The role of Herceptin in early breast cancer

Herceptin is widely regarded as the most important development in the treatment of breast cancer since Tamoxifen and the development of the multidisciplinary team (MDT). It is particularly exciting from an oncological polint of view as it represents success in the emerging field of specific targeted therapies to specific molecular abnormalities in tumour cells. This review will focus on the nature of the Her2 overexpression and the role of herceptin in the treatment of early breast cancer.     

The value of oral contrast ultrasonography in the diagnosis of gastric cancer in elderly patients

Background

This study aims to investigate the value of oral contrast ultrasonography (OCUS) in the diagnosis of gastric cancer in elderly patients.

Methods

OCUS data obtained from patients ≥?60?years old were retrospectively analyzed and compared with gastroscopy results.

Results

Among the 12,716 subjects examined by OCUS, 5021 subjects were ≥?60?years old, which accounted for 39.48% (5021/12,716). Gastritis, gastric polyp, benign ulcer, and gastric cancer were detected by OCUS in 1099 patients. Among them, 196 patients underwent gastroscopy. Furthermore, ulcerative lesions were detected in 32 patients by OCUS and in 51 patients by gastroscopy, and the coincidence rate was 62.74%. Among these patients, gastric cancer was diagnosed in 18 patients by OCUS with a detection rate of 1.64% (18/1099) and detected in 19 patients by gastroscopy with a diagnostic coincidence rate of 94.73% (18/19). Furthermore, benign ulcer was detected in 14 patients by OCUS and in 32 patients by gastroscopy, and the diagnostic coincidence rate was 43.75% (14/32).

Conclusion

OCUS helps to timely detect senile gastric cancer and can be used as a suitable technique for the detection of gastric diseases.

     

SPECT-CT localization of axillary sentinel lymph nodes for radiotherapy of early breast cancer

PurposeTo evaluate the opportunities of single photon emission tomography/computerized tomography (SPECT-CT) for localization of axillary sentinel lymph nodes (ASLNs) and subsequent radiotherapy planning in women with early breast cancer.Material and methodsIndividual topography of ASLN was determined in 151 women with clinical T1-2N0M0 breast cancer. SPECT-CT visualization of ASLNs was initiated 120 min after intra-peritumoral injection of 99mTc-radiocolloids. Doses absorbed by virtual ASLNs after the whole breast irradiation with standard and extended tangential fields were calculated on a treatment planning station.ResultsSPECT-CT demonstrated a large variability of ASLN localization. They were detected in the central subgroup in 94 (61%) patients, in pectoral – in 77 (51%), and in interpectoral – in 4 (3%) patients. Sentinel lymph nodes “lying on the chest” were revealed in 35 (23%) cases.We found that with standard tangential fields coverage of ASLNs was obtained only in 20% of evaluated women. Extended tangential fields can effectively irradiate ASLNs localized in all axillary sub-regions with the exception of ASLNs “lying on the chest”.ConclusionSPECT-CT mapping of ASLNs in women with cT1-2N0M0 breast cancer reveals their variable localization. This information can be important for planning of radiation treatment in women that underwent breast conserving surgery without an axillary surgery.     

Intraoperative gamma imaging of axillary sentinel lymph nodes in breast cancer patients

Sentinel lymph node (SLN) biopsy is now standard practice in the management of many breast cancer patients. Localization protocols vary in complexity and rates of success. The least complex involve only intraoperative gamma counting of radiotracer uptake or intraoperative visualization of blue-dye uptake; the most complex involve preoperative gamma imaging, intraoperative counting and intraoperative dye visualization. Intraoperative gamma imaging may improve some protocols. This study was conducted to obtain preliminary experience and information regarding intraoperative imaging. Sixteen patients were enrolled: 8 in a protocol that included intraoperative counting and dye visualization (probe/dye), 8 in a protocol that involved intraoperative imaging, counting and dye visualization (camera/probe/dye). Preoperative imaging of all 16 patients was performed using a GE 500 gamma camera with a LEAP collimator (300 cpm/μCi). The results of this imaging were not, however, given to the surgeon until the surgeon had completed the procedures required for the study. A Care Wise C-Trak probe was used for intraoperative counting. A Gamma Medica Inc. GammaCAM/OR (12.5 × 12.5 cm FOV) with a LEHR collimator (135 cpm/μCi) was used for intraoperative imaging. Times from start of surgery to external detection of a radioactive focus and to completion of excision of SLNs were recorded. Foci were detected preoperatively via imaging in 16/16 patients. Intraoperative external detection using the probe was accomplished in less than 4 min (mean = 1.5 min) in 15/16 patients, and via intraoperative imaging in 6/8 patients. The average time for completion of excision of nodes was 19 min for probe/dye and 28 min for camera/probe/dye. In one probe/dye case, review of the preoperative images prompted the surgeon to resume axillary dissection and remove one additional SLN.     

Prognostic role of c-met expression in breast cancer patients

Background

Hepatocyte growth factor plays an important role in tumor growth, metastasis and angiogenesis. C-met is HGF''s high affinity receptor.

