Incidence Of Advanced Breast Cancer Research Articles

What Has Changed During the COVID-19 Pandemic? - The Effect on an Academic Breast Department in Portugal.

One year ago, Portugal entered its first lockdown because of the coronavirus disease-2019 (COVID-19) pandemic. The impact of this on delays in cancer diagnosis and treatment is a major concern, which may negatively affect the outcomes of these patients. This retrospective, single-center analysis compared the clinical and pathological characteristics of breast cancer (BC) patients referred to a medical oncology first appointment between March 2020 and 2021, with the same period in the previous year. Strikingly, there was a 40% reduction in the number of BC patients during lockdown. However, there was a statistically significant increase in the proportion of metastatic BC patients admitted for the first time for systemic therapy (13.6% vs. 28.9%, p = 0.003). Additionally, a statistically significant increase in the number of patients with bilateral early BC at diagnosis after March 2020 was found (7.2% vs. 1.9%, p = 0.043). These findings support international recommendations for an accelerated restoration of BC screening, to reduce incidence of advanced breast cancer at diagnosis and mitigate the expected impact of the COVID-19 pandemic on patients with cancer. Further work is needed to examine in detail the impact of measures to manage the COVID-19 pandemic on breast cancer outcomes.

Clinicopathological profile of invasive ductal breast carcinoma in a government tertiary care center in eastern India

Introduction and Aim: There is an increasing incidence of breast cancer (BC) in our country. The study aimed to find out the demographic profile, clinical presentation, and management in patients treated for invasive ductal breast carcinoma (IDC) in a rural government teaching hospital and to study the association of sociodemographic factors with BC stage.
 Materials and Methods: The study retrospectively analyzed 100 IDC females treated at Midnapore medical college, West Bengal, India from January 2017 to December 2019. The study included female patients of all ages diagnosed with IDC who had undergone surgery. Male BC, bilateral BC, other pathological types of BC were excluded.
 Results: The mean age was 56.54±12.99 years. Sixty-seven cases were postmenopausal. Eighty-one cases were from rural areas. Seventy-three cases had education up to middle school. Eighty-six cases had a lower socioeconomic status. Ninety-eight cases had unilateral breast lump and only 2% had a nonpalpable breast lump. The left breast was more commonly involved. The mean tumour size was 4.33 cm. Ninety-eight cases underwent a modified radical mastectomy. Stage III was the most commonly observed BC and seen in 40 cases followed by stage II in 36 cases. Sixty-one cases had advanced BC. Liver metastasis was seen in 21cases. Sixty-nine cases had axillary node(ALN) positivity. Sixty-eight cases had lymphovascular emboli (LVE). High-grade tumour was seen in 77%. High-grade tumour was more common in young women. Seventy three cases of tumours were estrogen receptor-positive (ER+) while 66% progesterone receptor-positive (PR+). Eighteen cases were human epidermal growth factor 2 receptor-positive.
 Conclusion: High incidence of advanced BC is found in rural areas due to a lack of awareness and health infrastructure.

Understanding the Psychosocial Needs of Women who Present with Advanced Breast Cancer

Advanced breast cancer (ABC) remains common in Singapore. In 2019, 22.1% of breast cancer patients presented with ABC in our institution. Despite increasing affluence and the advent of national mammographic screening, the incidence of ABC has not changed significantly. This suggests inherent differences in women who present late. We aim to explore the socio-economic background, knowledge and attitudes of women who present with ABC. Between December 2013 and July 2015, 100 patients who presented consecutively with ABC in a tertiary institution in Singapore were recruited to participate in an interviewer-led questionnaire exploring psychosocial and economic issues. Among the 100 patients, 63 and 37 presented with stages 3 and 4 breast cancer respectively. Median age was 57 (27-86), 52% had at least secondary education, 53% had no formal employment and 71% were married; 88% were aware of breast cancer symptoms, 82% were aware that mammography can help detect cancer, 82% believed that current treatment modality for breast cancer is effective, 96% had never undergone a mammography and 52.9% felt mammograms were unnecessary. A total of 64% presented symptomatic from the breast tumour, with a median duration of 3 months. Many of the patients were aware of breast cancer symptoms and the utility of mammography. However, a group of patients did not comply with screening. This may be due to poor understanding about breast screening and detection in its asymptomatic phase. Further public education to improve understanding of breast cancer and screening mammography may help to improve rates for earlier detection of breast cancer.

