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BACKGROUND: The management of the axilla in breast cancer patients with isolated chest wall recurrence (CWR) after mastectomy remains controversial. Although sentinel lymph node biopsy (SLNB) for restaging is feasible, its role is unclear. We aimed to determine if the omission of axillary restaging surgery in female patients with operable presumably isolated CWRs could result in an increased risk of second recurrences. METHODS: In this retrospective multicentre study, patients who developed CWRs were reviewed. We excluded patients with suspected or concomitant regional/distant metastases, bilateral cancers and patients without CWR surgery. Patients' demographics, pathological data and subsequent recurrences were collected from a prospective database and were compared between patients with axillary lymph node dissection (ALND) and/or SLNB versus no axillary operation at CWR. FINDINGS: A total of 194 patients with CWRs were eligible. The median age at CWR was 56.0 (IQR 47.0-67.0) years old. At recurrence, 8 (4.1%), 5 (2.6%) and 181 (93.3%) patients had ALND, SLNB and no axillary operation, respectively. Patients with no axillary surgery during CWR were associated with, at primary cancer, a lower incidence of ductal carcinoma in situ as diagnosis (p = 0.007) and older age (p = 0.022). Subsequent ipsilateral axillary (p = 0.768) and second recurrences (p = 0.061) were not statistically different between patients with and without axillary surgery at CWR on median follow-up of 59.5 (IQR 27.3-105) months. INTERPRETATION: In patients without evidence of concomitant regional or distant metastasis at CWR diagnosis, omission of axillary restaging surgery was not associated with an increased ipsilateral axillary or second recurrences on long-term follow-up.
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PURPOSE: To assess the association of a polygenic risk score (PRS) for functional genetic variants with the risk of developing breast cancer. METHODS: Summary data-based Mendelian randomization (SMR) and heterogeneity in dependent instruments (HEIDI) were used to identify breast cancer risk variants associated with gene expression and DNA methylation levels. A new SMR-based PRS was computed from the identified variants (functional PRS) and compared to an established 313-variant breast cancer PRS (GWAS PRS). The two scores were evaluated in 3560 breast cancer cases and 3383 non-cancer controls and also in a prospective study (n = 10,213) comprising 418 cases. RESULTS: We identified 149 variants showing pleiotropic association with breast cancer risk (eQTLHEIDI > 0.05 = 9, mQTLHEIDI > 0.05 = 165). The discriminatory ability of the functional PRS (AUCcontinuous [95% CI]: 0.540 [0.526 to 0.553]) was found to be lower than that of the GWAS PRS (AUCcontinuous [95% CI]: 0.609 [0.596 to 0.622]). Even when utilizing 457 distinct variants from both the functional and GWAS PRS, the combined discriminatory performance remained below that of the GWAS PRS (AUCcontinuous, combined [95% CI]: 0.561 [0.548 to 0.575]). A binary high/low-risk classification based on the 80th centile PRS in controls revealed a 6% increase in cases using the GWAS PRS compared to the functional PRS. The functional PRS identified an additional 12% of high-risk cases but also led to a 13% increase in high-risk classification among controls. Similar findings were observed in the SCHS prospective cohort, where the GWAS PRS outperformed the functional PRS, and the highest-performing PRS, a combined model, did not significantly improve over the GWAS PRS. CONCLUSIONS: While this study identified potentially functional variants associated with breast cancer risk, their inclusion did not substantially enhance the predictive accuracy of the GWAS PRS.
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BACKGROUND: Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. METHODS: Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. RESULTS: Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. CONCLUSIONS: Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.
