Background: There is uncertainty about the lifetime risk of contralateral breast cancer (CBC) in a woman who is diagnosed with early stage breast cancer. Studies report a wide range of rates of CBC between 2% and 35%. Objectives: (i) To determine the risk of CBC in women with early stage breast cancer, and (ii) to evaluate the risk of CBC in women who undergo adjuvant systemic treatment and adjuvant radiation treatment. Methods: PubMed, Ovid MEDLINE, EMBASE, Healthstar, Cochrane Central Register for Controlled Trials were searched. Studies were included if participants had: unilateral invasive breast carcinoma; 5 years of median follow-up; a minimum of 100 participants. Randomized controlled trials were included for the meta-analysis. A random-effects meta-analysis was used to estimate the pooled rate of CBC. Results: 4571 articles were extracted out of which 22 randomized controlled trials were included in the final meta-analysis. The overall pooled rate of CBC was 0.36% per year, (95% CI, 0.32% - 0.41%). The rate of CBC in studies without adjuvant systemic treatment was higher than the rate without such treatment, 0.56% per year (95% CI, 0.40% to 0.77%) versus 0.35% per year (95% CI, 0.31% to 0.40%). The rate of CBC in studies with adjuvant radiation treatment was 0.26% per year (95% CI, 0.18% to 0.39%) which is similar to the rate in studies with radiation. Conclusions: The rate of CBC in women with early stage breast cancer is relatively low. This is important for breast cancer patients who are considering contralateral prophylactic mastectomy. / Thesis / Master of Science (MS) / The rate of contralateral breast cancer in women with early stage breast cancer is uncertain. In order to determine this rate, a systematic review and meta analysis was conducted. The rate of contralateral breast cancer in women with early stage breast cancer was found to be 0.36% per year. This rate appears to be constant for up to 10 years after the original breast cancer diagnosis. This data is important for women with breast cancer and their healthcare teams in order to make decisions about bilateral mastectomy.

This thesis assesses the main risk factors contributing to contralateral breast cancer(CBC) amongst high-risk breast cancer patients with a view to formulating clinicallyuseful guidelines. The work has focused on several keys areas; a literature review ofthe various factors contributing to CBC, changing trends towards increasingnumbers of contralateral risk-reducing mastectomies (CRRMs), internationalvariations amongst breast surgeons’ attitudes towards risk-reducing mastectomy(RRM), attitudes towards CRRM amongst UK breast and plastic surgeons,assessment of CBC risk amongst BRCA1/2 mutation carriers and finally theformation of the ‘Manchester Guidelines for CRRM’.Breast cancer patients harbouring mutations in high penetrance genes (i.e. BRCA1/2,TP53, CHEK2, PALB) have the highest risk of developing breast cancer. A positivefamily history also increases the risk of subsequent breast cancer, with not muchevidence to support variation in risk with histological type. Risk reducing strategiesinclude anti-endocrine treatment, risk-reducing bilateral salpingo-oophorectomy(RRBSO) and CRRM with the former likely to account for the global trend ofdecreasing rates of CBC.Over the last decade, rates of CRRM have trebled in the USA – such a clear trendhas not yet been confirmed in Europe. Factors driving this trend include young ageat diagnosis, histological type (lobular carcinoma, lobular carcinoma in situ [LCIS]and ductal carcinoma in situ [DCIS]) and female surgeons. A direct comparison(USA v 4 European countries) found that American surgeons overall had a greaterknowledge of cancer genetics and nearly all (including Dutch and British surgeons)had positive attitudes towards RRM.A proportion of British surgeons were quoting inaccurate levels of CBC risk to theirpatients. Practices in the UK varied regarding CRRM – only 58% of surgeons alwaysdiscussed these cases in the MDT, with less than a third ever seeking apsychological or formal genetic assessment. Surgeons primarily offered thisprocedure to high-risk patients (gene mutation carriers or positive family history)but felt that the main reason patients requested CRRM was to alleviate anxiety. Studying over 1000 breast cancer patients who also had a mutation in either BRCA1or BRCA2 gene revealed that the risk of CBC was approximately 2-3% per year, forat least 2 decades. Young age at first breast cancer development (<40 years) affectedthis risk most. The effect bilateral risk-reducing salpingo-oophorectomy (BRRSO)was initially significant in an unadjusted analysis, but when accounting for delayedentry BRRSO did not appear to affect CBC risk. The use of SNPs was not able tostratify risk of CBC further. By considering the above, the Manchester Guidelines for CRRM have beenformulated. This 5-step protocol allows clinicians to objectively assess the risk ofCBC based on the evidence base and makes suggestions of a multi-disciplinaryapproach to managing requests for CRRM. Several breast units in the UK havealready adopted these guidelines and future studies hope to validate them so thatthey can be used more widely.

