Displaying publications 1 - 20 of 209 in total

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  1. Abdullah A, Abdullah KL, Yip CH, Teo SH, Taib NA, Ng CJ
    Asian Pac J Cancer Prev, 2013;14(12):7143-7.
    PMID: 24460266
    BACKGROUND: The survival outcomes for women presenting with early breast cancer are influenced by treatment decisions. In Malaysia, survival outcome is generally poor due to late presentation. Of those who present early, many refuse treatment for complementary therapy.
    OBJECTIVE: This study aimed to explore the decision making experiences of women with early breast cancer.
    MATERIALS AND METHODS: A qualitative study using individual in-depth interviews was conducted to capture the decision making process of women with early breast cancer in Malaysia. We used purposive sampling to recruit women yet to undergo surgical treatment. A total of eight participants consented and were interviewed using a semi-structured interview guide. These women were recruited from a period of one week after they were informed of their diagnoses. A topic guide, based on the Ottawa decision support framework (ODSF), was used to facilitate the interviews, which were audio recorded, transcribed and analysed using a thematic approach.
    RESULTS: We identified four phases in the decision-making process of women with early breast cancer: discovery (pre-diagnosis); confirmatory ('receiving bad news'); deliberation; and decision (making a decision). These phases ranged from when women first discovered abnormalities in their breasts to them making final surgical treatment decisions. Information was vital in guiding these women. Support from family members, friends, healthcare professionals as well as survivors also has an influencing role. However, the final say on treatment decision was from themselves.
    CONCLUSIONS: The treatment decision for women with early breast cancer in Malaysia is a result of information they gather on their decision making journey. This journey starts with diagnosis. The women's spouses, friends, family members and healthcare professionals play different roles as information providers and supporters at different stages of treatment decisions. However, the final treatment decision is influenced mainly by women's own experiences, knowledge and understanding.
    Study site: Breast surgical units, Klang Valley, Malaysia
  2. Agarwal G, Pradeep PV, Aggarwal V, Yip CH, Cheung PS
    World J Surg, 2007 May;31(5):1031-40.
    PMID: 17387549
    Breast cancer is the leading cause of cancer-related deaths in Asia, and in recent years is emerging as the commonest female malignancy in the developing Asian countries, overtaking cancer of the uterine cervix. There have been no studies objectively comparing data and facts relating to breast cancer in the developed, newly developed, and developing Asian countries thus far.
  3. Ang BH, Ho WK, Wijaya E, Kwan PY, Ng PS, Yoon SY, et al.
    J Clin Oncol, 2022 May 10;40(14):1542-1551.
    PMID: 35143328 DOI: 10.1200/JCO.21.01647
    PURPOSE: With the development of poly (ADP-ribose) polymerase inhibitors for treatment of patients with cancer with an altered BRCA1 or BRCA2 gene, there is an urgent need to ensure that there are appropriate strategies for identifying mutation carriers while balancing the increased demand for and cost of cancer genetics services. To date, the majority of mutation prediction tools have been developed in women of European descent where the age and cancer-subtype distributions are different from that in Asian women.

    METHODS: In this study, we built a new model (Asian Risk Calculator) for estimating the likelihood of carrying a pathogenic variant in BRCA1 or BRCA2 gene, using germline BRCA genetic testing results in a cross-sectional population-based study of 8,162 Asian patients with breast cancer. We compared the model performance to existing mutation prediction models. The models were evaluated for discrimination and calibration.

    RESULTS: Asian Risk Calculator included age of diagnosis, ethnicity, bilateral breast cancer, tumor biomarkers, and family history of breast cancer or ovarian cancer as predictors. The inclusion of tumor grade improved significantly the model performance. The full model was calibrated (Hosmer-Lemeshow P value = .614) and discriminated well between BRCA and non-BRCA pathogenic variant carriers (area under receiver operating curve, 0.80; 95% CI, 0.75 to 0.84). Addition of grade to the existing clinical genetic testing criteria targeting patients with breast cancer age younger than 45 years reduced the proportion of patients referred for genetic counseling and testing from 37% to 33% (P value = .003), thereby improving the overall efficacy.