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Adenocarcinoma Mucinoso , Neoplasias da Mama , Receptor ErbB-2 , Receptores de Estrogênio , Humanos , Feminino , Receptor ErbB-2/metabolismo , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Pessoa de Meia-Idade , Idoso , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidade , Prognóstico , Receptores de Estrogênio/metabolismo , Adulto , Receptores de Progesterona/metabolismo , Estadiamento de Neoplasias , Carcinoma Ductal de Mama/terapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/metabolismo , Estudos de Coortes , Carcinoma Lobular/terapia , Carcinoma Lobular/patologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologiaRESUMO
BACKGROUND: Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients. METHODS: We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 individual CpGs (including 41,207 promoter regions) were evaluated using linear regression models adjusted for monocyte proportion. Gene set enrichment analyses (GSEA) were conducted to identify key Gene Ontology (GO) biological processes or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with chemotherapy. Results were validated in a separate cohort of breast cancer patients who were treated (n = 1273) and not treated (n = 872) by chemotherapy (1808 blood, 337 saliva). RESULTS: A total of 141 differentially methylated CpGs and 11 promoters were significantly associated with chemotherapy after multiple testing corrections in both the paired sample and single time point analyses. GSEA of promoter regions (pre-ranked by test statistics) identified six suppressed biological processes (p < 4.67e-8) related to sensory perception and detection of chemical stimuli, including smell perception (GO:0007606, GO:0007608, GO:0009593, GO:0050906, GO:0050907, and GO:0050911). The same six biological processes were significantly suppressed in the validation dataset (p < 9.02e-14). The KEGG pathway olfactory transduction (hsa04740) was also found to be significantly suppressed (ppaired-samples = 1.72e-9, psingle-timepoint-blood = 2.03e-15 and psingle-timepoint-saliva = 7.52e-56). CONCLUSION: The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell.
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Neoplasias da Mama , Metilação de DNA , Humanos , Feminino , Condutos Olfatórios , Ilhas de CpGRESUMO
Despite our understanding of the genetic basis of intra-tumoral heterogeneity, the role of stromal heterogeneity arising from an altered tumor microenvironment in affecting tumorigenesis is poorly understood. In particular, extensive study on the peri-tumoral stroma in the morphologically normal tissues surrounding the tumor is lacking. Here, we examine the heterogeneity in tumors and peri-tumoral stroma from 8 ER+/PR+/HER2- invasive breast carcinomas, through multi-region transcriptomic profiling by microarray. We describe the regional heterogeneity observed at the intrinsic molecular subtype, pathway enrichment, and cell type composition levels within each tumor and its peri-tumoral region, up to 7 cm from the tumor margins. Moreover, we identify a pro-inflammatory adipose-enriched peri-tumoral subtype which was significantly associated with poorer overall survival in breast cancer patients, in contrast to an adaptive immune cell- and myofibroblast-enriched subtype. These data together suggest that peri-tumoral heterogeneity may be an important determinant of the evolution and treatment of breast cancers.
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This is a case of a tumour that appeared largely unviable after near complete infarction. The lesion presented as a regular shaped mass with cystic appearance lacking definitive malignant radiological signs. Together with the initial non-diagnostic histological result, this could have easily led to a missed diagnosis of cancer.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Infarto/patologia , Cistos/patologia , Mamografia , Ultrassonografia Mamária , Necrose , BiópsiaRESUMO
BACKGROUND: The COVID-19 pandemic has led to a decrease in cancer screening due to the redeployment of health care resources and public avoidance of health care facilities. Breast cancer is the most common cancer diagnosed in female individuals, with improved survival rates from early detection. An avoidance of screening, resulting in late detection, greatly affects survival and increases health care resource burden and costs. OBJECTIVE: This study aimed to evaluate if a sustained decrease in public interest in screening occurred and to evaluate other search terms, and hence interest, associated with that. METHODS: This study used Google Trends to analyze public interest in breast cancer screening and symptoms. We queried search data for 4 keyword terms ("mammogram," "breast pain," "breast lump," and "nipple discharge") from January 1, 2019, to January 1, 2022. The relative search frequency metric was used to assess interest in these terms, and related queries were retrieved for each keyword to evaluate trends in search patterns. RESULTS: Despite an initial drastic drop in interest in mammography from March to April 2020, this quickly recovered by July 2020. After this period, alongside the recovery of interest in screening, there was a rapid increase in interest for arranging for mammography. Relative search frequencies of perceived breast cancer-related symptoms such as breast lump, nipple discharge, and breast pain remained stable. There was increase public interest in natural and alternative therapy of breast lumps despite the recovery of interest in mammography and breast biopsy. There was a significant correlation between search activity and Breast Cancer Awareness Month in October. CONCLUSIONS: Online search interest in breast cancer screening experienced a sharp decline at the beginning of the COVID-19 pandemic, with a subsequent return to baseline interest in arranging for mammography followed this short period of decreased interest.
