Review of concepts in therapeutic decision-making in HER2-negative luminal metastatic breast cancer.

PURPOSE: Hormone receptor (HR)-positive, Human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) requires a therapeutic approach that takes into account multiple factors, with treatment being based on anti-estrogen hormone therapy (HT). As consensus documents are valuable tools that assist in the decision-making process for establishing clinical strategies and optimize the delivery of health services, this consensus document has been created with the aim of developing recommendations on cretiera for hormone sensitivity and resistance in HER2-negative luminal MBC and facilitating clinical decision-making. METHODS: This consensus document was generated using a modification of the RAND/UCLA methodology, which included the definition of the project and identification of issues of interest, a non-exhaustive systematic review of the literature, an analysis and synthesis of the scientific evidence, preparation of recommendations, and external evaluation with a panel of 64 medical oncologists specializing in breast cancer. RESULTS: A Spanish panel of experts reached consensus on 32 of the 32 recommendations/conclusions presented in the first round and were accepted with an approval rate of 100% about definition of metastatic disease not susceptible to local curative treatment, definition of hormone sensitivity and hormone resistance in metastatic luminal disease and therapeutic decision-making. CONCLUSION: We have developed a consensus document with recommendations on the treatment of patients with HER2-negative luminal MBC that will help to improve therapeutic benefits.

MAMMARY GLAND ADENOCARCINOMA IN A MALE BORNEAN ORANGUTAN (PONGO PYGMAEUS).

An adult male Bornean orangutan ( Pongo pygmaeus ) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr postdetection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.

Primary neuroendocrine carcinoma of the breast A single Center experience and review of the literature.

Neuroendocrine carcinoma of the breast is an extremely rare tumor. A standard treatment has yet to be established because only a few cases have been reported in literature. The authors report five cases observed from January 2007 to December 2014 and a review of literature. Four patients underwent quadrantectomy and in two cases axillary nodal dissection and only one to mastectomy with axillary nodal dissection. Tumor size was from T1 to T2 with N0 to N1, according TNM classification. Pathological specimens were stained with hematoxylin and eosin and an immunohistochemical panel of antibodies (Neuron-specific enolase, Chromogranin, Synaptophysin, Estrogen and Progesterone receptors, c-erb and Ki-67). All cases showed markers positivity to Neuron-specific enolase, Chromogranin, Synaptophysin and Estrogen and Progesterone receptors were found. Ki-67 was higher than 40% in four patients. Adjuvant chemotherapy was administrated in patients with Ki-67>10%; every patients were treated with radiotherapy and with hormonal therapy too. Although Neuroendocrine breast tumor is considered a distinct entity, the best treatment seems to be correlate to the size of tumor and to the lymph node status and to Ki-67 index like the common breast cancer. KEY WORDS: Diagnosis, Neuroendocrine breast carcinoma.

[MALIGNANT MELANOMA--THE INFLUENCE OF HORMONAL FACTORS ON THE PROGRESSION AND PROGNOSIS. COMPARATIVE ANALYSIS BASED ON TWO CLINICAL CASES].

Malignant melanoma is the most aggressive form of skin cancer showing extremely high metastatic rate and leading to high levels of lethality. The continually growing incidence of malignant melanoma in the world and his difficult early diagnosis are the occasion for numerous studies. The individual risk for malignant transformation of melanocytes is determined by a number of etiologic factors--endogenous and exogenous. Ultraviolet radiation has a leading role in the group of exogenous factors. Within the group of endogenous factors, besides the well-known photo type skin, as well as genes mutations, are added and the sex hormones, with their significant prognostic importance. The differences, which are observed in the progression and prognosis of malignant melanoma in pre- and postmenopausal women, and men, have defined this cutaneous neoplasma as hormone-dependent tumor. We present two seemingly similar clinical cases of 52 year old woman and 53-year-old man diagnosed with malignant melanomas, developed on the basis of pigmented lesions located on the upper back, as we attempt a comparative analysis on etiopathogenetic factors led to radically different course and prognosis of the disease in these two patients.

[Sentinel lymph node metastasis in patients with ductal breast carcinoma in situ]. / Metástasis a ganglio centinela de pacientes con carcinoma ductal in situ de la mama.

