developing breast cancer were recruited and were randomly assigned (1:1) to either anastrozole (1 mg per day, oral) or matching placebo daily for 5 years. After treatment completion, women were followed on a yearly basis to collect data on breast cancer incidence, death, other cancers, and major adverse events (cardiovascular events and fractures). The primary outcome was all breast cancer., Findings: 3864 women were recruited between Feb 2, 2003, and Jan 31, 2012. 1920 women were randomly assigned to 5 years anastrozole and 1944 to placebo. After a median follow-up of 131 months (IQR 105-156), a 49% reduction in breast cancer was observed for anastrozole (85 vs 165 cases, hazard ratio [HR] 0·51, 95% CI 0·39-0·66, p<0·0001). The reduction was larger in the first 5 years (35 vs 89, 0·39, 0·27-0·58, p<0·0001), but still significant after 5 years (50 vs 76 new cases, 0·64, 0·45-0·91, p=0·014), and not significantly different from the first 5 years (p=0·087). Invasive oestrogen receptor-positive breast cancer was reduced by 54% (HR 0·46, 95% CI 0·33-0·65, p<0·0001), with a continued significant effect in the period after treatment. A 59% reduction in ductal carcinoma in situ was observed (0·41, 0·22-0·79, p=0·0081), especially in participants known to be oestrogen receptor-positive (0·22, 0·78-0·65, p<0·0001). No significant difference in deaths was observed overall (69 vs 70, HR 0·96, 95% CI 0·69-1·34, p=0·82) or for breast cancer (two anastrozole vs three placebo). A significant decrease in non-breast cancers was observed for anastrozole (147 vs 200, odds ratio 0·72, 95% CI 0·57-0·91, p=0·0042), owing primarily to non-melanoma skin cancer. No excess of fractures or cardiovascular disease was observed., Interpretation: This analysis has identified a significant continuing reduction in breast cancer with anastrozole in the post-treatment follow-up period, with no evidence of new late side-effects. Further follow-up is needed to assess the effect on breast cancer mortality., Funding: Cancer Research UK, the National Health and Medical Research Council Australia, Breast Cancer Research Foundation, Sanofi Aventis, and AstraZeneca., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: An institutional review board-approved, multicenter clinical trial was designed to determine the efficacy and outcome of percutaneous laser ablation (PLA) in the treatment of invasive ductal breast carcinoma (IDC). Post-ablation magnetic resonance imaging (MRI) was compared with surgical pathology in evaluation of residual post-ablation IDC and ductal carcinoma in situ., Methods: Patients with a single focus of IDC 20 mm or smaller by pre-ablation MRI were treated with PLA. The patients underwent a 28-day post-ablation MRI, followed by surgical resection. Cell viability criteria were applied to pre- and post-ablation pathology specimens, which evaluated hematoxylin-eosin (H&E), cytokeratin (CK) 8/18, estrogen receptor, and Ki67 staining patterns., Results: In this study, 61 patients were reported as the intention-to-treat cohort for determination of PLA efficacy. Of these 61 patients, 51 (84%) had complete tumor ablation confirmed by pathology analysis. One subject's MRI imaging was not performed per protocol, which left 60 subjects evaluable for MRI pathology correlation. Five patients (8.3%) had residual IDC shown by both MRI and pathology. Post-ablation discordance was noted between MRI and pathology, with four patients (6.7%) false-positive and four patients (6.7%) false-negative. The negative predictive value (NPV) of MRI for all the patients was 92.2% (95% confidence interval [CI], 71.9-91.9%). Of the 47 patients (97.9%) with tumors 15 mm or smaller, 46 were completely ablated, with an MRI NPV of 97.7% (95% CI, 86.2-99.9%)., Conclusions: Percutaneous laser ablation is a potential alternative to surgery for treatment of early-stage IDC. Strong correlations exist between post-ablation MRI and pathologic alterations in CK8/18, ER, and Ki67 staining.

