Survival in breast cancer after nipple-sparing subcutaneous mastectomy and immediate reconstruction with implants: a prospective trial with 13 years median follow-up in 216 patients.

AIM: Validation of the oncological safety of nipple-sparing subcutaneous mastectomy and immediate reconstruction with implants (NSM) and of the outcome in patients with locoregional recurrences (LRRs) after this procedure. METHODS: Two-hundred and sixteen patients, mean age of 52.8 (29-81) years with primary unilateral breast cancer, not suitable for partial mastectomy because of large (>3cm) or multifocal carcinoma, underwent NSM, a single procedure lasting about 1h 30min, between December 1988 and September 1994. Lymph node metastases were found in 40.3% of the patients, and 47 patients received radiotherapy (RT) postoperatively. All patients were monitored for at least 11.6 years or as long as they lived. Median follow-up was 13 years. The end-points were locoregional recurrence (LRR) or distant metastases (DM) as first events, disease-free survival (DFS) and overall survival (OS). RESULTS: Specificity at frozen section from sub-areolar tissues was 98.5%. LRR occurred in 52 patients and DM in 44 patients. DFS was 51.3% and OS was 76.4%. The frequency of LRR was 8.5% among irradiated and 28.4% among non-irradiated patients (p=0.025). These results compare well with results after conventional mastectomy in other trials. All patients were monitored for at least 6 years after the occurrence of LRR, finding 5 years freedom from further LRR or DM of 60% and OS of 82%. CONCLUSIONS: NSM is an oncologically safe procedure and could be offered to most patients with breast cancer unsuitable for sector resection only. RT effectively lowers the frequency of LRR. The occurrence of LRR after this operation does not significantly affect OS.

Capsular contracture around saline-filled and textured subcutaneously-placed implants in irradiated and non-irradiated breast cancer patients: five years of monitoring of a prospective trial.

One hundred and seven breast cancer patients underwent subcutaneous mastectomy and immediate reconstruction with a subcutaneously-placed, round, saline-filled prosthesis with a textured surface. The primary aim of this prospective study was to determine the frequency of capsular contracture in both irradiated and non-irradiated breasts after this operation. Two different types of round implants with different pore sizes on their textured surfaces, Siltex and Microcell, were randomly chosen. Twenty-four patients received radiotherapy within the first year following the operation. Capsular contracture was measured by the Baker/Palmer classification and by applanation tonometry at regular intervals for 5 years or as long as the patients lived (median 60 months). Twenty-two patients (20.6%) developed capsular contracture, defined as Baker three or four. Sixteen of those were reoperated, 15 with open capsulotomy with or without implant exchange, one with closed compression capsulotomy, and monitored thereafter for 5 years or until death (median 60 months). All 107 patients could be monitored for 2 years, while 87 reported for the 5-year follow-up. The rate of capsular contracture was significantly higher (p=0.01) for irradiated breasts than for non-irradiated ones, 41.7 and 14.5%, respectively. It was slightly higher (p<0.05) for large-pore implants than for those with smaller (and more numerous) pores. There was a good correlation between the two different methods for measuring capsular contracture. None of the 16 reoperated patients had a recurrence of capsular contracture within 5 years. The results indicate a high rate of capsular contracture after this operation, especially when followed by radiation. However, a fairly simple procedure to treat capsular contracture seems to give good long-term results.

A whole genome association study in Finnish multiple sclerosis patients with 3669 markers.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with complex genetic background. In the present study, based in the Finnish population, we typed a large number of microsatellite markers in separately pooled DNA samples from 195 MS patients and 205 controls. A total of 108 markers showed evidence of association. Five genomic regions containing two or more of these markers within a 1-Mb interval were identified, 1q43, 2p16, 4p15, 4q34 and 6p21 (the MHC region). Substantial overlap with previously published linkage genome screens is also seen.

Fluid retention in Bioplasty Misti Gold II breast prostheses with development of capsular contracture.

We compared the incidence of capsular contracture in an implant (Bioplasty Misti Gold II) which has a textured surface and is filled with polyvinyl-pirrolidone (PVP)-hydrogel, with that in saline-filled implants with textured surfaces when the implants are placed subcutaneously during immediate reconstruction after subcutaneous mastectomy. In 41 patients, mean age 55 years (range 30-81), with breast cancer that was not suitable for breast conservation, 20 patients had 22 Misti Gold II prostheses inserted (two patients bilaterally) and 21 patients had saline-filled prostheses (one patient bilaterally). The development of capsular contracture was assessed using Baker's classification and applanation tonometry. Fourteen patients with Misti Gold II implants were classified one year postoperatively as Baker 2 and 3 compared with five with saline-filled implants (p = 0.01). On applanation tonometry 16 of the Misti Gold II group had an operative:postoperative ratio of < or = 0.75, compared with 50% in the saline-filled group (p = 0.096). In the 12 Misti Gold II prostheses that were removed because of capsular contracture between 13-40 months postoperatively, the volume in the prostheses had increased by 48%. The poor results obtained with the Misti Gold II prosthesis can be explained by the volume that they gained after implantation as a result of osmosis.

The patched/hedgehog/smoothened signalling pathway in human breast cancer: no evidence for H133Y SHH, PTCH and SMO mutations.