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BACKGROUND: Encapsulated papillary carcinoma of the breast is rare, making difficult diagnosis and resulting in patients undergoing excision biopsy before definitive surgery. Evidence-based guidelines are sparse. We would like to further elucidate the clinicopathological, treatment and survival outcomes. MATERIALS AND METHODS: 54 patients identified, with a median follow up duration of 48 months. Patients' demographics, radiological and clinicopathological characteristics, treatment, adjuvant therapies as well as survival data were analysed. RESULTS: 18 (33.3%) cases were pure EPC, 12 (22.2%) were EPC associated with ductal carcinoma in situ (DCIS) and 24 (44.4%) cases had concurrent invasive ductal carcinoma. EPCs were more likely to present as a solid-cystic mass on sonography (63.8%), regular-shaped (oval or round) (97.9%), lack spiculations (95.7%) and lack suspicious microcalcifications (95.6%). Median tumour size was largest in the EPC with IDC group (18.5 mm). 2 patients developed loco-regional recurrence. Overall survival is good for EPCs of all subtypes. CONCLUSION: EPC is a rare tumour with excellent prognosis.
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Neoplasias da Mama , Carcinoma in Situ , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Carcinoma Papilar , Humanos , Feminino , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Prognóstico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/patologia , Estudos RetrospectivosRESUMO
Singapore launched a population-based organised mammography screening (MAM) programme in 2002. However, uptake is low. A better understanding of breast cancer (BC) risk factors has generated interest in shifting from a one-size-fits-all to a risk-based screening approach. However, public acceptability of the change is lacking. Focus group discussions (FGD) were conducted with 54 women (median age 37.5 years) with no BC history. Eight online sessions were transcribed, coded, and thematically analysed. Additionally, we surveyed 993 participants in a risk-based MAM study on how they felt in anticipation of receiving their risk profiles. Attitudes towards MAM (e.g., fear, low perceived risk) have remained unchanged for ~25 years. However, FGD participants reported that they would be more likely to attend routine mammography after having their BC risks assessed, despite uncertainty and concerns about risk-based screening. This insight was reinforced by the survey participants reporting more positive than negative feelings before receiving their risk reports. There is enthusiasm in knowing personal disease risk but concerns about the level of support for individuals learning they are at higher risk for breast cancer. Our results support the empowering of Singaporean women with personal health information to improve MAM uptake.
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Neoplasias da Mama , Feminino , Humanos , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Detecção Precoce de Câncer/métodos , Medição de RiscoRESUMO
BACKGROUND: Early detection of breast cancer (BC) through mammography screening (MAM) is known to reduce mortality. We examined the differential effect that mammography has on BC characteristics and overall survival and the sociodemographic determinants of MAM utilization in a multi-ethnic Asian population. METHODS: This study included 3739 BC patients from the Singapore Breast Cancer Cohort (2010-2018). Self-reported sociodemographic characteristics were collected using a structured questionnaire. Clinical data were obtained through medical records. Patients were classified as screeners (last screening mammogram ≤ 2 years before diagnosis), non-screeners (aware but did not attend or last screen > 2years), and those unaware of MAM. Associations between MAM behaviour (MB) and sociodemographic factors and MB and tumour characteristics were examined using multinomial regression. Ten-year overall survival was modelled using Cox regression. RESULTS: Patients unaware of screening were more likely diagnosed with late stage (ORstage III vs stage I (Ref) [95% CI]: 4.94 [3.45-7.07], p < 0.001), high grade (ORpoorly vs well-differentiated (reference): 1.53 [1.06-2.20], p = 0.022), nodal-positive, large size (OR>5cm vs ≤2cm (reference): 5.06 [3.10-8.25], p < 0.001), and HER2-positive tumours (ORHER2-negative vs HER2-positive (reference): 0.72 [0.53-0.97], p = 0.028). Similar trends were observed between screeners and non-screeners with smaller effect sizes. Overall survival was significantly shorter than screeners in the both groups (HRnon-screeners: 1.89 [1.22-2.94], p = 0.005; HRunaware: 2.90 [1.69-4.98], p < 0.001). Non-screeners and those unaware were less health conscious, older, of Malay ethnicity, less highly educated, of lower socioeconomic status, more frequently ever smokers, and less physically active. Among screeners, there were more reported personal histories of benign breast surgeries or gynaecological conditions and positive family history of breast cancer. CONCLUSIONS: Mammography attendance is associated with more favourable BC characteristics and overall survival. Disparities in the utility of MAM services suggest that different strategies may be needed to improve MAM uptake.
