Flap fixation in preventing seroma formation after mastectomy: an updated meta-analysis.

Seroma formation following mastectomy is one of the most experienced complications, with a very variable incidence ranging from 3 to 90%. In recent years, many publications have been realized to define an effective technique to prevent its formation and several approaches have been proposed. Given the potential of flap fixation in reducing seroma formation, we performed a meta-analysis of the literature to investigate the role of this approach as definitive gold standard in mastectomy surgery. Inclusion criteria regarded all studies reporting on breast cancer patients undergoing mastectomy with or without axillary lymph node dissection; studies that compared mastectomy with flap fixation to mastectomy without flap fixation were selected. Papers were eligible for inclusion if outcome was described in terms of seroma formation. As secondary outcome, also surgical site infection (SSI) was evaluated. The included studies were 12, involving 1887 female patients: 221/986 (22.41%) patients experienced seroma formation after flap fixation and 393/901 (43.61%) patients had this complication not receiving flap fixation, with a significant statistical difference between the two groups (OR = 0.267, p = 0.001, 95% CI 0.153, 0.464). About, SSI 59/686 (8.6%) in flap fixation group and 67/686 (9.7%) in patients without flap fixation, with no statistical differences between groups (OR = 0.59, p = 0.056, 95% CI 0.344, 1.013).The heterogeneity between included studies does not allow us to reach definitive conclusions but only to suggest the strong evaluation of this approach after mastectomy in seroma preventing and SSI reduction.

Palbociclib added to ongoing endocrine therapy for hormone receptor-positive HER2-negative metastatic breast cancer: A case report series.

Palbociclib is a potent cyclin-dependent kinase (CDK)4/6 inhibitor that disrupts cell cycle progression and has been recently approved in combination with an aromatase inhibitor or fulvestrant as first- and second-line treatment in hormone receptor (HR)+, human epidermal growth factor receptor (HER)2- metastatic breast cancer. There is evidence that palbociclib may reverse endocrine therapy resistance and that it may also be added to ongoing endocrine therapy beyond progression to obtain clinical benefit. The aim of the present study was to explore this possibility in 5 patients who received palbociclib + fulvestrant following disease progression while under treatment with fulvestrant alone. The median progression-free survival was not reached during a median follow-up of 25 months, and the most frequent best response was stable disease. Three patients remained under treatment on the last re-evaluation. All patients had highly endocrine-sensitive disease and had previously received fulvestrant for ≥12 months. The hypothesis that a selected subpopulation of patients with HR+/HER2- metastatic breast cancer may benefit from the addition of palbociclib to ongoing endocrine therapy beyond disease progression merits further investigation.

The role of MRI in predicting Ki-67 in breast cancer: preliminary results from a prospective study.

PURPOSE: In the last decade contrast-enhanced magnetic resonance imaging (MRI) has gained a growing role as a complementary tool for breast cancer diagnosis. Currently the relationship between the kinetic features of a breast lesion and pathologic prognostic factors has become a popular field of research. Our aim is to verify whether breast MRI could be considered a useful tool to predict Ki-67 score, thus resulting as a breast cancer prognosis indicator. METHODS: From June to December 2014, we enrolled patients with breast cancer who underwent preoperative dynamic contrast-enhanced MRI at the local health agency. We analyzed the time-signal intensity curves calculating the mean values of the following parameters: the basal enhancement (Ebase), the enhancement ratio (ENHratio), the maximum enhancement (Emax), and the steepest slope of the contrast enhancement curve (Smax). Scatterplots and Pearson correlation test were used to investigate the eventual associations among these parameters. RESULTS: A total of 27 patients underwent breast MRI during the study period. The mean ± SD Ki-67 percentage was 27.03 ± 16.8; the mean Emax, Smax, Ebase, and ENHratio were 433.9 ± 120.2, 267.3 ± 96.8, 165.5 ± 77.1, and 187.1 ± 94.8, respectively. Scatterplots suggest a positive correlation between Ki-67 and both Emax and Smax. The correlation tests between Ki-67 and Emax, Ki-67 and Smax showed statistical significance. CONCLUSIONS: Our preliminary data suggest that enhancement pattern is closely linked to breast cancer proliferation, thus proving the relationship between more proliferating tumors and more rapidly enhanced lesions. This is hypothesis-generating for further studies aimed at promoting breast MRI in the early estimation of cancer prognosis and tumor in vivo response to chemotherapy.