    CONCLUSION: Population-specific customization of mutation prediction models and clinical genetic testing criteria improved the accuracy of BRCA mutation prediction in Asian patients.

  4. Are C, Murthy SS, Sullivan R, Schissel M, Chowdhury S, Alatise O, et al.
    Lancet Oncol, 2023 Dec;24(12):e472-e518.
    PMID: 37924819 DOI: 10.1016/S1470-2045(23)00412-6
    The first Lancet Oncology Commission on Global Cancer Surgery was published in 2015 and serves as a landmark paper in the field of cancer surgery. The Commission highlighted the burden of cancer and the importance of cancer surgery, while documenting the many inadequacies in the ability to deliver safe, timely, and affordable cancer surgical care. This Commission builds on the first Commission by focusing on solutions and actions to improve access to cancer surgery globally, developed by drawing upon the expertise from cancer surgery leaders across the world. We present solution frameworks in nine domains that can improve access to cancer surgery. These nine domains were refined to identify solutions specific to the six WHO regions. On the basis of these solutions, we developed eight actions to propel essential improvements in the global capacity for cancer surgery. Our initiatives are broad in scope, pragmatic, affordable, and contextually applicable, and aimed at cancer surgeons as well as leaders, administrators, elected officials, and health policy advocates. We envision that the solutions and actions contained within the Commission will address inequities and promote safe, timely, and affordable cancer surgery for every patient, regardless of their socioeconomic status or geographic location.
  5. Balakrishnan N, Teo SH, Sinnadurai S, Bhoo Pathy NT, See MH, Taib NA, et al.
    World J Surg, 2017 11;41(11):2735-2745.
    PMID: 28653143 DOI: 10.1007/s00268-017-4081-9
    BACKGROUND: Reproductive factors are associated with risk of breast cancer, but the association with breast cancer survival is less well known. Previous studies have reported conflicting results on the association between time since last childbirth and breast cancer survival. We determined the association between time since last childbirth (LCB) and survival of women with premenopausal and postmenopausal breast cancers in Malaysia.

    METHOD: A historical cohort of 986 premenopausal, and 1123 postmenopausal, parous breast cancer patients diagnosed from 2001 to 2012 in University Malaya Medical Centre were included in the analyses. Time since LCB was categorized into quintiles. Multivariable Cox regression was used to determine whether time since LCB was associated with survival following breast cancer, adjusting for demographic, tumor, and treatment characteristics.

    RESULTS: Premenopausal breast cancer patients with the most recent childbirth (LCB quintile 1) were younger, more likely to present with unfavorable prognostic profiles and had the lowest 5-year overall survival (OS) (66.9; 95% CI 60.2-73.6%), compared to women with longer duration since LCB (quintile 2 thru 5). In univariable analysis, time since LCB was inversely associated with risk of mortality and the hazard ratio for LCB quintile 2, 3, 4, and 5 versus quintile 1 were 0.53 (95% CI 0.36-0.77), 0.49 (95% CI 0.33-0.75), 0.61 (95% CI 0.43-0.85), and 0.64 (95% CI 0.44-0.93), respectively; P trend = 0.016. However, this association was attenuated substantially following adjustment for age at diagnosis and other prognostic factors. Similarly, postmenopausal breast cancer patients with the most recent childbirth were also more likely to present with unfavorable disease profiles. Compared to postmenopausal breast cancer patients in LCB quintile 1, patients in quintile 5 had a higher risk of mortality. This association was not significant following multivariable adjustment.

    CONCLUSION: Time since LCB is not independently associated with survival in premenopausal or postmenopausal breast cancers. The apparent increase in risks of mortality in premenopausal breast cancer patients with a recent childbirth, and postmenopausal patients with longer duration since LCB, appear to be largely explained by their age at diagnosis.