We report the outcomes of the European prospective study on prepectoral breast reconstruction using preshaped acellular dermal matrix for complete breast implant coverage. Seventy-nine patients were enrolled between April 2014 and August 2015 all over Europe using a single protocol for patient selection and surgical procedure, according to the Association of Breast Surgery and British Association of Plastic Reconstructive and Aesthetic Surgeons joint guidelines for the use of acellular dermal matrix in breast surgery. The preshaped matrix completely wraps the breast implant, which is placed above the pectoralis major, without detaching the muscle. A total of 100 prepectoral breast reconstructions with complete implant coverage were performed. This series, with mean follow-up of 17.9 months, had two cases of implant loss (2.0%) including one necrosis of the nipple and one wound breakdown (1.0% respectively). No implant rotations were observed. Good cosmetic outcomes were obtained with natural movement of the breasts and softness to the touch; none of the patients reported experiencing pain or reduction in the movements of the pectoralis major muscle postoperatively. The use of preshaped acellular dermal matrix for a complete breast implant coverage in selected patients is safe and gives satisfactory results, both from the aesthetic view point and the low postoperative complication rates. Further studies reporting long-term outcomes are planned., (© 2017 Crown copyright. The Breast Journal © 2017 Wiley Periodicals, Inc. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)

Improvements in breast surgery techniques such as skin and nipple preserving mastectomy and innovative prosthetics (implants, acellular dermal matrices and meshes) is renewing interest in subcutaneous (pre-pectoral) implant reconstruction. The aim of this paper is to review the current literature in an attempt to provide a rationale that may support a return to subcutaneous implant placement, so minimising the pain and functional problems resulting from submuscular breast reconstruction., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: Women considering reconstructive breast surgery (RBS) require adequate information to make informed treatment decisions. This study explored patients' and health professionals' (HPs) perceptions of the adequacy of information provided for decision-making in RBS., Methods: Semi-structured interviews with a purposive sample of patients who had undergone RBS and HPs providing specialist care explored participants' experiences of information provision prior to RBS., Results: Professionals reported providing standardised verbal, written and photographic information about the process and outcomes of surgery. Women, by contrast, reported varying levels of information provision. Some felt fully-informed but others perceived they had received insufficient information about available treatment options or possible outcomes of surgery to make an informed decision., Conclusions: Women need adequate information to make informed decisions about RBS and current practice may not meet women's needs. Minimum agreed standards of information provision, especially about alternative types of reconstruction, are recommended to improve decision-making in RBS., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Four previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation., Methods: In the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35-70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928., Findings: Between April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16.0 years (IQR 14.1-17.6), 601 breast cancers have been reported (251 [7.0%] in 3579 patients in the tamoxifen group vs 350 [9.8%] in 3575 women in the placebo group; hazard ratio [HR] 0.71 [95% CI 0.60-0.83], p<0.0001). The risk of developing breast cancer was similar between years 0-10 (226 [6.3%] in 3575 women in the placebo group vs 163 [4.6%] in 3579 women in the tamoxifen group; hazard ratio [HR] 0.72 [95% CI 0.59-0.88], p=0.001) and after 10 years (124 [3.8%] in 3295 women vs 88 [2.6%] in 3343, respectively; HR 0.69 [0.53-0.91], p=0.009). The greatest reduction in risk was seen in invasive oestrogen receptor-positive breast cancer (HR 0.66 [95% CI 0.54-0.81], p<0.0001) and ductal carcinoma in situ (0.65 [0.43-1.00], p=0.05), but no effect was noted for invasive oestrogen receptor-negative breast cancer (HR 1.05 [95% CI 0.71-1.57], p=0.8)., Interpretation: These results show that tamoxifen offers a very long period of protection after treatment cessation, and thus substantially improves the benefit-to-harm ratio of the drug for breast cancer prevention., Funding: Cancer Research UK (UK) and the National Health and Medical Research Council (Australia)., (Copyright © 2015 Cuzick et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)