BACKGROUND: Sentinel lymph node biopsy in patients with ductal carcinoma in situ still controversial, with positive lymph node in range of 1.4-12.5% due occult invasive breast carcinoma in surgical specimen. OBJECTIVE: To know the frequency of sentimel node metastases in patients with ductal carcinoma in situ, identify differences between positive and negative cases. METHODS: Retrospective study of patients with ductal carcinoma in situ treated with sentinel lymph node biopsy because mastectomy indication, palpable tumor, radiological lesion = 5 cm, non-favorable breast-tumor relation and/or patients whom surgery could affect lymphatic flow drainage. RESULTS: Of 168 in situ carcinomas, 50 cases with ductal carcinoma in situ and sentinel lymph node biopsy were included, with a mean age of 51.6 years, 30 (60%) asymptomatic. The most common symptoms were palpable nodule (18%), nipple discharge (12%), or both (8%). Microcalcifications were common (72%), comedonecrosis pattern (62%), grade-2 histology (44%), and 28% negative hormonal receptors. Four (8%) cases had intra-operatory positive sentinel lymph node and one patient at final histo-pathological study (60% micrometastases, 40% macrometastases), all with invasive carcinoma in surgical specimen. Patients with intra-operatory positive sentinel lymph node where younger (44.5 vs 51 years), with more palpable tumors (50% vs 23.1%), and bigger (3.5 vs 2 cm), more comedonecrosis pattern (75% vs 60.8%), more indifferent tumors (75% vs 39.1%), and less cases with hormonal receptors (50% vs 73.9%), compared with negative sentinel lymph node cases, all these differences without statistic significance. CONCLUSIONS: One of each 12 patients with ductal carcinoma in situ had affection in sentinel lymph node, so we recommend continue doing this procedure to avoid second surgeries due the presence of occult invasive carcinoma.

Antecedentes: en pacientes con carcinoma ductal in situ la biopsia de ganglio centinela es motivo de controversia porque se reportan ganglios positivos en 1.4-12.5% debido al carcinoma invasor oculto en la pieza quirúrgica. Objetivo: conocer la frecuencia de metástasis en ganglio centinela en pacientes con carcinoma ductal in situ e identificar las diferencias entre los casos positivos y negativos. Material y métodos: estudio retrospectivo, transversal, analítico de pacientes con carcinoma ductal in situ a quienes se realizó una biopsia de ganglio centinela por requerir mastectomía, tener un tumor palpable, lesión radiológica = 5 cm, inadecuada relación mama-tumor o porque la escisión pudiera afectar el flujo linfático. Resultados: de 168 carcinomas in situ, se incluyeron 50 casos con carcinoma ductal in situ y biopsia de ganglio centinela, de pacientes con edad promedio de 51.6 años, 30 (60%) de ellas asintomáticas. Los signos reportados fueron: nódulo palpable (18%), secreción por el pezón (12%) o ambos (8%). Predominaron las microcalcificaciones (72%), comedonecrosis (62%) y grado histológico -2 (44%) con 28% de receptores hormonales negativos. En el estudio transoperatorio 4 (8%) pacientes tuvieron ganglio centinela positivo y un caso en estudio histopatológico definitivo (60% micrometástasis, 40% macrometástasis), todos con carcinoma invasor en la pieza quirúrgica. Las pacientes con ganglio centinela transoperatorio positivo eran más jóvenes (44.5 vs 51 años), con más tumores palpables (50 vs 23.1%), más grandes (3.5 vs 2 cm), más comedonecrosis (75 vs 60.8%), más indiferenciados (75% vs 39.1%) y menos receptores hormonales (50 vs 73.9%), que las que tenían ganglio centinela negativo, sin que estas diferencias tuvieran significación estadística. Conclusiones: puesto que 1 de cada 12 pacientes con carcinoma ductal in situ tiene afectación ganglionar en el ganglio centinela, se recomienda seguir tomando la biopsia para evitar segundas cirugías por un carcinoma invasor oculto.

A case of metastatic cancer with markedly elevated PSA level that was not detected by repeat prostate biopsy.

BACKGROUND: Prostate-specific antigen (PSA) is a widely used specific tumor marker for prostate cancer. We experienced a case of metastatic prostate cancer that was difficult to detect by repeat prostate biopsy despite a markedly elevated serum PSA level. CASE PRESENTATION: A 64-year-old man was referred to our hospital with lumbar back pain and an elevated serum PSA level of 2036 ng/mL. Computed tomography, bone scintigraphy, and magnetic resonance imaging showed systemic lymph node and osteoblastic bone metastases. Digital rectal examination revealed a small, soft prostate without nodules. Ten-core transrectal prostate biopsy yielded negative results. Androgen deprivation therapy (ADT) was started because of the patient's severe symptoms. Twelve-core repeat transrectal prostate biopsy performed 2 months later, and transurethral resection biopsy performed 5 months later, both yielded negative results. The patient refused further cancer screening because ADT effectively relieved his symptoms. His PSA level initially decreased to 4.8 ng/mL, but he developed castration-resistant prostate cancer 7 months after starting ADT. He died 21 months after the initial prostate biopsy from disseminated intravascular coagulation. CONCLUSION: CUP remains a considerable challenge in clinical oncology. Biopsies of metastatic lesions and multimodal approaches were helpful in this case.

