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Background:Risk-reducing mastectomy with tissue expander and then implant-based breast reconstruction conventionally involved immediate submuscular placement of tissue expanders during mastectomy and then, after expansion, replacement of expanders for permanent implants in a second-stage operation.

The last twenty years have seen a complete change in society's attitude to the strategy of risk reduction of breast cancer in high-risk individuals by means of proactive mastectomy. Once termed 'prophylactic mastectomy', risk reducing mastectomy (RRM) was considered two decades ago not only extreme, but in some quarters almost unethical. RRM is now commonly undertaken in specialist breast units for women at high individual breast cancer risk, by virtue of an inherited breast cancer related gene mutation or from calculated high statistical risk from family history data, and the efficacy of RRM in reducing subsequent incident diagnoses of breast cancer has been published from a number of centres. RRM is offered routinely in conjunction with total breast reconstruction, using the whole range of reconstructive surgical techniques. The public announcement by the actor Angelina Jolie in 2013 that she had inherited and harboured a BRCA1 gene mutation, and was undergoing RRM and breast reconstruction to lower her intrinsic breast cancer risk, had a significant effect on public attitudes and perception. Whilst there are other means of lowering breast cancer risk by means of selective oestrogen receptor modulators, such as tamoxifen and raloxifene, their lowering effect on risk of breast cancer remains substantially less than that afforded by surgical removal of 'at risk' breast tissue. The progressive development and increasing sophistication of techniques of breast reconstructive surgery has paralleled the trend for more RRM surgery, and the substantial majority of women who opt for RRM choose immediate breast reconstruction.

Clinics for women concerned about their family history of breast cancer are widely established. A Family History Clinic was set-up in Manchester, UK, in 1987 in a Breast Unit serving a population of 1.8 million. In this review, we report the outcome of risk assessment, screening and prevention strategies in the clinic and propose future approaches. Between 1987&ndash, 2020, 14,311 women were referred, of whom 6.4% were from known gene families, 38.2% were at high risk (&ge, 30% lifetime risk), 37.7% at moderate risk (17&ndash, 29%), and 17.7% at an average/population risk who were discharged. A total of 4168 (29.1%) women were eligible for genetic testing and 736 carried pathogenic variants, predominantly in BRCA1 and BRCA2 but also other genes (5.1% of direct referrals). All women at high or moderate risk were offered annual mammographic screening between ages 30 and 40 years old: 646 cancers were detected in women at high and moderate risk (5.5%) with a detection rate of 5 per 1000 screens. Incident breast cancers were largely of good prognosis and resulted in a predicted survival advantage. All high/moderate-risk women were offered lifestyle prevention advice and 14&ndash, 27% entered various lifestyle studies. From 1992&ndash, 2003, women were offered entry into IBIS-I (tamoxifen) and IBIS-II (anastrozole) trials (12.5% of invitees joined). The NICE guidelines ratified the use of tamoxifen and raloxifene (2013) and subsequently anastrozole (2017) for prevention, 10.8% women took up the offer of such treatment between 2013&ndash, 2020. Since 1994, 7164 eligible women at &ge, 25% lifetime risk of breast cancer were offered a discussion of risk-reducing breast surgery and 451 (6.2%) had surgery. New approaches in all aspects of the service are needed to build on these results.

BRCA1/2 mutation carriers with breast cancer are at high risk of contralateral disease. Such women often elect to have contralateral risk-reducing mastectomy (CRRM) to reduce the likelihood of recurrence. This study considers whether CRRM improves overall survival. 105 female BRCA1/2 mutation carriers with unilateral breast cancer who underwent CRRM were compared to controls (593 mutation carriers and 105 specifically matched) not undergoing CRRM and diagnosed between 1985 and 2010. Survival was assessed by proportional hazards models, and extended to a matched analysis using stratification by risk-reducing bilateral salpingo-oophorectomy (RRBSO), gene, grade and stage. Median time to CRRM was 1.1 years after the primary diagnosis (range 0.0–13.3). Median follow-up was 9.7 years in the CRRM group and 8.6 in the non-CRRM group. The 10-year overall survival was 89 % in women electing for CRRM (n = 105) compared to 71 % in the non-CRRM group (n = 593); p < 0.001. The survival advantage remained after matching for oophorectomy, gene, grade and stage: HR 0.37 (0.17–0.80, p = 0.008)—CRRM appeared to act independently of RRBSO. CRRM appears to confer a survival advantage. If this finding is confirmed in a larger series it should form part of the counselling procedure at diagnosis of the primary tumour. The indication for CRRM in women who have had RRBSO also requires further research.

