Expert consensus to optimize the treatment of elderly patients with luminal metastatic breast cancer

Most patients diagnosed with luminal metastatic breast cancer (MBC) who are seen in oncology consultations are elderly. MBC in elderly patients is characterized by a higher percentage of hormone receptor (HR) expression and a lower expression of human epidermal growth factor receptor 2 (HER2). The decision regarding which treatment to administer to these patients is complex due to the lack of solid evidence to support the decision-making process. The objective of this paper is to review the scientific evidence on the treatment of elderly patients with luminal MBC. For this purpose, the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Breast Cancer Research Group (GEICAM) and the SOLTI Group appointed a group of experts who have worked together to establish consensus recommendations to optimize the treatment of this population. It was concluded that the chronological age of the patient alone should not guide therapeutic decisions and that a Comprehensive Geriatric Assessment (CGA) should be performed whenever possible before establishing treatment. Treatment selection for the elderly population should consider the patient’s baseline status, the expected benefit and toxicity of each treatment, and the impact of treatment toxicity on the patient’s quality of life and functionality.

Expert consensus to optimize the treatment of elderly patients with luminal metastatic breast cancer.

Most patients diagnosed with luminal metastatic breast cancer (MBC) who are seen in oncology consultations are elderly. MBC in elderly patients is characterized by a higher percentage of hormone receptor (HR) expression and a lower expression of human epidermal growth factor receptor 2 (HER2). The decision regarding which treatment to administer to these patients is complex due to the lack of solid evidence to support the decision-making process. The objective of this paper is to review the scientific evidence on the treatment of elderly patients with luminal MBC. For this purpose, the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Breast Cancer Research Group (GEICAM) and the SOLTI Group appointed a group of experts who have worked together to establish consensus recommendations to optimize the treatment of this population. It was concluded that the chronological age of the patient alone should not guide therapeutic decisions and that a Comprehensive Geriatric Assessment (CGA) should be performed whenever possible before establishing treatment. Treatment selection for the elderly population should consider the patient's baseline status, the expected benefit and toxicity of each treatment, and the impact of treatment toxicity on the patient's quality of life and functionality.

Defining the optimal sequence for the systemic treatment of metastatic breast cancer

Metastatic breast cancer is a heterogeneous disease that presents in varying forms, and a growing number of therapeutic options makes it difficult to determine the best choice in each particular situation. When selecting a systemic treatment, it is important to consider the medication administered in the previous stages, such as acquired resistance, type of progression, time to relapse, tumor aggressiveness, age, comorbidities, pre- and post-menopausal status, and patient preferences. Moreover, tumor genomic signatures can identify different subtypes, which can be used to create patient profiles and design specific therapies. However, there is no consensus regarding the best treatment sequence for each subgroup of patients. During the SABCC Congress of 2014, specialized breast cancer oncologists from referral hospitals in Europe met to define patient profiles and to determine specific treatment sequences for each one. Conclusions were then debated in a final meeting in which a relative degree of consensus for each treatment sequence was established. Four patient profiles were defined according to established breast cancer phenotypes: pre-menopausal patients with luminal subtype, post-menopausal patients with luminal subtype, patients with triple-negative subtype, and patients with HER2-positive subtype. A treatment sequence was then defined, consisting of hormonal therapy with tamoxifen, aromatase inhibitors, fulvestrant, and mTOR inhibitors for pre- and post-menopausal patien ts; a chemotherapy sequence for the first, second, and further lines for luminal and triple-negative patients; and an optimal sequence for treatment with new antiHER2 therapies. Finally, a document detailing all treatment sequences, that had the agreement of all the oncologists, was drawn up as a guideline and advocacy tool for professionals treating patients with this disease (AU)

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Defining the optimal sequence for the systemic treatment of metastatic breast cancer.

