The role of mammography screening attendance and detection mode in predicting breast cancer survival-is there added prognostic value?

INTRODUCTION: The aim of this study was to examine whether screening exposure status, defined as detection mode (screening, interval or symptomatic) combined with breast cancer screening attendance prior to diagnosis, had any additional value over detection mode in predicting breast cancer survival. We also assessed the effect of hormone replacement therapy (HRT) on the association of detection mode with breast cancer survival. METHODS: We analysed and compared the associations of both screening exposure status and detection mode with 5-year breast cancer survival on a cohort of 3013 breast cancer patients, aged 50-74 years in Sweden. We used Cox proportional hazards modelling with adjustments for tumour size, grade, estrogen receptor (ER) and progesterone receptor (PR) status and lymph node involvement. We repeated the analyses after stratification for HRT use. RESULTS: Multivariate hazard ratios (HR) for cancers detected in patients at subsequent screens, interval cancers and symptomatic cancers in patients with and without previous screening attendance were 1.3 (95%CI 0.7-2.3), 1.8 (95%CI 1.0-3.2), 1.8 (95%CI 0.9-3.6) and 2.2 (95%CI 1.2-4.1) respectively, compared with cancers detected at the first screen. The regression model including screening exposure status had no additional prognostic value over the model including detection mode (P=0.63). HRT users showed a more favourable survival than non-users; this was not influenced by detection mode. CONCLUSION: The number of routine screening examinations attended in the 5-year period prior to diagnosis had no additional prognostic value over detection mode in predicting breast cancer survival.

The influence of menopausal hormone therapy on tumour characteristics and survival in endometrial cancer patients.

INTRODUCTION: Menopausal hormone therapy (MHT) is a well-established factor in endometrial carcinogenesis, and therefore, could have prognostic implications. We investigated the effects of ever use of MHT on tumour grade and depth of myometrial invasion and 5-year relative survival in postmenopausal endometrial cancer patients. MATERIALS AND METHODS: We used a nationwide, population-based case-case design, of 683 Swedish women aged 50-74 years diagnosed with endometrial cancer during 1994 to 1995, followed up to 5 years after diagnosis. We applied polytomous multiple logistic regression to investigate the associations between the use of MHT and tumour grade, and myometrial invasion and Poisson regression for modelling 5-year excess mortality. RESULTS: Compared to never use, ever use of any MHT entailed lower risks of having moderately and poorly differentiated tumours. The lowest odds ratios for poorly differentiated tumours were seen for ever users of cyclically combined oestrogen-progestin [OR=0.23 (95% CI=0.07-0.73)]. Ever users of any form of MHT; particularly, medium potency MHT users, had significantly lower risks for tumours with deep myometrial invasion. Adjusted estimated relative excess hazard ratios revealed significantly improved survival for ever users of any form of MHT [RER=0.40 (95% CI=0.16-0.97)]; in particular ever users of any form of oestrogens [RER=0.38 (95% CI=0.15-0.99)]. CONCLUSION: Endometrial cancer patients who were ever users of MHT had more favourable tumour characteristics and better survival compared to never users of MHT. These findings support the notion that MHT induces endometrial cancer with less aggressive characteristics.

Breast cancer incidence after hormonal infertility treatment in Sweden: a cohort study.

OBJECTIVE: To assess the impact of infertility treatment with causes of infertility on incidence of breast cancer. STUDY DESIGN: Historical prospective cohort study of 1135 women attending major university clinics for treatment of infertility in Sweden, 1961-1976. Women were classified as users of clomiphene citrate or gonadotropins, or a combination of both therapies. Standardized incidence ratios were calculated to estimate relative risk of breast cancer. RESULTS: We observed 54 cases of breast cancer during 1961-2004, which did not significantly exceed those expected. Users of high-dose clomiphene citrate had an almost 2-fold increased risk (standardized incidence ratio, 1.90; 95% confidence interval, 1.08-3.35). This association was more pronounced among women referred for nonovulatory factors, with 3-fold increased risk (standardized incidence ratio, 3.00; 95% confidence interval, 1.35-6.67). CONCLUSION: No overall increased risk for breast cancer was shown with infertility treatment. Women with nonovulatory causes treated with high-dose clomiphene citrate therapy may have an elevated risk for breast cancer.

The influence of menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer.

INTRODUCTION: Hormonal factors are implicated in tumor progression and it is possible that factors influencing breast cancer induction could affect prognosis. Our study investigated the effects of menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer. METHODS: We used a nationwide, population-based, case-case design of 2,640 Swedish women who were 50 to 74 years old and had postmenopausal breast cancer during 1993 to 1995. Follow-up was conducted until 31 December 2000. We used polytomous multiple logistic regression to investigate the relationships between menstrual factors (age at menarche, cycle length, irregular menstruation, lifetime number of menstrual cycles, and age at menopause), tumor characteristics (size, grade, estrogen receptor and progesterone receptor [PR] status, lymph node involvement, and histology), and Cox proportional hazards modeling for 5-year survival. RESULTS: Younger ages at menarche were significantly associated with grade and lymph node involvement. Women with an age at menarche of 11 years or younger had a more than twofold excess risk of medium-grade (odds ratio [OR] = 2.05; 95% confidence interval [CI] 1.00 to 4.18) and high-grade (OR = 2.04; 95% CI 1.01 to 4.16) tumors. Early menarche significantly increased the risk of lymph node metastases. Survival was poorest in women with the earliest age at menarche, with a 72% increased risk of dying within 5 years after diagnosis (hazard ratio = 1.72; 95% CI 1.02 to 2.89). No significant associations were observed for other menstrual factors with tumor characteristics or survival. CONCLUSIONS: Age at menarche has a significant impact on breast cancer prognosis and survival. It remains to be established whether the associations are attributable to age at menarche directly or are associated with the early-life physiological events of breast development and carcinogenesis also taking place during childhood and puberty, as menarche is only the culmination of this series of events.