Menopausal status: a possible predictive factor for recurrence in women with cancer of the uterine cervix without pelvic lymph node metastasis

Abstract Objectives to evaluate risk factors for recurrence of carcinoma of the uterine cervix among women who had undergone radical hysterectomy without pelvic lymph node metastasis, while taking into consideration not only the classical histopathological factors but also sociodemographic, clinical and treatment-related factors. Study desin This was an exploratory analysis on 233 women with carcinoma of the uterine cervix (stages IB and IIA) who were treated by means of radical hysterectomy and pelvic lymphadenectomy, with free surgical margins and without lymph node metastases on conventional histopathological examination. Women with histologically normal lymph nodes but with micrometastases in the immunohistochemical analysis (AE1/AE3) were excluded. Disease-free survival for sociodemographic, clinical and histopathological variables was calculated using the Kaplan-Meier method. The Cox proportional hazards model was used to identify the independent risk factors for recurrence. Twenty-seven recurrences were recorded (11.6%), of which 18 were pelvic, four were distant, four were pelvic + distant and one was of unknown location. The five-year disease-free survival rate among the study population was 88.4%. The independent risk factors for recurrence in the multivariate analysis were: postmenopausal status (HR 14.1; 95% CI: 3.7-53.6; P < 0.001), absence of or slight inflammatory reaction (HR 7.9; 95% CI: 1.7-36.5; P = 0.008) and invasion of the deepest third of the cervix (HR 6.1; 95% CI: 1.3-29.1; P = 0.021). Postoperative radiotherapy was identified as a protective factor against recurrence (HR 0.02; 95% CI: 0.001-0.25; P = 0.003). (To continue) Postmenopausal status is a possible independent risk factor for recurrence even when adjusted for classical prognostic factors (such as tumour size, depth of tumour invasion, capillary embolisation) and treatment-related factors (period of treatment and postoperative radiotherapy status)

The influence of menopausal status on bone turnover and disease control in breast cancer patients with metastatic bone disease treated with chemotherapy plus zoledronic acid : an exploratory retrospective cohort study

