Lower Breast Cancer Mortality Research Articles

Exploring educational disparities in breast cancer dynamics: a comprehensive analysis of incidence, death within 5 years of diagnosis, and mortality in the Belgian context

BackgroundBreast cancer is the most prevalent cancer worldwide. Belgium shows high age-standardized incidence rates, but also high survival rates. Like many health outcomes, breast cancer has been associated with multiple factors of socioeconomic status. This paper aims to (a) map educational differences in breast cancer incidence, mortality and death rates within 5 years of diagnosis, (b) update earlier trends in breast cancer mortality rates in Belgium for the 2004–2013 period and (c) investigate the role of fertility indicators as mediating factors in the association between education and breast cancer outcomes.MethodsData consisted of a linkage between the 2001 Belgian Census, register data on mortality and cancer incidence data (2004–2013) from the Belgian Cancer Registry. We calculated age standardized rates, rate ratios (Poisson regression) and hazard ratios (Cox regression) and furthermore also applied the method of Excess Portion Eliminated (EPE) in a mediation analysis of the fertility indicators. We stratified our analysis by age: younger than 50 (premenopausal) and 50 or older (postmenopausal).ResultsWe observed striking differences in breast cancer incidence, all-cause and cause-specific death rates 5-years after diagnosis by educational level. Higher educated women had higher breast cancer incidence, but also lower all-cause and lower cause-specific death rates; adding up to zero differences in breast cancer mortality in the postmenopausal group and lower breast cancer mortality in the premenopausal group.ConclusionA notable shift in the social gradient occurred since the 1990’s, favouring higher-educated women in recent years. Especially, with regards to survival after diagnosis there is potential for policy intervention. Stage at diagnosis played a crucial role, but differences between socioeconomic groups remained significant after including this parameter. While fertility indicators played a role, the impact was less pronounced than expected.

A Retrospective Analysis of Breast Cancer Mortality among Jewish and Muslim Arab Women in Israel: The Role of Sociodemographic Factors.

Breast cancer mortality rates vary across ethnic groups in Israel, where protective factors such as high fertility and breastfeeding rates may be moderated by socioeconomic factors and mammography rates. We aim to investigate disparities in breast cancer mortality between Jewish and Muslim Arab women in Israel and examine how sociodemographic variables and number of children are associated with mortality. Our retrospective follow-up study uses data from the Israeli Central Bureau of Statistics and multivariable Cox regression models, adjusting for age, number of children, country of origin, locality size, and socioeconomic status. Compared to Jewish women, Muslim Arab women exhibited lower breast cancer mortality rates. However, after adjusting for multiple sociodemographic variables, no significant differences persisted between Jewish and Muslim Arab women. Having more than three children was associated with lower mortality among Muslim Arab women but not among Jewish women. European/American origin, larger localities, and medium socioeconomic status were associated with higher mortality. Sociodemographic factors may therefore explain the disparities in breast cancer mortality between Jewish and Muslim Arab women in Israel. Targeted intervention programs that consider the unique characteristics and risk factors of different ethnic groups are needed to reduce disparities and improve outcomes.

Abstract PO2-14-07: Association between expression of androgen receptor in tumor tissue and risk of breast cancer recurrence among premenopausal Danish women