Introduction: For high-risk familial history of breast cancer, risk reducing mastectomy (RRM) is now regarded as one of the management options. The aim of this study is to analyse the outcome of women undergoing RRM from 1994 to 2010 during which surgical techniques evolved and were refined. Methods: A cohort of women undergoing RRM was followed from this single centre. Surgical and further details about demographics, comorbidities, and follow-up were retrieved form medical records. Analysis was carried out using the IBM®-SPSS®-Statistics-19system. Results: Of 154 women 139 had bilateral RRM and 15 had unilateral surgery after earlier contralateral breast cancer. Median age at operation was 39.4 years (22–63years). 54 (45.5%) women were BRCA1/2 gene mutation carriers. Most women had nipple sacrificing (86) skin-sparing mastectomy with immediate reconstruction. 132 (85.7%) had submuscular expander/implant reconstruction, whilst 9 had either LD flap reconstruction or TRAM flap reconstruction. 31 (20.1%) women had some complication including haematoma requiring evacuation, minor skin/nipple necrosis, but implant loss was rare (2). 52 (33.8%) women had revisional surgeries in 5 years post RRM of whom 29 had one unanticipated secondary operation. Complications were more common in the early years of the cohort. On histology, 3 women were identified with lobular carcinoma in-situ and one was associated with 1mm of microinvasion. 4 had ductal carcinoma in-situ and 2 of them were BRCA carriers. Two (1.2%) primary breast cancers were subsequently identified during a mean follow-up period of 9.82 years (2–18 years) but this was substantially less than prediction modelling. Both were BRCA gene mutation carriers - one had nipple sparing RRM and the other did not. Conclusions: In asymptomatic high-risk women, RRM is safe and efficacious in reducing medium term future breast cancer incidence. Surgery carries the risk of complications and cosmetic revisions can be anticipated. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-11.

Purpose: Tamoxifen reduces risk of recurrence after breast conservation surgery for ductal carcinoma in situ (DCIS), but no data exists on the effectiveness of aromatase inhibitors for DCIS. Cyclooxygenase-2 (COX-2) is overexpressed in DCIS, representing another potential therapeutic target. The aim of the study was to determine the effect of aromatase and/or COX-2 inhibition on epithelial proliferation and apoptosis in a presurgical study of estrogen receptor (ER)–positive DCIS. Methods: Postmenopausal women with ER-positive DCIS diagnosed by core biopsy were randomized to a 2 × 2 design of either 14 days of exemestane or placebo and celecoxib, or placebo immediately before surgery. Paired baseline and end point biopsies were analyzed for proliferation (Ki67), apoptosis, human epidermal growth factor receptor 2 (HER2), COX-2, and progesterone receptor (PR) expression by immunohistochemistry. The primary end point was a decrease in Ki67 between diagnosis and surgical excision. Results: Ninety women were randomized: all were ER positive, 49 (54%) had grade III tumors, and 29 (32%) were HER2 positive (3+). Exemestane reduced proliferation compared with placebo with a median reduction of 9% (95% confidence interval, 6-14; P < 0.001). Progesterone receptor was reduced by exemestane (mean decrease, 19%; 95% confidence interval, 9-28; P = 0.011). The effect of exemestane on proliferation was seen regardless of grade, HER2, or PR expression. Celecoxib had no effect on proliferation or apoptosis alone, or in combination with exemestane. Conclusions: Exemestane reduces proliferation in ER-positive DCIS. Aromatase inhibition is a potential alternative to tamoxifen in patients who have undergone breast conservation for ER-positive DCIS. Clin Cancer Res; 16(5); 1605–12

Purpose: The uptake of risk-reducing surgery in women at increased risk of breast and ovarian cancer is highly variable between countries and centers within countries. We have investigated the rate, timing, and age of uptake of surgery in the northwest of England to report the results after up to 7 years in a Regional Genetics center. Methods: Uptake was documented in 211 known unaffected BRCA1/2 mutation carriers from 509 families and in 3,515 women at >25% lifetime risk of breast cancer without known mutations. Results: Of the 211 mutation carriers, 40% opted for bilateral risk-reducing mastectomy (BRRM) and 45% underwent bilateral risk-reducing salpingo-oophorectomy (BRRSPO). Uptake of BRRM was significantly related to lifetime risk and age but continued over several years. In women not known to carry a BRCA mutation, 6.4% of women at 40% to 45% lifetime risk, 2.5% of women at 33% to 39% lifetime risk, and 1.8% of women at 25% to 32% lifetime risk underwent BRRM (P < 0.005). BRRSPO uptake was greater in BRCA1 (52%) than BRCA2 (28%) carriers but in both groups tended to occur within the first 2 years after gene test (except in the youngest age group) and in women between the ages of 35 and 45. Conclusion: To truly assess the uptake of risk-reducing surgery, longer-term follow-up is necessary particularly in younger women who are likely to delay BRRSPO. Careful risk counseling does seem to influence women's decisions for surgery, although the effect is not immediate. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2318–24)

Background: Increasingly women at high risk of breast cancer are opting for risk reducing surgery. The aim of this study was to assess the effectiveness of this approach in women at high risk in both carriers and non-carriers of BRCA1/2 . Methods: Data from 10 European centres that offer a genetic counselling and screening service to women at risk were obtained prospectively from 1995. Breast cancer risks were estimated from life tables and a control group of women at risk who did not undergo surgery. Results: The combined centres have data on 550 women who have undergone risk reducing mastectomy with greater than 3334 women years of follow-up. Operations were carried out on women with lifetime risks of 25–80%, with an average expected incidence rate of 1% per year. No breast cancers have occurred in this cohort in the “at risk” unaffected breast, whereas >34 would have been expected. A high rate (2–3.6%) of occult disease was identified in the at risk breast at the time of surgery. Interpretation: We conclude that risk reducing surgery is highly effective.

