Incidence of breast cancer subtypes in immigrant and non-immigrant women in Norway.

BACKGROUND: Breast cancer incidence differs between non-immigrants and immigrants from low- and middle-income countries. This study investigates whether immigrants also have different subtype-specific incidences. METHODS: We used national health registries in Norway and calculated subtype-specific incidence rate ratios (IRRs) for invasive breast cancer among women aged 20-75 and 20-49 years between 2005 and 2015. Immigrant groups were classified by country of birth broadly defined based on WHO regional groupings. Subtype was defined using estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status as luminal A-like (ER+ PR+ HER2-), luminal B-like/HER2- (ER+ PR- HER2-), luminal B-like/HER2+ (ER+ PR any HER2+), HER2+ (ER-PR-HER2+) and triple-negative breast cancer (TNBC) (ER-PR-HER2-). RESULTS: Compared to non-immigrants, incidence of the luminal A-like subtype was lower in immigrants from Sub-Saharan Africa (IRR 0.43 95% CI 0.28-0.66), South East Asia (IRR 0.63 95% CI 0.51-0.79), South Asia (IRR 0.67 95% CI 0.52-0.86) and Eastern Europe (IRR 0.86 95% CI 0.76-0.99). Immigrants from South Asia had higher rates of HER2 + tumors (IRR 2.02 95% CI 1.26-3.23). The rates of TNBC tended to be similar regardless of region of birth, except that women from South East Asia had an IRR of 0.54 (95% CI 0.32-0.91). CONCLUSIONS: Women from Eastern Europe, Sub-Saharan Africa and Asia had different subtype-specific incidences compared to women from high-income countries (including non-immigrants). These differences in tumor characteristics between immigrant groups should be taken into consideration when planning preventive or screening strategies.

In modern times, how important are breast cancer stage, grade and receptor subtype for survival: a population-based cohort study.

BACKGROUND: In breast cancer, immunohistochemistry (IHC) subtypes, together with grade and stage, are well-known independent predictors of breast cancer death. Given the immense changes in breast cancer treatment and survival over time, we used recent population-based data to test the combined influence of IHC subtypes, grade and stage on breast cancer death. METHODS: We identified 24,137 women with invasive breast cancer aged 20 to 74 between 2005 and 2015 in the database of the Cancer Registry of Norway. Kaplan-Meier curves, mortality rates and adjusted hazard ratios for breast cancer death were estimated by IHC subtypes, grade, tumour size and nodal status during 13 years of follow-up. RESULTS: Within all IHC subtypes, grade, tumour size and nodal status were independent predictors of breast cancer death. When combining all prognostic factors, the risk of death was 20- to 40-fold higher in the worst groups compared to the group with the smallest size, low grade and ER+PR+HER2- status. Among node-negative ER+HER2- tumours, larger size conferred a significantly increased breast cancer mortality. ER+PR-HER2- tumours of high grade and advanced stage showed particularly high breast cancer mortality similar to TNBC. When examining early versus late mortality, grade, size and nodal status explained most of the late (> 5 years) mortality among ER+ subtypes. CONCLUSIONS: There is a wide range of risks of dying from breast cancer, also across small breast tumours of low/intermediate grade, and among node-negative tumours. Thus, even with modern breast cancer treatment, stage, grade and molecular subtype (reflected by IHC subtypes) matter for prognosis.

Stage-specific survival has improved for young breast cancer patients since 2000: but not equally.

PURPOSE: The stage-specific survival of young breast cancer patients has improved, likely due to diagnostic and treatment advances. We addressed whether survival improvements have reached all socioeconomic groups in a country with universal health care and national treatment guidelines. METHODS: Using Norwegian registry data, we assessed stage-specific breast cancer survival by education and income level of 7501 patients (2317 localized, 4457 regional, 233 distant and 494 unknown stage) aged 30-48 years at diagnosis during 2000-2015. Using flexible parametric models and national life tables, we compared excess mortality up to 12 years from diagnosis and 5-year relative survival trends, by education and income as measures of socioeconomic status (SES). RESULTS: Throughout 2000-2015, regional and distant stage 5-year relative survival improved steadily for patients with high education and high income (high SES), but not for patients with low education and low income (low SES). Regional stage 5-year relative survival improved from 85 to 94% for high SES patients (9% change; 95% confidence interval: 6, 13%), but remained at 84% for low SES patients (0% change; - 12, 12%). Distant stage 5-year relative survival improved from 22 to 58% for high SES patients (36% change; 24, 49%), but remained at 11% for low SES patients (0% change; - 19, 19%). CONCLUSIONS: Regional and distant stage breast cancer survival has improved markedly for high SES patients, but there has been little survival gain for low SES patients. Socioeconomic status matters for the stage-specific survival of young breast cancer patients, even with universal health care.