Abstract Background: Breast cancer prognosis is influenced by tumor biomarker expression. For example, tumors that express the estrogen receptor (ER+) have a lower hazard of recurrence in the first five years following treatment than tumors that do not express the estrogen receptor. Identifying additional biomarkers that are prognostic of breast cancer recurrence may aid in risk stratification and the development of targeted therapies. The androgen receptor (AR) is one such candidate biomarker. While some previous studies have found lower breast cancer mortality associated with AR expression, others have shown no association. However, these studies were conducted in populations exclusively or primarily comprised of postmenopausal women. Since menopause is associated with an increased concentration of androgens relative to estrogens, the role of AR may differ in premenopausal women. Methods: Using the Predictors of Breast Cancer Recurrence cohort (N=5,959)—a prospective cohort study of premenopausal women diagnosed with stage I–III primary breast cancer between 2002 and 2011 and registered in the Danish Breast Cancer Cooperative Group (DBCG) clinical database—we measured the association between tumor AR expression and breast cancer recurrence. The majority of the cohort (77%) had ER+ tumors and were intended to be treated with tamoxifen. Primary paraffin-embedded tumors were collected from treating hospitals, and 2–3 cores were included in a tissue microarray for immunohistochemistry. AR staining of each core was automatically scored using a trained software application and quantified as the percent of tumor nuclei with positive staining. Patients were considered to have AR positive (AR+) tumors if the maximum score across replicate cores was >1% positive. Otherwise patients were classified as having AR negative (AR−) tumors. Patients were followed from breast cancer diagnosis until the first of recurrence, death, emigration, another malignancy, or 10 years. The DBCG defines breast cancer recurrence as any breast cancer diagnosed after the initial course of treatment, including contralateral breast cancers. The association between AR expression and breast cancer recurrence was computed as an unadjusted risk ratio and corresponding 95% confidence interval. Results: Among the 4,658 cohort members with available tumor tissue, 72% had AR+ tumors; 720 recurrences occurred over the 10-year follow-up. Patients with AR+ tumors were less likely to experience a recurrence than patients with AR− tumors [14% vs. 18% respectively; unadjusted risk ratio=0.80, 95% CI: (0.70, 0.92)]. Conclusion: AR expression in primary tumor tissue was associated with a lower risk of breast cancer recurrence in a large population-based cohort of premenopausal women. Additional analyses adjusting for clinical factors, examining the association by breast cancer subtype, and accounting for time to recurrence are forthcoming. Citation Format: Rebecca Nash, Anders Kjærsgaard, Kristina Christensen, Thomas Ahern, Lindsay Collin, Stephen Hamilton-Dutoit, Lauren McCullough, Joellen Schildkraut, Henrik Sørensen, Kevin Ward, Kirsten Woolpert, Timothy Lash, Deirdre Cronin-Fenton. Association between expression of androgen receptor in tumor tissue and risk of breast cancer recurrence among premenopausal Danish women [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-14-07.

Comprehensive diagnosis of advanced-stage breast cancer: exploring detection methods, molecular subtypes, and demographic influences – A cross-sectional study

BackgroundBrazil faces notable Breast Cancer (BC) mortality despite lower incidence rates versus developed countries. Despite guidelines from medical societies, Brazilian public policy recommends biennial mammographic screening for women aged 50 to 69. This study investigates sociodemographic and clinical factors related to BC detection methods and clinical stage at diagnosis. MethodsThe authors conducted a cross-sectional study at a São Paulo tertiary hospital. Patients were divided into ‘symptomatic’ and ‘mammographic’ detection groups. Bivariate analyses by detection method and clinical stage compared groups' profiles in terms of sociodemographic and clinical characteristics. Poisson regression analyses assessed sociodemographic and molecular subtypes´ influence on “mammographic detection” prevalence and “advanced-stage BC”, reporting prevalence ratios and 95 % Confidence Intervals. ResultsThe authors studied 1,536 BC patients admitted from January 2016 to December 2017. The “mammographic detection” group had a higher proportion of patients aged 50‒69 years (62.9 % vs. 44.1 %), white race (63.3 % vs. 51.6 %), Catholic religion (58.2 % vs. 51.1 %), and Luminal A subtype (25.2 % vs. 13.2 %) compared to the “symptomatic detection” group. Patients with early-stage disease were more likely to have higher education levels (8.1 % vs. 5.5 %) and be married (39.8 % vs. 46.6 %) compared to those with advanced-stage. Molecular subtypes were significantly associated with the detection method and stage. The prevalence of advanced-stage disease in "mammographic" (n=313) and "symptomatic" (n=1191) groups was 18.5 % and 55 %, respectively . Mammographic detection significantly reduced advanced-stage BC prevalence (PR = 0.40, 95 % CI 0.31‒0.51). ConclusionMammographic detection reduces advanced-stage breast cancer prevalence in Brazil, emphasizing the importance of regular screenings, especially among at-risk sociodemographic groups. Enhancing mammographic screening accessibility, lowering the starting age to 40, and extending coverage to include annual mammograms can significantly lower breast cancer mortality in Brazil, benefiting public health and patient outcomes.

Benefits and harms of breast cancer screening: Cohort study of breast cancer mortality and overdiagnosis.

