Clinical trial NCT03078036: International Breast Cancer Biomarker,Standard of Care and Real World Outcomes Study
Official title: BREAKOUT -International Breast Cancer Biomarker, Standard of Care and Real World Outcomes Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Keywords: HER2-ve metastatic breast cancer
gBRCA, sBRCA and HRR gene mutations
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Quintiles; University of Tubingen - Germany
First posted: 2017-03-13
Enrollment: 873
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Centers for primary care of metastatic HER2-ve breast cancer patients

Brief summary: BREAKOUT -International Breast Cancer Biomarker, Standard of Care and Real World Outcomes Study BREAKOUT is a prospective cross-sectional cohort study of human epidermal growth factor receptor 2 negative metastatic breast cancer patients who have started 1st line systemic cytotoxic chemotherapy. The study will estimate the prevalence of germline breast cancer susceptibility gene in an otherwise unselected population, describe the treatments administered and estimate the associated clinical outcomes of overall survival and progression-free survival amongst mutation carriers within the context of a low poly ADP ribose polymerase inhibitor treatment setting. Other exploratory analyses may be undertaken to describe somatic breast cancer susceptibility gene and other homologous recombination repair gene mutations.

Detailed description: Background/Rationale: Within the setting of metastatic human epidermal growth factor receptor 2 negative (HER2-ve) breast cancer limited epidemiological data exist on the prevalence of pathogenic mutations of breast cancer susceptibility gene (BRCA) and other homologous recombination repair (HRR) genes. There are also limited data on the treatments and clinical outcomes of patients with such germline and somatic genetic profiles, particularly within this setting. This epidemiologic study will estimate the prevalence of germline breast susceptibility gene (gBRCA) mutations among metastatic HER2-ve patients who have commenced 1st line systemic cytotoxic chemotherapy and, at that time, are considered to have exhausted hormone therapy options (if hormone receptor positive \[HR+ve\]), per investigator's opinion. Among those patients with a gBRCA gene mutation, treatment patterns and clinical outcomes will be described. This study may also explore the prevalence of somatic BRCA (sBRCA) mutations and other HRR gene mutations among metastatic HER2-ve patients who have commenced 1st line systemic cytotoxic chemotherapy. The treatment patterns and clinical outcomes may be described among those patients with a sBRCA gene mutation and those with other HRR gene mutations.

Eligibility criteria: Inclusion Criteria:

1. Provision of signed, written and dated informed consent.
2. Adult females (according to the age of majority/adulthood as defined by local regulations).
3. Histologically or cytologically confirmed HER2-ve breast cancer with evidence of metastatic disease.
4. Initiated treatment with 1st line systemic cytotoxic chemotherapy (not hormonal therapy) for metastatic breast cancer in the last 90 days and, at that time, are considered to have exhausted hormone therapy options (if HR+ve).

Exclusion Criteria:

1. Previous enrolment in this study.
2. Involvement in the planning and/or conduct of this study (applies to both AstraZeneca staff and/or staff at the study site).
3. Current participation in a clinical study with an investigational oncology product.
4. Previous PARPi therapy, including, but not limited to, participation in a previous clinical study that included PARPi therapy.
5. Current commencement of PARPi treatment.