Venous anomalies of the axilla: a single-institution experience.

AIM: Surgical treatment is still the cornerstone in the treatment of breast cancer, a very common neoplasia, particularly affecting the female elderly population. Axillary dissection is crucial in the treatment of some tumours, but variations in axillary vessels anatomy are poorly described in standard anatomy and surgical textbook. We aimed to describe anatomical variations in axillary vessels found in our institutional experience. PATIENTS AND METHODS: A prospective 3-year study was conducted in our institution from January 2012 to December 2014. Sixty-one consecutive axillary lymph node dissections (ALNDs) were performed in 61 patients who underwent surgery for stage II and III invasive breast cancer. Anatomical details of axillary vascular anatomy and its variations have been evaluated, described and stored in a prospective database. RESULTS: Sixty-one ALNDs have been performed in the study period. The anatomy of lateral thoracic vein, angular vein and axillary vein was studied and compared with standard anatomical description. Eighteen percentage of venous variations were found out of the 61 dissection performed. CONCLUSIONS: Vascular anatomy of axilla is complex and variable. A better knowledge of all possible variations might be helpful in preventing injuries during ALND.

Oxidative Stress Mediates the Antiproliferative Effects of Nelfinavir in Breast Cancer Cells.

The discovery of the anti-proliferative activity of nelfinavir in HIV-free models has encouraged its investigation as anticancer drug. Although the molecular mechanism by which nelfinavir exerts antitumor activity is still unknown, its effects have been related to Akt inhibition. Here we tested the effects of nelfinavir on cell proliferation, viability and death in two human breast cancer cell lines and in human normal primary breast cells. To identify the mechanism of action of nelfinavir in breast cancer, we evaluated the involvement of the Akt pathway as well as the effects of nelfinavir on reactive oxygen species (ROS) production and ROS-related enzymes activities. Nelfinavir reduced breast cancer cell viability by inducing apoptosis and necrosis, without affecting primary normal breast cells. The antitumor activity of nelfinavir was related to alterations of the cell redox state, coupled with an increase of intracellular ROS production limited to cancer cells. Nelfinavir treated tumor cells also displayed a downregulation of the Akt pathway due to disruption of the Akt-HSP90 complex, and subsequent degradation of Akt. These effects resulted to be ROS dependent, suggesting that ROS production is the primary step of nelfinavir anticancer activity. The analysis of ROS-producers and ROS-detoxifying enzymes revealed that nelfinavir-mediated ROS production was strictly linked to flavoenzymes activation. We demonstrated that ROS enhancement represents the main molecular mechanism required to induce cell death by nelfinavir in breast cancer cells, thus supporting the development of new and more potent oxidizing molecules for breast cancer therapy.