Purpose: To undertake the first substantial clinical study of breast radiotherapy toxicity in BRCA1 and BRCA2 mutation carriers in the United Kingdom. Experimental Design: Acute and late radiation effects were evaluated in a retrospective study of 55 BRCA1 and BRCA2 mutation carriers treated with radiotherapy for breast cancer at four centers between 1983 and 2002. Individual matching with controls who had sporadic breast cancer was undertaken for age at diagnosis, time since completion of radiation, and treatment variables. Detailed assessments were undertaken by one examiner. Median follow-up was 6.75 years for carriers and 7.75 years for controls. Rates of late events (rib fractures, lung fibrosis, necrosis of soft tissue/bone, and pericarditis) as well as LENT-SOMA scores and clinical photography scores of breast size, shape, and skin telangiectasia were the primary end points. Results: No increase in clinically significant late toxicity was seen in the mutation carriers. Conclusions: These data add substantial weight to the evidence that the outcomes in the treated breast from radiotherapy in women with BRCA1 or BRCA2 mutations are comparable with those in women with sporadic breast cancer.

Purpose: To evaluate acute toxicity induced by chemotherapy for breast cancer in a retrospective study of 62 BRCA1/2 mutation carriers matched 1:1 with women who had treatment for sporadic disease in the United Kingdom between 1983 and 2003. Experimental Design: All participants were interviewed by one of two researchers using standardized questionnaires, and their medical records were reviewed by one research nurse. The two main regimens received were cyclophosphamide, methotrexate, and fluorouracil and fluorouracil, epirubicin, and cyclophosphamide. The proportion of cases and controls receiving anthracycline-based treatment was equivalent, but fewer BRCA1 cases received this treatment than did BRCA2 mutation carriers. Toxicity was documented using the Eastern Cooperative Oncology Group Common Toxicity Criteria for hematologic, infective, and gastrointestinal toxicities. No increase in toxicity was seen in BRCA1/2 mutation carriers. Results: The only significant difference was that neutropenia was less evident in BRCA2 mutation carriers than in either BRCA1 mutation carriers or controls. As a result, there was no requirement for dose reduction among BRCA2 mutation carriers, in contrast to 10 of 39 BRCA1 carriers and 16 of 62 controls (P = 0.02). Conclusions: This result has implications for therapy and indicates that women with mutations in BRCA1 and BRCA2 may be given the same doses of chemotherapy as noncarriers.

Women with a family history are often offered mammographic surveillance at an earlier age and with greater frequency than those in the National Breast Screening Programme. In this study, we compared the survival of 62 breast cancer patients diagnosed in the context of a family history clinic offering 12-18 monthly mammographic screening with that of 1108 patients of the same age range but having no exposure to screening. We subtracted the expected additional observation time due to lead time from the survival of the screen-detected cases. Survival was significantly better in the family history group with relative hazards of 0.19 (95% CI 0.07-0.52, P0.001) for breast cancer death and 0.19 (95% CI 0.08-0.43, P0.001) for disease-free survival. After correcting for lead-time, the relative hazards were 0.24 (95% CI 0.09-0.66, P=0.005) for breast cancer death and 0.25 (95% CI 0.11-0.57, P0.001) for disease-free survival. These results strongly suggest that screening younger women with a family history of breast cancer leads to improved survival. More precise estimates of the benefit will accrue from further follow-up and other such studies.

To establish the uptake of contralateral risk reducing mastectomy in women informed of their risks and options at time of diagnosis of their primary unilateral breast cancer.We have assessed the surgical choices of 70 women diagnosed with breast cancer50 years as part of a family history surveillance program and fully informed about their contralateral risks and surgical options. We have compared this to women from other surgical clinics who were subsequently found to harbour a pathogenic BRCA1/2 mutation.Sixty-five percent (13/20) of BRCA1/2 mutation carriers and 59% (n=20/34) of those at the highest level of risk pre-diagnosis (33+% lifetime risk) opted for contra-lateral mastectomy in the study sample. In contrast only 10% (n=9/88) women identified as mutation carriers from other clinics opted for such surgery.We would suggest that women with a significant family history and therefore a high contra-lateral breast cancer risk, should have these risks and management options discussed at the time of diagnosis of breast cancer.

