scholarly journals Breast Cancer Incidence and Early Diagnosis in a Family History Risk and Prevention Clinic: 33-Year Experience in 14,311 Women

2021 ◽  
Author(s):  
D. Gareth R. Evans ◽  
Sacha J Howell ◽  
Ashu Gandhi ◽  
Elke M van Veen ◽  
Emma R Woodward ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Cancer Diagnosis ◽  
Breast Cancer Specific Survival ◽  
Breast Cancers ◽  
Cancer Specific Survival ◽  
Term Survival ◽  
Good For ◽  
Better Than

Abstract Purpose:Women at increased familial breast cancer risk have been offered screening starting at an earlier age and increased frequency than national Screening Programmes for over 30years. There are limited data on longer-term largescale implementation of this approach on cancer diagnosis.Methods:Women at our institution at ≥17% lifetime breast cancer risk have been offered enhanced screening with annual mammography starting at age 35 or 5-years younger than youngest affected relative, with upper age limit 50 for moderate and 60 for high-risk. Breast cancer pathology, stage and receptor status were assessed as well as survival from cancer diagnosis by Kaplan-Meier analysis.Results:Overall 14,311 women were seen and assessed for breast cancer risk, with 649 breast cancers occurring in 129,119.5 years follow up (post-prevalent annual incidence=4.55/1,000). Of 323/394 invasive breast cancers occurring whilst on enhanced screening, most were LN negative (72.9%), T1 (≤20mm,73.2%) and stage-1 (61.4%). Ten-year breast cancer specific survival was 91.3%(95%CI=87.4–94.0) significantly better than the 75.9%(95%CI=74.9-77.0) published for England in 2013-2017. As expected, survival was significantly better for women with screen detected cancers(p<0.001). Ten-year survival was particularly good for those with diagnosed ≤40 at 93.8% (n=75;95%CI=84.2–97.6). Women with lobular breast cancers had worse 10-year survival at 85.9% (95%CI=66.7–94.5). Breast cancer specific survival was good for 119 BRCA1/2 carriers with 20-year survival in BRCA1:91.2%(95%CI=77.8-96.6) and 83.8% (62.6-–93.5) for BRCA2Conclusions:Targeted breast screening in women aged 30-60 years at increased familial risk is associated with good long-term survival that is substantially better than expected from population data.

scholarly journals Considerations When Using Breast Cancer Risk Models for Women with Negative BRCA1/BRCA2 Mutation Results

2019 ◽  
Vol 112 (4) ◽  
pp. 418-422
Author(s):  
Robert J MacInnis ◽  
Yuyan Liao ◽  
Julia A Knight ◽  
Roger L Milne ◽  
Alice S Whittemore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Invasive Breast Cancer ◽  
Disease Incidence ◽  
Brca2 Mutation ◽  
Estimation Algorithm ◽  
Breast Cancers ◽  
Risk Models ◽  
Replication Studies

Abstract The performance of breast cancer risk models for women with a family history but negative BRCA1 and/or BRCA2 mutation test results is uncertain. We calculated the cumulative 10-year invasive breast cancer risk at cohort entry for 14 657 unaffected women (96.1% had an affected relative) not known to carry BRCA1 or BRCA2 mutations at baseline using three pedigree-based models (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, BRCAPRO, and International Breast Cancer Intervention Study). During follow-up, 482 women were diagnosed with invasive breast cancer. Mutation testing was conducted independent of incident cancers. All models underpredicted risk by 26.3%–56.7% for women who tested negative but whose relatives had not been tested (n = 1363; 63 breast cancers). Although replication studies with larger sample sizes are needed, until these models are recalibrated for women who test negative and have no relatives tested, caution should be used when considering changing the breast cancer risk management intensity of such women based on risk estimates from these models.

scholarly journals Polygenic risk score for the prediction of breast cancer is related to lesser terminal duct lobular unit involution of the breast

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Clara Bodelon ◽  
Hannah Oh ◽  
Andriy Derkach ◽  
Joshua N. Sampson ◽  
Brian L. Sprague ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Intermediate Step ◽  
Breast Cancers ◽  
Tissue Samples ◽  
Polygenic Risk ◽  
Age Related

Abstract Terminal duct lobular units (TDLUs) are the predominant anatomical structures where breast cancers originate. Having lesser degrees of age-related TDLU involution, measured as higher TDLUs counts or more epithelial TDLU substructures (acini), is related to increased breast cancer risk among women with benign breast disease (BBD). We evaluated whether a recently developed polygenic risk score (PRS) based on 313-common variants for breast cancer prediction is related to TDLU involution in the background, normal breast tissue, as this could provide mechanistic clues on the genetic predisposition to breast cancer. Among 1398 women without breast cancer, higher values of the PRS were significantly associated with higher TDLU counts (P = 0.004), but not with acini counts (P = 0.808), in histologically normal tissue samples from donors and diagnostic BBD biopsies. Mediation analysis indicated that TDLU counts may explain a modest proportion (≤10%) of the association of the 313-variant PRS with breast cancer risk. These findings suggest that TDLU involution might be an intermediate step in the association between common genetic variation and breast cancer risk.