Primary outcomes:
measure: BRCA Mutational status (BRCA1 mutated and/or BRCA2 mutated or BRCA wild type).
timeFrame: At one time point at inclusion in the study up to 12 months after the beginning of the study.
Secondary outcomes:
measure: Descriptive statistics for treatments administered by line of therapy from 1st line metastatic breast cancer.
timeFrame: 2.5 years (30 months) since the beginning of the study.
measure: Progression free survival by line of therapy
timeFrame: 2.5 years (30 months) since the beginning of the study.
measure: Overall survival by line of therapy
timeFrame: 2.5 years (30 months) since the beginning of the study.
Other outcomes:
Locations:
city: Santa Barbara
country: United States
facility: Research Site
state: California
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Denton
country: United States
facility: Research Site
state: Texas
city: Flower Mound
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Paris
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: The Woodlands
country: United States
facility: Research Site
state: Texas
city: Newport News
country: United States
facility: Research Site
state: Virginia
city: Vancouver
country: United States
facility: Research Site
state: Washington
city: Wenatchee
country: United States
facility: Research Site
state: Washington
city: Redcliffe
country: Australia
facility: Research Site
state: Queensland
city: Kurralta Park
country: Australia
facility: Research Site
state: South Australia
city: Ballarat
country: Australia
facility: Research Site
state: Victoria
city: Dobrich
country: Bulgaria
facility: Research Site
city: Ruse
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Kingston
country: Canada
facility: Research Site
state: Ontario
city: Kitchener
country: Canada
facility: Research Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Tubingen
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Szekszard
country: Hungary
facility: Research Site
city: Szolnok
country: Hungary
facility: Research Site
city: Carpi
country: Italy
facility: Research Site
state: Modena
city: Castellanza
country: Italy
facility: Research Site
state: Varese
city: Milano
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Reggio Emilia
country: Italy
facility: Research Site
city: Kamogawa-shi
country: Japan
facility: Research Site
state: Chiba-Ken
city: Matsuyama-shi
country: Japan
facility: Research Site
state: Ehime-Ken
city: Fukuoka-shi
country: Japan
facility: Research Site
state: Fukuoka-Ken
city: Sapporo-shi
country: Japan
facility: Research Site
state: Hokkaido
city: Sendai-shi
country: Japan
facility: Research Site
state: Miyagi-Ken
city: Osaka-shi
country: Japan
facility: Research Site
state: Osaka-Fu
city: Chuo-ku
country: Japan
facility: Research Site
state: Tokyo-To
city: Goyang-si
country: Korea, Republic of
facility: Research Site
state: Gyeonggi-do
city: Seongnam-si,
country: Korea, Republic of
facility: Research Site
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Ulsan
country: Korea, Republic of
facility: Research Site
city: Brzozow
country: Poland
facility: Research Site
city: Opole
country: Poland
facility: Research Site
city: Walbrzych
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wieliszew
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Zory
country: Poland
facility: Research Site
city: Chelyabinsk
country: Russian Federation
facility: Research Site
city: Krasnodar
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Pyatigorsk
country: Russian Federation
facility: Research Site
city: Ryazan
country: Russian Federation
facility: Research Site
city: Tomsk
country: Russian Federation
facility: Research Site
city: Terrassa
country: Spain
facility: Research Site
state: Barcelona
city: A Coruna
country: Spain
facility: Research Site
state: La Coruña
city: Alcorcon
country: Spain
facility: Research Site
state: Madrid
city: San Sebastian de los Reyes
country: Spain
facility: Research Site
state: Madrid
city: Barcelona
country: Spain
facility: Research Site
city: Burgos
country: Spain
facility: Research Site
city: Girona
country: Spain
facility: Research Site
city: Huelva
country: Spain
facility: Research Site
city: Changhua
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Antalya
country: Turkey
facility: Research Site
city: Diyarbakir
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Kocaeli
country: Turkey
facility: Research Site
city: Sakarya
country: Turkey
facility: Research Site
city: Samsun
country: Turkey
facility: Research Site
city: Tekirdag
country: Turkey
facility: Research Site
city: Trabzon
country: Turkey
facility: Research Site
city: Van
country: Turkey
facility: Research Site
city: Huntingdon
country: United Kingdom
facility: Research Site
state: Cambridgeshire
city: Peterborough
country: United Kingdom
facility: Research Site
state: Cambridgeshire
city: Truro
country: United Kingdom
facility: Research Site
state: Cornwall
city: Derby
country: United Kingdom
facility: Research Site
state: Derbyshire
city: Exeter
country: United Kingdom
facility: Research Site
state: Devon
city: Worthing
country: United Kingdom
facility: Research Site
state: East Sussex
city: London
country: United Kingdom
facility: Research Site
state: Greater London
city: Blackpool
country: United Kingdom
facility: Research Site
state: Lancashire
city: Lancaster
country: United Kingdom
facility: Research Site
state: Lancashire
city: Stoke on Trent
country: United Kingdom
facility: Research Site
state: Staffordshire
city: Warwick
country: United Kingdom
facility: Research Site
state: Warwickshire
city: Wolverhampton
country: United Kingdom
facility: Research Site
state: West Midlands
city: Huddersfield
country: United Kingdom
facility: Research Site
state: West Yorkshire
Study officials:
References:
citation: Koh SJ, Ohsumi S, Takahashi M, Fukuma E, Jung KH, Ishida T, Dai MS, Chang CH, Dalvi T, Walker G, Bennett J, O'Shaughnessy J, Balmana J. Prevalence of mutations in BRCA and homologous recombination repair genes and real-world standard of care of Asian patients with HER2-negative metastatic breast cancer starting first-line systemic cytotoxic chemotherapy: subgroup analysis of the global BREAKOUT study. Breast Cancer. 2022 Jan;29(1):92-102. doi: 10.1007/s12282-021-01283-4. Epub 2021 Aug 31.
citation: O'Shaughnessy J, Brezden-Masley C, Cazzaniga M, Dalvi T, Walker G, Bennett J, Ohsumi S. Prevalence of germline BRCA mutations in HER2-negative metastatic breast cancer: global results from the real-world, observational BREAKOUT study. Breast Cancer Res. 2020 Oct 27;22(1):114. doi: 10.1186/s13058-020-01349-9.