Can axillary node dissection be safely omitted in the elderly? A retrospective study on axillary management of early breast cancer in older women.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a minimally invasive technique to stage the axillary lymph node status. The burden of nodal metastasis is of great concern, as the clinical relevance and therapeutic implications of pN1mi and pN0(i+) in the sentinel lymph node (SLN) remain a matter of debate. MATERIALS AND METHODS: We examined the pathological features of 901 patients above the age of 65 presenting with clinical T1-T2 N0M0 breast tumours (<3 cm), detecting tumours related to llary non-sentinel node (NSN) metastases when the SLN was minimally involved. RESULTS: A total of 270 patients underwent complete axillary lymph node dissection (cALND) after their SLNB specimen tested positive for macrometastasis, micrometastasis and isolated tumour cells (ITCs). Seventy-six patients were diagnosed with micrometastatic disease pN1mi (27.5%), whilst ITCs (pN0i+) were detected in seven patients (2.5%). NSNs were found to be involved in two patients (2.6%) with micrometastases at the SLN. No further metastatic disease was detected in NSNs when the SLN contained ITCs. At a median follow-up period of 5.8 years, no axillary recurrence was observed among pN1mi and pN0(i+) patients. Lobular histotype, multicentricity and lymphovascular invasion were found to be associated with NSN involvement. DISCUSSION: The results from our case series are supported by IBCSG 23-01 level 1 evidence, which demonstrated a local recurrence rate of 1% in 'minimally involved not-surgical treated axilla'. CONCLUSIONS: Based on current evidence, we spare well-informed and consenting patients from further axillary surgery when the SLN is minimally involved in early breast cancer within an agreed protocol, whilst scheduling adjuvant treatment based on the patients' primary tumour characteristics.

Metabolic and anthropometric changes in early breast cancer patients receiving adjuvant therapy.

Weight gain and metabolic changes have been related to survival of early breast cancer patients (EBC). ''However, factors influencing metabolism post-diagnosis are not fully understood. We measured anthropometric [body mass index (BMI), body weight, waist and hip circumferences, and waist-to-hip ratio] and metabolic (levels of insulin, glucose, H1Ac, total, HDL, and LDL cholesterol, triglycerides, and the homeostasis model assessment score [HOMA]) parameters in 433 pre- and post-menopausal women with EBC at diagnosis and 3, 6, 9, 12, and 24 months thereafter. At diagnosis, compared with post-menopausal women, pre-menopausal patients were more likely to be leaner and to have a lower BMI, smaller waist and hip circumferences, and waist-to-hip ratio. They had also lower glucose, HbA1c, and triglyceride levels and a lower HOMA score. Furthermore, they were more likely to have an estrogen- and/or progesterone-positive tumor and a higher proliferating breast cancer. During the first two post-diagnosis years, all women showed a significant increase of weight (+0.72 kg/year, P < 0.001), waist circumference (+1.53 cm/year, P < 0.001), and plasma levels of LDL cholesterol (+5.4 mg/dl per year, P = 0.045) and triglycerides (+10.73 mg/dl per year, P = 0.017). In patients receiving chemotherapy only, there was a significant increase in hip circumference (+3.16 cm/year, P < 0.001) and plasma cholesterol levels (+21.26 mg/dl per year, P < 0.001). We showed that weight, body fat distribution, and lipid profile changed in EBC patients receiving adjuvant therapy. These changes occurred during the first 2 years after diagnosis and were not specifically related to chemotherapy, menopausal status, or initial body weight.

"Ductal adenocarcinoma in anular pancreas".

INTRODUCTION: The annular pancreas is a congenital anomaly in which pancreatic tissue partially or completely surrounds the second portion of the duodenum. Its often located above of papilla of Vater (85%), rarely below (15%). This pancreatic tissue is often easily dissociable to the duodenum but there is same cases where it the tissue is into the muscolaris wall of the duodenum. MATERIAL AND METHODS: We describe three case of annular pancreas hospitalized in our facility between January 2004 and January 2009. There were 2 male 65 and 69 years old respectively and 1 female of 60 years old, presented complaining of repeated episodes of mild epigastric pain. Laboratory tests (including tumor markers), a direct abdomen X-ray with enema, EGDS and total body CT scan were performed to study to better define the diagnosis. EUS showed the presence of tissue infiltrating the muscle layer all around the first part of duodenum. Biopsies performed found the presence of pancreatic tissue with focal areas of adenocarcinoma. Subtotal gastrectomy with Roux was performed. The histological examinations shows an annular pancreas of D1 with multiple focal area of adenocarcinoma. (T1aN0M0). RESULTS: We performed a follow up at 5 years. One patients died after 36 months for cardiovascular hit. Two patients, one male and one female, was 5-years disease-free. DISCUSSION: Annular pancreas is an uncommon congenital anomaly which usually presents itself in infants and newborn. Rarely it can present in late adult life with wide range of clinical severities thereby making its diagnosis difficult. Pre-operative diagnosis is often difficult. CT scan can illustrate the pancreatic tissue encircling the duodenum. ERCP and MRCP are useful in outlining the annular pancreatic duct. Surgery still remains necessary to confirm diagnosis and bypassing the obstructed segment.

