Breast Cancer Mortality In Women Research Articles

Bilateral Mastectomy and Breast Cancer Mortality

The benefit of bilateral mastectomy for women with unilateral breast cancer in terms of deaths from breast cancer has not been shown. To estimate the 20-year cumulative risk of breast cancer mortality among women with stage 0 to stage III unilateral breast cancer according to the type of initial surgery performed. This cohort study used the Surveillance, Epidemiology, and End Results (SEER) Program registry database to identify women with unilateral breast cancer (invasive and ductal carcinoma in situ) who were diagnosed from 2000 to 2019. Three closely matched cohorts of equal size were generated using 1:1:1 matching according to surgical approach. The cohorts were followed up for 20 years for contralateral breast cancer and for breast cancer mortality. The analysis compared the 20-year cumulative risk of breast cancer mortality for women treated with lumpectomy vs unilateral mastectomy vs bilateral mastectomy. Data were analyzed from October 2023 to February 2024. Type of breast surgery performed (lumpectomy, unilateral mastectomy, or bilateral mastectomy). Contralateral breast cancer or breast cancer mortality during the 20-year follow-up period among the groups treated with lumpectomy vs unilateral mastectomy vs bilateral mastectomy. The study sample included 661 270 women with unilateral breast cancer (mean [SD] age, 58.7 [11.3] years). After matching, there were 36 028 women in each of the 3 treatment groups. During the 20-year follow-up, there were 766 contralateral breast cancers observed in the lumpectomy group, 728 contralateral breast cancers in the unilateral mastectomy group, and 97 contralateral cancers in the bilateral mastectomy group. The 20-year risk of contralateral breast cancer was 6.9% (95% CI, 6.1%-7.9%) in the lumpectomy-unilateral mastectomy group. The cumulative breast cancer mortality was 32.1% at 15 years after developing a contralateral cancer and was 14.5% for those who did not develop a contralateral cancer (hazard ratio, 4.00; 95% CI, 3.52-4.54, using contralateral breast cancer as a time-dependent covariate). Deaths from breast cancer totaled 3077 women (8.54%) in the lumpectomy group, 3269 women (9.07%) in the unilateral mastectomy group, and 3062 women (8.50%) in the bilateral mastectomy group. This cohort study indicates that the risk of dying of breast cancer increases substantially after experiencing a contralateral breast cancer. Women with breast cancer treated with bilateral mastectomy had a greatly diminished risk of contralateral breast cancer; however, they experienced similar mortality rates as patients treated with lumpectomy or unilateral mastectomy.

MRI Surveillance and Breast Cancer Mortality in Women With BRCA1 and BRCA2 Sequence Variations

Magnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined. To compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not. Women with a BRCA1 or BRCA2 sequence variation were identified from 59 participating centers in 11 countries. Participants completed a baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years to document screening histories, incident cancers, and vital status. Women who had breast cancer, a screening MRI examination, or bilateral mastectomy prior to enrollment were excluded. Participants were followed up from age 30 years (or the date of the baseline questionnaire, whichever was later) until age 75 years, the last follow-up, or death from breast cancer. Data were analyzed from January 1 to July 31, 2023. Entrance into an MRI surveillance program. Cox proportional hazards modeling was used to estimate the hazard ratios (HRs) and 95% CIs for breast cancer mortality associated with MRI surveillance compared with no MRI surveillance using a time-dependent analysis. A total of 2488 women (mean [range] age at study entry 41.2 [30-69] years), with a sequence variation in the BRCA1 (n = 2004) or BRCA2 (n = 484) genes were included in the analysis. Of these participants, 1756 (70.6%) had at least 1 screening MRI examination and 732 women (29.4%) did not. After a mean follow-up of 9.2 years, 344 women (13.8%) developed breast cancer and 35 women (1.4%) died of breast cancer. The age-adjusted HRs for breast cancer mortality associated with entering an MRI surveillance program were 0.20 (95% CI, 0.10-0.43; P < .001) for women with BRCA1 sequence variations and 0.87 (95% CI, 0.10-17.25; P = .93) for women with BRCA2 sequence variations. Results of this cohort study suggest that among women with a BRCA1 sequence variation, MRI surveillance was associated with a significant reduction in breast cancer mortality compared with no MRI surveillance. Further studies of women with BRCA2 sequence variations are needed to ascertain these women obtain the same benefits associated with MRI surveillance.