Introduction: Acellular dermal matrix (ADM) may improve outcomes in implant-based breast reconstruction, but recent evidence suggests complication rates may be higher when ADM is used. We retrospectively compared early complications and implant loss in implant-based breast reconstruction (BR) with and without ADM to evaluate the safety of the procedure in our centre., Methods: Case-notes of consecutive women undergoing implant-based BR from May 2011 to November 2012 were retrospectively reviewed. Data were extracted using a standardised pro-forma and the rate of early complications, major complications and implant loss compared between procedure groups., Results: Forty-six implant-based reconstructions were performed for malignancy (n = 31, 67.4%) or prophylaxis (n = 15, 32.6%) in 31 women over the 18-month study period. ADM (Tecnoss Protexa(®), Tecnoss S.r.l.) was used in 31 (67.4%) cases. There were no differences in patient age, BMI, co-morbidities, smoking or chemotherapy between groups, but patients receiving ADM were more likely to have received radiotherapy prior to their reconstruction (n = 6, 30% vs. n = 0, 0%, p = 0.043). The overall rate of early complications was 26.1% (n = 12) but there was no significant difference between procedure groups (standard-n = 4, 27.7% vs. ADM-n = 8, 25.8%; p = 0.950). There were 2 (4.3%) major complications none of which were associated with ADM use (standard-n = 2, 13.3% vs. ADM-n = 0, 0.0%; p = 0.038). There were 6 (13.0%) implant losses of which 4 were in the ADM group (standard-n = 2, 13.3% vs. ADM-n = 4, 12.9%; p = 0.968). All of these were associated with pre-reconstruction radiotherapy., Conclusions: ADM-assisted implant-based reconstruction with Tecnoss Protexa(®) is safe and may improve outcomes for women by facilitating a single-stage procedure. Robust prospective evaluation is now needed to definitively evaluate the role of ADM in implant-based BR., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease., Methods: Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319., Findings: 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0-7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32-0·68, p<0·0001). The predicted cumulative incidence of all breast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836)., Interpretation: Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer., Funding: Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca., (Copyright © 2014 Cuzick et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)

Sentinel Lymph Node Biopsy (SLNB) is the standard of care for axillary staging in breast cancer. Multiple Step-section Frozen Section (MSFS) analysis is used in our institution for SLNB. This is performed intra-operatively by freezing sentinel lymph nodes to obtain multiple step-sections which are examined histologically for evidence of metastases. Patients whose sentinel lymph nodes contained macrometastases proceeded to an axillary node clearance during the same operation. 717 patients over a two and a half year period had MSFS analysis. With regards to macrometastases, MSFS analysis had a sensitivity of 93.8%, a specificity of 99.3%, a positive-predictive value of 97.4% and a negative-predictive value of 98.2%. MSFS analysis of sentinel lymph nodes is a safe and accurate procedure. It is a relatively cost-effective alternative to molecular technologies relying on DNA amplification and more accurate than standard frozen section or touch-prep cytology., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Survival from breast cancer in the United Kingdom is lower than in other developed countries. It is unclear to what extent waiting times for curative surgery affect survival., Methods: Using national databases for England (cancer registries, Hospital Episode Statistics and Office of National Statistics), we identified 53 689 women with localised breast cancer, aged ≥ 15 years, diagnosed between 1996 and 2009, who had surgical resection with curative intent within 62 days of diagnosis. We used relative survival and excess risk modelling to determine associations between waiting times and 5-year survival., Results: The median diagnosis to curative surgery waiting time among breast cancer patients was 22 days (interquartile range (IQR): 15-30). Relative survival was similar among women waiting between 25 and 38 days (RS: 93.5%; 95% CI: 92.8-94.2%), <25 days (RS: 93.0%; 95% CI: 92.5-93.4%) and between 39 and 62 days (RS: 92.1%; 95% CI: 90.8-93.4%). There was little evidence of an increase in excess mortality with longer waiting times (excess hazard ratio (EHR): 1.06; 95% CI: 0.88-1.27 comparing waiting times 39-62 with 25-38 days). Excess mortality was associated with age (EHR 65-74 vs 15-44 year olds: 1.23; 95% CI: 1.07-1.41) and deprivation (EHR most vs least deprived: 1.28; 95% CI: 1.09-1.49), but waiting times did not explain these differences., Conclusion: Within 62 days of diagnosis, decreasing waiting times from diagnosis to surgery had little impact on survival from localised breast cancer.