Socioeconomic inequalities in stage-specific breast cancer incidence: a nationwide registry study of 1.1 million young women in Norway, 2000-2015.

BACKGROUND: Women with high socioeconomic status (SES) have the highest incidence rates of breast cancer. We wanted to determine if high SES women only have higher rates of localized disease, or whether they also have higher rates of non-localized disease. To study this, we used data on a young population with universal health care, but not offered screening. MATERIAL AND METHODS: Using individually linked registry data, we compared stage-specific breast cancer incidence, by education level and income quintile, in a Norwegian cohort of 1,106,863 women aged 30-48 years during 2000-2015 (N = 7531 breast cancer cases). We calculated stage-specific age-standardized rates and incidence rate ratios and rate differences using Poisson models adjusted for age, period and immigration history. RESULTS: Incidence of localized and regional disease increased significantly with increasing education and income level. Incidence of distant stage disease did not vary significantly by education level but was significantly reduced in the four highest compared to the lowest income quintile. The age-standardized rates for tertiary versus compulsory educated women were: localized 28.2 vs 19.8, regional 50.8 vs 40.4 and distant 2.3 vs 2.6 per 100,000 person-years. The adjusted incidence rate ratios (tertiary versus compulsory) were: localized 1.40 (95% CI 1.25-1.56), regional 1.25 (1.15-1.35), distant 0.90 (0.64-1.26). The age-standardized rates for women in the highest versus lowest income quintile were: localized 28.9 vs 17.7, regional 52.8 vs 41.5 and distant 2.3 vs 3.2 per 100,000 person-years. The adjusted incidence rate ratios (highest versus lowest quintile) were: localized 1.63 (1.42-1.87), regional 1.27 (1.09-1.32), distant 0.64 (0.43-0.94). CONCLUSION: Increased breast cancer rates among young high SES women is not just increased detection of small localized tumors, but also increased incidence of tumors with regional spread. The higher incidence of young high SES women is therefore real and not only because of excessive screening.

Breast cancer-specific survival by clinical subtype after 7 years follow-up of young and elderly women in a nationwide cohort.

Age and tumor subtype are prognostic factors for breast cancer survival, but it is unclear which matters the most. We used population-based data to address this question. We identified 21,384 women diagnosed with breast cancer at ages 20-89 between 2005 and 2015 in the Cancer Registry of Norway. Subtype was defined using estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status as luminal A-like (ER+PR+HER2-), luminal B-like HER2-negative (ER+PR-HER2-), luminal B-like HER2-positive (ER+PR+/-HER2+), HER2-positive (ER-PR-HER2+) and triple-negative (TNBC) (ER-PR-HER2-). Cox regression estimated hazard ratios (HR) for breast cancer-specific 7-year survival by age and subtype, while adjusting for year, grade, TNM stage and treatment. Young women more often had HER2-positive and TNBC tumors, while elderly women (70-89) more often had luminal A-like tumors. Compared to age 50-59, young women had doubled breast cancer-specific mortality rate (HR = 2.26, 95% CI 1.81-2.82), while elderly had two to five times higher mortality rate (70-79: HR = 2.25, 1.87-2.71; 80-89: HR = 5.19, 4.21-6.41). After adjustments, the association was non-significant among young women but remained high among elderly. Young age was associated with increased breast cancer-specific mortality among luminal A-like subtype, while old age was associated with increased mortality in all subtypes. Age and subtype were strong independent prognostic factors. The elderly always did worse, also after adjustment for subtype. Tumor-associated factors (subtype, grade and stage) largely explained the higher breast cancer-specific mortality among young. Future studies should address why luminal A-like subtype is associated with a higher mortality rate in young women.

