Mammographic density and survival in interval breast cancers.

INTRODUCTION: Mammographic density (MD) is the strongest risk factor for breast cancer. It is also strongly associated with interval cancers (ICs) due to decreased screening sensitivity and possibly by also giving rise to more aggressive tumors. With this information as background, we compared survival in interval and screen-detected cancers, taking MD into consideration. METHODS: The patients were postmenopausal women ages 50 to 74 years who were diagnosed with breast cancer in Sweden between 1993 and 1995. A total of 1,115 women with screen-detected cancers and 285 with ICs had available mammograms. Cox proportional hazards models were used to compare breast cancer-specific survival between interval and screen-detected cancers stratified on MD. RESULTS: Hazard rates for breast cancer-specific survival were approximately three times higher in ICs than in screen-detected cancers, independent of MD. After adjustment for tumor size, a proxy for time to diagnosis, ICs in nondense breasts still had a statistically significantly increased hazard rate compared to screen-detected cancers in nondense breasts (5-yr survival hazard ratio (HR) 2.43, P = 0.001). In dense breasts, however, there was no longer evidence of a difference in survival between ICs and screen-detected cancers (5-yr survival HR 1.41, P = 0.486). CONCLUSIONS: In nondense breasts, ICs seem to be truly more aggressive than screen-detected cancers. In dense breasts, the poorer prognosis of ICs compared to that of screen-detected cancers may be attributable at least partially to later detection. However, to the best of our knowledge, this study is the first to investigate these relationships, and further studies are warranted to confirm our results.

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.

Menopausal hormone therapy in relation to breast cancer characteristics and prognosis: a cohort study.

INTRODUCTION: Menopausal hormone therapy has been reported to increase the risk of certain subtypes of breast cancer and to be associated with a favorable survival. These associations could either be due to an increased mammographic surveillance or to a biological effect. We assessed these associations in a Swedish cohort of postmenopausal breast cancer patients holding information on mammographic examinations, menopausal hormone therapy use, other breast cancer risk factors, and cancer treatment. METHODS: We analyzed 2,660 postmenopausal women aged 50 to 74 years, diagnosed with invasive breast cancer in 1993 to 1995 and followed until the end of 2003 (median follow-up, 9 years and 3 months). We assessed the influence of hormone therapy before diagnosis on tumor characteristics and breast cancer-specific survival. We analyzed hormone therapy before diagnosis by regimen (estrogen-progestin therapy or estrogen alone therapy), recency (current or past), and duration of use (<5 years or > or = 5 years). RESULTS: Current use, but not past use, compared with never use of hormone therapy before diagnosis seemed to be associated with tumors of low grade and with improved breast cancer-specific survival. The associations were stronger with longer duration, but did not vary significantly by regimen. The favorable survival among current users of hormone therapy was only partly explained by differences in available tumor characteristics and mammographic surveillance. CONCLUSIONS: We conclude that current menopausal hormone therapy, especially long term, is associated with favorable tumor characteristics and survival.

Risk factors for hormone receptor-defined breast cancer in postmenopausal women.

The effect of classic breast cancer risk factors on hormone receptor-defined breast cancer is not fully clarified. We explored these associations in a Swedish population-based study. Postmenopausal women ages 50 to 74 years, diagnosed with invasive breast cancer during 1993 to 1995, were compared with 3,065 age frequency-matched controls. We identified 332 estrogen receptor (ER-) and progesterone receptor (PR-) negative, 286 ER+PR-, 71 ER-PR+, 1,165 ER+PR+, and 789 tumors with unknown receptor status. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). Women ages >or=30 years, compared with those ages 20 to 24 years at first birth, were at an increased risk of ER+PR+ tumors (OR, 1.5; 95% CI, 1.2-1.8) but not ER-PR- tumors (OR, 1.1; 95% CI, 0.8-1.6). Women who gained >or=30 kg in weight during adulthood had an approximately 3-fold increased relative risk of ER+PR+ tumors (OR, 2.7; 95% CI, 1.9-3.8), but no risk increase of ER-PR- tumors (OR, 1.0; 95% CI, 0.5-2.1), compared with women who gained <10 kg. Compared with never users, women who used menopausal estrogen-progestin therapy for at least 5 years were at increased risk of ER+PR+ tumors (OR, 3.0; 95% CI, 2.1-4.1) but not ER-PR- tumors (OR, 1.3; 95% CI, 0.7-2.5). In conclusion, other risk factors were similarly related to breast cancer regardless of receptor status, but high age at first birth, substantial weight gain in adult age, and use of menopausal estrogen-progestin therapy were more strongly related to receptor-positive breast cancer than receptor-negative breast cancer.