Chemotherapy exerts a variable effect on nutritional status. It is not known whether loss of body fat or fat-free mass (FFM) during chemotherapy relates to diminished dietary intake, failure to meet elevated energy requirements, or to the presence of an acute-phase response. We sought to determine prospective measurements of body mass and composition, resting energy expenditure, energy and protein intake, and C-reactive protein over a course of chemotherapy in 82 patients with advanced cancer. There was a large dropout from the study. Prospective measurements were obtained in 19 patients with non-small-cell lung cancer (NSCLC), 12 with metastatic melanoma and 10 with metastatic breast cancer. There were significant increases in energy intake among patients with metastatic breast cancer, 873 (266–1480) kJ (mean 95% CI; P

Weight gain is a common problem amongst women receiving adjuvant chemotherapy for early breast cancer. We undertook a study to determine the causes of this weight gain. Prospective measurements of body mass and composition (skinfolds, bioelectrical impedance, total body potassium), energy balance (resting energy expenditure dietary intake, and physical activity), were determined in 17 women during and in the 6 months after commencing adjuvant chemotherapy. Women gained significant amounts of weight (5.0 +/- 3.8; p < 0.01) and body fat (7.1 kg +/- 4.5; p < 0.01) over the year. Waist circumference (5.1 +/- 4.5 cm; p < 0.01) and abdominal skinfold (16.2 +/- 10 mm; p < 0.01) were also increased but there was a decline in fat free mass (FFM); 1.7 +/- 2.5 kg. Women due to receive adjuvant chemotherapy had a greater resting energy expenditure (REE) compared with healthy subjects (n = 21); 100.5 +/- 8.0% Harris Benedict compared to 94.5 +/- 8.4% Harris Benedict (p = 0.05). REE declined by 3% during adjuvant chemotherapy (p < 0.05), and remained depressed until at least 3 months posttreatment. There were no significant changes in dietary intake or physical activity over the year. Failure of women to reduce their energy intake to compensate for the decreased energy requirement may account for some of the weight gain. Treatment of adjuvant chemotherapy causes gain of body fat because of reduced energy expenditure, and the failure of women to reduce their energy intake to compensate for the decline in energy requirement during and in the 6 months posttreatment. Since weight gain impacts on survival, patients should be counselled to reduce energy intake and exercise during and after adjuvant treatment.

BACKGROUND Breast conserving surgery (BCS) is common practice for unifocal ductal carcinoma in situ (DCIS) less than 4 cm in size, but the extent of tumor free margin width around DCIS necessary to minimize recurrence is unclear. METHODS Clinical and pathologic details were recorded from all patients with pure DCIS 1 mm) were divided up into 3 groups for analysis based on margin of normal tissue excised: 1.1–5 mm, 5.1–10 mm, and 10.1–40 mm. RESULTS There were 66 patients with close margins (≤ 1 mm), of which 25 cases (37.9%) recurred. The recurrence rates for the 3 clear margin groups ranged from 4.5–7.1%. Median followup was 47 months (range 12–197 mos). Risk of recurrence in the group with close margins was greater than the subgroups with clear margins (P < 0.001); no differences in recurrence was seen between the individual subgroups with clear margins. Nuclear Grade 3 was predictive of recurrence (P = 0.03). Following excision alone, the recurrence rate was 18.6%, compared with 11.1% when radiotherapy was given as adjuvant therapy. Women with clear margins following excision had a recurrence rate of only 8.1%. CONCLUSION After BCS for DCIS, close margins were associated with a high risk of local recurrence. Radiotherapy did not compensate for inadequate surgical clearance. Cancer 2001;91:9–16. © 2001 American Cancer Society.

Background: In Manchester, approximately 120 women at ≥1: 4 lifetime risk of breast cancer have considered preventative surgery since 1992. Women treated within the Manchester protocol receive two genetic counselling sessions, a psychological assessment and a surgical consultation pre-operatively and annual follow-up post-operatively. The vast majority of women have breast reconstruction. Methods: Since 1996, mental health and body image have been assessed in women attending annual follow-up using self-report questionnaires: the 28-item General Health Questionnaire (GHQ) and 10-item Body Image Scale (BIS). Women with high scores are assessed by clinical interview together with a proportion who have no significant problems. Results: Between 1995 and 1999, 76 women completed surgery. Ten were awaiting post-operative review and 60 (91%) attended for follow-up of whom 45 (75%) were interviewed. Questionnaire data were available for 52 (79%) women, mean age 40.8 years (range 27–58). Six women were gene mutation carriers and of these three had had breast cancer. One additional patient was affected but had not been genetically tested. Eight (17%) of 47 women with assessments in the first post-operative year scored in the ‘caseness’ range on the GHQ: the mean GHQ score was 3.8 (S.D. 6.7), range 0–25. Results were comparable with those for women attending the Family History Clinic for risk assessment. The mean score on the BIS was 5.1 (S.D. 5.5), range 0–25, comparable with scores for women undergoing conservative surgery for breast cancer. Twenty-one percent of women reported no negative change in body image following surgery (i.e. zero questionnaire summary scores) and the majority of changes reported were of minor degree (item scores 0 or 1). The most frequently reported changes were in sexual attractiveness (55%), feeling less physically attractive (53%) and self-consciousness about appearance (53%): a third of women felt less feminine to a minimal degree. These results appeared stable over time. A minority of women had more serious psychological or body image concerns, usually in relation to surgical complications: they received further psychiatric intervention. Conclusions: For the majority of women there is no evidence of significant mental health or body image problems in the first 3 years following Bilateral Prophylactic Mastectomy (BPM), but women who have complications warrant additional psychological help. Careful pre-operative preparation and long-term monitoring are advocated in this new field of cancer prevention. Copyright © 2000 John Wiley & Sons, Ltd.