Environmental pressures, tumor characteristics, and death rate in a female breast cancer cohort: a seven-years Bayesian survival analysis using cancer registry data from a contaminated area in Italy.

In Taranto, Southern Italy, adverse impacts on the environment and human health due to industrial installations have been studied. In the literature, few associations have been reported between environmental factors and breast cancer mortality in women. The aim of this study was to investigate the relationships between residence in areas with high environmental pressures, female breast cancer characteristics, and death rate. Data from the Taranto Cancer Registry were used, including all women with invasive breast cancer diagnosed between 01 January 2015 and 31 December 2020 and with follow-up to 31 December 2021. Bayesian mixed effects logistic and Cox regression models were fitted with the approach of integrated nested Laplace approximation, adjusting for patients and disease characteristics. A total of 10,445 person-years were observed. Variables associated with higher death rate were residence in the contaminated site of national interest (SIN) (HR 1.22, 95% CrI 1.01-1.48), pathological/clinical stage III (HR 2.77, 95% CrI 1.93-3.97) and IV (HR 17.05, 95% CrI 11.94-24.34), histological grade 3 (HR 2.50, 95% CrI 1.20-5.23), Ki-67 proliferation index of 21-50% (HR 1.42, 95% CrI 1.10-1.83) and > 50% (HR 1.81, 95% CrI 1.29-2.55), and bilateral localization (HR 1.65, 95% CrI 1.01-2.68). Variables associated with lower death rate were estrogen and/or progesterone receptor positivity (HR 0.61, 95% CrI 0.45-0.81) and HER2/neu oncogene positivity (HR 0.59, 95% CrI 0.44-0.79). The findings confirmed the independent prognostic values of different female breast cancer characteristics. Even after adjusting for patients and disease characteristics, residence in the SIN of Taranto appeared to be associated with an increased death rate.

Risk-reducing mastectomy and breast cancer mortality in women with a BRCA1 or BRCA2 pathogenic variant: an international analysis.

Risk-reducing mastectomy (RRM) is offered to women with a BRCA1 or BRCA2 pathogenic variant, however, there are limited data on the impact on breast cancer mortality. Participants were identified from a registry of women with BRCA1/2 pathogenic variants. We used a pseudo-randomised trial design and matched one woman with a RRM to one woman without a RRM on year of birth, gene, and country. We estimated the hazard ratio (HR) and 95% confidence intervals (CI) for dying of breast cancer in the follow-up period. There were 1654 women included; 827 assigned to the RRM arm and 827 assigned to the control arm. After a mean follow-up of 6.3 years, there were 20 incident breast cancers (including 15 occult cancers) and two breast cancer deaths in the RRM arm, and 100 incident breast cancers and 7 breast cancer deaths in the control arm (HR = 0.26; 95% CI 0.05-1.35; p = 0.11). The probability of dying of breast cancer within 15 years after RRM was 0.95%. In women with a BRCA1 or BRCA2 pathogenic variant, RRM reduces the risk of breast cancer, and the probability of dying of breast cancer is low.

The contribution of prognostic factors to socio-demographic inequalities in breast cancer survival in Victoria, Australia.

Breast cancer survival in Australia varies according to socio-economic status (SES) and between rural and urban places of residence. Part of this disparity may be due to differences in prognostic factors at the time of diagnosis. Women with invasive breast cancer diagnosed from 2008 until 2012 (n = 14,165) were identified from the Victorian Cancer Registry and followed up for 5 years, with death from breast cancer or other causes recorded. A prognostic score, based on stage at diagnosis, cancer grade, whether the cancer was detected via screening, reported comorbidities and age at diagnosis, was constructed for use in a mediation analysis. Five-year breast cancer mortality for women with breast cancer who were in the lowest quintile of SES (10.3%) was almost double that of those in the highest quintile (5.7%). There was a small survival advantage (1.7% on average, within each socio-economic quintile) of living in inner-regional areas compared with major cities. About half of the socio-economic disparity was mediated by prognostic factors, particularly stage at diagnosis and the presence of comorbidities. The inner-regional survival advantage was not due to differences in prognostic factors. Part of the socio-economic disparity in breast cancer survival could be addressed by earlier detection in, and improved general health for, more disadvantaged women. Further research is required to identify additional causes of socio-economic disparities as well as the observed inner-regional survival advantage.