RESUMO: Introdução: Uma meta-análise recente demonstrou que uso adjuvante de ácido zoledrónico (AZ) em mulheres pós-menopáusicas com cancro da mama precoce (CM) conduz a redução do risco de morte por CM em 17%. Investigámos o efeito do estado hormonal (pré [PrM] vs pós-menopausa tardia [PoM]) na remodelação óssea e controlo de doença em mulheres com CM e metástases ósseas (MO) tratadas com AZ e quimioterapia (QT). Métodos: Neste estudo de coorte retrospetivo, colhemos variáveis clinico-patológicas e quantificámos o telopéptido N-terminal (NTX) urinário e marcadores tumorais (MT) séricos em mulheres com CM e MO tratadas com QT e AZ. As doentes foram divididas em PrM (<45 anos) e PoM (>60 anos). Endpoints do estudo: variação do NTX, CA15.3 e CEA nos meses 3, 6 e 9, tempo até falência de QT de primeira-linha e sobrevivência. Quando apropriado foram usados os testes de Wilcoxon rank-sum, modelo de efeitos lineares mistos, teste log-rank e modelo de Cox. Resultados: Quarenta doentes foram elegíveis para análise (8 PrM e 32 PoM). Depois da introdução de AZ e QT, os níveis de NTX e MT caíram no coorte global. O perfil de resposta não diferiu entre grupos no mês 3 ou em tempos posteriores (valor-p para interação tempo-estado hormonal no mês 3=0.957). Ademais, o perfil de resposta dos MT também não diferiu entre grupos. O tempo mediano até falência de primeira-linha de QT em PrM e PoM foi de 15.2 e 17.4 meses, respetivamente. Não foi identificada diferença significativa entre grupos, quer em análise univariada quer após controlo para envolvimento visceral (p=0.399 e 0.469, respetivamente). Igualmente, não houve diferenças em termos de sobrevivência. Conclusões: Neste coorte, não foram identificadas diferenças no controlo de NTX ou MT em função do estado menopausico. Igualmente, não foi identificada diferença no tempo até falência de primeira-linha de CT ou sobrevivência.----------- ABSTRACT: Background: A recent meta-analysis showed that the adjuvant use of zoledronic acid (ZA) in postmenopausal women with early breast cancer (BC) leads to a reduction in the risk of breast cancer death by 17%. We investigated the effect of the hormonal status (pre [PrM] vs late post menopause [PoM]) on bone turnover and disease control among women with BC and boné metastases (BM) treated with ZA and chemotherapy (CT). Methods: In this retrospective cohort study, we collected clinicopathologic variables, urinary Nterminal telopeptide (NTX) and serum tumor marker levels from women with BC and BM treated with CT and ZA. Patients were divided in PrM (<45 years) and PoM (>60 years). Study endpoints were NTX, CA15.3 and CEA variation at 3, 6 and 9 months, and time to first-line CT failure and survival. We performed multilevel mixed-effects linear regression models to assess the variation of repeated measures and cox regression models for time to event outcomes. Results: Forty patients were eligible for analysis (8 PrM and 32 PoM). After introduction of ZA and CT, NTX and tumor markers declined in the overall cohort. Response profile was similar between menopausal groups at month 3 and at later time points (p-value for time-hormonal status interaction at month 3=0.957). Furthermore, tumor markers response profile was also equal between groups. Median time to first-line CT failure in PrM and PoM women was 15.2 and 17.4 months, respectively. No significant difference between groups was found, either using a univariate analysis or after controlling for visceral disease involvement (p=0.399 and 0.469, respectively). Likewise, no differences in survival were found. Conclusions: In this cohort, no differences were found in terms of NTX or tumor markers control according to menopausal status. Similarly, no difference in time to first-line CT failure or survival was found.

Impact of age and menopausal status on the postprandial triacylglycerol response in healthy women

Objective: To examine the impact of age and the natural menopause on the postprandial triacylglycerol (TAG) response in healthy women. Methods and results: Thirty-seven premenopausal and sixty-one postmenopausal women underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast and lunch given at 0 and 330 min respectively. Lipids and glucose were measured in the fasting sample, with TAG analysed in the postprandial samples. Postmenopausal women were shown to have higher fasting total cholesterol, low density lipoprotein cholesterol (LDL-C) and glucose (P < 0.02). Marked differences in the postprandial TAG response were evident between the groups, with a greater incremental area under the curve (IAUC) and maximum TAG concentration in the postmenopausal women (P < 0.04). Multivariate regression analysis revealed both age and fasting TAG to be independently associated with the summary measures of the postprandial TAG response in the premenopausal women only. Interestingly, sub-division of the women into both younger and older pre- and postmenopausal subgroups, showed the most marked difference in TAG-IAUC to be between the younger and the older premenopausal women, whereas differences in fasting LDL-C were most evident between the older premenopausal and the younger postmenopausal women. Conclusions: Our results suggest a divergence in the relationship of age and menopausal status with fasting LDL-C and postprandial TAG which may reflect differences in the metabolic effects of age and the menopause on these lipid risk markers or a greater impact of early oestrogen decline on pathways of TAG rather than LDL metabolism.