Metastatic breast cancer is a heterogeneous disease that presents in varying forms, and a growing number of therapeutic options makes it difficult to determine the best choice in each particular situation. When selecting a systemic treatment, it is important to consider the medication administered in the previous stages, such as acquired resistance, type of progression, time to relapse, tumor aggressiveness, age, comorbidities, pre- and post-menopausal status, and patient preferences. Moreover, tumor genomic signatures can identify different subtypes, which can be used to create patient profiles and design specific therapies. However, there is no consensus regarding the best treatment sequence for each subgroup of patients. During the SABCC Congress of 2014, specialized breast cancer oncologists from referral hospitals in Europe met to define patient profiles and to determine specific treatment sequences for each one. Conclusions were then debated in a final meeting in which a relative degree of consensus for each treatment sequence was established. Four patient profiles were defined according to established breast cancer phenotypes: pre-menopausal patients with luminal subtype, post-menopausal patients with luminal subtype, patients with triple-negative subtype, and patients with HER2-positive subtype. A treatment sequence was then defined, consisting of hormonal therapy with tamoxifen, aromatase inhibitors, fulvestrant, and mTOR inhibitors for pre- and post-menopausal patien ts; a chemotherapy sequence for the first, second, and further lines for luminal and triple-negative patients; and an optimal sequence for treatment with new antiHER2 therapies. Finally, a document detailing all treatment sequences, that had the agreement of all the oncologists, was drawn up as a guideline and advocacy tool for professionals treating patients with this disease.

SEOM clinical guidelines for the treatment of early breast cancer

The incidence is increasing due to mammographic screening and an ageing population. In some countries the mortality rate has decreased especially in middleaged and younger groups because of improved treatment and possibly earlier detection. However, breast cancer is still the leading cause of cancer-related death in European women. The purpose of this work was to elaborate a Spanish Society of Medical Oncology guideline on pharmacologic interventions for early breast cancer (BC). We have compiled the latest advances in the management of this pathology either in the adjuvant and neoadjuvant setting, cytostatic and hormonal treatment, so that in a simple way could be useful to oncologist, residents and other related specialties (AU)

Increase of the M phenotype among erythromycin-resistant Streptococcus pneumoniae isolates from Spain related to the serotype 14 variant of the Spain9V-3 clone.

Between 1998 and 2003 the rate of erythromycin resistance among pneumococci in Spain was 34.4%. Although the MLS(B) phenotype was prevalent (94.7%), the rate of the M phenotype increased from 3.3% to 8.9% (P < 0.01). Clonal dissemination of mef(E)-carrying strains of serotype 14 variant of the Spain(9V)-3 clone was the major contributor to this increase.

Opsonophagocytosis versus complement bactericidal killing as effectors following Neisseria meningitidis group C vaccination.

BACKGROUND: Opsonophagocytosis and complement-mediated Neisseria meningitidis killing after vaccination were investigated. METHODS: Twelve seronegative healthy volunteers received one dose of polysaccharide A/C vaccine and were followed for 3 years. Ex vivo serum killing rates with polymorphonuclear cells (PMN) and/or complement were performed at 0, 1.5, 6, 12, 18, 24, 30 and 36 months. RESULTS: High mean total and median bactericidal antibodies were detected over time in all subjects. Considerable reduction of the initial inoculum was obtained only in the presence of complement, with or without PMN (with significant differences compared to curves without complement) a long time after vaccination. CONCLUSION: PMN did not increase post-vaccination bacterial killing, suggesting that antibody complement-mediated killing, and not opsonophagocytosis, is the main immune effector of the vaccine protection against N. meningitidis.

Coriocarcinoma mediastínico primario con metástasis pulmonares, cerebrales y hepáticas / Primary mediastinal choriocarcinoma with lung, brain and liver metastases

Entre el 1 y el 4 por ciento de los tumores germinales (TG) pueden originarse en el mediastino, siendo esta su localización extragonadal más frecuente. De ellos, los tumores germinales mediastínicos (TGM) no seminomatosos como el coriocarcinoma son menos habituales, más agresivos y de peor pronóstico. Presentamos el caso de un paciente varón de 34 años, diagnosticado de inicio en Febrero del 2000 de un coriocarcinoma mediastínico primario con metástasis pulmonares bilaterales, hepáticas y cerebrales, aprovechando la ocasión para revisar algunas características de estos tumores, de su historia natural, diagnóstico y tratamiento (AU)

Impact of meningococcal vaccination with combined serogroups A and C polysaccharide vaccine on carriage of Neisseria meningitidis C.

