674 hot topic(s) found with the query "Breast cancer"
Postpartum Breast Cancer and Survival in Women With Germline BRCA Pathogenic Variants
(Posted: Apr 21, 2024 8AM)
From the article: "Is postpartum diagnosis an independent risk factor associated with mortality among patients with young-onset breast cancer with germline BRCA1/2 pathogenic variants (PVs)? Findings: This cohort study including 903 women with BRCA germline PVs found that a breast cancer diagnosis less than 10 years post partum was associated with higher risk of mortality compared with nulliparous women and women diagnosed at least 10 years post partum. Increased risk after childbirth varied, with highest risk at less than 5 years for women with ER-positive breast cancer vs 5 to less than 10 years for women with ER-negative breast cancer, and BRCA1 carriers had peak risk of mortality 5 to less than 10 years post partum, with no associations observed for BRCA2 carriers. Meaning: These findings suggest that a breast cancer diagnosis within 10 years of childbirth was independently associated with increased risk for mortality in patients with germline BRCA1/2 PVs, especially for carriers of BRCA1 PVs."
Socioecologic Factors and Racial Differences in Breast Cancer Multigene Prognostic Scores in US Women.
Ashwini Z Parab et al. JAMA Netw Open 2024 4 (4) e244862
(Posted: Apr 04, 2024 9AM)
From the abstract: " In this cohort study of 69?139 women with breast cancer, non-Hispanic Black and non-Hispanic American Indian and Alaska Native women were more likely to have tumors with high-risk RSs compared with non-Hispanic White women. For non-Hispanic Black women, area-level socioeconomic position, urban residence, and insurance status mediated 17% of the racial difference in the RSs, and racial differences between non-Hispanic Black and non-Hispanic White women in the RSs were observed only among urban women. These findings suggest that disproportionately aggressive breast tumor biology among non-Hispanic Black women may be partially explained by socioecologic factors."
PARP Inhibitors for Breast Cancer Treatment: A Review.
Stefania Morganti et al. JAMA Oncol 2024 3
(Posted: Mar 23, 2024 6AM)
From the abstract: "Poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors have revolutionized the treatment of patients with germline BRCA1/2-associated breast cancer, representing the first targeted therapy capable of improving outcomes in patients with hereditary tumors. However, resistance to PARP inhibitors occurs in almost all patients. This narrative review summarizes the biological rationale behind the use of PARP inhibitors in breast cancer, as well as the available evidence, recent progress, and potential future applications of these agents. Recent studies have shown that the benefit of PARP inhibitors extends beyond patients with germline BRCA1/2-associated metastatic breast cancer to patients with somatic BRCA1/2 variants and to those with germline PALB2 alterations. "
The promise of AI in personalized breast cancer screening: are we there yet?
Despina Kontos et al. Nat Rev Clin Oncol 2024 3
(Posted: Mar 21, 2024 7AM)
From the abstract: " The benefits and potential harms of mammography-based screening for breast cancer are often a matter of debate. Here, I discuss the promises and limitations of a recent study that tested an artificial intelligence-based tool for the detection of breast cancer in digital mammograms in a large, prospective screening setting."
Polygenic risk scores, radiation treatment exposures and subsequent cancer risk in childhood cancer survivors.
Todd M Gibson et al. Nat Med 2024 3
(Posted: Mar 12, 2024 0PM)
From the abstract: "Survivors of childhood cancer are at increased risk for subsequent cancers attributable to the late effects of radiotherapy and other treatment exposures; thus, further understanding of the impact of genetic predisposition on risk is needed. Combining genotype data for 11,220 5-year survivors from the Childhood Cancer Survivor Study and the St Jude Lifetime Cohort, we found that cancer-specific polygenic risk scores (PRSs) derived from general population, genome-wide association study, cancer loci identified survivors of European ancestry at increased risk of subsequent basal cell carcinoma (odds ratio per s.d. of the PRS: OR?=?1.37, 95% confidence interval (CI)?=?1.29–1.46), female breast cancer (OR?=?1.42, 95% CI?=?1.27–1.58), thyroid cancer (OR?=?1.48, 95% CI?=?1.31–1.67), squamous cell carcinoma (OR?=?1.20, 95% CI?=?1.00–1.44) and melanoma (OR?=?1.60, 95% CI?=?1.31–1.96) "
Cancer risks among first-degree relatives of women with a genetic predisposition to breast cancer.
Qingyang Xiao et al. J Natl Cancer Inst 2024 2
(Posted: Feb 22, 2024 9AM)
From the abstract: "We used women from two Swedish cohorts (KARMA and pKARMA), including 28,362 women with genotyping data and 13,226 with sequencing data. Using Swedish Multi-Generation Register, we linked these women to 133,389 first-degree relatives. Associations between protein-truncating variants (PTVs) in 8 risk genes and breast cancer polygenic risk score (PRS) in index women and cancer risks among their relatives were modeled via Cox regression.Female relatives of index women who were PTV carriers in any of the 8 risk genes had an increased breast cancer risk compared to those of non-carriers (HR 1.85, 95% CI: 1.52-2.27), with the strongest association found for PTVs in BRCA1/2. "
Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer.
Xia Wei et al. JAMA Netw Open 2024 2 (2) e2355324
(Posted: Feb 11, 2024 10AM)
From the abstract: This economic evaluation using a decision-analytic Markov model with a simulated cohort of women aged 30 years found that undergoing both risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) was most cost-effective, maximizing cancers prevented for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) pathogenic variants, while RRSO was cost-effective at age 45 years for women with RAD51C, RAD51D, and BRIP1 pathogenic variants." "
Combining rare and common genetic variants improves population risk stratification for breast cancer
A Bolze et al, Genetics in Medicine Open, February 2, 2024
(Posted: Feb 05, 2024 11AM)
From the abstract: " This study aimed to evaluate the performance of different genetic screening approaches to identify women at high-risk of breast cancer in the general population. We retrospectively studied 25,591 women with available electronic health records and genetic data, participants in the Healthy Nevada Project. Family history of breast cancer was ascertained on or after the record of breast cancer for 78% of women with both, indicating that this risk assessment method is not being properly utilized for early screening. Genetics offered an alternative method for risk assessment. 11.4% of women were identified as high-risk based on possessing a predicted loss-of-function (pLOF) variant in BRCA1, BRCA2 or PALB2 (hazard ratio = 10.4, 95% confidence interval: 8.1-13.5), or a pLOF variant in ATM or CHEK2 (HR = 3.4, CI: 2.4-4.8), or being in the top 10% of the polygenic risk score (PRS) distribution (HR = 2.4, CI: 2.0-2.8). "
Concurrent Tissue and Circulating Tumor DNA Molecular Profiling to Detect Guideline-Based Targeted Mutations in a Multicancer Cohort.
Wade T Iams et al. JAMA Netw Open 2024 1 (1) e2351700
(Posted: Jan 23, 2024 7AM)
In this cohort study of 3209 patients undergoing concurrent testing across 4 cancer types who received both tissue-based and ctDNA genomic profiling results, 45.1% had a guideline-based variant detected. Of these patients, 9.3% had a clinically actionable variant detected by ctDNA profiling that was not detected by solid-tissue testing, and 24.2% had a variant detected by solid-tissue testing but not by ctDNA profiling; for patients with breast cancer with actionable variants, 20.2% had a unique, guideline-based variant detected by ctDNA profiling; most (55.0%) of these unique ctDNA variants were in the ESR1 gene.