Mastectomy probably represents over-treatment for the majority of women with screen detected ductal carcinoma in situ (DCIS) and breast-conserving surgery is now widely advocated. In this study, biopsy cavity shavings were used to ensure complete excision in 129 women undergoing breast-conserving surgery for screen detected DCIS. A margin was considered clear if DCIS was > 1 mm from any margin of excision and shavings were clear. Patients with involved margins (DCIS at resection margin) underwent re-excision, irrespective of shaving status. After re-excision, 101 women (78%) had clear margins and 28 (22%) close margins (DCIS < or = 1 mm from resection margin). Cavity shavings were histologically clear of DCIS in all cases. Ipsilateral DCIS recurrence occurred in 12 (9.3%) patients. Two recurrences also contained invasive carcinoma. The median time to diagnosis was 14 months and all recurrences occurred at the site of the previous biopsy. Seven recurrences were detected at the first annual mammogram, four at the second and one at the third. Ipsilateral recurrence was related to margin status; only 2 out of 101 (2%) patients with clear margins recurred, compared with 10 out of 28 (36%) patients with close margins. Local recurrence and close margin status both correlated with a high modified Van Nuys prognostic index score. Our results indicate that local relapse represents residual DCIS rather than true recurrence in the majority of cases. Cavity shavings have proved ineffective in ensuring complete excision. We now ensure a minimum 10 mm margin of excision around all screen-detected DCIS lesions.

The aim of this study was to establish if risk-reducing surgery (RRS) increases survival among BRCA1/2 carriers without breast/ovarian cancer at the time of family referral. Female BRCA1/2 carriers were identified from the Manchester Genetic Medicine Database. Those patients alive and unaffected at the date of first family ascertainment were included in this study. Female first-degree relatives (FDRs) without predictive genetic testing who otherwise met eligibility criteria were also included. The effect of breast and ovarian RRS on survival was analysed. The survival experiences of RRS and non-RRS patients, stratified by BRCA status, were examined with Kaplan-Meier curves and contrasted using log-rank tests and Cox models. 691 female BRCA1/2 mutation carriers without breast or ovarian cancer at time of family ascertainment were identified; 346 BRCA1 and 345 BRCA2. 105 BRCA1 carriers and 122 BRCA2 carriers developed breast cancer during follow-up. The hazard of death was statistically significantly lower (P < 0.001) following RRS versus no RRS. 10-year survival for women having RRS was 98.9 % (92.4-99.8 %) among BRCA1 and 98.0 % (92.2-99.5 %) among BRCA2 carriers. This survival benefit with RRS remained significant after FDRs were added. Women who had any form of RRS had increased survival compared to those who did not have RRS; a further increase in survival was seen among women who had both types of surgery. However, formal evidence for a survival advantage from bilateral mastectomy alone requires further research.

Screen-detected breast cancers are smaller than those detected in symptomatic populations and, for any given size, they are associated with fewer lymph node metastases. The management of axillary lymph nodes in patients with screen-detected breast cancer remains controversial. We have previously reported that prevalence (initial screen)-detected cancers are associated with nodal metastases in 17.4% of cases overall. Cancers < or = 10 mm, of any grade, are associated with metastases in only 5% of cases, and grade I cancers

Aim: We have previously reported in a randomised controlled trial comparing intercostobrachial nerve (ICBN) preservation with division that no difference in symptoms was seen between the groups at 3 months follow-up although a reduced area of sensory loss was measured on the arm. To determine if longer follow-up provides evidence for ICBN preservation, follow-up of patients in the trial at 3 years (range 32–38 months) postoperatively was performed. Methods: Sensory symptoms and deficits, pain, shoulder movements, arm circumference and the presence of neuromas were documented in 73 patients from the original group of 120. Results: No difference in survival or axillary recurrence was observed. The only symptom which differed between the two groups was a subjective assessment of ‘different sensation’ ( P =0.006). No significant difference was observed in other sensory symptoms, pain, shoulder movement, arm circumference or presence of neuromas. A larger area of sensory deficit was measured in women with sacrificed nerves compared to preserved ( P =0.009). Conclusion: Preservation of the intercostobrachial nerve does not affect patient survival. It improves patient sensory deficit significantly and modestly improves long-term symptoms.