Background: Mammographic breast density is a strong risk factor for breast cancer. Tamoxifen, which reduces the risk of breast cancer in women at high risk, also reduces mammographic breast density. However, it is not known if tamoxifen-induced reductions in breast density can be used to identify women who will benefit the most from prophylactic treatment with this drug., Methods: We conducted a nested case-control study within the first International Breast Cancer Intervention Study, a randomized prevention trial of tamoxifen vs placebo. Mammographic breast density was assessed visually and expressed as a percentage of the total breast area in 5% increments. Case subjects were 123 women diagnosed with breast cancer at or after their first follow-up mammogram, which took place 12-18 months after trial entry, and control subjects were 942 women without breast cancer. Multivariable logistic regression was used to adjust for other risk factors. All statistical tests were two-sided., Results: In the tamoxifen arm, 46% of women had a 10% or greater reduction in breast density at their 12- to 18-month mammogram. Compared with all women in the placebo group, women in the tamoxifen group who experienced a 10% or greater reduction in breast density had 63% reduction in breast cancer risk (odds ratio = 0.37, 95% confidence interval = 0.20 to 0.69, P = .002), whereas those who took tamoxifen but experienced less than a 10% reduction in breast density had no risk reduction (odds ratio = 1.13, 95% confidence interval = 0.72 to 1.77, P = .60). In the placebo arm, there was no statistically significant difference in breast cancer risk between subjects who experienced less than a 10% reduction in mammographic density and subjects who experienced a greater reduction., Conclusion: The 12- to 18-month change in mammographic breast density is an excellent predictor of response to tamoxifen in the preventive setting.

Background: Breast reconstruction (BR) is undertaken to improve cosmetic outcomes, but how this is optimally assessed is uncertain. This review summarises current methods for assessing cosmesis after reconstructive surgery and makes recommendations for future practice., Methods: A comprehensive systematic review identified all studies with 20 or more participants that evaluated the cosmetic outcome of BR. Four evaluation criteria (reporting of study inclusion criteria, type and timing of BR and timing of assessment) were used to assess study quality. Articles reporting at least three of the four criteria were considered robust and further summarised to report methods of cosmetic assessment, assessor details and the scoring systems used., Results: 122 primary papers assessed cosmesis in 11,308 women with median follow-up of 28.8 months (range 18.0-42.9 months). Cosmesis was assessed by either healthcare professionals or patients in 33 (27.1%) and 37 studies (30.3%), respectively, and by both professionals and patients in 52 (42.6%). Professional assessments included 43 (40.2%) clinical, 49 (45.8%) photographic and 13 (12.1%) geometric assessments conducted by between 1 and 26 observers. Surgeons were most frequently involved in assessments (n = 71, 67.6%), but in 38 (36.1%) papers the assessor's profession was not reported. Twenty-seven (25.7%) papers used previously published assessment scale. Patients' views were assessed in 89 studies, using questionnaires (n = 63) or interviews (n = 12); 14 (15.7%) did not report how patients' views were obtained., Conclusions: Current methods for assessing the cosmetic outcome of BR vary widely. A valid patient-centred assessment method is required to fully understand the outcomes of BR and to inform decision-making.