The study suggests that concurrent ctDNA–based and tissue-based genomic profiling identified more patients with targetable, guideline-based variants than would have been discovered by tissue profiling alone, with a higher detection rate among patients with breast cancer. "
The Potential of Genetics in Identifying Women at Lower Risk of Breast Cancer.
Alexandre Bolze et al. JAMA Oncol 2023 12
(Posted: Jan 02, 2024 10AM)
From the abstract: "Can genetic information identify women for whom it is safe to delay mammogram screening? In this case-control study of 25?591 women, 2338 (9.1%) were classified as having low genetic risk for breast cancer; these women exhibited significantly later onset of breast cancer compared with average-risk or high-risk counterparts, indicating a potential to defer mammogram screening by 5 to 10 years. Delaying the age to start mammogram screenings for women at low genetic risk could optimize health care resource allocation.
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Pregnancy After Breast Cancer in Young BRCA Carriers An International Hospital-Based Cohort Study
M Lambertini et al, JAMA Network Open, December 7, 2023
(Posted: Dec 08, 2023 2PM)
From the abstract: "Among women carrying germline BRCA pathogenic variants, is pregnancy after breast cancer associated with adverse maternal or fetal outcomes? This international, hospital-based, retrospective cohort study including 4732 BRCA carriers showed that 1 in 5 patients conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with adverse maternal prognosis or fetal outcomes.
The cumulative incidence of pregnancy after breast cancer and disease-free survival in this large international cohort of young BRCA carriers may inform care for affected patients. "
Machine learning improves prediction of clinical outcomes for invasive breast cancers.
et al. Nat Med 2023 11
(Posted: Dec 01, 2023 7AM)
From the article: " A prognostic model for invasive breast cancer that is based on interpretable measurements of epithelial, stromal, and immune components outperforms histologic grading by expert pathologists. This model could improve clinical management of patients diagnosed with invasive breast cancer and address the concerns of pathologists about artificial intelligence (AI) trustworthiness by providing transparent and explainable predictions."
Latina immigrants' breast and colon cancer causal attributions: genetics is key.
Katie Fiallos et al. J Community Genet 2023 11
(Posted: Dec 01, 2023 7AM)
From the abstract: "Participants answered semi-structured, open-ended questions regarding the risk factors and rankings. Interviews were transcribed and subjected to thematic analysis. CCA showed no consensus around rank of causes for either cancer, and residual agreement analysis suggested the presence of two subcultural groups. “Genetics” and “hereditary factors” ranked first and second on average across participants for both cancers. Based on interview data, participants were less aware of colon cancer than breast cancer. Participants’ endorsement of heredity as a cause of breast and colon cancer was similar to beliefs reported in studies of primarily non-Latina populations. "
A population-level digital histologic biomarker for enhanced prognosis of invasive breast cancer.
Mohamed Amgad et al. Nat Med 2023 11
(Posted: Nov 29, 2023 9AM)
From the abstract: " Here we present the Histomic Prognostic Signature (HiPS), a comprehensive, interpretable scoring of the survival risk incurred by breast tumor microenvironment morphology. HiPS uses deep learning to accurately map cellular and tissue structures to measure epithelial, stromal, immune, and spatial interaction features. It was developed using a population-level cohort from the Cancer Prevention Study-II and validated using data from three independent cohorts."
Influence of family history on penetrance of hereditary cancers in a population setting.
Leigh Jackson et al. EClinicalMedicine 2023 11 102159
(Posted: Nov 14, 2023 8AM)
From the abstract: "Women with a pathogenic BRCA1 or BRCA2 variant had an increased risk of breast cancer that was higher in those with a first-degree family history (relative hazard 10.3 and 7.8, respectively) than those without (7.2 and 4.7). Penetrance to age 60 was also higher in those with a family history (44.7%, CI 32.2-59.3 and 24.1%, CI 17.5-32.6) versus those without (22.8%, CI 15.9-32.0 and 17.9%, CI 13.8-23.0). A similar pattern was seen in Lynch syndrome: individuals with a pathogenic MLH1, MSH2 or MSH6 variant had an increased risk of colorectal cancer that was significantly higher in those with a family history (relative hazard 35.6, 48.0 and 9.9) "
Neighborhood Deprivation and DNA Methylation and Expression of Cancer Genes in Breast Tumors.
Brittany D Jenkins et al. JAMA Netw Open 2023 11 (11) e2341651
(Posted: Nov 06, 2023 6PM)
From the abstract: "What is the association between neighborhood deprivation, DNA methylation, and gene expression in breast tissue for Black and White women with breast cancer? In a cross-sectional study of 185 women with breast cancer, higher neighborhood deprivation was associated with decreased methylation and gene expression of 2 tumor suppressor genes, LRIG1 and WWOX, for Black patients with breast cancer. These findings suggest that, for Black women, high neighborhood deprivation is associated with epigenetic differences in breast tumors that may lead to more aggressive disease, signaling the need for continued investment in public health interventions and policy changes at the neighborhood level. "
Predicting Breast Cancer Risk Using Radiomics Features of Mammography Images
Y Suzuki et al, JPM< October 24, 2023
(Posted: Oct 25, 2023 9AM)
From the abstract: " Mammography images contain a lot of information about not only the mammary glands but also the skin, adipose tissue, and stroma, which may reflect the risk of developing breast cancer. We aimed to establish a method to predict breast cancer risk using radiomics features of mammography images and to enable further examinations and prophylactic treatment to reduce breast cancer mortality. We used mammography images of 4000 women with breast cancer and 1000 healthy women from the ‘starting point set’ of the OPTIMAM dataset, a public dataset."
Ki-67, 21-Gene Recurrence Score, Endocrine Resistance, and Survival in Patients With Breast Cancer
J Li et al, JAMA Network Open, August 30, 2023
(Posted: Aug 30, 2023 1PM)
From the abstract: " Is Ki-67 expression associated with the 21-gene recurrence score (RS) and with outcomes in patients with breast cancer with a low RS?
In this cohort study of 2295 patients with breast cancer, a moderate correlation was observed between Ki-67 and RS. Ki-67 had a significant association with disease recurrence beyond 3 years and with secondary endocrine resistance in patients with a low RS."
Neighborhood Disadvantage, African Genetic Ancestry, Cancer Subtype, and Mortality Among Breast Cancer Survivors
HS Iyer et al, JAMA Network Open, August 30, 2023
(Posted: Aug 30, 2023 1PM)
From the abstract: "What are the relative strengths of associations of African genetic ancestry and neighborhood social environment with outcomes in Black breast cancer survivors? In this cohort study with 1575 Black female breast cancer survivors aged 20 to 75 years at diagnosis, African genetic ancestry was more strongly associated with tumor subtype than mortality. Associations between neighborhood socioeconomic status and mortality were attenuated following adjustment for potential mediators, including individual socioeconomic factors, lifestyle factors, and comorbidities."
Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk
N Wilcox et al, Nat Genetics, August 17, 2023
(Posted: Aug 18, 2023 7AM)
To evaluate the role of rare coding variants more comprehensively, we performed a meta-analysis across three large whole-exome sequencing datasets, containing 26,368 female cases and 217,673 female controls. Burden tests were performed for protein-truncating and rare missense variants in 15,616 and 18,601 genes, respectively. Associations between protein-truncating variants and breast cancer were identified for the following six genes at exome-wide significance (P?<?2.5?×?10-6): the five known susceptibility genes ATM, BRCA1, BRCA2, CHEK2 and PALB2, together with MAP3K1.
