Skin-sparing mastectomy and immediate breast reconstruction in the management of locally recurrent breast cancer.

AIM: To investigate whether skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) is a possible treatment option in selected cases of locally recurrent breast cancer after previous breast-conserving therapy (BCT). MATERIAL AND METHODS: Sixty consecutive patients were treated by SSM and IBR between 1995 and 2008 for ipsilateral breast tumour recurrence (IBTR). Selection criteria consisted of: IBTR <3 cm size, not infiltrating skin or chest wall, primarily node negative, recurrence >3 years after primary operation, and no metastases. Patient records were analysed retrospectively and follow-up data on patient outcome included. RESULTS: The reconstruction method consisted of 40 free abdominal flaps, 18 latissimus dorsi (LD) flaps with or without an implant, and two cases of implant only. Twenty-three patients received adjuvant oncological therapy. During median follow-up of 66 months, 11 patients (18%) developed disease relapse, including 6 (10%) local re-recurrences. CONCLUSION: IBR is a possible treatment option for patients who develop local recurrence following earlier BCT. Our local re-recurrence rate of 10% compares well with that following salvage mastectomy for IBTR. Of patients, 43% did not actually meet our selection criteria but yet appeared to fare well in terms of outcome. Therefore we should re-evaluate our selection criteria.

USAXS and SAXS from cancer-bearing breast tissue samples.

USAXS and SAXS patterns from cancer-bearing human breast tissue samples were recorded at beamline ID02 of the ESRF using a Bonse-Hart camera and a pinhole camera. The samples were classified as being ductal carcinoma, grade II, and ductal carcinoma in situ, partly invasive. The samples included areas of healthy collagen, invaded collagen, necrotic ducts with calcifications, and adipose tissue. The scattering patterns were analyzed in different ways to separate the scattering contribution and the direct beam from the observed rocking curve (RC) of the analyzer. It was found that USAXS from all tissues was weak, and the effects on the analyzer RC were observed only in the low-intensity tails of the patterns. The intrinsic RC was convolved with different model functions for the impulse response of the sample, and the best fit with experiment was obtained by the Pearson VII function. Significantly different distributions for the Pearson exponent m were obtained in benign and malignant regions of the samples. For a comparison with analyzer-based imaging (ABI) or diffraction enhanced imaging (DEI) a "long-slit" integration of the patterns was performed, and this emphasized the scattering contribution in the tails of the rocking curve.

The prevalence of and risk factors for four or more metastatic axillary lymph nodes in breast cancer patients undergoing sentinel node biopsy.

BACKGROUND: Our aim was to investigate the prevalence of and risk factors for having four or more positive axillary lymph nodes among breast cancer patients undergoing sentinel node (SN) biopsy. PATIENTS AND METHODS: Between February 2005 and July 2007, 1,062 breast cancer patients with the clinical tumour size not larger than 3 cm underwent SN biopsy and axillary clearance (AC), when SN was positive. These patients were identified in a prospectively collected database. RESULTS: Four or more positive axillary nodes were detected in 68 patients representing 6% of the entire study population and 16% of the 436 node positive cases. Features regarded as predictive for a very low risk included (1) T1a or T1b tumours, (2) grade I tumours, (3) tumours with a favourable subtype, that is mucinous, tubular or medullary breast cancer, (4) no nodal macrometastases and (5) SN ratio lower than 0.5. CONCLUSIONS: Only few patients with T1a-b tumours or grade 1 tumours, as well as those with minimal involvement of the sentinel nodes have four or more positive axillary lymph nodes. However, these risk factors can be definitely assessed only after surgery, decreasing their value in the clinical decision making.

The DNA damage signalling kinase ATM is aberrantly reduced or lost in BRCA1/BRCA2-deficient and ER/PR/ERBB2-triple-negative breast cancer.