274P Racial and ethnic disparities in breast cancer mortality in women with and without diabetes between 2005 and 2020

274P Racial and ethnic disparities in breast cancer mortality in women with and without diabetes between 2005 and 2020

Survival in male breast cancer over the past 3 decades.

Breast cancer mortality in women has declined statistically significantly over the past several years. In men, it is unclear whether survival has changed over time. We evaluated changes in breast cancer-specific survival (BCSS) and overall survival (OS) in male breast cancer over the past 3 decades. We evaluated men diagnosed with breast cancer between 1988 and 2017, reported in the Surveillance, Epidemiology, and End Results registry. Patients were categorized into 3 groups by year of diagnosis: 1988-1997, 1998-2007, and 2008-2017. BCSS and OS were estimated by Kaplan-Meier, and differences between groups were compared by log-rank test. Multivariable Cox regression evaluated the independent association of year of diagnosis with BCSS and OS. All tests were 2-sided. We included 8481 men. Overall, BCSS at 5 years was 83.69%, 83.78%, and 84.41% in groups 1988-1997, 1998-2007, and 2008-2017, respectively (P = .86). There was no statistically significant difference in BCSS between the 3 groups within each stage of disease. Among all patients, OS at 5 years was 64.61%, 67.31%, and 69.05% in groups 1988-1997, 1998-2007, and 2008-2017, respectively (P = .01). In adjusted Cox models, each additional year of diagnosis had no statistically significant association with BCSS (hazard ratio = 1.00, 95% confidence interval = 0.99 to 1.01, P = .75), but there was statistically significant improvement in OS (hazard ratio = 0.99, 95% CI = 0.98 to 0.99, P = .009). Over the past 3 decades, there has been no statistically significant improvement in BCSS in male breast cancer. Changes in OS over time are consistent with increasing life expectancy. Efforts to improve BCSS in male breast cancer are warranted.

Effectiveness of Mammography Screening on Breast Cancer Mortality - A Study Protocol for Emulation of Target Trials Using German Health Claims Data.

The efficacy of mammography screening in reducing breast cancer mortality has been demonstrated in randomized trials. However, treatment options - and hence prognosis - for advanced tumor stages as well as mammography techniques have considerably improved since completion of these trials. Consequently, the effectiveness of mammography screening under current conditions is unclear and controversial. The German mammography screening program (MSP), an organized population-based screening program, was gradually introduced between 2005 and 2008 and achieved nation-wide coverage in 2009. We describe in detail a study protocol for investigating the effectiveness of the German MSP in reducing breast cancer mortality in women aged 50 to 69 years based on health claims data. Specifically, the proposed study aims at estimating per-protocol effects of several screening strategies on cumulative breast cancer mortality. The first analysis will be conducted once 10-year follow-up data are available. We will use claims data from five statutory health insurance providers in Germany, covering approximately 37.6 million individuals. To estimate the effectiveness of the MSP, hypothetical target trials will be emulated across time, an approach that has been demonstrated to minimize design-related biases. Specifically, the primary contrast will be in terms of the cumulative breast cancer mortality comparing the screening strategies of "never screen" versus "regular screening as intended by the MSP". In Germany, the utilization of data from health insurances for scientific research is regulated by the Code of Social Law. All involved health insurance providers as well as the responsible authorities approved the use of the health claims data for this study. The Ethics Committee of the University of Bremen determined that studies based on claims data are exempt from institutional review. The findings of the proposed study will be published in peer-reviewed journals.

Androgens in Patients With Luminal B and HER2 Breast Cancer Might Be a Biomarker Promoting Anti-PD-1 Efficacy.