Confocal laser endomicroscopy in breast surgery: a pilot study.

BACKGROUND: Breast neoplasms include different histopathological entities, varying from benign tumors to highly aggressive cancers. Despite the key role of imaging, traditional histology is still required for a definitive diagnosis. Confocal Laser Endomicroscopy (CLE) is a new technique, which enables to obtain histopathological images in vivo, currently used in the diagnosis of gastrointestinal diseases. This is a single-center pilot feasibility study; the main aim is to describe the basic morphological patterns of Confocal Laser Endomicroscopy in normal breast tissue besides benign and malignant lesions. METHODS: Thirteen female patients (mean age 52.7, range from 22 to 86) who underwent surgical resection for a palpable breast nodule were enrolled. CLE was performed soon after resection with the Cellvizio® Endomicroscopy System (Mauna Kea Technologies, Paris, France), by using a Coloflex UHD-type probe; intravenous fluorescein was used as contrast-enhancing agent. The surgical specimen was cut along the main axis; dynamic images were obtained and recorded using a hand-held probe directly applied both to the internal part of the lesion and to several areas of surrounding normal tissue. Each specimen was then sent for definitive histologic examination. RESULTS: Histopathology revealed a benign lesion in six patients (46%), while a breast cancer was diagnosed in seven women (54%). Confocal laser endomicroscopy showed some peculiar morphological patterns. Normal breast tissue was characterized by a honeycomb appearance with regular, dark, round or hexagonal glandular lobules on a bright stroma background; tubular structures, representing ducts or blood vessels, were also visible in some frames. Benign lesions were characterized by a well-demarcated "slit-like" structure or by lobular structures in abundant bright stroma. Finally, breast cancer was characterized by a complete architectural subversion: ductal carcinoma was characterized by ill-defined structures, with dark borders and irregular ductal shape, formingribbons, tubules or nests; mucinous carcinoma showed smaller cells organized in clusters, floating in an amorphous extracellular matrix. CONCLUSIONS: This is the first pilot study to investigate the potential role of confocal laser imaging as a diagnostic tool in breast diseases. Further studies are required to validate these results and establish the clinical impact of this technique.

Clinically cN0 breast cancer in elderly: what surgery?

INTRODUCTION: Breast carcinoma is the most common cancer in women worldwide. The incidence increases with age. Elderly patients have more advanced disease than younger ones, but they have a more favorable biologic tumor profile overall. The management of breast cancer in elderly is controversial. We report our experience with breast cancer in older than 65 years in the last 5 years, in order to assess how many axillary dissection may have been avoided, according to disease free survival (DFS) and overall survival (OS). MATERIALS AND METHODS: We enrolled in our retrospective study all over 65 year old patients referred to the Breast Unit of our Department of Clinical Medicine and Surgery at the University of Naples Federico II from January 2009 to December 2013. The end points were: evaluation of the rate of axillary treatment avoidable, DFS and OS. RESULTS: We recruited 133 over 65 year old patients. Axillary lymph node was not palpable in 109 patients. The rate of involved axillae in patients without palpable nodes treated was 11.8%. The mean follow up was 35.7 months. At the time of data collection 3 patients had developed IBTR. No one had axillary recurrence, independently from the chosen treatment. 2 patients died for causes different from breast cancer. CONCLUSION: DFS and OS are the same both in patients with treated and no treated axilla. Even if evidences about the treatment of breast cancer in elderly are still controversial, each patient deserves a multidisciplinary approach to discuss the best treatment option.

