Clinical trial NCT05315154: Sentinel Lymph Node Biopsy Versus No Axillary Surgery in Early Breast Cancer
Official title: Sentinel Lymph Node Biopsy Versus No Axillary Surgery in Early Breast Cancer Clinically and Ultrasonographically Node-negative
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: Breast cancer
Sentinel Lymph Node
Lead sponsor: University of Campinas, Brazil
Sponsor class: OTHER
First posted: 2022-04-07
Enrollment: 800
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The VENUS trial is a prospective, multicenter, noninferiority, randomized, controlled clinical trial that compares sentinel lymph node biopsy versus no axillary surgery in women with early breast cancer (tumor \<5cm) and node-negative after clinical palpation and axillary ultrasound.

Detailed description: The standard approach to women with early breast cancer (BC) and clinically negative nodes is sentinel lymph node dissection (SLND). Studies showed that axillary lymph node dissection (ALND) can be safely omitted in presence of positive sentinel lymph node in patients treated with breast conserving therapy.Therefore, the pertinence of SLND in the approach to women with early BC is being questioned, once it is not injury-free.

The ACOSOG Z0011 trial examined the safety of omitting ALND in patients with early BC and up to 2 positive nodes at SLND, undergoing conservative surgery plus breast radiotherapy. The 10-year worth of data from this trial strongly suggested that omitting the procedure in these restrict, well-selected, subsets of patients maybe safe. Neoadjuvant chemotherapy (NAC) may be the starting treatment step for women with aggressive BC subtypes even in early stages.The SENTINA and ACOSOG Z1071 trials revealed that for women with three or more negative nodes in SLND, the procedure's accuracy and false-negative rate lie within acceptable boundaries. Our hypothesis is that for patients with early BC (regardless of neoadjuvant systemic therapy), with clinically and ultrasound negative axilla, avoiding SLND may be safe from the oncological perspective.The VENUS trial will investigate whether there may be still room for further de-escalation of the approach to the axilla in well-selected subsets of BC patients, by including women for whom the de-escalation has not been tested in previous trials dealing with the subject.

The VENUS trial is a prospective, noninferiority, multicenter, randomized controlled clinical trial that was approved by the Local Research Ethic Committee .The trial will compare SLND with no axillary surgery in women with T1-2 invasive BC and N0 disease, as ascertained after clinical palpation and axillary ultrasound. Mastectomy and primary systemic therapy are allowed whether node negative previous start the treatment . All women accrued to the trial must sign the informed consent. Randomization 1:1 will be stratified by age (≤50 and \>50 years old) and clinical tumor size (≤2 cm and \>2 cm).

The sample size estimated is 364 women in each arm (400 to account for losses to follow-up). Sample size was calculated according to the following parameters: 90% disease-free survival in patients undergoing SLND and a minimum 85% in those not undergoing the procedure, 80% power and 95% confidence intervals, with a tolerated risk ratio of 0.8. After surgery, regardless of adjuvant therapies, and for at least 48 months, patients will undergo physical examination of their breasts and axilla every 6 months and mammography will be performed annually or at closer intervals if indicated. Adjuvant chemotherapy and radiotherapy will be performed according to the protocol of each participating center and patients without axillary surgery should be considered N0 for decision making.

Eligibility criteria: Inclusion Criteria:

* Women
* Aged 18 years or older
* Histologically confirmed invasive breast carcinoma (core or open biopsy), independent of hormone receptor and HER2 status
* Tumor smaller than 5 cm (T1 or T2) in clinical and radiological exams
* Clinically negative axilla
* Sonographically negative axilla or negative core biopsy/ fine needle biopsy (FNB) when ultrasound is suspect (lymph node tissue is required in core/FNB sample)
* Planned breast conservative surgery or mastectomy
* Written informed consent

Exclusion Criteria:

* Previous diagnostic of any invasive neoplasia (excluded skin cancer no melanoma)
* Metastatic disease in biopsy or image before treatment
* Withdrawal from participating of the study
* Initiated treatment for current breast cancer prior to study enrollment
* Pregnancy
* Breastfeed

Primary outcomes:
measure: Disease free survival (DFS)
timeFrame: 5 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 5 years
measure: Locoregional free survival
timeFrame: 5 years
measure: Axillary recurrence rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Fortaleza
country: Brazil
facility: Hospital Geral de Fortaleza
state: CE
city: Goiânia
country: Brazil
facility: Maternidade Dona Iris
state: GO
city: Goiânia
country: Brazil
facility: Universidade Federal de Goiás
state: GO
city: Belo Horizonte
country: Brazil
facility: Hospital de Clínica da Universidade Federal de Minas Gerais
state: MG
city: Muriaé
country: Brazil
facility: Hospital do Câncer de Muriaé da Fundação Cristiano Varella
state: MG
city: Recife
country: Brazil
facility: Hospital Barão de Lucena
state: PE
city: Teresina
country: Brazil
facility: Oncocenter
state: PI
city: Teresina
country: Brazil
facility: Universidade Federal do Piauí
state: PI
city: Curitiba
country: Brazil
facility: Universidade Federal do Paraná
state: PR
city: Rio De Janeiro
country: Brazil
facility: Hospital Federal da Lagoa
state: RJ
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer
state: RN
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre - UFRS
state: RS
city: Barretos
country: Brazil
facility: Hospital de Amor - Fundação Pio XII
state: SP
city: Botucatu
country: Brazil
facility: Unesp
state: SP
city: Campinas
country: Brazil
facility: Hospital Celso Pierro - PUCC
state: SP
city: Campinas
country: Brazil
facility: Hospital da Mulher Prof.Dr. J A Pinotti - UNICAMP
state: SP
city: São Paulo
country: Brazil
facility: Hospital da Mulher
state: SP
city: São Paulo
country: Brazil
facility: Hospital do Servidor Público Estadual
state: SP
Study officials:
affiliation: Universidade Estadual de Campinas, Unicamp
name: Giuliano Duarte, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Araujo DCM, Duarte GM, Jales RM, Shinzato JY, Cardoso Filho C, Torresan RZ, Brenelli FP, Esteves SCB, Sarian LO. Sentinel lymph node biopsy vs no axillary surgery in early breast cancer clinically and ultrasonographically node negative: A prospective randomized controlled trial-VENUS trial. Breast J. 2020 Oct;26(10):2087-2089. doi: 10.1111/tbj.13994. Epub 2020 Jul 30. No abstract available.
citation: Duarte GM, Araújo DCM, Jales RM, Shinzato JY, Cardoso Filho C, Torresan RZ, Brenelli FB, Kraft MBPL, Esteves SCB, Sarian LOZ, Rahal RMS, Freitas Jr R, Pessoa EC, Lucena CEM, Damin APS, Biazus JV, Budel VM, Oliveira Jr I, Vieira RAC, Gomes JCN. Sentinel lymph node biopsy versus no axillary surgery in early breast cancer clinically and ultrasonographically node negative: A multicentre prospective randomized controlled trial (VENUS trial. Cancer Research. 2022 82 (4_Supplement): OT1-04-03. DOI: https://doi.org/10.1158/1538-7445.SABCS21-OT1-04-03 Published: 15 February 2022