  6. Benitez Fuentes JD, Morgan E, de Luna Aguilar A, Mafra A, Shah R, Giusti F, et al.
    JAMA Oncol, 2024 Jan 01;10(1):71-78.
    PMID: 37943547 DOI: 10.1001/jamaoncol.2023.4837
    IMPORTANCE: Stage at diagnosis is a key prognostic factor for cancer survival.

    OBJECTIVE: To assess the global distribution of breast cancer stage by country, age group, calendar period, and socioeconomic status using population-based data.

    DATA SOURCES: A systematic search of MEDLINE and Web of Science databases and registry websites and gray literature was conducted for articles or reports published between January 1, 2000, and June 20, 2022.

    STUDY SELECTION: Reports on stage at diagnosis for individuals with primary breast cancer (C50) from a population-based cancer registry were included.

    DATA EXTRACTION AND SYNTHESIS: Study characteristics and results of eligible studies were independently extracted by 2 pairs of reviewers (J.D.B.F., A.D.A., A.M., R.S., and F.G.). Stage-specific proportions were extracted and cancer registry data quality and risk of bias were assessed. National pooled estimates were calculated for subnational or annual data sets using a hierarchical rule of the most relevant and high-quality data to avoid duplicates.

    MAIN OUTCOMES AND MEASURES: The proportion of women with breast cancer by (TNM Classification of Malignant Tumors or the Surveillance, Epidemiology, and End Results Program [SEER]) stage group.

    RESULTS: Data were available for 2.4 million women with breast cancer from 81 countries. Globally, the proportion of cases with distant metastatic breast cancer at diagnosis was high in sub-Saharan Africa, ranging from 5.6% to 30.6% and low in North America ranging from 0.0% to 6.0%. The proportion of patients diagnosed with distant metastatic disease decreased over the past 2 decades from around 3.8% to 35.8% (early 2000s) to 3.2% to 11.6% (2015 onwards), yet stabilization or slight increases were also observed. Older age and lower socioeconomic status had the largest proportion of cases diagnosed with distant metastatic stage ranging from 2.0% to 15.7% among the younger to 4.1% to 33.9% among the oldest age group, and from 1.7% to 8.3% in the least disadvantaged groups to 2.8% to 11.4% in the most disadvantaged groups.

    CONCLUSIONS AND RELEVANCE: Effective policy and interventions have resulted in decreased proportions of women diagnosed with metastatic breast cancer at diagnosis in high-income countries, yet inequality persists, which needs to be addressed through increased awareness of breast cancer symptoms and early detection. Improving global coverage and quality of population-based cancer registries, including the collection of standardized stage data, is key to monitoring progress.