Em um estudo recente, Guadagnoli e Lee (2004) propuseram que o efeito de interferência contextual (IC) depende da dificuldade funcional de uma tarefa motora, com reversão do efeito de aprendizagem esperado quando a dificuldade imposta pela tarefa é elevada. No presente estudo esta hipótese foi testada em crianças na aprendizagem de uma tarefa de desenhos de padrões gráficos em uma base digitalizadora, recebendo feedback visual imediato invertido em um monitor de microcomputador. Foram avaliadas 30 crianças de 8-9 anos de idade, as quais foram designadas a três grupos: baixa IC, com prática variada entre blocos de tentativas possuindo o mesmo padrão gráfico; alta IC, com variação aleatorizada dos padrões gráficos entre as tentativas dentro de cada bloco; e controle, sem prática na tarefa. Após a etapa de prática, o tempo de movimento foi comparado entre os grupos em testes de retenção, transferência ipsilateral e transferência contralateral de aprendizagem. Os resultados mostraram que os dois grupos experimentais obtiveram resultados semelhantes de aprendizagem em todas as avaliações realizadas, com ambos os grupos apresentando resultados superiores ao grupo controle. A ausência de diferença entre os grupos experimentais indica que ambos os modos de variar a prática, sob baixa e alta IC, induziram efeitos semelhantes de aprendizagem, oferecendo apenas suporte parcial à hipótese de Guadagnoli e Lee. A vantagem dos grupos experimentais no teste de transferência contralateral indica que a adaptação devida à aprendizagem da tarefa não foi específica ao sistema neuromuscular empregado durante a prática / In a recent study, Guadagnoli and Lee (2004) proposed that the contextual interference (CI) effect depends on the functional difficulty of a motor task, with reversion of the expected learning effect when the difficulty imposed by a task is high. In the present study that hypothesis was tested in children in the learning of a task of drawing graphic patterns on a digitizing tablet while receiving immediate inversed visual feedback on a microcomputer monitor. Thirty 8-9 year-old children were assessed, who were assigned to three groups: low CI, with variability between blocks of trials composed of the same graphic pattern; high CI, with random variability within blocks of trials; and control, without practice on the task. Following the practice phase movement time was compared between the groups in retention, ipsilateral transfer, and contralateral transfer tests. Results showed that both experimental groups achieved similar results of learning in all tests, with the two groups presenting better results in comparison with the controls. Absence of difference between the experimental groups indicates that both modes of practice variability, under low and high CI, induced similar effects of learning, offering only partial support for the Guadagnoli and Lees hypothesis. The advantage of the experimental groups over the controls in the contralateral transfer of learning indicates that adaptation was not specific to the neuromuscular system employed during practice

Em um estudo recente, Guadagnoli e Lee (2004) propuseram que o efeito de interferência contextual (IC) depende da dificuldade funcional de uma tarefa motora, com reversão do efeito de aprendizagem esperado quando a dificuldade imposta pela tarefa é elevada. No presente estudo esta hipótese foi testada em crianças na aprendizagem de uma tarefa de desenhos de padrões gráficos em uma base digitalizadora, recebendo feedback visual imediato invertido em um monitor de microcomputador. Foram avaliadas 30 crianças de 8-9 anos de idade, as quais foram designadas a três grupos: baixa IC, com prática variada entre blocos de tentativas possuindo o mesmo padrão gráfico; alta IC, com variação aleatorizada dos padrões gráficos entre as tentativas dentro de cada bloco; e controle, sem prática na tarefa. Após a etapa de prática, o tempo de movimento foi comparado entre os grupos em testes de retenção, transferência ipsilateral e transferência contralateral de aprendizagem. Os resultados mostraram que os dois grupos experimentais obtiveram resultados semelhantes de aprendizagem em todas as avaliações realizadas, com ambos os grupos apresentando resultados superiores ao grupo controle. A ausência de diferença entre os grupos experimentais indica que ambos os modos de variar a prática, sob baixa e alta IC, induziram efeitos semelhantes de aprendizagem, oferecendo apenas suporte parcial à hipótese de Guadagnoli e Lee. A vantagem dos grupos experimentais no teste de transferência contralateral indica que a adaptação devida à aprendizagem da tarefa não foi específica ao sistema neuromuscular empregado durante a prática / In a recent study, Guadagnoli and Lee (2004) proposed that the contextual interference (CI) effect depends on the functional difficulty of a motor task, with reversion of the expected learning effect when the difficulty imposed by a task is high. In the present study that hypothesis was tested in children in the learning of a task of drawing graphic patterns on a digitizing tablet while receiving immediate inversed visual feedback on a microcomputer monitor. Thirty 8-9 year-old children were assessed, who were assigned to three groups: low CI, with variability between blocks of trials composed of the same graphic pattern; high CI, with random variability within blocks of trials; and control, without practice on the task. Following the practice phase movement time was compared between the groups in retention, ipsilateral transfer, and contralateral transfer tests. Results showed that both experimental groups achieved similar results of learning in all tests, with the two groups presenting better results in comparison with the controls. Absence of difference between the experimental groups indicates that both modes of practice variability, under low and high CI, induced similar effects of learning, offering only partial support for the Guadagnoli and Lees hypothesis. The advantage of the experimental groups over the controls in the contralateral transfer of learning indicates that adaptation was not specific to the neuromuscular system employed during practice

