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.

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.

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.

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.

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.

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.

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.

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.

Histochemical examination of energy metabolism in aortic vein grafts in rats.

The duration of the presumed metabolic depression of syngeneic vena cava to aorta transplants was determined in rats and the site and type of energy metabolism in the vein grafts assessed. The aerobic metabolic activity was measured from the histochemical reactivity of the enzymes, succinate dehydrogenase and cytochrome oxidase, and the anaerobic activity by staining with lactate dehydrogenase. The activity of the hexose-monophosphate shunt was assessed by the histochemical demonstration of glucose-6-phosphate dehydrogenase. Sixteen hours after grafting a pronounced metabolic depression was noted. Recovery occurred 24 hours after transplantation. The most intense staining was from lactate dehydrogenase in the vein grafts and in the non-transplanted veins. At the end of the observation period of four months the grafts were definitely more strongly stained than the non-transplanted veins, with most of the activity in the thickened intima. This layer had a metabolic profile resembling that of the media of the adjacent aorta.

The prognostic value of insulin-like growth factor-I in breast cancer patients. Results of a follow-up study on 126 patients.

The insulin-like growth factor-I is an important mitogen and has a growth promoting property, especially in breast cancer. This work analyses the prognostic value of the insulin-like growth factor receptor-I (IGFR-I), which belongs to the group of membrane receptors for growth factors. The study included 126 patients. 49 patients (39%) were IGFR positive (> or = 4.0%). There was a significant correlation between IGFR and oestrogen receptor (ER) status (P = 0.001), but not between IGFR and progesterone receptor status (PR; P = 0.07). There was no correlation between node status and IGFR. The expression of IGFR had a strong significance in the disease-free analysis (P = 0.0108). The IGFR status was not of predictive value in the node-negative subgroup (64 patients). Within the ER-negative group, the disease-free analysis further stratified with IGFR revealed that patients with IGFR-positive and ER-negative cancers are in a worse situation than IGFR-negative ER-negative cancer patients (P = 0.01).

Expression of tenascin-C in intraductal carcinoma of human breast: relationship to invasion.

Tenascin-C (Tn-C) is an extracellular matrix glycoprotein that appears in areas of epithelial-mesenchymal interaction during fetal development and in neoplasia. The immunohistochemical expression of Tn-C and its relationship to histology, nuclear grade, microinvasion, oestrogen (ER) and progesterone receptors (PR), and to cell proliferation measured by Ki-67 expression were studied in 89 intraductal breast carcinomas (DCIS). Periductal Tn-C was noted in 87% and stromal Tn-C in 25% of the tumours. Stromal expression was associated with moderate to strong periductal expression and microinvasion. Periductal expression was associated with comedo-type, nuclear grade, microinvasion, Ki-67 expression, and lack of PR. The distribution of Tn-C was compared in DCIS and in the intraductal component from another series of small axillary node-negative invasive breast carcinomas (n = 44). Tn-C was present in the stroma of pure DCIS in 25% and in the intraductal component of the other series in 82%. Thus, stromal or moderate to strong periductal Tn-C expression in DCIS may relate to early invasion. DCIS with weak periductal or missing Tn-C expression may be a subgroup with benign behaviour.

Wound tissue oxygen tension predicts the risk of wound infection in surgical patients.

OBJECTIVE: To test the hypothesis that subcutaneous wound oxygen tension (PsqO2) has a predictive relation to the development of wound infection in surgical patients. DESIGN: A noninterventional, prospective study. SETTING: A university department of surgery. PATIENTS: One hundred thirty operative general surgical patients at notable risk of infection as predicted by an anticipated Study on the Effect of Nosocomial Infection Control (SENIC) score of 1 or greater. OUTCOME MEASURES: PsqO2 was measured perioperatively. Its relation to the subsequent incidence of surgical wound infection was then determined and compared with the SENIC score as a criterion standard. RESULTS: Although the SENIC score and PsqO2 are inversely correlated, PsqO2 is the stronger predictor of infection. Low PsqO2 identified patients at risk and concentrated them in a cohort that was about half the size of that identified by the SENIC score. CONCLUSIONS: Subcutaneous perfusion and oxygenation are important components of immunity to wound infections. The SENIC score identifies systemic physiological variables that are important to the development of wound infection. Nevertheless, PsqO2 is the more powerful predictor of wound infection. Moreover, PsqO2 can be manipulated by available clinical means, and thus may direct interventions to prevent infection.

The impact of adjuvant radiotherapy and cytotoxic chemotherapy on the outcome of immediate breast reconstruction by tissue expansion after mastectomy for breast cancer.

In an attempt to evaluate the impact of radiation therapy and cytotoxic chemotherapy on the outcome of immediate breast reconstruction by tissue expansion after mastectomy a prospective study on 32 patients was performed. The radiation therapy significantly worsened the surgical outcome, because the irradiated patients more often had pectoral muscle stiffness making the expansion more painful and the reconstructed breast too small, hard and with insufficient ptosis to obtain a natural breast mould. These results indicate that this technique should be avoided in patients likely to receive postoperative adjuvant cytotoxic chemotherapy and radiation therapy, thus reducing the indication to a small group of patients undergoing mastectomy for widespread ductal carcinoma in situ.

The effect of patient and tumour characteristics on visualization of sentinel nodes after a single intratumoural injection of Tc 99m labelled human albumin colloid in breast cancer.

