As the survival rate increases, the importance of quality of life post-cancer is increasing. This, in conjunction with genetic screening, has increase the number of breast reconstructions 36%. The most common complication causing revision of reconstructive surgery is the formation of a dense scar capsule around the silicone implant called capsular contracture. Nearly all patients will experience this complication, though with different degrees of response, ranging from moderate scarring to major disfigurement and pain at the implant site. Presently, there is no way to predict the degree of contraction capsule formation that individual patients will suffer prospectively, nor is there clinical approach to preventing this complication. Patient information and tissue was collected in a uniform manner to address these lingering problems. Clinical data was used to construct a predictive model which can accurately predict capsular contracture severity in breast reconstruction patients. Histological analysis demonstrated differences in structure and cell composition between different capsule severities. Of particular note, a new region was described which could serve as the communication interface between innate immune cells and fibroblasts. RNA-seq analysis identified 1029 significantly dysregulated genes in severe capsules. Pathway enrichment was then performed which highlights IL4/13 signaling, extracellular matrix organization, antigen presentation, and interferon signaling as importantly dysregulated pathways. These RNA results were also compared to various clinical and histological measurements to evaluate novel correlations. PVT-1, a long non-coding RNA associated with cancer, was strongly correlated to capsules formed after cancer removal. This suggests cancerous transformations of cell types that remain after the tumor is removed. Furthermore, transgelin and caspase 7 correlated to myofibroblasts density, suggesting an abnormal fibroblasts that are resistant to cell death and may have enhanced contractile abilities. Capsule formation is a complex process however, with well controlled clinical models quantitative differences can be found. These results serve as stepping stone for the field to move beyond retrospective clinical trials and pursue treatments and preventative measures. / Ph. D.

Bakgrund: I Sverige är bröstcancer den vanligaste formen av kvinnlig cancer och utgör nära en tredjedel av kvinnlig cancer. I behandlingen av bröstcancer har kirurgi en betydande roll. Nära hälften av kvinnorna genomgår mastektomi, men det finns en stor variation inom landet. Att förlora ett bröst efter mastektomi har såväl en kroppslig som psykologisk innebörd. Avhandlingen omfattar fyra delstudier som beskriver detta på olika sätt. Syfte: Det övergripande syftet med avhandlingen är att studera betydelsen av att förlora ett bröst på grund av cancersjukdom samt motiv och beslutsprocess i ställningstagande till att leva med eller utan ett rekonstruerat bröst. Metod: Avhandlingen baseras på två populationer av kvinnor boende i norra Sverige som genomgått mastektomi på grund av bröstcancer: de kvinnor som genomgått mastektomi under 2003 (delstudie I–III) samt de kvinnor som genomgått mastektomi mellan oktober 2006 och september 2007 (delstudie IV). Dessa kvinnor identifierades via det regionala cancerregistret, onkologiskt centrum, Norrlands universitetssjukhus. Statistiska analyser genomfördes i delstudie I och IV och tematisk narrativ analys har tillämpats i delstudie II och III. Resultat: Delstudie I: År 2007 skickades ett nykonstruerat självskattningsformulär ”Life After Mastectomy” (LAM) ut till 149 kvinnor varav 85% (n=126) besvarades. Av dessa kvinnor hade 25% genomgått bröstrekonstruktion. Resultaten av en multipel regressionsanalys visade att bröstrekonstruktion var signifikant relaterat till lägre ålder, känsla av att vara attraktiv och sexuellt intresse. För att få en djupare och mer nyanserad förståelse kring innebörder av att förlora ett bröst efter mastektomi och motiv till att avstå från eller genomgå bröstrekonstruktion gjordes ett strategiskt urval av 15 kvinnor från delstudie I som deltog i en forskningsintervju(delstudie II). I den tematiska narrativa analysen identifierades tre typberättelser. I den första typberättelsen beskrevs mastektomin som ”no big deal” och att genomgå en bröstrekonstruktion var inte ens värt att överväga. I den andra typberättelsen beskrevs mastektomin som ”att förlora sig själv” och en bröstrekonstruktion beskrevs som ett sätt att återställa sig som person, kvinna och sexuell varelse. Den tredje typberättelsen intog en position mellan ”no big deal” och ”att förlora sig själv” och en bröstrekonstruktion beskrevs som ett välkommet erbjudande vilket gjorde det enklare att se och känna sig som kvinna. I delstudie III undersöktes sex kvinnors