Quantifying the benefits and harms of breast cancer screening accurately is important for planning and evaluating screening programs and for enabling women to make informed decisions about participation. However, few cohort studies have attempted to estimate benefit and harm simultaneously. We aimed to quantify the impact of mammographic screening on breast cancer mortality and overdiagnosis using a cohort of women invited to attend Australia's national screening program, BreastScreen. In a cohort of 41,330 women without prior breast cancer diagnosis, screening, or diagnostic procedures invited to attend BreastScreen Western Australia in 1994-1995, we estimated the cumulative risk of breast cancer mortality and breast cancer incidence (invasive and ductal carcinoma in situ) from age 50 to 85 years for attenders and non-attenders. Data were obtained by linking population-based state and national health registries. Breast cancer mortality risks were estimated from a survival analysis that accounted for competing risk of death from other causes. Breast cancer risk for unscreened women was estimated by survival analysis, while accounting for competing causes of death. For screened women, breast cancer risk was the sum of risk of being diagnosed at first screen, estimated using logistic regression, and risk of diagnosis following a negative first screen estimated from a survival analysis. For every 1,000 women 50 years old at first invitation to attend BreastScreen, there were 20 (95% CI 12-30) fewer breast cancer deaths and 25 (95% CI 15-35) more breast cancers diagnosed for women who attended than for non-attendees by age 85. Of the breast cancers diagnosed in screened women, 21% (95% CI 13%-27%) could be attributed to screening. The estimated ratio of benefit to harm was consistent with, but slightly less favourable to screening than most other estimates from cohort studies. Women who participate in organised screening for breast cancer in Australia have substantially lower breast cancer mortality, while some screen-detected cancers may be overdiagnosed.

Geospatial Associations between Female Breast Cancer Mortality Rates and Environmental Socioeconomic Indicators for North Carolina.

In North Carolina, over 6000 women will be diagnosed with breast cancer yearly, and over 1000 will die. It is well known that environmental conditions contribute greatly to health outcomes, and many of these factors include a geographic component. Using death data records from 2003-2019 extracted from North Carolina Vital Statistics Dataverse, a spatial database was developed to map and analyze female breast cancer mortality rates at the ZIP code scale in North Carolina. Thirty-nine hot spots and thirty cold spots of age-adjusted death rates were identified using the Getis-Ord analysis. Two-tailed t-tests were run between each cohort for environmental socioeconomic-related factors associated with breast cancer progression and mortality. The median age and household income of individuals who resided in ZIP codes with the highest breast cancer mortality were significantly lower than those who lived in ZIP codes with lower breast cancer mortality. The poverty rate, percentage of SNAP benefits, and the percentage of minorities were all significantly higher (p < 0.05, p < 0.001, and p < 0.001) in ZIP codes with high breast cancer rates. High-quality (ZIP code) granular cancer data were developed for which detailed analysis can be performed for future studies.

Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS?

Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce the risk of local recurrence (LR), including invasive LR, which carries a subsequent risk of breast cancer mortality. However, reliable and accurate individual risk prediction remains elusive and RT continues to be standardly recommended for most women with DCIS. Three molecular biomarkers have been studied to better estimate LR risk after BCS-Oncotype DX DCIS score, DCISionRT Decision Score and its associated Residual Risk subtypes, and Oncotype 21-gene Recurrence Score. All these molecular biomarkers represent important efforts towards improving predicted risk of LR after BCS. To prove clinical utility, these biomarkers require careful predictive modeling with calibration and external validation, and evidence of benefit to patients; on this front, further research is needed. Most trials do not incorporate molecular biomarkers in evaluating de-escalation of therapy for DCIS; however, one-the Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk DCIS (ELISA) trial-incorporates the Oncotype DX DCIS score in defining a low-risk population and is an important next step in this line of research.

Associations between Serum 25-Hydroxyvitamin D Levels and Health-Related Quality-of-Life Measures in Patients with Breast Cancer: A Longitudinal Study.

Recent evidence suggests that vitamin D might lower breast cancer mortality. There is also growing interest in vitamin D's potential association with health-related quality-of-life (HRQoL). Associations between circulating 25-hydroxyvitamin D (25OHD) concentrations and HRQoL were examined prospectively among breast cancer survivors at the time of diagnosis and 1 year later. 504 women with incident early-stage breast cancer at Roswell Park Comprehensive Cancer Center were included, and 372 patients provided assessments 1 year later. At each timepoint, participants provided blood samples and completed the SF-36 Health Survey, and surveys on perceived stress, depression, and fatigue. Season-adjusted serum 25OHD concentrations were analyzed in relation to HRQoL measures using multivariable logistic regression models. Approximately 32% of participants had deficient vitamin D levels at diagnosis, which decreased to 25% at 1 year. Concurrently, although SF-36 physical health summary scores were lower at 1 year, mental health summary scores improved, and levels of depression and perceived stress were lower. In comparison with women with sufficient 25OHD levels (>30 ng/mL) at diagnosis, those who were deficient (<20 ng/mL) had significantly worse HRQoL at diagnosis and 1 year later. Vitamin D deficiency 1 year post-diagnosis was also associated with worse HRQoL, particularly among breast cancer survivors who took vitamin D supplements. Breast cancer survivors with vitamin D deficiency were more likely to report lower HRQoL than those with sufficient levels at the time of diagnosis and 1 year post-diagnosis. Our results indicate a potential benefit of vitamin D supplementation for improving breast cancer survivorship.