The ataxia-telangiectasia-mutated (ATM) kinase is a key transducer of DNA damage signals within the genome maintenance machinery and a tumour suppressor whose germline mutations predispose to familial breast cancer. ATM signalling is constitutively activated in early stages of diverse types of human malignancies and cell culture models in response to oncogene-induced DNA damage providing a barrier against tumour progression. As BRCA1 and BRCA2 are also components of the genome maintenance network and their mutations predispose to breast cancer, we have examined the ATM expression in human breast carcinomas of BRCA1/2 mutation carriers, sporadic cases and familial non-BRCA1/2 patients. Our results show that ATM protein expression is aberrantly reduced more frequently among BRCA1 (33%; P=0.0003) and BRCA2 (30%; P=0.0009) tumours than in non-BRCA1/2 tumours (10.7%). Furthermore, the non-BRCA1/2 tumours with reduced ATM expression were more often estrogen receptor (ER) negative (P=0.0002), progesterone receptor (PR) negative (P=0.004) and were of higher grade (P=0.0004). In our series of 1013 non-BRCA1/2 cases, ATM was more commonly deficient (20%; P=0.0006) and p53 was overabundant (47%; P<0.0000000001) among the difficult-to-treat ER/PR/ERBB2-triple-negative subset of tumours compared with cases that expressed at least one of these receptors (10 and 16% of aberrant ATM and p53, respectively). We propose a model of 'conditional haploinsufficiency' for BRCA1/2 under conditions of enhanced DNA damage in precancerous lesions resulting in more robust activation and hence increased selection for inactivation or loss of ATM in tumours of BRCA1/2 mutation carriers, with implications for genomic instability and curability of diverse subsets of human breast cancer.

Late results of skin-sparing mastectomy followed by immediate breast reconstruction.

BACKGROUND: Skin-sparing mastectomy (SSM) facilitates optimal immediate breast reconstruction (IBR) by preserving the inframammary fold and most of the breast skin. Concerns persist that SSM might increase the rate of local recurrence as the surgical approach is less extensive. Patients who had SSM and IBR over 10 years at a single institution were reviewed. METHODS: A total of 207 consecutive women who underwent SSM and IBR from 1992 to 2001 were included in the study. The patient records were analysed retrospectively and follow-up data were included. RESULTS: Postoperative complications included native skin flap necrosis (10.1 per cent), haematoma (10.6 per cent), infection (3.4 per cent), anastomotic thrombosis (5.3 per cent) and hernia (2.6 per cent). During a mean follow-up of 70 months, 5.8 per cent of patients with stage 0-2 disease developed a locoregional recurrence, although none of these later had a systemic recurrence. The rate of locoregional recurrence was 31 per cent (five of 16) in women with stage 3 breast cancer. CONCLUSION: SSM followed by IBR was both surgically and oncologically safe, especially for early-stage breast cancer.

Local recurrence of stage 1 and 2 breast cancer after skin-sparing mastectomy and immediate breast reconstruction in a 15-year series.

AIMS: Since the introduction of skin-sparing mastectomy (SSM) in 1991 concerns on local control and recurrence rates have been discussed in the literature. The aim of this study is to examine in particular incidence of local recurrence in a 15-year consecutive series of breast cancer patients having undergone SSM and immediate breast reconstruction (IBR) at a single population-based institution. METHODS: One hundred and forty-six consecutive patients with either stage 1 or 2 breast cancer who underwent SSM followed by IBR from 1992 to 2006 were included in this study. A retrospective review of patient records was conducted. RESULTS: During a mean follow-up time of 51 months, four local recurrences of the native breast skin were accounted for. In addition, three regional lymph node recurrences and four systemic recurrences took place. All of the local and regional recurrences were handled by salvage surgery followed by adjuvant oncological therapies. During a mean follow-up of 35 months after the detection and treatment of the locoregional recurrences none of the patients developed new recurrences. CONCLUSIONS: Our present study concludes that SSM followed by IBR seems oncologically sound procedure for stage 1 and 2 breast cancer patients. In addition, local recurrences and regional lymph node recurrences are not always associated with systemic relapse.

Sentinel node biopsy with intraoperative diagnosis in patients undergoing skin-sparing mastectomy and immediate breast reconstruction.

AIMS: False negative cases in the intraoperative assessment of sentinel node (SN) metastases in breast cancer prompt for a secondary axillary lymph node dissection (ALND). Such ALND is technically demanding and prone to complications in patients with immediate breast reconstruction (IBR) if there is a microvascular anastomosis or the thoracodorsal pedicle of a latissimus dorsi flap in the axilla. This study aims to evaluate the feasibility of the intraoperative diagnosis of sentinel node biopsy (SNB) in breast cancer patients undergoing IBR. METHODS: Sixty-two consecutive breast cancer patients undergoing SNB with the intraoperative diagnosis of SN metastases simultaneously with mastectomy and IBR between 2004 and 2006 were included in this study. Results of the SNB and especially the false negative cases in the intraoperative diagnosis were evaluated. RESULTS: Eleven patients had tumor positive SN. Nine of these cases were detected intraoperatively. The two false negative cases in the intraoperative diagnosis constituted of isolated tumor cells only. CONCLUSIONS: Our present study suggests that SNB with intraoperative diagnosis of SN metastases is feasible in patients undergoing IBR if the risk of nodal metastasis is low and the sensitivity of intraoperative SNB diagnosis is high.