[Sebaceous breast carcinoma: report of a rare histological special subtype]. / Sebaziöses Mammakarzinom: Fallbericht eines seltenen speziellen Subtyps.

We report on a case of sebaceous carcinoma of the breast as a rare histological special subtype of breast cancer. Because these tumors are uncommon, differential diagnostic considerations and the exclusion of Muir-Torre syndrome are emphasized. Finally possible mechanisms of development and therapeutic strategies for this carcinoma are discussed.

[Determination of proliferation in breast cancer by immunohistochemical detection of Ki-67]. / Proliferationsbestimmung beim Mammakarzinom durch den immunhistochemischen Nachweis von Ki-67.

Gene expression profiling has demonstrated the prognostic relevance of genes associated with proliferation in breast cancer. The immunohistochemical marker Ki-67 enables routine assessment of proliferation activity in pathology. In a number of retrospective but only few prospective studies the prognostic relevance of Ki-67 in breast cancer could be shown. Although there is no standardized approach with regard to which area of a histological section and how many cells should be counted in a quantitative or semiquantitative fashion as well as to the threshold, Ki-67 is broadly applied in breast pathology. This can be explained by the good reproducibility of the degree of proliferation assessed by Ki-67, at least in the low and high ranges, the possibility to substantiate grading and better practicability in core biopsies in comparison to mitotic counting. In neoadjuvant therapy of hormone receptor positive breast cancer, Ki-67 can probably predict the efficacy of pure hormone receptor blockade without chemotherapy.

[Microviscosity of erythrocyte membranes in breast cancer patients: connection with the receptor phenotype of the tumor].

The state of the viscosity of erythrocyte membranes in breast cancer patients (68--in menopause and 32--with menstrual cycle) was studied in comparison with the content of steroid hormone receptors in the tumor tissue and the age of patients. It is showed that the less hormone dependence of the tumor the higher viscosity of erythrocyte membranes that manifested by a decrease in the coefficient of eximerization (CE) of pyrene in the protein/lipid and in particular, lipid/lipid membrane layers. Increasing CE of pyrene in lipid/lipid layer of erythrocyte membranes above 1.7 units, reflecting a decline in their microviscosity, could be considered as an additional extra-tumor criterion for identification of the tumor as of hormone dependent type.

Pulmonary lymphangioleiomyomatosis: literature update.

Pulmonary lymphangioleiomyomatosis is an uncommon disease of unknown etiology characterized by the proliferation of abnormal smooth muscle cells in the lungs, leading to parenchymal destruction and progressive respiratory failure. The natural history of this disease remains poorly understood, primarily seen in women of childbearing age. The diagnosis can be difficult because symptoms are nonspecific and very similar to other respiratory diseases like asthma, emphysema and bronchitis. Lymphangioleiomyomatosis may not be diagnosed until a pneumothorax, chylothorax, interstitial lung disease or angiomyolipomas are discovered. The recent advances in genetic and molecular research provide new hope to discover the intricate mechanism of disease and evaluate new therapies. Internists, primary care physicians and pulmonologists should be aware of this condition in order to avoid delay in the diagnosis and institute appropriate therapy. The clinical features, pathophysiology, molecular genetics and medical treatment will be reviewed.

Androgen glucuronides analysis by liquid chromatography tandem-mass spectrometry: could it raise new perspectives in the diagnostic field of hormone-dependent malignancies?

Breast and prostate constitute organs of intense steroidogenic activity. Clinical and epidemiologic data provide strong evidence on the influence of androgens and estrogens on the risk of typical hormone-dependent malignancies, like breast and prostate cancer. Recent studies have focused on the role of androgen metabolites in regulating androgen concentrations in hormone-sensitive tissues. Steroid glucuronidation has been suggested to have a prominent role in controlling the levels and the biological activity of unconjugated androgens. It is well-established that serum levels of androgen glucuronides reflect androgen metabolism in androgen-sensitive tissues. Quantitative analysis of androgen metabolites in blood specimens is the only minimally invasive approach permitting an accurate estimate of the total pool of androgens. During the past years, androgen glucuronides analysis most often involved radioimmunoassays (RIA) or direct immunoassays, both methods bearing serious limitations. However, recent impressive technical advances in mass spectrometry, and particularly in high performance liquid chromatography coupled with mass spectrometry (LC-MS/MS), have overcome these drawbacks enabling the simultaneous, quantitative analysis of multiple steroids even at low concentrations. Blood androgen profiling by LC-MS/MS, a robust and reliable technique of high selectivity, sensitivity, specificity, precision and accuracy emerges as a promising new approach in the study of human pathology. The present review offers a contemporary insight in androgen glucuronides profiling through the application of LC-MS/MS, highlighting new perspectives in the study of steroids and their implication in hormone-dependent malignancies.