Estrogen therapy and breast cancer in randomized clinical trials: a narrative review.

In the Women's Health Initiative (WHI) randomized trial with 10,739 postmenopausal women with prior hysterectomy, conjugated equine estrogen (CEE) alone significantly reduced breast cancer incidence and breast cancer mortality. In contrast, epidemiological studies in a meta-analysis from the Collaborative Group on Hormonal Factors in Breast Cancer (Collaborative Group) with 108,647 breast cancers and the Million Women's Study cohort significantly associated estrogen-alone therapy with higher breast cancer incidence and breast cancer mortality. The Collaborative Group included a meta-analysis of five smaller randomized trials and the WHI randomized trial; however, findings were restricted to the Collaborative Group appendix. Our objective is to facilitate understanding of these discordant results. Data sources supporting our review findings include the randomized WHI CEE-alone trial and the meta-analysis of five smaller randomized trials evaluating estrogen alone. We summarize the smaller randomized trials' details of breast cancer relevance and place the findings in clinical context. We review findings of the WHI randomized trial evaluating CEE alone in the context of issues raised by Collaborative Group and the Million Women Study authors. We trace the evolution of the time-from-menopause, "window of opportunity" concept and augment the Collaborative Group meta-analysis by including the most recent WHI findings. Consideration of the smaller randomized trials evaluating estrogen alone with breast cancer signals that the WHI findings of lower breast cancer incidence and lower breast cancer mortality with CEE-alone use are not a "stand-alone" outcome or due to the play of chance. The serial reports of consistent favorable breast cancer findings through 20 years of cumulative follow-up suggest CEE-alone use initiates changes that persist. After full consideration of risks and benefits, randomized trial evidence provides reassurance for postmenopausal women with prior hysterectomy who are close to menopause considering estrogen alone for climacteric symptom management.

Levels of Vitamin D and Expression of the Vitamin D Receptor in Relation to Breast Cancer Risk and Survival.

Previous research suggests associations between low systemic levels of vitamin D and poor breast cancer prognosis and between expression of the vitamin D receptor (VDR) in breast cancers and survival. This study aimed to study associations between pre-diagnostic systemic levels of vitamin D and expression of VDR in subsequent breast tumors, and interactions between vitamin D and VDR on breast cancer mortality. Systemic vitamin D levels were measured in women within the Malmö Diet and Cancer Study. The expression of VDR was evaluated immunohistochemically in a tissue microarray of subsequent breast cancers. Statistical analyses followed. Women with high levels of vitamin D had a smaller proportion of VDR negative breast tumors compared to women with low levels of vitamin D (odds ratio: 0.68; 95% confidence interval: 0.41–1.13). Vitamin D levels were not found to modify the association between low VDR expression and high breast cancer mortality. To conclude, there was no statistical evidence for an association between pre-diagnostic levels of vitamin D and the expression of VDRs in breast cancer, nor did vitamin D levels influence the association between VDR expression and breast cancer mortality. Further studies are needed in order to establish the effects of vitamin D on breast cancer.

Are there employment and income gains of a national breast cancer screening program?