BACKGROUND: The exact mechanism of capsular contracture (CC) is still unknown. The covalent modification of hyaluronan (HA) with the heavy chains (HC) of inter-?-inhibitor (I?I) has been identified as an important pathway in inflammation and tissue remodeling, where HC�HA formation is catalyzed by TSG-6 (the protein product of tumor necrosis factor stimulated gene-6). OBJECTIVE: The authors quantitatively assess the correlation between severity of CC (measured by Baker grade) and expression of HA, TSG-6, and I?I (ie, the polypeptides HC1, HC2, and bikunin) in periprosthetic breast capsules. METHODS: Immunofluorescent staining for HA, TSG-6, HC1, HC2, and bikunin was carried out on periprosthetic breast capsules (n = 7) of each Baker grade from four anatomical locations. Quantitative analysis was performed to identify differences in staining intensity. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine differences in TSG-6 gene expression levels. RESULTS: Severity of contracture was associated with reduced staining for both free HA (Pearson correlation coefficient, r = -0.645, P < .001) and TSG-6 (r = -0.642, P = .002). RT-qPCR showed a significant negative correlation between severity of contracture and TSG-6 gene expression levels (r = -0.750, P = .001). CONCLUSIONS: The negative correlation between TSG-6 expression levels and severity of CC suggests a possible protective role for TSG-6 in the context of CC formation, and this may have a clinically relevant role in prevention of breast CC.

Over the last 10–20 years breast surgery has undergone gradual but radical transformation, starting with the multicenter trials of mastectomy versus breast conservation in the 1980s. Surgical change has occurred in parallel with a substantial increase in the understanding of the biology of breast cancer, the mechanisms of estrogen action and blockade, more effective adjuvant chemotherapy and radiotherapy, and earlier diagnosis. The multidisciplinary team, the emergence of specialist breast surgeons from traditionally different historical surgical specialties, and an abandonment of the ‘one size fits all’ philosophy for oncological surgery and breast reconstructive surgery further enhance modern patient care. Better survival, quality of life issues, and increased patient and surgeon expectations have led not only to a surge in total breast reconstruction techniques, but also to the development of partial breast reconstruction after wide local excision for malignancy.

Over the last decade the whole approach to breast cancer surgery has changed radically from its ‘general surgery’ roots. There are few surgical specialties that have changed so much. The initial phase was the attention to wide local excision surgery, employing a more sensitive take on breast conservation, with scar placement and parenchymal reshaping. Then the concept of avoiding mastectomy by means of more extensive wide tumour excision together with partial breast reconstruction led to a flurry of innovations involving volume replacement and displacement techniques [1]. Oncoplastic breast surgery as a specialty now encompasses all elements of breast cancer surgery: appropriate cancer resection, skin-sparing mastectomy and immediate breast reconstruction, the full elements of total and partial breast reconstruction and adjustment for breast asymmetry by augmentation, reduction mammaplasty or mastopexy for the contralateral unaffected breast [2]. The legacy of historical surgical training has meant that until recently few surgeons have been equipped to offer this cancer surgery/cosmetic/reconstructive breast surgery hybrid approach. This is changing with training initiatives. Over the last decade approximately 90 surgeons in the United Kingdom have undergone 1-year-long senior fellowships in oncoplastic breast surgery in nine tertiary centres, trained by both breast and plastic surgeons seamlessly. This approach is changing the quality of surgical care for the benefit of women. It has also led to a rejuvenation of breast surgery away from purely resection-based operations that had remained unchanged for many decades, to an innovative specialty with creative concepts and aesthetic detail. In turn, the result in the UK has been marked interest amongst trainee surgeons to enter breast surgery as a career, and applications for the national fellowships are highly competitive. Nevertheless much breast cancer surgery is still delivered by general surgeons, so care for individual women may involve surgeons from general as well as plastic/reconstructive surgery backgrounds now working together in an ‘oncoplastic multidisciplinary team’. In 2007 extensive guidelines were developed in the UK to address inequalities in surgical provision. Oncoplastic Breast Surgery – a guide to good practice was a joint venture between the Association of Breast Surgery at BASO, the British Association of Plastic, Reconstructive and Aesthetic Surgery (BAPRAS), and the Breast Surgery Interface Training Committee at The Royal College of Surgeons of England [3]. This was intended to be for women with breast cancer, and all those involved in their care, to ensure the highest standards in setting up and delivering an oncoplastic breast service. In 2012 the guidelines were revised and newly published, and constitute a fully comprehensive document describing high standards of care for all aspects of oncoplastic and reconstructive breast surgery. They also cover aspects of the processes, the patient’s journey and arrangements for both equipment needs and team participants. The advantage of the revision is that the 5 years’ experience in developing models of care has been incorporated by the multispecialty team of writers into the 2012 document. The UK document is unique in its ambition to raise surgical quality nationally, to ensure that patients are aware of what is available, and to inform surgeons, allied professionals and hospital administrators about what is required to provide a modern high-quality standard of care for women with breast cancer. These guidelines can be accessed online through either the Association of Breast Surgery or BAPRAS websites: ‘Oncoplastic breast reconstruction – Guidelines for Best Practice, 2012, Eds Dick Rainsbury and Alexis Willet’ (http://www.associationofbreastsurgery.org.uk/media/23851/final_oncoplastic_guidelines_for_use.pdf). The role of surgery in the management of women with breast cancer remains all important and fundamental. Its role in the prevention of breast cancer for women at high risk by virtue of family history or gene mutation is increasing.