Aim

The aim of the study was to assess the correlations between c-met expression and clinic-pathological factors in breast cancer tissues. Furthermore, the purpose of the study was to evaluate the prognostic value of the hepatocyte growth factor receptor (HGFR, c-met) expressions in homogenous group of breast cancer patients.

Materials and methods

Tumor samples were collected from 302 patients with breast carcinoma treated with primary surgery. We have assessed the percentage of tumor cells with c-met expression, the intensity of reaction and the ratio of these two factors—immunoreactivity according to the Remmele score.

Results

We have observed no correlations between HGFR immunoreactivities and clinical parameters (tumor size, grade, axillary lymph node status, age). In 5-year observation we have found prognostic value of assessing c-met immunoreactivity in primary tumor.

Conclusion

Our study has revealed prognostic value of c-met. Unlike in other authors’ studies, our patients’ group is very homogenous which might contribute to obtained results.     

The evolving role of the dynamic thermal analysis in the early detection of breast cancer

It is now recognised that the breast exhibits a circadian rhythm which reflects its physiology. There is increasing evidence that rhythms associated with malignant cells proliferation are largely non-circadian and that a circadian to ultradian shift may be a general correlation to neoplasia.Cancer development appears to generate its own thermal signatures and the complexity of these signatures may be a reflection of its degree of development.The limitations of mammography as a screening modality especially in young women with dense breasts necessitated the development of novel and more effective screening strategies with a high sensitivity and specificity. Dynamic thermal analysis of the breast is a safe, non invasive approach that seems to be sensitive for the early detection of breast cancer.This article focuses on dynamic thermal analysis as an evolving method in breast cancer detection in pre-menopausal women with dense breast tissue. Prospective multi-centre trials are required to validate this promising modality in screening.The issue of false positives require further investigation using molecular genetic markers of malignancy and novel techniques such as mammary ductoscopy.     

Factors influencing psychological wellbeing of early breast cancer patients

AimThis paper aims to identify factors that influence the psychological wellbeing of patients newly diagnosed with localized breast cancer.BackgroundPsychological wellbeing plays a significant part in the personal experience of patients during their cancer journey. However, despite progress in treatments and outcomes in breast cancer, psychosocial services and emotional support of cancer patients have been given less attention.Materials and methodsData were collected through a retrospective review of 274 charts of women diagnosed with breast cancer between 2012 and 2017 that received care in a single cancer center. Disease specific parameters, social and demographic variables, and Edmonton Symptom Assessment System (ESAS) scores were extracted from the patient charts.ResultsSelf-reported scores of psychological-related symptoms were low (suggesting no or minimal psychological distress) at baseline and remained low in the majority of patients with breast cancer. Pain, depression, anxiety and wellbeing scores of 0–2 were observed in 78.5%, 81.4%, 63.5% and 70.1% of patients, respectively. Higher scores of anxiety at baseline were observed in patients with physical restrictions on the Eastern Cooperative Oncology Group performance status (ECOG PS) (14.9%), current smoking (20.5%) and history of mental illness (19.1%). Increasing scores for pain were observed in older patients during treatment as compared to baseline. Mastectomy was associated with increased scores for wellbeing (worsening wellbeing) as compared to lumpectomy. Of the patients with a history of mental illness (17.3%), 19.1% had more often increased scores for anxiety.ConclusionsThe findings highlight patients that may benefit from additional social and psychological supports at diagnosis and while undergoing treatment.     

Cytologic diagnosis of axillary lymph node metastasis in breast cancer

OBJECTIVE: To compare imprint cytology with histology as a method for rapid intraoperative diagnosis of axillary lymph node metastasis in breast cancer. STUDY DESIGN: We evaluated imprint cytology, comparing it with histopathology. A sample of 635 axillary lymph nodes was studied by imprint cytology using both Giemsa stain and hematoxylin-eosin. The results were compared with each other and with those of histopathologic examination. RESULTS: The Giemsa stain method, as compared to histopathology, had 94% accuracy, 97% sensitivity, 90% specificity and 94% positive prognostic value. The hematoxylin-eosin stain method was less accurate than the Giemsa stain method as compared to histopathology (accuracy 91%, sensitivity 96%, specificity 83% and positive prognostic value 92%). CONCLUSION: These data confirm the value of imprint cytology as a rapid, reliable method of intraoperative assessment of axillary lymph node metastasis in breast cancer. It results in better staging of the disease. It can be used intraoperatively, as an alternative to frozen section, if a pathology laboratory is not available, to exclude stage I patients from further treatment.     