Metaplastic breast cancer and BRCA1: first strong evidence of a link
D Gareth et al, EJHG, August 17, 2023
(Posted: Aug 17, 2023 11AM)
“I don’t need any more unknowns hanging over my head”: Cancer patients’ views on variants of uncertain significance and low/moderate risk results from genomic sequencing
S Shickh et al, Genet in Medicine, August 11, 2023
(Posted: Aug 11, 2023 11AM)
We sought to explore patient-reported utility of all types of cancer results from genomic sequencing (GS). This was a qualitative study, using semi-structured interviews with patients who underwent GS within a trial. Patients’ perceptions of the utility of cancer GS results hinged on whether they triggered clinical action. For example, when patients were enrolled into high-risk breast cancer surveillance programs for low/moderate risk breast cancer genes, they perceived the results to be very “useful” and of moderate-high utility. In contrast, patients receiving low/moderate risk or primary VUS results without clinical action perceived results as “concerning”, leading to harms such as hypervigilance about cancer symptoms.
Management of individuals with germline pathogenic/likely pathogenic variants in CHEK2: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)
H Hanson et al, Genetics in Medicine, July 25, 2023
(Posted: Jul 26, 2023 8AM)
Although CHEK2 is considered a moderate penetrance gene, cancer risks may be considered as a continuous variable, which are influenced by family history and other modifiers. Consequently, early cancer detection and prevention for CHEK2 heterozygotes should be guided by personalized risk estimates. Such estimates may result in both downgrading lifetime breast cancer risks to those similar to the general population or upgrading lifetime risk to a level at which CHEK2 heterozygotes are offered high-risk breast surveillance according to country-specific guidelines.
Changes in methylation-based aging in women who do and do not develop breast cancer.
Jacob K Kresovich et al. J Natl Cancer Inst 2023 7
(Posted: Jul 23, 2023 9AM)
Breast cancer survivors have increased incidence of age-related diseases, suggesting that some survivors may experience faster biological aging.
Among women who developed breast cancer, diagnoses occurred an average of 3.5 years after the initial blood draw and 4 years before the second draw. After accounting for covariates and biological aging metrics measured at baseline, women diagnosed and treated for breast cancer had higher biological aging at the second blood draw than women who remained cancer-free as measured by PhenoAgeAccel (standardized mean difference [ß] = 0.13, 95% confidence interval [CI) = 0.00 to 0.26), GrimAgeAccel (ß = 0.14, 95% CI = 0.03 to 0.25), and DunedinPACE (ß = 0.37, 95% CI = 0.24 to 0.50).
Clinical trials assess a precision-medicine approach to cancer screening
S Moutinho, Nature Medicine, July 18, 2023
(Posted: Jul 18, 2023 2PM)
For more than three decades, mass-population breast-cancer screening worldwide has been based solely on one risk factor: age. Most programs and guidelines recommend mammography every 2 or 3 years for women 40–50 years of age (depending on the country) up to 74 years of age — regardless of other risk factors. Researchers believe they can improve screening by stratifying women according to their risk, on the basis of genetic factors, personal and familial history, and offering them a more personalized screening routine.
Germline pathogenic variants in metaplastic breast cancer patients and the emerging role of the BRCA1 gene
G Corso et al, EJHG, July 18, 2023
(Posted: Jul 18, 2023 2PM)
we retrospectively reviewed all BC patients counseled at our Institute for genetic testing of at least BRCA1 or BRCA2 (BRCA) genes and we found that 23 (23/5226?=?0.4%) were affected by MpBC. About 65% (15/23) of MpBC patients harbored a germline pathogenic variant (PV): 13 in BRCA1 (86.7%), including two patients who received genetic testing for known familial PV, one in TP53 (6.7%), and one in MLH1 (6.7%). Our results confirmed that BRCA1 is involved in MpBC predisposition.
Construction and validation of a gene expression classifier to predict immunotherapy response in primary triple-negative breast cancer
ME Mendez et al, Comm Medicine, July 10, 2023
(Posted: Jul 10, 2023 11AM)
We built machine learning models based on pre-ICI treatment gene expression profiles to construct gene expression classifiers to identify primary TNBC ICI-responder patients. This study involved 188 ICI-naïve and 721 specimens treated with ICI plus chemotherapy, including TNBC tumors, HR+/HER2- breast tumors, and other solid non-breast tumors. The 37-gene TNBC ICI predictive (TNBC-ICI) classifier performs well in predicting pathological complete response (pCR) to ICI plus chemotherapy on an independent TNBC validation cohort (AUC?=?0.86). The TNBC-ICI classifier shows better performance than other molecular signatures, including PD-1 (PDCD1) and PD-L1 (CD274) gene expression (AUC?=?0.67).
Contralateral breast cancer risk in irradiated breast cancer patients with a germline-BRCA1/2 pathogenic variant.
Mark van Barele et al. J Natl Cancer Inst 2023 6
(Posted: Jul 01, 2023 9AM)
Radiation-induced secondary breast cancer may be a concern after radiotherapy for primary breast cancer (PBC), especially in young germline (g)BRCA-associated breast cancer patients with already high contralateral breast cancer (CBC) risk and potentially increased genetic susceptibility to radiation.
The aim of this study is to investigate whether adjuvant radiotherapy for PBC increases the risk of CBC in gBRCA1/2-associated BC patients.
The role of polygenic risk scores in breast cancer risk perception and decision-making.
Leslie Riddle et al. J Community Genet 2023 6
(Posted: Jun 20, 2023 7AM)
Polygenic risk scores (PRS) have the potential to improve the accuracy of clinical risk assessments, yet questions about their clinical validity and readiness for clinical implementation persist. Understanding how individuals integrate and act on the information provided by PRS is critical for their effective integration into routine clinical care, yet few studies have examined how individuals respond to the receipt of polygenic risk information.
Breast cancer risk stratification using genetic and non-genetic risk assessment tools for 246,142 women in the UK Biobank.
PJ Ho et al, Genetics in Medicine, Jun e 15, 2023
(Posted: Jun 16, 2023 1PM)
We studied the overlap of predicted high-risk individuals among 246,142 women enrolled in the UK Biobank. Risk predictors assessed include the Gail model (Gail), BC family history (FH, binary), BC polygenic risk score (PRS), and presence of LoF in BC predisposition genes. The best-performing combinatorial model comprises a union of high-risk women identified by PRS, FH, and, LoF (AUC2-year [95% CI]: 62.2 [60.8 to 63.6]). Assigning individual weights to each risk prediction tool increased discriminatory ability.
Germline Genetic Testing After Cancer Diagnosis.
Allison W Kurian et al. JAMA 2023 6
(Posted: Jun 06, 2023 8AM)
Among patients in the Surveillance, Epidemiology, and End Results registries diagnosed with cancer between 2013 and 2019, what was the prevalence of germline genetic testing? In this observational study that included 1?369?602 patients diagnosed with cancer in California and Georgia, germline genetic testing after cancer diagnosis was low (6.8%; n?=?93?052). Testing was highest in males with breast cancer (50%) and in patients with ovarian cancer (38.6%). Compared with non-Hispanic White patients, rates of testing were lower among Asian, Black, and Hispanic patients.