Menopausal status: A possible predictive factor for recurrence in women with cancer of the uterine cervix without pelvic lymph node metastasis

Objectives: To evaluate risk factors for recurrence of carcinoma of the uterine cervix among women who had undergone radical hysterectomy without pelvic lymph node metastasis, while taking into consideration not only the classical histopathological factors but also sociodemographic, clinical and treatment-related factors. Study design: This was an exploratory analysis on 233 women with carcinoma of the uterine cervix (stages IB and IIA) who were treated by means of radical hysterectomy and pelvic lymphadenectomy, with free surgical margins and without lymph node metastases on conventional histopathological examination. Women with histologically normal lymph nodes but with micrometastases in the immunohistochemical analysis (AE1/AE3) were excluded. Disease-free survival for sociodemographic, clinical and histopathological variables was calculated using the Kaplan-Meier method. The Cox proportional hazards model was used to identify the independent risk factors for recurrence. Results: Twenty-seven recurrences were recorded (11.6%), of which 18 were pelvic, four were distant, four were pelvic + distant and one was of unknown location. The five-year disease-free survival rate among the study population was 88.4%. The independent risk factors for recurrence in the multivariate analysis were: postmenopausal status (HR 14.1; 95% CI: 3.7-53.6; P < 0.001), absence of or slight inflammatory reaction (HR 7.9; 95% CI: 1.7-36.5; P = 0.008) and invasion of the deepest third of the cervix (FIR 6.1; 95% CI: 1.3-29.1; P = 0.021). Postoperative radiotherapy was identified as a protective factor against recurrence (HR 0.02; 95% CI: 0.001-0.25; P = 0.003). Conclusion: Postmenopausal status is a possible independent risk factor for recurrence even when adjusted for classical prognostic factors (such as tumour size, depth of turnout invasion, capillary embolisation) and treatment-related factors (period of treatment and postoperative radiotherapy status). (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Greene Climacteric Scale: norms in an Australian population in relation to age and menopausal status

Objectives The aim of this study was two-fold: to assess climacteric symptoms and provide normative data for the Greene Climacteric Scale during the menopause transition, and to investigate the prevalence of climacteric symptoms in a representative sample of postmenopausal Australian women. Method A cohort of 500 premenopausal, perimenopausal and postmenopausal women aged 40-80 years participated in the Longitudinal Study of Ageing in Women (LAW study) at the Royal Brisbane and Women's Hospital, Brisbane, Australia. In year 1 of the study (2001), all participants completed the Greene Climacteric Scale and information regarding their menopausal status and the use of hormone therapy (HT) was obtained through a clinical interview with a qualified medical practitioner. Results The 50-59-year age group achieved the highest scores on the vasomotor and the depression scales in comparison to other age groups. Significant differences were also evident on the vasomotor and the depression scales on the basis of menopausal status, especially in perimenopausal women. Approximately 10% of women in the 60-79-year age group continued to experience vasomotor symptoms. Conclusion Vasomotor symptoms, as assessed by the Greene Climacteric Scale, are common during the menopause transition and remain elevated for some years in a minority of older postmenopausal women. The norms presented in this study are appropriate for use in an Australian population.

Estágio menopausal e níveis hormonais no desenvolvimento muscular e funcional em mulheres de meia idade: um estudo transversal