Neuroendocrine differentiation in breast carcinoma with osteoclast-like giant cells. Report of a case and review of the literature.

Osteoclast-like giant cells (OGCs) may occur in several types of breast carcinomas (BS). Neuroendocrine differentiation may be present in BS but, associated with OGCs, neuroendocrine differentiation has been rarely reported. A case of invasive ductal carcinoma with OGCs and neuroendocrine differentiation diagnosed by fine needle cytology (FNC) is described. A 72-year-old woman with a nodular lesion of the right breast underwent to fine-needle cytology (FNC) The smears showed a dissociated cell population of monomorphous, mononucleated atypical cells with interspersed multinucleated giant cells osteoclast-like. The mononuclear cell component showed plasmacytoid features and frequent vacuoles of secretion. Immunostaining (IHC) performed on cell block sections showed oestrogen receptor positivity in the mononucleated cells and OGCs positivity for LCA and CD68. Histologically the tumour showed cell nests or cords separated by thin fibrovascular septa. The neoplastic cells were monomorphic, with round-oval nuclei, granular chromatin and evident nucleoli. The cytoplasm was indistinct and eosinophilic, finely granular, often containing eosinophilic globules that were positive at the PAS and mucicarmine stainings. Numerous non-neoplastic OGCs were also detected in the interstitial septa. The ICH showed positivity of the tumoral cells for E-Cadherin, oestrogen and progesterone receptors and c-ErbB2 negativity. Mitotic index was inconspicuous with a low Ki67 positivity rate (<10%). OCGs were CD68 and LCA positive. IHC also showed strong positivity for the chromogranin and synaptophysin. A diagnosis of invasive ductal BC with OGCs and neuroendocrine differentiation was performed. The expression of chromogranin and synaptophysin was then retrospectively assessed on CB sections too. The identification of OGCs component on breast FNA samples is not difficult, depending on a good sampling only. On contrary, the neuroendocrine differentiation still represents still a challenge in breast FNC.

Adrenocortical carcinoma: what the surgeon needs to know. Case report and literature review.

Adrenocortical carcinoma is a rare and aggressive cancer and its prognosis is frequently unsatisfactory. Due to its rarity there's a lack of prospective randomized studies. Without experience in the approach of this kind of tumor, managing becomes challenging and, moreover, we have only few recommendations, based on weak evidence. We report a case that has some peculiarities and is an excellent food for thought. Then we deal with a literature review to highlight and summarize most significant aspects of epidemiology, clinic, diagnosis, therapy and prognosis in an exquisitely surgical point of view.

Lobular intraepithelial neoplasia arising within breast fibroadenoma.

BACKGROUND: Fibroadenomas are the second most common breast pathology occurring in young women under the age of 35 years old. Fibroadenomas can be classified as simple or complex according to histological features. Complex fibroadenomas differ from simple fibroadenomas because of the presence of cysts (3 mm), sclerosing adenosis, epithelial calcifications, or papillary apocrine changes. Most fibroadenomas are clinically identifiable. In 25% of cases, fibroadenomas are non-palpable and are diagnosed with mammography and ultrasound. Differential diagnosis with well differentiated breast cancer is often necessary, particularly with medullary or mucinous tumors. Calcification findings within fibroadenomas by mammogram have to be investigated. The age of a lump is usually reflected by calcifications. Microcalcification can hide foci of carcinoma in situ when they are small, branching type, and heterogeneous. However, many morphological possibilities may not be reliable for deciding whether a certain calcification is the product of a malignant or a benign process. From a radiological point of view, fibroadenomas containing foci of carcinoma in situ can be indistinguishable from benign lesions, even if the incidence of carcinoma within fibroadenomas is estimated as 0.1-0.3%, and it could be a long-term risk factor for invasive breast cancer. CASE PRESENTATION: A 44-year-old woman presented with a 1.5-cm palpable, smooth, mobile lump in the lower-inner quadrant of her right breast. Standard mediolateral oblique and craniocaudal mammograms showed a cluster of eccentric popcorn-like calcifications within the fibroadenoma. After lumpectomy, a definitive histological examination confirmed the intra-operative diagnosis of a benign mass. However, lobular intraepithelial neoplasia foci were found, surrounded by atypical lobular hyperplasia. CONCLUSIONS: The possibility of an old benign breast lump might be supported by fine needle aspiration biopsy or core biopsy before initiating follow-up. According to our experience, when patients are older than 40 years and have a familial history of breast cancer, we prefer to carry out lumpectomy with follow up to avoid the risk of underestimation in situ foci within the lump.