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Neoplasias da Mama , Detecção Precoce de Câncer , Neoplasias da Mama/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Mamografia , Programas de RastreamentoRESUMO
Objective: Patients with breast cancer who have indeterminate extra-mammary lesions, for example in lung, liver or bone, without other metastatic lesions pose a clinical dilemma regarding subsequent management. This study aimed to investigate the prevalence, characteristics and outcomes of such lesions detected on initial staging imaging, and address the clinical significance of these incidental findings. Materials and Methods: Medical records of patients with newly diagnosed breast cancer who underwent computed tomography scans and bone scintigraphy between January 1, 2015 and June 30, 2021 were reviewed. Patients with indeterminate extra-mammary lesions on imaging were included. Patients with obvious metastatic disease were excluded. Lesion characteristics, breast cancer staging, duration of follow-up and natural history of disease progression were analysed. Results: The study included 52 patients with indeterminate lesions on pre-operative imaging. The median follow-up duration was 14 (range: 6-41) months. The most common site of occurrence of indeterminate lesions was the lung (60.9%) followed by the liver (26.1%). Forty-six had lesions that remained stable (88.5%), while six (11.5%) had progression to metastatic disease. Out of these six, only two (3.8%) developed metastasis in the same site as the original indeterminate lesion, whereas the remaining four developed metastases in other sites. Conclusion: Patients with breast malignancy found to have indeterminate extra-mammary lesions without obvious distant metastasis on initial staging scans are associated with a small risk of subsequently developing metastatic disease. Although most of these lesions remain quiescent, surveillance imaging is recommended because a small but significant proportion of patients with such lesions eventually harbour actual metastatic disease.
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BACKGROUND: The hypothesis that breast cancer (BC) susceptibility variants are linked to chemotherapy-induced toxicity has been previously explored. Here, we investigated the association between a validated 313-marker-based BC polygenic risk score (PRS) and chemotherapy-induced neutropenia without fever and febrile neutropenia (FNc) in Asian BC patients. METHODS: This observational case-control study of Asian BC patients treated with chemotherapy included 161 FNc patients, 219 neutropenia patients, and 936 patients who did not develop neutropenia. A continuous PRS was calculated by summing weighted risk alleles associated with overall, estrogen receptor- (ER-) positive, and ER-negative BC risk. PRS distributions neutropenia or FNc cases were compared to controls who did not develop neutropenia using two-sample t-tests. Odds ratios (OR) and corresponding 95% confidence intervals were estimated for the associations between PRS (quartiles and per standard deviation (SD) increase) and neutropenia-related outcomes compared to controls. RESULTS: PRS distributions were not significantly different in any of the comparisons. Higher PRSoverall quartiles were negatively correlated with neutropenia or FNc. However, the associations were not statistically significant (PRS per SD increase OR neutropenia: 0.91 [0.79-1.06]; FNc: 0.87 [0.73-1.03]). No dose-dependent trend was observed for the ER-positive weighted PRS (PRSER-pos) and ER-negative weighted PRS (PRSER-neg). CONCLUSION: BC PRS was not strongly associated with chemotherapy-induced neutropenia or FNc.