scholarly journals Epigenetic Biomarkers for Environmental Exposures and Personalized Breast Cancer Prevention

2020 ◽  
Vol 17 (4) ◽  
pp. 1181 ◽  
Author(s):  
Hannah Lui Park
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Alcohol Consumption ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Hormone Therapy ◽  
Environmental Exposures ◽  
Breast Cancers ◽  
Prevention Strategies ◽  
Epigenetic Biomarkers

Environmental and lifestyle factors are believed to account for >80% of breast cancers; however, it is not well understood how and when these factors affect risk and which exposed individuals will actually develop the disease. While alcohol consumption, obesity, and hormone therapy are some known risk factors for breast cancer, other exposures associated with breast cancer risk have not yet been identified or well characterized. In this paper, it is proposed that the identification of blood epigenetic markers for personal, in utero, and ancestral environmental exposures can help researchers better understand known and potential relationships between exposures and breast cancer risk and may enable personalized prevention strategies.

Breast cancer epidemiologic risk factors by HER2/neu status

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 585-585
Author(s):  
W. Y. Chen ◽  
G. A. Colditz ◽  
B. Rosner
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Risk Factor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Benign Breast Disease ◽  
Breast Disease ◽  
Breast Cancers ◽  
Cancer Risk Factors ◽  
Breast Cancer Risk Factors

585 Background: Although breast cancers categorized by estrogen receptor (ER) and progesterone receptor (PR) status are recognized to differ in their associations with standard breast cancer risk factors, little data exist on differences by HER2/neu status. Methods: The Nurses’ Health Study is a prospective cohort study of 121,700 registered nurses aged 30–55 in 1976 who answered biennial questionnaires to update medical and lifestyle factors and disease occurrence. Medical record review was used to confirm invasive breast cancer and abstract ER, PR, and HER2/neu status. Statistical analyses included both proportional hazards models to estimate relative risks and control for potential confounders and polytomous logistic regression to compare the effects. Only cases diagnosed from return of the 1998 questionnaire until June 2002 were included in the analysis since HER2/neu was only routinely assessed beginning with the 1998 follow-up cycle. Results: 211 HER2/neu positive and 770 HER2/neu negative cases were included in the analysis. In this predominantly postmenopausal group aged 52–77 in 1998, HER2neu negative cancers were more likely to be ER+/PR+ (72%) and less likely to be ER-/PR- (11%) than HER2/neu positive ones (58% ER+/PR+ and 24% ER-/PR-), but the majority of cancers were still ER+/PR+. In multivariate models, risk factor associations by HER2/neu status were similar with positive associations seen for family history, benign breast disease, body mass index, current postmenopausal hormone use, and cumulative alcohol consumption. However, when the subgroup of ER-/PR-/HER2/neu negative cancers were evaluated separately (N=83), most of these risk factor associations disappeared with the only significant risk factor being a prior history of benign breast disease. Conclusions: This is the first prospective data study to report on risk factor association by HER2/neu status. For the standard epidemiologic breast cancer risk factors, ER and PR status appear to better represent separate etiologic pathways, rather than HER2/neu status. However, the subgroup of ER/PR/HER2neu negative breast cancers appears to be distinct, although power was limited and HER2/neu status was not confirmed by central review. Additional analyses stratified by ER/PR status will also be presented. No significant financial relationships to disclose.

Metastatic-free intervals and risk of breast cancer-specific mortality among patients with hormone receptor-positive breast cancer: A population-based analysis from the Surveillance, Epidemiology, and End Results registries.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13034-e13034
Author(s):  
Gregory Sampang Calip ◽  
Ernest H Law ◽  
Colin Hubbard ◽  
Nadia Azmi Nabulsi ◽  
Alemseged Ayele Asfaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Diagnosis ◽  
Breast Cancer Diagnosis ◽  
Population Based ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival ◽  
Breast Cancer Specific Mortality ◽  
Specific Mortality ◽  
Cancer Specific Mortality ◽  
Positive Breast Cancer