BackgroundThe Dutch national breast cancer screening program invites women aged 50–75 for screening. By detecting the disease in an early phase, the program aims to achieve lower breast cancer mortality and improve breast cancer survivors’ health. Arguably, the latter also improves the employability of diagnosed women.ObjectiveThis study investigates the effects of the Dutch national breast cancer screening program on diagnosed women’s employment and income.MethodsThe empirical analysis uses data of 229,357 women aged 40–59, of whom 10,515 were diagnosed with breast cancer at an age in the range 47–53. A regression-based difference-in-differences estimator is used to identify program effects by comparing outcomes for women diagnosed at ages 47–49 with the outcomes for those diagnosed at ages 50–53. The empirical models account for individual fixed effects, and for age and year fixed effects by using a control group of women who were not diagnosed with breast cancer.ResultsWomen’s employment rates declined in the six-year period after a breast cancer diagnosis with, on average, about 3 percentage points and their incomes declined with, on average, about 5% over this period. The empirical evidence, based on a comparison of outcomes for women diagnosed at ages 47–49 with the outcomes for those diagnosed at ages 50–53 when covered by the breast cancer screening program, does not support that these declines in employment and income were affected by the program. The evidence also does not support short or medium-term survival gains of the program.ConclusionsThe findings of this study suggest that the Dutch national breast cancer screening program yields no discernible short or medium-term employment and income gains for women diagnosed with breast cancer.

Dietary influence on physical functioning in the Women’s Health Initiative (WHI) randomized Dietary Modification (DM) trial.

10552 Background: In the WHI DM randomized trial, randomization to the dietary intervention group was associated with a 21% lower breast cancer mortality (P = 0.02) (JCO 2020), and while not an intervention target, with higher physical activity as well. Therefore, we examined whether these lifestyle changes attenuate age-related physical functioning decline. Methods: From 1993-1998, 48,835 postmenopausal women, aged 50-79 years, were randomized to dietary intervention or usual diet comparison groups through 8 years intervention and 19 years cumulative follow-up. Breast cancer findings, as primary outcome, have been reported. Physical functioning was assessed using the RAND 36-Item Short Form Health Survey (SF-36), which assessed limitations of 10 hierarchical physical activities, scored from 0 to 100, with a higher score indicating less limited physical function. The trajectory of longitudinal physical functioning was the primary study outcome, assessed by comparing findings in the two randomization groups, overall, and by baseline physical activity and age decade. Additionally, findings were reported against a disability threshold (when assistance in daily activities is required). Results: Physical functioning was assessed nearly half a million times during the study (n = 495,317) with 11.0 (median) assessments per participant. Physical functioning score was significantly better in the intervention versus comparison groups during the 8-year intervention and extended follow-up through 12 years (median) (P = 0.001), representing a reduction in age-related functional decline. The intervention effect subsequently lost significance at 19 years and both randomization groups crossed the disability threshold at similar times. Differences between randomization groups in physical functioning emerged after stratification by physical activity and age decade (P-interaction = 0.007). Among all participants physically active at entry, the intervention initially had a statistically significant, favorable influence on physical functioning which attenuated post-intervention. In contrast, among younger, physically inactive women 50-59 years of age, the intervention had a persistent, statistically significant, favorable influence on physical functioning with associated delay in crossing the disability threshold. Conclusions: In the primary prevention setting of the WHI DM randomized trial, with long-term follow-up, a dietary intervention which has been shown to reduce breast cancer mortality also significantly reduced age-related functional decline through 12 years. Among all participants, the intervention effect was attenuated with longer follow-up. However, reduction in age-related functional decline was sustained in younger women in the intervention group who were inactive at entry, a potential target population for future behavior interventions. Clinical trial information: NCT00000611.

Harms and Benefits of Mammography Screening

Mammography is one of the most technically challenging areas of radiography, required high spatial resolution, excellent soft tissue contrast and low radiation dose. Mammography screening for breast cancer is worldwide available. Early detection of breast cancer through screening can lower breast cancer mortality rate and reduce the burden of this disease in the population, the benefits and harms of mammography screening have been debated in the past years. This review discuss the benefits and harms of mammography screening in light of findings from randomized trials and more recent observational studies performed in the era of modern diagnosis. The main benefit for mammography screening is reduces the risk of dying from breast cancer. Reduction vary from 15 to 20% in randomized trials to more recent estimates of 13 to 17% in analyses of observational studies. UK data of 2007 shows that for 1,000 women invited to biennial mammography screening for 20years to 50years age, 2-3 women’s are prevented from breast cancer. Main harm of mammography screening is the over diagnosis of breast cancer. 15 women’s over diagnosis for every 1000 women invited to biennial screening for 20 years from 50 years age. In an era of limiting health care services, screening services need to scrutinized and compared with each other regard to effectiveness, cost effectiveness and harms.

Menopausal Hormone Therapy and Breast Cancer.

