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Tailored Screening for Breast Cancer in Premenopausal Women

Not Applicable
Conditions
Breast Cancer
Interventions
Other: Tailored screening according to breast density
Other: Annual invitation to mammography
Registration Number
NCT02619123
Lead Sponsor
Cancer Prevention and Research Institute, Italy
Brief Summary

The Tailored Breast Screening Trial (TBST) is a population-based, non-inferiority randomised trial aimed at evaluating the impact of tailored screening strategies addressed to premenopausal women, by using breast density as indicator of risk.

44-45 years old women will be enrolled and invited to undergo a digital mammography. Women are then randomly allocated in two arms. In the intervention arm, women will receive a tailored screening strategy according to breast density.

The aim of this study is to assess the impact of a longer screening interval and the reduction of side effects for premenopausal women.

Detailed Description

Introduction: the Tailored Breast Screening Trial (TBST) is a population-based, non-inferiority randomised trial aimed at evaluating the impact of a change in the screening protocol in a service screening practice. "Tailored" means that the use of a breast density classification allocates women to a longer interval, decreasing the number of screening rounds in the 45-50-year age range. Density of the breast at the baseline is considered as an indicator of risk and also as a masking factor. The aim of this study is to assess the impact of a longer interval and the reduction of side effects for women allocated to the intervention group. In this study, any further intervention is offered to high-density women who are followed-up according to the usual care interval, since the study aimed at decreasing the screening burden.

Methods 44- 45 years old women resident in the screening centre catchment area will be invited to attend for mammography screening and will be asked for informed consent in order to be included in the study. After the enrolment, they will receive a high quality digital mammography; two views and breast density will be classified according with the BI-RADS classification. Women are randomly allocated either to an usual care group or to the intervention group. In the intervention group, women with a dense breast (3-4 categories in BI-RADS) will be invited again after 1 year, while the lower-density group in the intervention arm will be invited after 2 years. After the age of 50, all women will continue to be screened in the usual service screening programme. Density of the breast will be read by 2 readers, and controversies will be solved by a consensus. Allocation of women is blinded to the mammography readers.

EXPECTED RESULTS: the outcomes are: 1. cumulative incidence of interval-cancer cases by intention to treat grouping and by density group, aimed at assessing the non inferiority of screening performance; 2. cumulative incidence of T2+/node-positive status breast cancer cases between arms and by protocol. Screening performance parameters will be evaluated at each screening round. Interim and outcome analysis are expected at 3 and 6 years average follow-up, respectively, starting from the beginning of the screening.

SAMPLE SIZE: the non-inferiority limit is derived from the accepted level of interval cancers in women 50-69 years, which was considered acceptable by the European Community Guidelines. Assuming a 70%BI-RADS 1-2 at the baseline on the basis of the digital mammography experience, the estimated sample size with a power of 90% is 16,596 women per arm.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
33200
Inclusion Criteria
  • women 44-45 years old resident in the screening area
Exclusion Criteria
  • previous diagnosis of invasive or in situ breast cancer
  • women with family high risk for breast cancer
  • previous diagnosis of other cancers in the last 5 years
  • early menopause women or in hormone replacement therapy

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
invitation to tailored screeningTailored screening according to breast density44-45 years old women in this arm with a dense breast (3-4 categories in BI-RADS) at the baseline mammography are invited again after 1 year, while the lower-density group in the intervention arm are invited after 2 years. After the age of 50, all women will continue to be screened in the usual service screening programme.
invitation to mammography screeningAnnual invitation to mammography44-45 years old women in this arm are invited to attend for a mammography screening every 1 year. After the age of 50, all women will continue to be screened in the usual service screening programme.
Primary Outcome Measures
NameTimeMethod
Comparison of cumulative incidence of interval cancer cases by arm and by density groupthree and six years

An "interval cancer" is, according to European guidelines for quality assurance, a primary breast cancer which is diagnosed in a woman who had a screening test negative for malignancy within a time period equal to the screening interval. Interval cancers will be retrieved by linking the cancer registry and screening archive. The "cumulative incidence of interval cancers" is the number of interval cancers divided by the number of screened women

Comparison of cumulative incidence of T2+/node-positive status breast cancer cases by arm and by density group.three and six years

The "cumulative incidence of T2+/N+ breast cancer" is the number of cancers T2+/N+, regardless the modality of detection (screen-detected, interval cancer, etc.), divided by the number of screened women

Secondary Outcome Measures
NameTimeMethod
Comparison of false positive rates by arm and by density group3 and 6 years

The "false positive rate" is measured as the sum of women with a positive mammography in a screening round without a breast cancer divided by the sum of screened women in the same round.

Comparison of attendance to mammography screening by arm and by density group.1, 2, 3, 4, 5 and 6 year

The "attendance to mammography screening" is measured as the number of women attending screening mammography on the number of invited women.

Comparison of cumulative incidence of breast cancer cases by arm and by density group.3 and 6 years

The "cumulative incidence of breast cancer" is the cumulative number of breast cancers divided by the number of enrolled women.Breast cancer cases will be retrieved by linking the of enrolled women with cancer registry information

Trial Locations

Locations (5)

Local Health Unit

🇮🇹

Forlì, Forlì-Cesena, Italy

Local Health Unit n. 4

🇮🇹

Thiene, Vicenza, Italy

Cancer Prevention and Research Institute, ISPO

🇮🇹

Firenze, FI, Italy

CPO Piemonte

🇮🇹

Torino, Italy

Local Health Unit n. 13

🇮🇹

Mirano, Venezia, Italy

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