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AzTrials

Breast CancerNCT05570266

Genetic and Non-Genetic Breast Cancer Risk Prediction Evaluation in Indonesian Samples

An observational study of Breast Cancer, run by Nalagenetics Pte Ltd at 1 site in Indonesia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Breast cancer is the most common cancer and cause of cancer- related deaths among women, accounting for 1.67 million (25.2%) new cases and 521,907 (14.7%) deaths worldwide. The prevalence and survival rates of breast cancer differ per country. Read more about this study

Who is it for?
Ages 35 to 75 years, women onlyHealthy volunteers can take part
Conditions the study is for
Breast Cancer
What is being tested?
Breast Cancer Risk Prediction Software
How many people
322 participants
Where
1 siteIndonesia
Study dates
13 Oct 2020to 25 May 2023
How long will I take part?
3 Months
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 35 to 75 years
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: Controls are taken from clients who visited Breast Cancer Care Alliance (BCCA) We will not impose any selection to age at diagnosis for both cases and controls

Who may be able to join

  • For case group
  • Had been diagnosed with primary breast cancer or tested positive for high penetrance genes (e.g. BRCA 1/2)
  • Menarche age >12 years old
  • Premenopausal
  • For control group
  • Premenopausal
Show all 9Show fewer
  • Menarche age >12 years old
  • Asymptomatic
  • Consented for the study and follow up

Who cannot join

  • For case group:
  • First degree family history of breast or ovarian cancer
  • For control group:
  • Family history of breast or ovarian cancer
  • First-degree relationship with the cases

Trial locations and contacts

1 site in 1 country.

Indonesia1 site
  • MRCC Siloam Hospitals Semanggi

    Jakarta, Jakarta Special Capital Region, 12930

Other trials in Indonesia

About this study

Breast cancer is the most common cancer and cause of cancer- related deaths among women, accounting for 1.67 million (25.2%) new cases and 521,907 (14.7%) deaths worldwide. The prevalence and survival rates of breast cancer differ per country. In Indonesia, majority of patients (70.9%) go to the clinic with advanced stages of breast cancer. Five-year survival rate is 51.07%. One of the most important determinants of survival is education level and stage of breast cancer.

Current screening methods include mammography and radiology assessments, both of which have disadvantages specifically in Asian population. Mammography is less useful in Asian population because the population has denser breast, resulting to failure to diagnose cases of breast cancer in this population in 37-70% of cases. Moreover, screening methods provide binary answers, and therefore does not inform risk profile of the patients.

The investigators aim to implement PRS into the breast cancer screening process while observing the differences of genetic and non-genetic risk factor in patients with breast cancer and patients without any medical/family history of breast cancer in Indonesian population.

Read the detailed description

Breast cancer is the most common cancer and cause of cancer- related deaths among women, accounting for 1.67 million (25.2%) new cases and 521,907 (14.7%) deaths worldwide. The prevalence and survival rates of breast cancer differ per country. In Indonesia, majority of patients (70.9%) go to the clinic with advanced stages of breast cancer. Five-year survival rate is 51.07%. One of the most important determinants of survival is education level and stage of breast cancer.

Current screening methods include mammography and radiology assessments, both of which have disadvantages specifically in Asian population. Mammography is less useful in Asian population because the population has denser breast, resulting to failure to diagnose cases of breast cancer in this population in 37-70% of cases. Moreover, screening methods provide binary answers, and therefore does not inform risk profile of the patients.

Traditionally, risk prediction algorithms such as the GAIL model, BODACIEA, and Tyler-Cuzick use medical history and clinical factors of patients. However recently, genetics have grown in importance due to the heritability nature of cancer and availability of testing services and guidelines. About 10-30% of all cases are attributed to familial breast cancers, and of these, only 5%-10% correlate with hereditary factors linked with high penetrance. The most common genetic test to screen today is BRCA 1 and 2, and then other 22 genes curated by expert opinions on NCCN and other guidelines.

The prevalences estimated for carriers of mutations in BRCA1/2 are, respectively, 0.11% and 0.12% in the general population, and between 12.8%-16% in high risk families with three or more cases of breast or ovarian cancer. Approximately 10-15% of ovarian cancer cases are believed to be due to a BRCA1/2 mutation, however ~50% of individuals with a pathogenic BRCA mutation may not report a strong family history of cancer. NCCN, ASCO, St Gallen and has established guidelines to screen patients, but the low awareness in patients to go screening in the first place is hard.

Genetic testing using polygenic risk scores (PRS) combines the effects of low penetrance genes that together creates predictive value as strong as high-penetrance genes, but is much more common than high-penetrance gene testing. A PRS is most commonly calculated as a weighted sum of the number of risk alleles carried by an individual, where the risk alleles and their weights are defined by the loci and their measured effects as detected by genome wide association studies.