Two studies of meningococcal carriage state were carried out in Galicia (Spain) before and after a mass vaccination campaign between December 1996 and January 1997 against Neisseria meningitidis serogroup C with meningococcal serogroups A and C polysaccharide vaccine. The studies covered two areas with different incidence rates of meningococcal disease in 1996 (high and low incidence). Carriage rates of serogroup C showed a decrease in both areas, 47 and 65 % respectively, before and after the vaccination. Results showed a decrease in carrier state in the age groups 10-14- and 15-19-year-olds, but not in the 5-9-year-olds. These results demonstrate the effect of immunization on the reduction of the carriage state.

Antibiotic resistance of Neisseria gonorrhoeae in Spain: trends over the last two decades.

In vitro activities of six antimicrobial agents against 2966 strains of Neisseria gonorrhoeae, isolated in Spain between 1983 and 2001, were determined. The percentages of intermediately susceptible and resistant isolates to penicillin (MIC > or = 0.12 mg/L) and tetracycline (MIC > or = 0.5 mg/L) were very high over the period of study. Strains intermediately susceptible to cefoxitin were identified at a variable percentage during the study. All N. gonorrhoeae isolates were susceptible to spectinomycin and ceftriaxone. Recently, resistance to ciprofloxacin has emerged.

The epidemic wave of meningococcal disease in Spain in 1996-1997: probably a consequence of strain displacement.

During 1996 and 1997 an epidemic wave of meningococcal disease took place in Spain. Initial studies described the antigenic expression of the epidemic strain as C:2b:P1.2,5 and proposed that it was a variant of the previously identified Spanish C:2b:non-subtypable epidemic strain. To clarify this hypothesis, 1036 C:2b:P1.2(5) and 76 C:2b:NST isolates obtained during 1992-1999 were analysed by pulsed-field gel electrophoresis. The majority of the C:2b:P1.2,5 and C:2b:P1.2 isolates showed one of two very closely related profiles. During the epidemic period, 80% of the C:2b:NST strains showed these two pulsotypes. However, before the epidemic wave, most of these C:2b:NST strains (60%) showed a profile that was found infrequently among C:2b:P1.2,5 and C:2b:P1.2 isolates. A similar evolution was observed in C:2b:P1.5 isolates. Thirty-four C:2b:P1.2(5) and 10 C:2b:NST isolates, exhibiting representative pulsotypes, were subjected to multi-locus sequence typing. Isolates belonging to both A4 and ET-37 lineages were identified. These data point to the possibility that the A4 cluster has displaced the ET-37 complex among serogroup C meningococci in Spain.

[Pneumococcal meningitis in Spanish children: incidence, serotypes and antibiotic resistance. Prospective and multicentre study]. / Meningitis neumocócica en niños españoles: incidencia, serotipos y resistencia antibiótica. Estudio prospectivo multicéntrico.

OBJECTIVE: To determine the incidence, as well as the implicated serotypes and patterns of antibiotic resistance of Streptococcus pneumoniae meningitis in Spanish children. MATERIAL AND METHOD: We performed a prospective, multicenter study in five Autonomous Communities (Catalonia, Galicia, Madrid, Navarre and the Basque Country) for 1 year (1 February 2000 31 January 2001). All children aged 0-14 years with pneumococcal meningitis from all the hospitals in the Autonomous Communities studied were included. Diagnosis was based on clinical findings and isolation of S. pneumoniae in the cerebrospinal fluid/blood using routine methods or polymerase chain reaction. Serotyping was performed using the guellung reaction and/or immunoblotting and susceptibility to antibiotics was evaluated by the technique of agar dilution. The pediatric population aged 0-14 years in the Autonomous Communities studied comprises 2,290,304 children. RESULTS: Fifty-two cases were identified. One patient was aged less than 2 months old, 25 (48 %) were aged 2-12 months, and 12 patients (23 %) were aged 12-24 months. The annual incidence per 100,000 children aged between 1 and 2 years was 17.75 cases (95 % CI: 11.59 26.01) and 8.39 cases (95 % CI: 4.67 15.79) respectively, and that for children in the first 2 and 5 years of life was 13.13 (95 % CI: 9.29 18.02) and 6.29 (95 % CI: 4.57 8.,45) cases respectively. Nearly half the strains isolated (47.6 %) showed reduced sensitivity to penicillin. The most frequent serotype was 19F (12 cases [28.6 %]). Eighty percent of the isolated serotypes were included in the formula of the heptavalent conjugate vaccine. CONCLUSIONS: The incidence of pneumococcal meningitis in children from five Spanish Autonomous Communities is high, nearly twice that found in a prior retrospective studied performed in the same population 1-3 years previously. Almost all the isolated serotypes were included in the heptavalent conjugate vaccine. Half the strains showed reduced sensitivity to penicillin.