erfarenheter av att genomgå bröstrekonstruktion. Samtliga kvinnor var oförberedda på den krävande procedur som de genomgick. De beskrev processen som svår och smärtsam med upprepade operationer och en oväntat lång konvalescenstid. Även om kvinnorna var oförberedda på hur tufft det skulle komma att bli både fysiskt och emotionellt beskrevs bröstrekonstruktionen  som betydelsefull för dem. Delstudie IV: I denna uppföljningsstudie inkluderades kvinnorna 10 månader efter mastektomin då självskattningsformuläret LAM skickades ut. Datainsamlingen med samma formulär upprepades två år senare (tre år efter mastektomin). Kvinnornas (n=76) känsla av attraktivitet och kvinnlighet hade inte förändrats mellan de två mättillfällena, med undantag för vissa aspekter av sexualitet som hade försämrats. Vid uppföljningen hade 21% av kvinnorna genomgått bröstrekonstruktion och dessa kvinnor var yngre. I övrigt kundeinga signifikanta skillnader ses mellan de kvinnor som genomgått respektiveej genomgått bröstrekonstruktion. Slutsats: Denna avhandling ger en inblick i betydelsen av att förlora ett bröst efter mastektomi. Att förlora ett bröst efter mastektomi kan vara av mindre eller större betydelse. För de kvinnor som upplevde bröstförlusten som en förlust av sig själva, kom en bröstrekonstruktion att betraktas som en livsnödvändighet (delstudie II). De flesta av kvinnorna 75% i delstudie I och 79% i delstudie IV genomgick inte någon bröstrekonstruktion. De kvinnor som genomgick rekonstruktiv kirurgi beskrev proceduren som svår fysiskt och emotionellt, men trots detta sågs den som viktig för dem (delstudie III). Vid uppföljningen i delstudie IV, var kvinnornas upplevelse av attraktivitet och kvinnlighet oförändrade, men upplevelsen av att känna sig bekväm vid sexuell intimitet utvecklades negativt. Detta var oberoende av om kvinnan genomgått bröstrekonstruktion eller inte, vilket kan ses som överraskande. Det är viktigt att som sjukvårdpersonal uppmärksamma hur den enskilda kvinnan själv upplever betydelsen av att ha förlorat ett bröst för att inte låta sig styras av vaga schabloner kring relationen bröst–sexualitet–kvinnlighet. / Background: Breast cancer is the most common cancer in women, representing nearly one-third of all cancer cases among women in Sweden. The mainstay in breast cancer treatment is surgery and nearly half of the women undergo a mastectomy but there is considerable variation between different counties. Understanding the impact of losing a breast and what motivates women to decide for or against breast reconstructive surgery after mastectomy is necessary in caring for women affected by breast cancer. This PhD thesis comprises four studies that examine this topic in different ways. Aim: The overall aim of the thesis is to explore meanings of losing a breast after mastectomy and what motivates women to opt for reconstruction or no reconstruction of the lost breast. Methods: The thesis is based on two populations, all women who underwent mastectomy in 2003 (Studies I–III) and all women living in northern Sweden who underwent mastectomy during November 2006 to October 2007 (Study IV). The women were identified by the Oncological Centre, at Umeå University Hospital, Umeå, Sweden. In Studies I and IV statistical analyses were performed while in Studies II and III thematic narrative analyses were applied. Results: Study I: in 2007 149 women received a newly developed selfreported questionnaire titled ‘Life After Mastectomy (LAM)’. In total 85% (n=126) of the women completed and returned the questionnaire, 25% of whom had undergone breast reconstruction. Multiple regression analysis showed that these women were younger and scored lower on feelings of attractiveness and higher on sexual activity compared with the women who had opted not to have breast reconstruction. In Study II, to gain a more nuanced understanding of the women’s lived experiences of losing a breast and what had motivated them to opt for or against breast reconstruction, a strategic sample of 15 women from Study I were selected to participate in a research interview. Using thematic narrative analysis of the interviews we identified three types of storylines. In the first storyline the mastectomy was described as ‘no big deal’ and breast reconstruction was not even worth considering. In the second storyline the mastectomy was described as a ‘loss of self’ and the breast reconstruction was perceived as a means to be restored as a person, a woman and a sexual being. The third storyline fell in between ‘no big deal’ and ‘loss of self’, with breast reconstruction described as a welcome offer that made it easier to look and feel like a woman. In Study III, a pilot study, we explored six women’s experiences of undergoing breast reconstructive surgery. All women had not been prepared for the strenuous experience: the process was described as difficult and painful, consisting of several operations and an unexpectedly long recovery period. Although the women were ill prepared for how arduous it would be, both physically and emotionally, having a breast reconstruction had been important to all of them. Study IV: in this follow-up study, women completed the self-reported LAM questionnaire 10 months after mastectomy and again 2 years later, i.e. about 3 years after mastectomy. It appeared that their feelings of attractiveness and femininity had not changed during the follow-up time, except for some aspects of sexuality which had been negatively affected. At follow-up, 21% of the women had undergone breast reconstruction. When comparing these women with those who had not undergone reconstructive surgery, we found no significant differences apart from their younger age. Conclusion: This thesis provides insight into the meanings of losing a breast due to mastectomy. Loss of a breast can be of minor or major importance. For those women who experienced the loss of a breast as a loss of the self, breast reconstruction became a necessity for restoring personhood (Study II). However, most women studied, 75% in study I and 79% in study IV, chose not to undergo breast reconstruction. Those who did, described it as a very tough procedure, both physically and emotionally. Having a breast reconstruction had been important for them (Study III). After a 2-year follow-up of the women (Study IV), their feelings of attractiveness and femininity were unchanged, but not their experiences of sexual intimacy and comfort, which had decreased regardless of whether they had undergone breast reconstruction or not. This finding was unexpected. It is important for health care professionals to be attentive to how women themselves experience the personal meaning of losing a breast. Care professionals should guard against popular preconceptions of the female breast and how it is associated with sexuality and womanliness, and hence of the patient’s needs.

Introdução: enxerto autólogo de gordura é uma técnica cirúrgica que vem sendo utilizada nas reconstruções mamárias tardias para reparação de assimetrias causadas pela cirurgia conservadora e sequelas da radioterapia. Ainda não se sabe se há risco oncológico nesse tipo de procedimento, quando aplicado na reconstrução mamária imediata, pois até o momento não existem estudos publicados utilizando esse método. Objetivo: avaliar e comparar pacientes submetidas exclusivamente à cirurgia conservadora com pacientes submetidas ao enxerto autólogo de gordura como reconstrução imediata à cirurgia conservadora para desfecho de recorrência local e sistêmica nos três primeiros anos. Método: trata-se de um estudo de coorte histórica. Foram analisadas: (i) 167 pacientes submetidas a tratamento conservador sem reconstrução e (ii) 27 pacientes submetidas a tratamento conservador de mama com reconstrução imediata com enxerto autólogo de gordura, seguindo a técnica descrita por Coleman, e todas realizadas pelo mesmo cirurgião (foram seis controles para um caso). Todas as pacientes tinham carcinoma invasor como critério de seleção e foram observadas em um período de até 36 meses para avaliação da taxa de recorrência local. As pacientes avaliadas são do Serviço de Mastologia do Hospital de Clínicas de Porto Alegre (HCPA) e foram selecionadas no período de 2004 e 2011. Foram excluídas as pacientes que haviam realizado tratamento prévio para câncer de mama. Resultados: a incidência de recidiva local foi de 2,4% no grupo da cirurgia conservadora. Nenhuma paciente do grupo de lipoenxertia apresentou recorrência local durante o período do estudo. Para recorrência sistêmica, as taxas obtidas foram de 3,7% (1 paciente) para grupo lipoenxertia e 1,8% (3 pacientes) para grupo da cirurgia conservadora. Conclusão: durante o estudo, ambos os grupos não mostraram diferença significativa para recorrência local e sistêmica. O enxerto autólogo imediato de gordura parece ser um procedimento seguro. O seguimento mais longo dessas pacientes irá estabelecer qual o nível de segurança oncológica desse método. / Background: Autologous fat grafting has been used either for correcting contour or soft tissue defects in different specialties, for many years. In recent years, fat grafting was established to improve quality in breast reconstruction. The oncological risk is not known because there are no studies using this method in the immediate breast reconstruction. Aim: to evaluated patients who underwent breast conserving surgery with fat grafting in order to repair breast defect, in the same time of the surgery, for local and systemic recurrence, in the 36 months follow-up. Methods: a historical cohort study was performed. We analyzed: (i) 167 who women underwent breast conserving surgery without fat