Endocrine therapy is considered as an effective strategy for estrogen and progestogen receptor (ER and PR)-positive breast cancer (BRCA) patients, whereas resistance to these agents is the major cause of BRCA mortality in women. Immune checkpoint receptor (ICR) blockade is another approach to treat BRCA, but the response rate of this approach for non-triple-negative breast cancer (non-TNBC) is relatively low. Recently, the androgen receptor (AR) has been identified as a tumor suppressor in ER-positive BRCA; however, the relationship between the levels of androgens and ICRs on T cells in BRCA is unclear. We observed that testosterone and dihydrotestosterone (DHT) in patients with HER2 and Luminal B were significantly lower than those in healthy controls, and the expression of AR has significant correlation with overall survival (OS) advantage for Luminal B patients. Moreover, testosterone and DHT were positively correlated with the PD-1 expression on Vδ1+ T cells in HER2 and Luminal B patients. These results suggest a potential approach of combining androgens with PD-1 blockade for treating HER2 and Luminal B breast cancer.

Validation of the PREDICT breast cancer tool in a multiethnic population of U.S. women after a second primary breast cancer.

10551 Background: PREDICT is a widely used clinical tool to estimate prognosis based on treatment after a diagnosis of early-stage breast cancer (BC). However, it has not been validated for use in women diagnosed with a second primary BC. Methods: Women diagnosed with one or two BCs between 2000-2013 were identified from the US Surveillance, Epidemiology, and End Results (SEER) program. Validation analyses were conducted separately among women with one and two BCs. For each group, absolute and relative differences in predicted (P) and observed (O) 5-year BC-specific mortality were estimated stratified by estrogen receptor (ER) status. For women with two BCs, mortality prediction was based on demographic and tumor characteristics of their second BCs. Model discrimination was evaluated by receiver-operator curve (ROC) and area under the curve (AUC). Results: 6,729 women diagnosed with a second BC and 357,204 women with only one BC were included. Among women with one ER-positive BC, the predicted (P) and observed (O) BC mortality were comparable [absolute difference (P-O): -0.22%, 95%CI: -0.29%, -0.15%]. For women diagnosed with a second ER-positive disease, the model largely underestimated the BC mortality (P-O: -6.24%, 95%CI: -6.96%, -5.49%). An underestimation of 3%-15% in absolute BC mortality was observed in subgroup analyses based on age, race/ethnicity [P-O for Non-Hispanic (NH) White, NH Black, and Hispanic were -5.63%, -9,3%, and -9.24%], chemotherapy (P-O: -9.06, 95%CI: -10.79, -7.4), radiation therapy (P-O: -5.06, 95%CI: -6.29, -3.93) and tumor characteristics. PREDICT overestimated BC mortality for women diagnosed with one ER-negative BC (P-O: 4.54%, 95%CI: 4.27%, 4.86%) but it performed well for women diagnosed with a second ER-negative BC (P-O: -1.69%, -3.99%, 0.16%). However, in subgroup analyses among women with two BCs the tool underestimated mortality for women with a second ER-negative disease if their first cancer was diagnosed before age 50 years (P-O: -3.27, 95%CI: -6.48, -0.06), was poorly differentiated (P-O: -4.08, 95%CI: -7.09, -1.2), or ER-negative (P-O: -4.68, 95%CI: -7.62, -1.39). The overall AUCs for first and second ER-positive and ER-negative BCs ranged between 0.73 and 0.82. Conclusions: The PREDICT tool largely underestimated the 5-year BC-specific mortality in women diagnosed with a second ER-positive breast cancer and in many subgroups of women diagnosed with a second ER-negative cancer. Novel prognostic tools are needed for women diagnosed with a second breast cancer.

Abstract P2-10-04: Breast cancer risk assessment tool (BCRAT) predicted breast cancer incidence and breast cancer mortality in the women's health initiative