Adjusting for BMI in analyses of volumetric mammographic density and breast cancer risk.

BACKGROUND: Fully automated assessment of mammographic density (MD), a biomarker of breast cancer risk, is being increasingly performed in screening settings. However, data on body mass index (BMI), a confounder of the MD-risk association, are not routinely collected at screening. We investigated whether the amount of fat in the breast, as captured by the amount of mammographic non-dense tissue seen on the mammographic image, can be used as a proxy for BMI when data on the latter are unavailable. METHODS: Data from a UK case control study (numbers of cases/controls: 414/685) and a Norwegian cohort study (numbers of cases/non-cases: 657/61059), both with volumetric MD measurements (dense volume (DV), non-dense volume (NDV) and percent density (%MD)) from screening-age women, were analysed. BMI (self-reported) and NDV were taken as measures of adiposity. Correlations between BMI and NDV, %MD and DV were examined after log-transformation and adjustment for age, menopausal status and parity. Logistic regression models were fitted to the UK study, and Cox regression models to the Norwegian study, to assess associations between MD and breast cancer risk, expressed as odds/hazard ratios per adjusted standard deviation (OPERA). Adjustments were first made for standard risk factors except BMI (minimally adjusted models) and then also for BMI or NDV. OPERA pooled relative risks (RRs) were estimated by fixed-effect models, and between-study heterogeneity was assessed by the I2 statistics. RESULTS: BMI was positively correlated with NDV (adjusted r = 0.74 in the UK study and r = 0.72 in the Norwegian study) and with DV (r = 0.33 and r = 0.25, respectively). Both %MD and DV were positively associated with breast cancer risk in minimally adjusted models (pooled OPERA RR (95% confidence interval): 1.34 (1.25, 1.43) and 1.46 (1.36, 1.56), respectively; I2 = 0%, P >0.48 for both). Further adjustment for BMI or NDV strengthened the %MD-risk association (1.51 (1.41, 1.61); I2 = 0%, P = 0.33 and 1.51 (1.41, 1.61); I2 = 0%, P = 0.32, respectively). Adjusting for BMI or NDV marginally affected the magnitude of the DV-risk association (1.44 (1.34, 1.54); I2 = 0%, P = 0.87 and 1.49 (1.40, 1.60); I2 = 0%, P = 0.36, respectively). CONCLUSIONS: When volumetric MD-breast cancer risk associations are investigated, NDV can be used as a measure of adiposity when BMI data are unavailable.

Changing patterns of breast cancer incidence and mortality by education level over four decades in Norway, 1971-2009.

Background: In the last century, breast cancer incidence and mortality was higher among higher versus lower educated women in developed countries. Post-millennium, incidence rates have flattened off and mortality declined. We examined breast cancer trends by education level, to see whether recent improvements in incidence and mortality rates have occurred in all education groups. Methods: We linked individual registry data on female Norwegian inhabitants aged 35 years and over during 1971­2009. Using Poisson models, we calculated absolute and relative educational differences in age-standardised breast cancer incidence and mortality over four decades. We estimated educational differences by Slope and Relative Index of Inequality, which correspond to rate difference and rate ratio, comparing the highest to lowest educated women. Results: Pre-millennium, incidence and mortality of breast cancer were significantly higher in higher versus lower educated women. Post-millennium, educational differences in breast cancer incidence and mortality attenuated. During 2000­2009, breast cancer incidence was still 38% higher for higher versus lower educated women (Relative Index of Inequality: 1.38, 95% confidence interval: 1.31­1.44), but mortality no longer varied significantly by education level (Relative Index of Inequality: 1.09, 95% confidence interval: 0.99­1.19). Among women below 50 years, however, the education gradient for mortality reversed, and mortality was 28% lower for the highest versus lowest educated women during 2000­2009 (Relative Index of Inequality: 0.72, 95% confidence interval: 0.51­0.93). Results: Post-millennium improvements in breast cancer incidence and mortality have primarily benefited higher educated women. Breast cancer mortality is now highest among the lowest educated women below 50 years.