e13034 Background: Patients successfully treated for hormone receptor (HR)-positive early breast cancer remain at risk of recurrence and metastatic disease even after extended periods of disease-free years. Whether prolonged metastatic-free intervals ultimately confer a benefit to breast cancer-specific survival is not well understood. This study aimed to investigate metastatic-free intervals and risk of breast cancer-specific mortality among patients with HR-positive breast cancer after adjuvant therapy. Methods: We conducted a retrospective cohort study of women aged 18 years and older diagnosed with recurrent metastatic HR-positive breast cancer between 1990 and 2016 in the Surveillance, Epidemiology, and End Results registries. Patients with longitudinal information on primary stage I-III HR-positive breast cancer through the occurrence of metastatic disease and survival were included. Risks of breast cancer-specific mortality associated with metastatic-free intervals (defined as time from primary breast cancer diagnosis to metastasis) of ≥5 years compared to < 5 years were estimated. Fine and Gray competing risks regression models were used to calculate subdistribution hazard ratios (SHR) and 95% confidence intervals (CI). Results: Among 1,057 women with HR-positive breast cancer with a median age of 54 years at primary breast cancer diagnosis and 62 years at metastatic progression, 65% of women had a metastatic-free disease interval ≥5 years, whereas 35% had an interval of < 5 years. Overall, patients with metastatic-free intervals < 5 years had a five-year breast cancer-specific survival rate of 31% compared to 52% in women with intervals of ≥5 years. In multivariable analyses adjusted for age, race, diagnosis year, grade, treatment and sites of metastasis, patients with intervals of ≥5 years had decreased risk of breast cancer-specific mortality (SHR = 0.72, 95% CI 0.58-0.89, P = 0.002) compared to women with metastatic-free intervals of < 5 years. Conclusions: In this population-based study, rates of cancer-specific mortality among patients who experienced metastatic recurrence of HR-positive breast cancer were lower in women with metastatic-free intervals of 5 years or more. The results of this study may inform patient-clinician discussions surrounding prognosis and treatment selection among HR-positive patients.

scholarly journals The Other Side of the Coin: May Androgens Have a Role in Breast Cancer Risk?

2021 ◽  
Vol 23 (1) ◽  
pp. 424
Author(s):  
Chiara Chiodo ◽  
Catia Morelli ◽  
Fabiola Cavaliere ◽  
Diego Sisci ◽  
Marilena Lanzino
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Breast Tissue ◽  
Estrogen Receptor Α ◽  
Epidemiological Studies ◽  
Breast Cancers ◽  
Cancer Risk Factors ◽  
Increased Risk ◽  
The Impact

Breast cancer prevention is a major challenge worldwide. During the last few years, efforts have been made to identify molecular breast tissue factors that could be linked to an increased risk of developing the disease in healthy women. In this concern, steroid hormones and their receptors are key players since they are deeply involved in the growth, development and lifetime changes of the mammary gland and play a crucial role in breast cancer development and progression. In particular, androgens, by binding their own receptor, seem to exert a dichotomous effect, as they reduce cell proliferation in estrogen receptor α positive (ERα+) breast cancers while promoting tumour growth in the ERα negative ones. Despite this intricate role in cancer, very little is known about the impact of androgen receptor (AR)-mediated signalling on normal breast tissue and its correlation to breast cancer risk factors. Through an accurate collection of experimental and epidemiological studies, this review aims to elucidate whether androgens might influence the susceptibility for breast cancer. Moreover, the possibility to exploit the AR as a useful marker to predict the disease will be also evaluated.

scholarly journals 673Is weight more informative than body mass index for breast cancer risk

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Zhoufeng Ye ◽  
Gillian Dite ◽  
John Hopper
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Body Mass ◽  
Cox Regression ◽  
Menopausal Status ◽  
Familial Risk ◽  
Study Cohort ◽  
Breast Cancers

Abstract Background Our previous work on body mass index (BMI) and breast cancer risk found that the association depended on menopausal status but not on familial risk (Hopper, JL., et al, 2018). We now consider whether weight is a more informative risk factor for breast cancer than BMI. Methods We used data from the Prospective Family Study Cohort, a consortium of international prospective cohorts that are enriched for familial risk of breast cancer and include 16,035 unaffected women from 6701 families. Participants were followed for up to 20 years (mean 10.5 years) and there were 896 incident breast cancers with a mean age at diagnosis of 55.7 years. Cox regression was used to model risk associations as a function of age, menopausal status and underlying familial risk. We calculated robust confidence intervals by clustering by family. Model comparisons were made using the Bayesian Information Criterion (BIC). Results In repeating the best-fitting model from our original analyses, but using weight instead of BMI, we found that the log likelihood for the model using weight was 1.92 units greater than for the model using BMI (difference in BIC = 3.84). Therefore, the data are almost 50 times more likely under the model using weight. Conclusions The study found positive evidence that weight gives more information on risk than does BMI. Key messages Analysing breast cancer risk in terms of weight, rather than only BMI, might give greater insight and results that are easier to convey to the public.

scholarly journals Outcomes in different ethnic groups of New Zealand patients with screen-detected vs. non-screen-detected breast cancer