Abstract Purpose Commonly used breast cancer risk models estimate breast cancer incidence. However, such model performance, re-purposed to predict breast cancer mortality, are largely unknown. Therefore, we examined whether the BCRAT model predicts long-term breast cancer mortality in postmenopausal women in the WHI. Participants and Methods Of 161,808 WHI participants aged 50-79 years, after exclusions,145,408 were in the analysis. BCRAT risk was calculated, with incident breast cancers verified by central medical record review. Breast cancer mortality was related to BCRAT 5-year risk groups (&amp;lt; 1%, 1-2.99%, ≥ 3%) using unadjusted Cox proportional hazard models and in age-stratified, multi-variable models. An addition analysis compared proportion of participants with BCRAT risk ≥ 1.67% and ≥ 3% (former and current prevention thresholds). Results Of 145,408 participants, the ≥1.67% and the ≥3.0% risk groups included 40% and 9% of participants, respectively. Compared to women with BCRAT&amp;lt;1% risk, women with BCRAT ≥ 3% risk had more common breast cancer family history and lower BMI. After 20 years median follow-up, with 8,849 breast cancers and 1,076 deaths from breast cancer, risk of death from breast cancer in BCRAT risk group ≥ 3% was not higher compared to BCRAT risk group &amp;lt;1%. (Hazard Ratio [HR] 1.06 95% Confidence Interval [CI] 0.80-1.40, P = 0.76). Similarly, risk of death from breast cancer in BCRAT risk group 1-2.99% was not higher compared to BCRAT risk group &amp;lt;1 (HR 1.15 95% CI 0.93-1.43). Conclusions Current guideline recommendation for threshold for endocrine-targeted interventions substantially reduces postmenopausal prevention candidates from 40% to &amp;lt;10%. The BCRAT prediction model, even at the ≥ 3% 5-year risk threshold, does not identify women at significantly increased risk of death from breast cancer. Citation Format: Rebecca Nelson, Kathy Pan, Rowan Chlebowski, Thomas E Rohan, Joanne Mortimer, Jean Wactawski-Wende, Dorothy Lane, Laura Kruper. Breast cancer risk assessment tool (BCRAT) predicted breast cancer incidence and breast cancer mortality in the women's health initiative [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 P2-10-04.

Obesity and Its Risk on Breast Cancer among Women: A Meta-Analysis

Background: Breast cancer is the most common type of cancer experienced by women which can cause the most deaths in both developed and developing countries. The risk of breast cancer severity in women with BMI obesity category increased up to 30% compared with women who had normal weight. This study aims to analyze the effect of obesity on breast cancer mortality in women, with a meta-analysis of primary studies conducted by previous authors. Subjects and Method: This study is a systematic review and meta-analysis with the following PICO, population: breast cancer women. Intervention: obesity. Comparison: not obese. Outcome: mortality. The articles used in this study were obtained from four databases, namely Google Scholar, Pubmed, Science Direct and Springerlink. Keywords to search for articles “Obesity” OR “Obese Overweight” AND “Mortality” OR “Death” AND “Women with Breast Cancer” OR “Breast Cancer” OR “Breast Cancer Mortality” AND “Adjusted Hazard Ratio”. The included articles are full-text English with an observational cohort study design from 2012 to 2021 and report on the aOR in multivariate analyses. Article selection is done by using PRISMA flow diagram. Articles were analyzed using the Review Manager 5.3 application. Results: A total of 12 observational cohort studies from the United States, Denmark, Netherlands, UK, Spain, Malaysia and China were selected for systematic review and meta-analysis. The data collected showed that obesity increased the mortality risk of breast cancer women and was statistically significant (aOR = 1.23; 95% CI = 1.00 to 1.52; p = 0.050). Conclusion: Obesity increases the risk of mortality in breast cancer women. Keywords: obesity, breast cancer women, meta-analysis Correspondence: Ruth Apriyanti. Masters Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami 36A, Surakarta 57126, Central Java. Email: ruthyanti94.ras@gmail.com. Mobile: +6281375232120.

Survival in male breast cancer (MaBC) over the past three decades.