Background: Breast reconstruction after mastectomy for cancer requires accurate evaluation to inform evidence-based participatory decision making, but the standards of outcome reporting after breast reconstruction have not previously been considered., Methods: We used extensive searches to identify articles reporting surgical outcomes of breast reconstruction. We extracted data using published criteria for complication reporting modified to reflect reconstructive practice. Study designs included randomized controlled trials, cohort studies, and case series. The Cochrane Risk of Bias tool was used to critically appraise all study designs. Other criteria used to assess the studies were selection and funding bias, statistical power calculations, and institutional review board approval. Wilcoxon signed rank tests were used to compare the breadth and frequency of study outcomes, and χ² tests were used to compare the number of studies in each group reporting each of the published criteria. All statistical tests were two-sided., Results: Surgical complications following breast reconstruction in 42,146 women were evaluated in 134 studies. These included 11 (8.2%) randomized trials, 74 (55.2%) cohort studies, and 49 (36.6%) case series. Fifty-three percent of studies demonstrated a disparity between methods and results in the numbers of complications reported. Complications were defined by 87 (64.9%) studies and graded by 78 (58.2%). Details such as the duration of follow-up and risk factors for adverse outcomes were omitted from 47 (35.1%) and 58 (43.3%) studies, respectively. Overall, the studies defined fewer than 20% of the complications they reported, and the definitions were largely inconsistent., Conclusions: The results of this systematic review suggest that outcome reporting in breast reconstruction is inconsistent and lacks methodological rigor. The development of a standardized core outcome set is recommended to improve outcome reporting in breast reconstruction.

Introduction: The UK National Institute for Health and Clinical Excellence (NICE) recommends that breast cancer follow-up should be limited to 2-3 years stating this will 'release resources' making it 'possible for all women with breast symptoms to be seen within 2 weeks'. In 2000, breast cancer follow-up services in North Bristol were redesigned to reflect evidence-based best practice. The aim of this paper is to assess the impact of this policy on numbers of follow-ups, clinic capacity and waiting times., Patients and Methods: Data regarding the numbers of new and follow-up patients seen in breast clinic between January 2000 and December 2005 were collected from the hospital Patient Administration System. New patients were categorised as either 'routine' or 'urgent' according to '2-week wait' rule guidelines. Median waiting times were calculated for each group and nominal appointment times assigned in an attempt to assess the effect of any changes on clinic capacity., Results: The number of follow-ups decreased by 33% as a result of the new policy. Numbers of referrals over the same period, however, increased by 14%. Routine referrals declined, but there was a 27% increase in '2-week wait' patients. Waiting times for routine appointments initially decreased in response to reduced follow-up, but then rose as the number of '2-week wait' referrals increased., Conclusions: Reducing long-term follow-up is a simple and effective method of increasing clinic capacity but its effects are inadequate and transient in the face of increasing service demand. Additional innovative and creative strategies will be required if all breast patients are to be seen within 2 weeks.

The National Breast Screening Programme had dramatically impacted surgical practice. Up to 50% of all newly diagnosed cancers are now impalpable creating increased demand for image-guided localisation. Wire-guided localisation (WGL) is the current gold standard, but USS-guided localisation by radiologists is a well-documented and effective technique. Increasing numbers of surgeons are proficient in using ultrasound and may be as accurate as radiologists in localising lesions intra-operatively. Of 68 patients with screen-detected impalpable lesions referred to one surgeon in our unit between January 2005 and February 2006, 32 had mass lesions, which were well seen on ultrasound and underwent intra-operative USS-guided localisation performed by a surgeon. All lesions were correctly identified and 87.5% (n=28) were fully excised. Those lesions not fully excised were lobular cancers. Intra-operative sonographic localisation performed by surgeons is an accurate and effective technique. It may produce less patient anxiety and discomfort than WGL and allow more effective and efficient use of resources and theatre time.