  7. Bhoo Pathy N, Uiterwaal CS, Taib NA, Verkooijen HM, Yip CH
    J Clin Epidemiol, 2012 May;65(5):568-71.
    PMID: 22269329 DOI: 10.1016/j.jclinepi.2011.09.013
    Many recent studies investigated the prognostic value of new biomarkers in breast cancer using data from cancer registries. Some of these studies were conducted using only patients for whom biomarker status was available (or tested). Using human epidermal growth factor receptor 2 (HER2) as an example, we determined whether testing for a recently introduced biomarker was associated with the outcome of women with breast cancer.
  8. Bhoo-Pathy N, Yip CH, Hartman M, Saxena N, Taib NA, Ho GF, et al.
    Eur J Cancer, 2012 May;48(7):982-9.
    PMID: 22366561 DOI: 10.1016/j.ejca.2012.01.034
    Adjuvant! Online is a free web-based tool which predicts 10-year breast cancer outcomes and the efficacy of adjuvant therapy in patients with breast cancer. As its prognostic performance has only been validated in high income Caucasian populations, we validated the model in a middle income Asian setting.
  9. Bhoo-Pathy N, Yip CH, Hartman M, Uiterwaal CS, Devi BC, Peeters PH, et al.
    Eur J Cancer, 2013 Feb;49(3):703-9.
    PMID: 23040889 DOI: 10.1016/j.ejca.2012.09.014
    The incidence and mortality of breast cancer continues to rise rapidly in Asian countries. However, most of our current knowledge on breast cancer has been generated in Western populations. As the socio-economic profile, life style and culture of Asian and Western women are substantially different, and genetic backgrounds vary to some extent, we need to answer the question on whether to 'adopt' or 'adapt' Western knowledge before applying it in the Asian setting. It is generally accepted that breast cancer risk factors, which have mainly been studied in Western populations are similar worldwide. However, the presence of gene-environment or gene-gene interactions may alter their importance as causal factors across populations. Diagnostic and prognostic study findings, including breast cancer prediction rules, are increasingly shown to be 'setting specific' and must therefore be validated in Asian women before implementing them in clinical care in Asia. Interventional research findings from Caucasian patients may not be applicable in patients in Asia due to differences in tumour biology/profiles, metabolism of drugs and also health beliefs which can influence treatment acceptance and adherence. While breast cancer research in Asia is warranted in all domains of medical research, it is felt that for Asian breast cancer patients, needs are highest for diagnostic and prognostic studies. International clinical trials meanwhile need to include breast cancer patients from various Asian settings to provide an insight into the effectiveness of new treatment modalities in this part of the world.
  10. Bhoo-Pathy N, Hartman M, Yip CH, Saxena N, Taib NA, Lim SE, et al.
    PLoS One, 2012;7(2):e30995.
    PMID: 22363531 DOI: 10.1371/journal.pone.0030995
    The burden of breast cancer in Asia is escalating. We evaluated the impact of ethnicity on survival after breast cancer in the multi-ethnic region of South East Asia.
  11. Bhoo-Pathy N, Yip CH, Taib NA, Hartman M, Saxena N, Iau P, et al.
    Breast, 2011 Apr;20 Suppl 2:S75-80.
    PMID: 21316967 DOI: 10.1016/j.breast.2011.01.015
    Two hospital-based breast cancer databases (University Malaya Medical Center, Malaysia [n = 1513] and National University Hospital, Singapore [n = 2545]) were merged into a regional registry of breast cancer patients diagnosed between 1990 and 2007. A review of the data found 51% of patients diagnosed before the age of 50 years. and 72% percent of the women were Chinese followed by Malays (16%), Indians (8%), and other races (4%). Median tumor size at presentation was 26 mm and about 25% of patients presented with TNM stage III or IV disease. Most tumors were of ductal histology (87%). Fifty-seven percent of tumors were estrogen receptor positive and 40% were poorly differentiated. Of those patients who had surgery, 70% had mastectomy while 30% had breast conserving surgery. Overall, chemotherapy was administered to 56% of patients and hormonal treatment to 60%. Five-year overall survival was 82.5% in patients with TNM stage 0 to stage II cancer, and 30.2% in those with later stages.
