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Racial differences in breast cancer, cardiovascular disease, and all-cause mortality among women with ductal carcinoma in situ of the breast.

ABSTRACT: Ductal carcinoma in situ (DCIS) of the breast represents 15-20% of new breast cancer diagnoses in the US annually. However, long-term competing risks of mortality, as well as racial differences in outcomes among US women with DCIS, are unknown. Case data from the years 1978-2010 were obtained using SEER*Stat software available through the National Cancer Institute from the 2010 SEER registries. Included were all women aged 40 and over with newly diagnosed DCIS. There were 67,514 women in the analysis, including 54,518 white women and 6,113 black women. A total of 12,173 deaths were observed over 607,287 person-years of follow-up. The 20-year cumulative incidence of all-cause death among women with DCIS was 39.6% (CI 38.9-40.3). The corresponding 20-year rates for breast cancer death and CVD death were 3.2% (CI 3.0-3.4) and 13.2% (CI 12.8-13.7), respectively. Black women with DCIS had a higher risk of death compared to white women, with these hazard ratios elevated throughout the entire study period. For example, between 1990 and 2010, black women had a higher risk of all-cause death (HR 3.06, CI 2.39-3.91), breast cancer death (HR 5.78, CI 3.16-10.57), and CVD death (HR 6.43, CI 3.61-11.45) compared to white women diagnosed between 50 and 59 years of age. The risk of all-cause and CVD death was greater than breast cancer death among women diagnosed with DCIS over 20 years. Black women had higher risks of dying from all-causes compared to white women. These differences persisted into the modern treatment era.

SUBMITTER: Berkman A

PROVIDER: S-EPMC4372117 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Racial differences in breast cancer, cardiovascular disease, and all-cause mortality among women with ductal carcinoma in situ of the breast.

Berkman Amy A F Cole Bernard B Ades Philips A PA Dickey Samantha S Higgins Stephen T ST Trentham-Dietz Amy A Sprague Brian L BL Lakoski Susan G SG

Breast cancer research and treatment 20141018 2

Ductal carcinoma in situ (DCIS) of the breast represents 15-20% of new breast cancer diagnoses in the US annually. However, long-term competing risks of mortality, as well as racial differences in outcomes among US women with DCIS, are unknown. Case data from the years 1978-2010 were obtained using SEER*Stat software available through the National Cancer Institute from the 2010 SEER registries. Included were all women aged 40 and over with newly diagnosed DCIS. There were 67,514 women in the ana ...[more]

PMID: 25326349

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Project description:BackgroundDespite improvements in population health, marked racial and ethnic disparities in longevity and cardiovascular disease (CVD) mortality persist. This study aimed to describe risks for all-cause and CVD mortality by race and ethnicity, before and after accounting for socioeconomic status (SES) and other factors, in the MESA study (Multi-Ethnic Study of Atherosclerosis).MethodsMESA recruited 6814 US adults, 45 to 84 years of age, free of clinical CVD at baseline, including Black, White, Hispanic, and Chinese individuals (2000-2002). Using Cox proportional hazards modeling with time-updated covariates, we evaluated the association of self-reported race and ethnicity with all-cause and adjudicated CVD mortality, with progressive adjustments for age and sex, SES (neighborhood SES, income, education, and health insurance), lifestyle and psychosocial risk factors, clinical risk factors, and immigration history.ResultsDuring a median of 15.8 years of follow-up, 22.8% of participants (n=1552) died, of which 5.3% (n=364) died of CVD. After adjusting for age and sex, Black participants had a 34% higher mortality hazard (hazard ratio [HR], 1.34 [95% CI, 1.19-1.51]), Chinese participants had a 21% lower mortality hazard (HR, 0.79 [95% CI, 0.66-0.95]), and there was no mortality difference in Hispanic participants (HR, 0.99 [95% CI, 0.86-1.14]) compared with White participants. After adjusting for SES, the mortality HR for Black participants compared with White participants was reduced (HR, 1.16 [95% CI, 1.01-1.34]) but still statistically significant. With adjustment for SES, the mortality hazards for Chinese and Hispanic participants also decreased in comparison with White participants. After further adjustment for additional risk factors and immigration history, Hispanic participants (HR, 0.77 [95% CI, 0.63-0.94]) had a lower mortality risk than White participants, and hazard ratios for Black participants (HR, 1.08 [95% CI, 0.92-1.26]) and Chinese participants (HR, 0.81 [95% CI, 0.60-1.08]) were not significantly different from those of White participants. Similar trends were seen for CVD mortality, although the age- and sex-adjusted HR for CVD mortality for Black participants compared with White participants was greater than all-cause mortality (HR, 1.72 [95% CI, 1.34-2.21] compared with HR, 1.34 [95% CI, 1.19-1.51]).ConclusionsThese results highlight persistent racial and ethnic differences in overall and CVD mortality, largely attributable to social determinants of health, and support the need to identify and act on systemic factors that shape differences in health across racial and ethnic groups.