Background: Initial results from the first International Breast Cancer Intervention Study (IBIS-I) found that tamoxifen reduced the risk of invasive estrogen receptor (ER)-positive tumors by 31% in women at increased risk for breast cancer, but most of the follow-up at this time was during the active treatment phase. We report an updated analysis of IBIS-I that focuses on the period after active treatment was completed, a time for which little evidence from other trials is available., Methods: A total of 7145 women who were aged 35-70 years and at increased risk of breast cancer were randomly assigned to receive either tamoxifen (20 mg/day) or placebo for 5 years. The primary outcome measure was the incidence of breast cancer (including ductal carcinoma in situ), but side effects were also investigated. Relative risks were computed as the ratio of incidence rates. All statistical tests were two-sided., Results: After a median follow-up of 96 months after randomization, 142 breast cancers were diagnosed in the 3579 women in the tamoxifen group and 195 in the 3575 women in the placebo group (4.97 versus 6.82 per 1000 woman-years, respectively; risk ratio [RR] = 0.73, 95% confidence interval [CI] = 0.58 to 0.91, P = .004). The prophylactic effect of tamoxifen was fairly constant for the entire follow-up period, and no diminution of benefit was observed for up to 10 years after randomization. However, side effects in the tamoxifen group were much lower after completion of the active treatment period than during active treatment. For example, deep-vein thrombosis and pulmonary embolism were statistically significantly higher in the tamoxifen arm than in the placebo arm during active treatment (52 versus 23 cases, RR = 2.26, 95% CI = 1.36 to 3.87) but not after tamoxifen was stopped (16 versus 14 cases, RR = 1.14, 95% CI = 0.52 to 2.53). The two arms did not differ in the risk of ER-negative invasive tumors (35 in each arm, RR = 1.00, 95% CI = 0.61 to 1.65) across the entire follow-up period, but the risk of ER-positive invasive breast cancer was 34% lower in the tamoxifen arm (87 versus 132 cases, RR = 0.66, 95% CI = 0.50 to 0.87)., Conclusions: The risk-reducing effect of tamoxifen appears to persist for at least 10 years, but most side effects of tamoxifen do not continue after the 5-year treatment period.

Aim: To evaluate the role of ultrasound guided mammotome biopsy of the ducts beneath the nipple areola complex (NAC), as a new technique in detecting the occult involvement of the NAC in breast cancer patients prior to nipple preserving subcutaneous mastectomy., Method: A prospective study where 33 women requesting nipple preserving mastectomy for invasive or in situ disease were offered the procedure to determine if leaving the nipple was safe. A 5 mm skin incision was made after infiltration with local anaesthetic and the 11G mammotome needle was positioned beneath the nipple under ultrasound guidance which was turned through 360 degrees as the biopsies were taken. The procedures were performed by trained non-radiologists., Results: Thirty-three women had 36 procedures. Seven out of the 36 had a positive mammotome biopsy. Twenty-three patients had 26 NAC preserving mastectomies with immediate reconstruction. Three had bilateral procedures. Ten patients had NAC sacrificed. The histopathology of the mastectomy specimen correlated 100% with the mammotome biopsy., Conclusion: Preoperative ultrasound guided mammotome biopsy of the ducts beneath the NAC is a safe, reliable and accurate technique and is evolving as an oncologically safe procedure. The large mammotome needle can be visualized easily under high resolution, near field high frequency scanners and this increases the accuracy of the biopsy. It can replace the traditional frozen section and be used as an alternate. It can be performed safely by an appropriately trained non-radiologist (surgeon/breast clinician).

Aim: Previous in vitro studies have shown that tamoxifen down-regulates prolactin receptors in breast cancer cells. The aim of this study was to determine whether similar changes might provide the basis for a predictive test in patients., Methods: Biopsy specimens were obtained from 28 post-menopausal women immediately before initiation of treatment with tamoxifen (20 mg daily) and after treatment for 7 days. Prolactin receptor mRNA, determined by reverse-transcription polymerase chain reaction, was then expressed relative to 18S ribosomal RNA., Results: There was good evidence for a decline in receptor expression in response to treatment with tamoxifen in the whole group (p = 0.036) but with a particularly marked decrease (>60%) in a sub-group of 11 patients. No clear correlation with tumour type or grade, or with several other markers (progesterone receptor, c-erb B-2, pS2, or Bcl-2) was apparent., Conclusion: Tamoxifen reduces expression of mRNA encoding the prolactin receptor in a sub-group of breast tumours and might provide the basis for a predictive test for tamoxifen therapy.