  12. Bhoo-Pathy N, Verkooijen HM, Tan EY, Miao H, Taib NA, Brand JS, et al.
    Sci Rep, 2015;5:16252.
    PMID: 26536962 DOI: 10.1038/srep16252
    Up to 25% of breast cancer patients in Asia present with de novo metastatic disease. We examined the survival trends of Asian patients with metastatic breast cancer over fifteen years. The impact of changes in patient's demography, tumor characteristics, tumor burden, and treatment on survival trend were examined. Patients with de novo metastatic breast cancer from three hospitals in Malaysia and Singapore (N = 856) were grouped by year of diagnosis: 1996-2000, 2001-2005 and 2006-2010. Step-wise multivariable Poisson regression was used to estimate the contribution of above-mentioned factors on the survival trend. Proportions of patients presenting with metastatic breast cancer were 10% in 1996-2000, 7% in 2001-2005, and 9% in 2006-2010. Patients in 2006-2010 were significantly older, appeared to have higher disease burden, and received more chemotherapy, endocrine therapy, and surgery of primary tumor. The three-year relative survival in the above periods were 20·6% (95% CI: 13·9%-28·2%), 28·8% (95% CI: 23·4%-34·2%), and 33·6% (95% CI: 28·8%-38·5%), respectively. Adjustment for treatment considerably attenuated the relative excess risk of mortality in recent years, compared to other factors. Substantial improvements in survival were observed in patients with de novo metastatic breast cancer in this study.
  13. Bhoo-Pathy N, Verkooijen HM, Wong FY, Pignol JP, Kwong A, Tan EY, et al.
    Int J Cancer, 2015 Nov 15;137(10):2504-12.
    PMID: 26018878 DOI: 10.1002/ijc.29617
    The value of adjuvant radiotherapy in triple-negative breast cancer (TNBC) is currently debated. We assessed the association between adjuvant radiotherapy and survival in a large cohort of Asian women with TNBC. Women diagnosed with TNBC from 2006 to 2011 in five Asian centers (N = 1,138) were included. Survival between patients receiving mastectomy only, breast-conserving therapy (BCT, lumpectomy and adjuvant radiotherapy) and mastectomy with radiotherapy were compared, and adjusted for demography, tumor characteristics and chemotherapy types. Median age at diagnosis was 53 years (range: 23-96 years). Median tumor size at diagnosis was 2.5 cm and most patients had lymph node-negative disease. The majority of patients received adjuvant chemotherapy (n = 861, 76%) comprising predominantly anthracycline-based regimes. In 775 women with T1-2, N0-1, M0 TNBCs, 5-year relative survival ratio (RSR) was highest in patients undergoing mastectomy only (94.7%, 95% CI: 88.8-98.8%), followed by BCT (90.8%, 95% CI: 85.0-94.7%), and mastectomy with radiotherapy (82.3%, 95% CI: 73.4-88.1%). The adjusted risks of mortality between the three groups were not significantly different. In 363 patients with T3-4, N2-3, M0 TNBCs, BCT was associated with highest 5-year RSR (94.1%, 95% CI: 81.3-99.4%), followed by mastectomy with radiotherapy (62.7%, 95% CI: 54.3-70.1%), and mastectomy only (58.6%, 95% CI: 43.5-71.6%). Following multivariable adjustment, BCT and mastectomy with radiotherapy remained significantly associated with lower mortality risk compared to mastectomy only. Overall, adjuvant radiotherapy was associated with higher survival in women aged <40 years, but not in older women. Adjuvant radiotherapy appears to be independently associated with a survival gain in locally advanced as well as in very young TNBC.
  14. Bhoo-Pathy N, Balakrishnan N, See MH, Taib NA, Yip CH
    World J Surg, 2016 12;40(12):2913-2921.
    PMID: 27456497 DOI: 10.1007/s00268-016-3658-z
    BACKGROUND: Factors associated with surgery, adjuvant radiotherapy, and chemotherapy and whether there were missed opportunities for treatment in elderly patients were determined in an Asian setting.