569 Background: Breast cancer mortality in women has declined significantly over the past several years. In men, it is unclear whether survival has changed over time. The aim of this study was to evaluate changes in breast cancer-specific survival (BCSS) and overall survival (OS) in MaBC over the past three decades. Methods: We evaluated men diagnosed with breast cancer between 1988 and 2017, with known cause of death reported in the Surveillance, Epidemiology, and End Results registry. Patients were categorized into 3 groups by year of diagnosis: 1988-1997, 1998-2007 and 2008-2017. BCSS and OS were estimated by Kaplan-Meier and differences between groups were compared by log-rank test. Cox proportional hazards regression was used to evaluate the independent association of tumor and patient characteristics with BCSS and OS. Results: We included 8,412 men diagnosed between 1988-1997 (N = 1,033), 1998-2007 (N = 2,938) and 2008-2017 (N = 4,441). Median age for the overall population and within each decade of diagnosis was 68 years. Median follow-up was 23.6 years, 14.3 years and 4.5 years in periods 1988-1997, 1998-2007 and 2008-2017, respectively. Overall, BCSS at 5 years was 83.5%, 83.6% and 84.3% in periods 1988-1997, 1998-2007 and 2008-2017, respectively; p = 0.8. There was no significant difference in BCSS between the three periods of diagnosis within each stage of breast cancer (stage I, II, III and IV). Among all patients, OS at 5 years was 64.7%, 67.2% and 69.3% in periods 1988-1997, 1998-2007 and 2008-2017, respectively; p = 0.01. In multivariate Cox models, older age at diagnosis, black race, grade 3 disease, increasing stage, hormone receptor negative status and no surgery were all independently associated with worse BCSS and OS. In these adjusted Cox models, each additional year of diagnosis had no significant association with BCSS (hazard ratio, 1.0; 95% CI, 0.99 – 1.01; p = 0.78), and a significant improvement in OS (hazard ratio, 0.99; 95% CI, 0.98 – 0.99; p = 0.01). Conclusions: Over the past three decades, there has been no significant improvement in BCSS in MaBC. The changes in OS over time suggest increasing life expectancy. Efforts to improve BCSS in MaBC are warranted.

Effect of screening by clinical breast examination on breast cancer incidence and mortality after 20 years: prospective, cluster randomised controlled trial in Mumbai

ObjectiveTo test the efficacy of screening by clinical breast examination in downstaging breast cancer at diagnosis and in reducing mortality from the disease, when compared with no screening.DesignProspective, cluster randomised...

Abstract PS10-22: Breast cancer mortality in women with Her2+ disease treated in a large integrated healthcare system

Abstract BACKGROUND: Women with breast cancer are living longer, including those with risk factors such as having HER2+ tumors or diagnosed at later stages, but a dearth of information exists on patients’ outcomes beyond clinical trials. Thus, we aimed to describe breast-cancer specific mortality risk for women with HER2+ disease in a large community health plan. METHODS: We assembled a cohort of 3777 adult women (&amp;gt;18 years) with HER2+ breast cancer (AJCC TNM Stages I-IV) from a large California health plan, Kaiser Permanente Southern California, from 2009-2017 and followed them through December 2018. Subjects were identified from the health plan’s NCI-SEER affiliated tumor registry. All data elements were captured from the tumor registry and the electronic health records. ER, PR, and HER2 status were assessed by immunohistochemical or FISH techniques. Dates and causes of death were extracted from the inpatient records and state and national death databases. We computed breast cancer-specific mortality rates by exposure to trastuzumab, and by ER, PR, and tumor size. We followed women from the index date up to the date of death or end of study at December 31, 2018, whichever occurred first. Multivariable Cox proportional hazards regression was used to estimated adjusted hazard ratios (HR) and corresponding 95% confidence intervals. RESULTS: Of the 3777 women, the median age at diagnosis was 57 years (range: 22-99 years). The cohort was diverse and included 47% Whites; 12% African American/Blacks; 16% Asian/Pacific Islanders; 24% Hispanics; and 1% of other/mixed backgrounds. Roughly 67% (N=2464) were ER+ and/or PR+. A total of 3170 women (84%) received trastuzumab; N=112 (3%) other chemotherapy only; and N=495 (13%) neither (the majority [85%] had early stage I-II disease). The risk of breast cancer-specific death was 9.3% (351/3777) during a median follow-up of 4.4 years (maximum 10 years). Breast cancer mortality rate was markedly lower in those with trastuzumab (18.32/1,000 PY) therapy than those who did not receive trastuzumab (27.66/1,000 PY), corresponding to a 44% reduced risk (adj HR=0.56, 95% CI: 0.40-0.76) among those who received trastuzumab. Breast cancer mortality rates were higher in women with greater stage; ER-; PR-; tumors &amp;gt;2 cm and with positive lymph nodes. Compared to women diagnosed at Stage I, those with Stage II-III disease were 2.77 times (adj HR=2.77, 95% CI: 1.87-4.10) more likely to die of breast cancer, and this risk was even higher in those diagnosed at Stage IV (adj HR=11.11, 95% CI: 7.02-17.60), after accounting for trastuzumab use; diagnosis age and year; race/ethnicity; geocoded income; ER and PR status; surgery type; other adjuvant therapy (endocrine, radiation, chemotherapy); lymph node status; histology, BMI, Charlson Comorbidity Index. The adjusted breast cancer mortality risk was 37% greater (adj HR=1.37, 95% CI: 0.99-1.90) in those with ER- disease versus ER+, but the result was of borderline statistical significance. In those with tumors&amp;gt;2cm, breast cancer mortality risk was almost 90% greater (adj HR=0.67, 95% CI: 0.49-0.91) versus those with smaller tumors&amp;lt;2cm. CONCLUSION: This population-based study of patients with HER2+ invasive breast cancer confirms that receiving trastuzumab was significantly associated with a 44% reduced risk of breast-cancer mortality. Further, breast cancer mortality risk was greater in those with higher stages, with large tumors (&amp;gt;2 cm) and positive lymph nodes, even after accounting for trastuzumab use. Citation Format: Reina Haque, LieHong Chen, Karen W. Kwan, Nina Oestreicher, Deepa Lalla. Breast cancer mortality in women with Her2+ disease treated in a large integrated healthcare system [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-22.