grafting and (ii) 27 women who underwent a breast conserving surgery with immediate repair with autologous fat grafting that were performed according to the Coleman’s technique by a single surgeon (6 controls per fat grafting patient). Both groups were matched for main cancer criteria and the primary end point was locorregional recurrence. All patients are from Breast Cancer Unit, Hospital de Clínicas, Brazil, from 2004 to 2011. Results: The incidence of locorregional recurrences was 2.4% for the conservative group and no cases for fat grafting group, during the studied period. For systemic recurrence, we found 3.7% (1 patient) for fat grafting group and 1.8% (3 patients) for conservative group. Conclusions: During the study period, both groups showed no statistical difference for local and systemic recurrence. Autologous fat grafting seems to be a safe procedure in immediate breast reconstruction. Nevertheless this immediate technique needs longer follow up to confirm the oncological safety of this method.

Introdução: enxerto autólogo de gordura é uma técnica cirúrgica que vem sendo utilizada nas reconstruções mamárias tardias para reparação de assimetrias causadas pela cirurgia conservadora e sequelas da radioterapia. Ainda não se sabe se há risco oncológico nesse tipo de procedimento, quando aplicado na reconstrução mamária imediata, pois até o momento não existem estudos publicados utilizando esse método. Objetivo: avaliar e comparar pacientes submetidas exclusivamente à cirurgia conservadora com pacientes submetidas ao enxerto autólogo de gordura como reconstrução imediata à cirurgia conservadora para desfecho de recorrência local e sistêmica nos três primeiros anos. Método: trata-se de um estudo de coorte histórica. Foram analisadas: (i) 167 pacientes submetidas a tratamento conservador sem reconstrução e (ii) 27 pacientes submetidas a tratamento conservador de mama com reconstrução imediata com enxerto autólogo de gordura, seguindo a técnica descrita por Coleman, e todas realizadas pelo mesmo cirurgião (foram seis controles para um caso). Todas as pacientes tinham carcinoma invasor como critério de seleção e foram observadas em um período de até 36 meses para avaliação da taxa de recorrência local. As pacientes avaliadas são do Serviço de Mastologia do Hospital de Clínicas de Porto Alegre (HCPA) e foram selecionadas no período de 2004 e 2011. Foram excluídas as pacientes que haviam realizado tratamento prévio para câncer de mama. Resultados: a incidência de recidiva local foi de 2,4% no grupo da cirurgia conservadora. Nenhuma paciente do grupo de lipoenxertia apresentou recorrência local durante o período do estudo. Para recorrência sistêmica, as taxas obtidas foram de 3,7% (1 paciente) para grupo lipoenxertia e 1,8% (3 pacientes) para grupo da cirurgia conservadora. Conclusão: durante o estudo, ambos os grupos não mostraram diferença significativa para recorrência local e sistêmica. O enxerto autólogo imediato de gordura parece ser um procedimento seguro. O seguimento mais longo dessas pacientes irá estabelecer qual o nível de segurança oncológica desse método. / Background: Autologous fat grafting has been used either for correcting contour or soft tissue defects in different specialties, for many years. In recent years, fat grafting was established to improve quality in breast reconstruction. The oncological risk is not known because there are no studies using this method in the immediate breast reconstruction. Aim: to evaluated patients who underwent breast conserving surgery with fat grafting in order to repair breast defect, in the same time of the surgery, for local and systemic recurrence, in the 36 months follow-up. Methods: a historical cohort study was performed. We analyzed: (i) 167 who women underwent breast conserving surgery without fat grafting and (ii) 27 women who underwent a breast conserving surgery with immediate repair with autologous fat grafting that were performed according to the Coleman’s technique by a single surgeon (6 controls per fat grafting patient). Both groups were matched for main cancer criteria and the primary end point was locorregional recurrence. All patients are from Breast Cancer Unit, Hospital de Clínicas, Brazil, from 2004 to 2011. Results: The incidence of locorregional recurrences was 2.4% for the conservative group and no cases for fat grafting group, during the studied period. For systemic recurrence, we found 3.7% (1 patient) for fat grafting group and 1.8% (3 patients) for conservative group. Conclusions: During the study period, both groups showed no statistical difference for local and systemic recurrence. Autologous fat grafting seems to be a safe procedure in immediate breast reconstruction. Nevertheless this immediate technique needs longer follow up to confirm the oncological safety of this method.