Introduction: Hypoestrogenism is the main characteristic of female aging. It promotes significant changes in body composition, both in fat mass as in lean body mass, leading to a decrease in muscle strength and physical performance. Objective: The aim of this study was to test whether menopausal status and hormone levels are associated with muscular strength and physical performance in middle-aged women. Methods: In a cross-sectional study it was collected sociodemographic data, gynecological history, anthropometric and biochemical measures in women aged 40 to 65 years in Parnamirim-RN. The menopause status (pre, peri and post menopause) was determined by menstrual history. All women underwent three dimensions of physical performance assessment: handgrip dynamometry, gait speed and chair stands test - Short Physical Performance Battery (SPPB). Categorical data were presented as absolute and relative frequencies. Quantitative data were showed as mean and standard deviation and the normality of distribution was verified with Kolmogorov-Smirnov (KS) test. Biochemical measures of estradiol and follicle-stimulating hormone (FSH) were transformed to log10. ANOVA with Tukey post-test for comparison of variables between the groups pre, peri and post-menopausal was performed and then multiple linear regression analyzes. Results: Two hundred and seventy eight women aged 50.2 (±5.58) years composed this study, being 50 women in premenopausal status (18%), 122 in perimenopausal (43.9%), and 106 postmenopausal stage (38.1%). The groups were different in age (p=0.001), marital relationship duration (p <0.001), number of pregnancies (p=0.001) and parity (p=0.001). Differences in biochemical measures were observed among the groups: estradiol (p<0.001), FSH (p<0.001), total cholesterol (p=0.001). There were no differences in gait velocity between menopausal status. Values in mean of grip strength decreased by postmenopausal women to perimenopausal and premenopausal ones (24.5 ± 5.1, 25.6 ± 5.4, 26.9 ± 4.9 for post-stage, pre and peri menopausas, respectively, p = 0.02) and the performance of chair stands test was better in premenopausal women compared with that in peri and postmenopausal status (p = 0.02). In multiple linear regression for muscle strength, the variables that remained were: age, estradiol and somatic symptoms measured by Menopause Rating Scale-MRS (R2=0.15). While for the xiv chair-stands test the predictors were number of births and FSH values (R2=0.04). Conclusion: There is a relationship between the stages of menopause and muscle performance in measures of grip strength and sit-up test and these are influenced by the fall of estrogens levels. Data suggest that the decrease in muscle strength and physical performance already appear in the transition to menopause stage, pointing to the need for more research in this area and appropriate preventive interventions

Country of birth, country of residence, and menopausal transitions and symptoms: British birth cohort and Australian Longitudinal Study on Women's Health

Objective: To explore endocrine-related and general symptoms among three groups of middle-aged women defined by country of birth and country of residence, in the context of debates about biological, cultural and other factors in menopause. Methods: British-born women participating in a British birth cohort study (n=1,362) and age-matched Australian-born (n=1,724) and British-born (n=233) Australian women selected from the Australian Longitudinal Study on Women's Health (ALSWH) responded to two waves of surveys at ages 48 and 50. Results: Australian-Australian and British-Australian women report reaching menopause later than British-British women, even after accounting for smoking status and parity. Hormone replacement therapy (HRT) use was lower and hysterectomy was more common among both Australian groups, probably reflecting differences in health services between Britain and Australia. The Australian-Australian and British-Australian groups were more likely to report endocrine-related symptoms than the British-British group, even after adjusting for menopausal status. British-British women were more likely to report some general symptoms. Conclusions: Symptom reporting is high among Australian and British midlife women and varies by country of residence, country of birth and menopausal status. Implications: The data do not support either a simple cultural or a simple biological explanation for differences in menopause experience.

The association of depression status with menopause symptoms among rural midlife women in China.

Objective: This study aims to evaluate the association of depression with menopausal status and some menopause symptoms (vasomotor symptoms and poor sleep). Methods: A total of 743 participants aged 40-60 years were recruited. Depression status was evaluated by using Self-Rating Depression Scale (SDS). Sleep quality and vasomotor symptoms were evaluated by specific symptoms questionnaire. Results: The prevalence of depression among participants was 11.4%. Depression was found more likely to occur in participants with poor sleep (OR, 6.02; 95%CI, 3.61, 10.03) or with vasomotor symptoms (VMS) (OR, 2.03; 95%CI, 1.20, 3.44) after controlling for age, education level, marital status, menopause status, monthly family income and chronic diseases. Menopause status was not associated with depression. Stratification analysis showed a significant association between poor sleep and depression across different menopause stages, while VMS were associated with depression only in premenopausal status. Conclusion: The majority of Chinese rural midlife women do not experience depression. The relationship between depression, VMS and sleep disturbances tends to change with menopausal status in Chinese rural midlife women.

[climacteric Syndrome In A Northeastern Brazilian City: A Household Survey].