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BACKGROUND: Human leukocyte antigen (HLA) genes play critical roles in immune surveillance, an important defence against tumors. Imputing HLA genotypes from existing single-nucleotide polymorphism datasets is low-cost and efficient. We investigate the relevance of the major histocompatibility complex region in breast cancer susceptibility, using imputed class I and II HLA alleles, in 25,484 women of Asian ancestry. METHODS: A total of 12,901 breast cancer cases and 12,583 controls from 12 case-control studies were included in our pooled analysis. HLA imputation was performed using SNP2HLA on 10,886 quality-controlled variants within the 15-55 Mb region on chromosome 6. HLA alleles (n = 175) with info scores greater than 0.8 and frequencies greater than 0.01 were included (resolution at two-digit level: 71; four-digit level: 104). We studied the associations between HLA alleles and breast cancer risk using logistic regression, adjusting for population structure and age. Associations between HLA alleles and the risk of subtypes of breast cancer (ER-positive, ER-negative, HER2-positive, HER2-negative, early-stage, and late-stage) were examined. RESULTS: We did not observe associations between any HLA allele and breast cancer risk at P < 5e-8; the smallest p value was observed for HLA-C*12:03 (OR = 1.29, P = 1.08e-3). Ninety-five percent of the effect sizes (OR) observed were between 0.90 and 1.23. Similar results were observed when different subtypes of breast cancer were studied (95% of ORs were between 0.85 and 1.18). CONCLUSIONS: No imputed HLA allele was associated with breast cancer risk in our large Asian study. Direct measurement of HLA gene expressions may be required to further explore the associations between HLA genes and breast cancer risk.
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Neoplasias da Mama , Antígenos HLA , Alelos , Povo Asiático/genética , Neoplasias da Mama/genética , Feminino , Predisposição Genética para Doença , Genótipo , Antígenos HLA/genética , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Physical activity (PA) is known to reduce breast cancer (BC) risk and improve patient prognosis. However, the association between pre-diagnostic PA and the aggressiveness of BC is unclear. We investigated the associations between PA, BC tumour characteristics, and survival. This retrospective observational study included 7688 BC patients from the Singapore Breast Cancer Cohort (2010−2016). PA information from the questionnaire included intensity (light/moderate/vigorous) and duration (<1 h/1−2 h/>2 h per week). A PA score (1−5) incorporating intensity and duration was calculated. Associations between PA score and tumour characteristics such as stage, histological grade, nodal and hormone receptor status were examined using multinomial regression. Moreover, 10-year overall survival was estimated using Cox regression analysis in 6572 patients after excluding patients with invalid survival data and stage IV disease. Breast tumours associated with higher PA score were more likely to be non-invasive (ORinvasive vs. non-invasive(reference) [95% CI]: 0.71 [0.58−0.87], p-trend = 0.001), of lower grade (ORpoorly vs. well differentiated(reference): 0.69 [0.52−0.93], p = 0.014), ER-positive (ORER-negative vs. ER-positive(reference): 0.94 [0.89−1.00], p-trend = 0.049), PR-positive (ORPR-negative vs. PR-positive(reference): 0.82 [0.67−0.99], p = 0.041), HER2-negative (ORHER2-negative vs. HER2-positive(reference): 1.29 [1.02−1.62], p-trend = 0.002), and less likely to be of HER2-overexpressed subtype (ORHER2-overexpressed vs. Luminal A(reference): 0.89 [0.81−0.98], p-trend = 0.018). These associations (odds ratios) were more pronounced among post-menopausal patients. A higher PA score did not improve survival. Higher levels of pre-diagnostic PA were associated with less aggressive tumours in BC patients. This illustrated another benefit of PA in addition to its known role in BC risk reduction.
