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Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.Findings Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p < 0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p < 0.0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1.43, 1.33-1.52, p < 0.001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p < 0.006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p < 0.01 for both comparisons).Interpretation The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.Funding Cancer Research UK.

BackgroundSeveral reports have shown that less aggressive patterns of diagnostic activity and care are provided to elderly breast carcinoma patients. We sought to investigate whether differences in the management of older women with breast cancer are associated with survival.Methods and findingsIn an observational study using a population-based clinical breast cancer register of one health-care region in Sweden, we identified 9,059 women aged 50-84 y diagnosed with primary breast cancer between 1992 and 2002. The 5-y relative survival ratio was estimated for patients classified by age group, diagnostic activity, tumor characteristics, and treatment. The 5-y relative survival for breast cancer patients was lower (up to 13%) in women 70-84 y of age compared to women aged 50-69 y, and the difference was most pronounced in stage IIB-III and in the unstaged. Significant differences in disease management were found, as older women had larger tumors, had fewer nodes examined, and did not receive treatment by radiotherapy or by chemotherapy as often as the younger women. Adjustment for diagnostic activity, tumor characteristics, and treatment diminished the relative excess mortality in stages III and in the unstaged, whereas the excess mortality was only marginally affected in stage IIB.ConclusionsLess diagnostic activity, less aggressive treatment, and later diagnosis in older women are associated with poorer survival. The large differences in treatment of older women are difficult to explain by co-morbidity alone.

Epidemiologic studies have shown that cancer survival is poorer in low compared with high socioeconomic groups. We investigated whether these differences were associated with disparities in tumour characteristics and management. This cohort study was based on 9,908 women aged 20-79 years at diagnosis with primary breast cancer identified in a Swedish population-based clinical register. Information on socioeconomic standing was obtained from a social database. The 5-year cause-specific survival (CSS) and mortality hazard ratios (HR) were estimated by Cox proportional hazard models to assess differences in survival between socioeconomic groups while adjusting for diagnostic intensity, tumour characteristics and treatment. Following adjustment for age, year and stage at diagnosis, the risk of dying of breast cancer was 35% lower among women with high education compared with that of low education (HR = 0.65, 95% CI 0.53-0.80). When compared with women with high education, a lower percentage of women with low education had been investigated for proliferation (84 vs. 76%) or hormone receptor status (89 vs. 81%), had tumours ≤20 mm (68 vs. 64%), were treated at a main hospital (75 vs. 68%) and had received radiation treatment (80 vs. 67%) or chemotherapy (31 vs. 18%). However, these proportional differences could not explain the observed social gradient in survival. To minimize social differences in breast cancer survival, further research should address not only factors leading to inequities in management but also focus on patient factors such as health awareness, comorbidity burden and compliance to adjuvant treatment. © 2008 Wiley-Liss, Inc. Inc.