Long-term cultures of stem/progenitor cells from lobular and ductal breast carcinomas under non-adherent conditions.

A small subpopulation of stem/progenitor cells can give rise to the diversity of differentiated cells that comprise the bulk of the tumor. Are proliferating cells, within the bulk of tumor, few cells with uncommon features? The cell biological approach provides a limitless model for studying the hierarchical organization of progenitor subpopulation and identifying potential therapeutic targets. Aim of the study was to expand patients' breast cancer cells for evaluating functional cell properties, and to characterize the protein expression profile of selected cells to be compared with that of primary tumors. Breast cancer cells from estrogen receptor (ERα) positive, HER2 negative lobular (LoBS cells) and ductal (DuBS cells) histotype were cultured under non-adherent conditions to form mammospheres. Sorting of the cells by their surface expression of CD24 and CD44 gave rise to subpopulations which were propagated, enriched and characterized for the expression of epithelial and stromal markers. We found that non-adherent culture conditions generate mammospheres of slowly proliferating cells; single cells, dissociated from mammospheres, grow in soft agar; long-term cultured LoBS and DuBS cells, CD44+/CD24low, express cytokeratin 5 (CK5), α-smooth muscle actin (α-sma) and vimentin, known as markers of basal/myoepithelial cells; and ERα (only DuBS cells), HER1 (EGF-Receptor), activated HER2, and cyclinD1 as markers of luminal epithelial cell. Isolates of cells from breast cancer patients may be a tool for a marker-driven testing of targeted therapies.

Combined inhibitory effect of formestane and herceptin on a subpopulation of CD44+/CD24low breast cancer cells.

In breast cancer, stromal cells surrounding cancer epithelial cells can influence phenotype by producing paracrine factors. Among many mediators of epithelial-stromal interactions, aromatase activity is perhaps one of the best studied. Clinical data suggest that estrogen-independent signaling leads to increased proliferation even during therapy with aromatase inhibitors (AIs). Molecular mechanism of crosstalk between the estrogen receptor (ER) and the epidermal growth factor receptor (HER) family have been implicated in resistance to endocrine therapy, but this interaction is unclear. The ability of aromatase to induce estradiol biosynthesis provides a molecular rationale to combine agents that target aromatase activity and the HER pathway. We targeted stromal-epithelial interactions using formestane, which exerts antiaromatase activity, combined with the monoclonal anti-HER2 antibody herceptin, in a subpopulation of CD44+/CD24low cells sorted from epithelial-mesenchymal co-cultures of breast cancer tissues. The growth inhibition was respectively 16% (P < 0.01) in the response to herceptin, 25% to formestane (P < 0.01), and 50% (P < 0.001) with the combination of the two drugs, suggesting that herceptin cooperates with formestane-induced inhibition of aromatase and this effect could be mediated through HER family receptors. In cells which expressed ERalpha, formestane/herceptin combination suppressed the mRNA expression of aromatase and HER2 and decreased cyclin D1 expression. These results show that combination therapies involving AIs and anti-HER2 can be efficacious for the treatment of cancer in experimental models and suggest that subtyping breast tumors gives useful information about response to treatment.