2019 ◽  
Vol 26 (4) ◽  
pp. 197-203
Author(s):  
Ross Lawrenson ◽  
Chunhuan Lao ◽  
Gregory Jacobson ◽  
Sanjeewa Seneviratne ◽  
Nina Scott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
New Zealand ◽  
Ethnic Groups ◽  
Stage Iv ◽  
P Value ◽  
Breast Cancer Specific Survival ◽  
Breast Cancers ◽  
Luminal A ◽  
Cancer Specific Survival ◽  
Detection Mode

Objective To compare characteristics and survival of New Zealand European, Māori, and Pacific women with screen-detected vs. non-screen-detected breast cancer. Methods Women aged 45–69 diagnosed with invasive breast cancer between January 2005 and May 2013 were identified from the Waikato and Auckland Breast Cancer Registries. Patient demographics and tumour characteristics were described by detection mode and ethnicity. Kaplan–Meier method was used to estimate the five-year breast cancer-specific survival of women with stage I–III breast cancer by ethnicity and detection mode. Results Women with screen-detected cancers were older, had smaller tumours, fewer stage IV (0.8% vs. 7.6%), fewer high grade (16.8% vs. 39.0%), and fewer lymph node positive diseases (26.3% vs. 51.5%) than women with non-screen-detected cancers. There were more Luminal A (70.0% vs. 54.0%), fewer human epidermal growth factor receptor 2 positive non-Luminal (4.4% vs. 8.8%), and fewer triple negative cases (7.0% vs. 13.8%) in screen-detected than non-screen-detected cancers. If not screen detected, 22.7% of breast cancers in Pacific women were stage IV compared with 2.4% if screen detected. If not screen detected, the five-year breast cancer-specific survival was 91.1% for New Zealand European women, 84.2% for Māori women, and 80.2% for Pacific women (p-value <0.001). For screen-detected breast cancer, survival between different ethnic groups was similar. Conclusions Breast cancers detected through screening are diagnosed at an earlier stage and have a greater proportion of subtypes, with better outcome. Variations in survival for Māori and Pacific women are only found in women with non-screen-detected breast cancer.

scholarly journals Performance of Breast Cancer Risk-Assessment Models in a Large Mammography Cohort

2019 ◽  
Vol 112 (5) ◽  
pp. 489-497 ◽  
Author(s):  
Anne Marie McCarthy ◽  
Zoe Guan ◽  
Michaela Welch ◽  
Molly E Griffin ◽  
Dorothy A Sippo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Predictive Accuracy ◽  
Growth Factor Receptor ◽  
Cancer Risk Assessment ◽  
Breast Cancers ◽  
Risk Assessment Models ◽  
Breast Cancer Risk Assessment ◽  
Epidermal Growth

Abstract Background Several breast cancer risk-assessment models exist. Few studies have evaluated predictive accuracy of multiple models in large screening populations. Methods We evaluated the performance of the BRCAPRO, Gail, Claus, Breast Cancer Surveillance Consortium (BCSC), and Tyrer-Cuzick models in predicting risk of breast cancer over 6 years among 35 921 women aged 40–84 years who underwent mammography screening at Newton-Wellesley Hospital from 2007 to 2009. We assessed model discrimination using the area under the receiver operating characteristic curve (AUC) and assessed calibration by comparing the ratio of observed-to-expected (O/E) cases. We calculated the square root of the Brier score and positive and negative predictive values of each model. Results Our results confirmed the good calibration and comparable moderate discrimination of the BRCAPRO, Gail, Tyrer-Cuzick, and BCSC models. The Gail model had slightly better O/E ratio and AUC (O/E = 0.98, 95% confidence interval [CI] = 0.91 to 1.06, AUC = 0.64, 95% CI = 0.61 to 0.65) compared with BRCAPRO (O/E = 0.94, 95% CI = 0.88 to 1.02, AUC = 0.61, 95% CI = 0.59 to 0.63) and Tyrer-Cuzick (version 8, O/E = 0.84, 95% CI = 0.79 to 0.91, AUC = 0.62, 95% 0.60 to 0.64) in the full study population, and the BCSC model had the highest AUC among women with available breast density information (O/E = 0.97, 95% CI = 0.89 to 1.05, AUC = 0.64, 95% CI = 0.62 to 0.66). All models had poorer predictive accuracy for human epidermal growth factor receptor 2 positive and triple-negative breast cancers than hormone receptor positive human epidermal growth factor receptor 2 negative breast cancers. Conclusions In a large cohort of patients undergoing mammography screening, existing risk prediction models had similar, moderate predictive accuracy and good calibration overall. Models that incorporate additional genetic and nongenetic risk factors and estimate risk of tumor subtypes may further improve breast cancer risk prediction.

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