Project description:OBJECTIVE:To evaluate the long term risks of invasive breast cancer and death from breast cancer after ductal carcinoma in situ (DCIS) diagnosed through breast screening. DESIGN:Population based observational cohort study. SETTING:Data from the NHS Breast Screening Programme and the National Cancer Registration and Analysis Service. PARTICIPANTS:All 35?024 women in England diagnosed as having DCIS by the NHS Breast Screening Programme from its start in 1988 until March 2014. MAIN OUTCOME MEASURES:Incident invasive breast cancer and death from breast cancer. RESULTS:By December 2014, 13?606 women had been followed for up to five years, 10?998 for five to nine years, 6861 for 10-14 years, 2620 for 15-19 years, and 939 for at least 20 years. Among these women, 2076 developed invasive breast cancer, corresponding to an incidence rate of 8.82 (95% confidence interval 8.45 to 9.21) per 1000 women per year and more than double that expected from national cancer incidence rates (ratio of observed rate to expected rate 2.52, 95% confidence interval 2.41 to 2.63). The increase started in the second year after diagnosis of DCIS and continued until the end of follow-up. In the same group of women, 310 died from breast cancer, corresponding to a death rate of 1.26 (1.13 to 1.41) per 1000 women per year and 70% higher than that expected from national breast cancer mortality rates (observed:expected ratio 1.70, 1.52 to 1.90). During the first five years after diagnosis of DCIS, the breast cancer death rate was similar to that expected from national mortality rates (observed:expected ratio 0.87, 0.69 to 1.10), but it then increased, with values of 1.98 (1.65 to 2.37), 2.99 (2.41 to 3.70), and 2.77 (2.01 to 3.80) in years five to nine, 10-14, and 15 or more after DCIS diagnosis. Among 29?044 women with unilateral DCIS undergoing surgery, those who had more intensive treatment (mastectomy, radiotherapy for women who had breast conserving surgery, and endocrine treatment in oestrogen receptor positive disease) and those with larger final surgical margins had lower rates of invasive breast cancer. CONCLUSIONS:To date, women with DCIS detected by screening have, on average, experienced higher long term risks of invasive breast cancer and death from breast cancer than women in the general population during a period of at least two decades after their diagnosis. More intensive treatment and larger final surgical margins were associated with lower risks of invasive breast cancer.