Introdução: enxerto autólogo de gordura é uma técnica cirúrgica que vem sendo utilizada nas reconstruções mamárias tardias para reparação de assimetrias causadas pela cirurgia conservadora e sequelas da radioterapia. Ainda não se sabe se há risco oncológico nesse tipo de procedimento, quando aplicado na reconstrução mamária imediata, pois até o momento não existem estudos publicados utilizando esse método. Objetivo: avaliar e comparar pacientes submetidas exclusivamente à cirurgia conservadora com pacientes submetidas ao enxerto autólogo de gordura como reconstrução imediata à cirurgia conservadora para desfecho de recorrência local e sistêmica nos três primeiros anos. Método: trata-se de um estudo de coorte histórica. Foram analisadas: (i) 167 pacientes submetidas a tratamento conservador sem reconstrução e (ii) 27 pacientes submetidas a tratamento conservador de mama com reconstrução imediata com enxerto autólogo de gordura, seguindo a técnica descrita por Coleman, e todas realizadas pelo mesmo cirurgião (foram seis controles para um caso). Todas as pacientes tinham carcinoma invasor como critério de seleção e foram observadas em um período de até 36 meses para avaliação da taxa de recorrência local. As pacientes avaliadas são do Serviço de Mastologia do Hospital de Clínicas de Porto Alegre (HCPA) e foram selecionadas no período de 2004 e 2011. Foram excluídas as pacientes que haviam realizado tratamento prévio para câncer de mama. Resultados: a incidência de recidiva local foi de 2,4% no grupo da cirurgia conservadora. Nenhuma paciente do grupo de lipoenxertia apresentou recorrência local durante o período do estudo. Para recorrência sistêmica, as taxas obtidas foram de 3,7% (1 paciente) para grupo lipoenxertia e 1,8% (3 pacientes) para grupo da cirurgia conservadora. Conclusão: durante o estudo, ambos os grupos não mostraram diferença significativa para recorrência local e sistêmica. O enxerto autólogo imediato de gordura parece ser um procedimento seguro. O seguimento mais longo dessas pacientes irá estabelecer qual o nível de segurança oncológica desse método. / Background: Autologous fat grafting has been used either for correcting contour or soft tissue defects in different specialties, for many years. In recent years, fat grafting was established to improve quality in breast reconstruction. The oncological risk is not known because there are no studies using this method in the immediate breast reconstruction. Aim: to evaluated patients who underwent breast conserving surgery with fat grafting in order to repair breast defect, in the same time of the surgery, for local and systemic recurrence, in the 36 months follow-up. Methods: a historical cohort study was performed. We analyzed: (i) 167 who women underwent breast conserving surgery without fat grafting and (ii) 27 women who underwent a breast conserving surgery with immediate repair with autologous fat grafting that were performed according to the Coleman’s technique by a single surgeon (6 controls per fat grafting patient). Both groups were matched for main cancer criteria and the primary end point was locorregional recurrence. All patients are from Breast Cancer Unit, Hospital de Clínicas, Brazil, from 2004 to 2011. Results: The incidence of locorregional recurrences was 2.4% for the conservative group and no cases for fat grafting group, during the studied period. For systemic recurrence, we found 3.7% (1 patient) for fat grafting group and 1.8% (3 patients) for conservative group. Conclusions: During the study period, both groups showed no statistical difference for local and systemic recurrence. Autologous fat grafting seems to be a safe procedure in immediate breast reconstruction. Nevertheless this immediate technique needs longer follow up to confirm the oncological safety of this method.