Update of international guidelines for breast cancer screening

In the last decade, the number of breast cancer cases has increased by 35% worldwide. The screening mammography clearly reduces the relative risk of breast cancer mortality in women between 50 and 59 years old, the decrease being more important for the age range 60-69 years old. The United States of America together with international specialized groups recommend mammographic screening in women between 50 and 74 years old every 1-2 years, depending on the individual risk factors and on the patient’s desire. Japan’s position is that of recommending mammographic screening without clinical examination of the breasts for women between the ages of 40 and 74. In the European Union, population screening by mammography in women aged 50-69 has been recognized as a priority, along with the screening for cervical and colon cancer, since 2003. Romania presents a major delay in the implementation of organized screening of the population for breast cancer compared to other EU members, although the number of cases is increasing.

Annual mammographic screening to reduce breast cancer mortality in women from age 40 years: long-term follow-up of the UK Age RCT.

There remains disagreement on the long-term effect of mammographic screening in women aged 40-49 years. The long-term follow-up of a randomised controlled trial that offered annual mammography to women aged 40-49 years. The estimation of the effect of these mammograms on breast cancer and other-cause mortality, and the effect on incidence, with implications for overdiagnosis. An individually randomised controlled trial comparing offering annual mammography with offering usual care in those aged 40-48 years, and thus evaluating the effect of annual screening entirely taking place before the age of 50 years. There was follow-up for an average of 23 years for breast cancer incidence, breast cancer death and death from other causes. We analysed the mortality and incidence data by Poisson regression and estimated overdiagnosis formally using Markov process models. Twenty-three screening units in England, Wales and Scotland within the NHS Breast Screening Programme. Women aged 39-41 years were recruited between 1990 and 1997. After exclusions, a total of 53,883 women were randomised to undergo screening (the intervention group) and 106,953 women were randomised to have usual care (the control group). The intervention group was invited to an annual breast screen with film mammography, two view at first screen and single view thereafter, up to and including the calendar year of their 48th birthday. The control group received no intervention. Both groups were invited to the National Programme from the age of 50 years, when screening is offered to all women in the UK. The main outcome measures were mortality from breast cancers diagnosed during the intervention phase of the trial (i.e. before the first National Programme screen at 50 years), mortality from all breast cancers diagnosed after randomisation, all-cause mortality, mortality from causes other than breast cancer, and the incidence of breast cancer. There was a statistically significant 25% reduction in mortality from breast cancers diagnosed during the intervention phase at 10 years' follow-up (relative rate 0.75, 95% confidence interval 0.58 to 0.97; p = 0.03). No reduction was observed thereafter (relative rate 0.98, 95% confidence interval 0.79 to 1.22). Overall, there was a statistically non-significant 12% reduction (relative rate 0.88, 95% confidence interval 0.74 to 1.03; p = 0.1). The absolute benefit remained approximately constant over time, at one death prevented per 1000 women screened. There was no effect of intervention on other-cause mortality (relative rate 1.02, 95% confidence interval 0.97 to 1.07; p = 0.4). The intervention group had a higher incidence of breast cancer than the control group during the intervention phase of the trial, but incidence equalised immediately on the first National Programme screen at the age of 50-52 years. There was 31% average non-compliance with screening and three centres had to cease screening for resource and capacity reasons. Annual mammographic screening at the age of 40-49 years resulted in a relative reduction in mortality, which was attenuated after 10 years. It is likely that digital mammography with two views at all screens, as practised now, could improve this further. There was no evidence of overdiagnosis in addition to that which already results from the National Programme carried out at later ages. There is a need for research on the effects of modern mammographic protocols and additional imaging in this age group. Current Controlled Trials ISRCTN24647151. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 55. See the NIHR Journals Library website for further project information. Other funding in the past has been received from the Medical Research Council, Cancer Research UK, the Department of Health and Social Care, the US National Cancer Institute and the American Cancer Society.

