Patient-reported outcomes and their predictors at 2- and 3-year follow-up after immediate latissimus dorsi breast reconstruction and adjuvant treatment.

BACKGROUND: The aim of this study was to estimate the impact 2 and 3 years after surgery of implant-assisted latissimus dorsi (LDI) and autologous latissimus dorsi (ALD) flap breast reconstructions on patient-reported outcomes (PROs), and, secondarily, to determine whether baseline characteristics can predict PROs. METHODS: This was a multicentre prospective cohort study. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and breast cancer module (QLQ-BR23), Functional Assessment of Cancer Therapy - Breast (FACT-B), and Hospital Anxiety and Depression Scale (HADS) PROs were completed before surgery and at 2 and 3 years after breast reconstruction. The effects of LDI and ALD, adjusted for baseline clinicodemographic characteristics, were estimated with multiple linear regressions. Effect sizes above 0·5 were considered clinically important. RESULTS: Some 206 patients (LDI 93, ALD 113) were recruited in 2007-2013; 66·5 per cent were node-negative and 34·6 per cent received radiotherapy. Women with adverse clinicopathological factors were more likely to have received radiotherapy and to undergo ALD. Patients in both surgical groups showed clinically important effects at 2 and 3 years, including improvements in emotional scales, but worse physical functioning, social well-being, body image and anxiety. Radiotherapy adversely affected social functioning at 2 years (P = 0·002). Women undergoing ALD reconstruction had significantly improved sexual functioning at 3 years (P = 0·003) relative to those who had LDI procedures, even after adjusting for case mix (P = 0·007). At 3 years, younger women experienced worse physical well-being than older women (P = 0·006), and chemotherapy was associated with worse arm symptoms (P = 0·005). CONCLUSION: Clinically important changes occurred in physical functioning, breast symptoms, body image and psychological distress. These results will guide selections of key PRO domains and sample-size calculation of future studies.

The real-time intra-operative evaluation of sentinel lymph nodes in breast cancer patients using One Step Nucleic Acid Amplification (OSNA) and implications for clinical decision-making.

INTRODUCTION: One Step Nucleic Acid Amplification (OSNA) method for the intraoperative analysis of sentinel lymph nodes (SLNs) in breast cancer, obviates a second operation to the axilla and thereby expedites progression to adjuvant therapy. Recent NICE guidelines have approved OSNA as a method of sentinel node diagnosis to support the above case.(1) METHOD: This is a single centre prospective cohort analysis of all patients undergoing breast cancer surgery including sentinel node biopsy from February 2010 to June 2012. Patients with negative SLN(s) on OSNA had no further axillary surgery. A validation phase was performed prior to using OSNA routinely. Those with micrometastases underwent a level 1 clearance, and >one SLN with macrometastases, underwent treatment by level 2 axillary dissection. The length of time from sentinel node retrieval to OSNA result was recorded. RESULTS: Four hundred and forty nodes were analysed in 212 patients with a mean age of 55 years (range 24-98). The sensitivity and specificity of OSNA was 93% and 94% respectively in cases of macrometastases. The process required additional median anaesthesia time of 20 min (range -48 to +65 min). Non-sentinel node positivity was 5% and 48% for micrometastasis and macrometastasis respectively. CONCLUSION: OSNA identified 62 of 212 patients with at least one positive sentinel node, thereby sparing 29% from a second procedure to clear the axilla subsequently. The median waiting time of 20 min for node results from completion of breast procedure is acceptable and allows for an efficient operating list. OSNA can be incorporated into routine practice and with improved methods of imaging preoperatively, can be an excellent adjunct to the breast cancer patient pathway of care.

Randomized clinical trial on the effect of fibrin sealant on latissimus dorsi donor-site seroma formation after breast reconstruction.