Made available in DSpace on 2016-12-23T14:38:01Z (GMT). No. of bitstreams: 1 Corpos marcados e fe na vida.pdf: 513051 bytes, checksum: 9fadb60bc3771725942c9cfa43672c2b (MD5) Previous issue date: 2007-09-10 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Historicamente, a população foi mantida distante das discussões em torno das políticas públicas de saúde no Brasil, marcadas por interesses muitas vezes distantes das necessidades da população e por uma relação autoritária, técnica e mercantil entre médico e paciente e entre serviços de saúde e população. Com a Reforma Sanitária e a implementação do SUS, nas décadas de 1980 e 1990, passa-se a pensar a saúde numa nova ótica, integrando ações curativas e preventivas construídas com a participação popular. Em se tratando do câncer de mama, que é a principal causa de neoplasia e a segunda causa de mortalidade por câncer entre mulheres no Brasil, a participação dos usuários na elaboração e acompanhamento da efetivação destas políticas é essencial. Este estudo objetivou explorar repercussões do câncer de mama na vida das mulheres, as demandas decorrentes e suas relações com as Políticas Públicas de Saúde. Participaram 08 mulheres que tiveram câncer de mama e realizaram o tratamento pelo SUS em Vitória/ES. Todas tiveram o diagnóstico há pelo menos três anos. Este critério deveu-se ao fato de que estas mulheres puderam relatar tanto as experiências atuais, como as vivências e enfrentamentos que passaram no período do diagnóstico, da cirurgia e do tratamento. Considerando a importância do contexto vivenciado pelas mulheres ao longo de toda a vida na elaboração da experiência do câncer de mama, utilizou-se a técnica de História Oral na coleta de dados. Dessa forma, ao se trabalhar com as narrativas das mulheres sobre suas histórias de vida, foi enfocada, dentro de cada história, a vivência da mastectomia. A análise dos dados foi feita utilizando a Análise de Conteúdo. Foi possível observar que as mulheres possuíam, antes do diagnóstico, uma representação do câncer como morte inevitável e imediata . O momento do diagnóstico foi marcado por muito sofrimento, e as dificuldades em conseguir uma vaga para consulta e cirurgia aumentaram ainda mais a angústia. Após a cirurgia, as restrições das atividades cotidianas e o desejo de reconstrução da mama foram questões que afligiram as participantes. Ainda assim, relataram uma luta constante em busca de qualidade de vida, considerando-se vencedoras. Percebe-se que as Políticas de Saúde contemplam na legislação as mulheres com câncer de mama, entretanto, isto não se efetiva totalmente na prática. Apesar do investimento em campanhas preventivas, as mulheres ficam meses aguardando por uma consulta após detectarem um nódulo. Além disso, a reconstrução mamária, direito garantido pelo SUS, não está sendo realizada no Espírito Santo, pois os profissionais alegam que o valor recebido pelo procedimento não é o suficiente. Tais resultados apontam a necessidade da mobilização social buscando garantir que os direitos assegurados pela lei sejam cumpridos. / The population has always been away from the discussion involving public health policies in Brazil. Most of the time it reflects a mere technical relationship between doctor and patient, as well as public health services and the population. In the 80 s and 90 s decade there is a reengineering of the system and SUS is implemented. Prevention and cure are integrated and the population is also heard. Considering how lethal breast cancer can be, it is essential to keep the population participative. The purpose of this study was to explore the consequences of breast cancer in women s life, their demands, as well as their relationship with the public health policies. Eight women who had had breast cancer and had the assistance of SUS during the treatment in Vitória, ES, were interviewed. All of them had the diagnosis about three years ago. These women were able to share their experiences from the time they learned about their illness, to the surgery and treatment. The data was collected using the Oral Story technique, taking into account the importance of the context lived by those women throughout their life, especially their experience with breast cancer, focusing on mastectomy. The Content Analysis was used to study this data. It was possible to observe that, before the diagnosis, these women thought about cancer as immediate and certain death , which consisted in great suffering. After the surgery they had to face the restriction of routine activities and the wish of breast reconstruction. Even so, they were able to fight for life quality. It is possible to see that, although the public health policies offer service to the women who have breast cancer, it takes them several months to get an appointment with the doctor after they find out about it. Besides, the professionals in Espírito Santo say they earn very little for the breast reconstruction, and this service was interrupted. It is important that everybody fights for their rights.