Project description:The cardiotoxic effects of breast cancer therapies are well documented in clinical trials. However, clinical trials often underrepresent those at highest risk for cardiovascular disease (CVD)related outcomes and have limited generalizability to the larger breast cancer population. In addition, racial differences in treatment-associated CVD mortality have yet to be explored. In this study, we sought to quantify the relationship between breast cancer therapies and CVD mortality, and explore whether this effect differed between non-Hispanic black (NHB) and white (NHW) women. Using data from the Georgia Cancer Registry, we identified women diagnosed with a first primary invasive breast cancer [2010-2014], residing in the metropolitan Atlanta area (n=3,580 NHB; n=4,923 NHW), and followed them for mortality through December 31, 2018. Exposures of interest included therapies with potential cardiotoxic effects including chemotherapy and hormone therapy, which are routinely collected by the GCR. Individual agents are not captured within the GCR, therefore trastuzumab was identified using natural language processing of textual descriptions. We used propensity score weighted Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between each treatment modality and CVD mortality among the overall cohort and by race. In the overall cohort, similar hazards of CVD mortality were found among women treated with chemotherapy (HR =1.10, 95% CI: 0.62, 1.96) and hormone therapy (HR =0.94, 95% CI: 0.59, 1.50), compared to women who did not receive the respective treatments. In contrast, women treated with trastuzumab had a higher hazard of CVD mortality compared to women not treated with trastuzumab (HR =2.05, 95% CI: 0.76, 5.52). In race-specific models, hormone therapy was associated with a higher hazard of CVD mortality among NHB women (HR =2.18, 95% CI: 0.78, 6.12), but not NHW women (HR =0.66, 95% CI: 0.39, 1.13). Similar, albeit attenuated, associations were found for chemotherapy. We were unable to investigate race-specific effects of trastuzumab due to low prevalence and insufficient number of events. In our study, we observed more pronounced associations of chemotherapy and hormone therapy with CVD mortality among NHB women, for whom we know have greater CVD-related comorbidities at breast cancer diagnosis. Patients may benefit from treatment plans that find a balance between curative breast cancer treatment and prevention of CVD-related events and mortality. CVD-related outcomes may be most relevant for women with hormone receptor positive disease due to shared risk factors (e.g., obesity, tobacco use, physical activity) and longer survival.

Project description:BackgroundDuctal carcinoma in situ (DCIS) accounts for approximately 20% of mammographically detected breast cancers. Although DCIS is generally highly curable, some women with DCIS will develop life-threatening invasive breast cancer, but the determinants of progression to infiltrating ductal cancer (IDC) are largely unknown.MethodsIn the current study, we used multiplex ligation-dependent probe amplification (MLPA), a multiplex PCR-based test, to compare copy numbers of 21 breast cancer related genes between laser-microdissected DCIS and adjacent IDC lesions in 39 patients. Genes included in this study were ESR1, EGFR, FGFR1, ADAM9, IKBKB, PRDM14, MTDH, MYC, CCND1, EMSY, CDH1, TRAF4, CPD, MED1, HER2, CDC6, TOP2A, MAPT, BIRC5, CCNE1 and AURKA.ResultsThere were no significant differences in copy number for the 21 genes between DCIS and adjacent IDC. Low/intermediate-grade DCIS showed on average 6 gains/amplifications versus 8 in high-grade DCIS (p?=?0.158). Furthermore, alterations of AURKA and CCNE1 were exclusively found in high-grade DCIS, and HER2, PRDM14 and EMSY amplification was more frequent in high-grade DCIS than in low/intermediate-grade DCIS. In contrast, the average number of alterations in low/intermediate and high grade IDC was similar, and although EGFR alterations were exclusively found in high grade IDC compared to low/intermediate-grade IDC, there were generally fewer differences between low/intermediate-grade and high-grade IDC than between low/intermediate-grade and high-grade DCIS.ConclusionIn conclusion, there were no significant differences in copy number for 21 breast cancer related genes between DCIS and adjacent IDC, indicating that DCIS is genetically as advanced as its invasive counterpart. However, high grade DCIS showed more copy number changes than low/intermediate grade DCIS with specifically involved genes, supporting a model in which different histological grades of DCIS are associated with distinct genomic changes that progress to IDC in different routes. These high grade DCIS specific genes may be potential targets for treatment and/or predict progression.

Dataset Information

Racial differences in breast cancer, cardiovascular disease, and all-cause mortality among women with ductal carcinoma in situ of the breast.

Publications

Racial differences in breast cancer, cardiovascular disease, and all-cause mortality among women with ductal carcinoma in situ of the breast.

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