A banking strategy toward customized therapy in breast cancer.

In breast cancer, various clinical parameters are assessed to define clinical stage and thus obtain a more accurate prognosis. However, banks of tumor tissues are an important source of material for studies of risk of recurrence and of features governing clinical outcome in breast cancer. Although the heterogeneous characteristics of individual tumors, subtle phenotypes and stem cells can only be identified in viable cells, tissue banks often give low priority to the preservation of living cells because it is labor-intensive and expensive. The present study was designed to evaluate the feasibility of introducing, within the routine procedures of tissue preservation, a cryopreservation protocol that allows the recovery of living cells after storage. We analyzed the effect of storage time on cell viability, growth rates, and protein expression of ten human breast cancer specimens subjected to various cryopreservation techniques. Cryopreservation of cancer tissue specimens for 12 months allowed protein characterization but not the recovery of living cells. Here we show that enzymatic digestion immediately before slow freezing, and storage in liquid nitrogen permits the recovery and expansion of living cells that can be tailored to specific requirements and projects.

Dual-time-point 18F-FDG PET/CT versus dynamic breast MRI of suspicious breast lesions.

OBJECTIVE: The purpose of our study was to compare dual-time-point (18)F-FDG PET/CT, performed with the patient in the prone position, and contrast-enhanced MRI in patients with suspected breast malignancy. SUBJECTS AND METHODS: Forty-four patients with 55 breast lesions underwent two PET/CT scans (dual-time-point imaging) in the prone position and breast MRI. Sensitivity, specificity, and overall accuracy were calculated. In addition, the average percentage of change in standard uptake values (Delta%SUV(max)) between time point 1 and time point 2 was calculated for PET/CT. A final histopathologic diagnosis was available for all patients. RESULTS: MRI showed an overall accuracy of 95%, with sensitivity and specificity of 98% and 80%. Conversely, dual-time-point PET/CT showed an accuracy of 84% for lesions with an SUV(max) > or = 2.5 or with a positive Delta%SUV(max), with sensitivity and specificity of 80% and 100% versus 69% accuracy, 62% sensitivity (both, p < 0.001), and 100% specificity (p not significant) for single-time-point PET/CT. On PET/CT, malignant lesions showed an increase in FDG between time points 1 and 2, with a Delta%SUV(max) of 11 +/- 24. Benign lesions showed either no change or a decrease in SUV(max) between time points 1 and 2, with a Delta%SUV(max) of -21 +/- 7. CONCLUSION: A dual time point improves PET/CT accuracy in patients with a suspected breast malignancy over single-time-point PET/CT. On PET/CT, FDG is increasingly taken up over time in breast tumors; conversely, benign lesions show a decrease in FDG uptake over time. These changes in SUV might represent a reliable parameter that can be used to differentiate benign from malignant lesions of the breast on PET/CT examination.

Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials.

PURPOSE: We conducted a meta-analysis of randomized trials that evaluated the efficacy of incorporating taxanes into anthracycline-based regimens for early breast cancer (EBC). We aimed to determine whether this approach improves disease-free survival (DFS) and overall survival (OS) and whether benefits are maintained across relevant patient subgroups. METHODS: Studies were retrieved by searching the PubMed database and the proceedings of major conferences. We extracted hazard ratios (HR) and 95% CIs for DFS and OS from each trial and obtained pooled estimates using an inverse-variance model. RESULTS: Thirteen studies were included in the meta-analysis (N = 22,903 patients). The pooled HR estimate was 0.83 (95% CI, 0.79 to 0.87; P < .00001) for DFS and 0.85 (95% CI, 0.79 to 0.91; P < .00001) for OS. Risk reduction was not influenced by the type of taxane, by estrogen receptor (ER) expression, by the number of axillary metastases (N1 to 3 v N4+), or by the patient's age/menopausal status. Sensitivity analysis showed that taxanes given in combination with anthracyclines, unlike sequential administration, did not significantly improve OS. However, the test for interaction showed that HR did not differ between the two schedules (P = .54). Taxane administration resulted in an absolute 5-year risk reduction of 5% for DFS and 3% for OS. CONCLUSION: The addition of a taxane to an anthracycline-based regimen improves the DFS and OS of high-risk EBC patients. The DFS benefit was independent of ER expression, degree of nodal involvement, type of taxane, age/menopausal status of patient, and administration schedule.