Meningitis neumocócica en niños españoles: incidencia, serotipos y resistencia antibiótica. Estudio prospectivo multicéntrico / Pneumococcal meningitis in spanish children: incidence, serotypes and antibiotic resistance

Objetivo: Conocer la incidencia, así como los serotipos implicados y los patrones de resistencia antibiótica de meningitis producidas por Streptococcus pneumoniae en niños españoles. Material y método: Estudio prospectivo, multicéntrico, realizado en 5 comunidades autónomas (Cataluña, Galicia, Madrid, Navarra y País Vasco) a lo largo de 1 año (1 de febrero de 2000 a 31 de enero de 2001). Se incluyeron todos los niños entre 0 y 14 años con meningitis neumocócica diagnosticados por sintomatología y líquido cefalorraquídeo (LCR) sugerente con aislamiento de S. pneumoniae en LCR/sangre por métodos habituales o por técnica de reacción en cadena de la polimerasa (PCR), de la totalidad de hospitales de las comunidades autónomas estudiadas. La serotipia se realizó mediante la reacción de quellung y/o immunoblotting y susceptibilidad a antibióticos por la técnica de dilución en agar. La población infantil de 0-14 años de estas comunidades es de 2.290.304 niños. Resultados: Se encontraron 52 casos. Uno tenía menos de 2 meses de edad, 25 (48%) entre 2 y 12 meses y 12 (23%) entre 12 y 24 meses. La incidencia anual por 100.000 niños en el primer y segundo año de vida fue de 17,75 casos (intervalo de confianza [IC] al 95%, 11,59-26,01) y 8,39 casos (IC 95%, 4,67-15,79) respectivamente, siendo en los primeros 2 y 5 años de vida de 13,13 (IC 95%, 9,29-18,02) y 6,29 (IC 95%, 4,57-8,45) casos, respectivamente. Casi la mitad de las cepas aisladas (47,6%) mostraron sensibilidad disminuida a la penicilina. El serotipo 19F fue el más frecuente (12 casos: 28,6%). El 80% de los serotipos aislados estuvieron incluidos en la formulación de la vacuna conjugada heptavalente. Conclusión: La incidencia de meningitis neumocócica en niños de las 5 comunidades autónomas españolas es elevada, casi el doble que la encontrada en un estudio previo de diseño retrospectivo, realizado en la misma población 1-3 años antes. Casi todos los serotipos aislados están incluidos en la vacuna conjugada heptavalente. La mitad de las cepas mostraron sensibilidad disminuida a la penicilina (AU)

Antimicrobial susceptibility and pneumococcal serotypes.

The increase in antibiotic resistance and the possible changes in serotype prevalence as a consequence of a new conjugated vaccine have contributed to renewed interest in the study of pneumococcal serotypes and their antibiotic resistances. Spain still has one of the highest penicillin resistance rates, but in the past 4-5 years a slight decrease has been observed. The level of resistance has not increased either, 12.7% of the 11 165 isolates studied showed high-level penicillin resistance but 94% of these had an MIC of only 2 mg/L. Serotypes 6, 9, 14, 19 and 23 included 83% of the penicillin-resistant pneumococci; the remaining 17% belonged to 18 different serotypes. We analysed these minor penicillin-resistant serotypes in view of their potential increase following a possible child vaccination programme. Four of these serotypes (11, 15, 21 and 35) were the most prevalent, and among them serotype 15 was particularly frequent with >50% of its strains resistant. The effective control of these minor penicillin-resistant serotypes should be based on continuous surveillance of pneumococcal epidemiology.

Association between asymptomatic carriage and sporadic (endemic) meningococcal disease in an open community.

