Artigo

MRI Surveillance and Breast Cancer Mortality in Women With BRCA1 and BRCA2 Sequence Variations

Autor(es): Jan Lubinski, MD, PhD; Joanne Kotsopoulos, PhD; Pal Moller, MD; Tuya Pal, MD; Andrea Eisen, MD; Larissa Peck, MSc; Beth Y. Karlan, MD; Amber Aeilts, MSc; Charis Eng, MD, PhD; Louise Bordeleau, MD; William D. Foulkes, MBBS, PhD; Nadine Tung, MD; Fergus J. Couch, PhD; Robert Fruscio, MD; Teresa Ramon y; Cajal, MD; Christian F. Singer,MD, MPH; Susan L. Neuhausen, PhD; Dana Zakalik, MD; Cezary Cybulski, MD, PhD; Jacek Gronwald, MD, PhD; Tomasz Huzarski, MD; Klaudia Stempa, MD, PhD; Jeffrey Dungan, MD; Carey Cullinane, MD; Olufunmilayo I. Olopade, MD; Kelly Metcalfe, PhD; Ping Sun, PhD; Steven A. Narod, MD; for the Hereditary Breast Cancer Clinical Study Group

ABSTRACT

IMPORTANCE – Magnetic resonance imaging (MRI) surveillance is offered to women with a
pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer.
Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI
surveillance with mortality risk has not been well defined.

OBJECTIVE – To compare breast cancer mortality rates in women with a BRCA1 or BRCA2
sequence variation who entered an MRI surveillance program with those who did not.

DESIGN, SETTING, AND PARTICIPANTS – Women with a BRCA1 or BRCA2 sequence variation
were identified from 59 participating centers in 11 countries. Participants completed a
baseline questionnaire between 1995 and 2015 and a follow-up questionnaire every 2 years
to document screening histories, incident cancers, and vital status.Women who had breast
cancer, a screening MRI examination, or bilateral mastectomy prior to enrollment were
excluded. Participants were followed up from age 30 years (or the date of the baseline
questionnaire, whichever was later) until age 75 years, the last follow-up, or death from
breast cancer. Data were analyzed from January 1 to July 31, 2023.

EXPOSURES – Entrance into an MRI surveillance program.

MAIN OUTCOMES AND MEASURES – Cox proportional hazards modelingwas used to estimate
the hazard ratios (HRs) and 95%CIs for breast cancer mortality associated with MRI
surveillance compared with no MRI surveillance using a time-dependent analysis.

RESULTS – A total of 2488 women (mean [range] age at study entry 41.2 [30-69] years), with a
sequence variation in the BRCA1 (n = 2004) or BRCA2 (n = 484) genes were included in the
analysis. Of these participants, 1756 (70.6%) had at least 1 screening MRI examination and
732 women (29.4%) did not. After a mean follow-up of 9.2 years, 344 women (13.8%)
developed breast cancer and 35 women (1.4%) died of breast cancer. The age-adjusted HRs
for breast cancer mortality associated with entering an MRI surveillance program were 0.20
(95%CI, 0.10-0.43; P < .001) for women with BRCA1 sequence variations and 0.87 (95%CI,
0.10-17.25; P = .93) for women with BRCA2 sequence variations.

CONCLUSION AND RELEVANCE – Results of this cohort study suggest that among women with a
BRCA1 sequence variation, MRI surveillance was associated with a significant reduction in
breast cancer mortality compared with no MRI surveillance. Further studies of women with
BRCA2 sequence variations are needed to ascertain these women obtain the same benefits
associated with MRI surveillance.

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29/02/2024

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