Incidence of advanced-stage breast cancer in regular participants of a mammography screening program: a prospective register-based study

BackgroundThe European Guidelines for breast cancer screening suggest that the impact of population-based mammography screening programmes (MSP) may be assessed using the relative reduction in the incidence of advanced breast cancer (ABC, that is, stage UICC II and higher) as a surrogate indicator of screening effectiveness.MethodsThis prospective, population register-based study contained individual data of 1,200,246 women (aged 50–69 years) who attended the initial prevalence screening between 2005 and 2009. Of them, 498,029 women returned for the regular (i.e., within 24 months) first subsequent, and 208,561 for the regular second subsequent incidence screenings. The incidence rate of ABC was calculated for the 24-months period following, but not including, the initial screening by incorporating all interval ABCs and all ABCs detected at the regular first incidence screening; the ABC rate for the second 24-months period was determined in the same way, including ABCs detected in the interval after the first and, respectively, at the second incidence screening. The relative reduction in the ABC incidence was derived by comparing the age-standardized rates in these two periods with an age-standardized reference incidence rate, observed in the target population before the MSP implementation. The strengths and weaknesses of this particular study design were contrasted with a recently published checklist of main methodological problems affecting studies of the effect of MSP on ABC incidence.ResultsThe age-standardized ABC incidence rate was 291.6 per 100,000 women for the 24-months period subsequent to the initial screening, and 275.0/100,000 for the 24-months period following the first subsequent screening. Compared to the 2-year incidence of 349.4/100,000 before the start of the MSP, this amounted to a relative reduction of 16.5 and 21.3%, respectively, in the incidence of ABC among regular MSP participants.ConclusionsThe design employed in this study avoids some of the substantial methodological limitations that compromised previous observational studies. Nevertheless, specific limitations prevail that demand a cautious interpretation of the results. Therefore, the study findings, indicating a reduction in ABC for regular MSP participants, need to be followed with respect to potential impacts on breast cancer mortality rates.

Breast health awareness in an Arabic culture: A qualitative exploration.

To explore breast health awareness and the early diagnosis and detection methods of breast cancer from the perspective of women and primary healthcare providers in Saudi Arabia. A high incidence of advanced breast cancer exists in Saudi Arabia, particularly among younger women. This is due to poor awareness of breast cancer and its management, social customs and poor breast health awareness among healthcare providers. Qualitative exploratory study. This qualitative study was conducted in eight states across the Jizan region of Saudi Arabia. Purposive sampling was used to recruit Saudi women (N=24), general practitioners (N=20), and nurses (N=20). Semi-structured interviews were conducted from November 2015-February 2016. Inductive thematic analysis was undertaken. Overarching themes centred on culture, religion, and resources. Novel key findings from this study confirm that Saudi women require more health education about breast cancer and breast cancer screening. The study has provided important new knowledge in relation to Islamic concept of preserving health, social barriers, cultural taboos, misconceptions, and myths that currently exist surrounding breast cancer in Saudi Arabia. This study provides new evidence on the complexity of poor breast health awareness and lack of resources in Saudi Arabia. Additional resources are needed to remove such barriers and provide targeted health education and services. This research informs breast cancer service provision for Muslim or Arab women internationally as they share cultural resources or Islamic principles to follow a healthy lifestyle and help promote the uptake of breast cancer screening services.

Targeted Therapy for Premenopausal Women with HR+, HER2− Advanced Breast Cancer: Focus on Special Considerations and Latest Advances

The incidence of advanced breast cancer in premenopausal women is increasing, and breast cancer in younger women is often more aggressive and has a worse prognosis compared with breast cancer in older women. Premenopausal women with hormone receptor-positive (HR+) breast cancer are frequently under-represented in clinical trials, and treatment strategies in the premenopausal setting are usually extrapolated from data from postmenopausal patients, with the addition of ovarian function suppression to endocrine therapy in HR+ disease. However, the underlying biology of breast cancer in premenopausal women can be different from postmenopausal women, and treatment strategies should ideally be specifically tested in premenopausal patients. Recent phase III trials have now investigated cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in premenopausal patients with HR+, HER2- advanced breast cancer: Palbociclib and abemaciclib have been tested in a subset of premenopausal patients in the PALOMA-3 and MONARCH-2 studies, and ribociclib has been tested in the phase III MONALEESA-7 trial, which was entirely dedicated to premenopausal women. This comprehensive review summarizes the differences in the biology of HR+, HER2- breast cancer in the premenopausal population compared with the postmenopausal population; discusses special considerations for treatment of premenopausal women; and reviews the evidence from clinical trials investigating endocrine therapy, other targeted treatments, and ovarian function suppression in the HR+, HER2- advanced breast cancer setting. Clin Cancer Res; 24(21); 5206-18. ©2018 AACR.