The effects of auditory efferent activity on peripheral physiology may be examined by presenting broadband noise (BBN) to the contralateral ear during otoacoustic emission (OAE) recordings. The presentation of BBN typically produces a reduction of OAE amplitudes in comparison to a condition without BBN. This is termed contralateral suppression. Limited information exists regarding the effects of contralateral BBN on responses observed at higher levels in the auditory system. The present study employed this paradigm to investigate interactions of attention and laterality on the transient evoked otoacoustic emission (TEOAE), auditory brainstem response (ABR) and cortical auditory evoked potentials (CAEP) P1-N1-P2. TEOAEs were evoked by 60 dB SPL clicks; ABRs and CAEPs were evoked by 60 dB SPL 2.0 kHz tone pips in 15 normally hearing adults. Four conditions were employed for each ear: 1) quiet (no noise); 2) 60 dB SPL contralateral BBN; 3) words (at -3 dB SNR) embedded in 60 dB SPL contralateral BBN while subjects classified words as animal versus food items; 4) words from condition #3 played backwards and embedded in 60 dB SPL contralateral BBN. For TEOAEs: 1) more suppression was evident in the active attention condition than the passive listening conditions and 2) right ear OAE amplitudes for the 8-18 ms time period exhibited more suppression in the presence of BBN for all noise conditions, although this did not meet statistical significance. For the ABR experiment, amplitudes in the noise conditions decreased in all epochs for the right ear, but not for the left. For the CAEP experiment, asymmetries were evident in temporal regions and an effect of contralateral noise was evident. The outcome of this investigation suggests that efferent activation by noise and active attention has diverse modulatory effects on electroacoustic and electrophysiologic responses along the auditory pathway.

El presente trabajo se realizó con el propósito de evaluar el efecto de la transferencia embrionaria ipsilateral y contralateral a la posición del cuerpo lúteo sobre la tasa de preñez en llamas. Se utilizaron 43 llamas hembras receptoras de 4 a 6 años, distribuidas aleatoriamente en 4 grupos de estudio: G1 (n=10): Cuerpo lúteo en ovario derecho y transferencia ipsilateral, G2 (n=10): Cuerpo lúteo en ovario derecho y transferencia contralateral, G3 (n=15): Cuerpo lúteo en ovario izquierdo y transferencia ipsilateral y G4 (n=8): Cuerpo lúteo en ovario izquierdo y transferencia contralateral. Se utilizaron 10 llamas hembras como donadoras de embriones, las cuales fueron sincronizadas con LH (1ml), superovuladas con 1000 UI de eCG y se provocó luteólisis con prostaglandina (1ml), siendo empadradas posteriormente. El día del empadre las llamas receptoras recibieron tratamiento con LH, con el propósito de sincronizarlas con las donadoras. Siete días post empadre se realizó el lavado uterino para la recolección, evaluación y transferencia de los embriones. La transferencia embrionaria a los grupos experimentales se realizó con embriones frescos el mismo día. Los resultados obtenidos señalan una tasa de preñez de 60% (G1) y 75% (G3) en las hembras con transferencia embrionaria ipsilateral derecha e izquierda respectivamente, mientras que en la transferencia contralateral derecha e izquierda fueron 30% (G2) y 25%(G4) respectivamente. Sin embargo, no se registraron diferencias significativas (p>0.05) entre el grupo G1 con los grupos G2, G3 y G4, además G2 no muestra diferencias significativas (p>0.05) con G4. Mientras que se encontró diferencia (p menor 0.05) entre el grupo G3 con los grupos G2 y G4. Estos resultados indicarían una mayor tasa de sobrevivencia embrionaria en llamas al realizar la transferencia en el cuerno ipsilateral a la posición del cuerpo lúteo ubicado en el ovario izquierdo. / The study was carried out with the objective of to evaluate the embryo survival after the embryo transfer to the uterine horn ipsilateral and contralateral to the corpus luteum (CL) in llamas. Fourtythree llamas recipient females, from 4 to 6 years old were randomly assigned in 4 groups: G1 (n=10): CL in right ovary and ipsilateral embryo transfer, G2 (n=10): CL in right ovary and contralateral transfer, G3 (n=15): CL in left ovary and ipsilateral transfer, and G4 (n=8): CL in left ovary and contralateral transfer. Ten llamas were used as embryo donors, they were synchronized with LH (1ml), then superovulated with 1000 UI eCG and induced to luteolysis with PGF2α; after that, all of them were mated. The same day of mating, the recipients were treated with LH, with the purpose of synchronization with donors. Seven days postmating, the uterine horns were flushed to recover, evaluate and transfer the embryos. The nonsurgical embryo transfer was used the same day with fresh embryos. The results of pregnancy rate were 60% (G1) and 75% (G3) in recipient females with ipsilateral embryo transfer right and left respectively. On the other hand, contralateral embryo transfer right and left were 30% (G2) and 25% (G4) respectively. However, the differences did not reach significance (p>0.05) between G1 with G2, G3 and G4. Furthermore, G2 not differ (p>0.05) from G4. Whereas, there is difference (p less 0.05) between G3 with G2 and G4. These results indicate that pregnancy rate is major in llamas when the embryo transfer was to the uterine horn ipsilateral to the CL in the left ovary.