BACKGROUND: Latissimus dorsi (LD) flap procedures comprise 50 per cent of breast reconstructions in the UK. They are frequently complicated by seroma formation. Fibrin sealants may reduce seroma volumes at the donor site. The aim was to investigate the effect of fibrin sealant (Tisseel(®)) on total seroma volumes from the breast, axilla and back (donor site) after LD breast reconstruction. Secondary outcomes were specific back seroma volumes together with incidence and severity of wound complications. METHODS: Consecutive women undergoing implant-assisted or extended autologous LD flap reconstruction were randomized to either standard care or application of fibrin sealant to the donor-site chest wall. All participants were blinded for the study duration but assessors were only partially blinded. Non-parametric methods were used for analysis. RESULTS: A total of 107 women were included (sealant 54, control 53). Overall back seroma volumes were high, with no significant differences between control and sealant groups over 3 months. Fibrin sealant failed to reduce in situ back drainage volumes in the 10 days after surgery, and did not affect the rate or volume of seromas following drain removal. CONCLUSION: This randomized study, which was powered for size effect, failed to show any benefit from fibrin sealant in minimizing back seromas after LD procedures.

Randomized clinical trial of the effect of quilting latissimus dorsi flap donor site on seroma formation.

BACKGROUND: Latissimus dorsi (LD) flap breast reconstruction is associated with a high incidence of donor site seromas, despite the use of surgical drains. The aim of this study was to evaluate the use of donor site quilting sutures, as well as drains, on the incidence, volume and frequency of seroma aspiration. METHODS: The trial randomized 108 women undergoing LD breast reconstruction to quilting procedures (54) or control group (52) for intention-to-treat analysis; two were excluded. Outcome measures were the incidence and volume of postoperative seroma. Secondary outcome measures included postoperative back pain, analgesic consumption, shoulder movement and duration of hospital stay. RESULTS: Quilting significantly reduced the overall incidence of seroma from 46 of 48 (96 per cent) to 43 of 52 (83 per cent) (P = 0.036), including the 38 women who had extended LD flap (with or without implants). There were further significant reductions in seroma volume (P = 0.004), frequency of aspiration (P = 0.001) and overall seroma volumes, including surgical drainage and symptomatic seromas (P = 0.013). Subset analyses for LD-implant (60 women) and extended LD (with or without implant) showed similar significance. Quilting did not affect back pain or compromise shoulder mobility. CONCLUSION: Quilting significantly reduced overall seroma volumes after LD breast reconstruction including extended LD, and is recommended in combination with surgical drains.

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS).

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS) is in progress. The study design, accrual to date, and related research projects are described. Revised accrual rates and expected recruitment are given. 15 cancers have been detected to date, from a total of 1236 screening measurements. This event rate and the tumour grades reported are compared with recent reports from other studies in women at high risk of breast cancer.

Comparison of the short-term biological effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer.

7Alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (ICI 182,780; Faslodex) is a novel steroidal antiestrogen. This partially blind, randomized, multicenter study compared the effects of single doses of long-acting ICI 182,780 with tamoxifen or placebo on estrogen receptor (ERalpha) and progesterone receptor (PgR) content, Ki67 proliferation-associated antigen labeling index (Ki67LI), and the apoptotic index in the primary breast tumors of postmenopausal women. Previously untreated patients (stages T(1)-T(3); ER-positive or -unknown) were randomized and received a single i.m. dose of ICI 182,780 50 mg (n = 39), ICI 182,780 125 mg (n = 38), or ICI 182,780 250 mg (n = 44) or oral tamoxifen 20 mg daily (n = 36) or matching tamoxifen placebo (n = 43) for 14-21 days before tumor resection surgery with curative intent. The ER and PgR H-scores, together with the Ki67LI were determined immunohistochemically in the matched pretreatment biopsy and the posttreatment surgical specimens. The apoptotic index was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling on the same samples. The effects of treatment on each of these parameters were compared using analysis of covariance. ICI 182,780 produced dose-dependent reductions in ER and PgR H-scores and in the Ki67LI. The reductions in ER expression were statistically significant at all doses of ICI 182,780 compared with placebo (ICI 182,780 50 mg, P = 0.026; 125 mg, P = 0.006; 250 mg, P = 0.0001), and for ICI 182,780 250 mg compared with tamoxifen (P = 0.024). For PgR H-score, there were statistically significant reductions after treatment with ICI 182,780 125 mg (P = 0.003) and 250 mg (P = 0.0002) compared with placebo. In contrast, tamoxifen produced a significant increase in the PgR H-score relative to placebo, and consequently, all doses of ICI 182,780 produced PgR values that were significantly lower than those in the tamoxifen-treated group. All doses of ICI 182,780 significantly reduced Ki67LI values compared with placebo (ICI 182,780 50 mg, P = 0.046; 125 mg, P = 0.001; 250 mg, P = 0.0002), but there were no significant differences between any doses of ICI 182,780 and tamoxifen. ICI 182,780 did not alter the apoptotic index when compared with either placebo or tamoxifen. Short-term exposure to ICI 182,780 reduces the ERalpha in breast tumor cells in a dose-dependent manner by down-regulating ER protein concentration. The reductions in tumor PgR content by ICI 182,780 demonstrate that ICI 182,780, unlike tamoxifen, is devoid of estrogen-agonist activity. Reductions in tumor cell proliferative activity (as indicated by Ki67LI) show that ICI 182,780 is likely to have antitumor activity in the clinical setting.

Fat necrosis of the female breast--Hadfield re-visited.

Examination of pathology records from three hospitals over an 8-year period identified 42 cases of primary fat necrosis of the female breast. The mean age of the women was 56 (range 24-85) and the lump was most commonly in the upper, inner quadrant of the breast having been present for a mean of 11 weeks (range 1-56). Twenty-one percent of patients gave a history of trauma which had occurred a mean of 69 weeks (range 3-208) previously. The mammograms gave an appearance of malignancy in 12 of the 22 cases where they were performed. Cytology was suspicious in five cases. Thirty-seven patients subsequently underwent wide local excision to confirm the diagnosis. The histology was re-examined by a pathologist and a subgroup of patients were identified who had fat necrosis associated with periductal mastitis. Two patients who had a core biopsy diagnosis of fat necrosis were found to have malignancy on wide local excision. Here we review the changes in presentation since the original description of the condition, and highlight that although this series reflects difficult cases, fat necrosis remains a condition which can still be difficult to diagnose.

Factors affecting surgical margin clearance in screen-detected breast cancer and the effect of cavity biopsies on residual disease.

One hundred and fourteen localization biopsies for screen-detected breast cancers were assessed for surgical margin clearance and presence of tumour in the cavity biopsies or subsequent resections. Inadequate surgical clearance (< or = 1 mm from the margin) in 88 patients was associated with high nuclear grade ductal carcinoma in situ, or extensive in-situ change accompanying invasive carcinomas, vs pure invasive carcinomas. Smaller localization biopsies (< or =50 g), larger tumours, and absence of a definite fine-needle aspiration cytological diagnosis of malignancy were also associated with inadequate excision. The radiographic characteristics of the tumours did not correlate with inadequate excision. Sixty-five patients had cavity biopsies taken at the time of surgery and 23 (35%) biopsies were positive, 20 of which were associated with incompletely excised tumours. Further excision in 78 patients yielded residual disease in 63%, most of whom had had inadequate surgical clearance. When cavity biopsies were taken with incompletely excised tumours, 15 of 88 subsequent resection specimens harboured residual disease compared with 29 of 88 without cavity biopsies. Although cavity biopsies increase the clearance margin, a negative cavity biopsy is not always an assurance of adequate excision.

Adjuvant chemotherapy for colorectal cancer.