Comprehensive analysis of the ATM, CHEK2 and ERBB2 genes in relation to breast tumour characteristics and survival: a population-based case-control and follow-up study.

BACKGROUND: Mutations in the ataxia-telangiectasia mutated (ATM) and checkpoint kinase 2 (CHEK2) genes and amplification of the v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) gene have been suggested to have an important role in breast cancer aetiology. However, whether common variation in these genes has a role in the development of breast cancer or breast cancer survival in humans is still not clear. METHODS: We performed a comprehensive haplotype analysis of the ATM, CHEK2 and ERBB2 genes in a Swedish population-based study, which included 1,579 breast cancer cases and 1,516 controls. We followed the cases for 8.5 years, on average, and retrieved information on the date and cause of death during that period from the nationwide Swedish causes of death registry. We selected seven haplotype-tagging SNPs (tagSNPs) in the ATM gene, six tagSNPs in the CHEK2 gene and seven tagSNPs in the ERBB2 gene that predicted both haplotypic and single locus variations in the respective genes with R2 values > or = 0.8. These tagSNPs were genotyped in the complete set of cases and controls. We computed expected haplotype dosages of the tagSNP haplotypes and included the dosages as explanatory variables in Cox proportional hazards or logistic regression models. RESULTS: We found no association between any genetic variation in the ATM, CHEK2 or ERBB2 genes and breast cancer survival or the risk of developing tumours with certain characteristics. CONCLUSION: Our results indicate that common variants in the ATM, CHEK2 or ERBB2 genes are not involved in modifying breast cancer survival or the risk of tumour-characteristic-defined breast cancer.

Menopausal hormone therapy and other breast cancer risk factors in relation to the risk of different histological subtypes of breast cancer: a case-control study.

INTRODUCTION: Breast cancers of different histology have different clinical and prognostic features. There are also indications of differences in aetiology. We therefore evaluated the risk of the three most common histological subtypes in relation to menopausal hormone therapy and other breast cancer risk factors. METHODS: We used a population-based case-control study of breast cancer to evaluate menopausal hormone therapy and other breast cancer risk factors for risk by histological subtype. Women aged 50 to 74 years, diagnosed with invasive ductal (n = 1,888), lobular (n = 308) or tubular (n = 93) breast cancer in Sweden in 1993 to 1995 were compared with 3,065 age-frequency matched controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for ductal, lobular, and tubular cancer. RESULTS: Women who had used medium potency estrogen alone were at increased risks of both ductal and lobular cancer. Medium potency estrogen-progestin was associated with increased risks for all subtypes, but the estimates for lobular and tubular cancer were higher compared with ductal cancer. We found OR 5.6 (95% CI 3.2-9.7) for lobular cancer, OR 6.5 (95% CI 2.8-14.9) for tubular cancer and OR 2.3 (95% CI 1.6-3.3) for ductal cancer with > or =5 years use of medium potency estrogen-progestin therapy. Low potency oral estrogen (mainly estriol) appeared to be associated with an increased risk for lobular cancer, but the association was strongest for short-term use. Reproductive and anthropometric factors, smoking, and past use of oral contraceptives were mostly similarly related to the risks of the three breast cancer subtypes. Recent alcohol consumption of > 10 g alcohol/day was associated with increased risk only for tubular cancer (OR 3.1, 95% CI 1.4-6.8). CONCLUSION: Menopausal hormone therapy was associated with increased risks for breast cancer of both ductal and lobular subtype, and medium potency estrogen-progestin therapy was more strongly associated with lobular compared with ductal cancer. We also found medium potency estrogen-progestin therapy and alcohol to be strongly associated with tubular cancer. With some exceptions, most other risk factors seemed to be similarly associated with the three subtypes of breast cancer.