BACKGROUND: Men with nonsmall cell lung cancer (NSCLC) are more susceptible to weight loss than women. The composition and aetiology of these gender specific weight changes are not known. METHODS: Measurements of body mass, body composition and energy balance (resting energy expenditure and energy intake) were made in 15 men and six women before and after chemotherapy for NSCLC. RESULTS: Over the course of chemotherapy minimal weight change was observed in both men and women. Men increased body fat from 25.0 +/- 5.5 to 27.9 +/- 7.9% (P < 0.05) whereas fat free mass (FFM) tended to decrease (P = 0.063). There was no change in body fat or FFM in the women. In the men resting energy expenditure decreased over the course of chemotherapy from 113.2 +/- 15.9 to 105.1 +/- 10.1% of the value predicted from the Harris Benedict equation (P < 0.05). In the women resting energy expenditure (REE) did not alter. CONCLUSION: Over the course of chemotherapy for NSCLC, men and women appear to have different patterns of change in body composition and in energy expenditure.

This paper describes a protocol for women at high risk of breast cancer wishing to undergo preventative mastectomy. The protocol described is a holistic approach to each woman involving the use of a multidisciplinary team. The protocol takes a number of months from initiation to surgery. A time delay is deliberate to allow women to fully address the issues involved with a decision for surgery. Early evidence suggests that this prepares the women emotionally and physically for their surgery.

Higher levels of evidence proving difficult

Objective : To determine the effect of early discharge from hospital after surgery for breast cancer on physical and psychological illness. Design : Randomised controlled trial comparing discharge two days after surgery (before removal of drain) with standard management (discharge after removal of drain). Setting : Regional breast unit. Subjects : 100 women with early breast cancer undergoing mastectomy and axillary node clearance (20) or breast conservation surgery (80). Main outcome measures : Physical illness (infection, seroma formation, shoulder movement) and psychological illness (checklist of concerns, Rotterdam symptom questionnaire, hospital anxiety and depression scale) preoperatively and at one month and three months postoperatively. Results : Women discharged early had greater shoulder movement (odds ratio 0.28 (95% confidence interval 0.08 to 0.95); P=0.042) and less wound pain (odds ratio 0.28 (0.10 to 0.79); P=0.016) three months after surgery compared with women given standard management. One month after surgery scores were significantly lower on the Rotterdam symptom questionnaire in patients who were discharged early (ratio of geometric mean scores 0.73 (0.55 to 0.98); P=0.035), but rates of psychological illness generally did not differ between groups. Conclusions : Increased rates of physical or psychological illness did not result from early discharge after surgery for breast cancer. This policy can be recommended for patients with support at home.

Background Complications of axillary surgery occur due to severance of the intercostobrachial nerve (ICBN). The feasibility and benefit of preserving the ICBN to prevent sensory loss was studied prospectively. Methods Sensory symptoms and deficits were documented, and shoulder movement and arm circumference were measured at discharge and 3 months later in 120 patients randomized to either preservation or division of the ICBN. Results Preserving the ICBN was feasible in 39 (65 per cent) of the 60 patients randomized to the preservation group. Preserving the nerve prolonged the procedure by a median of 5 min. No difference in sensory symptoms between the groups was seen at 3 months. At 3 months 53 per cent of patients randomized to ICBN preservation had a sensory deficit compared with 84 per cent of those randomized to ICBN sacrifice (P ≤ 0·05). Conclusion Preserving the ICBN reduces the incidence of sensory deficit (but not symptoms) in patients after axillary clearance.

BACKGROUND Ductal carcinoma in situ (DCIS) represents 20%-30% of breast cancers detected by clinical screening (i.e., mammography). More than 50% of DCIS lesions may be estrogen receptor negative and, therefore, hormone independent. However, the role of estrogen in the natural history of DCIS is unknown. PURPOSE A novel in vivo (i.e., xenograft) model was developed to determine to what degree DCIS lesions depend on estrogen for growth. METHODS Specimens of breast tissue were collected from 52 women during diagnostic or therapeutic surgical procedures. Portions of each specimen were randomly selected and analyzed by histology and thymidine labeling (to measure cell proliferation). The remainder of each specimen was implanted into five to 18 athymic BALB/c nu/nu mice (depending on the amount of tissue available), with eight pieces of approximately 2 mm x 2 mm x 1 mm implanted at different locations on the back of each mouse. Half of the mice received implants containing estrogen (2 mg 17 beta-estradiol), and the other half received placebo implants. Levels of cell proliferation in xenografts, recovered after 14, 28, 42, or 56 days in the mice, were measured by thymidine labeling or by immunohistochemistry through use of an antibody specific for the Ki-67 nuclear antigen. Immunohistochemistry was also used to measure the levels of estrogen receptor in the tissue specimens. Serum 17 beta-estradiol levels in the mice were measured by radioimmunoassay. RESULTS Initial levels of cell proliferation were approximately 10-fold higher in 10 specimens with estrogen receptor-negative, comedo (i.e., more malignant in appearance) DCIS than in four specimens with estrogen receptor-positive DCIS (mean proliferation indices: 22% versus 1.9%, respectively; two-sided P < .001). Xenografts from the majority of specimens survived up to 56 days in the mice and maintained good architectural and cellular preservation. Estrogen treatment of the xenograft-bearing mice had no effect on the high level of cell proliferation observed in estrogen receptor-negative, comedo DCIS specimens (two-sided P = .89). In contrast, increased levels of cell proliferation in response to estrogen supplementation were measured in three estrogen receptor-positive, noncomedo DCIS specimens (two-sided P < .001). However, even with estrogen treatment, cell proliferation levels in estrogen receptor-positive DCIS specimens did not reach those seen in estrogen receptor-negative DCIS specimens. CONCLUSION AND IMPLICATION Estrogen receptor-negative, comedo DCIS lesions appear to be estrogen independent; therefore, antiestrogen (e.g., tamoxifen) therapy may not benefit patients with comedo DCIS.