Associations of estrogen-alone and estrogen plus progestin with breast cancer incidence and related mortality are reviewed from observational studies (The Collaborative Group on Hormonal Factors in Breast Cancer and The Million Women Study, 2019) and the Women's Health Initiative's (2020) two randomized trials evaluating conjugated equine estrogen alone, for women with prior hysterectomy or with medroxyprogesterone acetate. Findings are generally concordant for estrogen plus progestin use with both observational and randomized studies reporting higher breast cancer incidence. Findings are discordant for estrogen-alone use where, in the WHI randomized trial, a lower incidence and lower breast cancer mortality was seen. In contrast, in the observational studies, estrogen-alone use was associated with higher breast cancer incidence and higher breast cancer mortality. Although these discordant findings are difficult to fully reconcile, we conclude with a discussion of public health implications of the available evidence on menopausal hormone therapy and breast cancer.

Abstract P3-12-02: Loss of PTEN expression, PIK3CA mutations, and breast cancer survival in the Nurses’ health studies

Abstract Background: PTEN loss and/or PIK3CA mutation are hypothesized to predict more aggressive tumor behavior and worse outcomes in women with breast cancer. However, the results of previous studies with small sample size have been conflicting. Methods: We followed pre- and postmenopausal women with invasive breast cancer from the Nurses’ Health Study (diagnosed 1976-2011) and Nurses’ Health Study II (1989-2011) with data available on PTEN cytoplasmic expression (n=4316, breast cancer-specific deaths=777) and/or PIK3CA mutation (n=2930, breast cancer-specific deaths=317). PTEN protein expression was evaluated by immunohistochemistry and scored as a digitally quantified continuous measure (1-100%). Polymerase chain reaction and pyrosequencing of six hot spot mutations of PIK3CA were performed on DNA extracted from formalin-fixed paraffin-embedded tumors. Information on other covariates was self-reported at baseline and repeatedly measured with follow-up questionnaires every two to four years. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between loss of PTEN expression and/or PIK3CA mutation and breast cancer-specific mortality were estimated using Cox proportional hazards regression models. Results: In this large epidemiological study, the loss of tumor cell PTEN cytoplasmic staining expression (≤10%) occurred in 17.6% of cases, and the overall mutation of PIK3CA occurred in 10.8% of cases. After adjusting for tumor characteristics, treatment, and lifestyle factors, the loss of PTEN expression (versus expression &amp;gt;10%) was not associated with worse breast cancer survival among overall samples (HR =0.85; 95%CI=0.71-1.03) and among estrogen receptor (ER)-positive tumors (HR =1.11; 95%CI=0.84-1.47). However, among women with ER-negative tumors, PTEN expression loss was strongly associated with lower breast cancer mortality (HR =0.68; 95%CI=0.48-0.96). Overall mutation status of PIK3CA was not associated with breast cancer mortality (HR =1.06; 95%CI=0.78-1.45). Combining PTEN and PIK3CA status, compared with tumors without PTEN loss and without PIK3CA mutation (wild type), those with PTEN loss and/or PIK3CA mutation were not at higher risk (HR =1.05; 95%CI=0.85-1.32). However, women with PTEN loss and PIK3CA mutation jointly (n=39, breast cancer-specific deaths=15) had increased breast cancer mortality (HR =2.05; 95%CI=1.07-3.94). Conclusion: This study is the largest to date examining PTEN and PIK3CA status and breast cancer survival, in which we found that the prognostic value of PTEN status differed by ER status, and the joint status of PTEN loss of expression and PIK3CA mutation was associated with worse breast cancer survival. Citation Format: Tengteng Wang, Yujing J Heng, Gabrielle M Baker, Vanessa C Bret-Mounet, Susan E Hankinson, Michelle D Holmes, Wendy Y. Chen, Walter C. Willett, Bernard A. Rosner, Rulla M Tamimi, A. Heather Eliassen. Loss of PTEN expression, PIK3CA mutations, and breast cancer survival in the Nurses’ health studies [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-02.

Addressing breast cancer mortality in low-income and middle-income countries: if you can't measure it, it doesn't exist.