Estimating clinical risk in gene regions from population sequencing cohort data.
James D Fife et al. Am J Hum Genet 2023 5
(Posted: Jun 02, 2023 9AM)
While pathogenic variants can significantly increase disease risk, it is still challenging to estimate the clinical impact of rare missense variants more generally. Even in genes such as BRCA2 or PALB2, large cohort studies find no significant association between breast cancer and rare missense variants collectively. Here, we introduce REGatta, a method to estimate clinical risk from variants in smaller segments of individual genes.
Prediction of breast cancer risk for sisters of women attending screening.
Xinhe Mao et al. J Natl Cancer Inst 2023 5
(Posted: May 30, 2023 7AM)
We included 53,051 women from the KARMA study. Established risk factors were derived using self-reported questionnaires, mammograms, and SNP genotyping. Using the Swedish Multi-Generation Register, we identified 32,198 sisters of the KARMA women. We found that a higher breast cancer polygenic risk score, a history of benign breast disease, and higher breast density in women were associated with an increased risk of breast cancer for both women and their sisters.
Diagnostic yield and clinical relevance of expanded germline genetic testing for nearly 7000 suspected HBOC patients
J Henkel et al, AJHG, May 16, 2023
(Posted: May 15, 2023 9AM)
Clinical utility of polygenic risk scores: a critical 2023 appraisal
S Koch et al, J Comm Genetics, May 3, 2023
(Posted: May 03, 2023 7AM)
We surveyed the current state of PRSs for various diseases, including breast cancer, diabetes, prostate cancer, coronary artery disease, and Parkinson disease, with an extra focus upon the potential improvement of clinical scores by their combination with PRSs. We observed that the diagnostic and prognostic performance of PRSs alone is consistently low, as expected. Moreover, combining a PRS with a clinical score at best led to moderate improvement of the power of either risk marker. Despite the large number of PRSs reported in the scientific literature, prospective studies of their clinical utility, particularly of the PRS-associated improvement of standard screening or therapeutic procedures, are still rare.
Assessment of the HER2DX Assay in Patients With ERBB2-Positive Breast Cancer Treated With Neoadjuvant Paclitaxel, Trastuzumab, and Pertuzumab.
Adrienne G Waks et al. JAMA Oncol 2023 4
(Posted: Apr 28, 2023 8AM)
Can the HER2DX assay predict pathologic complete response (pCR) in patients with early-stage ERBB2 (formerly HER2)–positive breast cancer who were treated with neoadjuvant paclitaxel, trastuzumab, and pertuzumab? In this diagnostic study of biopsy specimens from 80 patients with early-stage ERBB2-positive breast cancer, the HER2DX assay was administered on baseline tumor biopsy specimens from patients treated during the phase 2 DAPHNe clinical trial. In a multivariable model that incorporated established predictive gene expression–based and clinicopathologic variables, including hormone receptor status, the HER2DX pCR likelihood score was significantly associated with pCR.
Assessment of a Genomic Assay in Patients With ERBB2-Positive Breast Cancer Following Neoadjuvant Trastuzumab-Based Chemotherapy With or Without Pertuzumab.
Coralia Bueno-Muiño et al. JAMA Oncol 2023 4
(Posted: Apr 28, 2023 8AM)
Can the HER2DX genomic assay (Reveal Genomics) predict response to neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab in early-stage ERBB2-positive breast cancer? In this diagnostic study of 155 patients with ERBB2 (formerly HER2)-positive breast cancer, the assay-reported pathologic complete response (pCR) score showed statistically significant association with pCR following trastuzumab-based chemotherapy independently of pertuzumab use. More importantly, a statistically significant increase in pCR rates with the addition of pertuzumab was only observed in assay-reported pCR-high disease, which represented 1 of 3 patients with ERBB2-positive breast cancer.
Neighborhood Disadvantage and Breast Cancer-Specific Survival.
Neha Goel et al. JAMA Netw Open (4) e238908
(Posted: Apr 25, 2023 7AM)
Is living in a disadvantaged neighborhood associated with breast cancer–specific survival in a majority-minority population? In this cohort study of 5027 patients with breast cancer, neighborhood disadvantage was associated with shorter breast cancer–specific survival. This finding was noted after adjusting for individual-level sociodemographic, comorbidity, breast cancer risk factor, access to care, tumor, and National Comprehensive Cancer Network guideline-concordant treatment characteristics.
Race and Ethnicity as a Sociopolitical Construct That Is Biologically Relevant in Breast Cancer.
Lisa A Newman et al. JAMA Surg 2023 4
(Posted: Apr 15, 2023 8AM)
Breast cancer polygenic risk scores derived in White European populations are not calibrated for women of Ashkenazi Jewish descent.
E Roberts et al, Genetics in Medicine, April 12, 2023
(Posted: Apr 13, 2023 6AM)
Integration of a Cross-Ancestry Polygenic Model With Clinical Risk Factors Improves Breast Cancer Risk Stratification.
Placede T Tshiaba et al. JCO precision oncology 2023 2 e2200447
(Posted: Mar 03, 2023 4PM)
We used diverse retrospective cohort data with longitudinal follow-up to develop a caPRS and integrate it with the Tyrer-Cuzick (T-C) clinical model. We tested the association between the caIRS and BC risk in two validation cohorts including > 130,000 women. Adding a caPRS to the T-C model improves BC risk stratification for women of multiple ancestries, which could have implications for screening recommendations and prevention.
Circulating tumor DNA reveals complex biological features with clinical relevance in metastatic breast cancer.
Aleix Prat et al. Nature communications 2023 3 (1) 1157
(Posted: Mar 02, 2023 9AM)
Association of Social Determinants and Tumor Biology With Racial Disparity in Survival From Early-Stage, Hormone-Dependent Breast Cancer.
Kent F Hoskins et al. JAMA oncology 2023 2
(Posted: Feb 18, 2023 8AM)
What are the relative contributions of social determinants of health and tumor biology to racial disparities in cancer-related death among Black and White women with estrogen receptor–positive, axillary node-negative breast cancer. Racial differences in indicators of aggressive tumor biology that included a genomic biomarker mediated the same proportion of the survival disparity as individual and neighborhood disadvantage. Disproportionately aggressive tumor biology among Black women may be an important driver of racial disparities in survival from estrogen receptor–positive, early-stage breast cancer.
Towards precision medicine based on a continuous deep learning optimization and ensemble approach.
Jian Li et al. NPJ digital medicine 2023 2 (1) 18
(Posted: Feb 04, 2023 7AM)
We developed a continuous learning system (CLS) based on deep learning and optimization and ensemble approach, and conducted a retrospective data simulated prospective study using ultrasound images of breast masses for precise diagnoses. We developed a continuous learning system (CLS) based on deep learning and optimization and ensemble approach, and conducted a retrospective data simulated prospective study using ultrasound images of breast masses for precise diagnoses.
Defining genomic, transcriptomic, proteomic, epigenetic, and phenotypic biomarkers with prognostic capability in male breast cancer: a systematic review.
Subarnarekha Chatterji et al. The Lancet. Oncology 2023 2 (2) e74-e85
(Posted: Feb 03, 2023 7AM)
We identified knowledge gaps in the existing literature, discussed limitations of the included studies, and outlined potential approaches for translational biomarker discovery and validation in male breast cancer. We also recognized STC2, DDX3, and DACH1 as underexploited markers of male-specific prognostic value in breast cancer.