Several studies report an increased incidence of breast cancer in women taking hormone replacement therapy (apparently a duration dependent phenomenon)1 2 3; however, a decreased mortality from breast cancer has been reported in women using the treatment.1 We assessed the prognostic factors for breast cancers detected by screening at one unit to determine if cancers developing in women who used hormone replacement therapy have a better prognosis. All postmenopausal women (>12 months since last menstrual period or women over 50 who had had a hysterectomy) with invasive breast cancer detected at our screening unit between 1989 and 1994 were identified. Prognostic factors and history of use of hormone replacement therapy were recorded. Women taking hormone replacement therapy for more than three months within the year before their breast cancer diagnosis were considered “users.” After definitive surgery, pathological tumour size, grade, …

There has been a reluctance to treat patients with invasive lobular carcinoma by breast-conserving therapy because of the possibility of increased rates of local recurrence. This study is a retrospective review of 226 patients with pure invasive lobular carcinoma 4 cm or less treated by breast conservation therapy or mastectomy. Local relapse occurred in four of 52 patients (8 per cent) after breast conservation compared with 21 of 174 (12 per cent) after mastectomy. Breast conservation for invasive lobular carcinoma did not result in a higher incidence of local relapse and patients with invasive lobular and ducta carcinomas may be managed in a similar fashion.

Background: Radiotherapy is a treatment alternative to axillary node clearance following a positive sentinel node biopsy. However level III lymph nodes are not usually treated with current axillary radiotherapy protocols, raising the concern of inadequate treatment.Methods: A retrospective review of 636 patients undergoing sentinel node biopsy for breast cancer, following normal axillary ultrasound, to identify factors predicting for level III involvement.Results:In total 115 (18% of 636 women undergoing sentinel node biopsy had node involvement. Subsequent axillary node clearance in these patients identified 50% with further axillary node involvement. Further lymph node involvement was not predicted by standard pathological factors (oestrogen/progesterone/Her 2 neu receptor status/tumour size/grade). The Memorial Sloane Kettering Cancer Center (MSKCC) breast nomogram for additional node metastases had limited clinical utility. The mean (range) score to predict node involvement in node positive patients was 22% (4-95%) and node negative patients was 13% (5-33%) (p=0.01). 11% of patients had metastatic disease in level III nodes at surgery. Level III involvement was not predicted by routine clinicopathological factors, and although the MSKCC breast nomogram gave higher scores for the prediction of patients with subsequent level III involvement (level III positive: 32% (6-95%); negative: 14% (4-69%)), it was not discriminatory.Conclusion: Neither the MSKCC breast nomogram or standard clinicopathological factors predict for level III node involvement following positive sentinel node biopsy. Level III axillary node clearance must therefore be recommended as the gold standard for positive axillary disease to avoid the risk of undertreating 11% of patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1015.

A 34 year old female presented 7 weeks post-partum with acute diffuse arthritic manifestations and pyrexia. Extensive investigations (grossly raised erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], normal serology and others) were performed to pursue a diagnosis. Subsequently a breast abscess was diagnosed. Surgical treatment of this led to almost immediate resolution of the joint complaints and return of ESR/CRP to normal levels. This was considered a hitherto unreported case of acute non-purulent inflammatory arthritis concomitant to an existing infection elsewhere in the body. The pathogenic mechanism is unclear but speculatively toxin-mediated.

Axillary node fine needle aspiration cytology was performed prior to axillary clearance from 100 axillae in 99 women with breast cancer (1 bilateral). Only 25 samples contained sufficient cells for assessment: 12 were positive for malignant cells and 13 contained benign lymphoid elements. In cellular aspirates, sensitivity was 69%, positive predictive value 92% and negative predictive value 62%. Owing to the low rates of cellularity, this technique cannot be recommended for routine practice.