To assess the prevalence of Climacteric Syndrome (CS) in women from a municipality of Northeastern Brazil which is less developed socioeconomically. A prospective household survey was performed in São Luís, Maranhão, Brazil with 1,210 climacteric women aged 45 to 60 years. Interviews were applied using previously tested standard questionnaires from April to July 2008. The severity of climacteric symptoms was analyzed by circulatory and psychological indexes and the latter were associated with menopausal status. Multiple correspondence analysis was used to assess the relation among climacteric symptoms. Most patients were 55 to 60 years old (35.3%), mulatto (37.9%), with 9-11 years of schooling (39.8%), with a partner (56%), Catholic (73.9%) and belonged to the socioeconomic class C (51.1%). The prevalence of CS was 85.9%, and hot flashes (56.4%) and sweating (50.4%) were the most prevalent symptoms. The most frequent psychological symptoms were nervousness (45%) and emotional liability (44.8%). The severity of vasomotor and psychological symptoms was significantly higher during the peri and postmenopausal period (p<0.05). Vaginal dryness (62.7%) was the most prevalent urogenital complaint. The prevalence of CS was high among women from São Luís, Maranhão, Brazil.

What is a healthy weight for middle aged women?

OBJECTIVE: To explore associations between body mass index (BMI) and selected indicators of health and well-being and to suggest a healthy weight range (based on BMI) for middle aged Australian women. DESIGN: population based longitudinal study (cross-sectional baseline data). SUBJECTS: 13431 women aged 45-49 y who participated in the baseline survey for the Australian Longitudinal Study on Women's Health. RESULTS: Forty-eight percent of women had a BMI>25kg/m(2). Prevalence of medical problems (for example, hypertension, diabetes), surgical procedures (cholescystectomy, hysterectomy) and symptoms (for example, back pain) increased monotonically with BMI, while indicators of health care use (for example, visits to doctors) showed a 'J' shaped relationship with BMI. Scores for several sub-scales of the MOS short form health survey (SF36) (for example, general health, role limitations due to emotional difficulties, social function, mental health and vitality) were optimal when BMI was around 19-24 kg/m(2). After adjustment for area of residence, education, smoking, exercise and menopausal status, low BMI was associated with fewer physical health problems than mid-level or higher BMI, and the nationally recommended BMI range of 20-25 was associated with optimum mental health, lower prevalence of tiredness and lowest use of health services. CONCLUSIONS: Acknowledging the limitations of the cross-sectional nature of these data, the results firmly support the benefits of leanness in terms of reducing the risk of cardiovascular disease, diabetes and gall bladder disease. The findings are moderated, however, by the observation that both low and high BMI are associated with decreased vitality and poorer mental health. The optimal range for BMI appears to be about 19-24 kg/m(2). From a public health perspective this study provides strong support for the recommended BMI range of 20-25 as an appropriate target for the promotion of healthy weight in middle aged Australian women.

Breastfeeding, menopause, and epithelial ovarian cancer

No previous study has examined the modifying effect of menopausal status on the association between lactation and ovarian cancer risk. We recruited 824 epithelial ovarian cancer cases and 855 community controls in three Australian states, collecting reproductive and lactation histories by means of a contraceptive calendar and pregnancy and breastfeeding record. We report results in women with at least one liveborn infant for unsupplemented breastfeeding, in line with a biological model linking suppression of ovulation to reduction in ovarian cancer risk. We derived odds ratios from multiple logistic regression models including number of liveborn children, age, age at first or last birth, and other potential confounders, overall and by menopausal status. Estimates of relative risk of ovarian cancer per month of full lactation were 0.99 [95% confidence interval(CI) = 0.97-1.00] overall and 1.00 (95% CI = 0.99-1.01) and 0.98 (95% CI = 0.95-1.01) among post- and premenopausal women, respectively. We tailored a lactation variable to the incessant ovulation hypothesis by progressively discounting breastfeeding the longer after birth it occurred, finding odds ratios similar to those for the unmodified duration variable. We found no association of note among postmenopausal women. Breastfeeding seems to be somewhat protective against ovarian cancer, but only before menopause.