Black women are most likely to receive mastectomies, yet the least likely to have receipt of breast reconstruction. This disparity in breast and plastic surgery care is unethical and has been documented in the literature and has been witnessed clinically, but far most importantly, it is continued to be lived by Black women all over the nation. The bioethical principles of agency and social justice are called into question as Black women are not given an adequate understanding of their reconstructive options and are not being treated equally or equitably by the healthcare system. As noted by literature, race and ethnicity, socioeconomic and insurance status as well as comorbidities are contributing to this gap in care. As far as solutions go, there must be a multifaceted approach to mitigating this disparity. I have adopted Dr. Butler’s categorization of solutions to understand the exact approach we need to have, which includes patient education, legislation and academic medical institution, to make the recovery from breast cancer ethical for all women. In this thesis, I will go through the literature and garner perspectives from surgeons as well as patients who received breast reconstruction to aid in the understanding of this disparity and what needs to be done to fix it. / Urban Bioethics

Radiotherapy has major therapeutic benefits for cancer patients, but ionizing radiation causes damage of surrounding healthy tissues with poor wound healing a common side effect. Therefore, further oncoplastic, reconstructive surgery is challenging and often problematic. Current research models use normal human dermal fibroblasts irradiated in vitro to mimic radiation damage, but this is not comparable to ionising radiation and only measures acute changes. Since radiotherapy may induce epigenetic changes leading to alterations in dermal fibroblast phenotype, the first aim of this study was to compare fibroblasts cultured from irradiated skin with non-irradiated skin. As mesenchymal stem cells isolated from adipose tissue may offer beneficial effects in the regenerative capacity of irradiated tissue, the second part of this study was to compare those cultured from non-irradiated and irradiated breast tissue. Histological changes in the structural organisation of breast tissue in situ from donors exposed to radiotherapy was compared to untreated breast. Primary cultures of dermal fibroblasts from irradiated and non-irradiated breast skin were established and comparisons quantitated in proliferation (CyQuant), metabolism (Alamar Blue), migration (scratch-wound assay), collagen production (Sircol), levels of proteases and protease inhibitors (human protease/protease inhibitor array) and gene expression of COL1A1, COL3A1, MMP1, MMP2, TIMP1 and PPAR-γ mRNA (qPCR). Cells from the stromal vascular fraction (SVF) were cultured and characterised by immunocytochemistry and compared to human preadipocytes sourced commercially. The secretion of FGF, adiponectin and VEGF by the preadipocyte and the SVF mesenchymal cells was compared and the ability of their secretome to modulate dermal fibroblast proliferation, metabolism and migration was evaluated. Radiotherapy caused extensive disorganisation of the reticular dermis and flattening of the epidermal-dermal junction. Dermal fibroblasts cultured from irradiated skin had a pronounced spindle shaped morphology with longer thinner projections and took approximately twice as long to explant and grow. They had a lower proliferative and higher basal metabolic rate and did not respond to FGF-2. While they secreted similar amounts of total collagen they demonstrated distinct differences in proteolytic enzyme and protease inhibitor expression. This is the first report to culture cells from the SVF of irradiated breast tissue. The cells expressed the preadipocyte markers CD10, CD73 and CD105 and no CD45 (negative marker). SVF cells cultured displayed a typical ASC fibroblastoid morphology. Analysis of the secretome identified the presence of FGF, adiponectin and VEGF, while functional analysis demonstrated a stimulatory effect on normal dermal fibroblast migration, although irradiated dermal fibroblasts were unresponsive. Radiotherapy induces long term, detrimental changes in breast skin. This is the first quantitative characterisation of dermal fibroblasts and mesenchymal cells from the SVF, subjected to ionising radiation in situ. Changes in their phenotype that alter their function will impact on wound healing. Further characterisation of these cells may explain their dysfunctional behaviour, and lead to therapies to reverse or reduce this deleterious side-effect and significantly improve treatments facilitating wound healing following radiation injury. / Plastic Surgery and Burns Research unit