We analysed a strain collection representative of the overall Neisseria meningitidis population circulating in an open community (46,000 inhabitants, Spain) during an endemic period (30 isolates from patients and 191 from throat cultures of healthy individuals) by both phenotypic and molecular techniques. Almost all patient isolates were assigned to three hyper-virulent lineages (ET-5 complex, ET-37 complex and cluster A4) by both multilocus enzyme electrophoresis (MEE) and pulsed-field gel electrophoresis (PFGE). In contrast, MEE and PFGE assigned 20% and 15% respectively of carrier isolates to the hyper-virulent clones (4% for both methods together). There was also a higher correlation between PFGE and phenotypes associated with virulent clones. These notable differences between the two molecular methods were further observed in more than half the carrier isolates, suggesting that the associations between these strains were distorted by recombination events. However, almost one-third of total endemic strains from symptom-free carriers and almost all patient strains belonged to clones defined by MEE and PFGE, with no known epidemiological connection. These data indicate low transmission and a weak clonal structure for N. meningitidis.

Necrólisis epidérmica tóxica postradioterapia / Toxic epidermal necrolysis post-radiotherapy

Propósito: Presentamos un caso de Necrolisis Epidérmica Tóxica ocurrido después de radioterapia en un paciente diagnosticado de carcinoma epidermoide de lengua. Material y método: Varón de 62 años, en tratamiento con Omeprazol y Finasteride por UIcus péptico e Hipertrofia benigna de próstata, que tras serle aplicado un protocolo de quimioterapia en régimen Al-Sarraf por el carcinoma de lengua previamente descrito y radioterapia en sesiones de manera fraccionada, 21 días después de la última sesión de radioterapia, desarrolla un cuadro compatible clínicamente con Necrolisis Epidérmica Tóxica que ocasiona el éxitus del mismo. Resultados: La necrolisis epidérmica tóxica (NET) es una dermatosis ampollosa de etiopatogenia desconocida, en la que han sido implicados múltiples agente causales, entre ellos la aplicación de radioterapia, y que dada la gravedad de la misma, así como las complicaciones que de ella se pueden derivar, requiere estrecha vigilancia. Conclusiones: Incidimos en la relación causa-efecto existente entre radioterapia y NET, así como el tratamiento de la misma basado en medidas de soporte evitando la administración de corticoides sistémicos (AU)

Investigation for a more virulent variant among the c:2b:P1.2,5 Spanish meningococcal epidemic strains by molecular epidemiology.

A rise in the incidence of meningococcal disease has occurred in Spain in recent years, especially in some regions in the north-west of the country. Most cases have been caused by meningococci characterised as Neisseria meningitidis C:2b:P1.2,5. A total of 107 C:2b:P1.2,5 meningococcal isolates (60 from patients and 47 from carriers) and 12 isolates showing related antigenic combinations (C:2b:NST, C:2b:P1.2, C:2b:P1.5, C:NT:P1.2,5) was analysed by pulsed-field gel electrophoresis to determine the genetic variability of the epidemic and related strains. Endonucleases BglII and NheI were used to cut chromosomal DNA. When BglII was used, most of the C:2b:P1.2,5 isolates showed the same pulsotype regardless of whether they were from clinical cases or carriers. Isolates showing the principal profile after digestion with endonuclease BglII were analysed with NheI. Four pulsotypes were identified, of which two were found in only one isolate each. The major profiles (1 and 2) showed differential distribution among clinical and carrier isolates; pulsotype 1 was the most frequent among clinical isolates. However, the proportions of isolates showing profiles 1 and 2 were similar among carrier isolates. This could indicate that there are two variants of the C:2b:P1.2,5 strain with differing pathogenicity.

Ex vivo bactericidal activity against group C Neisseria meningitidis in seronegative subjects.

BACKGROUND: To determine the anti-meningococcal C immunological activity by adding functional tests (opsonophagocytosis) to the classical serology techniques. SUBJECTS AND METHODS: 42 adult volunteers were screened using serological methods (determination of total and bactericidal antibodies). Seronegative subjects were tested by opsonophagocytosis. RESULTS: 24 subjects (57%) showed serological evidence of previous contact with Neisseria meningitidis group C antigens: 19 subjects had both total and bactericidal antibodies, two subjects had only total antibodies and three subjects had only bactericidal antibodies. Of the 18 seronegative subjects, five showed ex vivo activity in killing curves with or without polymorphonuclear cells: two subjects exhibited only complement-mediated bactericidal activity, one subject only opsonophagocytosis, and two subjects exhibited both activities. CONCLUSION: The addition of functional tests to the classical serological determination increases the evidence of previous contact with N. meningitidis antigens by 12%.