Clinical Criteria as Predictive Factors of Response to Primary Hormone Therapy in Locally Advanced Breast Cancer

This study investigates the efficacy of clinical criteria in selecting patients for primary tamoxifen therapy. A total of 60 breast cancer patients with large primary tumors and unknown hormonal receptor status were subjected to primary hormone therapy. Inclusion criteria were age over 60 years old or menopausal status for at least 10 years and no clinical evidence of inflammatory disease and fast tumor growth. The objective response rate was 55%. There was a positive correlation between the lack of clinical response and axillary lymph node metastasis (p = 0.009). Patients with objective response had significantly improved disease-free (p = 0.045) and overall (p = 0.0002) survival over those who did not have response to hormonal therapy. In multivariate analysis, the clinical response to therapy was the most powerful prognostic factor. This analysis demonstrates that clinical criteria were very effective predictor of response to neo-adjuvant hormone therapy in large breast tumors for postmenopausal women. Response to therapy is the major prognostic factor in primary tamoxifen-treated breast cancer.

Changes in physical symptoms during the menopause transition

This article analyzes physical symptoms experienced by mid-age Australian women in different stages of the menopause transition. A total of 8,623 women, aged 45 to 50 years in 1996, who participated the mid-age cohort of the Australian Longitudinal Study on Women's Health, completed Survey I in 1996 and Survey 2 in 1998. Women were assigned to I of 6 menopause groups according to their menopausal status at Surveys 1 and 2, and compared on symptoms experienced at Surveys I and 2, adjusted for lifestyle, behavioral and demographic factors. At Survey 1, the most commonly reported symptoms were headaches, back pain, stiff joints, tiredness, and difficulty sleeping. Perimenopausal women were more likely than premenopausal or postmenopausal women to report these symptoms. Hot flushes and night sweats were more common among postmenopausal women. Compared with those who remained premenopausal, women who were in the early stages of menopause or perimenopausal were more likely to report tiredness, stiff joints, difficulty sleeping, and hot flushes at Survey 2. Women who remained perimenopausal were also more likely to report back pain and leaking urine. Compared with premenopausal women, odds ratios for night sweats increased for women in consecutive stages of the menopause transition and remained high in the postmenopausal women.

Relative importance of female-specific and non-female-specific effects on variation in iron stores between women

Women have lower iron stores than men because of iron loss during their reproductive years. However, variation between women could result from differences in iron loss, aspects of iron homeostasis common to men and women, or a combination of both. We compared the effects of age, menopause, menstrual blood loss and the number of pregnancies (sex-specific factors), and the effects of genetic variation, on markers of iron stores. We assessed how much the same genes or other familial factors influence iron status in both men and women. Data from 2039 female twins who participated in studies of reproductive health and iron status were used to estimate the proportions of variation that could be ascribed to genes, environment and measured factors. Significant effects of age, menopausal status and magnitude of menstrual blood loss were demonstrated, accounting for up to 18% of variance in serum ferritin in this sample, but number of children had no significant effect. Genetic effects were more than twice as great as sex-specific effects. The within-pair similarity of ferritin values in dizygotic female twin pairs was greater than for dizygotic opposite-sex pairs, but this difference was not quite significant, consistent with a minor role for sex-specific factors; and the opposite-sex within-pair differences did not diminish significantly with age. We conclude that the contribution of genetic differences between women to variation in iron stores outweighs the comparatively small effects of interindividual variation in iron loss through variation in menstruation and number of pregnancies.