La reconstruction mammaire post-mastectomie améliore le bien-être psychosocial, et l’image corporelle des patientes. Parcontre, la reconstruction mammaire demeure faiblement utilisée et même inaccessible à des patients dû à des facteurs limitants. Les taux de reconstruction et les facteurs qui influencent l’accès à la reconstruction n’ont pas été évalués dans la province du Québec. Avec une revue de dossier rétrospective, l’objectif de notre étude est d’identifier les taux de reconstruction mammaire dans un centre tertiaire à Montréal et les facteurs qui influencent l’accès à la reconstruction, avec un revu de dossier rétrospective. Ensuite, nous avons évaluer directement dans la même cohorte de patientes, leur désire d’avoir une consultation en chirurgie plastique pour discuter d’une reconstruction. Il y avait un taux total de reconstruction mammaire post-mastectomie de 21%, dont 14% était immédiat et 8% tardif. Les patientes qui ont eu une reconstruction étaient plus jeunes, plus de tendance à avoir une plus grande proportion de mastectomie bilatérale, avaient des cancers non-invasifs et habitaient plus loin de l’hôpital (>10km). Environ la moitié des patientes avec une mastectomie sont intéresser à avoir une consultation avec un chirurgien plasticien mais seulement 38% ont eu une reconstruction. Les chances d’avoir subi une reconstruction, augmentent lorsqu’une reconstruction est offerte et expliquée. Présentement, il existe des barrières autres que les désires de la patiente qui empêchent l’accès à la reconstruction mammaire post-mastectomie. / Breast reconstruction post-mastectomy has been shown to improve psychosocial wellbeing, and body image. However, accessibility and acceptance of breast reconstruction is limited, with patients being unequally privileged based a number of limiting factors. To date, no evaluation on the rates of reconstruction and the factors that influence patient access has been performed in the province of Quebec. The objective of the research was two-fold with the first component being to identify the rates of breast reconstruction at a tertiary care center in Montreal and the factors influencing the rates of reconstruction through a retrospective chart review. The second component was to directly evaluate in the same cohort of breast cancer patients; their interest in a consultation with plastic surgery through a telephone questionnaire. There was a total rate of PMBR of 21%, where 14% of patients had an immediate reconstruction and 8% of eligible patients underwent a delayed reconstruction. Patients that received a PMBR were younger, more likely to have bilateral mastectomies, had non-invasive breast cancer and resided further then 10km from the hospital. Approximately half of patients with a mastectomy were interested in consulting a plastic surgeon but only 38% of all patients underwent a reconstruction. The offer and awareness of reconstruction increased the chance of opting to have a reconstruction. There are barriers outside of the patient’s own desires that impede their access to breast reconstruction.

An ongoing objective in healthcare is the development of tools to improve patient decision-making and surgical outcomes for patients with breast cancer that have undergone or plan to undergo breast reconstruction. In keeping with the bioethical concept of autonomy, these decision models are patient-oriented and expansive, covering a range of different patient decision-makers. In pursuit of these goals, this dissertation contributes to the development of a prototype shared decision support system that will guide patients with breast cancer and their physicians in making decisions about breast reconstruction. This dissertation applies principles in decision analysis to breast reconstruction decision-making. In this dissertation, we examine three important areas of decision-making: (1) the options available to decision-makers, (2) the validity of probabilistic information assessed from reconstructive surgeons, and (3) the feasibility of applying multiattribute utility theory. In addition, it discusses the influences of breast aesthetics and proposes a measure for quantifying such influences. The dissertation concludes with a fictional case study that demonstrates the integration of the findings and application of decision analysis in patient-oriented shared breast reconstruction decision-making. Through the implementation of decision analysis principles, cognitive biases and emotion may be attenuated, clearing the decision-maker’s judgment, and ostensibly leading to good decisions. While good decisions cannot guarantee good outcomes at the individual level, they can be expected to improve outcomes for patients with breast cancer as a whole. And regardless of the outcome, good decisions yield clarity of action and grant the decision-maker a measure of peace in an otherwise uncertain world. / text