Background: Three clinical trials on the use of tamoxifen to prevent breast cancer have reported mixed results. The overall evidence supports a reduction in the risk of breast cancer, but whether this benefit outweighs the risks and side-effects associated with tamoxifen is unclear., Methods: We undertook a double-blind placebo-controlled randomised trial of tamoxifen, 20 mg/day for 5 years, in 7152 women aged 35-70 years, who were at increased risk of breast cancer. The primary outcome measure was the frequency of breast cancer (including ductal carcinoma in situ). Analyses were by intention to treat after exclusion of 13 women found to have breast cancer at baseline mammography., Findings: After median follow-up of 50 months (IQR 32-67), 69 breast cancers had been diagnosed in 3578 women in the tamoxifen group and 101 in 3566 in the placebo group (risk reduction 32% [95% CI 8-50]; p=0.013). Age, degree of risk, and use of hormone-replacement therapy did not affect the reduction. Endometrial cancer was non-significantly increased (11 vs 5; p=0.2) and thromboembolic events were significantly increased with tamoxifen (43 vs 17; odds ratio 2.5 [1.5-4.4], p=0.001), particularly after surgery. There was a significant excess of deaths from all causes in the tamoxifen group (25 vs 11, p=0.028)., Interpretation: Prophylactic tamoxifen reduces the risk of breast cancer by about a third. Temporary cessation of tamoxifen should be considered and the use of appropriate antithrombotic measures is recommended during and after major surgery or periods of immobilisation. Prophylactic use of tamoxifen is contraindicated in women at high risk of thromboembolic disease. The combined evidence indicates that mortality from non-breast-cancer causes is not increased by tamoxifen. The overall risk to benefit ratio for the use of tamoxifen in prevention is still unclear, and continued follow-up of the current trials is essential.

Aim and Method: The aim of this questionnaire study was to identify knowledge of breast and colorectal cancer symptoms among 100 patients attending one-stop breast clinics and rectal bleeding clinics and to determine the source of the information., Results: Seventy-five breast clinic (mean age 46 years, all female) and 78 colorectal clinic patients (mean age 59 years, 51% male) responded. Knowledge of breast was significantly greater than bowel cancer in both groups (P<0.0001, McNemar's chi(2)). There was no difference in knowledge of symptoms of breast cancer or bowel cancer between patients attending either clinic. There was a positive association between cancer knowledge, family history and female gender but no association with age. Knowledge of Bowel Cancer Awareness Week was positively associated with colorectal cancer knowledge., Conclusion: Knowledge of colorectal cancer is much less than breast cancer in clinic attenders. Seventy-five per cent of women attending breast clinic could name a breast cancer symptom whereas only 37% of patients attending colorectal clinic could name a bowel cancer symptom. These findings have implications when considering patients' anxiety, expectations of a cancer diagnosis and breaking bad news.

Why, given similar medical circumstances-high familial risk of breast cancer-will some women elect to join a trial of drugs designed to reduce that risk but others choose not to take part? The aim of this study was to identify measurable differences between women who elect to join a placebo-controlled, double-blind randomised trial of the drug tamoxifen and women who elect not to join. One hundred and six women attending a breast care clinic completed questionnaires covering demographic details, health locus of control, perception of risk and adequacy of medical communication. All were eligible for inclusion in the tamoxifen trial. Only half (n=53) of the sample elected to join, the other half (n=53) declined. Those who declined the trial were significantly more aware of lifestyle factors thought to influence the development of cancers-diet, exercise and oestrogen-prolonging activities (p<0.001), and they also appeared to find the information given by the hospital about tamoxifen harder to understand than did the group who had joined the trial (p=0.01). They could think of significantly fewer positive reasons for joining (p<0.001) and were significantly younger (p=0.001). Participants in both groups significantly overestimated the relative risks of breast cancer. The average estimation of risk for women aged 30 with a family history of breast cancer was 22 times higher than that given by their consultant. This gives rise to considerable concerns about the information underpinning informed consent.