In vitro expansion of human breast cancer epithelial and mesenchymal stromal cells: optimization of a coculture model for personalized therapy approaches.

Molecularly targeted, customized therapies are designed based on the molecular portraits of cancer tissue. The efficacy of targeted therapy in individual patients depends on the contribution of single individual cancer cells within the context of their microenvironment. We have developed an in vitro model of human mammary epithelial-stromal cocultures to answer specific clinical questions related to breast cancer, to provide a tool with which to identify a signature in each breast tumor, and to identify the metabolic molecular targets of therapy in an attempt to optimize the efficacy of targeted therapy in each patient. Fifty-five human breast cancer samples were obtained through surgery. Epithelial and stromal cells were isolated from tissue specimens by differential centrifugation, and cryopreserved. Western blot analysis and RT-PCR were used to identify the tissue-specific expression patterns of cancer cells. Dose-response curves were constructed for the aromatase inhibitor formestane and for herceptin, and a 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay was done for combined treatment. We collected and cryopreserved, for future use, viable living cells from 55 breast tumor specimens from which we derived short-term cocultures. The presence of cytokeratins and vimentin was evaluated in 20 samples, and pHER2/neu and aromatase were evaluated in 4 cocultures. Formestane and herceptin had a cumulative growth-inhibitory effect on cocultures expressing epidermal growth factor receptors and aromatase. The in vitro model of human mammary epithelial-stromal cocultures reported herein can be used to examine, and to store, a patient's tumor-derived, living cells that retain the characteristics of the mother-tissue and respond, in vitro, to therapy.

Triplet repeat instability correlates with dinucleotide instability in primary breast cancer.

The expansion of triplet repeat microsatellite sequences is the molecular correlate of anticipation in a number of rare Mendelian neurodegenerative disorders. This finding prompted us to study these sequences in primary breast cancer in which there is evidence of genetic anticipation. We used a PCR/silver stain method to determine whether triplet-repeat instability (TRI) was present in DNA from malignant breast tumors, and analyzed microsatellite instability (MSI) in triplets SCA1, SCA2, SCA3, SCA6, HD, DRPLA and X25-GAA. We studied 54 consecutive primary breast cancers previously analyzed for dinucleotide instability (DI) at 9 loci. Microsatellite instability (TRI and/or DI) was found in 28/54 (52%) cases, ranging from 0 to 56% in each patient. Dinucleotide instability occurred at > or =2 loci in 19/54 (35%) cases and TRI in 6/54 (11%). Considering single locus instability, we found DI in 26/54 (48%) tumors and TRI in 13/54 (24%). Triplets DRPLA and X25-GAA were most frequently unstable (14% of cases); SCA2 instability was not detected. Interestingly, most tumors with TRI had DI (11/13, 85%). There was a correlation between TRI and DI in the same tumor (42 vs 7% in DI+ and DI- tumors respectively, p=0.0028). Furthermore, TRI appears more frequently associated with lymph node metastases and more advanced clinical stages and more frequent in patients <50 years old, with positive steroidal hormone receptor status, positive p185 and negative p53. These findings are of interest because they demonstrate a relationship between TRI and the clinicopathological characteristics of cancer aggressiveness. Triplet repeat alterations can interfere with gene expression and proteomic functions, which suggests they can play a role in the neoplastic progression of mammary cells. Furthermore, the association of TRI and DI in the same tumor suggests that alterations in the DNA repair gene could culminate in selective phenotypes and breast cancer progression in a considerable number of patients.