Susceptibilidade genética para cancro da mama

RESUMO: O cancro da mama é a patologia oncológica mais frequente nas mulheres sendo o responsável pela maior taxa de mortalidade por cancro no sexo feminino. Contudo, as causas inerentes a esta patologia permanecem por esclarecer. Nos últimos anos tem-se verificado que o risco para patologia neoplásica depende de factores ambientais e genéticos, estando estes últimos associados à variabilidade genética inter-individual. Polimorfismos genéticos em genes envolvidos no metabolismo de hormonas sexuais, de cancerígenos ambientais e na reparação da lesão genética, são potenciais candidatos a estarem associados à susceptibilidade individual para esta patologia. Assim, neste trabalho desenvolveram-se estudos de associação caso-controlo na população Portuguesa, com vista a avaliar-se o papel atribuído aos polimorfismos na susceptibilidade para cancro da mama. Foram seleccionados polimorfismos em genes envolvidos em diferentes vias mecanicistas: destoxificação de cancerígenos, metabolismo de estrogénios, reparação por excisão de bases, reparação por excisão de nucleótidos, reparação mismatch e reparação por recombinação homóloga. Os resultados obtidos revelaram associação entre os seguintes polimorfismos e a susceptibilidade individual para cancro da mama: os dois SNPs estudados no gene XRCC1 (Arg194Trp e Arg399Gln) e o SNP no gene XRCC3 (Thr241Met) após estratificação pelo status menopausico. Mediante estratificação por status de amamentação os SNPs identificados nos genes MnSOD (Val16Ala) e XRCC2 (Arg118His); um SNP no gene MLH3 (Leu844Pro), e por fim como resultado de interacção gene-gene as interacções descritas por MSH3 Ala1045Thr/MSH6 Gly39Glu e MSH4 Ala97Thr/MLH3 Leu844Pro. Os resultados obtidos e apresentados na presente dissertação, revelam que o estudo de polimorfismos pode representar um papel determinante na etiologia do cancro da mama. No entanto, mais estudos envolvendo estes mesmos polimorfismos em populações casuisticamente superiores serão uma mais-valia nos estudos de associação para esta neoplasia. Adicionalmente, a utilização da metodologia de Pools de DNA, poderá ser uma ferramenta útil na pré-selecção dos polimorfismos mais relevantes a estudar, na medida em que permite estimar a frequência alélica de cada SNP numa determinada população.-----------------------------------ABSTRACT: Breast cancer is the most common form of cancer among women, being the responsible for the highest mortality rate from cancer among the female sex. However, the main causes related to this pathology remain unclear. The risk of neoplasic disease has been connected with genetic and environmental factors. In fact, genes and the environment share the stage for most, if not all, common non-familial cancers, and are related to individual susceptibility. Genetic polymorphisms identified in genes encoding enzymes involved in estrogen metabolism, xenobiotics and DNA repair pathways are believed to be candidates for associations with breast cancer. Therefore, it was our intention to develop case-control studies among the Portuguese population, in order to evaluate the potential role of several genetic polymorphisms in breast cancer susceptibility. We selected polymorphisms in genes involved in different pathways: carcinogenic detoxification, estrogen metabolism, base excision repair, nucleotide excision repair, mismatch repair and double strand break repair by homologous recombination. The results obtained revealed potential associations between some polymorphisms studied and individual susceptibility to breast cancer. Regarding this fact, our results suggest the potential involvement of two XRCC1 gene polymorphisms (Arg194Trp and Arg399Gln) and XRCC3 gene polymorphism (Thr241Met) after stratification to menopausal status and after stratification to breastfeeding status an association of MnSOD gene polymorphism (Val16Ala) and XRCC2 (Arg188His) with the disease. The SNP identified in MLH3 gene (Leu844Pro), and the interaction gene-gene described by MSH3 Ala1045Thr/MSH6 Gly39Glu and MSH4 Ala97Thr/MLH3 Leu844Pro were also related to breast cancer susceptibility. The results shown in the present dissertation have revealed the potential role of polymorphisms in breast cancer etiology. However, further studies will be needed with larger populations to confirm these results. Additionally, the use of DNA pools methodology, as a pre-selection tool, could allow the identification of the most relevant polymorphisms to be studied, estimating the allelic frequency of each SNPs in different populations.