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Introduction: Statins, HMG-CoA reductase inhibitors, are commonly used cholesterol-lowering medications which are also increasingly recognized to have anti-cancer properties for various cancers, including breast cancer. Most clinical evidence supports a protective effect of statin on reducing breast cancer recurrence, particularly in hormone-receptor positive breast cancers.This study seeks to study the impact of statin use on breast cancer recurrence in an Asian population. Methods: This is a retrospective study of patients diagnosed with breast cancer at the National Cancer Centre and Singapore General Hospital from 2005-2015. Statin use was defined as use after surgery. Associations between statin use, breast cancer recurrence and overall survival were estimated using Cox proportional hazards regression with adjustment for age, TNM stage, grade, ER/HER2 status, and co-morbidities. Associations between statin-use and disease-specific survival were estimated using competing risks regression. Results: A total of 7858 females with breast cancer were studied, 1353(17.2%) were statin users, 6505(82.8%) were non-statin users, with a median follow-up of 8.67 years. Distribution of cancer stage, histology, molecular subtypes and grades were similar in both groups. Estrogen receptor(ER) positive (HR 0.57,95%CI 0.43-0.76,p<0.001) and HER2 negative (HR 0.74,95%CI 0.57-0.96,p=0.026) invasive cancers had a lower risk of recurrence in statin users. Statin users trended towards a long term recurrence-risk reduction (all subtypes,HR 0.48,p=0.002; ER-, HR 0.34,p=0.036; HER2+,HR 0.10,p=0.002). The risk-reduction benefit is not appreciated in statin users with DCIS, possibly due to small recurrence event numbers. Disease-specific survival benefit was seen in statin users with ER+ cancers (adjusted SHR 0.71,95%CI 0.53-0.96,p=0.027), especially ER+ invasive cancers (adjusted SHR 0.72, 95%CI 0.53-0.97,p=0.028), but with no statistically significant benefit in overall survival for statin users (all subtypes). Conclusion: This is the first known retrospective study on the effect of statin use and breast cancer recurrence in an Asian population. Similar to previous international studies, statin use is associated with a risk reduction in breast cancer recurrence. This is especially beneficial in patients who have ER+ and HER2- invasive breast cancer. Statin use is also associated with a reduced risk of breast cancer recurrence in all subtypes of breast cancer in the long term (>6 years post diagnosis).
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PURPOSE: Emerging evidence from animal models suggests that intermittent hypoxia due to obstructive sleep apnea (OSA) is a risk factor for breast cancer. Despite their biological plausibility, human epidemiological studies have reported conflicting results. Therefore, we conducted a meta-analysis to delineate this relationship. METHODS: We searched the PubMed, Embase, Scopus, and Cochrane Library databases for eligible studies from inception until June 6, 2021. Two reviewers selected randomized trials or observational studies reporting the association between OSA and breast cancer incidence compared with those without OSA. Two reviewers extracted relevant data and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and Newcastle-Ottawa Scale (NOS). We pooled the maximally covariate-adjusted hazard ratios (HRs) using a random-effects inverse variance-weighted meta-analysis and performed pre-specified subgroup analyses. RESULTS: We included six studies out of 1,707 records, comprising a combined cohort of 5,165,200 patients. All studies used the International Classification of Diseases codes to classify OSA and breast cancer. OSA patients had a 36% increased breast cancer risk (HR, 1.36; 95% confidence interval [CI], 1.03-1.80; N = 6, I² = 96%) compared to those without OSA. Most studies adjusted for confounders, such as age, sex, obesity, diabetes mellitus, alcohol use, and hypertension. Subgroup analyses for studies with (1) multivariate adjustment and (2) at least five years of follow-up yielded HRs of 1.35 (95% CI, 0.98-1.87; N = 5, I² = 96%) and 1.57 (95% CI, 1.14-2.18; N = 4; I² = 90%), respectively. One Mendelian randomization study suggested a causal relationship, with a two-fold increase in the odds of breast cancer in patients with OSA. CONCLUSION: This meta-analysis suggested that OSA is a risk factor for breast cancer. Future studies should explore the dose-response relationship between OSA and breast cancer, and whether treatment may mitigate breast cancer risk or progression.