Demonstrating Higher Incidence of Advanced Breast Malignancies in Our Young Hispanic Population

Historically, the Hispanic population in the United States has had a lower incidence of cancer than the matched non-Hispanic population, despite disparities in access to health care, screening, and prevention. Our experience in Austin, Texas, directly contradicts this. We have seen a disproportionate amount of young Hispanic patients with advanced malignancies, particularly of the breast. The aim of this study was to compare the incidence of advanced breast malignancies. We performed a retrospective review over a 10-year period (2003-2013) of all newly diagnosed breast cancer patients. Data were collected from the cancer registry. Patients were divided into two groups: Hispanic versus non-Hispanic descent, with a subgroup of those aged less than 50 years. Primary outcome was the incidence of advanced cancers (stage 3 or 4). There were a total of 3968 breast cancer patients seen in our Shivers Cancer Center from 2003 to 2013, with an overall incidence of advanced breast cancer of 11.5 per cent. Of the patients aged less than 50 years, 14.2 per cent had advanced breast cancer. However, the rate among Hispanic patients was 21.3 per cent, whereas in non-Hispanic patients it was 13.5 per cent, P = 0.002. Being Hispanic was found to be an independent predictor of having advanced malignancies at a young age (odds ratio 1.7, confidence interval 1.1-2.5, P = 0.01). Here in Austin, Texas, we have found a higher overall incidence of breast cancer among young Hispanic women. This is important to recognize because more efforts may be required to increase screening and health-care access to this population.

Breast health awareness in an Arabic culture: a qualitative exploration

Background: There is a high incidence of advanced breast cancer (BC) in young women in the Kingdom of Saudi Arabia (KSA) (SCR, 2007; 2008), but no standardised information regarding breast self-examination, nor a national screening programme promoting clinical breast examination and mammography (Donnelly and Hwang, 2013).

The impact of mammography screening programmes on incidence of advanced breast cancer in Europe: a literature review

BackgroundObservational studies have reported conflicting results on the impact of mammography service screening programmes on the advanced breast cancer rate (ABCR), a correlation that was firmly established in randomized controlled trials. We reviewed and summarized studies of the effect of service screening programmes in the European Union on ABCR and discussed their limitations.MethodsThe PubMed database was searched for English language studies published between 01-01-2000 and 01–06-2018. After inspection of titles and abstracts, 220 of the 8644 potentially eligible papers were considered relevant. Their abstracts were reviewed by groups of two authors using predefined criteria. Fifty studies were selected for full paper review, and 22 of these were eligible. A theoretical framework for their review was developed. Review was performed using a ten-point checklist of the methodological caveats in the analysis of studies of ABCR and a standardised assessment form designed to extract quantitative and qualitative information.ResultsMost of the evaluable studies support a reduction in ABCR following the introduction of screening. However, all studies were challenged by issues of design and analysis which could at least potentially cause bias, and showed considerable variation in the estimated effect. Problems were observed in duration of follow-up time, availability of reliable reference ABCR, definition of advanced stage, temporal variation in the proportion of unknown-stage cancers, and statistical approach.ConclusionsWe conclude that much of the current controversy on the impact of service screening programmes on ABCR is due to observational data that were gathered and/or analysed with methodological approaches which could not capture stage effects in full. Future research on this important early indicator of screening effectiveness should focus on establishing consensus in the correct methodology.

Is the incidence of advanced-stage breast cancer affected by whether women attend a steady-state screening program?