Made available in DSpace on 2014-06-12T15:54:11Z (GMT). No. of bitstreams: 2 arquivo5301_1.pdf: 523784 bytes, checksum: 5d53cf11e783a44bb84658e706ea3cff (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2006 / O efeito da influência da lesão cortical contralateral sobre a Depressão Alastrante (DA) foi estudado em 19 ratos adultos bem-nutridos (alimentados por uma dieta comercial com 23% de proteína) e 18 desnutridos (amamentados por mães que receberam uma dieta deficiente dieta básica regional, com 8% de proteína). A DA foi deflagrada no córtex frontal direito em intervalos de 20 min e sua propagação foi monitorada em dois pontos da superfície parietal. Após um período de registro basal (2h), o córtex contralateral foi longitudinalmente cortado, com um bisturi elétrico, com a finalidade de interromper as fibras que vão em direção ao outro hemisfério através do corpo caloso (6,7mm de extensão, 3-5mm de profundidade e 1-2 mm da linha média, de acordo com o Atlas de Paxinos e Watson). Logo após a lesão, o registro foi continuado por mais duas horas. A lesão das fibras calosas foi histologicamente confirmada em todos os animais. Em comparação aos valores basais, as velocidades após a lesão aumentaram significativamente nos animais bem-nutridos e desnutridos (bem-nutridos, 3,34 ± 0,09 vs 4,03 ± 0,14 mm/min; desnutridos, 4,08 ± 0,20 vs 4,23 ± 0,29; P0,05, teste t pareado). Transcorridos 3-7 dias (período de recuperação), um segundo registro da DA (2h), realizado nos mesmos animais, revelaram uma persistência no aumento da velocidade da DA, indicando que este efeito é duradouro. Nenhuma diferença foi encontrada nos ratos controles (21 bem-nutridos e 21 desnutridos). O aumento na velocidade foi também observado num grupo adicional (n=8) submetido a lesão na linha média (calosotomia), sugerindo o envolvimento de fibras calosas sobre o efeito observado. Os resultados dão respaldo à hipótese de um papel inibitório da atividade cortical contralateral sobre a DA, que parece ser duradouro e que não é influenciado pela desnutrição precoce