The role of endocrine therapy in primary breast cancer

A recent overview of the results of all trials of adjuvant chemotherapy suggests a clinically and statistically significant advantage for premenopausal women with positive axillary nodes. The results of the same approach for all other women with early breast cancer are very disappointing. These data suggest that contrary to the original hypothetical model, adjuvant chemotherapy is exerting its effect indirectly via chemical castration. In contrast, the results of trials of adjuvant tamoxifen have been more promising and, again, in contrast to the original premises, it would appear that a modest improvement in survival and delay in recurrence can be achieved amongst all groups of women independent of age, nodal status and oestrogen receptor content of the primary tumour. In order to explain these counter-intuitive observations, it is necessary to elaborate an alternative biological model. This paper describes the current thinking on the mode of action of the "anti-oestrogens" and the possible role of inhibitory growth factors activated indirectly by anti-oestrogens. Future trials of adjuvant systemic therapy for early breast cancer should include studies on the duration of tamoxifen, comparing 2 yr with longer, and a comparison of tamoxifen alone with polychemotherapy for premenopausal node positive patients.     

Partial breast irradiation techniques in early breast cancer

Whole breast irradiation represents an integral part of combined breast-conserving treatment of early breast cancer. A new concept includes replacing traditionally fractionated whole breast postoperative radiotherapy by accelerated partial breast irradiation. The latter involves a variety of techniques and may be applied intraoperatively or shortly after the surgery. The intraoperative techniques include photon or electron external beam irradiation and interstitial high dose rate (HDR) brachytherapy, whereas the postoperative techniques comprise interstitial brachytherapy, be it HDR, pulse dose rate (PDR) or low dose rate (LDR), intracavitary brachytherapy and external beam radiotherapy using electrons, photons or protons. This article presents accelerated partial breast irradiation techniques, ongoing phase III trials evaluating their value and recommendations for clinical practice.     

Prognostic factors for recurrence and survival in axillary node-negative breast cancer

The question of which node-negative breast cancer patients should be treated with adjuvant systemic therapy is a debatable topic. Our approach in San Antonio is to examine the risk profile for an individual patient and attempt to classify the patient into a good risk group or a high risk group in terms of disease recurrence. Features such as small tumor size (less than 2 cm), diploid tumors with low proliferative rate, and nuclear grade I, all indicate a good prognosis with a disease-free survival of approx. 90% at 5 yr. Examination of the cost vs benefits in this category of patients suggest that routine treatment with systemic adjuvant therapy is not appropriate.     

The role of estrogen in the initiation of breast cancer

Estrogens are considered to play a major role in promoting the proliferation of both the normal and the neoplastic breast epithelium. Their role as breast carcinogens has long been suspected and recently confirmed by epidemiological studies. Three major mechanisms are postulated to be involved in their carcinogenic effects: stimulation of cellular proliferation through their receptor-mediated hormonal activity, direct genotoxic effects by increasing mutation rates through a cytochrome P450-mediated metabolic activation, and induction of aneuploidy. Recently it has been fully demonstrated that estrogens are carcinogenic in the human breast by testing in an experimental system the natural estrogen 17β-estradiol (E₂) by itself or its metabolites 2-hydroxy, 4-hydroxy, and 16-a-hydroxy-estradiol (2-OH-E₂, 4-OH-E₂, and 16--OH E₂), respectively, by inducing neoplastic transformation of human breast epithelial cells (HBEC) MCF-10F in vitro to a degree at least similar to that induced by the chemical carcinogen benz(a)pyrene (BP). Neither Tamoxyfen (TAM) nor ICI-182,780 abrogated the transforming efficiency of estrogen or its metabolites. The E₂ induced expression of anchorage independent growth, loss of ductulogenesis in collagen, invasiveness in Matrigel, is associated with the loss of 9p11-13 and only invasive cells that exhibited a 4p15.3-16 deletion were tumorigenic. Tumors were poorly differentiated ER- and progesterone receptor negative adenocarcinomas that expressed keratins, EMA and E-cadherin. The E₂ induced tumors and tumor-derived cell lines exhibited loss of chromosome 4, deletions in chromosomes 3p12.3-13, 8p11.1-21, 9p21-qter, and 18q, and gains in 1p, and 5q15-qter. The induction of complete transformation of the human breast epithelial cell MCF-10F in vitro confirms the carcinogenicity of E₂, supporting the concept that this hormone could act as an initiator of breast cancer in women. This model provides a unique system for understanding the genomic changes that intervene for leading normal cells to tumorigenesis and for testing the functional role of specific genomic events taking place during neoplastic transformation.     

The possible role of lipid peroxidation in breast cancer risk

Breast cancer remains the commonest cause of death from cancer in women in most of the Western world. There is considerable evidence that breast cancer risk is influenced by environmental factors and can therefore potentially be modified. In this paper we describe evidence suggesting a relationship of lipid peroxidation to breast cancer risk, and propose that the method used to generate this information might usefully be applied to other disease states, and make some suggestions for further work. We have compared the urinary excretion of the mutagen malonaldehyde (MDA) in premenopausal women at different risks for breast cancer as determined by the appearance of the breast parenchyma on mammography. MDA was measured in 24-h urine samples from both groups and excretion in 30 women with mammographic dysplasia (high risk) was found to be approximately double that of 16 women without these radiological changes (p less than 0.02). These results suggest that mammographic dysplasia may be associated with lipid peroxidation. Further study of environmental factors associated with states that precede the development of breast and other cancers may lead to the identification of factors that can be modified and that may prevent the development of malignant disease.