    METHODS: All 5616 patients, diagnosed with breast cancer in University Malaya Medical Centre from 1999 to 2013 were included. In 945 elderly patients (aged 65 years and above), multivariable logistic regression was performed to identify factors associated with treatment, following adjustment for age, ethnicity, tumor, and other treatment characteristics. The impact of lack of treatment on survival of the elderly was assessed while accounting for comorbidities.

    RESULTS: One in five elderly patients had comorbidities. Compared to younger patients, the elderly had more favorable tumor characteristics, and received less loco-regional treatment and chemotherapy. Within stage I-IIIa elderly breast cancer patients, 10 % did not receive any surgery. These patients were older, more likely to be Malays, have comorbidities, and bigger tumors. In elderlies with indications for adjuvant radiotherapy, no irradiation (30 %) was associated with increasing age, comorbidity, and the absence of systemic therapy. Hormone therapy was optimal, but only 35 % of elderly women with ER negative tumors received chemotherapy. Compared to elderly women who received adequate treatment, those not receiving surgery (adjusted hazard ratio: 2.30, 95 %CI: 1.10-4.79), or radiotherapy (adjusted hazard ratio: 1.56, 95 %CI: 1.10-2.19), were associated with higher mortality. Less than 25 % of the survival discrepancy between elderly women receiving loco-regional treatment and no treatment were attributed to excess comorbidities in untreated patients.

    CONCLUSION: While the presence of comorbidities significantly influenced loco-regional treatment decisions in the elderly, it was only able to explain the lower survival rates in untreated patients up to a certain extent, suggesting missed opportunities for treatment.

  15. Bhoo-Pathy N, Verkooijen HM, Taib NA, Hartman M, Yip CH
    Br J Surg, 2011 Nov;98(11):1566-72.
    PMID: 21858791 DOI: 10.1002/bjs.7650
    Advanced breast cancer is common in less affluent parts of Asia. The impact of breast surgery on survival of women presenting with metastatic breast cancer in this setting was investigated.
  16. Bhoo-Pathy N, Ng CW, Lim GC, Tamin NSI, Sullivan R, Bhoo-Pathy NT, et al.
    J Oncol Pract, 2019 06;15(6):e537-e546.
    PMID: 31112479 DOI: 10.1200/JOP.18.00619
    BACKGROUND: Financial toxicity negatively affects the well-being of cancer survivors. We examined the incidence, cost drivers, and factors associated with financial toxicity after cancer in an upper-middle-income country with universal health coverage.

    METHODS: Through the Association of Southeast Asian Nations Costs in Oncology study, 1,294 newly diagnosed patients with cancer (Ministry of Health [MOH] hospitals [n = 577], a public university hospital [n = 642], private hospitals [n = 75]) were observed in Malaysia. Cost diaries and questionnaires were used to measure incidence of financial toxicity, encompassing financial catastrophe (FC; out-of-pocket costs ≥ 30% of annual household income), medical impoverishment (decrease in household income from above the national poverty line to below that line after subtraction of cancer-related costs), and economic hardship (inability to make necessary household payments). Predictors of financial toxicity were determined using multivariable analyses.

    RESULTS: One fifth of patients had private health insurance. Incidence of FC at 1 year was 51% (MOH hospitals, 33%; public university hospital, 65%; private hospitals, 72%). Thirty-three percent of households were impoverished at 1 year. Economic hardship was reported by 47% of families. Risk of FC attributed to conventional medical care alone was 18% (MOH hospitals, 5%; public university hospital, 24%; private hospitals, 67%). Inclusion of expenditures on nonmedical goods and services inflated the risk of financial toxicity in public hospitals. Low-income status, type of hospital, and lack of health insurance were strong predictors of FC.

    CONCLUSION: Patients with cancer may not be fully protected against financial hardships, even in settings with universal health coverage. Nonmedical costs also contribute as important drivers of financial toxicity in these settings.

  17. Bhoo-Pathy N, Subramaniam S, Khalil S, Kimman M, Kong YC, Ng CW, et al.
    JCO Oncol Pract, 2021 10;17(10):e1592-e1602.
    PMID: 34077232 DOI: 10.1200/OP.20.01052
    PURPOSE: To determine household spending patterns on complementary medicine following cancer and the financial impact in a setting with universal health coverage.

    METHODS: Country-specific data from a multinational prospective cohort study, Association of Southeast Asian Nations Costs in Oncology Study, comprising 1,249 cancer survivors were included. Household costs of complementary medicine (healthcare practices or products that are not considered as part of conventional medicine) throughout the first year after cancer diagnosis were measured using cost diaries. Study outcomes comprised (1) shares of household expenditures on complementary medicine from total out-of-pocket costs and health costs that were respectively incurred in relation to cancer, (2) incidence of financial catastrophe (out-of-pocket costs related to cancer ≥ 30% of annual household income), and (3) economic hardship (inability to pay for essential household items or services).