Disparities in cancer outcomes within and between countries have become increasingly more visible in the past two decades; some regions have achieved reductions both cancer incidence and mortality, whereas others are falling dramatically behind. In The Lancet Oncology, Catherine Duggan and colleagues 1 Duggan C Trapani D Ilbawi AM et al. National health system characteristics, breast cancer stage at diagnosis, and breast cancer mortality: a population-based analysis. Lancet Oncol. 2021; (published online Oct 12.)https://doi.org/10.1016/S1470-2045(21)00462-9 Summary Full Text Full Text PDF PubMed Scopus (12) Google Scholar report that 20 countries have achieved sustained mean reductions in breast cancer mortality of at least 2% for 3 consecutive years since 1990, all of which are either high-income or upper-middle-income countries. All 20 of these countries with sustained mortality reductions had at least 60% of patients with breast cancer diagnosed at early stages (stage I or II) of disease. In the multivariable analysis, the Universal Health Care Service Coverage Index score and number of public cancer centres per 10 000 patients with cancer were significantly and independently negatively associated with age-standardised mortality rates (β=–0·12, 95% CI −0·16 to −0·08, and β=–0·23, −0·36 to −0·10, respectively). These results provide useful additional information on which future research might be based. National health system characteristics, breast cancer stage at diagnosis, and breast cancer mortality: a population-based analysisCountries with low breast cancer mortality rates are characterised by increased levels of coverage of essential health services and higher numbers of public cancer centres. Among countries achieving sustained mortality reductions, the majority of breast cancers are diagnosed at an early stage, reinforcing the value of clinical early diagnosis programmes for improving breast cancer outcomes. Full-Text PDF

National health system characteristics, breast cancer stage at diagnosis, and breast cancer mortality: a population-based analysis.

In some countries, breast cancer age-standardised mortality rates have decreased by 2-4% per year since the 1990s, but others have yet to achieve this outcome. In this study, we aimed to characterise the associations between national health system characteristics and breast cancer age-standardised mortality rate, and the degree of breast cancer downstaging correlating with national age-standardised mortality rate reductions. In this population-based study, national age-standardised mortality rate estimates for women aged 69 years or younger obtained from GLOBOCAN 2020 were correlated with a broad panel of standardised national health system data as reported in the WHO Cancer Country Profiles 2020. These health system characteristics include health expenditure, the Universal Health Coverage Service Coverage Index (UHC Index), dedicated funding for early detection programmes, breast cancer early detection guidelines, referral systems, cancer plans, number of dedicated public and private cancer centres per 10 000 patients with cancer, and pathology services. We tested for differences between continuous variables using the non-parametric Kruskal-Wallis test, and for categorical variables using the Pearson χ2 test. Simple and multiple linear regression analyses were fitted to identify associations between health system characteristics and age-standardised breast cancer mortality rates. Data on TNM stage at diagnosis were obtained from national or subnational cancer registries, supplemented by a literature review of PubMed from 2010 to 2020. Mortality trends from 1950 to 2016 were assessed using the WHO Cancer Mortality Database. The threshold for significance was set at a p value of 0·05 or less. 148 countries had complete health system data. The following variables were significantly higher in high-income countries than in low-income countries in unadjusted analyses: health expenditure (p=0·0002), UHC Index (p<0·0001), dedicated funding for early detection programmes (p=0·0020), breast cancer early detection guidelines (p<0·0001), breast cancer referral systems (p=0·0030), national cancer plans (p=0·014), cervical cancer early detection programmes (p=0·0010), number of dedicated public (p<0·0001) and private (p=0·027) cancer centres per 10 000 patients with cancer, and pathology services (p<0·0001). In adjusted multivariable regression analyses in 141 countries, two health system characteristics were significantly associated with lower age-standardised mortality rates: higher UHC Index levels (β=-0·12, 95% CI -0·16 to -0·08) and increasing numbers of public cancer centres (β=-0·23, -0·36 to -0·10). These findings indicate that each unit increase in the UHC Index was associated with a 0·12-unit decline in age-standardised mortality rates, and each additional public cancer centre per 10 000 patients with cancer was associated with a 0·23-unit decline in age-standardised mortality rate. Among 35 countries with available breast cancer TNM staging data, all 20 that achieved sustained mean reductions in age-standardised mortality rate of 2% or more per year for at least 3 consecutive years since 1990 had at least 60% of patients with invasive breast cancer presenting as stage I or II disease. Some countries achieved this reduction without most women having access to population-based mammographic screening. Countries with low breast cancer mortality rates are characterised by increased levels of coverage of essential health services and higher numbers of public cancer centres. Among countries achieving sustained mortality reductions, the majority of breast cancers are diagnosed at an early stage, reinforcing the value of clinical early diagnosis programmes for improving breast cancer outcomes. None.