For some common adult-onset diseases, the polygenic risk conveyed to a substantial segment (10-20%) of the population whose genomes are enriched in risk alleles is comparable to the risk conveyed by commonly used clinical risk factors. A recent large-scale comprehensive GWAS for breast cancer found that 45% of familial relative risk of breast cancer can be explained by genetic variants captured by genotyping and imputation. As genotyping technologies advance, and consortia build algorithms on more samples, the predictive values of PRS algorithms are maturing. After analysis of 120,000 patients and optimizing for highest predictability, a PRS score combining 313 SNPs and clinical factors have a predictive value of 68%, compared to only 58% using clinical risk factors. A study conducted in the Breast Cancer Association Consortium showed that PRS combined with environmental risk factors can be used to distinguish women at different levels of breast cancer risk in the general population.

This score gives providers the opportunity to stratify the patients may result in some people with higher risk profile to start risk-reducing therapy earlier, start screening at a younger age, and modify their lifestyles with the aim of reducing their risk. For example, those who are at the top 1.5% of polygenic risk score have an odds ratio of 3 or more compared to the general population.

Polygenic risk scores have been applied in leading institutions in the world as clinical trials and in the commercial settings. However, there has been little application in developing countries to use polygenic risk score to increase awareness of risk-reducing strategies of breast cancer in patients.

One of the main concerns about the clinical implementation of population-based genetic screening is experts' availability post-test. A study in the UK for physicians' attitude towards risk stratification of ovarian cancer showed that 70% oncologists and 50% of GPs would be willing to offer genetic testing to their patients. About 60% believe that the test would give patients a sense of control, and over 80% of providers are willing to personalize recommendations based on risk stratification.

The investigators aim to implement PRS into the breast cancer screening process while observing the differences of genetic and non-genetic risk factor in patients with breast cancer and patients without any medical/family history of breast cancer in Indonesian population.

Conditions
Breast Cancer
Being tested
Breast Cancer Risk Prediction Software
Keywords
Breast Cancer, Polygenic Risk Score
Medical subject headings
Breast Neoplasms, Genetic Risk Score

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Breast Cancer Risk Prediction SoftwareDiagnostic test

    Genotyping of known breast cancer-related markers (313 variants) will be conducted using a microarray genotyping chip (Genetic Risk). Survey answers will determine Gail Model scores and thus Clinical Risk Score.

Study groups in NCT05570266
Study groupRoleWhat they receive
CasesCases are taken by recruiting women who: * have no first degree family history of breast or ovarian cancer * are or had been diagnosed with primary breast cancer or tested positive for high penetrance genes (e.g. BRCA 1/2) * menarche age >12 years old * premenopausal
Receives: Diagnostic Test: Breast Cancer Risk Prediction Software
CohortControls are taken from clients who visited Breast Cancer Care Alliance (BCCA) and: * have no family history of breast or ovarian cancer * premenopausal * menarche age >12 years old * asymptomatic * do not have any first-degree relationship with the cases * consented for the study and follow up
Receives: Diagnostic Test: Breast Cancer Risk Prediction Software

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Absolute risk difference between breast cancer patients and non-breast cancer patients in terms of their non-genetic risk

    Absolute non-genetic risk is calculated using the MDCalc Gail Model

    Measured: First quarter of 2023

  2. Absolute risk difference between breast cancer patients and non-breast cancer patients in terms of their genetic risk

    Genetic risk is derived from polygenic risk score acquired from running a microarray sample result through an algorithm (see Mavaddat et al 2019)

    Measured: First quarter of 2023

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2022
  2. Study start13 Oct 2020
  3. Primary completion10 Jan 2023
  4. Study completion25 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
322 participants (actual)
Target duration
3 Months
IDs, dates and publications
ClinicalTrials.gov ID
NCT05570266
Sponsor's protocol ID
ID-RPSBC-01-20201012
Status last verified
Sep 2023
First submitted
4 Oct 2022
Last updated
13 Sep 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Costa M, Saldanha P. Risk Reduction Strategies in Breast Cancer Prevention. Eur J Breast Health. 2017 Jul 1;13(3):103-112. doi: 10.5152/ejbh.2017.3583. eCollection 2017 Jul.