    RESULTS: One third of patients reported out-of-pocket household expenditures on complementary medicine in the immediate year after cancer diagnosis, accounting to 20% of the total out-of-pocket costs and 35% of the health costs. Risk of financial catastrophe was higher in households reporting out-of-pocket expenditures on complementary medicine (adjusted odds ratio: 1.39 [95% CI, 1.05 to 1.86]). Corresponding odds ratio within patients from low-income households showed that they were substantially more vulnerable: 2.28 (95% CI, 1.41 to 3.68). Expenditures on complementary medicine were, however, not associated with economic hardship in the immediate year after cancer diagnosis.

    CONCLUSION: In settings with universal health coverage, integration of subsidized evidence-based complementary medicine into mainstream cancer care may alleviate catastrophic expenditures. However, this must go hand in hand with interventions to reduce the use of nonevidence-based complementary therapies following cancer.

  18. Bhoo-Pathy N, Subramaniam S, Taib NA, Hartman M, Alias Z, Tan GH, et al.
    Br J Cancer, 2014 Apr 29;110(9):2187-94.
    PMID: 24736587 DOI: 10.1038/bjc.2014.183
    BACKGROUND: Within a setting without organised breast cancer screening, the characteristics and survival of very early breast cancer were determined.

    METHODS: All 4930 women diagnosed with breast cancer in University Malaya Medical Center, Malaysia from 1993 to 2011 were included. Factors associated with very early presentation (stage I) at diagnosis were identified. Tumour characteristics, management patterns, and survival of very early breast cancer were described, and where appropriate, compared with other settings.

    RESULTS: Proportion of women presenting with stage I breast cancer significantly increased from 15.2% to 25.2% over two decades. Factors associated with very early presentation were Chinese ethnicity, positive family history of breast cancer, and recent period of diagnosis. Within stage I breast cancers, median tumour size at presentation was 1.5 cm. A majority of stage I breast cancer patients received mastectomy, which was associated with older age, Chinese ethnicity, postmenopausal status, and larger tumours. Chemotherapy was administered in 36% of patients. Five-year age-adjusted relative survival for women with stage I breast cancer was 99.1% (95% CI: 97.6-99.6%).

    CONCLUSIONS: The proportion of women presenting with very early breast cancer in this setting without organised screening is increasing. These women seem to survive just as well as their counterparts from affluent settings.

  19. Bhoo-Pathy NT, Inaida S, Tanaka S, Taib NA, Yip CH, Saad M, et al.
    Cancer Epidemiol, 2017 06;48:56-61.
    PMID: 28371729 DOI: 10.1016/j.canep.2017.03.007
    BACKGROUND: The benefit of adjuvant chemotherapy in women with T1N0M0 breast cancers is unclear. While gene expression-based prognostic assays may aid management of women with early estrogen receptor (ER) positive tumors, therapeutic decision-making in women with early stage ER negative tumors remains fraught with difficulties. We investigated the association between adjuvant chemotherapy and overall survival in women with T1N0M0, hormone receptor negative breast cancers.

    METHOD: All newly diagnosed breast cancer patients with node-negative and hormone receptor negative tumors measuring≤2cm at the University Malaya Medical Centre (Malaysia) from 1993 to 2013 were included. Mortality of patients with and without adjuvant chemotherapy were compared and adjusted for possible confounders using propensity score.