Colorectal cancer is the second most common cancer in the Western world, and yet the survival after potentially curative excisional surgery has improved little over the last half century. Newer tumour prognostic markers are not superior to conventional Dukes' staging and there are currently no markers which predict response to chemotherapy. Adjuvant chemotherapy has had a chequered past, but recently a number of important prospective studies have demonstrated its proven benefit in patients with Dukes' stage C colorectal cancer. However, several issues still require clarification. (1) Do immunomodulators such as levamisole have a significant role in adjuvant chemotherapy? (2) Which patients derive most benefit from adjuvant chemotherapy? (3) Do prognostic markers have a role in predicting these patients? Approximately 30% of patients with Dukes' stage B cancers die of metastatic disease and the role of adjuvant chemotherapy in patients with these tumours seems worth exploring. Only a large randomised trial can give answers to these important questions. Such a trial would also encourage the widespread introduction of standard methods of surgical and pathological assessment.

Gynaecological cytology and pelvic ultrasonography in patients with breast cancer taking tamoxifen compared with controls.

The objective of this study was to look at the effect of tamoxifen on the endometrium by comparing gynaecological cervical and endometrial cytology in breast cancer patients on tamoxifen for 3 years compared with controls. In addition, pelvic ultrasonography was employed to detect ovarian abnormalities and to measure endometrial thickness. Patients followed-up after primary surgical therapy for breast cancer were invited for gynaecological assessment consisting of clinical examination pelvic ultrasonography and a cervical smear and endometrial sampling. The patients taking tamoxifen (n = 49) has been on adjuvant hormone therapy for a minimum of 3 years. Control patients (n = 45) were also being followed-up for breast cancer. On examination the tamoxifen patients had very similar clinical findings to the control patients with regard to the cervix (normal in 84% of tamoxifen takers compared to 87% of controls). The uterus was clinically enlarged in eight patients on tamoxifen and in none of the control patients (P = 0.006) and only one ovarian cyst was clinically detectable in a patient taking tamoxifen. Pelvic ultrasonography between the two groups of patients was not statistically different (chi 2 test) and ovarian cysts were noted in nine patients from each group (tamoxifen patients 18% vs control patients 20%, n.s.). There was a highly significant difference in endometrial thickness in premenopausal patients (9.2 mm) compared with postmenopausal patients (6.4 mm, P = 0.001). There was also a suggestion that endometrial thickness was greater in tamoxifen treated patients (P = 0.08). In general, a greater proportion of patients taking tamoxifen had cervical and endometrial cells exhibiting hyperplastic nuclei, and in endocervical smears, this difference achieved statistical significance (Mann-Whitney test, P = 0.046). These findings show that a significantly increased proportion of patients taking tamoxifen had endocervical nuclear hyperplasia, and a trend towards increased endometrial thickness. These findings confirm that tamoxifen has mild oestrogenic activity. However, the lack of any difference in the incidence of dysplasia suggests that the carcinogenic potential of tamoxifen on the uterus is very low and the beneficial effects of tamoxifen as an adjuvant therapy for breast cancer outweighs its theoretical risks.

The prognostic value of argyrophil nucleolar organiser regions (AgNORs) in colorectal cancer.

Argyrophil nucleolar organiser regions (AgNORs) are increased in a variety of malignant cells compared with normal cells, and a recent study has claimed that AgNORs have prognostic value in colorectal cancer. We have studied the AgNOR counts in tumours from 95 colonic resections performed in 94 patients in whom a minimum 5 year follow-up was available. In 71 pathological specimens adjacent normal mucosa was also examined. There was a significant difference between AgNORs per cell in normal mucosa (median 1.46, range 1.10-1.80) compared with tumour cells (median 1.92, range 1.42-2.95, P less than 0.001). There were no significant differences in average AgNORs per cell between tumours in each Dukes' stage or category of differentiation. The average AgNORs per cell in tumours of patients surviving disease-free for 5 years was the same as that in tumours of patients dying of colonic cancer recurrence. We conclude that AgNORs have no prognostic value in colorectal cancer and are not correlated with Dukes' staging or differentiation of the tumour.