Guidelines on the standards for the training of specialised health professionals dealing with breast cancer.

According to EUSOMA position paper 'The requirements of a specialist breast unit', each breast unit should have a core team made up of health professionals who have undergone specialist training in breast cancer. In this paper, on behalf of EUSOMA, authors have identified the standards of training in breast cancer, to harmonise and foster breast care training in Europe. The aim of this paper is to contribute to the increase in the level of care in a breast unit, as the input of qualified health professionals increases the quality of breast cancer patient care.

A second radioisotope injection enhances intraoperative sentinel node identification in breast cancer patients without visualized nodes on preoperative lymphoscintigraphy.

PURPOSE: To evaluate the influence of a second radioisotope injection on the intraoperative success rate in patients with non-visualized axillary sentinel nodes (SN). MATERIAL AND METHODS: Altogether, 534 consecutive breast cancer patients with lymphoscintigraphy (LS) and SN biopsy and were included. An intratumoral injection of 99mTc-labeled human albumin colloid with a median dose of 93 MBq was applied. Forty-two of the 80 patients without axillary hot spots on LS received a second tracer injection with a median dose of 70 MBq. RESULTS: The visualization rate of axillary SN was 454/534 (85%). The intraoperative SN identification rate was 97% in patients with and 69% in patients without visualized SN in the axilla (P<0.00005), but the success rate was higher (88%) with a second radioisotope injection than without it (47%; P<0.0002). CONCLUSION: The failure rate in intraoperative SN identification was minimized using a second radioisotope injection in patients without axillary SN on LS.

Adjusting the radioisotope tracer dose according to the body mass index does not enhance the visualization of axillary sentinel lymph nodes.

PURPOSE: To investigate whether the visualization of axillary sentinel nodes (SN) in the lymphoscintigraphy (LS) can be enhanced by adjusting the amount of radioactivity in accordance with the patient's body mass index (BMI). MATERIAL AND METHODS: Group I consisted of 356 consecutive breast cancer patients who underwent LS and SN biopsy after a single, intratumoral radioactive tracer injection with a median dose of 92 MBq. In group II (178 consecutive patients), the dose of the tracer was adjusted according to BMI; 80, 100, or 140 MBq. RESULTS: The visualization rate of axillary SN was 86% in group I and 83% in group II (P = 0.303). In patients with BMI >30 with visualized axillary SN, the median number of SN was 1 (1-4) in group I and 3 (1-7) in group II (P = 0.002). CONCLUSION: Adjusting the tracer dose in accordance with patient BMI did not enhance the visualization rate of axillary SN in LS.

Tumour-positive sentinel node findings in patients with ductal carcinoma in situ.

BACKGROUND: Our aim was to evaluate the prevalence of and risk factors for tumour-positive sentinel node (SN) findings in patients with ductal carcinoma in situ (DCIS). METHODS: Altogether 1,470 patients underwent sentinel node biopsy (SNB) between April 2001 and March 2005 in our unit. According to a histopathological review, 11 of them had microinvasive and 74 pure DCIS and were included in the study. RESULTS: Five patients (7%) with pure DCIS had SN metastases. Three of them had isolated tumour cells (ITC) only. Axillary clearance without further metastatic findings was performed in three patients. The median histological size of DCIS was larger, 50 (45-60) mm in patients with metastatic SN findings than the median of 18 (2-110) mm in those with tumour-negative SN, P=0.0103. All five patients with metastatic SN findings underwent mastectomy. Metastatic SN findings were detected in one (9%) patient with microinvasive DCIS. CONCLUSIONS: Metastatic SN findings in patients with pure DCIS may be a sign of missed invasion.

The prevalence of axillary lymph-node metastases in patients with pure tubular carcinoma of the breast and sentinel node biopsy.

AIMS: We aimed to evaluate the prevalence of and the risk factors for axillary lymph-node metastases in pure tubular carcinoma (PTC) of the breast. The role of axillary staging and treatment in PTC was also evaluated. METHODS: Between March 2001 and August 2004, 33 PTC patients underwent sentinel node (SN) biopsy as a part of their surgical treatment. Level I/II axillary clearance was carried out in case of tumour positive SN findings. To confirm the correct histological diagnosis (PTC, >90% tubular component), the breast tumours were reviewed by an expert breast pathologist. RESULTS: The SN were successfully harvested in all patients. The median number of SN harvested in the axilla was 3 (range 1-10). Nine (27%) of the 33 patients had axillary nodal metastases. The median number of metastatic nodes was 1 (range 1-3). The median size of the SN metastases was 0.5 mm (mean 1.7 mm, range 0.4-5 mm). In six patients, micrometastases were the only tumour positive SN findings. The median histological tumour size was similar, 9 vs 10mm, in patients with or without axillary metastases. The median patient age was 54 (range 44-71) and 57 (range 39-80) years, respectively. After the histopathological review, six of the 27 patients with true PTC had axillary metastases. The review did not significantly change the risk factors for axillary metastases. CONCLUSIONS: Every fourth PTC patient has axillary lymph-node metastases, most often micrometastases. SN biopsy appears as a feasible method for axillary staging in PTC patients.