In this cross-sectional population-based study, we assessed the incidence of advanced breast cancer based on screening attendance. Women from the Netherlands Cancer Registry were included if aged ≥49 years and diagnosed with breast cancer between 2006 and 2011, and data were linked with the screening program. Cancers were defined as screen-related (diagnosed <24 months after screening) or nonscreened (all other breast cancers). Two cut-offs were used to define advanced breast cancer: TNM-stage (III-IV vs 0-I-II) and T-stage alone (≥15 mm vs <15 mm or DCIS). The incidence rates were adjusted for age and logistic regression was used to compare groups. Of the 72,612 included women diagnosed with breast cancer, 44,246 (61%) had screen-related breast cancer. By TNM stage, advanced cancer was almost three times as likely to be at an advanced TNM stage in the nonscreened group compared with the screen-related group (38 and 94 per 100,000, respectively; OR: 2.86, 95%CI: 2.72-3.00). By T-stage, the incidence of advanced cancer was higher overall, and in nonscreened women was significantly higher than in screened women (210 and 169 per 100,000; OR: 1.85, 95%CI: 1.78-1.93). Data on actual screening attendance showed that the incidence of advanced breast cancer was significantly higher in nonscreened women than in screened women, supporting the expectation that screening would cause a stage shift to early detection. Despite critical evaluations of breast cancer screening programs, our data show that breast cancer screening is a valuable tool that can reduce the disease burden in women.

382 (PB-015) - Does breast screening decrease the incidence of advanced breast cancer? Understanding the psyche of women who present with advanced breast cancer

382 (PB-015) - Does breast screening decrease the incidence of advanced breast cancer? Understanding the psyche of women who present with advanced breast cancer

Abstract OT3-07-01: Update of the randomized, non-inferiority LORD trial testing safety of active surveillance for women with screen-detected low risk ductal carcinoma in situ (EORTC-1401-BCG/BOOG 2014-04, DCIS)

Abstract The introduction of population-based breast cancer screening and implementation of digital mammography have led to an increased incidence of ductal carcinoma in situ (DCIS) without a decrease in the incidence of advanced breast cancer. This suggests DCIS overdiagnosis exists. We hypothesize that asymptomatic, low-grade DCIS can safely be managed by active surveillance. If progression to invasive breast cancer would still occur, this will be low-grade and hormone receptor positive with excellent survival rates. Also, breast-conserving treatment will still be an option, if no prior radiotherapy has been applied. Management by active surveillance also may save many low-grade DCIS patients intensive treatment. Therefore, we will compare active surveillance with conventional treatment, being either mastectomy, wide local excision (WLE) only, or WLE plus radiotherapy, possibly followed by hormonal therapy for primary low-grade DCIS. For this, we conduct a phase III, open-label, non-inferiority, multi-center, randomized clinical trial sponsored by the European Organization for Research and Treatment of Cancer (EORTC-1401-BCG). The Dutch Centers are coordinated by the Dutch Breast Cancer Research Group (BOOG) (BOOG 2014-04). This trial is developed and implemented in close collaboration with patient advocates. Randomization will be in a 1:1 ratio among one of the following arms: (1) active surveillance or (2) standard treatment per local policy. In total, 1,240 women (≥ 45 years) will be included without prior breast cancer, but with asymptomatic, pure, low-grade DCIS, based on a minimum of tissue harvested by biopsy from calcifications detected by population-based or opportunistic screening. Assuming 25% of randomized women qualified to enroll in the study will drop out or will be excluded from per protocol evaluation, at least 1,240 women need to be randomized to obtain the 930 patients required for the evaluation of the primary endpoint. The same follow-up scheme will be applied in both study arms, i.e. annual mammography for a period of 10 years. The primary end-point is ipsilateral invasive breast tumor-free rate at 10 years. Secondary end-points are among others: overall survival, breast cancer-specific survival, mastectomy rate, patient reported outcomes and cost-effectiveness. Accrual has started in the Netherlands in February 2017 and will start internationally in over 30 centers shortly. Acknowledgements: This trial is funded by Pink Ribbon Netherlands, the Dutch Cancer Society and Dutch Cancer Society/Alpe d'HuZes, and Cancer Research UK. Citation Format: Wesseling J, Elshof LE, Tryfonidis K, Poncet C, Aalders K, van Leeuwen-Stok E, Skinner V, Loo C, Winter-Warnars G, Bleiker E, Retèl V, Pijnappel R, Bijker N, Rutgers E, van Duijnhoven F. Update of the randomized, non-inferiority LORD trial testing safety of active surveillance for women with screen-detected low risk ductal carcinoma in situ (EORTC-1401-BCG/BOOG 2014-04, DCIS) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-07-01.