    RESULTS: Of 6732 breast cancer patients, 341 (5.1%) had small (≤2cm), node-negative and hormone receptor negative tumors at diagnosis. Among them, only 214 (62.8%) received adjuvant chemotherapy. Five-year overall survival was 88.1% (95% confidence interval (CI): 82.0%-94.2%) for patients receiving chemotherapy and 89.6% (95% CI: 85.1%-94.1%) for patients without chemotherapy. Chemotherapy was not associated with survival following adjustment for age, ethnicity, tumor size, tumor grade, HER2 status, lympho-vascular invasion, type of surgery and radiotherapy administration. However, chemotherapy was associated with a significant survival advantage (adjusted hazard ratio: 0.35, 95%CI: 0.14-0.91) in a subgroup of women with high-grade tumors.

    CONCLUSION: Adjuvant chemotherapy does not appear to be associated with a survival benefit in women with T1N0M0, hormone receptor negative breast cancer except in those with high-grade tumors.

  20. Breast Cancer Association Consortium, Mavaddat N, Dorling L, Carvalho S, Allen J, González-Neira A, et al.
    JAMA Oncol, 2022 Mar 01;8(3):e216744.
    PMID: 35084436 DOI: 10.1001/jamaoncol.2021.6744
    IMPORTANCE: Rare germline genetic variants in several genes are associated with increased breast cancer (BC) risk, but their precise contributions to different disease subtypes are unclear. This information is relevant to guidelines for gene panel testing and risk prediction.

    OBJECTIVE: To characterize tumors associated with BC susceptibility genes in large-scale population- or hospital-based studies.

    DESIGN, SETTING, AND PARTICIPANTS: The multicenter, international case-control analysis of the BRIDGES study included 42 680 patients and 46 387 control participants, comprising women aged 18 to 79 years who were sampled independently of family history from 38 studies. Studies were conducted between 1991 and 2016. Sequencing and analysis took place between 2016 and 2021.

    EXPOSURES: Protein-truncating variants and likely pathogenic missense variants in ATM, BARD1, BRCA1, BRCA2, CHEK2, PALB2, RAD51C, RAD51D, and TP53.

    MAIN OUTCOMES AND MEASURES: The intrinsic-like BC subtypes as defined by estrogen receptor, progesterone receptor, and ERBB2 (formerly known as HER2) status, and tumor grade; morphology; size; stage; lymph node involvement; subtype-specific odds ratios (ORs) for carrying protein-truncating variants and pathogenic missense variants in the 9 BC susceptibility genes.

    RESULTS: The mean (SD) ages at interview (control participants) and diagnosis (cases) were 55.1 (11.9) and 55.8 (10.6) years, respectively; all participants were of European or East Asian ethnicity. There was substantial heterogeneity in the distribution of intrinsic subtypes by gene. RAD51C, RAD51D, and BARD1 variants were associated mainly with triple-negative disease (OR, 6.19 [95% CI, 3.17-12.12]; OR, 6.19 [95% CI, 2.99-12.79]; and OR, 10.05 [95% CI, 5.27-19.19], respectively). CHEK2 variants were associated with all subtypes (with ORs ranging from 2.21-3.17) except for triple-negative disease. For ATM variants, the association was strongest for the hormone receptor (HR)+ERBB2- high-grade subtype (OR, 4.99; 95% CI, 3.68-6.76). BRCA1 was associated with increased risk of all subtypes, but the ORs varied widely, being highest for triple-negative disease (OR, 55.32; 95% CI, 40.51-75.55). BRCA2 and PALB2 variants were also associated with triple-negative disease. TP53 variants were most strongly associated with HR+ERBB2+ and HR-ERBB2+ subtypes. Tumors occurring in pathogenic variant carriers were of higher grade. For most genes and subtypes, a decline in ORs was observed with increasing age. Together, the 9 genes were associated with 27.3% of all triple-negative tumors in women 40 years or younger.

    CONCLUSIONS AND RELEVANCE: The results of this case-control study suggest that variants in the 9 BC risk genes differ substantially in their associated pathology but are generally associated with triple-negative and/or high-grade disease. Knowing the age and tumor subtype distributions associated with individual BC genes can potentially aid guidelines for gene panel testing, risk prediction, and variant classification and guide targeted screening strategies.

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