The consequences of long-time arm morbidity in node-negative breast cancer patients with sentinel node biopsy or axillary clearance.

BACKGROUND: The aim was to evaluate long-time morbidity in breast cancer patients 3 years after sentinel node biopsy (SNB) or axillary clearance (AC) emphasizing the consequences of morbidity like work-related events and the need of physiotherapy. PATIENTS AND METHODS: Morbidity was evaluated in 92 breast cancer patients 3 years after SNB only and in 47 patients after AC using a questionnaire. The circumferences of the upper extremities and the range of the shoulder movements were also measured. RESULTS: Two SNB and eight AC patients were not able to use the ipsilateral upper extremity to former extent P < 0.005. One SNB and one AC patient were retired or on a long-time sick leave because of arm morbidity. Clinically apparent upper extremity lymphoedema was observed in one SNB patient and in six AC patients, P < 0.005. Two SNB patients had received manual lymph drainage, one of them because of breast oedema. Seven patients had received manual lymph drainage after AC, three of them wore also compression sleeve, P < 0.05 between AC and SNB. CONCLUSIONS: The risk of remarkable long-time arm morbidity after SNB is minimal. Work-related events seem uncommon due to arm morbidity, regardless of the extent of axillary surgery.

Sentinel node biopsy is not sensible in breast cancer patients with large primary tumours.

AIMS: We aimed to evaluate the outcome of sentinel node biopsy (SNB) in breast cancer patients with large primary tumours. METHODS: Nine hundred and eighty-four patients with invasive breast cancer and SNB were studied. The histological tumour size was larger than 3 cm in 70 patients. The advantages of SNB like avoiding axillary clearance (AC) or more accurate staging by detecting micrometastases or parasternal sentinel node metastases were evaluated in relation to the tumour size. RESULTS: Axillary metastases were detected in 351/914 patients with a tumour size of 3 cm or smaller and in 50/70 patients with larger tumours (p<<0.0001). Micrometastases or isolated tumour cells only, were observed in 134/351 node positive patients with tumours not larger than 3 cm and in 10/50 cases with larger tumours (p=0.022). Parasternal sentinel node metastases were detected in 17/914 patients with a tumour size of 3 cm or smaller and 2/70 patients with larger tumours (p=ns). AC was omitted because of tumour negative sentinel node findings 168 of the 232 patients with stage T1 a-b tumours and 281 of those 489 with T1c tumours. Twenty of the 70 patients with tumours larger than 3 cm avoided AC. CONCLUSIONS: SNB is not sensible in breast cancer patients with tumours larger than 3 cm, because of the small proportion avoiding AC after SNB.

One-year morbidity after sentinel node biopsy and breast surgery.

Posttreatment morbidity within 1 year after sentinel node biopsy was evaluated objectively by physical examination and also by evaluating patients self-reports of symptoms in a questionnaire. These patients were compared with patients who underwent axillary clearance. At 2 weeks after surgery patients who had undergone sole sentinel node biopsy had made significantly better recoveries than those who had undergone axillary clearance. Although every fourth patient complained of at least mild arm symptoms 1 year after sole SNB, the risk of severe long-term morbidity is minimal. In particular, the risk of disabling lymphoedema seems to be negligible after SNB only.

The prevalence of non-sentinel node metastases in breast cancer patients with sentinel node micrometastases.

AIMS: The aim of the study was to estimate the prevalence of and risk factors for non-sentinel node (NSN) involvement in breast cancer patients with sentinel node (SN) micrometastases. METHODS: Eighty-four patients with SN micrometastases were included. Both the SN and NSN were examined using serial sectioning and immunohistohemistry. Various indices were evaluated as possible risk factors for NSN involvement. RESULTS: NSN involvement was found in 22/84 patients. The median size of the NSN metastases was 1.25 mm (0.01-12 mm). The NSN metastases were larger than 2 mm in 8 patients and smaller than 0.2 mm in 6 patients. NSN involvement was observed in 14/35 patients with metastatic findings in all removed SN. Three of the 23 patients with 2 or 3 tumour negative SN had NSN metastases. None of the 12 patients with 4 or more uninvolved SN had NSN metastases. NSN involvement could not excluded by other patient, tumour or sentinel node related factors. CONCLUSIONS: Every fourth patient will have residual disease in the axilla, 10% even large metastases, if axillary clearance is omitted in patients with SN micrometastases. The risk of NSN involvement seems negligible in patients with a single SN micrometastasis and four or more healthy SN harvested.