The patched/hedgehog/smoothened signalling pathway has been implicated in the development of sporadic tumours associated with the naevoid basal cell carcinoma (Gorlin) syndrome (NBCCS). Mutations in sporadic basal cell carcinomas (BCCs) of the skin and medulloblastomas have been found in genes encoding all three proteins of the pathway. A substantial proportion of breast carcinomas has recently been suggested to contain missense mutations in the human patched (PTCH) and sonic hedgehog (SHH) homologues. However, an independent study showed that the implicated mutation in SHH (H133Y) was absent in a large number of BCCs, medulloblastomas, breast, ovary and colorectal tumours. We searched for the H133Y SHH mutation in 84 primary breast carcinomas, but did not detect this change in any sample. In addition, a subset of 45 primary breast tumours was analysed for mutations in the PTCH coding region and 48 samples in previously implicated exons of human smoothened, but no mutations were found. Although our results do not exclude the presence of clonal alterations of these genes in a small proportion of breast carcinomas, these data do not support the existence of frequent mutations in genes encoding major protein partners of this signalling pathway. The absence of nucleotide changes in PTCH may point to another linked gene in the chromosome region 9q22-q23, previously suggested to contain a breast cancer susceptibility gene.

Refinement of the LOH region 1 at 11q23.1 deleted in human breast carcinomas and sublocalization of 11 expressed sequence tags within the refined region.

Loss of constitutive heterozygosity at 11q23 has been detected in various human solid tumors. Here, we described the analysis of a series of normal and tumor pairs from 110 breast carcinomas for the presence of loss of heterozygosity at 11q23 loci. The overall frequency of LOH was 48%, confirming the importance of deletions at 11q23 in breast tumorigenesis. Previously, we have identified two independent regions of LOH at 11q23, the LOH region 1 at 11q23.1 and the LOH region 2 at 11q23.3. The most telomeric region was recently refined between loci D11S1345 and D11S1316, a region of about 1 Mb. However, the LOH region 1, most centromeric, was still not finely refined: the boundaries were defined by loci D11S2000 and D11S897, separated by about 8 Mb. Here, we refined its boundaries between loci D11S1347 and D11S927, a region of about 2 Mb. We have mapped 11 expressed sequence tags (ESTs) within this region and excluded another 20. This study represents a further step toward the identification of the putative tumor suppressor gene found within the LOH region 1 at 11q23.1.

The influence of radiotherapy on skin circulation of the breast after subcutaneous mastectomy and immediate reconstruction.

The skin circulation was measured in 43 breast cancer patients following subcutaneous mastectomy and immediate reconstruction with a prosthesis, at least 1 year after radiotherapy (46 Gy) following surgery (19 patients) or if no radiotherapy was given, at least 1 year postoperatively (24 patients). The skin circulation was measured by laser Doppler fluxmetry (LDF) and fluorescein flowmetry within three areas: 2 cm above the border of the areola, within the nipple-areola complex, and 2 cm below the border of the areola. The results show that there was no reduction in skin circulation. On the contrary LDF and fluorescein flowmetry showed in the operated breast an increased circulation in the nipple-areola complex in the irradiated breast compared with the non-irradiated by 26% and 30%, respectively (P < 0.05). The results indicate that radiotherapy following subcutaneous mastectomy and immediate reconstruction with a prosthesis does not lead to long-term reduction in basal skin circulation in the breast.

Touch sensibility in the breast after subcutaneous mastectomy and immediate reconstruction with a prosthesis.

Touch sensibility was assessed with von Frey's monofilaments in the breasts of 10 healthy women (controls) and of 80 women with breast cancer who at least 1 year previously had undergone subcutaneous mastectomy and immediate reconstruction with a prosthesis. Touch thresholds were measured at nine positions on each breast. Low threshold values (< 3.2 mN) and good reproducibility were found in the controls. In the patients' surgically treated breasts normal (< 3.2 mN) or subnormal (< 20 mN) median threshold values were found outside the areola. Higher median values were noted on the areola and nipple; on the nipple, however, one third of the patients had normal sensibility while 14% lacked sensibility. The only factors found to influence the results were simultaneous subcutaneous reduction mammaplasty (lower touch thresholds) and the localisation of the incision (slightly lower thresholds for lazy-S than inframammary incision). These results confirm the clinical impression that touch sensibility is substantially retained after subcutaneous mastectomy and immediate reconstruction with a prosthesis.

Influence of radiation therapy on skin circulation in the breast after breast conservative surgery.

It is not known whether the skin circulation is altered in the long term by radiotherapy following breast conservative surgery. The skin circulation in the breast was therefore measured in 24 breast cancer patients (mean age 57 years; range 40-76), one year after radiotherapy (50 Gy) following lumpectomy. None of the patients showed any persistent redness of the skin. The skin circulation was measured using laser Doppler fluxmetry (LDF) and fluorescein flowmetry within three areas: 2 cm above the border of the areola (position 1), within the nipple areola complex (position 2) and 2 cm below the border of the areola (position 3). It was found that when measured with LDF, the skin circulation expressed as the ratio of operated irradiated to non-operated non-irradiated breast was 0.99 in position 1, 1.07 in position 2 and 0.91 in position 3; and when measured by fluorescein flowmetry, 1.00 in position 1, 1.08 in position 2 and 1.00 in position 3. The results indicate that radiotherapy following breast conservative surgery does not lead to long-term changes in basal skin circulation in the breast.