Abstract CT137: Standard therapy versus active surveillance for low grade DCIS: the LORD trial

Abstract The introduction of population-based breast cancer screening and implementation of digital mammography have led to an increased incidence of ductal carcinoma in situ (DCIS) without a decrease in the incidence of advanced breast cancer. This suggests DCIS overdiagnosis exists. We hypothesize that asymptomatic, low-grade DCIS can safely be managed by active surveillance. If progression to invasive breast cancer would still occur, this will be low-grade and hormone receptor positive with excellent survival rates. Also, breast-conserving treatment will still be an option, if no prior radiotherapy has been applied. It also may save many low-grade DCIS patients from intensive treatment. We will compare active surveillance with conventional treatment, being either wide local excision (WLE) only, WLE plus radiotherapy or mastectomy, possibly followed by hormonal therapy for primary low-grade DCIS, detected by calcifications only, in a phase III, open-label, non-inferiority, multi-center, randomized clinical trial legally supported by the Breast Cancer Group of the European Organisation for the Research and Treatment of Cancer (EORTC-1401-BCG). The Dutch Centers are coordinated by the BOOG Study Center (BOOG 2014-04). Randomization will be 1:1 in to one of the following arms: active surveillance or standard treatment per local policy. In total, 1240 women (≥ 45 years) with asymptomatic, pure, low-grade DCIS, based on vacuum-assisted biopsies of calcifications as detected by population-based or opportunistic screening, without prior breast cancer, will be included. Assuming 25% of randomized women qualified to enroll in the study will drop out or will be excluded from per protocol population, at least 1,240 women need to be randomized to obtain the 930 patients required for the evaluation of the primary endpoint. The same follow-up scheme will be applied in both study arms, i.e. annual mammography for a period of 10 years. The primary end-point is ipsilateral invasive breast tumor-free rate at 10 years. Secondary end-points are among others: overall survival, breast cancer-specific survival, mastectomy rate and patient reported outcomes. Accrual has started in January 2017. Acknowledgements: This trial is funded by Pink Ribbon Netherlands, the Dutch Cancer Society and Dutch Cancer Society/Alpe d’HuZes. Citation Format: Jelle Wesseling, Frederieke van Duijnhoven, Konstantinos Tryfonidis, Aleksandra Peric, Elise van Leeuwen-Stok, Nina Bijker, Lotte Elshof, Emiel Rutgers. Standard therapy versus active surveillance for low grade DCIS: the LORD trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT137. doi:10.1158/1538-7445.AM2017-CT137

Breast cancer incidence: Decreasing trend in large tumours in women aged 50-74.

Objective A decrease in advanced breast cancer incidence is considered an early indicator of breast cancer mortality reduction in a screening programme. We describe trends in breast cancer incidence according to tumour size and age in three French administrative areas, where an organized screening programme was implemented during the 1990s. Methods Our study included all 28,092 invasive breast cancers diagnosed from 2000 to 2010 in women living in three areas (Hérault, Isère, Loire-Atlantique). Age, year of diagnosis, and size of tumour at diagnosis was provided by the three area cancer registries. Poisson regression models were fitted to estimate changes in incidence over time, after adjustment for age and administrative area. Results From 2000 to 2010, the incidence rate of large (tumour size >20 mm) breast cancer linearly decreased in women aged 50-74 (target age of the screening programme) from 108.4 to 84.1/100,000 (annual percent change = -1.9%, p < 0.001). No change in large breast cancer incidence rate was found in women aged 20-49, or older than 74. Conclusions A decreasing trend in incidence of large tumour size breast cancer in the target age of the screening programme is demonstrated for the first time in France. The overall 20.9% linear decrease over 11 years in these three areas is encouraging and should be closely monitored and extended to other areas of France, where the screening programme was generally implemented only in 2004.