Towards reasonable workload in diagnosis of sentinel lymph nodes: comparison of two frozen section methods.

AIMS: To compare two methods of histological assessment with intraoperative diagnosis of sentinel node metastases in breast cancer. METHODS AND RESULTS: A total of 204 consecutive breast cancer cases with lymphatic mapping, sentinel node biopsy and intraoperative diagnosis were included. The sentinel nodes in the first 102 cases (method A) were bisected and serially sectioned. In the other 102 cases (method B) the nodes were sliced thinly with a razor blade. All 1-1.5 mm thick slices were mounted on prechilled mounting medium on frozen section buttons. Cytological imprints were also made of the attached tissue slices. Postoperative diagnosis of sentinel lymph node metatases was taken as gold standard. Sentinel node metastases were found in 28 (27%) cases in group A and in 42 (40%) cases in group B (P = 0.05). The median size of the sentinel node metastases was 4.3 mm in group A and 3.3 mm in group B (P < 0.05). CONCLUSION: Method B finds more and smaller metastases and takes less time and effort in the laboratory. When using method A, many small metastases are not detected at all.

Safety of immediate breast reconstruction.

The benefits of immediate breast reconstructions (IBR) compared with late reconstructions are one operation instead of two and excellent aesthetic result with the skin-sparing mastectomy technique. Indications for mastectomy vary from risk reduction of healthy women to preinvasive, invasive and locally recurrent breast cancer. IBR has been successfully performed in all of these patient groups and local control has been comparable with the series treated with breast conservation or mastectomy without reconstruction. We review this literature and discuss patient selection, the use of skin-sparing mastectomy, possibilities of nipple conservation and limitations with the use of implants. Cooperation of multidisciplinary breast cancer teams is needed to tailor the treatment of breast cancer for each individual patient. To define guidelines for the use of IBR, multicentre studies with follow-up data of large enough series stratified by patient, tumour and treatment characteristics are needed.

The sensitivity of axillary staging when using sentinel node biopsy in breast cancer.

AIMS: We aimed to study factors, which enhance the sensitivity of sentinel node biopsy. METHODS: Three hundred and sixty-three clinically node negative breast cancer patients with successful sentinel node biopsy were studied. All focally radioactive and/or blue nodes in the axilla were harvested. All palpably suspicious lymph nodes were also removed for a similar histological evaluation. RESULTS: Sentinel node metastases were found in 129 patients. The metastasis was detected in the three first retrieved sentinel nodes in 126 cases and in the fourth or fifth node in three cases. The 'hottest' sentinel node was not the involved one in 18 cases. Five patients with tumour negative sentinel nodes had metastases in other palpably suspicious nodes. CONCLUSIONS: Harvesting all focally radioactive and/or blue nodes and other palpably suspicious nodes minimises the false negative rate in sentinel node biopsy. Removal of more than five nodes does not significantly improve the sensitivity of axillary staging.

Immediate breast reconstruction.

Immediate breast reconstruction (IBR) in conjunction with mastectomy for cancer or high risk of breast cancer is safe from an oncological point of view. The cosmetic outcome can be excellent, especially when performing mastectomy by sparing the skin of the breast and reconstructing the breast mound with autogenous tissue. The majority of women at their working age are willing to have their breast reconstructed. Patients with newly diagnosed cancer undergoing major surgery need extra support compared with those undergoing late reconstructions. Immediate reconstructions with one operation, one hospital stay and one sick leave are economically favourable by diminishing the demand of delayed reconstructions. Preference in patient selection for IBR should be in patients with good prognoses like those with diffuse non-invasive cancer and those with a considerable risk to develop breast cancer. Women with axillary-node negative invasive cancer and women with late local recurrences in a breast earlier conservatively treated are also suitable for IBR. If needed, oncological treatments can be given after IBR, although radiotherapy after pure implant reconstructions is not recommended. In order to give all eligible patients an equal opportunity to have IBR, treatment of breast patients should be centralised to hospitals with a team comprising breast cancer surgeons, pathologists, radiologists, and plastic surgeons.