Analysis of the scope of surgical breast cancer treatment in countries with the low associated mortality-to-incidence ratio (review)

The worldwide implementation of «breakthrough» surgical approaches such as breast-conserving techniques, the development of mammoplasty, as well as new guidelines for performing biopsy of sentinel lymph nodes incentivized the transition to a higher level of quality in breast cancer care. This review summarizes the modern tendencies in audits of main breast cancer surgical treatments based on last experience of few countries demonstrating the low breast cancer mortality and high incidence (lowest breast cancer mortality-to-incidence ratio).

Dietary intervention influence on physical activity in the Women’s Health Initiative randomized Dietary Modification trial.

10511 Background: In the Women’s Health Initiative (WHI) Dietary Modification (DM) randomized trial, after 8.5 years dietary intervention and 19.5 years cumulative (median) follow-up, dietary intervention participation was associated with a statistically significantly 22% lower breast cancer mortality (P = 0.02). In observational studies, physical activity has been associated with lower breast cancer risk with emerging results now indicating, compared to inactivity, any increase in physical activity has health benefits. Currently, longitudinal data on whether an intervention targeting dietary change influences other health-related behaviors as a gateway effect is limited. To evaluate whether randomization to a dietary intervention was associated with self-directed change in physical activity. Methods: In the WHI DM trial, 48,835 postmenopausal women, ages 50-79 years, with no prior breast cancer and baseline normal mammogram were randomized at 40 US clinical centers to a dietary intervention (19,541) or a comparison group. Dietary goals were to reduce fat intake to 20% of energy and increase intake of vegetable, fruit, and grains addressed in 18 group sessions in year 1 then quarterly. Neither randomization group received specific or ongoing instructions to increase physical activity, but physical activity was referenced in written materials given to the intervention groups in 7 of the 56 sessions. Episodes per week of moderate or vigorous recreational physical activity (MVPA) were collected at baseline and serially through 15.9 years follow-up by self-report questionnaire. Marginal longitudinal logistic regression models were used to assess physically inactive (MVPA = 0) or physically active (MVPA &gt; 0) participants by randomization group. Marginal Poisson regression models estimated mean weekly MVPA by randomization group. Results: 45.6% of participants reported 0 MVPA at baseline which largely persisted throughout follow-up. During cumulative follow-up, relative to the comparison group, dietary intervention group participation was associated with 7% lower physical inactivity rate (odds ratio [OR] 0.93 95% confidence interval [CI] 0.91, 0.95, P &lt; 0.001) and a 4% higher mean MVPA (ratio of means [RM] 1.04 95% CI 1.02, 1.06, P &lt; 0.001). The association between dietary intervention participation with higher physical activity level was stronger with increasing BMI (P-interaction 0.01) and for women with waist circumference ≥ 88 cm (P-interaction 0.02). Conclusions: In conclusion, in a randomized trial setting, a low-fat dietary pattern intervention was associated with a significantly lower physical inactivity rate and significantly higher moderate and vigorous physical activity level which could be associated with health benefits. Clinical trial information: NCT00000611 .

State of art and optimization perspectives for breast imaging

Breast screening with mammography is the most effective method of detecting early-stage breast cancer and reducing related mortality. Among the intrinsic limits of mammography, in terms of clinical performance, the overlapping of normal and pathological tissues is one of the most influential. Some new techniques as Digital Breast Tomosynthesis (DBT) is expected to overcome this limitation by providing a quasi-three-dimensional (3D) image that could lead to improve the accuracy of mammography. Another way to increase accuracy and sensitivity is represented by a double exposure of the patient before and after intravenous injection of contrast media, this technique is called Contrast-enhanced digital (or spectral) mammography (CEDM, CESM). Furthermore, highly specialized software has been developed which is able to detect suspicious mammographic findings. This technology is very interesting especially in the screening field, in fact there are multiple ongoing studies evaluating the use of Artificial Intelligence (AI) as a second reader.To date, screening mammography is the only imaging modality that has proven to significantly lower breast cancer mortality. Tomosynthesis demonstrated excellent sensitivity and specificity but the technique did not meet the expectations given the risk of over diagnosis as well as the lack of reduction in the number of interval breast cancer. CESM could in some cases serve as an alternative imaging tool to MRI. AI, seems to be competing with the breast radiologist and its use as a second reader in breast screening programs is already being proposed.