When It Comes to Breast Cancer, Sometimes It’s All in the Family
G Miller, CDC Cancer, Blog, October 2022
(Posted: Oct 28, 2022 9AM)
Has anyone ever told you that you have your mother’s eyes? Or that you look just like your grandmother? We all get our looks and physical traits from our families, but we may not always think about risks we share for diseases like cancer, including breast cancer. The good news is that knowing your family cancer history can give you a head start toward preventing breast cancer. No matter your gender, it’s important to know your risk and learn how to protect yourself.
Invasive Lobular Carcinoma of the Breast: Toward Tailoring Therapy?
Djerroudi Lounes et al. Journal of the National Cancer Institute 2022 10
(Posted: Oct 16, 2022 7AM)
Breast Cancer Awareness Month 2022 Digital Media Toolkit
CDC, October 5, 2022
(Posted: Oct 11, 2022 2PM)
In support of the national Breast Cancer Awareness Month October 2022 observance, the CDC Division of Cancer Prevention and Control will focus messaging and activities on finding cancer early, when it’s easiest to treat. Content and activities will be structured to empower people to take the steps needed to find breast cancer early, when it’s easiest to treat by: Knowing your risk for breast cancer; Knowing how you can lower your risk of breast cancer
Knowing your family history; Knowing when to get a breast cancer screening; Knowing where to get a breast cancer screening
To prevent unnecessary biopsies, scientists train an AI model to predict breast cancer risk from MRI scans
JW Lee, Stat News, October 3, 2022
(Posted: Oct 03, 2022 7AM)
In a new paper, Witowski and his colleagues at NYU and Jagiellonian University in Poland present an artificial intelligence tool that can predict the probability of breast cancer in MRI scans as well as a panel of board-certified radiologists. In a retrospective analysis, it was also capable of reducing unnecessary biopsies by up to 20% for patients whose MRIs show suspicious lesions that might warrant a biopsy, officially known as BI-RADS category 4 lesions.
Two Factors to ID Men at Highest Risk for Prostate Cancer Death
R Nelson, Medscape, September 2022
(Posted: Oct 03, 2022 7AM)
A family history of prostate cancer has long been one of the few universally accepted risk factors for the disease. New findings now provide evidence that risk stratification based on family history and inherited polygenic risk can identify men at highest risk of dying from the disease before age 75. Men in the upper quartile of polygenic risk score or who had a family history of prostate or breast cancer accounted for close to 100% of prostate cancer deaths by age 75. This strategy can also identify men at low risk for prostate cancer, potentially sparing them from intensive prostate cancer screening.
Improving breast cancer diagnostics with deep learning for MRI.
Witowski Jan et al. Science translational medicine 2022 9 (664) eabo4802
(Posted: Sep 30, 2022 7AM)
arly detection is key to improving breast cancer outcomes. Witowski et al. developed a deep learning pipeline that improves the specificity of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of breast tissue, a technology that is sometimes used for women at higher risk of breast cancer. The authors validated this pipeline on independent cohorts, demonstrating that by decreasing false positives, this method has the potential to reduce unnecessary biopsies.
Precision medicine for advanced breast cancer- Matching genomic alterations to targeted therapies could unlock the benefits of precision medicine — but tools for interpreting genomic data are crucial.
K O'Leary, Nature Medicine, September 26, 2022
(Posted: Sep 27, 2022 8AM)
Patients with the same type of cancer can have different genomic alterations that drive those cancers. The concept of precision medicine is based on matching a patient’s own molecular profile to an effective, targeted therapy, but knowing how best to interpret and act on comprehensive genomic data remains a challenge.
Metabolomic profiles predict individual multidisease outcomes
T Buergel et al, Nature Medicine, September 22, 2022
(Posted: Sep 23, 2022 7AM)
We trained a neural network to learn disease-specific metabolomic states from 168?circulating metabolic markers measured in 117,981?participants with ~1.4?million person-years of follow-up from the UK Biobank and validated the model in four independent cohorts. We found metabolomic states to be associated with incident event rates in all the investigated conditions, except breast cancer.
An Overview of Clinical Development of Agents for Metastatic or Advanced Breast Cancer Without ERBB2 Amplification (HER2-Low)
A Prat et al, JAMA Oncology, September 15, 2022
(Posted: Sep 16, 2022 9AM)
This review suggests that ERBB2-low may be a distinct, clinically relevant breast cancer entity warranting reassessment of traditional diagnostic and therapeutic paradigms. Ongoing clinical trials and further investigations may provide optimized strategies for diagnosing and treating ERBB2-low breast cancer, including reproducible, consistent definitions to identify patients in this diagnostic category and demonstration of benefits of emerging therapies.
Application of Artificial Intelligence Techniques to Predict Risk of Recurrence of Breast Cancer: A Systematic Review
C Mazo et al, J Per Med, September 13, 2022
(Posted: Sep 14, 2022 3AM)
This review found three areas that require further work. First, there is no agreement on artificial intelligence methodologies, feature predictors, or assessment metrics. Second, issues such as sampling strategies, missing data, and class imbalance problems are rarely addressed or discussed. Third, representative datasets for breast cancer recurrence are scarce, which hinders model validation and deployment. We conclude that predicting breast cancer recurrence remains an open problem despite the use of artificial intelligence.
Precision medicine improves outcomes in metastatic breast cancer.
et al. Nature 2022 9
(Posted: Sep 09, 2022 8AM)
For breast cancers that have spread, a randomized phase II clinical trial shows that using genomic analysis to target therapies can improve outcomes, but only in people with a genetic alteration that has previously been associated with antitumor activity in clinical trials.
Polygenic risk scores and risk-stratified breast cancer screening: Familiarity and perspectives of health care professionals.
Lapointe Julie et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 9
(Posted: Sep 05, 2022 6AM)
A total of 593 professionals completed more than 2 items and 453 responded to all questions. A total of 432 (94%) participants were female, 103 (22%) were physicians, and 323 (70%) were nurses. Participants reported to be unfamiliar with (20%), very unfamiliar (32%) with, or did not know (41%) the concept of PRS. Most participants reported not having enough knowledge about risk-stratified BC screening (61%) and that they would require more training (77%).
Clustering Molecular Subtypes in Breast Cancer, Immunohistochemical Parameters and Risk of Axillary Nodal Involvement
A Pereira et al, J Per Medicine, August 29, 2022
(Posted: Aug 30, 2022 7AM)
Integrative genomic and transcriptomic analyses illuminate the ontology of HER2-low breast carcinomas.
Berrino Enrico et al. Genome medicine 2022 8 (1) 98
(Posted: Aug 30, 2022 7AM)
Broad clinical manifestations of polygenic risk for coronary artery disease in the Women’s Health Initiative
SL Clarke et al, Comm Medicine, August 25, 2022
(Posted: Aug 26, 2022 8AM)
Polygenic risk for CAD is associated with a variety of biomarkers, clinical measurements, behaviors, and diagnoses related to traditional risk factors, as well as risk-enhancing factors. Analysis of adjudicated outcomes shows a graded association between atherosclerosis related outcomes, with the highest odds ratios being observed for the most severe manifestations of CAD. We find associations between increased polygenic risk for CAD and decreased risk for incident breast and lung cancer, with replication of the breast cancer finding in an external cohort.
Bowel cancer: what role do our genes play?
