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. 2002 Apr 27;359(9316):1471-7.
doi: 10.1016/S0140-6736(02)08434-9.

Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status

Bruce G Haffty  1 , Elizabeth Harrold, Atif J Khan, Pradip Pathare, Tanya E Smith, Bruce C Turner, Peter M Glazer, Barbara Ward, Daryl Carter, Ellen Matloff, Allen E Bale, Mayra Alvarez-Franco
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Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status

Bruce G Haffty et al. Lancet. .

Abstract

Background: Management of early-stage breast cancer in young women with mutations in BRCA1 or BRCA2 remains controversial. This study assessed the long-term risks of ipsilateral and contralateral breast cancer in a cohort of young women who underwent breast-conserving surgery followed by radiotherapy.

Methods: Between 1975 and 1998, 290 women with breast cancer diagnosed at age 42 years or younger underwent lumpectomy followed by radiotherapy at our hospital. We recruited 127 of these women for complete sequencing of BRCA1 and BRCA2. Demographic, clinical, pathological, and outcome data were recorded. The primary endpoints were rates of ipsilateral and contralateral breast cancer, in relation to germline BRCA1/2 status.

Findings: 105 women were classified as having sporadic disease (94 with wild-type or known polymorphisms and 11 with variants of unclear significance) and 22 as having genetic predisposition (deleterious mutations in BRCA1 [15] or BRCA2 [seven]). At 12 years of follow-up, the genetic group had significantly higher rates of ipsilateral (49% vs 21%, p=0.007) and contralateral events (42% vs 9%, p=0.001) than the sporadic group. The majority of events were classified as second primary tumours. No patient in the genetic group had undergone oophorectomy or was taking prophylactic agents such as tamoxifen.

Interpretation: Patients with germline mutations in BRCA1 or BRCA2 have a high risk of developing late ipsilateral and contralateral second primary tumours. With breast-conserving therapy, chemoprophylaxis or other interventions to reduce the rate of second cancers may be valuable. Alternatively, bilateral mastectomy may be considered, to minimise the risk of second tumours in the breasts.

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