Breast-cancer mortality in screened versus unscreened women: Long-term results from a population-based study in Queensland, Australia

In the context of a mature mammographic screening programme, the aim of this population-based study was to estimate rates of breast-cancer mortality among participants versus non-participants in Queensland, Australia. The Queensland Electoral Roll was used to identify women aged 50-65 in the year 2000 (n = 269,198). Women with a prior history of invasive or in situ breast cancer were excluded (n = 6,848). The study population was then linked to mammography records from BreastScreen Queensland together with the Wesley Breast Screening Clinic (the largest provider of private screening in Queensland) to establish a screened cohort (n = 187,558) and an unscreened cohort (n = 74,792). Cohort members were matched and linked to cancer notifications and deaths through the state-based Queensland Oncology Repository. Differences in breast-cancer mortality between the two cohorts were measured using Cox proportional hazards regression. After 16 years of follow-up, women in the screened cohort showed a 39% reduction in breast-cancer mortality compared to the unscreened cohort (HR = 0.61, 95%CI = 0.55-0.68). Cumulative mortality over the same period was 0.47% and 0.77% in the screened and unscreened cohorts, respectively. This study found a significant reduction in breast-cancer mortality for women who participated in mammographic screening compared to unscreened women. Our findings of a breast-cancer mortality benefit for women who have mammographic screening are in line with other observational studies.

Helping Women 75 and Older Decide About Screening Mammography

Unlike screening mammography in younger women, such screening does not appear to reduce breast cancer mortality in women aged ≥75 (NEJM JW Womens

Impact of chronic diseases on effect of breast cancer screening.

BackgroundAlthough breast cancer screening reduces breast cancer mortality at the population level, subgroups of women may benefit differently. We investigated the impact of health status on the effect of breast cancer screening.MethodsThe study included 181 299 women invited in two population‐based screening programs in Denmark and 1 526 446 control subjects, followed from April 1981 to December 2014. Poisson regressions were used to compare the observed breast cancer mortality rate in women invited to screening with the expected rate in the absence of screening among women with and without chronic diseases. Chronic diseases were defined as any diagnosis in the Charlson Comorbidity Index during 4 years before the first invitation to screening.ResultsAlmost 10% of women had chronic diseases before first invitation to screening. Whereas we observed a reduction in breast cancer mortality following invitation to screening of 28% (95% CI, 20% to 35%) among women without chronic diseases, only a 7% (95% CI, −39% to 37%) reduction was seen for women with chronic diseases (P‐value for interaction = .22). For participants, the reduction, corrected for selection bias, was 35% (95% CI 16% to 49%) for women without, and 4% (95% CI −146% to 62%) for women with chronic diseases (P‐value for interaction = .43).ConclusionOur data indicate a marginal effect of mammography screening on breast cancer mortality in women with chronic diseases. If our results are confirmed in other populations, the presence of chronic diseases will be an important factor to take into consideration in personalized screening.