Trends in advanced breast cancer incidence rates after implementation of a mammography screening program in a German population

BackgroundMammography screening programs (MSPs) aim to detect early-stage breast cancers in order to decrease the incidence of advanced-stage breast cancers and to reduce breast cancer mortality. We analyzed the time trends of advanced-stage breast cancer incidence rates in the target population before and after implementation of the MSP in a region of northwestern Germany. MethodsThe MSP in the Münster district started in October 2005. A total of 13,874 women with an incident invasive breast cancer (BC) was identified by the population-based epidemiological cancer registry between 2000 and 2013 in the target group 50–69 years. Multiple imputation methods were used to replace missing data on tumor stages (10.4%). The incidence rates for early-stage (UICC I) and advanced-stage (UICC II+) BC were determined, and Poisson regression analyses were performed to assess trends over time. ResultsThe incidence rates for UICC I breast cancers increased during the step-up introduction of the MSP and remained elevated thereafter. By contrast, after increasing from 2006 to 2008, the incidence rates of UICC II+ breast cancers decreased to levels below the pre-screening period. Significantly decreasing UICC II+ incidence rates were limited to the age group 55–69 years and reached levels that were significantly lower than incidence rates in the pre-screening period. DiscussionThe incidence rates of advanced-stage breast cancers decreased in the age groups from 55 years to the upper age limit for screening eligibility, but not in the adjacent age groups. The findings are consistent with MSP lead time effects and seem to indicate that the MSP lowers advanced-stage breast cancer rates in the target population.

Understanding breast health awareness in an Arabic culture: qualitative study protocol.

To explore breast health awareness and the early diagnosis and detection methods of breast cancer from the perspective of women and primary healthcare providers in the Jizan region of the Kingdom of Saudi Arabia. Although there is a high incidence of advanced breast cancer in young women in the Kingdom of Saudi Arabia, there is no standardized information about breast self-examination, or is there a national screening programme involving clinical breast examination and mammography available. Qualitative exploratory study. Data collection will consist of 36 face-to-face semi-structured interviews: 12 with general practitioners; 12 with nurses at primary healthcare centres and with 12 women who attend the health centres. This study will be carried out in eight states across the Jizan region (four rural and four urban) to reflect the cultural diversity of Jizan. The data will be analysed using thematic content analysis. Research Ethics Committee approval was obtained in June 2015. While we understand the enablers and barriers to breast health awareness outside of Saudi culture, in the Kingdom of Saudi Arabia, particularly in rural populations such as Jizan, there is a lack of research. This study will add positively to the international knowledge base of this topic. The findings will give evidence and inform policy about women and healthcare providers' experiences in Jizan, in a society where such topics are taboo.

Reduction of advanced breast cancer stages at subsequent participation in mammography screening

Purpose: The decline in advanced breast cancer stages is presumably the most relevant surrogate parameter in mammography screening. It represents the last step in the causal cascade that is expected to affect breast cancer-related mortality. To assess the effectiveness of population-based screening, we analyzed the 2-year incidence rates of advanced breast cancers between women participating in the initial and in the first subsequent round. Materials and methods: The study included data from 19 563 initial and 18 034 subsequent examinations of one digital screening unit (2008 – 2010). Data on tumor stages, detected by screening or within the following interval of two years (2-year incidence), were provided by the epidemiological cancer registry. Rates of all and combined UICC stages 2, 3 and 4 (advanced stages) were reported for a two-year period. Proportions were tested for significance by using chi-square tests (p Results: The 2-year incidence rate of all stages was significantly lower in participants in subsequent screening than in initial screening (0.85 vs. 1.29 per 100 women (%); p Conclusion: During the change from prevalent to incident phase mammography screening, a program impact is seen by a lower 2-year incidence of advanced breast cancers within subsequent compared to initial participants, predominately in women aged 60 to 69 years. Key Points:

Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement.