    PubMed 28894848
  • Mavaddat N, Michailidou K, Dennis J, Lush M, Fachal L, Lee A, Tyrer JP, Chen TH, Wang Q, Bolla MK, Yang X, Adank MA, Ahearn T, Aittomaki K, Allen J, Andrulis IL, Anton-Culver H, Antonenkova NN, Arndt V, Aronson KJ, Auer PL, Auvinen P, Barrdahl M, Beane Freeman LE, Beckmann MW, Behrens S, Benitez J, Bermisheva M, Bernstein L, Blomqvist C, Bogdanova NV, Bojesen SE, Bonanni B, Borresen-Dale AL, Brauch H, Bremer M, Brenner H, Brentnall A, Brock IW, Brooks-Wilson A, Brucker SY, Bruning T, Burwinkel B, Campa D, Carter BD, Castelao JE, Chanock SJ, Chlebowski R, Christiansen H, Clarke CL, Collee JM, Cordina-Duverger E, Cornelissen S, Couch FJ, Cox A, Cross SS, Czene K, Daly MB, Devilee P, Dork T, Dos-Santos-Silva I, Dumont M, Durcan L, Dwek M, Eccles DM, Ekici AB, Eliassen AH, Ellberg C, Engel C, Eriksson M, Evans DG, Fasching PA, Figueroa J, Fletcher O, Flyger H, Forsti A, Fritschi L, Gabrielson M, Gago-Dominguez M, Gapstur SM, Garcia-Saenz JA, Gaudet MM, Georgoulias V, Giles GG, Gilyazova IR, Glendon G, Goldberg MS, Goldgar DE, Gonzalez-Neira A, Grenaker Alnaes GI, Grip M, Gronwald J, Grundy A, Guenel P, Haeberle L, Hahnen E, Haiman CA, Hakansson N, Hamann U, Hankinson SE, Harkness EF, Hart SN, He W, Hein A, Heyworth J, Hillemanns P, Hollestelle A, Hooning MJ, Hoover RN, Hopper JL, Howell A, Huang G, Humphreys K, Hunter DJ, Jakimovska M, Jakubowska A, Janni W, John EM, Johnson N, Jones ME, Jukkola-Vuorinen A, Jung A, Kaaks R, Kaczmarek K, Kataja V, Keeman R, Kerin MJ, Khusnutdinova E, Kiiski JI, Knight JA, Ko YD, Kosma VM, Koutros S, Kristensen VN, Kruger U, Kuhl T, Lambrechts D, Le Marchand L, Lee E, Lejbkowicz F, Lilyquist J, Lindblom A, Lindstrom S, Lissowska J, Lo WY, Loibl S, Long J, Lubinski J, Lux MP, MacInnis RJ, Maishman T, Makalic E, Maleva Kostovska I, Mannermaa A, Manoukian S, Margolin S, Martens JWM, Martinez ME, Mavroudis D, McLean C, Meindl A, Menon U, Middha P, Miller N, Moreno F, Mulligan AM, Mulot C, Munoz-Garzon VM, Neuhausen SL, Nevanlinna H, Neven P, Newman WG, Nielsen SF, Nordestgaard BG, Norman A, Offit K, Olson JE, Olsson H, Orr N, Pankratz VS, Park-Simon TW, Perez JIA, Perez-Barrios C, Peterlongo P, Peto J, Pinchev M, Plaseska-Karanfilska D, Polley EC, Prentice R, Presneau N, Prokofyeva D, Purrington K, Pylkas K, Rack B, Radice P, Rau-Murthy R, Rennert G, Rennert HS, Rhenius V, Robson M, Romero A, Ruddy KJ, Ruebner M, Saloustros E, Sandler DP, Sawyer EJ, Schmidt DF, Schmutzler RK, Schneeweiss A, Schoemaker MJ, Schumacher F, Schurmann P, Schwentner L, Scott C, Scott RJ, Seynaeve C, Shah M, Sherman ME, Shrubsole MJ, Shu XO, Slager S, Smeets A, Sohn C, Soucy P, Southey MC, Spinelli JJ, Stegmaier C, Stone J, Swerdlow AJ, Tamimi RM, Tapper WJ, Taylor JA, Terry MB, Thone K, Tollenaar RAEM, Tomlinson I, Truong T, Tzardi M, Ulmer HU, Untch M, Vachon CM, van Veen EM, Vijai J, Weinberg CR, Wendt C, Whittemore AS, Wildiers H, Willett W, Winqvist R, Wolk A, Yang XR, Yannoukakos D, Zhang Y, Zheng W, Ziogas A; ABCTB Investigators; kConFab/AOCS Investigators; NBCS Collaborators; Dunning AM, Thompson DJ, Chenevix-Trench G, Chang-Claude J, Schmidt MK, Hall P, Milne RL, Pharoah PDP, Antoniou AC, Chatterjee N, Kraft P, Garcia-Closas M, Simard J, Easton DF. Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes. Am J Hum Genet. 2019 Jan 3;104(1):21-34. doi: 10.1016/j.ajhg.2018.11.002. Epub 2018 Dec 13.

    PubMed 30554720
  • Sinaga ES, Ahmad RA, Shivalli S, Hutajulu SH. Age at diagnosis predicted survival outcome of female patients with breast cancer at a tertiary hospital in Yogyakarta, Indonesia. Pan Afr Med J. 2018 Nov 7;31:163. doi: 10.11604/pamj.2018.31.163.17284. eCollection 2018.

    PubMed 31086616

Questions about this trial

What is this clinical trial studying?

An observational study of Breast Cancer, run by Nalagenetics Pte Ltd at 1 site in Indonesia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Absolute risk difference between breast cancer patients and non-breast cancer patients in terms of their non-genetic risk (time frame: First quarter of 2023). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05570266, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.

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