Genetics Education Program, August 19, 2022
(Posted: Aug 21, 2022 3PM)
A person’s risk of developing colorectal cancer is influenced by lifestyle factors, such as a low-fiber diet and lack of regular physical activity; however, as is the case with breast cancer, some inherited genetic variants increase the likelihood of a person developing colorectal cancer. In this article, we look at two genetically inherited syndromes and examine how and why they increase a person’s risk of this particular cancer.
Interactive exploration of a global clinical network from a large breast cancer cohort
N Sella et al, NPJ Diital Medicine, August 10, 2022
(Posted: Aug 10, 2022 8AM)
Despite unprecedented amount of information now available in medical records, health data remain underexploited due to their heterogeneity and complexity. Simple charts and hypothesis-driven statistics can no longer apprehend the content of information-rich clinical data. There is, therefore, a clear need for powerful interactive visualization tools enabling medical practitioners to perceive the patterns and insights gained by state-of-the-art machine learning algorithms. Here, we report an interactive graphical interface for use as the front end of a machine learning causal inference server (MIIC), to facilitate the visualization and comprehension by clinicians of relationships between clinically relevant variables.
A digital pathway for genetic testing in UK NHS patients with cancer: BRCA-DIRECT randomised study internal pilot.
Torr Bethany et al. Journal of medical genetics 2022 7
(Posted: Jul 24, 2022 11AM)
We designed a rapid, digital pathway, supported by a genetics specialist hotline, for delivery of germline testing of BRCA1/BRCA2/PALB2 (BRCA-testing), integrated into routine UK NHS breast cancer care. We piloted the pathway, as part of the larger BRCA-DIRECT study, in 130 unselected patients with breast cancer and gathered preliminary data from a randomized comparison of delivery of pretest information digitally (fully digital pathway) or via telephone consultation with a genetics professional (partially digital pathway). Uptake of genetic testing was 98.4%, with good satisfaction reported for both the fully and partially digital pathways. Similar outcomes were observed in both arms regarding patient knowledge score and anxiety.
Genomic and epigenomic BRCA alterations predict adaptive resistance and response to platinum-based therapy in patients with triple-negative breast and ovarian carcinomas
F Menghi et al, Sci Trans Med, July 6, 2022
(Posted: Jul 06, 2022 2PM)
The authors examined the differences in response to platinum therapy of patients with TNBC and OvCa who had BRCA loss or genetic alterations as compared to promotor methylation of BRCA. They saw that both patients and mice with promotor methylation were able to adaptively lose methylation, gain BRCA1 expression, and acquire resistance to platinum therapy. These findings have broad implications in using BRCA alteration status to better predict patient.
Can breast cancer prevention strategies be tailored to biologic subtype and unique reproductive windows?
Schedin Pepper et al. Journal of the National Cancer Institute 2022 6
(Posted: Jul 03, 2022 8AM)
UK National Screening Committee's approach to reviewing evidence on artificial intelligence in breast cancer screening
S Taylor-Phillips et al, The Lancet Digital Health, July, 2022
(Posted: Jun 22, 2022 11AM)
When considering cancer detection, AI test sensitivity alone is not sufficiently informative, and additional information on the spectrum of disease detected and interval cancers is crucial to better understand the benefits and harms of screening. Although large retrospective studies might provide useful evidence by directly comparing test accuracy and spectrum of disease detected between different AI systems and by population subgroup, most retrospective studies are biased due to differential verification (ie, the use of different reference standards to verify the target condition among study participants).
How does re-classification of variants of unknown significance (VUS) impact the management of patients at risk for hereditary breast cancer?
Kwong Ava et al. BMC medical genomics 2022 6 (1) 122
(Posted: Jun 04, 2022 7AM)
The popularity of multigene testing increases the probability of identifying variants of uncertain significance (VUS). While accurate variant interpretation enables clinicians to be better informed of the genetic risk of their patients, currently, there is a lack of consensus management guidelines for clinicians on VUS. A review of archival variants from BRCA1 and BRCA2 genetic testing changed the management for 31.8% of the families due to increased or reduced risk. We encourage regular updates of variant databases, reference to normal population and collaboration between research laboratories on functional studies to define the clinical significances of VUS better.
Breast cancer risk stratification in women of screening age: Incremental effects of adding mammographic density, polygenic risk, and a gene panel.
Evans D Gareth R et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022 4
(Posted: Apr 19, 2022 7AM)
Breast tumor microenvironment structures are associated with genomic features and clinical outcome
E Danenberg et al, Nature Genetics, April 18, 2022
(Posted: Apr 19, 2022 7AM)
Assessment of psychosocial difficulties by genetic clinicians and distress in women at high risk of breast cancer: a prospective study
A Bredart et al, EJHG, April 11, 2022
(Posted: Apr 11, 2022 2PM)
We examined how often genetic clinicians correctly identify psychosocial difficulties in women at high breast cancer risk and explored effects of this assessment and the genetic test result on counselees’ distress. Our findings suggest that the genetic test result is a suboptimal indicator for psychological referral. Instead, clinicians should focus on emotions expressed by counselees to appraise their needs for psychological support.
Incorporating Polygenic Risk Scores and Nongenetic Risk Factors for Breast Cancer Risk Prediction Among Asian Women
Y Yang et al, JAMA Network Open, March 21, 2022
(Posted: Mar 23, 2022 8AM)
How well do breast cancer risk prediction models that incorporate polygenic risk scores (PRSs) and nongenetic risk factors perform for Asian women? In this diagnostic study of 126?894 women, a PRS including 111 genetic variants was developed and tested using data from a prospective cohort study. The PRS was significantly associated with breast cancer risk, and adding 7 nongenetic risk factors improved the model’s accuracy. These findings support the utility of prediction models in identifying Asian women with high risk of breast cancer.
Laboratory-related outcomes from integrating an accessible delivery model for hereditary cancer risk assessment and genetic testing in populations with barriers to access
LM Amendola et al, Genetics in Medicine, March 16, 2022
(Posted: Mar 19, 2022 10AM)
This study aimed to evaluate the laboratory-related outcomes of participants who were offered genomic testing based on cancer family history risk assessment tools. Patients from clinics that serve populations with access barriers, who are screened at risk for a hereditary cancer syndrome based on adapted family history collection tools (the Breast Cancer Genetics Referral Screening Tool and PREMM5), were offered exome-based panel testing for cancer risk and medically actionable secondary findings. Of all the participants, 87% successfully returned a saliva kit. Overall, 5% had a pathogenic/likely pathogenic cancer risk variant and 1% had a secondary finding. Almost all (14/15, 93%) participants completed recommended consultations with nongenetics providers after an average of 17 months. The recommended actions (eg, breast magnetic resonance imaging) were completed by 17 of 25 participants.
Racial Differences in Genomic Profiles of Breast Cancer.
Goel Neha et al. JAMA network open 2022 3 (3) e220573
(Posted: Mar 03, 2022 8AM)
Recent advancements in precision oncology contribute to these disparities by underrepresenting Black patients and Asian patients, limiting the discovery of variations and potentially targetable genes in diverse populations.4 To bridge this critical gap, we examined tumor genomic profiles by race in a large, diverse patient cohort. We identified that Black patients with metastatic breast cancer were less likely than White patients or Asian patients to have actionable genetic variations, specifically in PIK3CA.