Update of the 2009 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for breast cancer. The USPSTF reviewed the evidence on the following: effectiveness of breast cancer screening in reducing breast cancer-specific and all-cause mortality, as well as the incidence of advanced breast cancer and treatment-related morbidity; harms of breast cancer screening; test performance characteristics of digital breast tomosynthesis as a primary screening strategy; and adjunctive screening in women with increased breast density. In addition, the USPSTF reviewed comparative decision models on optimal starting and stopping ages and intervals for screening mammography; how breast density, breast cancer risk, and comorbidity level affect the balance of benefit and harms of screening mammography; and the number of radiation-induced breast cancer cases and deaths associated with different screening mammography strategies over the course of a woman's lifetime. This recommendation applies to asymptomatic women aged 40 years or older who do not have preexisting breast cancer or a previously diagnosed high-risk breast lesion and who are not at high risk for breast cancer because of a known underlying genetic mutation (such as a BRCA1 or BRCA2 gene mutation or other familial breast cancer syndrome) or a history of chest radiation at a young age. The USPSTF recommends biennial screening mammography for women aged 50 to 74 years. (B recommendation) The decision to start screening mammography in women prior to age 50 years should be an individual one. Women who place a higher value on the potential benefit than the potential harms may choose to begin biennial screening between the ages of 40 and 49 years. (C recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening mammography in women aged 75 years or older. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the benefits and harms of digital breast tomosynthesis (DBT) as a primary screening method for breast cancer. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of adjunctive screening for breast cancer using breast ultrasonography, magnetic resonance imaging (MRI), DBT, or other methods in women identified to have dense breasts on an otherwise negative screening mammogram. (I statement).

Reduction of Advanced Breast Cancer Stages at Subsequent Participation in Mammography Screening.

The decline in advanced breast cancer stages is presumably the most relevant surrogate parameter in mammography screening. It represents the last step in the causal cascade that is expected to affect breast cancer-related mortality. To assess the effectiveness of population-based screening, we analyzed the 2-year incidence rates of advanced breast cancers between women participating in the initial and in the first subsequent round. The study included data from 19,563 initial and 18,034 subsequent examinations of one digital screening unit (2008 - 2010). Data on tumor stages, detected by screening or within the following interval of two years (2-year incidence), were provided by the epidemiological cancer registry. Rates of all and combined UICC stages 2, 3 and 4 (advanced stages) were reported for a two-year period. Proportions were tested for significance by using chi-square tests (p < 0.001). The 2-year incidence rate of all stages was significantly lower in participants in subsequent screening than in initial screening (0.85 vs. 1.29 per 100 women (%); p < 0.0001). A significantly lower 2-year incidence of advanced stages was observed for subsequent screening compared to initial screening (0.26 % vs. 0.48 %; p = 0.0007). Among women aged 50 to 59 years, the incidence of advanced stages was less clearly different (0.21 % vs. 0.35 %; p = 0.07) than in women aged 60 to 69 years (0.31 % vs. 0.70 %; p = 0.0008). During the change from prevalent to incident phase mammography screening, a program impact is seen by a lower 2-year incidence of advanced breast cancers within subsequent compared to initial participants, predominately in women aged 60 to 69 years. • The incidence of advanced tumor stages represents the most relevant surrogate parameter for screening effectiveness. • For the first time the 2-year incidence of advanced breast cancer stages after subsequent mammography screening was analyzed. • We observed a significant effect of screening on the 2-year incidence of advanced stages, predominately in the age group 60 to 69 years.

Genome-wide DNA methylation profiling reveals parity-associated hypermethylation of FOXA1.

Early pregnancy in women by the age of 20 is known to have a profound effect on reduction of lifelong breast cancer risk as compared to their nulliparous counterparts. Additional pregnancies further enhance the protection against breast cancer development. Nationwide trend of delayed pregnancy may contribute to the recently reported increase in the incidence of advanced breast cancer among young women in this country. The underlying mechanism for the parity-associated reduction of breast cancer risk is not clearly understood. The purpose of the current study is to use whole-genome DNA methylation profiling to explore a potential association between parity and epigenetic changes in breast tissue from women with early parity and nulliparity. Breast tissue was collected from age-matched cancer-free women with early parity (age < 20; n = 15) or nulliparity (n = 13). The methyl-CpG binding domain-based capture-sequencing technology was used for whole-genome DNA methylation profiling. Potential parity-associated hypermethylated genes were further verified by locus-specific pyrosequencing, using an expanded cohort of parous (n = 19) and nulliparous (n = 16) women that included the initial samples used in the global analysis. Our study identified six genes that are hypermethylated in the parous group (P < 0.05). Pyrosequencing confirmed parity-associated hypermethylation at multiple CpG islands of the FOXA1 gene, which encodes a pioneer factor that facilitates chromatin binding of estrogen receptor α. Our work identifies several potential methylation biomarkers for parity-associated breast cancer risk assessment. In addition, the results are consistent with the notion that parity-associated epigenetic silencing of FOXA1 contributes to long-term attenuation of the estrogenic impact on breast cancer development.