Over recent years, specialist breast care nurses have become increasingly recognized as core members of any breast care team within the UK. Part of the role is to support patients at the highly stressful stage of receiving a diagnosis. This paper describes an 'advocacy' style of nurse counsellor intervention which aims to improve patients' preparation for, and involvement in, the diagnostic consultation and provides a framework for future counselling support. One hundred and three women undergoing surgery following diagnosis of breast cancer or a benign breast lump were supported using either this advocacy intervention or a more conventional model of care. The aim was to identify the most effective and appropriate method of intervening at this important stage. Assessment took place before surgery, with 2-week and 6-month follow-ups, and included the Hospital Anxiety and Depression Scale, Rotterdam Symptom Check List and semi-structured interviews addressing perceived quality of care, involvement in decision-making and psycho-social functioning. Whilst the results of many measures were similar for women in the two intervention groups, qualitative data support the implementation of the advocacy method by the breast care nurse.

Expression of the pS2 protein in breast carcinoma is a useful guide to prognosis and response to tamoxifen. We have investigated pS2 protein expression in both the primary tumour and lymph node metastases (LNM) using a computer-assisted image analysis system. In a consecutive series of 208 patients undergoing surgical excision of primary breast cancer with axillary clearance, 89 patients were found to have involved lymph nodes. We found a highly significant correlation between pS2 expression in primary tumours and their LNM when 5% was taken as the cut-off for positive staining (Fischer Exact, P < 0.0001). There was also a highly significant correlation between the proportion of positive staining between the local metastases and primary tumours (Spearman's rank order correlation = 0.87; P < 0.0001). We conclude that the pS2 status of LNM can be accurately predicted from the pS2 status of the primary tumour. As such, appropriate adjuvant therapy for primary breast cancer, or second line therapy for disseminated disease can be selected on the pS2 status of the primary tumour alone.

Fine-needle aspirates from 52 breast cancers in 50 patients over 70 years of age were immunocytochemically stained for pS2 protein. All patients were treated with tamoxifen 40 mg/day and followed up at intervals of 2 months. The size of the tumour was serially assessed with calipers and portable ultrasonography. Change in tumour size was confirmed mammographically. Clinical monitoring was performed bind of the pS2 status. Twenty-five tumours were pS2 positive, of which 23 showed a significant response; ten went into complete remission (mean time to complete remission 6.8 (range 2-14) months) and 13 demonstrated partial remission (mean follow-up 8.9 (range 6-19) months). Two tumours remained static. Twenty-seven tumours were pS2 negative and none of these responded to tamoxifen; six remained static (mean follow-up 11.5 (range 6-14) months) and 21 progressed (mean time to progression 7.0 (range 3-14) months) (P < 0.001). Immunocytochemical assessment of fine-needle aspirates from elderly women with breast cancer accurately predicts a worthwhile response to tamoxifen.

pS2 protein is a cysteine-rich polypeptide, of unknown function, the expression of which is induced in the human cancer cell line MCF-7 by oestrogen. The availability of a murine monoclonal antibody to human pS2 protein has prompted us to evaluate its expression in 47 cases of primary breast carcinoma. Using a double indirect immunoperoxidase technique, we compared the expression of pS2 protein in fine needle aspiration (FNA) cytology smears with that in formalin-fixed, paraffin-embedded sections from subsequently excised tumours from the same patients. We also compared the expression of pS2 protein and oestrogen receptor (ER) status using immunocytochemical assay (ER-ICA) in formalin-fixed, paraffin-embedded sections from 22 primary breast carcinomas. We found the application of immunocytochemistry in the assessment of pS2 protein expression in FNA cytology to be a reliable and cost-effective technique, having a sensitivity of 84% and a specificity of 100%. There was also a good correlation between the expression of pS2 protein and ER status.