Prevalent versus incident breast cancers: benefits of clinical and radiological monitoring in women with pathogenic BRCA1/2 variants
C Saule et al, EJHG, February 25, 2022
(Posted: Feb 25, 2022 9AM)
We compared two groups of women: the incidental breast cancer group (IBCG) were followed before breast cancer diagnosis (N?=?103), whereas the prevalent breast cancer group (PBCG) (N?=?417) had no specific follow-up for high risk before breast cancer diagnosis. Breast cancers were diagnosed at an earlier stage in the IBCG than in the PBCG: T0 in 64% versus 19% of tumors, (p?<?0.00001), and N0 in 90% vs. 75% (p?<?0.00001), respectively. Treatment differed significantly between the 2 groups: less neoadjuvant chemotherapy (7.1% vs. 28.5%, p?<?0.00001), adjuvant chemotherapy (47.7% vs. 61.9%, p?=?0.004) and more mastectomies (60% vs. 42% p?<?0.0001) in the IBCG vs PBCG groups respectively.
Advances in Breast Cancer-Screening and Treatment Get Personal
NIH News in Health, February 2022
(Posted: Feb 11, 2022 8AM)
Researchers are studying the risk factors for different types of breast cancer. They’re also searching for more personalized treatments. Breast cancer is caused by a combination of factors. Your genes, lifestyle, and environment all contribute to your risk. Researchers are trying to better understand how each plays a role. People with a family history of breast cancer are at increased risk for the disease. Some are born with rare versions of certain genes that put them at high risk. These include the genes BRCA1 and BRCA2. But the vast majority of patients have no known family history and no known gene that causes cancer.
AI as a new paradigm for risk-based screening for breast cancer.
Houssami Nehmat et al. Nature medicine 2022 1
(Posted: Jan 18, 2022 7AM)
Breast cancer (BC) is the most common female cancer worldwide and is amenable to early detection using mammography screening, which has been shown to reduce BC deaths. AI may represent a new tool in the risk assessment and screening pathway of breast cancer. To realize its potential, the effect of AI-supported decisions on relevant clinical outcomes must be prospectively evaluated.
Aiming at a Tailored Cure for ERBB2-Positive Metastatic Breast Cancer: A Review.
Tarantino Paolo et al. JAMA oncology 2022 1
(Posted: Jan 14, 2022 8AM)
A number of clinical and pathologic features allow physicians to identify patients with ERBB2-positive MBC who are more likely to experience a long-lasting response to chemotherapy and ERBB2-blockade. Long-term responders tend to be de novo metastatic, have a reduced disease burden, and tend to show deep responses to systemic treatment. In pathologic terms, features associated with long-term response are high ERBB2 expression, lack of detrimental genomic aberrations, and antitumor immune activation. These patients may potentially derive benefit from a tailored escalation of frontline treatment with novel anti-ERBB2 drugs.
Polygenic risk scores for prediction of breast cancer risk in Asian populations
WK Ho et al, Genetics in Medicine, December 15, 2021
(Posted: Dec 17, 2021 6AM)
Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We developed PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups.The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases).
Multi-omic machine learning predictor of breast cancer therapy response
SJ Sammut et al, Nature, December 7, 2021
(Posted: Dec 08, 2021 8AM)
We collected clinical, digital pathology, genomic and transcriptomic profiles of pre-treatment biopsies of breast tumors from 168 patients treated with chemotherapy +/- HER2-targeted therapy prior to surgery. Pathology endpoints (complete response or residual disease) at surgery3 were then correlated with multi-omic features in these diagnostic biopsies. Here we show that response to treatment is modulated by the pre-treated tumor ecosystem, and its multi-omics landscape can be integrated in predictive models using machine learning.
Germline breast cancer susceptibility genes, tumor characteristics, and survival
PJ Ho et al, Genome Medicine, December 2, 2021
(Posted: Dec 03, 2021 11AM)
Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. We found that PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients.
21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer
K Kalinsky et al, NEJM, December 1, 2021
(Posted: Dec 02, 2021 8AM)
Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease–free survival and distant relapse–free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy.
Readiness for mammography and artificial intelligence
CD Lehman et al, The Lancet, November 20, 2021
(Posted: Nov 19, 2021 6AM)
One area that has attracted great attention for the use of deep learning artificial intelligence (AI) in health care is medical imaging, especially mammography. Many initial AI studies proclaimed remarkable improvement in accuracy over the performance of radiologists, but a recent systematic review highlighted there is insufficient scientific evidence to support such findings.
The Association of ERBB2-Low Expression With the Efficacy of Cyclin-Dependent Kinase 4/6 Inhibitor in Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer
KKH Bao et al, JAMA Network Open, November 5, 2021
(Posted: Nov 06, 2021 9AM)
We investigated the association between low levels of ERBB2 expression and clinical outcomes among patients with HR+/ERBB2- MBC treated with CDK4/6 inhibitors. Among patients with HR+/ERBB2- MBC treated with CDK4/6 inhibitors, we observed that ERBB2-low expression was associated with an inferior PFS. This may serve as a potential marker candidate associated with CDK4/6 inhibitor efficacy.
Analysis of Sociodemographic, Clinical, and Genomic Factors Associated With Breast Cancer Mortality in the Linked Surveillance, Epidemiology, and End Results and Medicare Database
TJ Robinson et al, JAMA Network Open, October 29,2021
(Posted: Nov 01, 2021 4PM)
EER-Medicare data were available for 3522 women (mean [SD] age, 70.9 [2.6] years; 3049 [86.6%] White), of whom 1555 (44.2%) were diagnosed by screening mammogram. In the SEER-Medicare cohort, factors associated with increased BCS mortality included symptomatic detection (hazard ratio [HR], 1.49 [95% CI, 1.16-1.91]), advanced disease stage (HR for stage III, 2.33 [95% CI, 1.41-3.85]), and high-grade disease (HR, 1.85 [95% CI, 1.46-2.34]). The molecular cohort of 130 cases with luminal A/B cancer further revealed increased all-cause mortality associated with genomic upregulation of transforming growth factor ß activation and p53 dysregulation (eg, p53 dysregulation: HR, 2.15 [95% CI, 1.20-3.86]) and decreased mortality associated with androgen receptor, macrophage, cytotoxicity, and Treg signaling (eg, androgen receptor signaling: HR, 0.23 [95% CI, 0.12-0.45]).
Polygenic risk for breast cancer: in search for potential clinical utility
T Wang et al, Int J Epi, October 31, 2021
(Posted: Oct 31, 2021 8PM)
The use of a polygenic risk score (PRS) as an independent risk factor for common diseases is becoming mainstream. The initial hype on their clinical applicability appears to be maturing into appraisals of their characteristics in relation to traditional risk assessment schemes, the particular statistical modelling characteristics that would be necessary for their global use in various populations7 and their potential added public health value
Genetic Counseling and Testing in African American Patients With Breast Cancer: A Nationwide Survey of US Breast Oncologists.
Ademuyiwa Foluso O et al. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2021 10 JCO2101426
(Posted: Oct 21, 2021 8AM)
We demonstrated that racial differences exist in oncology physicians' perceived barriers to GCT for patients with breast cancer. This nationwide survey will serve as a basis for understanding physicians' determinants of GCT for African American women and highlights the necessity of education and interventions to address bias among physicians. Awareness of such physician biases can enable further work to address inequities, ultimately leading to improved GCT equity for African American women with breast cancer.