AIMS: The aim of the study was to study the influence of patient- or tumour-related factors on the lymphatic drainage patterns in breast cancer. METHODS: The study included 290 consecutive breast cancer patients with lymphatic mapping and sentinel node biopsy. Lymphoscintigraphy was performed a median of four hours after a single intratumoral injection of (99m)Tc labelled human albumin colloid with two different particle sizes. RESULTS: Lymphoscintigraphy showed axillary sentinel nodes in 253 (87%) and parasternal sentinel nodes in 49 (17%) patients. The median number of nodes seen in the axilla was one (range 0-5). No sentinel nodes were visualized in 27 (9%) patients. The number of the visualized axillary nodes was influenced by the particle size of the radiocolloid, and by metastatic involvement of the axillary nodes and the age and body mass index (BMI) of the patient. Patients with parasternal sentinel nodes were younger, had a lower BMI and had more often a non-palpable tumour. CONCLUSIONS: The age and BMI of the patient and the palpability of the tumour influence lymphatic drainage patterns in breast cancer. The metastatic involvement of axillary nodes seems to modify lymphatic drainage to the axilla.

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.

The role of Tc99m-sestamibi scintimammography in combination with the triple assessment of primary breast cancer.

AIM: The aim of this study was to evaluate if Tc99m-sestamibi scintimammography in addition to the triple assessment consisting of clinical examination, mammography, breast ultrasonography and fine needle aspiration cytology (FNA) enhances the diagnosis of breast cancer and helps in avoiding unnecessary operative biopsies. METHODS: Pre-operational scintimammography was performed within 2 weeks of operation to 46 consecutive patients with abnormal findings in clinical breast examination, mammography or ultrasonography. Three patients had abnormalities in both breasts. Histological diagnosis was obtained in all 49 cases. RESULTS: The histological diagnosis was benign in 18 (37%) cases and malignant in 31 (63%) cases. The overall sensitivity of scintimammography was 77% and the specificity was 61%. The sensitivity of scintimammography was 95% in invasive ductal carcinoma, 50% in invasive lobular carcinoma and 25% in ductal carcinoma in situ. Scintimammography showed 100% sensitivity in cases with invasive carcinoma, with highly suspicious findings for malignancy in the other examinations. The sensitivity was 63% in cases with indeterminate or contradictory findings in mammography, ultrasonography and FNA. CONCLUSIONS: Adding scintimammography to the triple assessment does not seem to be helpful in the diagnosis of breast abnormalities because of low sensitivity in malignant cases with a challenging diagnosis by mammography, ultrasonography and FNA, and because of low overall specificity.

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.

Hereditary breast cancer and handling of patients at risk.

The identification of BRCA1 and BRCA2, the two known genes causing a dominantly inherited susceptibility for breast and ovarian cancer has allowed genetic testing and identification of high risk individuals in a proportion of breast cancer families. In the future, when both the surveillance methods and prophylactic measures will be further developed this will have even more important clinical value in the management of breast cancer families. To date, as prophylactic mastectomy and/or oophorectomy have been shown to offer a significant risk reduction, these should be considered at least for known mutation carriers. Before considering this, patients should be referred for genetic counseling including risk assessment and genetic testing. Identification of a mutation in the family facilitates carrier detection by allowing predictive testing of healthy individuals. In mutation positive families, a negative test result for an individual has great value as it releases from coping with high risk of cancer and from intensive surveillance. When prophylactic surgery is considered, young age is an important determinant. A skin-sparing mastectomy with implant or autologous tissue transfer is the reconstruction method of choice. Other options like surveillance or chemoprevention can be accepted, but their uncertainty should be pointed out.

Assessment of metabolic activity in aortic vein grafts in rats by histochemical examination of hydrolases.

The metabolic pattern of aortic vein grafts in rats was studied by estimating histochemically the activity of the hydrolytic enzymes alfa-esterase, aminopeptidase, adenosine triphosphatase, acid phosphatase and alkaline phosphatase. The enzyme activity was lowest in the 16 hour and 1 day old grafts, and recovery was noted at three days. Five days after transplantation the enzyme activities were higher than in the non-transplanted veins. The rapid increase in enzymatic activity found in histochemical studies on wound healing was not seen in these vein grafts. At four weeks some grafts showed intimal thickening the activity of which did not exceed that of the other layers of the graft wall. At the end of the observation period of sixteen weeks most of the grafts showed intimal thickening, and this layer stained intensely especially for ATPase. The staining pattern of most of the grafts at sixteen weeks resembled that of the aortic media.

Preoperative assessment of proliferative activity and hormonal receptor status in carcinoma of the breast: a comparison of needle aspiration and needle-core biopsies to the surgical specimen.

The applicability and reliability of estimates of proliferative activity in breast carcinomas using fine-needle aspiration (FNA) and needle-core biopsies (NC) was evaluated in 98 breast carcinoma patients. The Ki-67, Estrogen receptor (ER), and progesteron receptor (PR) immunolabelling of FNA and NC was compared with that of the surgical specimen. A statistically significant consistency between labelling was found in the Ki-67-NC (kappa = 0.474), ER-FNA (kappa = 0.318), ER-NC (kappa = 0.518), and PR-FNA (kappa = 0.404) groups. The consistency in the Ki-67-FNA group was less significant (kappa = 0.182), and there was no consistency in the PR-NC group (kappa = 0.062). There was a positive correlation of Ki-67 labelling in FNA and NC biopsies (Spearman rank, rho = 0.4; P = 0.0007), and also in ER labeling (Spearman rank rho = 0.6; P = 0.0001). These results indicate that NC and FNA can be used for preoperative assessment of proliferative activity and hormonal status in breast carcinoma.