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BACKGROUND: Family history, and genetic and non-genetic risk factors can stratify women according to their individual risk of developing breast cancer. The extent of overlap between these risk predictors is not clear. METHODS: In this case-only analysis involving 7600 Asian breast cancer patients diagnosed between age 30 and 75 years, we examined identification of high-risk patients based on positive family history, the Gail model 5-year absolute risk [5yAR] above 1.3%, breast cancer predisposition genes (protein-truncating variants [PTV] in ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, or TP53), and polygenic risk score (PRS) 5yAR above 1.3%. RESULTS: Correlation between 5yAR (at age of diagnosis) predicted by PRS and the Gail model was low (r=0.27). Fifty-three percent of breast cancer patients (n=4041) were considered high risk by one or more classification criteria. Positive family history, PTV carriership, PRS, or the Gail model identified 1247 (16%), 385 (5%), 2774 (36%), and 1592 (21%) patients who were considered at high risk, respectively. In a subset of 3227 women aged below 50 years, the four models studied identified 470 (15%), 213 (7%), 769 (24%), and 325 (10%) unique patients who were considered at high risk, respectively. For younger women, PRS and PTVs together identified 745 (59% of 1276) high-risk individuals who were not identified by the Gail model or family history. CONCLUSIONS: Family history and genetic and non-genetic risk stratification tools have the potential to complement one another to identify women at high risk.
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Neoplasias da Mama , Povo Asiático , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Medição de RiscoRESUMO
BACKGROUND: HER2-low breast cancer (BC) is currently an area of active interest. This study evaluated the impact of low expression of HER2 on survival outcomes in HER2-negative non-metastatic breast cancer (BC). METHODS: Patients with HER2-negative non-metastatic BC from 6 centres within the Asian Breast Cancer Cooperative Group (ABCCG) (n = 28,280) were analysed. HER2-low was defined as immunohistochemistry (IHC) 1+ or 2+ and in situ hybridization non-amplified (ISH-) and HER2-zero as IHC 0. Relapse-free survival (RFS) and overall survival (OS) by hormone receptor status and HER2 IHC 0, 1+ and 2+ ISH- status were the main outcomes. A combined TCGA-BRCA and METABRIC cohort (n = 1967) was also analysed to explore the association between HER2 expression, ERBB2 copy number variation (CNV) status and RFS. RESULTS: ABCCG cohort median follow-up was 6.6 years; there were 12,260 (43.4%) HER2-low BC and 16,020 (56.6%) HER2-zero BC. The outcomes were better in HER2-low BC than in HER2-zero BC (RFS: centre-adjusted hazard ratio (HR) 0.88, 95% CI 0.82-0.93, P < 0.001; OS: centre-adjusted HR 0.82, 95% CI 0.76-0.89, P < 0.001). On multivariable analysis, HER2-low status was prognostic (RFS: HR 0.90, 95% CI 0.85-0.96, P = 0.002; OS: HR 0.86, 95% CI 0.79-0.93, P < 0.001). These differences remained significant in hormone receptor-positive tumours and for OS in hormone receptor-negative tumours. Superior outcomes were observed for HER2 IHC1+ BC versus HER2-zero BC (RFS: HR 0.89, 95% CI 0.83-0.96, P = 0.001; OS: HR 0.85, 95% CI 0.78-0.93, P = 0.001). No significant differences were seen between HER2 IHC2+ ISH- and HER2-zero BCs. In the TCGA-BRCA and METABRIC cohorts, ERBB2 CNV status was an independent RFS prognostic factor (neutral versus non-neutral HR 0.71, 95% CI 0.59-0.86, P < 0.001); no differences in RFS by ERBB2 mRNA expression levels were found. CONCLUSIONS: HER2-low BC had a superior prognosis compared to HER2-zero BC in the non-metastatic setting, though absolute differences were modest and driven by HER2 IHC 1+ BC. ERBB2 CNV merits further investigation in HER2-negative BC.