Care of men with cancer-predisposing BRCA variants
R Horton et al, BMJ, October 14,2021
(Posted: Oct 15, 2021 6AM)
Men and women are equally likely to inherit or pass on a cancer-predisposing BRCA variant—family history of cancers needs to encompass both sides of the family- Men with cancer-predisposing BRCA variants have an increased risk of developing breast cancer and are advised to be breast aware- Men with cancer-predisposing BRCA2 variants have an increased risk of developing aggressive prostate cancer (men with cancer-predisposing BRCA1 variants may also have an increased risk); it is not yet known whether prostate specific antigen screening reduces mortality in men with cancer-predisposing BRCA variants.
Machine Learning to Predict Tamoxifen Nonadherence Among US Commercially Insured Patients With Metastatic Breast Cancer.
Yerrapragada Gayathri et al. JCO clinical cancer informatics 2021 8 814-825
(Posted: Aug 30, 2021 6AM)
A total of 3,022 patients were included with 40% classified as nonadherent. All models had moderate predictive accuracy. Logistic regression (area under receiver operating characteristic 0.64) was interpreted with 94% sensitivity (95% CI, 89 to 92) and 0.31 specificity (95% CI, 29 to 33). The model accurately classified adherence (negative predictive value 89%) but was nondiscriminate for nonadherence (positive predictive value 48%). Variable importance identified top predictive factors, including age = 55 years and pretreatment procedures (lymphatic nuclear medicine, radiation oncology, and arterial surgery).
Association of Genetic Testing Results with Mortality Among Women with Breast Cancer or Ovarian Cancer.
Kurian Allison W et al. Journal of the National Cancer Institute 2021 8
(Posted: Aug 23, 2021 7AM)
Breast cancer and ovarian cancer patients increasingly undergo germline genetic testing. However, little is known about cancer-specific mortality among carriers of a pathogenic variant (PV) in BRCA1/2 or other genes in a population-based setting. Georgia and California Surveillance Epidemiology and End Results (SEER) registry records were linked to clinical genetic testing results. Among breast cancer and ovarian cancer patients treated with chemotherapy in the community, BRCA1/2 and other gene PV carriers had equivalent or lower short-term cancer-specific mortality than non-carriers
This Breast Cancer Gene Is Less Well Known, but Nearly as Dangerous- PALB2 is not as well known as BRCA, but mutations of the gene can raise a woman’s risk for breast cancer almost as much.
S Berger, NY Times, August 17, 2021
(Posted: Aug 18, 2021 3PM)
For years, women with breast cancer in their families have been getting tested for mutations in two genes, known as BRCA1 and BRCA2, to determine whether they have a sharply elevated risk of the disease. Now, doctors are increasingly recommending that anyone who was tested before 2014 go through genetic testing again — to look for a different mutation, one much less widely known.
A Data Set and Deep Learning Algorithm for the Detection of Masses and Architectural Distortions in Digital Breast Tomosynthesis Images
M Buda et al, JAMA Network Open, August 16, 2021
(Posted: Aug 17, 2021 7AM)
In this diagnostic study, a curated and annotated data set of DBT studies that contained 22?032 reconstructed DBT volumes from 5060 patients was made publicly available. A deep learning algorithm for breast cancer detection was developed and tested, with a sensitivity of 65% on a test set.
Polygenic Risk Scores for Breast Cancer—Can They Deliver on the Promise of Precision Medicine?
PD Shah, JAMA Network Open, August 4, 2021
(Posted: Aug 04, 2021 0PM)
Currently, guidelines advise against the clinical use of PRSs due to limitations in interpretation and encourage further research. Essential objectives of this research must be to examine if, when, and in whom PRSs are useful. Studies will need to not only consider discriminatory capacity, equity, and clinical utility, but also psychosocial impact and cost-effectiveness, each in context. Polygenic risk scores may well personalize cancer risk management and improve patient outcomes, but we will need to further investigate these critical issues before determining whether they can fully deliver.
Generalizability of Polygenic Risk Scores for Breast Cancer Among Women With European, African, and Latinx Ancestry
C Liu et al, JAMA Network Open, August 4, 2021
(Posted: Aug 04, 2021 11AM)
In this multicenter cohort study linking electronic medical records to genotyping data that including 39?591 women, PRSs were significantly associated with breast cancer risk in women of all ancestries, although the effect sizes were smaller in women with African ancestry.
Breast cancer polygenic risk scores: a 12-month prospective study of patient reported outcomes and risk management behavior
T Yanes et al, GIM, August 2, 2021
(Posted: Aug 02, 2021 4PM)
Of the 208 participants, 165 (79%) received their PRS. Among receivers, there were no changes in anxiety or distress following testing. However, compared to women with a low PRS, those with a high PRS reported greater genetic testing–specific distress, perceived risk, decisional regret, and less genetic testing–positive response. At 12 months, breast screening and uptake of risk-reducing strategies were consistent with current guidelines of breast cancer risk management.
Risk-Stratified Approach to Breast Cancer Screening in Canada: Women’s Knowledge of the Legislative Context and Concerns about Discrimination from Genetic and Other Predictive Health Data
S Alarie et al, JPM, July 2021
(Posted: Aug 02, 2021 4PM)
Adjuvant olaparib — should all patients with breast cancer have genetic testing?
SA Narod, Nat Rev Clin Onc, July 2021
(Posted: Jul 23, 2021 7AM)
The paradigm of precision medicine implies that breast cancer treatment should be tailored based on inherent risk of recurrence and/or individual sensitivity to various chemotherapies. A recent trial of olaparib in women with a BRCA1/2 mutation provides supporting evidence for this paradigm and suggests that the identification of genetic variants at the time of diagnosis might benefit an increasing number of patients.
Potential of polygenic risk scores for improving population estimates of women's breast cancer genetic risks.
Wolfson Michael et al. Genetics in medicine : official journal of the American College of Medical Genetics 2021 7
(Posted: Jul 08, 2021 8AM)
The Canadian heritable breast cancer risk distribution was estimated using a novel genetic mixing model (GMM). A realistically representative sample of women was synthesized based on empirically observed demographic patterns for appropriately correlated family history. Generally, the PRS was most predictive for identifying women at high risk, while family history was the weakest. Only the PRS identified any women at low risk of breast cancer.
Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer.
Tutt Andrew N J et al. The New England journal of medicine 2021 6 (25) 2394-2405
(Posted: Jun 24, 2021 6AM)
Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo.
A DNA methylation-based liquid biopsy for triple-negative breast cancer
K Cristal et al, NPJ Precision Oncology, June 16, 2021
(Posted: Jun 19, 2021 7AM)
Based on a multiplexed targeted sequencing approach, this assay included 53 amplicons from 47 regions. Analysis of a previously characterized cohort of women with metastatic TNBC with limited quantities of plasma (<2?ml) produced an AUC of 0.92 for detection of a tumor with a sensitivity of 76% for a specificity of 100%.
Men With Breast Cancer Need More Treatment Options and Access to Genetic Counseling
FDA, June 2021
(Posted: Jun 17, 2021 9AM)
If a close relative – their mother, father, brother, sister, child – has breast cancer, men are also at slightly higher risk to develop the disease. Men who have a BRCA mutation, a mutation or change in a gene that predisposes them to breast cancer, are at a greater risk. Although their chance of developing breast cancer is still low (only about 5% to 6%), men with a mutation in BRCA2 have a 100 times greater risk of developing breast cancer than men in the general population.