Made available in DSpace on 2014-06-12T15:55:34Z (GMT). No. of bitstreams: 2 arquivo6303_1.pdf: 523772 bytes, checksum: 6150ce66f8fd0ae8088672cf1d7636b4 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2006 / O efeito da influência da lesão cortical contralateral sobre a Depressão Alastrante (DA) foi estudado em 19 ratos adultos bem-nutridos (alimentados por uma dieta comercial com 23% de proteína) e 18 desnutridos (amamentados por mães que receberam uma dieta deficiente dieta básica regional, com 8% de proteína). A DA foi deflagrada no córtex frontal direito em intervalos de 20 min e sua propagação foi monitorada em dois pontos da superfície parietal. Após um período de registro basal (2h), o córtex contralateral foi longitudinalmente cortado, com um bisturi elétrico, com a finalidade de interromper as fibras que vão em direção ao outro hemisfério através do corpo caloso (6,7mm de extensão, 3-5mm de profundidade e 1-2 mm da linha média, de acordo com o Atlas de Paxinos e Watson). Logo após a lesão, o registro foi continuado por mais duas horas. A lesão das fibras calosas foi histologicamente confirmada em todos os animais. Em comparação aos valores basais, as velocidades após a lesão aumentaram significativamente nos animais bem-nutridos e desnutridos (bem-nutridos, 3,34 ± 0,09 vs 4,03 ± 0,14 mm/min; desnutridos, 4,08 ± 0,20 vs 4,23 ± 0,29; P0,05, teste t pareado). Transcorridos 3-7 dias (período de recuperação), um segundo registro da DA (2h), realizado nos mesmos animais, revelaram uma persistência no aumento da velocidade da DA, indicando que este efeito é duradouro. Nenhuma diferença foi encontrada nos ratos controles (21 bem-nutridos e 21 desnutridos). O aumento na velocidade foi também observado num grupo adicional (n=8) submetido a lesão na linha média (calosotomia), sugerindo o envolvimento de fibras calosas sobre o efeito observado. Os resultados dão respaldo à hipótese de um papel inibitório da atividade cortical contralateral sobre a DA, que parece ser duradouro e que não é influenciado pela desnutrição precoce

No description available.

The mature central nervous system (CNS) has the capacity to reorganise when there is a change in sensory input. However, studies using the N1 cortical auditory evoked potential, or its magnetic homolog N1m, have not consistently demonstrated evidence of plasticity in adults with late onset unilateral deafness. In addition, little is known about the time course of experience-related plasticity in adults with unilateral deafness. The aim of the studies described in this thesis was to investigate plasticity in adults with unilateral deafness, using N1 auditory evoked potentials. Deafness occurred as a result of surgery for the removal of an acoustic neuroma. The stimuli were 500-Hz and 4-kHz tones presented monaurally to the intact ear, and the data were analysed using global field power and dipole source analysis. In the first study (Chapter 3), hemispheric asymmetries in the N1 response were measured in a group of 24 normally hearing adults at presentation levels of 40, 60 and 80 dB sensation level (SL). The results revealed that the mean hemispheric asymmetry was greater for the 4-kHz stimulus but there was no significant effect of presentation level. In addition, the results revealed that the magnitude of hemispheric asymmetry depended on the ear of stimulation; a trend for larger asymmetries was observed following stimulation of the left ear. The results of the study provide confidence that the methodology is suitable for measuring hemispheric asymmetries in individuals with unilateral deafness. The effect of stimulus level is important since this will vary in plasticity studies involving individuals with late onset unilateral deafness due to their pure tone sensitivity thresholds. Clarifying the effect of stimulus frequency in normally hearing adults is important since the effect of stimulus frequency on plasticity following unilateral deafness has not been reported previously.In the second study (Chapter 4), N1 responses were measured in 19 adults with unilateral deafness (10 and 9 right- and left-sided deafness respectively). Stimuli were typically presented at 60 dB SL. The results revealed that there was significantly greater mean activity and a shift towards reduced hemispheric asymmetries compared with 19 audiogram-matched controls. Similar changes were apparent after both right- and left-sided deafness, and for both 500-Hz and 4-kHz stimuli. Therefore the results reveal evidence of experience-related plasticity that mirrors the findings reported in animal models. The reduced hemispheric asymmetries were reflected in the dipole source model used in this thesis by changes in dipole strength, location and orientation. These findings may explain the inconsistencies reported in previous studies that have used N1 or N1m, where dipole location and orientation have not always been taken into adequate consideration.In the third study (Chapter 5), longitudinal measurements were made in six adults just prior to the onset of complete unilateral deafness, and at 1-, 3- and 6-months after the onset (4 right-sided and 2 left-sided deafness respectively). The results from the second study were further analysed by splitting the data into two groups: nine participants with <2 years deafness and 10 with ≥2 year's deafness. The results from the longitudinal data revealed that there was a significant difference in mean activity across the four conditions. For both stimulus types an increase in mean activity occurred after the onset of deafness, and hemispheric asymmetries were reduced. The biggest changes occurred within 1-month, although further increases were noted in some individuals with ≥2 year's duration of deafness. Changes that continue over this period of time suggest different physiological mechanisms for plasticity within the human central auditory system.